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31 May 2024, Volume 21 Issue 3
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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
2024, 21(3):  187-195.  doi:10.3870/j.issn.1672-8009.2024.03.001
Abstract ( 78 )   PDF (4634KB) ( 63 )  
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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.
Role of RIPK3 in LPS / D-GalN Induced Acute Liver Failure #br#
YU Qian, BIAN Shu, ZHANG Yuting, ZHAO Sai, LIU Liangming
2024, 21(3):  196-202.  doi:10.3870/j.issn.1672-8009.2024.03.002
Abstract ( 137 )   PDF (3406KB) ( 41 )  
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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.

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
2024, 21(3):  203-210.  doi:10.3870/j.issn.1672-8009.2024.03.003
Abstract ( 33 )   PDF (4148KB) ( 34 )  
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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.

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
2024, 21(3):  211-216.  doi:10.3870/j.issn.1672-8009.2024.03.004
Abstract ( 46 )   PDF (1554KB) ( 42 )  
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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.

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
2024, 21(3):  217-223.  doi:10.3870/j.issn.1672-8009.2024.03.005
Abstract ( 28 )   PDF (5418KB) ( 22 )  
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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.

Expressions of CLEC1B, DKK1 and DRD4 in Primary Hepatic Cancer Tissues and Their Clinical Significance #br# #br#
DAI Yunlong, HUANG Jiwei
2024, 21(3):  224-230.  doi:10.3870/j.issn.1672-8009.2024.03.006
Abstract ( 46 )   PDF (3095KB) ( 26 )  
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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.

Formononetin Inhibits Proliferation, Migration and Invasion of Esophageal Carcinoma Cells by HNF4A #br#
ZHOU Jincai, ZANG Ting , LI Zhao , YANG Zhao , LI Wenhai
2024, 21(3):  231-238.  doi:10.3870/j.issn.1672-8009.2024.03.007
Abstract ( 29 )   PDF (8182KB) ( 27 )  
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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.

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
2024, 21(3):  239-246.  doi:10.3870/j.issn.1672-8009.2024.03.008
Abstract ( 29 )   PDF (6980KB) ( 23 )  
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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.

Mechanism of LINC00319 Regulating PENK / PI3K / AKT Signaling Pathway in Osteosarcoma #br#
XIA Fei, ZHANG Haiping
2024, 21(3):  247-253.  doi:10.3870/j.issn.1672-8009.2024.03.009
Abstract ( 39 )   PDF (3268KB) ( 31 )  
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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.

Effect of Blocking PI3K / Akt / mTOR Signaling Transduction on Leukemia HL-60 Cells #br#
GUO Chen, TANG Jing
2024, 21(3):  254-258.  doi:10.3870/j.issn.1672-8009.2024.03.010
Abstract ( 26 )   PDF (1624KB) ( 22 )  
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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.

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
2024, 21(3):  259-263.  doi:10.3870/j.issn.1672-8009.2024.03.011
Abstract ( 29 )   PDF (1261KB) ( 21 )  
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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.
GSK484 Inhibits Neutrophil Extracellular Traps Formation and Inflammatory Response in Ankylosing Spondylitis #br#
LI Rulin, DU Zhuangwen, WANG Enliang
2024, 21(3):  264-269.  doi:10.3870/j.issn.1672-8009.2024.03.012
Abstract ( 33 )   PDF (2104KB) ( 33 )  
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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.
Changes of LECT2 and FGF21 Levels in T2DM Patients Complicated with NAFLD and Their Clinical Significance #br#
LU Junru, HOU Kaiwen, WANG Deying
2024, 21(3):  270-274.  doi:10.3870/j.issn.1672-8009.2024.03.013
Abstract ( 30 )   PDF (955KB) ( 23 )  
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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.

Canagliflozin Alleviates Renal Fibrosis in Diabetic Nephropathy Mice by PDGF / SIRT1 #br#
ZENG Weixin, YUN Chuan, LI Xiaoyan, LI Dawei
2024, 21(3):  275-279.  doi:10.3870/j.issn.1672-8009.2024.03.014
Abstract ( 20 )   PDF (1323KB) ( 21 )  
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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.

LINC01138 Regulates Proliferation, Migration, and Invasion of SW620 Colorectal Cancer Cells through Targeting miR-559 #br#
GAO Dongyun, SUN Ting, CHEN Ping, ZHOU Xuefeng
2024, 21(3):  280-286.  doi:10.3870/j.issn.1672-8009.2024.03.015
Abstract ( 35 )   PDF (2438KB) ( 19 )  
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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.
Research Progress on Aspergillus fumigatus Associated C-type Lectin Receptor #br#
CHENG He, MIAO Guizhi, MA Yan
2024, 21(3):  287-292.  doi:10.3870/j.issn.1672-8009.2024.03.016
Abstract ( 42 )   PDF (1581KB) ( 39 )  
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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.