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Mechanism of Fam172a Gene Knockout Exacerbating Non-alcoholic Fatty Liver Disease #br#

LI Mengqi#, WEI Herui#, AN Wen, LOU Jing, HE Lingling, YANG Junru, XIAO Fan, Δ, WEI Hongshan, Δ

Journal of Medical Molecular Biology 2024, 21 (1): 1-8. DOI: 10.3870/j.issn.1672-8009.2024.01.001

Abstract （483）

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ObjectiveTo explore the mechanism of Fam172a gene knockout in enhancing endoplasmic reticulum stress (ERS) induced nonalcoholic fatty liver disease (NAFLD). Methods Mice were intraperitoneally injected with PBS, tunicamycin ( TM), or the NF-κB inhibitor DHMEQ. The hepatic function and hepatic lipid accumulation were then evaluated, and protein levelswere assessed via Western blotting. Results Compared to the control group, the Fam172a ^{- / -} -TMgroup had significantly increased levels of serum ALT and AST, along with the increased liver structure damage and lipid accumulation. Additionally, the relative expression levels of GRP78, CHOP,and pNF-κB / NF-κB in liver tissues were significantly up-regulated in the Fam172a ^{- / -} -TM group. Furthermore, DHMEQ significantly reduced liver injury, lipid accumulation, and ERS inFam172a^{- / -} mice. Conclusion Fam172a knockout could enhance the ERS-induced NAFLD byactivation of NF-κB pathway.

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miR-30b-3p Regulates Sodium Oxalate Induced Apoptosis and Oxidative Stress in HK-2 Cells by Targeting ZNRF1 #br#

YU Dapeng, DING Youpeng, LI Mianzhou, ZHANG Rongyuan,

Journal of Medical Molecular Biology 2024, 21 (1): 9-16. DOI: 10.3870/j.issn.1672-8009.2024.01.002

Abstract （271）

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Objective To explore the effect of miR-30b-3p on HK-2 cell proliferation, apoptosis and oxidative stress induced by sodium oxalate and the mechanism by targeting ZNRF1. Methods HK-2 cells were treated with 0. 2 μmol / L or 0. 6 μmol / L sodium oxalate. miR-30b-3p mimic and miR-30b-3p inhibitor and their corresponding control were transfected into HK-2 cells. The proliferation, invasion and migration of HK-2 cells were detected by CCK-8, transwell and wound-healing assay, respectively. Intracellular ROS was measured by flow cytometry. The activities of LDH, MDA and GSH were detected by ELISA. The expression levels of Bax and Bcl-2 were analyzed by Western blotting. Luciferase gene reporter assay was used to verify the targeting relationship between miR-30b-3p and ZNRF1. The relationship between miR-30b-3p and ZNRF1 was analyzed by RNA immunoprecipitation. Results Sodium oxalate treatment significantly increased ROS, LDH and MDA levels and decreased GSH levels in HK-2 cells (P< 0. 01). Sodium oxalate also inhibited the proliferation, migration and invasion, and promoted apoptosis of HK-2 cells. miR-30b-3p promoted the effect of sodium oxalate on HK-2 cells. The results of gene target prediction and luciferase assay indicated that ZNRF1 is a direct target of miR-30b-3p in HK-2 cells, and ZNRF1 silencing reversed the effect of miR-30b-3p on sodium oxalate induced HK-2 cell damage. Conclusion miR-30b-3pcan promote the apoptosis and oxidative stress induced by sodium oxalate in HK-2 cells, and inhibitcell proliferation, invasion and migrationvia ZNRF1.

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miR-126-5p Inhibits Oxygen-glucose Deprivation / Reperfusion Mediated Apoptosis and Inflammatory Response in HT22 Cells by Targeting TRAF3 #br#

ZHAO Li, ZHAO Lei, XIE Ailing, WANG Yamei, WU Yujuan, TANG Shuang

Journal of Medical Molecular Biology 2024, 21 (1): 17-24. DOI: 10.3870/j.issn.1672-8009.2024.01.003

Abstract （258）

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Objective To explore the effect of miR-126-5p on apoptosis and inflammatory response in mouse hippocampal neuron HT22 cells mediated by oxygen-glucose deprivation / reperfusion (OGD / R) by targeting tumor necrosis factor receptor-associated factor 3 (TRAF3). Methods The OGD / R cell model was established in vitro by simulating ischemia / reperfusion (I / R) injury. The targeting relationship between miR-126-5p and TRAF3 and the effect of miR-126-5p on apoptosis and inflammatory response in HT22 cells were analyzed. Results The level of miR-126-5p inthe OGD / R group was down-regulated while the mRNA and expression levels of TRAF3 were upregulated when compared with those in the control group. The cell survival rate and the Bcl-2 expression level in the OGD / R group were decreased while the lactate dehydrogenase ( LDH) release, the apoptosis rate and the protein expression levels of Bax and cleaved caspase-3 in the OGD / Rgroup were increased when compared with those in the control group (all P< 0. 05). The protein expression levels of TRAF3, Bax and cleaved caspase-3, the LDH release, the apoptosis rate were significantly decreased in the OGD / R + miR-mimic group and the OGD + miR-mimic + pcDNA group while the cell survival rate and the protein expression level of Bcl-2 were increased when compared with those in the OGD / R + mimic-NC group. In addition, the above indicators were elevated in the OGD + miR-mimic + pcDNA-TRAF3 group while the cell survival rate was significantly lowered when compared with those in the OGD/R+mimic-NC group (all P<0.05). Conclusion miR-126-5p can inhibit the OGD/R-mediated apoptosis of and inflammatory response in HT22 cells by targeting TRAF3, thus playing a protective role on neuronal cells.

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miR-200c Regulates Proliferation and Apoptosis of Cervical Cancer Cells via Targeting ZEB1 Expression #br#

FENG Baoju, JIANG Ying, LV Xijun

Journal of Medical Molecular Biology 2024, 21 (1): 25-31. DOI: 10.3870/j.issn.1672-8009.2024.01.004

Abstract （237）

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Objective To study the effect of miR-200c on the proliferation and apoptosis ofcervical cancer cells and its possible mechanism. Methods RT-PCR was used to detect the expression level of miR-200c in 52 cases of cervical cancer tissues and adjacent tissues. The miR-200c mimic or inhibitor was used to transfect cervical cancer cell lines, and the transfection efficiency was verified by RT-PCR. CCK8 assay was used to detect the proliferation activity of transfected cells, while the apoptosis was detected by flow cytometry. The target gene of miR-200c was predicted by bioinformatics analysis, and the dual-luciferase gene reporter assay was applied to verify the targeting relationship. RT-PCR was used to detect the expression level of the target gene in cancer tissuesand adjacent tissues. Pearson correlation analysis between miR-200c and target gene expression wasanalyzed. RT-PCR and Western blotting were used to detect the expression level of target gene incells transfected with siRNA or plasmid. Results The expression level of miR-200c in cervicalcancer tissues was significantly lower than that in adjacent tissues. The proliferation activity of HT3 cells transfected with miR-200c mimics was significantly reduced, and the apoptosis was significantly increased, while the proliferation activity of HeLa cells transfected with miR-200c inhibitors was significantly increased, and the apoptosis of the above cells was significantly reduced. Dual-luciferase gene reporter assay confirmed that ZEB1 is an indicator target of miR-200c, and miR-200c mimics significantly reduced the expression level of ZEB1, while the inhibitor exerted the opposite effect. The expression level of ZEB1 in cervical cancer tissues was significantly higher than that in adjacent tissues, and its expression was significantly negatively correlated with the expression of miR-200c. Knockdown of ZEB1 significantly inhibited the proliferation of HT3 cells and promotedthe apoptosis of cells, while the overexpression of ZEB1 had the opposite effect. Conclusion miR-200c regulates the proliferation and apoptosis of cervical cancer cells by targeting the expression of ZEB1, thereby participating in the occurrence and development of cervical cancer.

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Clearance Mechanism of NLRP3 Against Pseudomonas aeruginosa via TLR4 / NF-κB Pathway #br#

LIU Xin, LI Maoxin, YAN Bingjian, XU Zongjie

Journal of Medical Molecular Biology 2024, 21 (1): 32-38. DOI: 10.3870/j.issn.1672-8009.2024.01.005

Abstract （300）

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Objective To investigate the clearance mechanism of NLRP3 against Pseudomonas aeruginosa (PA) based on TLR4 / NF-κB pathway. Methods PA-infected HP-1-induced differentiated macrophages and primary human monocyte-derived macrophages were used for following experiments. NLRP3 and TLR4 were later silenced in macrophages by siRNAs (si-NLRP3 and si-TLR4), and the expression levels of IL-1β and IL-8 in the supernatant were detected by ELISA. The mRNA expression levels of NLRP3 and caspase-1 were detected by RT-PCR. The protein expression levelsof TLR4 and p-NF-κB P65 were detected by Western blotting. Results The levels of IL-1β, IL-8,the mRNA expression levels of NLRP3, caspase-1 and TLR4, and the protein expression level of pNF-κB P65 were significantly increased in the supernatants or cells of the PA-infected THP-1-induced differentiated macrophages and primary human monocyte-derived macrophages hMDMs (P <0. 05). The levels of IL-1β, IL-8, the expression levels of NLRP3, caspase-1 mRNA and TLR4,p-NF-κB P65 protein in the supernatants of the si-NLRP3 and si-TLR4 groups (NLRP3 and TLR4were silenced in THP-1-induced differentiated macrophages and primary human monocyte-derivedmacrophages hMDMs) were significantly reduced when compared with those in the si-NC group (P< 0. 05). The clearance rate was significantly increased in NLRP3 and / or TLR4 silenced PA-infected THP-1 macrophages and primary human monocyte-derived macrophage hMDMs when comparedwith that in the si-NC group (P < 0. 05). Conclusion Silencing NLRP3 increases the clearance of Pseudomonas aeruginosa by macrophages, and the mechanism may be related to the inhibition ofTLR4 / NF-κB signaling pathway activation.

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Mechanism of HMGB1 Neutralizing Antibody Inhibiting Pyroptosis and Improving Lung Injury in Mice with Systemic Lupus Erythematosus #br#

LI Mingyuan, MENG Yan, WU Yun

Journal of Medical Molecular Biology 2024, 21 (1): 39-44. DOI: 10.3870/j.issn.1672-8009.2024.01.006

Abstract （365）

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Objective To investigate the effect of neutralizing antibody of high mobility groupprotein 1 (HMGB1) on lung injury in systemic lupus erythematosus (SLE) mice and the underlying mechanism. Methods Thirty MRL / lpr mice were randomly divided into 3 groups: MRL / lprgroup, MRL / lpr + anti-HMGB1 group and MRL / lpr + MCC950 group, with 10 mice in each group, and another 10 wild-type C57BL / 6 mice were taken as the control group. Mice in each group were administered for 4 weeks. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the lung histopathological changes and collagen fiber deposition in each group. The levels of interleukin-1β ( IL-1β), IL-6, IL-18 and tumor necrosis factor-α ( TNF-α) in alveolar lavage fluid of mice in each group were detected by enzyme-linked immunosorbent assay ( ELISA). The fluorescence expression of nucleotide-binding oligomerized domain-like receptor protein 3 (NLRP3) in lung tissues of mice in each group was observed by immunofluorescence staining. The expression levels of HMGB1 and NLRP3, apoptosis-related spect-like protein containing a CARD (ASC) protein, Caspase-1, gasdermin D ( GSDMD) in mice lung tissues were detected by Western blotting. Results The lung tissues in the MRL / lpr group showed serious pathological injury symptoms,the collagen fiber deposition area was significantly increased (P< 0. 05), and the levels of IL-1β,IL-6, IL-18 and TNF-α in alveolar lavage fluid were significantly increased, when compared withthose in the control group (P < 0. 05). In addition, the mean fluorescence intensity of NLRP3 in lung tissues in the MRL / lpr group was significantly increased (P< 0. 05), and the relative proteinexpression levels of HMGB1 and NLRP3, ASC, Caspase-1, GSDMD were significantly up-regulated when compared with those in the control group (P< 0. 05). The lung tissue injuries in the MRL /lpr + anti-HMGB1 group and the MRL / lpr + MCC950 group were significantly improved, and the collagen fiber deposition area was significantly reduced, when compared with those in the MRL / lprgroup (P< 0. 05). In addition, the levels of IL-1β, IL-6, IL-18 and TNF-α in alveolar lavage fluid in the MRL / lpr + anti-HMGB1 group and the MRL / lpr + MCC950 group were significantly decreased (P< 0. 05), the mean fluorescence intensity of NLRP3 in lung tissues was significantly decreased (P < 0. 05), and the relative protein expression levels of HMGB1 and NLRP3, ASC,Caspase-1, GSDMD in lung tissues were significantly down-regulated, when compared with those inthe control group (P< 0. 05). Conclusion HMGB1 neutralizing antibody can ameliorate lung injury in mice with SLE, which may be achieved by inhibiting pyroptosis.

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Corosolic Acid Inhibits Excess Proliferation and Induces Apoptosis of Human Ovarian Cancer Cells SKOV-3 #br#

SUN Zhe, WANG Junfeng, LI Huiying, YAO Huixin

Journal of Medical Molecular Biology 2024, 21 (1): 45-50. DOI: 10.3870/j.issn.1672-8009.2024.01.007

Abstract （274）

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Objective To investigate the effect of corosolic acid ( CRA) on the proliferationand apoptosis of human ovarian cancer cells SKOV-3 and its mechanism. Methods Cells were divided into 4 groups: Ctrl group, CRA-10 μmol / L group, CRA-20 μmol / L group, and CRA-50 μmol / L groups, each group was treated with corresponding concentration of CRA. CCK-8 assay was used to measure cell growth. Flow cytometry was used to detect cell apoptosis. The protein expression levels of Ki67, Cyclin D1, CDK6, Bcl-2, Bax, cleaved-caspase-3, cleaved-caspase-9, PI3K, AKT, p-AKT were determined by Western blotting. In addition, the cell line derived xenograft model was established by transplanting the human ovarian cancer cells SKOV-3 in nude mice, the volume of the tumors from the nude mice were measured, the rates of Ki67 or VEGF positive cellswere detected by immunohistochemistry. Results In cytological experiments, the cell growth levels, the Bcl-2 / Bax and p-AKT / AKT ratios, the protein expression levels of Ki67, Cyclin D1, CDK6, PI3K in the CRA groups (10, 20, 50 μmol / L) were decreased significantly, and the cell apoptosis rate, protein expression levels of cleaved-caspase-3 and cleaved-caspase-9 were increased notably, when compared with those in the Ctrl group. In animal experiments, the tumor volume, the rates of Ki67 or VEGF positive cells in the CRA groups (10, 20, 50 μmol / L) were decreased markedly, when compared with those in the Ctrl group. Conclusion Corosolic acid can inhibit the excess proliferation of SKOV3 cells, and induce their apoptosis, the mechanism may related to the inhibition of PI3K / AKT signaling pathway.

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Predictive Values of Serum CERP, SF, α-Klotho and FGF-23 in Progression of Albuminuria in Patients with Type 2 Diabetes #br#

ZHANG Qianjin, HU Jin’e, HU Yichuan

Journal of Medical Molecular Biology 2024, 21 (1): 51-56. DOI: 10.3870/j.issn.1672-8009.2024.01.008

Abstract （168）

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Objective To analyze the values of serum CERP, SF, α-Klotho and FGF-23 in predicting the progression of albuminuria in patients with type 2 diabetes (T2D). Methods A totalof 120 patients with T2D repeatedly admitted to the Department of Endocrinology of Shuyang Hospital for blood glucose control from June 2020 to May 2022 were selected for the retrospective cohort study. The hospitalization data during the index hospitalization and the readmission were used as the baseline data and follow-up data respectively. Patients were divided into 3 groups: non-albuminuria group, micro-albuminuria group, macro-albuminuria group, according to the albuminuria level of baseline data. The levels of CERP, SF α-Klotho and FGF-23 in patient of different groups were compared. The progression of albuminuria was evaluated according to the follow-up data, and the baseline clinical data and levels of CERP, SF, α-Klotho, FGF-23 between patients with and with out albuminuria were compared. The influencing factors of albuminuria progression were analyzed by logistic regression, and the predictive indicators of albuminuria progression were analyzed by ROCcurve. Results The levels of CERP, SF and FGF-23 were increased and the level of α-Klotho wasdecreased with the increase of the albuminuria level in T2D patients (P< 0. 05). The duration of diabetes in the T2D patients with albuminuria progression was longer than that in the T2D patients without albuminuria progression. The proportions of using metformin and SGLT2 inhibitor (SGLT2i) and the level of α-Klotho in the T2D patients with albuminuria progression were lower than those in the T2D patients without albuminuria progression, and the proportion of hypertension, the levels of FBG, UA, CERP, SF and FGF-23 in the T2D patients with albuminuria progression were higherthan those in the T2D patients without albuminuria progression (P< 0. 05). Logistic regression analysis showed that the elevated levels of CERP, SF and FGF-23 were risk factors for the progression of albuminuria, the use of metformin and SGLT2i and the increase of α-Klotho level were protective factors for the progression of albuminuria. ROC curve analysis showed that the levels of serum CERP, SF, α-Klotho and FGF-23 had predictive values for the development of albuminuria, the sensitivity and specificity by using the combined index in predicting the progression of albuminuriawere both higher than those by using single indexes. Conclusion Increased levels of serum CERP,SF, FGF-23 and decreased level of α-Klotho are related with the development of albuminuria in T2D patients. Those four serum indicators have predictive values for the progression of albuminuria.

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Identification of LTBP1 as Biomarker for Prognosis of Gastric Cancer and Its Correlation with Tumor Immune Microenvironment #br#

WANG Xiaorui, WANG Mizhu

Journal of Medical Molecular Biology 2024, 21 (1): 57-62. DOI: 10.3870/j.issn.1672-8009.2024.01.009

Abstract （235）

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Objective To explore the biological functions of latent transforming growth factor beta binding protein 1 (LTBP1) in the occurrence, development, and immune microenvironment ofgastric cancer. Methods The expression level of LTBP1 in gastric cancer was analyzed by using TCGA databases, the results were then validated in the gastric cancer tissues and the para-cancerous tissues. The association between LTBP1 expression level and the clinicopathological variables were analyzed by regression proportional analysis method. Cox regression analysis and Kaplan-Meier plots were used to assess the prognostic value of LTBP1 in gastric cancer. The correlation between the expression level of LTBP1 and the immune cells infiltration was analyzed by TIMER. Immunohistochemical staining was used to detect the expression level of LTBP1 protein in gastric cancer tissues and adjacenttissues. Results LTBP1 was significantly up-regulated in the gastric cancer tissues when comparedwith that in the normal samples. Its expression level was significantly correlated with the pathologic TNM stages. Higher LTBP1 expression indicated poor overall survival (OS) in patients with gastric cancer. We identified that LTBP1 expression had a positive correlation with 3 kinds of immune cells infiltration by TIMER. Immunohistochemical results showed that LTBP1 was significantly overexpressedin gastric cancer tissues. Conclusion LTBP1 can be a potential prognostic biomarker for gastric cancer patients and influences tumor immune microenvironment in gastric cancer.

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Effect of Breviscapine on Porphyromonas gingivalis Lipopolysaccharide Induced Injury in Human Gingival Fibroblasts #br#

CHAO Xiaoqin, ZHAO Guoting, DONG Zhenyao, MA Minying, YAO Yizhang

Journal of Medical Molecular Biology 2024, 21 (1): 63-68. DOI: 10.3870/j.issn.1672-8009.2024.01.010

Abstract （186）

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Objective To investigate the effect of breviscapine (BVP) on the Porphyromonasgingivalis lipopolysaccharide ( Pg-LPS, hereinafter referred to as LPS) induced injury in humangingival fibroblasts ( HGFs). Methods HGFs cells were cultured in vitro and divided into 5groups: control group, LPS group, LPS + BVP low-, medium- and high-dose groups. CCK-8 method was used to detect cell proliferation. ELISA method was used to detect the levels of inflammatory factors interleukin-1β ( IL-1β), tumor necrosis factor-α ( TNF-α), interleukin-6 ( IL-6 ) and the activity of superoxide dismutase (SOD). Western blotting method was used to detect the expression levels of cyclin D1, cyclin B1 and apoptosis-related B-cell lymphocytoma-2 ( Bcl-2 ), BCL-2-associated X protein (Bax), Caspase-3 proteins in cells. TBA colorimetric method was used to detect the level of malondialdehyde ( MDA) in cells. DCFH-DA method was used to determinethe level of reactive oxygen species ( ROS) in cells. Results The HGFs cell survival rate, thecell migration rate, the protein expression levels of Cyclin B1, Cyclin D1, Bcl-2 and the SOD activity in the LPS group were significantly decreased when compared with those in the control group (P< 0. 05). The apoptosis rate, the protein expression levels of Bax, Caspase-3, the levels of inflammatory factors TNF-α, IL-1β, IL-6, and the levels of MDA and ROS in the LPS group weresignificantly increased when compared with those in the control group (P< 0. 05). The cell survivalrate, the cell migration rate, the protein expression levels of Cyclin B1, Cyclin D1, Bcl-2 and SOD activity in the LPS + BVP low-, medium-and high-dose groups were significantly increased when compared with those in the LPS group, and the apoptosis rate, the protein expression levels of Bax, Caspase-3, the levels of inflammatory factors TNF-α, IL-1β, IL-6, and the levels of MDA and ROS in the LPS + BVP low-, medium- and high-dose groups were significantly decreased whencompared with those in the LPS group (P< 0. 05). Conclusion BVP can reduce LPS-induced HGFs injury through anti-inflammatory and antioxidant mechanism.

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Advances in Development and Function of Peripheral Glial Cells #br#

YU Yue#, DENG Hao#, LIU Simin#, QI Zhihui, YE Zhiming, LIU Mengjie, YAO Maojin

Journal of Medical Molecular Biology 2024, 21 (1): 69-76. DOI: 10.3870/j.issn.1672-8009.2024.01.011

Abstract （653）

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Glial cells are essential components of the central nervous system. There’s growingevidence that they play crucial roles in regulating brain function, supporting synaptic growth, and ensuring the blood-brain barrier remains intact. Furthermore, they are implicated in the development and progression of neurodegenerative conditions like Alzheimer’s and Parkinson’s disease, as well as other central nervous system-related inflammatory diseases. However, research on glial cells in peripheral organs has been under-investigated, and their developmental pathways and physiological functions remain to be elucidated. In this review, our main focus is on the origins and functions of glial cells in peripheral tissues. We also delve into the cellular and molecular processes they’re involved in when it comes to central nervous system diseases, aiming to shed more light on their role outside the brain.

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Advances in Novel Compounds and Targets Against Candida albicans #br#

WANG Yuxi, YANG Jing

Journal of Medical Molecular Biology 2024, 21 (1): 77-80. DOI: 10.3870/j.issn.1672-8009.2024.01.012

Abstract （470）

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In recent years, fungal infections have been rampant worldwide, affecting approximately hundreds of millions of people annually, with nearly 1. 5 million deaths, posing a significantthreat to human health. Candida albicans is one of the most important pathogens responsible for fungal infections, and it causes invasive candidiasis with a mortality rate of 40 % -50 % . However, the limited variety of available antifungal drugs and the increasing severity of drug resistance make theclinical treatment of Candida albicans particularly challenging. Therefore, it is particularly importantto search for new antifungal compounds and unique molecular targets for antifungal therapy. This review summarizes some novel antifungal compounds with significant potential against Candida albicansand some new antifungal targets in recent years.

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Advances in Long Non-coding RNA in Primary Glomerulonephritis #br#

ZHAO Yuanmei, HU Wengang, TAN Xiaohong, ZHANG E, DU Jing

Journal of Medical Molecular Biology 2024, 21 (1): 81-85. DOI: 10.3870/j.issn.1672-8009.2024.01.013

Abstract （183）

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Primary glomerulonephritis is a group of common renal disease syndromes, whichcan deteriorate the quality of life of patients and increase the risk of renal disease progression. Long non-coding RNA (lncRNA) is a kind of non-coding regulatory RNA that can regulate a variety of cell biological processes. More and more reports have confirmed that lncRNA is closely related to the occurrence and development of primary nephrotic syndrome. Further researches on the relationship between lncRNA and primary glomerulonephritis are expected to lay a theoretical foundation for finding new biomarkers and therapeutic targets for primary glomerulonephritis.

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Emerging Roles of Regulators of G Protein Signaling Proteins in Cancer #br#

ZHANG Xuanhe, YE Qing, ZHANG Shushan

Journal of Medical Molecular Biology 2024, 21 (1): 86-92. DOI: 10.3870/j.issn.1672-8009.2024.01.014

Abstract （322）

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G protein coupled receptors (GPCRs) belong to a superfamily of cell surface receptors, which activate heterotrimeric G proteins that transduce a vast variety of extracellular stimuli, including hormones, ions, organic molecules, and light into the intracellular “effectors” to generate cellular responses. It is widely accepted that GPCR signaling pathways have emerged as the critical mediators for oncogenic signaling. Regulators of G protein signaling ( RGS) proteins are key proteins in GPCR signaling regulations. Many members in the RGS family play pivotal roles in the development of malignant tumors and serve as important targets for cancer diagnosis, treatment and prognosis. This review introduces the structural features, biological effects, and regulatory mechanisms of the RGS family, highlights the recent studies of specific roles of RGS proteins in multiple cancer types, and further explains the general characteristics of RGS in Pan-cancer. In addition, this review summarizes the unique role of RGS in tumor microenvironments as well as the current efforts made on cancer therapy via targeting RGS proteins.

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Comparison of Protein Characteristics of Human WASH468 and WASH465 #br#

ZHENG Aixue, ZHANG Luping, TANG Tuo, LI Ping, HONG Xian, DENG Zhihui, WANG Tao

Journal of Medical Molecular Biology 2024, 21 (2): 93-99. DOI: 10.3870/j.issn.1672-8009.2024.02.001

Abstract （275）

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Objective To investigate the differences between two well recognized WiskottAldrich syndrome protein and SCAR homolog ( WASH) with different sequences. Methods Immunofluorescence, immunoprecipitation, and laser micro-irradiation were used to analyze the differences between WASH468 and WASH465 in localization patterns, the interaction with FAM21 or Ku proteins, the recruitment to DNA damage sites and the protein stabilities. To analyze the universality and conservation of the two types of WASH sequences, the WASH protein sequences in various organisms were compared, and the WASH coding sequences in various cell types commonly used forbiological and medical research were detected. Results Both WASH exhibited a similar way in localizing to endosome. WASH468 exhibited a stronger interaction with FAM21, and was more stable than WASH465. WASH465 exhibited a stronger interaction with Ku protein, and the recruitment of WASH465 to DNA damage sites was more robust than that of WASH468. The degree of similarity observed between the sequence of WASH468 in humans and the sequences of WASH in other organisms was significantly greater than that observed with WASH465. Moreover, the coding sequences of WASH in various cell types, which are commonly utilized in biological and medical research, exhibited concordance with the sequence of WASH468. Conclusion There are differences in the biological characteristics between WASH468 and WASH465, and WASH468 is significantly more universal and conserved than WASH465. Therefore, WASH468 is the conserved human WASH sequence.

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Role of Circulating Eosinophils Mediated by Plasma SPARC in Gastric Cancer: A Multivariable Mendelian Randomization Study and Mediation Analysis #br#

HAN Zhengxuan, YANG Chaogang, XIONG Hao, XIONG Bin,

Journal of Medical Molecular Biology 2024, 21 (2): 100-107. DOI: 10.3870/j.issn.1672-8009.2024.02.002

Abstract （368）

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Objective East Asia exhibits one of the highest global incidence rates of gastriccancer. The intricate relationship between peripheral blood immune cell counts and the onset and progression of gastric cancer is often obscured by reverse causality and confounders. This study employs Mendelian randomization analysis to mitigate associated biases, aiming to elucidate the causalconnection between peripheral immune cell counts and gastric cancer. Methods Both univariateand multivariate Mendelian randomization methods were employed to explore the causal relationship between diverse immune cell subtypes in peripheral blood and the risk of gastric cancer using data from Genome-wide association studies ( GWAS). Exposure factors included counts of white blood cells, granulocytes, neutrophils, eosinophils, basophils, lymphocytes, and monocytes. The primary approach for univariate Mendelian randomization analysis involved the inverse variance-weighted method. Afterwards, a two-step mediation analysis was conducted to investigate the potential roleof plasma proteins in this process. Results Mendelian randomization analysis revealed a causal relationship between lymphocytes ( OR = 1. 094, 95 % CI: 1. 009-1. 185, P = 0. 029) and eosinophils (OR = 0. 881, 95 % CI: 0. 813-0. 955, P = 0. 002 ) and the incidence of gastric cancer. Sensitivity analysis corroborated the reliability of these results. Furthermore, the association between decreased eosinophil counts and a reduced risk of gastric cancer persisted in multivariate Mendelian randomization analysis ( OR = 0. 807, 95 % CI: 0. 671-0. 970, P = 0. 023). Reverse causality was not significant. The secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix protein that involves in various cell-matrix interactions and cellular signaling pathways, playing a significant role in tumor development. The mediation analysis of 1 124 plasma proteins suggested that plasma SPARC might mediate the protective effect of eosinophils against gastric cancer(Beta = - 0. 030, 95 % CI: - 0. 072-0. 000, P = 0. 024). Conclusion Mendelian randomizationanalysis establishes eosinophil counts as an independent factor in diminishing the incidence of gastric cancer. Plasma SPARC acts as a mediator in this process, suggesting that circulating eosinophil count and plasma SPARC have the potential to become early clinical indicators and therapeutic targets for gastric cancer. The Mendelian randomization method effectively mitigates biases stemming from reverse causality and psychosocial factors. Nevertheless, additional research is imperative to validate its underlying biological mechanisms.

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Effect of PKM2 Neddylation Modification on Right Ventricular Fibrosis in Pulmonary Hypertension Rats #br#

GUO Wenyun, WANG Lixia, WANG Jinlin

Journal of Medical Molecular Biology 2024, 21 (2): 108-114. DOI: 10.3870/j.issn.1672-8009.2024.02.003

Abstract （888）

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Objective Exploring the effect of PKM2 neddylation modification on myocardial fibrosis in pulmonary hypertension rats. Methods SD rats were randomly divided into 3 groups: control group, model group, and MLN4924 group. Pulmonary arteries were detected by HE staining, and right ventricular fibrosis was detected by Masson staining. Primary cardiac fibroblasts were isolated from rats and the expression of α-Smooth muscle actin (α-SMA) was measured by immunofluorescence assay. The si-NC, si-PKM2, and pcDNA3. 1-PKM2 were transfected into the primary cardiac fibroblasts and the expression levels of PKM2, fibrosis related proteins Collagen Ⅰ , Collagen Ⅲ , MMP2, and MMP9 were detected by Western blotting. Immunoprecipitation assay was used to detect the PKM2 neddylation modification. Real time fluorescence quantitative PCR method was used to detect the mRNA expression level of PKM2 in the rat heart tissues. The degradation of PKM2 protein was detected by Western blotting, and the half-life of PKM2 was determined. Results The HE staining results showed that the space between pulmonary arterioles (fibrous layer) and intima (inner transport protein) in the model group was significantly widened and the intermediate layer were thickened. Masson staining showed that the collagen deposition was increased and the fibrosis was more severe in the model group when compared with those in the control group. The expression level of PKM2 protein in the model group was higher than that in the control group, while there was no significant difference in the mRNA expression level. PKM2 underwent neddylation modification in the right ventricular tissues of pulmonary hypertension rats. Knocking down Nedd8 in cardiac fibroblasts or inhibiting neddylation modification with MLN4924 could downregulate the expression levels of PKM2 and fibrosis related proteins Collagen Ⅰ , Collagen Ⅲ , MMP2, MMP9, etc. , promotingthe degradation of PKM2 protein [ (3. 03 ± 0. 23) - (11. 97 ± 0. 66) h, t = - 12. 82, P <0. 001] . However, the overexpression of Nedd8 could increase the expression level of PKM2 protein. The degree of right ventricular fibrosis and the expression level of α-SMA protein in theMLN4924 group were lower than those in the model group. Conclusion Neddylation modificationenhances the protein stability of PKM2, thereby promoting the process of right ventricular fibrosis inthe rat model of pulmonary arterial hypertension.

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LncHAGLR Promotes Inflammatory Response and Apoptosis of Chondrocytes in Osteoarthritis Rats by Targeting miR-26a and Activation of NF-κB #br#

MENG Xiaoyuan, Wuerkan Yeerken, WANG Zhigang, MA Le

Journal of Medical Molecular Biology 2024, 21 (2): 115-123. DOI: 10.3870/j.issn.1672-8009.2024.02.004

Abstract （222）

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Objective To investigate the effect and potential mechanism of long non-codingRNA HAGLR on the inflammatory response and apoptosis of chondrocytes in rats with osteoarthritis. Methods StarBase and luciferase gene reporter assay were used to predict and verify the interaction between lncHAGLR and miR-26a. To investigate the regulatory role of lncHAGLR on miR-26a expression, C518 cells were divided into 4 groups: si-lncHAGLR group, si-NC group, miR-26ainhibitor group, and inhibitor-NC group. Furthermore, to study whether lncHAGLR regulates in flammation and apoptosis in C518 cells by modulating miR-26a, C518 cells were divided into 5 groups: Control group, IL-1β group, IL-1β + si-NC group, IL-1β + si-lncHAGLR group, and IL-1β + si-lncHAGLR + miR-26a-inhibitor group. Real-time quantitative PCR ( qRT-PCR) was used to analyze the expression levels of lncHAGLR and miR-26a. The proliferation, cytotoxicity and apoptosis of C518 cells were detected by MTT, lactate dehydrogenase (LDH) Kit and flow cytometry (FCM). Western blotting assay was used to detect the protein expression levels of cleavedCASPASE3, NF-κB P65, and phosphorylated NF-κB P65 (P-NF-κB P65). The levels of releasedinflammatory factors (TNF-α and IL-6) were detected by ELISA. Results lncHAGLR directly targeted miR-26a. The expression level of lncHAGLR in the IL-1β group was significantly higher than that in the Control group, and the expression level of miR-26a was significantly lower than that inthe Control group (all P< 0. 05). In addition, cells in the IL-1β + si-lncHAGLR group had reducedIL-1β-induced chondrocyte inflammation, inhibited apoptosis, increased cell viabilities, decreased release of LDH, inhibited expression of cleaved-CASPASE3, and decreased secretions of TNF-αand IL-6 ( all P < 0. 05). Moreover, the expression level of P-NF-κB P65 was decreased (P<0. 05). Adding of miR-26a-inhibitor ( IL-1β + si-lncHAGLR + miR-26a-inhibitor group) reversedthe performances of cells in the IL-1β + si-lncHAGLR group (all P < 0. 05). Conclusion lncHAGLR promotes the inflammatory response and apoptosis of chondrocytes in osteoarthritis rats by inhibiting the activation of NF-κB through targeting miR-26a, suggesting that lncHAGLR may be avaluable therapeutic target for osteoarthritis treatment.

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Correlation Analysis of Serum Asprosin Levels and Elderly Patients with Type 2 Diabetic Nephropathy #br#

LIU Tian, FAN Jingjing, CHEN Mengnan, GUO Mengyuan, LU Hailong

Journal of Medical Molecular Biology 2024, 21 (2): 124-128. DOI: 10.3870/j.issn.1672-8009.2024.02.005

Abstract （354）

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Objective To analyze the correlation between serum Asprosin levels and elderlytype 2 diabetic nephropathy (DN) to provide clues for the search of new early indicators of DN inclinical practice. Methods A total of 183 patients with type 2 diabetes mellitus (T2DM) admittedto our hospital from August 2021 to March 2022 were included for this study. According to whether the patients have DN or not, the patients were divided into 2 groups: the T2DM group alone (85 cases) and the combined DN group (98 cases). Another 50 healthy patients were selected for the control group. The serum Asposin levels in each group was detected and the diagnostic efficacy of Asposin in early DN was analyzed. Results Asprosin levels were significantly higher in the T2DMgroup [ (1. 64 ± 0. 41) ng / mL] and the combined DN group [ (2. 45 ± 0. 52) ng / mL] whencompared with that in the control group [ (1. 15 ± 0. 23 ng / mL], and Asprosin level in the combined DN group was higher than that in the T2DM group (P < 0. 05). Asprosin level was positively correlated with the values of BUN, Cr, UA, HbA1c, FINS, HOMA-IR, UAER ( P < 0. 05 ) . The level of Asprosin, HbA1c and UAR were risk factors affecting the occurrence of DN ( P <0. 05). The area under the curve for the diagnosis of DN by Asprosin combined with UAER was0. 879 (95 % CI: 0. 813-0. 974, P < 0. 05), the diagnostic specificity was 84. 19 % , and thesensitivity was 94. 57 % . Conclusion Elderly DN patients exhibit higher expression of serum Asprosin levels, which may serve as an early diagnostic indicator for the presence of diabetic nephropathy in elderly type 2 diabetes patients.

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Role of CCDC25 Mediated Neutrophil Extracellular Traps in Promoting Proliferation, Migration and Invasion of Osteosarcoma Cells #br#

Muteli Maimaiti, XU Leilei, LI Wenqiang, YAN Feihua

Journal of Medical Molecular Biology 2024, 21 (2): 129-134. DOI: 10.3870/j.issn.1672-8009.2024.02.006

Abstract （287）

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Objective To investigate the role and underlying mechanisms of neutrophil extracellular traps ( NETs ) in the proliferation, migration, and invasion of osteosarcomacells. Methods A total of 20 osteosarcoma patients and 20 healthy subjects were enrolled. Levels ofPAD4 and H3cit in serum were measured by ELISA. Neutrophils were isolated from peripheral blood of both groups to compare NETs formation. Co-culturing experiments were conducted by incubating NETs with osteosarcoma cells (MG63), with the addition of DNA degrading enzyme DNaseⅠ . The groups included Control, NETs, and NETs + DNase Ⅰ groups. CCDC25 protein expression level was detected using Western blotting, cell proliferation was assessed using CCK-8 assay, and cell migration and invasion were evaluated using Transwell assay. MG63 cells were transfected with si-NC and si-CCDC25, then co-cultured with NETs, cells were then divided into 2 groups: si-NC and siCCDC25 groups. CCDC25 protein expression, cell proliferation, and invasion were assessed as described above. Results Compared to healthy subjects, osteosarcoma patients showed elevated levels of PAD4 and H3cit in serum ( P < 0. 05 ), indicating enhanced NETs formation capacity. Compared to the Control group, the NETs group exhibited elevated CCDC25 protein expressionlevel, increased cell proliferation and cell migration and invasion (P < 0. 05). The NETs + DNaseⅠ group showed reduced CCDC25 protein expression level, decreased cell proliferation, cell migration and invasion compared to the NETs group (P < 0. 05). The si-CCDC25 group, when compared to the si-NC group, demonstrated decreased CCDC25 protein expression level, cell proliferation, cell migration and invasion (P<0.05). Conclusion NETs activate osteosarcoma cell CCDC25 expression through released DNA, thereby promoting tumor cell proliferation, and cell migration and invasion.

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Effect of Sufentanil on Cervical Cancer Cell Cycle and Apoptosis Through Long Non-coding RNA CCAT1 #br#

WEN Xu, PANG Xiaoyi, WEN Yan, WANG Rong, DU Qian, XIAO Song

Journal of Medical Molecular Biology 2024, 21 (2): 135-140. DOI: 10.3870/j.issn.1672-8009.2024.02.007

Abstract （245）

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Objective To investigate the molecular mechanisms by which sufentanil affects cervical cancer (CC) cells. Methods Real-time quantitative PCR ( RT-qPCR) assay was used todetect the expression level of lncRNA CCAT1 in CC tissues and precancerous tissues, and in the cervical epithelial cells GH329 and CC cell lines (HeLa, CaSki, Siha and C4-1) . Subsequently, CC cells CaSki were randomly divided into 4 groups: blank group, sufentanil group, sufentanil + oe-NC group and sufentanil + CCAT1 group. RT-qPCR assay was then used to examine the expression level of lncRNA CCAT1 in each group. Cell Counting Kit-8 (CCK-8) assay was used to detect the cell proliferation ability. Flow cytometry was used to detect the changes of cell cycle and the cellapoptosis. Results lncRNA CCAT1 was highly expressed in CC tissues and the CC cell lines (HeLa, CaSki, Siha and C4-1) when compared with that in the precancerous tissues and that in theGH329 cells respectively (P < 0. 01) . The expression level of lncRNA CCAT1 in and the proliferation ability of CaSki cells were significantly decreased (P < 0. 01), while the proportion of cells in the G 0 / G1 phase and the apoptosis rate were significantly increased (P<0. 01) in the sufentanil groupwhen compared with those in the blank group. The expression level of lncRNA CCAT1 and the proliferation ability of CaSki cells in the sufentanil + oe-CCAT1 group were significantly increased (P < 0. 01), while the proportion cells in the G0 / G1 phase and cell apoptosis rate were significantly decreased (P<0. 01) when compared with those in the sufentanil + oe-NC group. Conclusion Sufentanil could blockthe CC cell cycle by decreasing lncRNA CCAT1 expression in CC cells, ultimately inhibiting the proliferative ability of CC cells and promoting cell apoptosis.

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Sennoside B Inhibits the Proliferation, Apoptosis and Invasion of Retinoblastoma HXO-Rb44 Cells via Wnt / β-catenin Pathway #br#

SUN Mengmeng, CUI Bokun, JIA Meng, RAN Liu, WANG Danrong, FENG Suting, ZHANG Hu, HAO Jianzhang

Journal of Medical Molecular Biology 2024, 21 (2): 141-145. DOI: 10.3870/j.issn.1672-8009.2024.02.008

Abstract （246）

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Objective To investigate the effect of sennoside B on proliferation, apoptosis, invasion and Wnt / β-catenin signaling pathway of retinoblastoma HXO-Rb44 cells. Methods HXORB44 cells were treated with different doses (0, 5, 10 and 20 μmol / L) of sennoside B, and the cells were randomly divided into four groups: Control group, sennoside B 5 μmol / L group, sennoside B 10 μmol / L group and sennoside B 20 μmol / L group. Cell viability was detected by MTT assay. Colony formation assay was used to detect the colony formation rate. Cell apoptosis rate was detected by flow cytometry. Cell invasion were detected by Transwell assay. Cell pellet-forming experiment was used to detect the diameters and numbers of cell pellets. The protein expression levels of Cleaved Caspase-3, Caspase-3, MMP-2, MMP-9, SOX2, OCT4, CD44, Wnt1, β-cateninwere detected by Western blotting. Results The cell viabilities and colony formation rates in thesennoside B 10 and 20 μmol / L groups were significantly decreased when compared with those in theControl group ( P < 0. 05), the cell apoptosis rates and cleaved Caspase-3 / Caspase-3 expression levels were significantly increased when compared with those in the Control group (P < 0. 05). Thenumbers of invaded cells and the protein expression levels of MMP-2 and MMP-9 were significantlydecreased in the sennoside B 10 and 20 μmol / L groups (P < 0. 05), the cell pellet diameters, thecell pellet numbers and the protein expression levels of SOX2, OCT4 and CD44 were significantly decreased (P< 0. 05), and the protein expression levels of Wnt1 and β-catenin were significantlydecreased in the sennoside B 10 and 20 μmol / L groups when compared with those in the Controlgroup (P< 0. 05). Conclusion Sennoside B can induce apoptosis, inhibit the proliferation, invasion and stem-like characteristics of retinoblastoma HXO-Rb44 cells, and inhibit the activation of Wnt / β-catenin signaling pathway.

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Resveratrol Inhibits Renal Fibrosis and Reduces Kidney Damage Caused by Unilateral Ureteral Obstruction #br#

ZHAN Hongyi, SONG Yaling, HE Shaolin, ZHOU Yangyang

Journal of Medical Molecular Biology 2024, 21 (2): 146-153. DOI: 10.3870/j.issn.1672-8009.2024.02.009

Abstract （302）

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Objective To investigate the effect of resveratrol on renal fibrosis and kidney damage induced by unilateral ureteral obstruction and its related mechanism. Methods Sprague-dawley( SD) rats and NRK-49F fibroblasts were used as experimental subjects for in vivo study and in vitrovalidation. In vivo, TIF rat model was establish by surgery to induce the unilateral ureteral obstruction in SD rats, and the rats were then randomly divided into 4 groups: sham operation + blankgroup, sham operation + resveratrol group, model + blank group and model + resveratrol group, 12rats in each group. In vitro: NRK-49F cells were treated with recombinant TGF-β1 (5 ng / mL) orresveratrol (10 and 100 μmol / L) and randomly divided into 4 groups: control group, TGF-β1 group, TGF-β1 + resveratrol low-dose group and TGF-β + resveratrol high-dose group. Masson’ s staining was used to detect total collagen deposition in the kidney. Immunohistochemical staining was used to detect the expression of E-cadherin, GFAP and Ki67 in the tissues. Immunofluorescence staining was used to detect the expression of Ki67 in cells. Western blotting was used to detect the expression level of Vimentin, N-cadherin, Racl, c-Myc, Bcl-2, Cyclin D1, α-SMA, type I collagen and type Ⅲ collagen, E-cadherin. Results Resveratrol could inhibit the excessive depositionof total collagen in kidneys of UUO rats, down-regulate α-SMA-positive myofibroblasts, reduce the expression of vimentin, type I and type Ⅲ collagen, and inhibit the up-regulation of Rac1, GFAP and down-regulation of N-cadherin. Resveratrol could significantly reduce the ratio of Ki67-positive cells in UUO rats and inhibit the expression level of c-Myc, Bcl-2 and cyclin D1. Resveratrol inhibited the activation of proliferation-related pathway Wnt / β-catenin. The in vitro experimentsshowedthat resveratrol treatment could reduce the proliferation of fibroblasts and TECs, thereby inhibiting

TGF-β1-mediated phenotypic transformation and ECM accumulation. Conclusion	Resveratrol in
hibits the activity of Wnt / β-catenin pathway and the accumulation of myofibroblasts, and reduces
renal tubulointerstitial fibrosis.

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Expressions of miR-144-3p and Its Target Gene PTEN in Ovarian Granule Cells and Their Functions in Patients with Polycystic Ovary Syndrome #br#

SU Jing, ZHANG Rongxue, ZHONG Jixiang, QIU Fenglong, JIA Yuanyuan, XUE Huiying

Journal of Medical Molecular Biology 2024, 21 (2): 154-160. DOI: 10.3870/j.issn.1672-8009.2024.02.010

Abstract （230）

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Objective To investigate the expressions of miR-144-3p and its target gene PTEN in ovarian granule cells and their functions in patients with polycystic ovary syndrome. Methods Twenty patients with PCOS and 20 controls were recruited. Granulosa cells were collected in both groups and the expression level of miR-144-3p in cells was analyzed. The target genes of miR-144-3p were predicted by TargetScan database, and the binding relationship was verified by dual luciferase gene reporter assay. The human ovarian granulosa cells ( KGN) were resuscitated and transfected with miR-144-3p mimic / mimic NC, or miR-144-3p inhibitor / inhibitor NC, or si-PTEN / siRNANC, and were then accordingly divided into 6 groups: miR-144-3p mimic group, mimic NC group, miR-144-3p inhibitor group, inhibitor NC group, si-PTEN and siRNA-NC group. Cell apoptosis was detected by TUNEL assay. RT-PCR and Western blotting method were used to detect the relative expression levels of miR-144-3p and PTEN. Results RT-PCR results showed that the expression level of miR-144-3p in the PCOS group was significantly lower than that in the control group(P< 0. 05). Flow cytometry results showed that the apoptosis rate of granulosa cells in the miR-144- 3p mimic group was significantly lower than that in the mimic-NC group (P< 0. 05), while the apoptosis rate of granulosa cells in the miR-144-3p inhibitor group was significantly higher than that inthe inhibitor-NC group (P< 0. 05). PTEN was predicted as the target gene of miR-144-3p by bioinformatics analysis, and the luciferase gene reporter experiments had confirmed that miR-144-3pcould specifically bind to the PTEN-3 ′ UTR and down-regulate the expression level of PTEN gene. RT-PCR assay results showed that the expression level of PTEN mRNA in the PCOS group was significantly higher than that in the control group (P < 0. 05), and was negatively correlated with the expression level of miR-144-3p (r = - 0. 91, P< 0. 001). The results of qRT-PCR and Westernblotting showed that the mRNA and protein expression levels of PTEN in the miR-144-3p mimicgroup were significantly lower than those in the NC mimic group (P< 0. 05), while the mRNA andprotein expression levels of PTEN in the miR-144-3p inhibitor group were significantly higher thanthose in the inhibitor NC group (P< 0. 05). Flow cytometry showed that the apoptosis rate of granulosa cells in the si-PTEN group was significantly lower than that in the siRNA-NC group ( P <0. 05), while the apoptosis rate of granulosa cells in the miR-144-3p inhibitor + si-PTEN group wassignificantly lower than that in the miR-144-3p inhibitor group (P < 0. 05). Conclusion The expression level of miR-144-3p in ovarian granule cells in PCOS patients is significantly reduced,while the expression level of PTEN gene is significantly increased, which may have promoted theapoptosis of ovarian granule cells in PCOS patients.

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Effect of SRPK1 on Malignant Progression of Triple Negative Breast Cancer Cells by Activation of the PI3K / AKT Pathway #br#

JIANG Li, WANG Huihui, KE Longzhu, LI Gongzhuo, LUO Li

Journal of Medical Molecular Biology 2024, 21 (2): 161-165. DOI: 10.3870/j.issn.1672-8009.2024.02.011

Abstract （240）

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Objective To explore the role of SRPK1 and PI3K / AKT signaling pathway in themalignant progression of triple negative breast cancer ( TNBC) cells. Methods The expressionlevel of SRPK1 in TNBC tissues and adjacent tissues was detected by immunohistochemistry. TNBCcell line MDA-MB-231 cells were divided into three groups: siSRPK1 group, siNC group andLY294002 group. The proliferation ability of MDA-MB-231 cells was detected by MTT assay. Transwell assay was used to analyze the invasion ability of MDA-MB-231 cells. The apoptosis rate of MDA-MB-231 cells was analyzed by flow cytometry. The expression of PI3K / AKT signalingpathway related proteins and SRPK1 protein were detected by Western blotting. Results The expression level of SRPK1 was increased in the TNBC tissues when compared with that in the adjacenttissues. The growth rates of MDA-MB-231 cells in the siSRPK1 and LY294002 groups were decreased when compared with that in the siNC group (P < 0. 05). The numbers of invasive MDA-MB- 231 cells in the siSRPK1 and LY294002 groups were significantly decreased (P < 0. 05). The apoptosis rates of MDA-MB-231 cells in the siSRPK1 and LY294002 groups were significantly increased (P< 0. 05). The protein expression levels of PI3K and AKT in MDA-MB-231 cells were significantly decreased in the siSRPK1 and LY294002 groups ( P < 0. 05). Conclusion SRPK1 is highly expressed in TNBC tissues. After inhibiting the expression of SRPK1, the proliferation and invasion ability of TNBC MDA-MB-231 cells are decreased, and the apoptosis rate is increased. This process is related to the regulation of SRPK1 on PI3K / AKT pathway.

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Research Progress on Role of let-7i-5p in Tumor #br#

OU Yong, DONG Jiaqi, WANG Ban, LI Yuanyuan, WANG Shukai, CHAO Xu

Journal of Medical Molecular Biology 2024, 21 (2): 166-170. DOI: 10.3870/j.issn.1672-8009.2024.02.012

Abstract （240）

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let-7i-5p is a member of non-coding small molecule RNA (miRNA), which inhibits tumor growth, proliferation and migration through multiple targets and signaling pathways. It also has the effect of regulating tumor microenvironment to delay cancer progression and improve tumor drug resistance. This article reviews the research progress of the mechanism of let-7i-5p in liver cancer, breast cancer, colon cancer, cervical cancer, nasopharyngeal cancer, kidney cancer and glioblastoma. It is expected to explore the role that let-7i-5p can play as a new tumor marker to provide a new strategy for tumor prevention and treatment.

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Advances in Gene Expression Regulatory Mechanism of Helicobacter pylori Virluence Factor CagA #br#

WANG Mengmeng, YU Mengchao, WANG Lili, ZHAO Zhenyu, DONG Quanjiang

Journal of Medical Molecular Biology 2024, 21 (2): 171-175. DOI: 10.3870/j.issn.1672-8009.2024.02.013

Abstract （377）

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About half of the global population has been found to be infected with Helicobacter pylori (H. pylori), with particularly high rates in developing countries. Currently, H. pylori infection has been listed as a high-risk factor for the development of gastric cancer. The pathogenesis of H. pylori infection is believed to be associated with complex interactions between environment factors, host susceptibilities, and bacterial pathogenicity. Therefore, this article reviews the molecularmechanism of the regulation of Helicobacter pylori independent factor cagA expression, in order tobetter understand the pathogenicity of cagA and to provide a theoretical reference for the future prevention and treatment of diseases caused by H. pylori.

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Research Progress on Glucocorticoids Induced Dysfunction of Trabecular Meshwork #br#

REN Jing, DUAN Shichao, CUI Huiling, WANG Di, ZHAO Rumeng, LI Haijun

Journal of Medical Molecular Biology 2024, 21 (2): 176-181. DOI: 10.3870/j.issn.1672-8009.2024.02.014

Abstract （286）

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Glucocorticoids (GCs) could induce the morphological changes and dysfunction oftrabecular meshwork tissues. The changes in the trabecular meshwork tissues of the glucocorticoids ( GCs) induced glaucoma is similar with those of the primary open angle glaucoma ( POAG). However, the pathogenesis of POAG is still unclear, elucidating how GCs induce morphological changes of trabecular meshwork and the increase of aqueous humor outflow resistance is beneficial for exploring the pathogenesis of POAG. The effects of GCs on trabecular meshwork are summarized in this review.

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Advances in Mechanism of Hypoxia in the Progression and Treatment Tolerance of Lung Cancer #br#

CHEN Keming, YU Wanjun, WANG Huaying, FU Zhongming

Journal of Medical Molecular Biology 2024, 21 (2): 182-186. DOI: 10.3870/j.issn.1672-8009.2024.02.015

Abstract （287）

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Hypoxia is an intrinsic feature of lung cancer. It affects the metabolism, proliferationand migration of lung cancer through genomic and proteomic regulation, and up-regulates the tolerance of lung cancer to radiotherapy and induces the resistance of lung cancer to chemotherapy and immunotherapy through complex mechanisms, which make it an important factor leading to the poor prognosis of lung cancer. This article reviews the mechanism of hypoxia in the drug resistance of lung cancer and its potential application as a therapeutic target in the clinical treatment of lung cancer.

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Study of Mutual Regulation between TRIM21 and TRIM8 in Glioma U251 Cells#br#

WANG Lin∗ , LIU Xuemei∗ , LI Hui, HUANG Aixue, ZHAO Yuechao, XIAO Can, GAO Bo, SHAO Ningsheng

Journal of Medical Molecular Biology 2024, 21 (3): 187-195. DOI: 10.3870/j.issn.1672-8009.2024.03.001

Abstract （1008）

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Objective To explore the mutual regulation between TRIM21 and TRIM8 in glioma U251 cells. Methods TRIM21 and TRIM8 were overexpressed or knocked down respectively in U251cells, and their protein and mRNA expression levels were detected by Western blotting and RT-PCR respectively. Immunofluorescence experiment was used to analyze the subcellular localization of TRIM21 and TRIM8. The interaction between TRIM21 and TRIM8 was verified by immunoprecipitation experiment. The ubiquitination modification of TRIM21 or TRIM8 was analyzed by intracellular ubiquitination experiment. Protease inhibitor MG-132 was used to inhibit protease activity. U251 cell apoptosis was detected by flow cytometry assay. Results TRIM21 and TRIM8 could negatively regulate each other on theprotein level in U251 cells which resulted in cell apoptosis inhibition. Mechanism study showed that there was an interaction between TRIM21 and TRIM8 in U251 cells, that interaction furtherly activated ubiquitin-proteasome-dependent degradation pathway through ubiquitination. Conclusion Negatively mutualregulation between TRIM21 and TRIM8 is achieved through ubiquitination modification, following ubiquitin-proteasome-dependent degradation. Our results suggested that it is important to maintain a balance between TRIM21 and TRIM8 on protein level, that is, three might exist an E3 ubiquitin ligase protein homeostasis. The homeostasis disorder will be highly related to the tumorigenesis.

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Role of RIPK3 in LPS / D-GalN Induced Acute Liver Failure #br#

YU Qian, BIAN Shu, ZHANG Yuting, ZHAO Sai, LIU Liangming

Journal of Medical Molecular Biology 2024, 21 (3): 196-202. DOI: 10.3870/j.issn.1672-8009.2024.03.002

Abstract （558）

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Objective To study the role of receptor-interacting protein kinase 3 ( RIPK3) in acute liver failure induced by lipopolysaccharide / D-galactosamine (LPS / D-GalN). Methods SPFgrade male BALB / c mice were randomly divided into 3 groups (n = 5). The ALF animal model wasestablished by intraperitoneal injection of LPS combined with D-GalN. One hour before intraperitoneal drug injection, the mice were pretreated with intravenous injections of 0. 1 % DMSO and the RIPK3-specific antagonist GSK872 (dissolved in 0. 1 % DMSO), respectively. The degree of liver injury was assessed by blood biochemical tests and histological changes in the liver tissue. PCR was used to detect the expression levels of mRNA, while Western blotting and immunohistochemistrywas used to detect the expression levels of proteins. Results Animal experimental results showedthat LPS / D-GalN-challenged mice exhibited significant inflammatory hemorrhagic necrotic damageand increased infiltration of F4 / 80 + cells in liver tissues, and a notable elevation of ALT and AST levels in blood (both P < 0. 01) when compared with the control. In addition, the mRNA levels of F4 / 80, Mcp-1, Tnf-α, Il-6, Ripk3 and Mlkl, as well as the levels of RIPK3 protein and pMLKL / MLKL protein ratio, were all upregulated in liver tissues in comparison with the controlgroup, with all differences being statistically significant ( all P < 0. 05). Compared to the mice in the LPS / D-GalN group, the GSK872-pretreated mice displayed a marked reduction in the degree ofliver inflammatory injury, a significant decrease in the infiltration of F4 / 80 + cells in the liver, anda substantial decline in serum ALT and AST levels (both P < 0. 01). The mRNA levels of F4 / 80,Mcp-1, Tnf-α, Il-6, Ripk3, and Mlkl as well as the levels of RIPK3 protein and p-MLKL / MLKLprotein ratio, were all downregulated in liver tissues, with all differences being statistically significant (all P< 0. 05). Conclusion The RIPK3 inhibitor GSK872 can significantly block the expression of RIPK3 in LPS / D-GalN-induced ALF in mice, mitigate liver tissue damage and inflammatorycell infiltration, and suppress the expression of necroptosis-related proteins. This suggests thatRIPK3 might promote the pathogenesis of ALF by influencing the molecules of the hepatic necroptotic apoptosis pathway.

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All-trans Retinoic Acid Alleviates Endoplasmic Reticulum Stress and Improves Isoproterenol Induced Myocardial Fibrosis and Myocardial Remodeling in Rats #br#

WEI Junping, MENG Qingwen, LIN Daofei, LIN Yanzai, FU Dajia

Journal of Medical Molecular Biology 2024, 21 (3): 203-210. DOI: 10.3870/j.issn.1672-8009.2024.03.003

Abstract （323）

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Objective To investigate the effects of all-trans retinoic acid (ATRA) on myocardial fibrosis and myocardial remodeling induced by isoproterenol (ISO) in rats, and to analyze itsmechanism. Methods The rats were randomly divided into 4 groups: control group, ISO group,ATRA + ISO group, 4-phenylbutyric acid (4-PBA) + ISO group, with 10 rats in each group. Rats in the ATRA + ISO group and the 4-PBA + ISO group were administrated with ATRA and 4-PBA through intraperitoneal injection respectively. Rats in the ISO group, the ATRA + ISO group and the 4-PBA + ISO group were administrated with ISO through subcutaneous injection on the back. The left ventricular internal diameter in diastole ( LVIDd), left ventricular internal diameter in systole ( LVIDs), left ventricular ejection fraction (EF) and fractional shortening (FS) were detected by cardiac ultrasound. The body weight, whole heart mass and left ventricular mass of rats were weighed, and the whole heart mass index ( HMI) and left ventricular mass index ( LVMI) were calculated. The level of serum N-terminal pro B type natriuretic peptide ( NT-proBNP) was determined by ELISA. HE staining and Masson staining were used to observe the histopathological changes and the degree of collagen fibrosis in rat myocardial tissues, respectively. The protein expression levels of G protein-coupled receptor 78 (GRP78), C / EBP homologous protein (CHOP), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), and transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), Collagen-I and Collagen-Ⅲ in myocardial tissues were determined by Western blotting. Results When compared with those in the control group, the EF and FS in the ISO group were significantly decreased (P < 0. 05), the LVIDd, LVIDs, HMI and LVMI were significantly increased (P< 0. 05), the level of serum NT-proBNP was significantly increased (P< 0. 05), thepathological injury of myocardial tissues was observed, the areas with collagen fiber had significantlyincreased (P< 0. 05), the protein expression levels of GRP78, CHOP, PERK, P-EIF2α, TGF-β1, α-SMA, Collagen Ⅰ and Collagen Ⅲ in the myocardial tissues were significantly up-regulated(P< 0. 05). When compared with those in the ISO group, the EF and FS in the ATRA + ISO group and the 4-PBA + ISO group were significantly increased ( P < 0. 05), the LVIDd, LVIDs, HMI and LVMI were significantly decreased (P< 0. 05), and the level of serum NT-proBNP was significantly decreased (P< 0. 05), the degree of myocardial injury was significantly reduced, the area with collagen fiber had significantly reduced ( P < 0. 05 ), and the protein expression levels ofGRP78, CHOP, PERK, P-EIF2α, TGF-β1, α-SMA, Collagen Ⅰ and Collagen Ⅲ in the myocardial tissue were significantly down-regulated (P< 0. 05). Conclusion ATRA can alleviate ISOinduced myocardial injury and fibrosis, inhibit myocardial remodeling and improve cardiac function through the inhibition of endoplasmic reticulum stress response.

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HDAC3 Inhibitor RGFP966 Alleviates Endometrial Fibrosis by Regulation of AIM2 Inflammasome and EMT through TGF-β1 / SMAD3 / STAT-1 Signaling Pathway #br#

LU Jianjun, ZHANG Xinyue

Journal of Medical Molecular Biology 2024, 21 (3): 211-216. DOI: 10.3870/j.issn.1672-8009.2024.03.004

Abstract （220）

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Objective To investigate the molecular mechanisms of HDAC3 inhibitor RGFP966 in alleviating endometrial fibrosis. Methods A total of 18 female SD rats (6-8 weeks) were randomly divided into 3 groups: Control group, IUA Model group (intrauterine adhesion rat Model), and RGFP966 Treatment group ( IUA model group rats were treated with HDAC3 inhibitor RGFP966), with 6 rats in each group. IUA rat model was established. ELISA was used to determine the levels of the serum inflammatory cytokines TNF-α, IL-1β and IL-6. qPCR was used to determine the relative mRNA expression levels of EMT markers E-cadherin, N-cadherin, α-SMA and Vimentin. Western blotting was used to determine the protein expression levels of TGF-β1, SMAD3, phosphorylated STAT-1, STAT-1, AIM2, IL-18, cleaved IL-1β and IL-1β. Results The walls of uterine horn in the IUAModel group were thinner, the levels of serum inflammatory cytokines TNF-α, IL-1β and IL-6 were increased when compared with those in the Control group (P<0. 05). The relative expression levels of Ecadherin mRNA were decreased, while the relative expression levels of N-cadherin, α-SMA and Vimentin mRNA were increased (P < 0. 05). The expression levels of TGF-β1, SMAD3, p-STAT-1 were enhanced (P < 0. 05). And the expression levels of AIM2, IL-18, cleaved IL-1β were increased (P <0. 05). The above indicators were partially reversed in RGFP966 Treatment group when compared withthose in the IUA Model group (P<0. 05). No significant differences in the expression levels of STAT-1and IL-1β were seen among the three groups (P >0. 05). Conclusion HDAC3 inhibitor RGFP966 canalleviate endometrial fibrosis by down-regulating TGF-β1/ SMAD3/ STAT-1 signaling pathway to inhibitAIM2 inflammasome activation and EMT.

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Effect of Insulin-like Growth Factor 1 Gene Transfected Bone Marrow Mesenchymal Stem Cells on Fracture Healing and Angiogenesis #br#

WANG Gui, LI Zuncheng, LIU Jingxin, CHEN Yuxing

Journal of Medical Molecular Biology 2024, 21 (3): 217-223. DOI: 10.3870/j.issn.1672-8009.2024.03.005

Abstract （172）

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Objective To investigate the effect of insulin-like growth factor 1 ( IGF1) genetransfected bone marrow mesenchymal stem cells (BMSCs) on fracture healing and angiogenesis inrats. Methods The rat femoral fracture model was established, and the BMSCs with or withoutIGF1 gene transfection were used to treat the rats. X-ray imaging system and micro-CT scanner wereused to observe the fracture healing. HE staining was used to observe the histopathological changes offemur. Immunofluorescence staining was used to observe the expression of vascular endothelial marker CD31. Western blotting was used to detect the expression levels of bone morphogenetic protein 2( BMP-2 ), osteopontin ( OPN ), osteocalcin ( OCN ), vascular endothelial growth factor(VEGF) and angiopoietin-1 ( Ang-1). Results When compared with those in the model group,the fracture lines of the rats in the BMSC group and the IGF1-BMSC group were blurred and the formation of healing callus was observed, the values of BMD and BV / TV were increased (P < 0. 05), the value of Tb. N was increased (P < 0. 05), the value of Tb. Sp was decreased (P < 0. 05), theCD31 fluorescence expression was enhanced, the relative protein expression levels of BMP-2,OPN, OCN, VEGF and Ang-1 were all up-regulated ( P < 0. 05). When compared with those inthe BMSC group, the fracture line of rats in the IGF1-BMSC group was almost disappeared, andthe healing effect was better, the values of BMD and BV / TV were increased (P < 0. 05), the value of Tb. N was increased (P < 0. 05), the value of Tb. Sp was decreased (P < 0. 05), and CD31 fluorescence expression was stronger in the IGF1-BMSC group, the relative protein expression levelsof BMP-2, OPN, OCN, VEGF and Ang-1 were further up-regulated ( P < 0. 05). Conclusion IGF1 gene transfection with BMSC can effectively promote femoral fracture healing and acceleratevascular formation in rats, and the effect is better than that of BMSC alone.

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Expressions of CLEC1B, DKK1 and DRD4 in Primary Hepatic Cancer Tissues and Their Clinical Significance #br# #br#

DAI Yunlong, HUANG Jiwei

Journal of Medical Molecular Biology 2024, 21 (3): 224-230. DOI: 10.3870/j.issn.1672-8009.2024.03.006

Abstract （203）

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ObjectiveTo analyze the expression and clinical significance of C-type lectin domain family 1 member B (CLEC1B), Dickkopf 1 (DKK1) and dopamine receptor D4 (DRD4)in primary hepatic cancer ( PHC) tissues. Methods A retrospective study was conducted among138 patients who underwent liver cancer resection at West China Hospital of Sichuan University fromJanuary 2022 to January 2023 and were diagnosed with PHC by postoperative pathology. Paraffin-embedded specimens of the patients’cancer tissues and adjacent tissues were collected to analyze thedifferences in the expression of CLEC1B, DKK1 and DRD4, and their relationship with clinicopathological parameters. Pearson method was used to analyze the correlation among CLEC1B,DKK1, and DRD4. Results The expression levels of CLEC1B and DRD4 in the liver cancer tissues were lower than those in the adjacent tissues. The expression level of DKK1 protein in the livercancer tissues was significantly higher than that in the adjacent tissues (P < 0. 05). The above threeproteins were mainly distributed in the cytoplasm. Low expression of CLEC1B were found in 97 cases(70. 29 % ), high expression of DKK1 in 91 cases (65. 94 % ), and low expression of DRD4 in78 cases (56. 52 % ). The low expression of CLEC1B in PHC patients was closely related to thepreoperative AFP level, vascular invasion, distant metastasis, and tumor bleeding ( P < 0. 05).The high expression of DKKI was closely related to the preoperative AFP level, BCLC Kinki staging, tumor number, and tumor size (P< 0. 05). The low expression of DRD4 was closely related tothe preoperative AFP level, tumor number, tumor size, satellite nodule, and vascular invasion(P< 0. 05). Pearson correlation analysis found that the expression levels of CLEC1B, DRD4 and DKK1 in PHC patients were negatively correlated (r = - 0. 809, r = - 0. 774, P < 0. 001). The expression levels of CLEC1B and DRD4 were positively correlated ( r = 0. 748, P < 0. 001 ). Conclusion CLEC1B and DRD4 are lowly expressed in the PHC tissues, and DKK1 is highly expressed, and their expression changes are all related to the clinicopathological parameters. CLEC1B, DKK1, and DRD4 may be involved in the occurrence and development of PHC. Therefore, they are worthy of detection.

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Formononetin Inhibits Proliferation, Migration and Invasion of Esophageal Carcinoma Cells by HNF4A #br#

ZHOU Jincai, ZANG Ting , LI Zhao , YANG Zhao , LI Wenhai

Journal of Medical Molecular Biology 2024, 21 (3): 231-238. DOI: 10.3870/j.issn.1672-8009.2024.03.007

Abstract （189）

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Objective To analyze the mechanism of formononetin on inhibiting the proliferation, migration and invasion of esophageal carcinoma (EC) cells by hepatocyte nuclear factor 4α(HNF4A). Methods It was concluded by network pharmacology analysis that HNF4A might beone of the targets of formononetin. The expression level of HNF4A was closely related to clinical phenotypes of EC. EC109 and KYSE510 were treated with different concentrations of formononetin. The relative survival rate of cells was detected by CCK8. The cells proliferation was detected by CCK-8. The cancer cells were cultured by cells cloning assay. The number of colony cells before and afterformononetin treatment was detected. The migration and invasion of EC109 and KYSE510 cells before and after formononetin treatment were detected by transwell assay. Nude mice were subcutaneously injected with tumor cells and treated with formononetin to observe the changes in volume andweight of xenograft tumors. The expression level of Ki67 protein in xenograft tissues was detected byimmunohistochemistry. The effect of formononetin on the expression of HNF4A gene were detected byWestern blotting. EC109 and KYSE510 cell lines with stable overexpression of HNF4A were constructed and treated with formononetin to observe the effect on the expression of HNF4A. Results After formononetin treatment, the relative survival rates of EC109 and KYSE510 cells were significantly decreased (P< 0. 05). Compared with that of cells without formononetin treatment, the relative survival rate of cells was significantly decreased after treated with formononetin (≥150 μmol / Lfor EC109 cell line, and ≥ 120 μmol / L for KYSE510 cell line) ( P < 0. 05). The proliferation,migration and invasion of EC109 and KYSE510 cells in the formononetin group was significantly decreased when compared with those in the control group (P< 0. 05). The volume and weight of xenograft tumors were significantly decreased in the formononetin group (P< 0. 05), and the expression level of Ki67 protein was significantly lower than that in the control group (P< 0. 05). The effect offormononetin on the down-regulation of HNF4A protein was dependent on the concentration and time of the treatment. HNF4A overexpression could promote cells proliferation, invasion and migrationwhich were inhibited by formononetin (P< 0. 05). Conclusion formononetin can inhibit the proliferation, migration and invasion of EC cells by regulation of HNF4A.

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Effect of miR-592 on Migration, Invasion and Autophagy of Renal Cell Carcinoma via Targeting PRDM5 #br#

LI Shunlai, SONG Xiaolin, JIANG Tingqi, WANG Wenzhen

Journal of Medical Molecular Biology 2024, 21 (3): 239-246. DOI: 10.3870/j.issn.1672-8009.2024.03.008

Abstract （191）

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Objective To explore the effect of miR-592 on the migration, invasion and autophagy of renal cell carcinoma ( RCC) via targeting PR domain zinc finger protein 5 ( PRDM5).Methods RT-qPCR and Western blotting were used to detect the expression levels of miR-592 andPRDM5 mRNA and protein in RCC tissues and cells. A498 and 786-O cells were divided into 4groups: anti-miR-NC group, anti-miR-592 group, anti-miR-592 + si-NC group and anti-miR-592 + si-PRDM5 group. RNA immunoprecipitation (RIP) was used to determine the combination of miR-592 and PRDM5. CCK-8, wound-healing assay and transwell test were used to analyse the cell proliferation, migration and invasion. Transmission electron microscopy was used to observe the autophagosome formation. Western blotting was used to detect the expression levels of PRDM5, matrix metalloproteinase ( MMP ) -2, MMP-9, Beclin1, microtubule-associated protein 1 light chain 3( LC3) Ⅱ / Ⅰ . Nude mice model of transplanted tumors was established to analyze the effect of knocking down miR-592 on the growth of transplanted tumors. Results PRDM5 mRNA and protein expression levels in the RCC tissues and cells were decreased (P< 0. 05). After knocking down the expression of miR-592, the cell A450 value, the number of migrated and invaded cells, the expression levelsof MMP-2 and MMP-9 were decreased, while the number of autophagosomes, the expression levels ofBeclin1 and LC3 II / I were increased (P< 0. 05). Knocking down the expression of PRDM5 could partially reverse the effect of miR-592 knock-down on cell proliferation, invasion and autophagy (P <0. 05). Knocking down the expression of miR-592 could inhibit the growth of transplanted tumors innude mice (P<0. 05). Conclusion miR-592 promotes the proliferation, invasion and migration ofRCC cells, and inhibits autophagy by targeting the expression of PRDM5.

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Mechanism of LINC00319 Regulating PENK / PI3K / AKT Signaling Pathway in Osteosarcoma #br#

XIA Fei, ZHANG Haiping

Journal of Medical Molecular Biology 2024, 21 (3): 247-253. DOI: 10.3870/j.issn.1672-8009.2024.03.009

Abstract （253）

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Objective To explore the mechanism of LINC00319 regulating PENK / PI3K / AKTsignal pathway in osteosarcoma (OS). Methods The expression levels of LINC00319 and PENK inthe peripheral blood RNAs from OS patients and non-OS patients were detected using qPCR, and the correlation between LINC00319 and PENK expression were analyzed. Knockdown or overexpression of LINC00319 were performed in the MG63 cells, and the mRNA and protein expression levels of PENK were detected using qPCR and Western blotting methods, respectively. The mouse OS transplanted tumor model was established and mice were divided into 2 groups: shNC group and shLINC00319 group. The tumor weight was measured, and the expression levels of PENK, AKT, p-AKT, and PI3K in the tumor tissues were detected through immunohistochemistry experiments. MG63 cells were divided into 3 groups: shNC group, shLINC00319 group, shLINC00319 + shPENK group. Cell proliferation was detected by EdU. Cell invasion was detected via transwell method. The protein expression levels of AKT, p-AKT, and PI3K were detected using Westernblotting. Results The expression level of LINC00319 was higher in the peripheral blood of OS patients, and the expression level of PENK was lower when compared to those in the peripheral blood of non-OS patients. The expression level of PENK was negatively correlated with the expression level of LINC00319. After knocking down LINC00319, PENK mRNA and protein levels were upregulated, while overexpression of LINC00319 resulted in decreased expression level of PENK mRNA and protein. Compared to mice in the shNC group, mice in the shLINC00319 group showed decreased tumor weight, unchanged expression level of AKT protein in tumor tissues, and deceased expression levels of p-AKT, PI3K protein. Compared to cells in the shNC group, MG63 cells in the shLINC00319 group showed decrease abilities in cell proliferation and invasion, the expression levels of p-AKT and PI3K proteins were decreased in the shLINC00319 group as well. Cells in the shLINC00319 + shPENK group showed increase abilities in cell proliferation and invasion, and the expression levels of p-AKT and PI3K proteins were increased when compared to those in theshLINC00319 group. Conclusion LINC00319 is highly expressed in the peripheral blood of OS patients, while PENK is lowly expressed in the peripheral blood of OS patients, and their expression levels are negatively correlated. LINC00319 promotes OS cell proliferation and invasion by inhibiting PENK levels and activating the PI3K / AKT signaling pathway.

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Effect of Blocking PI3K / Akt / mTOR Signaling Transduction on Leukemia HL-60 Cells #br#

GUO Chen, TANG Jing

Journal of Medical Molecular Biology 2024, 21 (3): 254-258. DOI: 10.3870/j.issn.1672-8009.2024.03.010

Abstract （127）

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Objective To investigate the effect of blocking PI3K / Akt / mTOR signaling on leukemia cells. Methods Acute myeloid leukemia cell line HL-60 was selected, cells were randomly divided into 4 groups: blank control group, low concentration group, medium concentration group and high concentration group. Cells in the blank control group was given normal saline, cells in the low concentration group, medium concentration group and high concentration group were treated with 10, 25 and 50 Pmol / L PI3K / Akt / mTOR signaling blocker GDC-0349. CCK-8 method was used to detect the cell proliferation. Cell apoptosis was detected by flow cytometry, and the expression level of PI3K / Akt / mTOR and apoptosis related proteins were detected by Western blotting. Results Compared with those in the low and medium concentration groups, the absorbance ratios (A values) of cells in the high concentration group at 24, 48 and 72 h time-points were significantly lower (P < 0. 05). The apoptosis rates of cells in the low, medium and high concentration groups were significantly higher than that of cells in the blank control group ( P < 0. 05), and theapoptosis rate of cells in the high concentration group was significantly lower than those of cells inthe low and medium concentration groups (P < 0. 05). The relative expression levels of P110, Aktand mTOR in the high concentration group were significantly lower than those in the blank controlgroup, low and medium concentration groups (P < 0. 05). The relative expression levels of Bcl2 andCaspase3 proteins in the low, medium and high concentration groups were significantly lower thanthat in the blank control group (P < 0. 05). The relative expression levels of Bcl2 and Caspase3 in the high concentration group were significantly lower than those in other groups (P < 0. 05). Conclusion Blocking PI3K / Akt / mTOR signaling can inhibit the proliferation and promote the apoptosis of HL-60 cells.

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Expressions of miRNA-218 and miRNA-21 in Gastric Cancer Patients with Helicobacter pylori Infection and Their Clinical Significance #br#

ZOU Ling, ZHANG Heng, WU Jian, LIN Wei, CHEN Xin

Journal of Medical Molecular Biology 2024, 21 (3): 259-263. DOI: 10.3870/j.issn.1672-8009.2024.03.011

Abstract （149）

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Objective To explore expressions of miRNA-218 (miR-218) and miR-21 in gastric cancer related to Helicobacter pylori (Hp) infection and their clinical significance. Methods A total of 104 patients with gastric cancer undergoing surgical resection were enrolled. The relationship between miR-218, miR-21 and clinicopathological factors and postoperative recurrence was analyzed. Results The expression Level of miR-218 was lower in the Hp-positive group than in theHp-negative group, while the expression level of miR-21 and the 2-year recurrence rate were higherin the Hp-positive group (P < 0. 05). The expression level of miR-218 was lower in the gastric cancer tissues than in the para-carcinoma tissues, while the expression level of miR-21 was higher in thegastric cancer tissues (P < 0. 05). The expression levels of miR-218 and miR-21 were correlated withthe differentiation degree, TNM staging, depth of tumor invasion, lymph node metastasis and progression-free survival rate, which were of high predictive value for the 2-year recurrence situation after surgery. Conclusion The expression levels of miR-218 and miR-21 are different between gastric cancer patients with or without Hp-infection. The abnormal expressions of miR-218 and miR-21 are related with the clinicopathological factors and prognosis of gastric cancer patients with Hp infection.

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GSK484 Inhibits Neutrophil Extracellular Traps Formation and Inflammatory Response in Ankylosing Spondylitis #br#

LI Rulin, DU Zhuangwen, WANG Enliang

Journal of Medical Molecular Biology 2024, 21 (3): 264-269. DOI: 10.3870/j.issn.1672-8009.2024.03.012

Abstract （342）

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Objective To investigate the effect of GSK484 on neutrophil extracellular traps(NETs) formation and inflammatory response in ankylosing spondylitis (AS) and its related mechanisms. Methods The levels of PAD4, H3cit, IL-1β, IL-6, and the formation of NETs were assessedin peripheral blood from AS patients and healthy subjects. Thirty Balb/ c mice were divided into 3 groups: control, model, and GSK484 treatment groups. The model and GSK484 treatment groups were subjected to an AS model induction, followed by oral administration of 4 mg / kg GSK484 for a week in the treatment group, while the other groups received an equivalent volume of saline. Ankle joint damage scores, NETs levels, and the levels of PAD4, H3cit, IL-6, and IFN-γ were compared among the groups aftertreatment. Results Compared to healthy subjects, AS patients showed elevated levels of PAD4, H3cit,IL-1β, IL-6, and increased formation of NETs. The GSK484 treatment group exhibited reduced ankle joint damage scores, NETs formation, and levels of PAD4, H3cit, IL-1β, IL-6 compared to the modelgroup. Conclusion GSK484 inhibits the formation of NETs, offering a new therapeutic strategy for alleviating the inflammatory response in AS.

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Changes of LECT2 and FGF21 Levels in T2DM Patients Complicated with NAFLD and Their Clinical Significance #br#

LU Junru, HOU Kaiwen, WANG Deying

Journal of Medical Molecular Biology 2024, 21 (3): 270-274. DOI: 10.3870/j.issn.1672-8009.2024.03.013

Abstract （189）

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Objective To investigate the changes and clinical significance of serum leukocytederived chemotaxin 2 (LECT2) and fibroblast growth factor 21 (FGF-21) in patients with type 2diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease ( NAFLD). Methods A total of 142 T2DM patients admitted to the General Hospital of the Western Theater Region of the People’s Liberation Army of China from October 2019 to October 2021 were divided into 2 groups according to whether complicated with NAFLD: with-NAFLD group (68 cases) and without-NAFLD group (74 cases). Clinical indicators of the patients were collected, and the levels of LECT2 and FGF-21 were detected by ELISA. The differences in clinical indicators between the two groups were compared, and the correlations between the levels of LECT2 and FGF-21 and the other clinical indicators were analyzed. Logistic regression analysis was used to analyze the independent influencing factors of T2DM with NAFLD. ROC curve was used to analyze the efficacy of each variable in predicting T2DM with NAFLD. Results The values of BMI, WHR, SBP, DBP, FPG, FINS, FCP,HbAlc, HOMA-IR, TC, TG, LDL-C, ALT, AST, GGT, LECT2 and FGF21 in the withNAFLD group were higher than those in the without-NAFLD group, the values of HOMA-β andHDL-C were lower than those in the without-NAFLD group (P< 0. 05). Correlation analysis showedthat the level of LECT2 was positively correlated with the values of BMI, WHR, FPG, FINS, FCP, HbAlc, HOMA-IR, TC, GGT, and was negatively correlated with the values of HOMA-βand HDL-C (P<0. 05). The level of FGF21 was positively correlated with the values of FPG, FINS,FCP, HbAlc, HOMA-IR, TC and TG, but negatively correlated with the values of HOMA-β andHDL-C (P<0. 05). Logistic analysis showed that HOMA-IR, HDL-C, LECT2 and FGF21 were independent influencing factors of T2DM with NAFLD (P<0. 05). ROC curve analysis showed that theoptimal truncation values of LECT2 and FGF21 for predicting T2DM with NAFLD were 30. 72 ng / mL and 138. 66 ng / L, with 72. 61 % and 71. 36 % sensitivity and 72. 54 % and 73. 75 % specificity, respectively. The AUC values for LECT2 and FGF21 were 0. 732 and 0. 753, respectively. And the combined sensitivity, specificity and AUC values were 85. 72 % , 87. 44 % and 0. 863, respectively(P<0. 001). Conclusion LECT2 and FGF-21 are correlated with insulin resistance indicators andlipid levels, which can be used as indicators to predict T2DM with NAFLD.

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Canagliflozin Alleviates Renal Fibrosis in Diabetic Nephropathy Mice by PDGF / SIRT1 #br#

ZENG Weixin, YUN Chuan, LI Xiaoyan, LI Dawei

Journal of Medical Molecular Biology 2024, 21 (3): 275-279. DOI: 10.3870/j.issn.1672-8009.2024.03.014

Abstract （236）

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Objective To investigate the potential mechanism of canagliflozin alleviating renal fibrosis in diabetic nephropathy mice through PDGF / SIRT1. Methods The diabetic nephropathymouse model was established using streptozotocin ( STZ), and the following groups were set up:① control mice, ② STZ mice, ③ STZ mice treated with canagliflozin, ④ BSA treated STZ mice,⑤ STZ treated with PDGF antibody, ⑥ STZ mice co-treated with canagliflozin and BSA, ⑦ STZmice co-treated with canagliflozin and PDGF antibody. The kidney tissues and serum of mice in eachgroup were collected. The mRNA and protein expression levels of myofibroblast markers (type I collagen, fibronectin, α-SMA ) were detected. The mitochondrial biogenesis indicators ( the mitochondrial DNA copy number and the expression levels of key regulatory factors SIRT1 and differentsubunits of electron transport chain proteins) were analyzed. And the levels of serum PDGF weremeasured. Results STZ significantly enhanced the mRNA and protein expression levels of type Icollagen, fibronectin and α-SMA. However, the expression levels of these myofibroblast markerswere returned to normal levels after canagliflozin treatment. STZ reduced mitochondrial DNA copynumber, and canagliflozin prevented this decline. At the same time, STZ-induced reductions in SIRT1, PHB1, HSP60, VDHC, SDHA, and Cox IV were blocked by canagliflozin. Furthermore, the STZ-induced rise in PDGF level was restored by the presence of canagliflozin. The expression level of SIRT1 in the kidneys of STZ and PDGF co-treated mice was lower and the mRNA expression levels of myofibroblast markers were higher, when compared with those in the kidneys of of STZtreated mice. And there were no significant differences in the expression levels of SIRT1 and mRNA expression levels of myofibroblast markers in the kidneys of mice co-treated with STZ, PDGF and canagliflozin, when compared with those of the STZ mice co-treated with canagliflozin andBSA. Conclusion Canagliflozin therapy can reduce renal fibrosis in diabetic nephropathy mice andthe mechanism is dependent on the PDGF / SIRT1-mediated mitochondrial biogenesis axis.

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LINC01138 Regulates Proliferation, Migration, and Invasion of SW620 Colorectal Cancer Cells through Targeting miR-559 #br#

GAO Dongyun, SUN Ting, CHEN Ping, ZHOU Xuefeng

Journal of Medical Molecular Biology 2024, 21 (3): 280-286. DOI: 10.3870/j.issn.1672-8009.2024.03.015

Abstract （220）

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Objective To investigate the effect of LINC01138 on the proliferation, migration, and invasion of SW620 colorectal cancer cells and its mechanism. Methods RT-qPCR was used to detect the expression levels of LINC01138 and miR-559 in the human normal colonic mucosal cells (FHC) and the colorectal cancer cells (SW620). SW620 cells cultured in vitro were randomly divided into 6 groups: si-NC, si-LINC01138, si-LINC01138 + si-miR-559, mimic NC, miR-559 mimic and LINC01138 mimic + miR-559 mimic. CCK-8 assay, wound-healing assay, and transwellassay were performed to evaluate cell proliferation, migration, and invasion, respectively. The interaction between LINC01138 and miR-559 was validated using a dual-luciferase reporter assay. Results The expression level of LINC01138 was upregulated, while the expression level of miR-559 was downregulated in the SW620 cells when compared to those in the FHC. Inhibition of LINC01138 or upregulation of miR-559 attenuated the proliferation, migration, and invasion abilities of SW620 cells. Conclusion This study confirms the interaction between LINC01138 and miR-559 in colorectal cancer cells and reveals that LINC01138 regulates the proliferation, migration,and invasion of colorectal cancer cells through targeting miR-559. These findings provide new targetsand strategies for the treatment of colorectal cancer.

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Research Progress on Aspergillus fumigatus Associated C-type Lectin Receptor #br#

CHENG He, MIAO Guizhi, MA Yan

Journal of Medical Molecular Biology 2024, 21 (3): 287-292. DOI: 10.3870/j.issn.1672-8009.2024.03.016

Abstract （249）

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Aspergillus fumigatus (A. fumigatus) is the most prevalent airborne fungal pathogenand can cause fatal invasive aspergillosis in immunocompromised patients. The interaction of the pathogen with the host immune system is a key process in understanding pathogenicity. Recognition of conserved molecular structures on the surface of pathogens by conserved transmembrane or soluble pattern recognition receptors ( PRRs ) is referred to as pathogen-associated molecular patterns (PAMPs). C-type lectin receptors ( CLRs) are one of the major receptor families in PRRs, and CLRs can recognize fungal cell wall components such as β-glucan, mannose, and chitin through Ctype lectin-like domains ( CTLDs), thus inducing both innate and acquired immunity to clearpathogens. Currently, the main CLRs involved in A. fumigatus are Dectin-1, Dectin-2, MelLec, DC-SIGN, etc. These CLRs play a crucial role in host cell recognition of A. fumigatus, and novelanti-fumigatus drugs have been developed against Dectin-1 and Dectin-2. Therefore, further understanding of the effect of various CLRs associated with A. fumigatus and its mechanism and the relatedsignaling pathways will provide us new perceptions for the development of novel antifungal drugs. Inthis case, this paper presents a review of the latest research progress of CLRs related to Aspergillus fumigatus.

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GATA3 Inhibits Migration of Human Breast Cancer Cells by Regulating LIFR #br#

ZHANG Lu, ZHANG Rui, LIU Jun, YANG Angang

Journal of Medical Molecular Biology 2024, 21 (4): 293-299. DOI: 10.3870/j.issn.1672-8009.2024.04.001

Abstract （495）

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Objective To explore the effect of GATA binding protein 3 on the migration abilityof breast cancer cells. Methods Lentivirus-mediated GATA3-knockdown cell line was establishedto study the expression levels and function of GATA3 by performing real-time quantitative fluorescentPCR, Western blotting and Transwell assay in vitro. The binding sites of GATA3 in LIFR promoterregion was detected by Chromatin immunoprecipitation assay ( ChIP-qPCR) assay in MCF7 andT47D cells. LIFR was overexpressed in MCF7 cells with reduced GATA3 expression, and the migration capacity of MCF7 cells was measured by Wound healing assay and Transwell assay. Results Compared with the control group, the group of MCF7 cells that knocked down GATA3 had enhancedmigration ability (all P< 0. 05), and decreased expression of LIFR ( all P < 0. 05). ChIP-qPCRdata showed a physical binding of GATA3 on the promoter region of LIFR in MCF7 and T47D cells(all P< 0. 05). Overexpression of LIFR rescued the enhanced cell migration induced by depletion of GATA3 in MCF7 cells (all P< 0. 05). Conclusion GATA3 inhibits the migration of breast cancercells MCF7 through transcriptional activation of LIFR.

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Effect of miR-155 Target Gene CEBPβ on Apoptosis and Inflammatory Response of Intervertebral Disc Chondrocytes in Rat with Cervical Spondylosis through Regulation of NF-κB Signaling Pathway #br#

NA Qing, Tuersunayi Abudureyimu, WU Gang

Journal of Medical Molecular Biology 2024, 21 (4): 300-308. DOI: 10.3870/j.issn.1672-8009.2024.04.002

Abstract （188）

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Objective To explore the role and potential mechanisms of CCAAT-enhancerbinding protein β (C / EBPβtargeted by microRNA (miR) -155 in apoptosis and inflammatory response of rat intervertebral disc chondrocytes with cervical spondylosis. Methods Forty adult maleSD rats were randomly divided into 4 groups with 10 rats in each group: Sham group, CervicalSpondylosis group, Cervical Spondylosis + C / EBPβ overexpression group, and Cervical Spondylosis + empty vector group. Rat chondrocyte cell line, atdc5 cells, were divided into 6 groups: control group, tumor necrosis factor α ( TNF-α) stimulation group, empty vector + TNF-α group, C / EBPβ overexpression + TNF-α group, mimic-NC + C / EBPβ overexpression + TNF-α group, and miR-155 mimic + C / EBPβ overexpression + TNF-α group. The expression of miR-155, apoptosis-related proteins (cleaved-caspase3, Bax, Bcl-2, PPARγ), NF-κB signaling pathway proteins (pNF-κB P65, NF-κB P65, IκB), pro-inflammatory cytokines ( TNF-α, IL-6, IL-1β), and C / EBPβ in rat cartilage tissues and atdc5 cells were detected using qRT-PCR and Western blotting experiments. Dual-luciferase reporter gene assay was conducted to determine the targeted regulatoryeffect of miR-155 on C / EBPβ expression. Results miR-155, cleaved-caspase3, Bax, PPARγ,p-NF-κB P65, TNF-α, IL-6, and IL-1β were upregulated in the Cervical Spondylosis group when compared with those in the Sham group, while Bcl-2, IκB, and C / EBPβ were downregulated inthe Cervical Spondylosis group (P< 0. 05)Ceaved-caspase3, Bax, PPARγ, p-NF-κB P65, TNF-α, IL-6, and IL-1β were downregulated in the Cervical Spondylosis + C / EBPβ overexpression group when compared with those in the Cervical Spondylosis + empty vector group, while Bcl-2, IκB, and C / EBPβ were upregulated in the Cervical Spondylosis + C / EBPβ overexpression group(P< 0. 05), but there were no significant change in miR-155 expression level (P > 0. 05). There was a significant negative correlation between the expression levels of miR-155 and C / EBPβ in thecartilage of rats with cervical spondylosis (r = - 0. 721, P < 0. 05). The TNF-α group showed upregulations of miR-155, cleaved-caspase3, Bax, PPARγ, p-NF-κB P65, IL-6, and IL-1β expression (P< 0. 05), and downregulations of Bcl-2, IκB, and C / EBPβ expression when compared with the control group (P< 0. 05). The C / EBPβ overexpression + TNF-α group showed downregulations of cleaved-caspase3, Bax, PPARγ, p-NF-κB P65, IL-6, and IL-1β expression, and upregulations of Bcl-2, IκB, and C / EBPβ expression when compared with the empty vector + TNF-α group (P < 0. 05), but no significant change was observed in miR-155 expression level ( P >0. 05). The mimic + C / EBPβ overexpression + TNF-α group showed upregulations of miR-155,cleaved-caspase3, Bax, PPARγ, p-NF-κB P65, IL-6, and IL-1β expression ( P < 0. 05), anddownregulations of Bcl-2, IκB, and C / EBPβ expression when compared with the mimic-NC + C /EBPβ overexpression + TNF-α group ( P < 0. 05). Dual-luciferase reporter gene assay confirmedCEBPβ as a target gene of miR-155 in chondrocytes. Conclusion miR-155 promotes the activationof the NF-κB signaling pathway in intervertebral disc cartilage tissues and chondrocytes in rat withcervical spondylosis by inhibiting the target gene CEBPβ, which leads to enhanced apoptosis and inflammatory response.

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Effect of Extracellular Histone on Epithelial Mesenchymal Transformation and Invasion of Bladder Cancer Cells by Regulation of TLR4 / NF-κB Pathway #br#

HAN Zhijun, SHU Linfei, YI Xiangmeng, TAN Huajun, ZHENG Guoqiu, YANG Fan

Journal of Medical Molecular Biology 2024, 21 (4): 309-314. DOI: 10.3870/j.issn.1672-8009.2024.04.003

Abstract （206）

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Objective To investigate the effect of extracellular histone on epithelial mesenchymal transformation (EMT) and invasion of bladder cancer cells by regulating toll-like receptor 4(TLR4) / nuclear factor-κB (NF-κB) pathway. Methods T24 bladder cancer cells were culturedand divided into 7 groups: control group, histone H3 groups with different concentrations (50, 100, 200 μg / mL), solvent control (0. 1 % DMSO) group, histone H3 (200 μg / mL) + solvent control (0. 1 % DMSO) group, and histone H3 (200 μg / mL) + NF-κB inhibitor Bay11-7082 (10 μmol / L) group. The number of invasion cells and the protein expression levels of E-cadherin, N-cadherin, Vimentin, TLR4 and phosphorylated P65 NF-κB ( p-P65 NF-κB) were detected 24 h after administration. Results The number of invasion cells and the expression levels ofN-cadherin, Vimentin, TLR4 and p-P65 NF-κB in the histone H3 groups were higher than those inthe control group, and the protein expression level of E-cadherin was lower than that in the controlgroup (P < 0. 05), the number of invasion cells and the expression levels of those proteins werechanged with the concentration of histone H3 treatment in a dose-dependent manner. The number ofcell invasion and the protein expression levels of N-cadherin, Vimentin and p-P65 NF-κB in thehistone H3 + Bay11-7082 group were lower than those in the histone H3 + solvent control group,and the expression level of E-cadherin was higher than that in the histone H3 + solvent control group(P< 0. 05). Conclusion Extracellular histone promotes EMT and invasion of bladder cancer cells,which is related to the activation of TLR4 / NF-κB pathway.

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Effect of TLR2-mediated Microglia Activation and Neuroinflammation on Vascular Dementia Progression #br#

SUN Yangzi, WU Zhenyu, ZENG Chaosheng, YOU Yong

Journal of Medical Molecular Biology 2024, 21 (4): 315-322. DOI: 10.3870/j.issn.1672-8009.2024.04.004

Abstract （326）

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Objective To investigate the effect of TLR2 in mediating the pathological activation of microglia and neuronal injury in vascular dementia ( VaD) rat model and its molecularmechanisms. Methods In vitro experiments were carried out by using LPS-induced activation of human microglia cell line HMC3 cells. The proliferation ability of HMC3 cells was determined by CCK- 8 assay. Systemic TLR2 knockdown was performed by using Adv-TLR2 shRNA or Adv-shRNA NT. The VaD rat model was established by permanent bilateral common carotid artery occlusion (2VO) . The expression levels of TLR2, NF-κB, Iba-1, Claudin-5 and ZO-1 in HMC3 cells and rats’white matter tissues were determined by Western blotting. The levels of inflammatory cytokines IL-6, IL-1β and TNF-α, and the ferroptosis-related indicators of Fe2 + , malondialdehyde (MDA) and glutathione (GSH) in rats’white matter tissues were determined by ELISA. Morris water maze (MWM) test was used to determine rats’brain neuronal injury. Results The expression levels ofTLR2, NF-κB and Iba-1 in the LPS group were enhanced when compared with those in the Controlgroup (P< 0. 05). The expression levels of the above proteins in the Adv-TLR2 shRNA group were decreases when compared with those in the LPS groups ( P < 0. 05). The expression levels ofTLR2 / NF-κB and Iba-1 were up-regulated, and those of Claudin-5 and ZO-1 were down-regulatedin the white matter tissues of Model group rats, when compared with those of the Sham group, (P<0. 05). In addition, the levels of inflammatory cytokines IL-6, IL-1β and TNF-α were up-regulated(P< 0. 05), the Fe2 + and MDA levels were increased, and the GSH levels were decreased (P <0. 05). TLR2 knockdown had reversed the values of above indicators in the Model + Adv-TLR2 shRNA group when compared with those in the Model group (P< 0. 05). Morris water maze test showedthat rats in the Model group and Model + Adv-TLR2 shRNA group took longer time to find the targetquadrant (upper left quadrant) ( P < 0. 05), stayed shorter time in the target quadrant ( P <0. 05) when compared with those in the Sham group, the swimming routes of rats in the four quadrants of MWM were evenly distributed. Compared with Model group, the Model + Adv-TLR2 shRNAgroup showed a reversion in the values of above indicators and had a denser distribution of swimroutes in the target quadrant. Conclusion Knock-down of TLR2 could inhibit the activation of microglia and its mediated tight junction protein degradation and cerebrovascular barrier network leakage, and reduce nerve damage in the vascular dementia rat model.

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Effect of Knocking down Astrocyte Elevated Gene-1 on Diethylnitrosamine-induced Primary Hepatocellular Carcinoma in Rats #br#

CHEN Jianxiong, JI Ru, CAI Qing, ZHANG Qian

Journal of Medical Molecular Biology 2024, 21 (4): 323-328. DOI: 10.3870/j.issn.1672-8009.2024.04.005

Abstract （162）

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Objective To explore the effect of knocking down astrocyte elevated gene-1 (AEG-1 ) on diethylnitrosamine ( DEN ) -induced primary hepatocellular carcinoma ( PHC ). Methods A total of 60 rats were randomly divided into 4 groups: Control group, DEN group,AEG-1 NC KO DEN group and AEG-1 KO DEN group, 15 rats in each group. Rats were given intragastric administration of DEN to construct PHC models in each group except in the Control group, while rats in the Control group were given the same volume of normal saline. The rats in AEG-1 KO DEN group and AEG-1 NC KO DEN group were given intraperitoneal injection of HCCLM6 withstably transfected AEG-1 shRNA or shRNA-NC lentivirus expression vector, respectively. The liver cell damage, apoptosis, levels of superoxide dismutase ( SOD), malondialdehyde ( MDA) and glutathione peroxidase (GSH), liver function, levels of serum IL-6 and TNF-α, expressions of caspase-3 (Cas-3), caspase-9 ( Cas-9 ) and P65 in liver tissues were compared among eachgroup. Results The expression level of AEG-1 in the DEN group was significantly higher than that in the Control group ( P < 0. 05). The mortality of rats and incidence of ascites in the AEG-1 KO DEN group were lower than those in the DEN group ( P < 0. 05), and the levels of serum AST, ALT, IL-6 and TNF-α were lower than those in the DEN group ( P < 0. 05), SOD activity was higher than that in the DEN group (P< 0. 05), levels of GSH and MDA were lower than those in the DEN group (P< 0. 05), and expressions levels of cleaved cas9 / cas9, cleaved cas3 / cas3 and p-P65 / P65 were lower than those in the DEN group (P< 0. 05). Conclusion Knocking out AEG-1can reduce the levels of oxidative stress and inflammatory factors induced by DEN, relieve liver tissue damage and improve liver function in rats.

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Effect of MRPL21 on Activity of Non-small Cell Lung Cancer A549 Cells by Regulating YAP1 / TAZ Pathway #br#

FANG Hanlin, PAN Huaguang, CHEN Yu, ZHANG Renquan

Journal of Medical Molecular Biology 2024, 21 (4): 329-333. DOI: 10.3870/j.issn.1672-8009.2024.04.006

Abstract （187）

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Objective To investigate the effect of MRPL21 and YAP1 / TAZ pathway on theactivity of non-small cell lung cancer A549 cells, so as to provide new ideas for the treatment ofnon-small cell lung cancer. Methods Non-small cell lung cancer tissues and adjacent tissues were obtained from 9 patients with non-small cell lung cancer who underwent surgical treatment in the First Affiliated Hospital of Anhui Medical University between June, 2021 and September, 2023. Theexpression of MRPL21 in the tissues was analyzed by immunohistochemistry. A549 cells were randomly divided into three groups: siNC group, siMRPL21 group and BPD-MA group. CCK-8 assay and Hoechst staining were used to detect the proliferation of A549 cells. Transwell assay was used to analyze the invasion ability of A549 cells. TUNEL staining was used to detect the apoptosis of A549 cells. Western blotting assay was used to detect the expression levels of MRPL21, YAP1 and TAZproteins in A549 cells. Results The results of immunohistochemistry showed that the expression ofMRPL21 was up-regulated in the non-small cell lung cancer tissues compared with that in the adjacent tissues (P < 0. 05). Compared with the A549 cells in the siNC group, cells in the siMRPL21group and the BPD-MA group showed decreased proliferation ability as detected by CCK8 assay and Hoechst staining assay (P< 0. 05). Transwell assay showed that the invasion abilities of A549 cells in the siMRPL21 group and the BPD-MA group were decreased ( P < 0. 05 ). TUNEL stainingshowed that the apoptosis rates of A549 cells were increased in the siMRPL21 group and the BPDMA group (P< 0. 05). Western blotting results showed that the siMRPL21 group and the BPD-MA group had significant reduced protein levels of YAP1 and TAZ in A549 cells (P< 0. 05). Conclusion MRPL21 is highly expressed in non-small cell lung cancer tissues. After inhibiting the expression of MRPL21, the proliferation activity and invasion ability of A549 cells are weakened, and the apoptosis rate is increased, which is related to the regulation of YAP1 / TAZ signaling pathway. MRPL21 is expected to be a new target for the treatment of non-small cell lung cancer.

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Effect of miR-424 on Proliferation and Apoptosis of Multiple Myeloma Cells by Targeting FBXW7 #br#

DUAN Xiaojuan, XI Zhenfang, HOU Ruihong

Journal of Medical Molecular Biology 2024, 21 (4): 334-340. DOI: 10.3870/j.issn.1672-8009.2024.04.007

Abstract （152）

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Objective To investigate the effect of miR-424 on the proliferation and apoptosisof multiple myeloma ( MM) cells by targeting the F-box and WD repeat domain containing 7(FBXW7). Methods Real-time fluorescence quantitative PCR ( RT-qPCR) experiment was applied to detect the expression levels of miR-424 and FBXW7 in human normal bone marrow plasma cells and MM cell lines MM. 1S, RPMI 8226, U266. U266 cells were cultured in vitro and randomly separated into 5 groups: control group, miR-424 inhibitor group, FBXW7 overexpression group, negative control group, miR-424 inhibitor + FBXW7 knockdown group. Edu staining and TUNELstaining were applied to detect the cell proliferation and apoptosis, respectively. Western blotting assay was applied to detect the expression levels of proliferation related proteins ( Cyclin D1, PCNA), apoptosis related proteins (Bax, Bcl-2), and FBXW7 protein. A nude mouse model of multiple myeloma transplantation was constructed by subcutaneous inoculation of transfected U266 cells in the right axilla of nude mice, the growth of the transplanted tumors were detected and the transplanted tumor volume was compared on the 21st day. Dual luciferase reporter experiment was applied to verify the targeted regulatory effect of miR-424 on FBXW7 in U266 cells. Results In comparisonwith those in the normal human bone marrow plasma cells, the expression of miR-424 in theMM. 1S, RPMI 8226, and U266 cells were increased ( P < 0. 05 ), while the expression of FBXW7 mRNA were decreased ( P < 0. 05). In addition, when compared with the control group, the miR-424 inhibitor group and the FBXW7 overexpression group showed decreased cell proliferation rate, lower protein expression levels of Cyclin D1, PCNA and Bcl-2, and decreased transplanted tumor volume on the 21st day (P < 0. 05), and increased apoptosis rate, FBXW7 mRNA and protein expression levels, and Bax protein expression level ( P < 0. 05). There was no significant difference in the indicators in cells of the negative control group (P > 0. 05). Moreover, when compared with the miR-424 inhibitor group, the miR-424 inhibitor + FBXW7 knockdown group exhibited increased cell proliferation rate, Cyclin D1, PCNA and Bcl-2 protein expression, and transplanted tumor volume on the 21st day (P < 0. 05), and decreased apoptosis rate, FBXW7 mRNA and protein expression levels, and Bax protein expression level ( P < 0. 05). It was also observed that miR-424 was able to targetly downregulate FBXW7 expression in U266 cells. Conclusion Down-regulation of miR-424 can inhibit MM cell proliferation and growth in nude mice, and promote the apoptosis by up-regulating FBXW7 expression.

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Nerve Growth Factor Combined with BMSCs Exosomes Alleviates Neural Injury in Rats with Intracerebral Haemorrhage through Keap1 / NQO1 / Nrf2 Signaling Pathway #br#

LI Fang, TANG Shijun, Maimaitiyiming Tuoheti

Journal of Medical Molecular Biology 2024, 21 (4): 341-346. DOI: 10.3870/j.issn.1672-8009.2024.04.008

Abstract （183）

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Objective To explore the therapeutic effect and mechanisms of rat nerve growthfactor (RtNGF) combined with bone marrow mesenchymal stem cell-derived exosomes ( BMSCs exosomes) on neural injury of intracerebral haemorrhage (ICH) rats. Methods The BMSCs exosomes were prepared for the following experiments. Sixty rats were randomly divided into 5 groups: Sham group, ICH group, ICH + RtNGF group, ICH + BMSCs exosomes group, and ICH + RtNGF + BMSCs exosomes group, with 12 rats in each group. A ICH rat model was established and RtNGF or BMSCs exosomes were treated alone or in combination. Paraffin embedded tissue sections of rat brain tissues in each group were prepared and HE staining was performed. qPCR and Immunohistochemistry were used to determine the mRNA and protein expression levels of genes in the Keap1 / NQO1 /Nrf2 signaling pathway. Results Significant existence of tissue lacunes and blood clots were observed in the ICH group rather than in the Sham group. RtNGF or / and BMSCs treatments improved that situation, and the combination of RtNGF and BMSCs exosomes treatment had the best effect on alleviating neural injury. The mRNA expression levels of Keap1, NQO1 and Nrf2 in the brain tissues, and the IHC relative staining scores of the three proteins in the ICH group were increasedwhen compared with those in the Sham group ( allP < 0. 05). The levels of the above indicators inthe ICH + RtNGF group, ICH + BMSCs exosomes group, and ICH + RtNGF + BMSCs exosomesgroup were decreased when compared with those in the ICH group (P< 0. 05), with the values the lowest in the ICH + RtNGF + BMSCs exosomes group ( P < 0. 05). Conclusion RtNGF combinedwith BMSCs exosomes has significant effect on reducing oxidative stress and alleviating neural injury through Keap1 / NQO1 / Nrf2 signaling pathway in ICH rats.

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hsa_ circRNA_ 002178 Gene Interference Inhibits Malignant Biological Behavior of Ovarian Cancer Cells #br#

PENG Hu, LONG Chenglan, LUO Ting, YIN Bangchao, ZHOU Jian

Journal of Medical Molecular Biology 2024, 21 (4): 347-353. DOI: 10.3870/j.issn.1672-8009.2024.04.009

Abstract （114）

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Objective To study the effect of circRNA_ 002178 gene interference on malignant biological behavior of ovarian cancer cells. Methods Human ovarian cancer SKOV3 cells were divided into 4 groups: control group, short hairpin RNA negative control (shRNA-NC) group, circRNA_ 002178-shRNA 1 group and circRNA_ 002178-shRNA 2 group. The expression level of circRNA_ 002178 was detected by real-time fluorescence quantitative polymerase chain reaction (RTPCR). Flow cytometry was used to detect the cell apoptosis and mitochondrial membrane potential and to select the stem cell positive (CD44, CD133) cell lines. The stem cell spheroidization test was used to detect the sphere formation rate and the diameter of spheres. Transwell assay was used to detect the cell invasion. Western blotting was used to detect the expression levels of the proteins. Thetransplanted tumor model was constructed to observe the effect of circRNA_ 002178 gene interference on tumor formation. Results CircRNA_ 002178 interference significantly promoted the apoptosis ofSKOV3 cells, decreased the number of CD44 and CD133 positive cells, the rate of sphere formation, the diameter of spheres and the number of invasive cells, intensified the changes of mitochondrial membrane potential, and inhibited tumor growth and Akt / mTOR pathway activation in transplanted tumor rats. Conclusion CircRNA_ 002178 interference can inhibit the malignant biologicalbehavior of ovarian cancer cells. The mechanism may be related to the inhibitory effect on Akt / mTOR pathway.

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Anti-Tumor Effect of Kaempferol on Esophageal Squamous Cell Carcinoma through PI3K / AKT Signaling Pathway #br#

YANG Zhao, ZANG Ting , MA Kai , WANG Zhuangzhuang , LI Wenhai , ZHOU Jincai

Journal of Medical Molecular Biology 2024, 21 (4): 354-360. DOI: 10.3870/j.issn.1672-8009.2024.04.010

Abstract （148）

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Objective To investigate the anti-tumor effect and potential mechanism ofkaempferol on esophageal squamous cell carcinoma (ESCC) cells. Methods CCK-8, colony formation and flow cytometry were used to determine the effect of kaempferol on the proliferation andapoptosis of ECA-109 cells. Transwell assay was used to detect cell invasion. Western blotting wasemployed to measure the protein expression levels. Results Compared with the 0 μmol / L kaempferol group, the 40 μmol / L and 60 μmol / L kaempferol groups had significantly inhibited proliferationand invasion of ECA-109 cells and enhanced apoptosis. Moreover, kaempferol (40 μmol / L and 60μmol / L ) had significantly decreased expression levels of proliferating cell nuclear antigen (PCNA) and Ki67, and lower phosphorylation levels of phosphatidylin-ositol-3-kinase ( PI3K) and protein kinase B ( AKT), and increased expression levels of pro-apoptosis-related proteins. In addition, PI3K activator 740Y-P reversed the regulatory effect of kaempferol on proliferation, invasion and apoptosis of ECA-109 cells. Conclusion Kaempferol inhibits the proliferation, invasion and inducesthe apoptosis of ECA-109 cells by inhibiting PI3K / AKT signaling pathway.

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Expression of MyD88 / IL-23 and Liver Regeneration after Hepatectomy in Mice with Subcutaneous Infection of E. granulosus #br#

CHEN Jun, YU Peng

Journal of Medical Molecular Biology 2024, 21 (4): 361-365. DOI: 10.3870/j.issn.1672-8009.2024.04.011

Abstract （171）

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Objective To explore the influence of Echinococcus granulosus, (E. granulosus)infection on liver regeneration in hepatectomy model in mice, and to investigate the expression ofMyD88 / IL-23 in the liver regeneration of E. granulosus-infected mice post hepatectomy and its significance. Methods A mouse model with 70 % hepatectomy following subcutaneous infection of E- . granulosus was established. A total of 18 E. granulosus-infected mice and 18 healthy mice as controls were chosen for the surgery. The amount and rate of liver regeneration at different time points post-surgery in mice between the two groups were analyzed. The expression levels of MyD88 and IL-23 in mouse serum at different time points were measured by ELISA. The changes in hepatic functionindicators AST and ALT were also monitored. Results Compared to the control mice, the E-. granulosus -infected mice demonstrated decreased liver regeneration amount and regeneration ratepost hepatectomy, with significant differences apparent at the time points of 12 hours, 1 day, and2 days post-surgery. In comparison to the control mice, the E. granulosus-infected mice exhibitedmarkedly increased levels of AST and ALT in peripheral blood 1 day post-surgery, and notably increased levels of MyD88 and IL-23 2 hours post-surgery. Conclusions E. granulosus infection significantly decelerates the liver regeneration process following hepatectomy in mice, which maythrough increasing the levels of MyD88 and IL-23.

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Bioinformatics Analysis of circRNA-miRNA-mRNA ceRNA Network for Prognosis in Gastric Cancer #br#

HUANG Xinyi, ZHOU Jintao, JIANG Chenshan

Journal of Medical Molecular Biology 2024, 21 (4): 366-373. DOI: 10.3870/j.issn.1672-8009.2024.04.012

Abstract （217）

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Objective To construct a prognostic circRNA-miRNA-mRNA ceRNA network ingastric cancer ( GC) and explore the diagnostic and therapeutic targets. Methods Differentiallyexpressed circular RNAs (circRNA), related microRNAs (miRNA) and mRNAs in GC were obtained from GEO and TCGA databases. Cytoscape was utilized to construct the circRNA-miRNA-mRNA ceRNA network, to understand the biological functions of differentially expressed mRNAs and identifying the hub genes. Kaplan-Meier survival analysis was used to verify the prognostic values. Results The ceRNA network was consisted of 2 circRNAs, 5 miRNAs and 349 mRNAs thatwere differentially expressed. Functional enrichment analysis revealed that mRNAs were significantly enriched in terms and pathways like “ muscle system process”, “ metal ion transmembrane transporter activity”, “synaptic membrane” and “calcium signaling pathway” . A PPI network containing 125 nodes and 165 edges was constructed and 10 hub genes were identified. Survival analysis implied that low ADAR1D or PTGFR expression levels might lead to poor prognosis of GC patients. Conclusion The circRNA-miRNA-mRNA ceRNA network involved in prognosis of GC issuccessfully constructed. Two axes, the hsa _ circ _ 0001190 / hsa-miR-7-5p / ADRA1D and the hsa_ circ_ 0036287 / hsa-miR-3127-5p / PTGFR, are identified with potential prognostic values in GC, providing a new target for diagnosis andtreatment of GC.

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Bioinformatics Analysis of Common Key Genes and Signal Pathways in Liver Cancer and Diabetes #br#

ZHOU Yilin, JI Haitao, WANG Yanfeng

Journal of Medical Molecular Biology 2024, 21 (4): 374-379. DOI: 10.3870/j.issn.1672-8009.2024.04.013

Abstract （281）

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Objective To explore the gene features and pathogenic mechanisms shared byhepatocellular carcinoma and diabetes mellitus using bioinformatics methods. Methods The hepatocellular carcinoma dataset (GSE121248) and diabetes mellitus dataset ( GSE29221) were downloaded from the GEO (Gene Expression Omnibus) database, and were analyzed by R. Venn diagrams were used to obtain the shared differentially expressed genes (DEGs). GO (gene ontology) and KEGG ( kyoto encyclopedia of genes and genomes) enrichment analyses were performed on DEGs, and Cytoscape software was used to obtain the key modules and core genes in the proteinprotein interaction (PPI) network. The network interaction analyses of genes, transcription factors and mi-RNAs were performed in NetworkAnalyst database. DGIdb database was used for gene-drug interaction analysis. The prognostic values of the core genes were analyzed by Kaplan-Meier Plotterdatabase. Results A total of 39 DEGs were screened out, which were significantly enriched inpathways such as extracellular matrix, positive regulation of insulin-like growth factor receptor signaling pathway, heparin binding, and P53 signaling pathway. 6 core genes ( THBS1, DCN, BGN, COL14 A1, LUM and PCOLC) were screened out, of which two core genes (DCN and THBS1) could interacted with some tumor therapeutic agents and one core gene (DCN) was associated with the prognosis of hepatocellular carcinoma patients. Conclusion DCN may be a potentialdrug therapeutic target for patients with both diabetes and hepatocellular carcinoma.

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Relationship between Serum Hcy, CysC, D-D Levels and Condition of Patients with Acute Ischemic Stroke and Their Short-term Prognosis after Intravenous Thrombolysis #br#

WANG Wenjing, LI Lina, WANG Jicun

Journal of Medical Molecular Biology 2024, 21 (4): 380-385. DOI: 10.3870/j.issn.1672-8009.2024.04.014

Abstract （160）

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Objective To investigate the relationship between serum homocysteine ( Hcy),cystatin C (CysC) and D-dimer ( D-D) levels and the condition and short-term prognosis of patients with acute ischemic stroke ( AIS) after intravenous thrombolysis. Methods A total of 100AIS patients who received intravenous thrombolytic therapy in Shunyi District Hospital from October2019 to June 2023 were selected. According to the National Institutes of Health Stroke Scale (NIHSS) score, the patients were divided into 3 groups: mild defect group (1-4 points, 44 cases), moderate defect group (5-15 points, 29 cases) and severe defect group (16-42 points, 27 cases). According to the volume of cerebral infarction, the patients were divided into 3 groups: small infarction group ( < 5 cm³, 40 cases), moderate infarction group (5 ~ 15 cm3, 37 cases), and large infarction group ( > 15 cm3, 23 cases). Three months after intravenous thrombolysis, the patients were divided into 2 groups: good prognosis group (≤2 points, 75 cases) and poor prognosis group ( > 2 points, 25 cases), according to the modified Rankin scale score. Baseline data of patients were collected, and serum Hcy, CysC and D-D levels were detected. The changes of serum Hcy, CysC and D-D levels in AIS patients with different degrees of neurological deficit, cerebral infarction volume and short-term prognosis were compared. Pearson correlation coefficient was used to analyze the correlation between serum Hcy, CysC and D-D levels and AIS condition. Multivariate logistic regression was used to analyze the independent influencing factors of short-term prognosis of AIS. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum Hcy, CysC and D-D levels for short-term prognosis after AIS intravenous thrombolysis. Results The levels of serum Hcy, CysC and D-D in the mild defect group were the lowest, followed by the moderate defect group, and the severe defect group was the highest, with statisticallysignificant (P< 0. 05). The levels of serum Hcy, CysC and D-D in the small infarction group werethe lowest, followed by the moderate infarction group, and the large infarction group was the highest, the difference between the groups was statistically significant (P < 0. 05). Pearson correlationcoefficient analysis showed that serum Hcy, CysC and D-D levels were positively correlated withNHISS score (r = 0. 424, 0. 573, 0. 716, all P < 0. 001) and cerebral infarction volume ( r =0. 633, 0. 479, 0. 548, all P< 0. 001). Univariate analysis showed that the levels of serum Hcy,CysC and D-D in the good prognosis group were lower than those in the poor prognosis group (all P< 0. 05). Multivariate logistic regression analysis showed that Hcy, CysC and D-D (OR = 1. 093,1. 343, 1. 146) were independent predictors of short-term prognosis of AIS (P< 0. 05). ROC curveanalysis showed that the area under the curve of serum Hcy, CysC, D-D and the combination of thethree in predicting the short-term prognosis of AIS was 0. 853, 0. 873, 0. 792 and 0. 946, respectively, and the combination of the three had the highest predictive value. Conclusion The levels ofserum Hcy, CysC and D-D are positively correlated with the severity of AIS patients, which can beused as predictors of short-term prognosis after intravenous thrombolysis in AIS patients.

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Progress in the Application of Lipidomics in Lung Cancer Research #br#

LIANG Yi, YU Wanjun, LI Jiawei, XU Tao

Journal of Medical Molecular Biology 2024, 21 (4): 386-390. DOI: 10.3870/j.issn.1672-8009.2024.04.015

Abstract （643）

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In recent years, the application of lipidomics in lung cancer research has receivedincreasing attention, providing new perspectives on understanding the pathogenesis and therapeutic strategies of lung cancer. With technological advances, lipidomics will play a more critical role in lung cancer research and provide more specific biomarkers and pharmacodynamic evaluation tools for early diagnosis, condition monitoring, and personalized treatment of lung cancer. This review discusses the critical roles of core technologies like mass spectrometry and bioinformatics in lung cancer research. It also emphasizes the importance of serum and tissue-based lipidomics analysis in exploring specific biomarkers and differences between subtypes of lung cancer. Novel lipidomics strategies provide new directions for elucidating lung cancer pathogenesis and therapeutic strategy selection.

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Effect of Acteoside on Lung Injury in Rats with Severe Acute Pancreatitis by Regulating IRE1α/ TXNIP / NLRP3 Signaling Pathway #br#

WEN Cai, ZHOU Jing , WAN Xiaoqin

Journal of Medical Molecular Biology 2024, 21 (5): 391-398. DOI: 10.3870/j.issn.1672-8009.2024.05.001

Abstract （290）

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Objective This study aims to investigate the effect of acteoside on lung injury inrats with severe acute pancreatitis ( SAP ) by regulating the inositol-requiring enzyme 1α(IRE1α) / thioredoxin interacting protein ( TXNIP) / nucleotide binding oligomerization domain-like receptor protein 3 ( NLRP3 ) pathway. MethodsRats were randomly separated into SAPgroup, normal group, acteoside low-dose ( ACT-L ) group, acteoside high-dose ( ACT-H )group, ulinastatin group, ACT-H + empty-vector group, and ACT-H + Ad-IRE1α group, with 12rats in each group. SAP model were constructed by injecting 5 % sodium taurocholate solution into the bile duct of rats. SAP model rats were then administered with acteoside, ulinastatin or AdIRE1α once a day for 2 days. The changes in serum lipase and amylase levels, and lung wet weight / dry weight ratio were detected. HE staining was used to detect the pathological changes of pancreas and lung tissues and to evaluate the pathological scores. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase ( SOD) in lung tissues were detected by kits. ELISA was applied to detect the levels of interleukin-18 and IL-1β in lung tissues. Western blotting was applied to detect the levels of IRE1α, TXNIP, NLRP3, and caspase-1 proteins inlung tissues. Results Pancreatic edema and a large number of cell necrosis and inflammatory cellinfiltration were observed in rats in the SAP group, the inflammatory cell infiltration in lung tissues was observed, and alveolar congestion and alveolar wall edema were severe when compared with those in the normal group. The pancreatic and lung histological scores, the levels of lipase and amylase in serum, the wet / dry lung weight ratio, the levels of MDA, ROS, IL-18, IL-1β in lung tissues, and the expression levels of IRE1α, TXNIP, NLRP3, and caspase-1 proteins were elevated in the SAP group, and the level of SOD in lung tissues was decreased when compared with those inthe normal group (P< 0. 05). The pancreatic and lung tissue damages in rats in the ACT-L group,ACT-H group, and ulinastatin group were improved when compared with those in the SAP group. The pancreatic and lung histological scores, the levels of lipase and amylase in serum, the wet / dry lung weight ratio, the levels of MDA, ROS, IL-18, IL-1β in lung tissues, and the expression levels of IRE1α, TXNIP, NLRP3, and caspase-1 proteins were decreased, and the level of SOD in lung tissues was increased in the ACT-L group, ACT-H group, and ulinastatin groupwhen compared with those in the SAP group (P< 0. 05). The pancreatic and lung tissue damages inthe ACT-H + Ad-IRE1α group were aggravated, and the pancreatic and lung histological scores, the levels of lipase and amylase in serum, the wet / dry lung weight ratio, the levels of MDA, ROS, IL-18, IL-1β in lung tissues, and the expression levels of IRE1α, TXNIP, NLRP3, and caspase-1 proteins were increased, while the level of SOD in lung tissues was decreased when compared withthose in the ACT-H + empty vector group (P< 0. 05). Conclusion The mechanism by which acteoside improves lung injury in SAP rats may be related to the inhibition of IRE1α / TXNIP / NLRP3pathway activation.

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Inhibition of Survivin Alleviates Etoposide Resistance in Small Cell Lung Cancer and Its Mechanism#br#

Kadilia Abuduweili, Aziguli Tuersunmaimaiti, HUI Jing, Mairehaba Halike

Journal of Medical Molecular Biology 2024, 21 (5): 399-404. DOI: 10.3870/j.issn.1672-8009.2024.05.002

Abstract （222）

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Objective To investigate the effect and mechanism of Survivin on the proliferationand apoptosis of etoposide resistant small cell lung cancer cell lines. Methods Etoposide resistancesmall cell lung cancer cell lines were constructed in NCI-H82 and NCI-H446 cell lines (NCI-H82 /ER and NCI-H446 / ER), the IC50 and resistance index of NCI-H82 / ER and NCI-H446 / ER weredetermined. qRT PCR and Western blotting assay were used to detect the expression level of Survivinin the cell lines. Survivin siRNA (si-Survivin group) and Survivin siRNA Negative Control (si-NCgroup) were transfected into NCI-H82 / ER and NCI-H446 / ER cells. Cell proliferation was determined by CCK8, apoptosis was determined by flow cytometry, and phosphorylation levels of PI3K,AKT, and mTOR were detected by Western blotting. Results The IC50 of NCI-H82 / ER and NCIH446 / ER were 154. 5 μmol / L and 130. 5 μmol / L, respectively, with resistance indices of 5. 40and 6. 21. Compared with the NCI-H82 and NCI-H446 cells, the NCI-H82 / ER and NCI-H446 / ERcells had significantly increased expression levels of Survivin mRNA and protein ( P < 0. 001 ).Compared with the cells in the si-NC group, NCI-H82 / ER and NCI-H446 / ER cells in the si-Survivin group had significantly reduced proliferation abilities (P< 0. 05), and significantly increased level of apoptosis ( P < 0. 001), and significantly reduced phosphorylation levels of PI3K, AKT, and mTOR (P< 0. 001). Conclusion Inhibiting Survivin can inhibit the PI3K / AKT / mTOR signaling and affect the proliferation and apoptosis of etoposide resistant small cell lung cancer cells.

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miR-542-5p Inhibits Proliferation, Migration and Invasion of Hepatocellular Carcinoma by Targeting ENSA #br#

DAI Hanli, WANG Guohua, XU Xiangyong

Journal of Medical Molecular Biology 2024, 21 (5): 405-412. DOI: 10.3870/j.issn.1672-8009.2024.05.003

Abstract （205）

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Objective To explore the effect of miR-542-5p on proliferation, migration and invasion of hepatocellular carcinoma (HCC) by targeting ENSA. Methods The expression of miR-542-5p in HCC tissues and para-carcinoma tissues was analyzed by GSE36915 data matrix. miR-542- 5p overexpression were performed in the HCC cell lines HepG2 and Hep3B and verified by RTPCR. The proliferation, migration and invasion of cells were detected by CCK-8, wound healing and Transwell assays. miR-542-5p overexpressed Hep3B cells were used to establish the transplanted tumor model in nude mice. The volume and weight of transplanted tumors were measured. The miR- 542-5p expression level in transplanted tumors was detected by RT-PCR. The differential expression genes of GSE101728 and GSE7642 were analyzed by GEO2R, and the target genes of miR-542-5pwere predicted by miRWalk, ENSA gene was then screened out. The expression level of ENSA inHCC tissues and para-carcinoma tissues was analyzed by TCGA HCC data. The expression level of ENSA in miR-542-5p overexpressed HepG2 and Hep3B cells was detected by RT-PCR. The cell proliferation, migration and invasion were detected in miR-542-5p overexpressed HepG2 and Hep3Bcells after transfected with ENSA overexpression plasmid. Results The expression level of miR-542-5p in the HCC tissues was significantly lower than that in the para-carcinoma tissues (P < 0. 01).The proliferation rate, migration rate and relative number of invasion cells in the miR-542-5p overexpressed cells were significantly lower than those in miR-NC overexpressed cells (P < 0. 01). The results ofin vivoexperiments showed that the volume and weight of tumors in the miR-542-5p overexpression group were significantly lower than those in the miR-NC overexpression group (P< 0. 01).The expression level of ENSA in the HCC tissues was significantly higher than that in the para-carcinoma tissues (P< 0. 01), and ENSA could promote HCC progression. The protein expression levelof ENSA in the miR-542-5p overexpressed cells were significantly lower than that in the miR-NCoverexpressed cells (P< 0. 01). The proliferation rate, migration rate and relative number of invasion cells in cells with miR-542-5p + ENSA overexpression were significantly higher than those incells with miR-542-5p overexpression (P< 0. 01). Conclusion miR-542-5p can inhibit the proliferation, migration and invasion of HCC cells by inhibiting ENSA.

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Asiaticoside Inhibits Cell Growth and Invasion of Imatinib-resistant K562 Cells #br#

ZHENG Runtao, ZHUANG Minli, ZHANG Wenxia

Journal of Medical Molecular Biology 2024, 21 (5): 413-418. DOI: 10.3870/j.issn.1672-8009.2024.05.004

Abstract （166）

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Objective To study the effect of asiaticoside on the proliferation, invasion and cellcycle arrest of chronic myelogenous leukemia (CML) cells, and to explore its regulation on GATA-1 expression. Methods CML cell line K562, imatinib (IM) -resistant K562 cells (K562r) andhuman original CML cells were used for experiments. Cell viability was determined by CCK-8 assay. K562r cells were treated with 0, 25, 50, 100 μmol / L asiaticoside, then cell proliferation wasdetermined by colony formation assay, cell migration was determined by transwell assay, the cell cycle was measured by flow cytometry, the expression levels of cyclin A, CDK2, CDK4, cyclinD1, Ki67, PCNA, VEGF, MMP-9 and MMP-14 were detected by Western blotting. Results Compared with the control group, asiaticoside treatment significantly reduced the number of K562rcell colonies and migration cells, and induced the cell cycle arrest. In addition, the expression levelof GATA-1 in K562r cells was significantly up-regulated after asiaticoside treatment. Conclusion Asiaticoside can inhibit the proliferation and migration of K562r cells and induce cell cycle arrest,and the mechanism may be related to the up-regulation of GATA-1 expression.

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Prognostic Value of Interleukin-4 Combined with APACHE Ⅱ Score for Carbapenem-resistant Acinetobacter baumannii Infection #br#

YUAN Zhifa, QIU Jingxing, WU Kefeng

Journal of Medical Molecular Biology 2024, 21 (5): 419-424. DOI: 10.3870/j.issn.1672-8009.2024.05.005

Abstract （200）

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Objective To analyze the prognostic value of interleukin-4 (IL-4) combined withacute physiology and chronic health evaluation ( APACHE Ⅱ ) in the infection of carbapenem-resistant Acinetobacter baumannii ( CRAB). Methods A total of 143 patients with CRAB infectiontreated in Affiliated Hospital of Guangdong Medical University from November 2021 to October 2023were set as the study group, and 49 patients with carbapenem-sensitive Acinetobacter baumannii infection treated in the same period were taken as the control group. According to the clinical outcome of the patients in the study group, they were divided into 2 groups: death group (n = 46) and survival group (n = 97), and the differences of IL-4 and APACHE Ⅱ scores between the study groupand the control group, as well as the death group and the survival group were compared. Pearson correlation analysis was used to calculate the correlation between serum IL-4 level and APACHE Ⅱ score in patients with CRAB infection. Receiver operating characteristic curves (ROC) was used to evaluate the application value of IL-4, APACHE Ⅱ score and joint diagnosis in predicting the adverse clinical outcome of patients with CRAB infection. Results The level of IL-4 and the APACHEⅡ score in the death group were significantly higher than those in the survival group (P < 0. 05).The results of Pearson correlation analysis showed that the two indexes (the level of IL-4 and the APACHE Ⅱ score) had obvious positive correlation ( r = 0. 093, P < 0. 001) . The AUC of serumIL-4, APACHE Ⅱ score and the combined index in evaluating the prognosis of patients with CRABinfection were 0. 712 (95 % CI = 0. 606-0. 817, P < 0. 001), 0. 849 (95 % CI = 0. 763-0. 936, P < 0. 001) and 0. 956 (95 % CI = 0. 927-0. 985, P < 0. 001), respectively. Conclusion Theserum IL-4 and APACHE Ⅱ scores of CRAB patients with poor prognosis are significantly higher than those of survival patients. The combination of serum IL-4 and APACHE Ⅱ scores can be used in the prognosis evaluation of such patients, which is helpful to provide reference for their clinical treatment.

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Long Non-coding RNA B3GALT5-AS1 Inhibits Proliferation, Invasion and Tumorigenicity of Non-small Cell Lung Cancer A549 Cells #br#

PENG Qiang, ZHAO Hui, YAO Qiuying

Journal of Medical Molecular Biology 2024, 21 (5): 425-431. DOI: 10.3870/j.issn.1672-8009.2024.05.006

Abstract （205）

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Objective To explore the effect of overexpression of long non-coding RNA ( lncRNA) B3GALT5-AS1 on the growth and invasion ability in non-small cell lung cancer (NSCLC).Methods qRT-PCR was employed to examine the expression level of B3GALT5-AS1 in clinicalsamples. A549 cells were divided into 3 groups: control group, pcDNA-scramble group, and pcDNA-B3GALT5-AS1 group, the pcDNA-scramble and pcDNA-B3GALT5 AS1 vectors were transfected into cells respectively. The colony formation experiment was employed to evaluate the colony-forming ability of A549 cells, qRT-PCR was used to detect the mRNA expression level of Ki67 and Survivin. Flow cytometry was used to analyse cell apoptosis, Transwell assay was used to test cell invasion, and Western blotting was used to detect the expression level of P27, P53, VEGF and Vimentin proteins. A549 cells transfected with pcDNA-scramble or pcDNA-B3GALT5-AS1 were injected subcutaneously into nude mice. The tumor volume and weight were measured, the expression level of B3GALT5-AS1 in tumor tissues was detected by qRT-PCR, and the expression of Ki67 and VEGF were determinded by immunohistochemistry. Results The relative mRNA expression level ofB3GALT5-AS1 in the lung cancer tissues was significantly lower than that in the adjacent normal tissues when compared with that in the paracancerous tissues (P< 0. 05). The colony forming ability of cells in the pcDNA-B3GALT5-AS1 group was reduced ( P < 0. 05), the expression of Ki67 and Survivin was obviously down-regulated (P< 0. 05), the apoptosis rate of cell was clearly increased (P< 0. 05), and the number of invasion cells was evidently reduced (P < 0. 05), the expression level of P27 and P53 proteins was up-regulated (P< 0. 05), and the expression of VEGF and Vimentin protein was significantly down-regulated (P< 0. 05). The results of in vivo xenotransplantationexperiments showed that overexpression of B3GALT5-AS1 clearly reduced tumor volume and weight(P< 0. 05), and the numbers of Ki67 and VEGF positive cells in tumor tissues were obviously reduced (P< 0. 05) when compared with that in the pcDNA-scramble group. Conclusion Overexpression of B3GALT5-AS1 obviously inhibits the proliferation and invasion of NSCLC cells and induces apoptosis, it also blocks the growth of tumor tissues in vivo and plays an anti-cancer effect in NSCLC.

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Canagliflozin Alleviates Kidney Damage in STZ-induced Diabetic Nephropathy Mice by TGF-β/ STAT3 #br#

ZENG Weixin, YUN Chuan, LI Xiaoyan, LI Dawei

Journal of Medical Molecular Biology 2024, 21 (5): 432-436. DOI: 10.3870/j.issn.1672-8009.2024.05.007

Abstract （173）

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Objective To explore the potential mechanism by which canagliflozin alleviateskidney injury in streptozotocin ( STZ ) -induced diabetic nephropathy mice through TGF-β /STAT3. Methods A diabetic nephropathy mouse model was established using STZ. Mice were divided into 5 groups: control group, STZ-induced diabetic nephropathy mice group, canagliflozintreated group, TGF-β inhibitor-treated group, and STAT3 inhibitor-treated group. Renal weight / body weight ratio, urinary albumin, renal function parameters, serum TGF-β level and the phosphorylation level of STAT3 in the kidney tissues were measured. Results Mice with diabetic nephropathy exhibited signs of renal injury, including a significant increase in renal weight / bodyweight ratio and urinary albumin (P < 0. 05), whereas these indices returned to normal levels aftercanagliflozin treatment. The serum TGF-β level and phosphorylation level of STAT3 in tissues wereelevated in diabetic nephropathy mice (P < 0. 05), while they returned to similar levels as that inthe control after canagliflozin treatment. In addition, the TGF-β expression level was positively correlated with the STAT3 phosphorylation level (P < 0. 05). Conclusion Canagliflozin attenuated renal injury in diabetic nephropathy by modulating TGF-β and STAT3 pathways.

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miR-139-5p Targets Notch1 to Inhibit Proliferation, Migration and Invasion of Lung Adenocarcinoma Cells #br#

DONG Yuehua, WANG Guigang, YANG Yanjun, WEI Yulei, GAO Yongshan, JIANG Weihua

Journal of Medical Molecular Biology 2024, 21 (5): 437-444. DOI: 10.3870/j.issn.1672-8009.2024.05.008

Abstract （186）

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Objective To investigate the role and regulatory mechanism of miR-139-5p in the progression of lung adenocarcinoma (LUAD). Methods The expression levels of miR-139-5p andNotch homolog 1 (Notch1) in LUAD tissues and cells were detected and the transfection efficiency after cell transfection was verified by Quantitative real-time PCR ( qRT-PCR) and Western blotting. The proliferation, migration and invasion of LUAD cells were determined by CCK-8, wound healing and Transwell assay. The targeting relationship of miR-139-5p to Notch1 was analyzed using a dual luciferase reporter gene assay. Western blotting was employed to detect the expression levels ofPI3K / AKT / mTOR signaling pathway related proteins. Results miR-139-5p was significantly downregulated (P < 0. 01) and Notch1 was significantly up-regulated in the LUAD tissues and cells (P < 0. 01), when compared with those in the normal tissues and human normal bronchial epithelialcells. miR-139-5p overexpression suppressed the proliferation, migration and invasion of LUADcells, and down-regulated the expression levels of p-PI3K, p-AKT and p-mTOR ( P < 0. 01 ).Notch1 was identified as a target of miR-139-5p that could directly bind to it. Overexpression of Notch1 attenuated the inhibitory effects of miR-139-5p on proliferation, migration and invasion ofLUAD cells (P < 0. 05). In vivo experiment showed that the overexpression of miR-139-5p inhibited the growth of xenograft tumor in nude mice when compared with that in the control group ( P < 0. 05). Conclusion miR-139-5p inhibits the proliferation, migration and invasion of LUAD cellsby targeting Notch1 and inactivation of PI3K / Akt / mTOR pathway.

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Value of miR-550a-5p in Diagnosis of Spinal Bone Metastasis of Nonsmall Cell Lung Cancer #br#

XU Kun, AO Man, HAO Jiaying, CAO Sheng, ZHANG Yilong, WANG Jianhua

Journal of Medical Molecular Biology 2024, 21 (5): 445-451. DOI: 10.3870/j.issn.1672-8009.2024.05.009

Abstract （173）

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Objective To explore the value of microRNAs (miR-550a-5p) in the diagnosis ofspinal bone metastases in non-small cell lung cancer (NSCLC), and to provide reference for clinical prevention and treatment. Methods Sixty-two NSCLC patients with the presence of spinal bonemetastasis and 44 NSCLC patients without spinal bone metastasis admitted to the Affiliated Hospital of Chengde Medical College from January 2019 to January 2023 were selected and included in the spinal bone metastasis group and the no spinal bone metastasis group, respectively, based on the confirmation of magnetic resonance imaging or CT examination. Serum miR-550a-5p, lung tumor markers [ carcinoembryonic antigen ( CEA ), cytokeratin-19 soluble fragment ( CYFRA21-1 ), neuron-specific enolase (NSE)], bone metabolism markers [type I collagen pyridine cross-linked amino-terminal peptide (NTx), bone transmutation alkaline phosphatase (BALP), Type I collagen carboxyl terminal peptide (ICTP)] were detected and compared between the two groups. The level of serum miR-550a-5p in NSCLC patients with different clinical characteristics was compared, and the association between the grade of NSCLC spine bone metastasis and the level of serum miR- 550a-5p was analyzed. The diagnostic value of serum miR-550a-5p in NSCLC spine bone metastasiswas analyzed by receiver operating characteristic curve (ROC). Results The levels of serum miR-550a-5p, CEA, NSE, CYFRA21-1, BALP, ICTP and NTx in the spinal bone metastasis groupwere higher than those in the non-spinal bone metastasis group (P < 0. 05). There were statisticallysignificant differences in the level of miR-550a-5p among NSCLC patients in spinal bone metastasis group with different tumor diameter, degree of differentiation, TNM stage, number of bone metastases, lymph node metastases, bone-related events and symptoms of bone pain (P< 0. 05). There weresignificant differences in the level of serum miR-550a-5p, NSE, BALP, CEA, ICTP, CYFRA21-1and NTx among NSCLC patients with different bone metastasis grades (P< 0. 05). The levels of serummiR-550a-5p, lung tumor markers and bone metabolism markers were increased with the increase of bone metastasis grade. Spearman correlation analysis showed that the level of serum miR-550a-5p was positively correlated with bone metastasis grade, and the levels of CEA, NSE, CYFRA21-1, BALP,ICTP and NTx (P< 0. 05). The AUC value of serum miR-550a-5p combined with lung tumor markers and bone metabolic markers was 0. 941 (95 % CI: 0. 878-0. 978) (P < 0. 05), which was higher than that of lung tumor markers combined with bone metabolic markers only [0. 902 (95 % CI:0. 829-0. 951)]. Conclusion miR-550a-5p has a high value in the diagnosis of spinal bone metastasisof NSCLC, and its level is closely related to bone metastasis grade, and level of lung tumor markers,and bone metabolic markers. Application of miR-550a-5p combined with lung tumor markers and bonemetabolic markers can improve the diagnostic value.

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Expression of FtMt Protein in Non-small Cell Lung Cancer and Its Clinicopathological Significance #br#

XU Meirong, SHEN Xiaowen, GU Lingli, SHEN Hongmei, HUANG Linling

Journal of Medical Molecular Biology 2024, 21 (5): 452-457. DOI: 10.3870/j.issn.1672-8009.2024.05.010

Abstract （180）

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Objective To study the relationships between the expression level of mitochondrialferritin (FtMt) and the clinical pathology and molecular characteristics in non-small cell lung cancer (NSCLC). Methods A total of 154 surgical specimens with pathologically confirmed NSCLCfrom September 2018 to December 2020 were selected. Immunohistochemistry was used to determine the expression of FtMt protein. Amplification refractory mutation system was used to detect the mutations of EGFR, ALK, and KRAS genes. Fluorescence quantitative PCR was used to detect the mRNA expression levels of epithelial-mesenchymal transformation markers N-cadherin, E-cadherin, Vimentin, and mitochondrial pathway apoptotic proteins B-lymphoblastoma-2 (Bcl-2), Bcl2-associated X-protein ( Bax), caspase-3, and ferroptosis markers glutathione peroxidase 4 ( GPX4), solute carrier family 7 member 11 (SLC7A11). Patients with NSCLC were followed-up for the tumorfree survival and overall survival. Results The positive expression rate of FtMt in the NSCLC tissueswas higher than that in the adjacent tissues ( P < 0. 05). The positive expression rates of FtMt inNSCLC tissues with low differentiation, pTNM stage Ⅲ , and lymph node metastasis were higherthan those with high differentiation, pTNM stage Ⅰ -Ⅱ , and no lymph node metastasis ( P <0. 05). The mRNA expression levels of N-cadherin, Vimentin, Bcl-2, GPX4, SLC7A11 and the mutant rate of EGFR in the NSCLC tissues with positive FtMt expression were increased, while themRNA expression levels of E-cadherin, Bax, and Caspase-3, as well as the tumor free survival rate and overall survival rate were decreased when compared with those in the NSCLC tissues withnegative FtMt expressions (P < 0. 05). Conclusion The positive expression of FtMt in NSCLC isassociated with pathological progression, EGFR mutation, and reduced survival. The biologicalmechanisms may associate with abnormal epithelial mesenchymal transformation, ferroptosis and mitochondrial pathway apoptosis.

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Expression of C-C Motif Chemokine Receptor 2 and Th1 / Th2 Cells in Renal Interstitial Fibrosis of Rats with IgA Nephropathy and Its Significance #br#

ZHU Jianping, HE Linghui, XIANG Yong

Journal of Medical Molecular Biology 2024, 21 (5): 458-463. DOI: 10.3870/j.issn.1672-8009.2024.05.011

Abstract （345）

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Objective To investigate the expression of C-C motif chemokine receptor 2(CCR2) and the numbers of helper T cell 1 / 2 (Th1 / Th2) in renal interstitial fibrosis of rats withIgA nephropathy and their significance. Methods A total of 40 male SD rats were randomly dividedinto 2 groups, each group included 20 rats. Immunoglobulin A (IgA) nephropathy in rats was induced by using a combined treatment of lipopolysaccharide (LPS), modified bovine serum albumin (BSA), and carbon tetrachloride ( CCl4 ). The pathological changes and IgA deposition were observed, the percentage of collagen fibers in renal tissues was calculated, and the Katafuchi score was used to evaluate the degree of tubulointerstitial injury. Western blotting was used to detect the expression level of CCR2 in renal tissues. Serum levels of interleukin-4 ( IL-4) and interferon-γ (IFN-γ) were measured by double-antibody sandwich enzyme-linked immunosorbent assay. Flowcytometry was used to measure the proportion of Th1 / Th2 cells. Results The percentage of collagenfiber area and the Katafuchi score in the model group were significantly higher than those in the control group (P < 0. 05). The expression level of CCR2 in renal tissues, the serum level of IL-4, thenumber of Th2 cells and the ratio of IL-4 / IFN-γ in the model group were significantly higher than those in the control group, while the serum level of IFN-γ and the number of Th1 cells were significantly lower than those in the control group (P< 0. 05). The levels of CCR2 and IL-4 and the ratioof IL-4 / IFN-γ were positively correlated with the collagen fiber area percentage and the Katafuchiscore (P< 0. 05), while the level of IFN-γ was negatively correlated with collagen fiber area percentage and the Katafuchi score ( P < 0. 05). Conclusion The abnormal expression of CCR2 andthe Th1 / Th2 Imbalance are involved in the occurrence and development of renal interstitial fibrosis in IgA nephropathy rats, meanwhile, antagonizing CCR2 and regulating Th1 / Th2 balance may reduce the changes of renal fibrosis in IgA nephropathy rats.

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Protective Effect of Hypericum perforatumExtract on Myocardial Injury in Rats with Autoimmune Myocarditis and Its Influence on Myocardial Collagen Metabolism #br#

WANG Xiufang, LI Yanjun, LI Hongzhong

Journal of Medical Molecular Biology 2024, 21 (5): 464-469. DOI: 10.3870/j.issn.1672-8009.2024.05.012

Abstract （223）

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Objective To explore the protective effect of Hypericum perforatum extract (HPE)on myocardial injury in rats with autoimmune myocarditis and its influence on myocardial collagenmetabolism. Methods Six-week-old Lewis rats were enrolled as the research subjects. The experimental autoimmune myocarditis (EAM) rat model was established by subcutaneous injection of porcine cardiac myosin emulsion into the hind foot pad. The EAM model rats were randomly classifiedinto 4 groups: model group, and low-dose, middle-dose and high-dose HPE groups, with 10 ratsin each group. The rats in each group were given intragastric administration of normal saline, 20mg / kg HPE, 50 mg / kg HPE or 100 mg / kg HPE, with twice a day for 28 days. The blank control group was additionally set and was given normal saline according to the same course of treatment. The clinical manifestations of rats were observed, and the heart weight ( HW) and body weight (BW) were measured, and BW/ HW ratio was calculated. The pathological changes of heart were observed under optical microscope after HE staining. Cardiac parameters such as left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) were measured by echocardiography. The levels of serum myocardial injury indicators [creatine kinase isoenzyme MB (CK-MB), cardiac troponin T ( cTnT)] and collagen metabolism indicators ( type I collagen, type Ⅲ collagen) were detected, and tumor necrosis factor-alpha ( TNF-α) and transforminggrowth factor-β1 (TGF-β1) protein level was determined by Western blotting. Results The valuesof LVEDD, LVESD, HW/ BW, and the expression levels of CK-MB, cTnT, type I collagen, type Ⅲ collagen, TNF-α protein and TGF-β1 protein in the EAM model rats were increased, the pathological score of myocardial tissues were enhanced, while the values of LVFS and LVEF weredecreased, when compared with those in the blank control group (P < 0. 05). After HPE administration, the values of LVEDD, LVESD, HW/ BW, and the expression levels of CK-MB, cTnT, type I collagen, type Ⅲ collagen, TNF-α protein and TGF-β1 protein were reduced in the lowdose, middle-dose and high-dose HPE groups, and the myocardial tissue pathological score weredeclined, while the values of LVFS and LVEF were risen (P< 0. 05). Conclusion The traditionalChinese medicine Hypericum perforatum extract can improve myocardial injury in EAM model rats,which may be related to its inhibition of myocardial tissue inflammation and reduction of collagen deposition.

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Predictive Value of Keratin17 Combined with HPV E6 / E7 mRNA in the Outcome of Cervix Low-grade Squamous Intraepithelial Lesions #br#

WU Ying, LI Yuan, WANG Xiaoyan

Journal of Medical Molecular Biology 2024, 21 (5): 470-474. DOI: 10.3870/j.issn.1672-8009.2024.05.013

Abstract （245）

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Objective To study the predictive value of Keratin17 (Krt17) combined with human papillomavirus (HPV) E6 / E7 mRNA in the prognosis of cervical low-grade squamous intraepithelial lesions (LSIL). Methods Patients diagnosed with LSIL from January 2020 to September2021 and completed 24 months of follow-up were selected and grouped according to the histologicalfindings of the lesions at the 24th month of return visit. Patients with LSIL regression or maintenancewere classified as the non-lesion progression group, and patients with LSIL progression to a highergrade were classified as the lesion progression group. The clinical data, Krt17 mRNA expression level and E6 / E7 copy number of the two groups were compared at the time of first diagnosis. The riskfactors of LSIL lesion progression were analyzed by multivariate logistic step-by-step regression, andthe predictive value of Krt17 combined with E6 / E7 on LSIL lesion progression was analyzed by ROCcurve. Results Among the 98 LSIL patients, 19 cases ( 19. 39 % ) progressed and 79 cases(80. 61 % ) did not progress. The age, smoking rate, menopause rate, Krt17 mRNA expressionlevel and E6 / E7 copy number of LSIL patients in the lesion progression group were higher than thosein the non-lesion progression group (P < 0. 05). Multivariate logistic regression analysis showed that age ≥ 45 years, smoking, increased Krt17 mRNA expression level and E6 / E7 copy number were risk factors for the progression of LSIL lesions. ROC curve analysis showed that Krt17 and E6 / E7had predictive value for the progression of LSIL lesions, and the sensitivity and specificity of thecombined prediction of the two indexes were respectively 81. 01 % and 94. 74 % . Conclusion Krt17 combined with HPV E6 / E7 can predict the progression of LSIL lesions.

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Effect of Shikonin on Proliferation and Apoptosis of Ovarian Cancer Cells #br# #br#

JIAO Peiying, DU Qiaoqian, LI Na, WANG Jiao

Journal of Medical Molecular Biology 2024, 21 (5): 475-480. DOI: 10.3870/j.issn.1672-8009.2024.05.014

Abstract （164）

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Objective To explore the effect of shikonin on the proliferation and apoptosis of ovarian cancer cells and the expression of c-Jun N-terminal kinase ( JNK) signaling pathway.Methods Human ovarian cancer cell ( SKOV-3 ) cells cultured in vitro were divided into 4groups: control group ( 0 μmol / L ), low-dose Shikonin group ( 2. 5 μmol / L ), middle-dose Shikonin group (5 μmol / L) and high-dose Shikonin group (10 μmol / L). Cell proliferation and apoptosis were detected in each group. The expression levels of proliferating cell nuclear antigen (PCNA), cleaved Caspase-9 and Caspase-3 proteins, and c-Jun N-terminal kinase 1 / 2 ( JNK1 /2) phosphorylation were detected by Western blotting. Results The inhibitory effect of shikoninon the proliferation of SKOV-3 cells showed dependence of drug concentration, with the semi-inhibitory concentration (IC50) of 10. 59 μmol / L. The cells survival rate and colony formation rate weresignificantly decreased in the middle-dose Shikonin group and high-dose Shikonin group ( P <0. 05), the apoptosis rate was significantly increased (P < 0. 05), the expression levels of PCNAand (p-JNK1 / 2) / (JNK1 / 2) were significantly decreased (P < 0. 05), and the levels of cleavedCaspase-9 / Caspase-9 and cleaved Caspase-3 / Caspase-3 were significantly increased (P < 0. 05), ifcompared with those in the control group. Conclusion Shikonin can inhibit the proliferation ofSKOV-3 cells, inhibit JNK signaling pathway, and induce apoptosis.

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Downregulation of Long Non-coding RNA XIST Alleviates IL-1β-induced Chondrocyte Apoptosis by Targeting miR-124 / NF-κB Axis #br#

TAN Jifeng, YAN Hong, JIANG Luoyong

Journal of Medical Molecular Biology 2024, 21 (5): 481-486. DOI: 10.3870/j.issn.1672-8009.2024.05.015

Abstract （225）

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Objective To explore the effect of long non-coding RNA ( lncRNA) X inactivespecific transcript ( XIST) on interleukin-1β ( IL-1β ) -induced chondrocyte apoptosis and itsmechanism. Methods The targeting relationship between XIST and miR-124 was predicted bybioinformatics and verified by dual luciferase reporter gene assay. Ten experimental groups were set as follows: normal group, IL-1β group, si-NC group, si-XIST group, miR-124-NC group, miR-124 mimics group, si-NC + inhibitor-NC group, si-XIST + inhibitor-NC group, si-NC + miR-124inhibitor group, si-XIST + miR-124 inhibitor group. qRT-PCR was used to detect the expression levels of XIST and miR-124 in cells. Western blotting was used to detect the expression level of nuclearfactor kappa B P65 ( NF-κB P65 ) protein. Flow cytometry was used to detect cell apoptosis. Results There was a targeting relationship between lncRNA XIST and miR-124. The expressionlevels of lncRNA XIST and NF-κB P65 protein and the apoptosis rate in the IL-1β-induced chondrocytes were increased, while the expression level of miR-124 was decreased when compared withthose in the normal group (P < 0. 05). The expression level of NF-κB P65 protein and the apoptosisrate in the si-XIST group and the miR-124 mimics group were reduced when compared with those inthe IL-1β group (P < 0. 05). The expression level of NF-κB P65 protein and the cell apoptosis rate in the si-XIST + inhibitor-NC group were reduced when compared with those in the si-NC + inhibitorNC group. The expression level of NF-κB P65 protein and the apoptosis rate in the si-XIST + miR-124 inhibitor group were decreased when compared with those in the si-NC + miR-124 inhibitorgroup, ( P < 0. 05). Conclusion Down-regulation of lncRNA XIST can target and regulate themiR-124 / NF-κB axis, thereby alleviating the apoptosis of chondrocytes induced by IL-1β.

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Research Progress of KCNQ1 Channel Structure and Function #br#

LIU Hongyu , XIE Jinyan ,

Journal of Medical Molecular Biology 2024, 21 (5): 487-491. DOI: 10.3870/j.issn.1672-8009.2024.05.016

Abstract （293）

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The KCNQ1 channel is a voltage-gated potassium channel subunit, which is assembled with the proteins of KCNE family to form a functional potassium channel. Changes in the structure and function of KCNQ1 channels affect the pathophysiological processes of various diseases in vivo. In this paper, the structure of KCNQ1, its role in various molecular biological processes, andthe interaction between KCNQ1 and the KCNE family or non-KCNE family are discussed, and the biophysical research progress on KCNQ1 channels are summarized systematically.

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Advances in Effect of B Cell Activating Factor/ A Proliferation-inducing Ligand on B Cell Function in Idiopathic Inflammatory Myopathies #br#

XIAO Yao, YU Fei, HU Shaoxian

Journal of Medical Molecular Biology 2024, 21 (5): 492-496. DOI: 10.3870/j.issn.1672-8009.2024.05.017

Abstract （200）

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Research Progress on Mechanism of Scutellaria baicalensis and Its Compounds Preparations against Candida albicans Infection #br#

NIU Chunyu, FENG Wenli

Journal of Medical Molecular Biology 2024, 21 (5): 497-500. DOI: 10.3870/j.issn.1672-8009.2024.05.018

Abstract （213）

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In recent years, the incidence of candidiasis has increased significantly due to the COVID-19 pandemic. Candida albicans infection and resistance of commonly used therapeutic drugs have become increasingly serious public health problems globally. The extract of Scutellaria baicalensis, its monomer components and the traditional Chinese medicine compounds preparations have been proved to have good anti- Candida albicans activities in experiments and clinics. However, themechanisms seem to be very complex, which may be related to inhibiting adhesion and invasion, affecting biofilm formation, inducing apoptosis, disrupting calcium homeostasis, disrupting glycolysis, inhibiting effecting pump, fighting inflammation and improving immunity.

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ERK Pathway Activation by Fam172a Gene Knockdown Aggravates Lipotoxic Hepatocyte Injury #br#

LI Mengqi, WEI Herui, LOU Jing, AN Wen, SONG Aqian, HE Lingling, YANG Junru, WEI Hongshan, #, XIAO Fan, #

Journal of Medical Molecular Biology 2024, 21 (6): 501-507. DOI: 10.3870/j.issn.1672-8009.2024.06.001

Abstract （305）

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Objective To preliminarily explore the mechanism of Fam172a gene knockout in lipid toxic liver cell injury. Methods Fam172a gene knockout (Fam172a - / - ) mice was used to assess liver function, liver tissue lipid accumulation, and inflammatory cytokine levels. Fam172a geneknockdown HepG2 cell lines were performed to assess intracellular lipid accumulation and inflammato
ry cytokine levels. Protein levels were analyzed via Western blotting. Results Compared to the controlgroup, Fam172a - / - mice exhibited significantly elevated serum ALT and AST levels, aggravated hepatic structural damage, lipid accumulation, and inflammation. Moreover, there was a significant upregulation in hepatic pERK/ ERK relative expression levels. Fam172a gene knockdown led to increased triglyceride content and inflammatory cytokine levels in HepG2 cells, along with a significant elevation in the relative expression level of pERK/ ERK. However, the administration of the ERK inhibitor U0126 notably mitigated the lipotoxic hepatocyte injury induced by Fam172a gene knockdown. Conclusion Fam172a gene knockdown exacerbates hepatocyte lipotoxicity through the activation of the ERK pathway.

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Inhibitory Effect of FOXO4 on Lipopolysaccharide-induced Apoptosis in Cardiomyocytes #br#

LI Hongjian, WANG Siyue

Journal of Medical Molecular Biology 2024, 21 (6): 508-514. DOI: 10.3870/j.issn.1672-8009.2024.06.002

Abstract （195）

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Objective This study was to investigate the effects of FOXO4 on lipopolysaccharide(LPS) -induced inflammation and apoptosis of cardiomyocytes, and to explore the potential molecular mechanism. Methods LPS treated H9C2 cells were treated with FOXO4 recombinant lentiviralvector (LPS + Lv-FOXO4), control vector ( LPS + Lv-NC group) and / or nigericin ( LPS + LvFOXO4 + N group) respectively. Real-time quantitative polymerase chain reaction ( RT-qPCR) was used to detect the expression level of FOXO4 mRNA. The levels of TNF-α and IL-1β in cell supernatant were detected by enzyme-linked immunosorbent assay. The apoptosis was detected by flow cytometry. The expression levels of FOXO4 and NF-κB / NLRP3 pathway-related proteins was analyzed by Western blotting. Results LPS treatment could inhibit the expression of FOXO4 in myocytes (P < 0. 05), while overexpression of FOXO4 could decrease the levels of TNF-α and IL-1β,inhibit the apoptosis of myocytes, decrease the expression level of pro-apoptotic protein Bax and increase the expression level of anti-apoptotic protein Bcl-2 in myocytes treated with LPS (P < 0. 05).In addition, overexpression of FOXO4 could inhibit the activation of NF-κB signaling pathway by inhibiting P65, IκBα phosphorylation and P65 nuclear shift ( P < 0. 05). Overexpression of FOXO4inhibited NLRP3 inflammasome activation and pyroptosis by inhibiting NLRP3, ASC, cleavedcaspase-1, and N-GSDMD protein expression ( P < 0. 05 ). The NLRP3 inflammasome activator Nigeritin could reverse the protective effect of FOXO4 overexpression on LPS-induced myocardialcell injury ( P < 0. 05). Conclusion Overexpression of FOXO4 can protect cardiomyocytes fromLPS-induced inflammation and apoptosis, possibly by inhibiting pyroptosis mediated by NF-κB / NLRP3 inflammasome signaling pathway.

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Anti-tumor Effect of Pterostilbene on Tongue Squamous Cell Carcinoma CAL-27 Cells #br#

DAI Xiaoyan, WANG Yansong, DAI Juan, ZHAI Yan

Journal of Medical Molecular Biology 2024, 21 (6): 515-520. DOI: 10.3870/j.issn.1672-8009.2024.06.003

Abstract （339）

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Objective Explore the effect of Pterostilbene on the biological behavior of humantongue squamous cell carcinoma CAL-27 cells. Methods CAL-27 cells were divided into 2 groups:control group and experimental group. Cells in the experimental group were treated with Pterostilbene(10, 20, 40 μmol / L). CCK-8 assay, colony formation assay and EdU staining were used to measure the proliferation of CAL-27 cells. Flow cytometry was used to determine the apoptosis of CAL-27cells. Wound-healing and Transwell assay were used to detect the migration and invasion ability of CAL-27 cells. Western blotting was used to detect the expression levels of epithelial-mesenchymaltransition (EMT) -related proteins in CAL-27 cells. Xenograft model was used to verify the effect ofpterostilbene on tumor in vivo. Results The proliferation, migration and invasion abilities of CAL-27 cells were weakened, the apoptosis rate was increased, the expression levels of Bax, E-cadherin and Claudin1 proteins in the cells were increased, and the expression levels of Bcl-2, N-cadherin, Vimentin and Snail proteins were decreased after 24 h treatment with 20 and 40 μmol / Lpterostilbene when compared with those in the control group ( P < 0. 05). After treatment with 30mg / kg pterostilbene, the weight and volume of transplanted tumors in nude mice decreased significantly, the number of Ki67 and Vimentin positive cells decreased significantly, and the number of TUNEL positive cells increased significantly ( P < 0. 05). Conclusion Pterostilbene can inhibitCAL-27 cells proliferation, migration, invasion and EMT and induce its apoptosis.

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Effect of Tanshinone Ⅱ-A on Th17 / Treg Balance and TLR4 Related Pathways in Osteoarticular Cartilage Degeneration Rats #br#

SUN Mengdi, SHANG Xiaolin, WANG Xiaojing

Journal of Medical Molecular Biology 2024, 21 (6): 521-529. DOI: 10.3870/j.issn.1672-8009.2024.06.004

Abstract （148）

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Objective To investigate the effect of tanshinone Ⅱ -A (TSⅡ -A) on regulatory T(Treg) / helper T cell 17 (Th17) in osteoarthritis (OA) cartilage degeneration rats, and its regulation on the expression of Toll like receptor 4 (TLR4) signaling pathway related genes. Methods The rat OA model was constructed by injecting papain into the joint cavity, rats then were dividedinto 3 groups for drug intervention: TS Ⅱ -A low-dose group ( TS Ⅱ -A-L), TS Ⅱ -A high-dosegroup (TSⅡ -A-H), and glucosamine sulfate (DGS) group as positive control. Enzyme linked immunosorbent assay was used to detect the levels of tumor crossing factor-α (TNF-α) and interleukin-6 ( IL-6) in serum. TUNEL assay was used to detect the cell apoptosis in rat cartilage tissues. Flow cytometry was used to detect the proportion of Treg and Th17 in spleen tissues. qRT-PCRwas used to detect the mRNA expression levels of TLR4, myeloid differentiation factor 88(MyD88), nuclear factor κB ( NF-κB), aggrecan, Collagen Ⅱ , forkhead / winged helix transcription factor 3 (Foxp3), IL-17, B cell lymphoma-2 (Bcl-2), and Bcl-2 associated x protein(Bax) in rat knee joint cartilage tissues. Western blotting assay was used to detect the expressionlevels of TLR4, MyD88, p-NF-κB, Bcl-2 and Bax in the cartilage tissues. Results The proportion of Treg cells, and the expression levels of aggrecan, Collagen Ⅱ , Foxp3, and Bcl-2 in theOA group were significantly decreased, and the levels of TNF-α and IL-6, the cell apoptosis rate,the proportion of Th17 cells, and the expression levels of IL-17, TLR4, MyD88, p-NF-κB andBax were significantly increased when compared with those in the Sham group. The proportion of Tregcells, and the expression levels of aggrecan, Collagen Ⅱ , Foxp3, and Bcl-2 in the TSⅡ -A-Lgroup, TSⅡ -A-H group, and DGS group were significantly increased, and the levels of TNF-αand IL-6, the cell apoptosis rate, the proportion of Th17 cells, and the expression levels of IL-17,TLR4, MyD88, p-NF-κB and Bax were significantly decreased when compared with those in theOA group. The proportion of Treg cells and the expression levels of aggrecan, Collagen Ⅱ , Foxp3,and Bcl-2 in the TSⅡ -A-H group and the DGS group were significantly increased, and the levels ofTNF-α and IL-6, the cell apoptosis rate, the proportion of Th17 cells, and the expression levels ofIL-17, TLR4, MyD88, p-NF-κB and Bax were significantly decreased when compared with thosein the TSⅡ -A-L group ( all P < 0. 05). No statistically significance in those above indexes werefound between the TSⅡ -A-H group and the DGS group (P> 0. 05). Conclusion Tanshinone Ⅱ -A(TSⅡ -A) could significantly inhibit the expression of TLR4, MyD88, p-NF-κB and reduce thecell apoptosis rate in the articular cartilage tissues of OA rats, which may be related to the improvement of Treg / Th17 imbalance in rats.

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Cordycepin Relieves Brain Tissue Damage in Rats with Cerebral Ischemia and Reperfusion by Activating Nrf2 / HO-1 / NQO1 Pathway#br#

WU Shuang, DAI Xubo, CUI Zhen, JIANG Fengying, PANG Suqiu

Journal of Medical Molecular Biology 2024, 21 (6): 530-536. DOI: 10.3870/j.issn.1672-8009.2024.06.005

Abstract （181）

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Objective To investigate the protective effect of cordycepin (COR) on brain tissue damage in rats with cerebral ischemia-reperfusion, and to preliminarily clarify the protectivemechanism. Methods Sixty Wistar rats were divided into 3 groups: Normal control group, modelgroup, and model plus drug group. Detection of learning and memory capacities in rats by step-down test and Y maze test. HE staining was employed to observe the pathological changes of brain tissues. Dry and wet weight ratio was used to calculate brain water content and brain index. TUNEL was used to observe cell apoptosis in brain tissues. The levels of serum SOD, MDA and LDH of rats were determined by ELISA. Western blotting was used to detect the expression levels of Bax / Bcl-2,cleaved cas9 / cas9, cleaved cas3 / cas3, Nrf2, HO-1 and NQO1 proteins. Results Compared withthe model group, COR can dose dependently improve brain tissue damage, inhibit oxidative stress,and promote activation of the Nrf2 / HO-1 / NQO1 pathway. Conclusion Cordycepin can improve brain tissue damage by upregulating the Nrf2 pathway.

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Effect of M2-type Macrophage-derived Exosomes on Multiple Myeloma Cell Metastasis by Regulation of HGF / c-Met Pathway #br#

Mukeremu Aikepaer, Vinila Tuerhong, Bahaguli Yusufu, Aikebaier Abudureyimu

Journal of Medical Molecular Biology 2024, 21 (6): 537-543. DOI: 10.3870/j.issn.1672-8009.2024.06.006

Abstract （149）

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Objective To investigate the effect of M2-type macrophage-derived exosomes on human multiple myeloma cell metastasis and its mechanism. Methods THP-1 cells were induced to differentiate into M0 and M2 macrophages in vitro. Real-time fluorescent quantitative polymerase reaction ( RT-qPCR) was used to detect the expression levels of hemoglobin scavenger receptor ( CD163 ), interleukin-10 ( IL-10 ), arginase-1 ( Arg-1 ) and transforming growth factor-β1 ( TGF-β1 ) in induced M2 macrophages. Exosomes derived from M2 macrophages were isolated. RPMI-8226 cells were divided into 3 groups: control group, M0-Exos group and M2-Exos group. Then the cell migration and invasion were detected by Transwell. The expression levels of Ncadherin, Vimentin, E-cadherin and the transcription factor Snail, and hepatocyte growth factor (HGF) / c-Met related proteins were detected by Western blotting. Moreover, RPMI-8226 cells were then divided into 4 groups: control group, M2-Exos group, SU11274 group and SU11274 + M2-Exos group, and cell migration and invasion were detected by Transwell, and the expressionlevels of N-cadherin, Vimentin, E-cadherin and Snail were detected by Western blotting. Results The mRNA expression levels of CD163, IL-10, Arg-1 and TGF-β1 in the M2 macrophages weresignificantly up-regulated when compared with those in the M0 macrophages (P< 0. 05). The particles isolated from the M2 macrophages showed protein expressions of CD9, CD63, TSG101 and ALIX, and were identified as exosomes. The numbers of cell migration and invasion in the M2-Exosgroup were significantly increased when compared with those in the control group (P < 0. 05), theprotein expression levels of N-cadherin, Vimentin and Snail, and the HGF protein expression andp-c-Met / c-Met ratio were significantly increased (P< 0. 05), and the protein expression level of Ecadherin was significantly decreased (P< 0. 05). The numbers of cell migration and invasion in theSU11274 + M2-Exos group were significantly decreased when compared with those in the M2-Exosgroup (P< 0. 05), the protein expression levels of N-cadherin, Vimentin and Snail were significantly decreased (P< 0. 05), and the protein expression level of E-cadherin was significantly increased (P< 0. 05). Conclusion M2-type macrophage-derived exosomes can promote the migration, invasion and EMT of human multiple myeloma cells, which exacerbate tumor cell metastasis, the mechanism may relate to the regulation of HGF / c-Met pathway.

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Mechanism of Upregulation of Numb to Increase Chemotherapy Sensitivity of Gastric Cancer Cells by Regulating Iron Death Pathway #br#

WANG Yongqi, LI Qiang, HE Donglei, CHEN Yong, LIU Lijie

Journal of Medical Molecular Biology 2024, 21 (6): 544-550. DOI: 10.3870/j.issn.1672-8009.2024.06.007

Abstract （123）

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Objective To investigate the effect of up-regulated cell fate determinant Numb on chemotherapy sensitivity of gastric cancer cells and its mechanism. Methods pcDNA3. 1 plasmidvector and PCDNA3. 1-Numb plasmid were transfected into gastric cancer cell line BGC-823 by liposome transfection technique. The transfected BGC-823 cells were treated with different concentrations of doxorubicin ( ADM ), and the cell proliferation inhibition rate was determined by MTT assay. BGC-823 cells were divided into 4 groups: control group, NC group, Numb group, and Numb + Ferrostatin-1 ( Fer-1) group, and the cell proliferation inhibition rate of each group was determined, and the level of reactive oxygen species (ROS) in each group was detected by DCFH-DA fluorescent probe method. The levels of glutathione (GSH), malondialdehyde (MDA) and theactivity of superoxide dismutase (SOD) were measured by kits, and the concentration of iron ionin cells was determined by the iron ion detection kit. The expression levels of Numb, iron death related pathway factor P53, glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11(SLC7A11) were detected by qRT-PCR and Western blotting. Results The mRNA and protein relative expression levels of Numb in the Numb group were significantly up-regulated (P < 0. 05), and the cell proliferation inhibition rate was significantly increased after ADM treatment (P< 0. 05)when compared with those in the control and NC groups. In comparison of those in the control group and NC group, the cell proliferation inhibition rate in the Numb group was significantly increased( P< 0. 05), the levels of ROS and MDA in cells were significantly increased (P< 0. 05), the level of GSH content and the activity of SOD was significantly decreased (P < 0. 05), the Fe2 + concentration was significantly increased (P< 0. 05), the expression level of P53 was significantly increased (P< 0. 05), and the expression levels of GPX4 and SLC7A11 were significantly decreased (P < 0. 05). After the intervention by Fer-1 treatment, the proliferation inhibition rate of BGC-823 cells in the Numb + Fer-1 group was significantly decreased (P<0. 05), the levels of ROS and MDA were significantly decreased (P<0. 05), the GSH level and SOD activity were significantly increased (P<0. 05), the Fe2 + concentration was significantly decreased (P < 0. 05), the expression level of P53 were significantly decreased (P<0. 05), and the expression levels of GPX4 and SLC7A11 were significantly up-regulated (P< 0. 05) when compared with those in the Numb group. Conclusion Up-regulation of Numb can enhance the sensitivity of gastric cancer cells to ADM, which may be related to the regulation of P53 / SLC7A11 / GPX4 pathway to induce ferroptosis.

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Effect of Interaction Between miR-146a-5p and miR-21 on Risk and Severity of Primary Nephrotic Syndrome #br#

CHEN Jinghe, ZHANG Yanqin, LI Wendong

Journal of Medical Molecular Biology 2024, 21 (6): 551-556. DOI: 10.3870/j.issn.1672-8009.2024.06.008

Abstract （143）

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Objective To investigate the relationship between the interaction of microRNA-146a-5p (miR-146a-5p) and microRNA-21 ( miR-21) and its effect on the risk and severity ofprimary nephrotic syndrome (NS). Methods A total of 103 patients with NS from August 2021 toAugust 2023 were selected as the study group, and another 103 healthy volunteers who underwent physical examination during the same period were selected as the control group. Compare the different pathological types [minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS)] and the degree of renal injury in the two groups, and study the relative expression levels of serum miR-146a-5p and miR-21 in patients. Analyze the diagnostic value and interactive effects of miR-146a-5p and miR-21 on NS, and further analyze the correlationbetween miR-146a-5p, miR-21, and disease severity. Results The relative expression level ofmiR-146a-5p in the study group was lower than that in the control group, and the relative expressionlevel of miR-21 was higher than that in the control group (P < 0. 05). The relative expression levels of serum miR-146a-5p and miR-21 in patients with different pathological types or different degrees ofrenal injury in the study group showed significant differences (both P< 0. 05). The AUC of the combined diagnosis of NS by miR-146a-5p and miR-21 was 0. 923 (95 % CI: 0. 877 - 0. 955), thesensitivity was 78. 64 % , and the specificity was 90. 29 % , which were significantly better than those of miR-146a-5p and miR-21 alone. The optimal cut-off value was used to divide miR-146a-5p and miR-21 into high expression group and low expression group. The low expression of miR-146a-5p and high expression of miR-21 had a positive interaction on the risk of NS development, which was a sub-multiplication model. miR-146a-5p was negatively correlated with NS pathological types andthe degree of kidney injury (r = - 0. 613, - 0. 657, P< 0. 05), while miR-21 was positively correlated with NS pathological types and the degree of kidney injury (r = 0. 664, 0. 702, P< 0. 05). Conclusion The abnormal expression of miR-146a-5p and miR-21 in the serum of NS patients isassociated with the degree of kidney injury in patients. In addition, miR-146a-5p and miR-21 have a positive interactive effect on the risk of NS, and their simultaneous exposure can increase the risk of NS.

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Effect of miR-660-5p on High Glucose-induced Glomerular Mesangial Cell Injury by Regulation of P53 #br#

GU Liang, MA Xiaoxi, JIN Zhimin

Journal of Medical Molecular Biology 2024, 21 (6): 557-561. DOI: 10.3870/j.issn.1672-8009.2024.06.009

Abstract （116）

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Objective To investigate the effect of miR-660-5p on high glucose-induced glomerular mesangial cell injury by regulating P53. Methods SV40-MES-13 cells were divided into two groups: control group and high glucose group, to analyze the effect of high glucose on cell viability and expression of miR-660-5p / P53. Then SV40-MES-13 cells treated with high glucose were divided into four groups: miR NC group, miR-660-5p mimic group, siNC group and siP53 group. The expression levels of miR-660-5p and P53 in SV40-MES-13 cells were detected by real-time fluorescence quantitative PCR. The growth ability of SV40-MES-13 cells was analyzed by methyl thiazolyl tetrazolium (MTT) assay. The apoptosis rate of SV40-MES-13 cells was analyzed by TUNEL and flow cytometry. Targetscan and luciferase reporter assay were used to analyze the targeting relationship between miR-660-5p and P53 in SV40-MES-13 cells. The expression level of P53 protein wasanalyzed by Western blotting. Results Compared with cells in the control group, SV40-MES-13cells treated with high glucose showed decreased proliferation activity, increased apoptosis rate, decreased expression level of miR-660-5p and increased expression level of P53. The proliferation activity of SV40-MES-13 cells treated with miR-660-5p mimic was increased, and the apoptosis rate was decreased when compared with those in the miR-660-5p NC group. The proliferation activity of SV40-MES-13 cells treated with siP53 was increased, and the apoptosis rate was decreased when compared with those in the siNC group. miR-660-5p could bind with P53 and inhibit the expressionof P53. Conclusion The expression level of miR-660-5p is decreased and the expression level ofP53 is increased in high glucose-treated mesangial cells. Up-regulation of miR-660-5p expression in high glucose-treated mesangial cells increases the proliferation activity and decreases the apoptosis rate, and the effect of miR-660-5p is related to the inhibition of P53 expression.

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The Role and Mechanism of miR-499a-3p/ GAB1 Axis in Heart Failure #br#

GUO Mei, XIA Li, XIE Zhiwen

Journal of Medical Molecular Biology 2024, 21 (6): 562-567. DOI: 10.3870/j.issn.1672-8009.2024.06.010

Abstract （142）

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Objective To explore the expression level of miR-499a-3p in the plasma of patients with heart failure (HF) and its potential mechanism. Methods The plasma from HF patients andhealthy controls was collected, and the expression level of miR-499a-3p was detected by RTqPCR. After transfecting miR-499a-3p mimics into human cardiomyoblast cells, CCK-8 was used to detect the effect of miR-499a-3p on cell proliferation. Flow cytometry and TUNEL were used to detect apoptosis, and Western blotting was used to detect the expression levels of apoptosis-related proteins. The heart failure cell model was established, and miR-499a-3p inhibitor was transfected, CCK-8 and flow cytometry were used to detect cell viability and apoptosis. Dual luciferase reporter gene assay was used to investigate the targeted binding of miR-499a-3p to GAB1. The effect of miR- 499a-3p on GAB1 expression were detected. Finally, miR-499a-3p mimics and GAB1 plasmid wereco-transfected into human cardiomyoblast cells to detect the functional changes. Results Compared with the healthy volunteers, the expression level of miR-499a-3p in the plasma of patients with HFwas significantly higher ( t = 77. 47, P < 0. 01). miR-499a-3p mimics significantly decreased theproliferation rate of human cardiomyoblast cells and increased the proportion of apoptotic cells andTUNEL-positive cells (P < 0. 05). After transfection of miR-499a-3p mimics, the expression levelof apoptosis-inhibiting protein Bcl-2 was decreased, while the expression levels of apoptosis-promoting proteins Caspase-3 and Bax were up-regulated. Further studies showed that miR-499a-3p was significantly overexpressed in heart failure cells, and after inhibiting the expression of miR-499a- 3p, the proliferation rate of heart failure cells was significantly increased, and the apoptosis ratiowas significantly decreased (P< 0. 05). miR-499a-3p could bind to the 3′-untranslated region (3′-UTR) of GAB1, and targetly inhibit GAB1 mRNA and protein expression. Moreover, overexpression of GAB1 reversed the effect of miR-499a-3p on proliferation and apoptosis of human cardiomyoblast cells. Conclusion miR-499a-3p is upregulated in patients with HF, which can affect the proliferation and apoptosis of human cardiomyoblast cells through targeted inhibition of GAB1 protein expression, thus participating in the progression of HF.

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Reparative Effect of Mesenchymal Stem Cells Overexpressing LincRNA-p21 on Acute Lung Injury in Mice #br#

YAO Lidan, TANG Yongjun, ZHANG Yuhua, Yushanjiang ZHU MAHE, ZHANG Hongyu

Journal of Medical Molecular Biology 2024, 21 (6): 568-575. DOI: 10.3870/j.issn.1672-8009.2024.06.011

Abstract （140）

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Objective To investigate the reparative effect of mesenchymal stem cells (MSCs)overexpressing long intergenic non-coding RNA ( lincRNA) -p21 on acute lung injury ( ALI) inmice. Methods Seventy male C57BL / 6 mice were randomly divided into 7 groups, with n = 10 ineach group. The 7 groups were as follows: sham group, ALI group, MSC + ALI group, p21-MSC + ALI group, empty vector-MSC + ALI group, p21 + ALI group, and empty vector + ALI group. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression level of lincRNA-p21 in lung tissues of each group. ELISA was used to detect the levels of TNF-α, IL- 1β, IL-8, IL-6, IL-10, IL-13, IL-1Ra, and caspase3 in bronchoalveolar lavage fluid. The effects on arterial blood oxygen pressure ( PaO2 ), lung index ( LI), lung permeability index (LPI), and oxygenation index (OI) were evaluated. Flow cytometry was used to detect and ana
lyze the proportion of apoptotic cells in lung tissues. Western blotting was used to detect the expression levels of Bcl-2, Bax, caspase3, and cleaved-caspase3 in lung tissues. Results The levels of lincRNA-p21, IL-10, IL-13, IL-1Ra, Bcl-2, and the values of PaO2 and OI in the ALI group were decreased, while LI, LPI, TNF-α, IL-1β, IL-8, IL-6, Bax, caspase3, cleaved-caspase3 were upregulated, and the proportion of apoptotic cells was increased when compared with those inthe sham group ( all P < 0. 05). The levels of IL-10, IL-13, IL-1Ra, Bcl-2, and the values ofPaO 2and OI were all increased in the MSC + ALI group, and the levels of TNF-α, IL-1β, IL-8, IL-6, Bax, caspase3 and cleaved caspase3, and the values of LI were all decreased when compared with those in the ALI group, the proportion of apoptotic cells was decreased (all P< 0. 05).The expression level of lincRNA-p21 and the value of LPI had no significant change between abovegroups (P > 0. 05). The levels of lincRNA-p21, IL-10, IL-13, IL-1Ra, Bcl-2, and the valuesof PaO 2and OI were increased, while values of LI, LPI, and levels of TNF-α, IL-1β, IL-8, IL- 6, Bax, caspase3, cleaved-caspase3 were decreased, and the proportion of apoptotic cells was decreased in the p21-MSC + ALI group when compared with those in the empty vector-MSC + ALIgroup (all P< 0. 05). The levels of lincRNA-p21, IL-10, IL-13, IL-1Ra, Bcl-2, and the values of PaO 2and OI in the p21 + ALI group were increased (all P < 0. 05), and the levels of TNF-α,IL-1β, IL-8, IL-6, Bax, caspase3, and cleaved caspase3, and the values of LI, LPI were decreased, and the proportion of apoptotic cells was decreased when compared with those in the emptyvector + ALI group (all P< 0. 05). Conclusion MSCs overexpressing lincRNA-p21 have an inhibitory effect on inflammatory injury and lung cell apoptosis in ALI mice.

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Effect of P38 MAPK on Osteogenic Differentiation of Periodontal Ligament Stem Cells by Regulating Wnt / Ca2 + Signaling Pathways under Inflammatory Microenvironment #br#

CHEN Qi, ZHOU Chun, QI Xue, XIA Jingping

Journal of Medical Molecular Biology 2024, 21 (6): 576-580. DOI: 10.3870/j.issn.1672-8009.2024.06.012

Abstract （186）

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Objective To explore the effect of P38 mitogen-activated protein kinase (MAPK)on osteogenic differentiation and Wnt / Ca2 + signaling pathways in periodontal ligament stem cells(PDLSC) under microinflammatory environment. Methods Human PDLSC were divided into 4groups: control group, TNF-α group, TNF-α + SB203580 group ( 20 μmol / L SB20358 ) and TNF-α + SB203580 + XAV939 group (20 μmol / L SB20358 + 10 μmol / L XAV939). Except for cells in the control group, cells in the other groups were given 10 ng / mL TNF-α to simulate inflammatory microenvironment. The osteogenic differentiation ability was detected by alizarin red staining. The activity of alkaline phosphatase (ALP) in each group was compared. The expression levels of RUNt-related transcription factor 2 (Runx2), osteocalcin (OCN), Osterix (OSX) and osteopontin (OPN) were detected by qRT-PCR, and the expression levels of P38 MAPK, β-catenin, calmodulin dependent protein kinase Ⅱ (CaMKⅡ ) and Nemo-like (NLK) were detected byWestern blotting. Results The staining intensity and number of calcification nodules in the TNF-αgroup were significantly decreased, and in comparison of those in the TNF-α group, the staining intensity and number of calcification nodules were significantly improved in the TNF-α + SB203580 group, but there was no significant difference in staining intensity or number of calcification nodules between the TNF-α + SB203580 + XAV939 group and the TNF-α + SB203580 group. Compared with those in the control group, the activity of ALP and mRNA expression levels of Runx2, OCN, OSXand OPN were decreased in the TNF-α group (P< 0. 05), the expression level of P38 MAPK protein was increased (P< 0. 05), and the expression levels of β-catenin, CaMKⅡ and NLK proteins were decreased (P< 0. 05). Compared with those in the TNF-α group, the activity of ALP and mRNA expression levels of Runx2, OCN, OSX and OPN were increased in the TNF-α + SB203580group (P< 0. 05), the expression level of P38 MAPK protein was decreased (P< 0. 05), and the expression levels of β-catenin, CaMKⅡ and NLK proteins were increased (P < 0. 05). Comparedwith those in the TNF-α + SB203580 group, the expression level of β-catenin protein was decreasedin the TNF-α + SB203580 + XAV939 group (P< 0. 05), but there was no significant difference inALP activity, mRNA expression levels of Runx2, OCN, OSX and OPN or expression levels of P38MAPK, CaMKⅡ and NLK proteins between the two groups (P> 0. 05). Conclusion P38 MAPKinhibitor can improve osteogenic differentiation of PDLSC under inflammatory microenvironment, which may be related to activating Wnt / Ca2 + signaling pathways.

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Non Coding RNA TUG1 Affects the in vitro Metastatic Activity of Bladder Cancer Cells by Regulating P38 MAPK Signaling Pathway #br#

GAO Bo, FAN Xiaomeng, CUI Jun, LI Wenhua, SHI Jiabao

Journal of Medical Molecular Biology 2024, 21 (6): 581-585. DOI: 10.3870/j.issn.1672-8009.2024.06.013

Abstract （139）

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Objective To investigate the effect of Long non-coding RNA taurine-upregulatedgene 1 (lnc TUG1) on the metastasis of bladder cancer cells and the related mechanism. Methods Tissue samples were collected from patients with bladder urothelial carcinoma treated in BaodingSecond Hospital, and the expression levels of lnc TUG1 and P38 mitogen-activated protein kinases(P38 MAPK) in tissues were detected by real-time fluorescence quantitative PCR. Human bladdercancer cell line 5637 cells were divided into three groups: siNC group, si TUG1 group and si P38 group. The siNC, si TUG1 and si P38 plasmids were transfected into the corresponding experimentalgroups, and the cell growth ability, invasion ability, apoptosis rate and the expression level of P38 MAPK were detected by cell colony formation assay, Transwell assay, flow cytometry and Westernblotting. Results The expression level of TUG1 was increased, while the expression level of P38MAPK was decreased in the cancer tissues when compared with those in the cancer tissues. The number of colony formation and invasion of bladder cancer cells in the si TUG1 group was significantly decreased, the apoptosis rate was significantly increased, and the expression level of P38MAPK protein in the si TUG1 group was significantly up-regulated when compared with those in thesi NC group. However, the number of colony formation and invasion of bladder cancer cells in the si P38 group were significantly increased, and the apoptosis rate was significantly decreased whencompared with those in the siNC group. Conclusion Inhibition of lnc TUG1expression can inhibit the colony formation ability and invasion ability of bladder cancer cells, and promote the apoptosis of bladder cancer cells, and the potential mechanism might be associated with the inhibition of P38 MAPK.

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Influence of Ischemic Postconditioning on Cardiac Function, Myocardial Apoptosis and Expressions of Myocardial Tissue Mitochondrial Apoptosis-related Molecules in Rats with Myocardial Ischemia-reperfusion #br#

WANG Tao, HAO Engang

Journal of Medical Molecular Biology 2024, 21 (6): 586-590. DOI: 10.3870/j.issn.1672-8009.2024.06.014

Abstract （104）

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Objective To analyze the influence of ischemic postconditioning (IP) on cardiacfunction, myocardial apoptosis and expressions of myocardial tissue mitochondrial apoptosis-relatedmolecules in rats with myocardial ischemia-reperfusion (IR). Methods Forty 8-week-old male SDrats were fed in separate cages with 5 rats in each cage for 7 days of adaptive feeding, and were randomly divided into 4 groups: blank control group ( control group), sham operation group ( S group), myocardial IR model group ( IR group) and myocardial IR model + IP treatment group (IP group), with 10 rats in each group. At 4 hours after surgery, the cardiac function indicators [left ventricular systolic pressure ( LVSP), left ventricular end-diastolic pressure ( LVEDP), maximum rate of left ventricular pressure change ( ± dp / dtmax)] were recorded by biological functional system, and the apoptosis of myocardial cells was detected by TUNEL method. RT-PCR was used to detect the relative expression levels of myocardial apoptosis-related proteins BCL-2, BAX, cysteinyl aspartate specific protease-3 ( Caspase-3), farnesoid X receptor ( FXR) and small heterodimer partner (SHP). Western blotting was applied to detect the release of myocardial mitochondrial apoptosis pathway marker cytochrome C ( Cyt-C). Results The LVEDP, apoptosis index ofmyocardial cells, and the expression levels of BAX, CASPASE-3, FXR and SHP in myocardial tissues and the expression level of Cyt-C protein in myocardial cytoplasm were higher in the IP andIR groups than those in the S and control groups ( P < 0. 05), moreover, the above indicators in the IR group were higher than those in the IP group (P < 0. 05). The LVSP, ± dp / dtmax and theexpression level of BCL-2 in myocardial tissues in the IP group and IR group were lower than thosein the S group and control group (P< 0. 05), and the above indicators were lower in the IR group than those in the IP group (P < 0. 05). Conclusion IP treatment can alleviate the myocardial IRinjury and improve the cardiac function in rats, which may be related to the regulations of apoptosisrelated signal proteins such as BCL-2 / BAX and FXR / SHP.

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Expression of GATA3 Protein in Thyroid Carcinoma and Its Relationship with Clinicopathologic Features and Surgical Prognosis #br#

XUE Cui’e, WANG Xinlei, WANG Yahong

Journal of Medical Molecular Biology 2024, 21 (6): 591-596. DOI: 10.3870/j.issn.1672-8009.2024.06.015

Abstract （149）

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Objective To analyze the expression of GATA binding protein 3 ( GATA3) inthyroid carcinoma and its relationship with clinicopathological features and surgical prognosis. Methods A total of 150 patients with thyroid carcinoma treated by surgery in Xilingol LeagueCentral Hospital, Inner Mongolia from August 2016 to December 2017 were selected, and the expression level of GATA3 protein was detected by immunohistochemistry between the cancer tissues and the normal tissues at the cutting edge. The expression level of GATA3 protein was compared between the cancer tissues and the normal tissues at the cutting edge, and the expression level of GATA3 protein in the thyroid carcinoma tissues of patients with different clinical and pathological characteristics was also compared. The relationship between the expression level of GATA3 protein incancer tissues and the surgical prognosis was analyzed after 5 years follow-up. Results The expression level of GATA3 protein in the thyroid carcinoma tissues was lower than that in the normal tissues (P < 0. 05). The expression level of GATA3 protein was lower in the thyroid carcinoma tissuesof undifferentiated and medullary carcinoma, TNM stage Ⅲ -Ⅳ, multiple lesions, maximum tumor diameter ≥ 2 cm, and patients with lymph node metastasis than in the thyroid carcinoma tissues of papillary adenocarcinoma and follicular adenocarcinoma, TNM stage Ⅰ -Ⅱ , single lesion, maximum tumor diameter < 2 cm, and patients without lymph node metastasis (P < 0. 05). During thefollow-up period, the survival rate of thyroid cancer patients was 83. 45 % , and the mortality ratewas 16. 55 % . Undifferentiated carcinoma ( RR = 1. 772, 95 % CI: 1. 221-2. 571 ), medullary carcinoma (RR = 2. 423, 95 % CI: 1. 609-3. 650), TNM stage Ⅲ -Ⅳ ( RR = 2. 020, 95 % CI:1. 447-2. 818), multiple lesions (RR = 1. 914, 95 % CI: 1. 421-2. 578), maximum tumor diameter ≥ 2 cm (RR = 1. 818, 95 % CI: 1. 129-2. 928), lymph node metastasis (RR = 1. 937, 95 %CI: 1. 241-3. 022), GATA3 protein expression (RR = 0. 488, 95 % CI: 0. 333-0. 715) were allfactors affecting the death of thyroid carcinoma patients ( P < 0. 05). The survival rate of patientswith high expression of GATA3 protein was higher than that of patients with low expression of GATA3 protein (P< 0. 05). Conclusion The expression of GATA3 protein is low in thyroid cancertissues, and the expression of GATA3 protein is related to pathological type, TNM stage, numberof lesions, tumor size and lymph node metastasis. The above indicators are all factors affecting theprognosis of patients after surgery.

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