Objective To investigate the mRNA expression levels of immune infiltration-related genes in cervical cancer and cervical precancerous lesions and the relationship with prognosis. Methods A total of 74 patients with cervical cancer (cervical cancer group), 74 patients with cervical precancerous lesions (cervical pre-cancer lesions group), and another 74 patients who underwent hysterectomy for uterine fibroids (normal cervix group) in Affiliated Hospital of Yan’an University from January 2017 to January 2019 were selected. The mRNA expression levels of the immune infiltration-related genes [ human leukocyte antigen G ( HLA-G), forked-head helix transcription factor 3 (FOXP3), T cell immunoglobulin and mucin domain 3 (TIM-3)], and the malignant biological behavior related genes [invasive gene P21-activated kinase 6 (PAK-6), zeste 2 multiple comb inhibitory complex 2 subunit enhancer (EZH2), proliferative gene angiopoietin-like protein 4 ( ANGPTL4), homologous box gene B7 (HOXB7)] were compared among the above three groups. The relationship between the expression levels of the immune infiltration-related genes and the carcinogenesis and malignancy of cervical cancer were analyzed. The 3-year survival rate of patients with high or low mRNA expression levels of immune infiltration-related genes were compared. Results The relative mRNA expression levels of HLA-G, FOXP3 and TIM-3 in the cervical cancer group were the highest, and were lower in the cervical pre-cancer lesions group, the relative mRNA expression levels of the three genes were lowest in the normal cervix group (all P < 0. 05). Statistical significant differences were found in the relative mRNA expression levels of HLA-G, FOXP3, TIM-3, PAK-6, EZH2, ANGPTL4 and HOXB7 in patients with different clinical stages, degrees of differentiation, and presence or absence of lymph node metastasis and vascular infiltration (P< 0. 05). The risks of progression of cervical pre-cancer lesions to cervical cancer in patients with high mRNA expression levels of HLA-G, FOXP3 and TIM-3 were 3. 005, 4. 654 and 3. 343 times higher than those in patients with low expression levels respectively. The mRNA expression levels of HLA-G, FOXP3 and TIM-3 were positively correlated with the mRNA expression levels of PAK-6, EZH2, ANGPTL4 and HOXB7 (P< 0. 05). In 3 years of follow-up, 2 cases of cervical cancer were lost, the 3-year survival rate of the cervical cancer patients was 68. 06 % (49 / 72 ), and the 3-year survival rate of patients with high mRNA expression levels of HLA-G, FOXP3 and TIM-3 was lower than that of patients with low expression levels (P < 0. 05). Conclusion The mRNA of Immune infiltration-related genes HLA-G, FOXP3 and TIM-3 are upregulated in cervical cancer and cervical pre-cancer lesions, which significantly increases the risk of cervical cancer carcinogenesis and malignancy, it also have an important impact on the survival prognosis of cervical cancer patients.

Objective To investigate the influences of isoflurane on high glucose-induced cardiomyocyte injury in H9C2 cells and its mechanism through phosphatidylinositol 3 kinase (PI3K) / protein kinase B (AKT) / mammalian target of rapamycin (mTOR) signaling pathway. Methods H9C2 cardiomyocytes in the logarithmic growth phase were selected and grouped into 5 groups: control group ( untreated H9C2 cardiomyocytes), high glucose group (35 mmol / L glucose), isoflurane low-dose group (35 mmol / L glucose + 1 % isoflurane), isoflurane high-dose group (35 mmol / L glucose + 2 % isoflurane), isoflurane + LY294002 group (35 mmol / L glucose + 2 % isoflurane + 50 μmol / L LY294002). The proliferation of cells in each group was detected by CCK-8 method. The autophagy of cells in each group was observed by transmission electron microscope. The apoptosis of cells in each group was detected by flow cytometry. The expression levels of Beclin1, Bax, and PI3K/ Akt / mTOR pathway related proteins in the cells of each group were measured by Western blotting. Results The autophagosomes formed in the cells of the high glucose group could be observed obviously. The proliferation rate, and the levels of p-PI3K/ PI3K, p-Akt / Akt, and p-mTOR/ mTOR in high glucose group were decreased, while the apoptosis rate, and the expression levels of Bax and Beclin1 proteins were increased significantly when compared with those in the control group (P< 0. 05). After treated with different concentrations of isoflurane, the cell proliferation rate, and the levels of p-PI3K/ PI3K, p-Akt / Akt and p-mTOR/ mTOR were increased significantly, while the numbers of autophagosomes, the apoptosis rate, and expression levels of Bax and Beclin1 proteins were decreased significantly when compared with those in the high glucose group (P < 0. 05). The cell proliferation rate, levels of p-PI3K/ PI3K, p-Akt / Akt and p-mTOR/ mTOR decreased in the isoflurane + LY294002 group when compared with those in the isoflurane high-dose group, while the number of autophagosomes, the apoptosis rate, and the expression levels of Bax and Beclin1 proteins were increased significantly (P < 0. 05). Conclusion Isoflurane can inhibit the high-glucose induced autophagy and apoptosis in the H9C2 cardiomyocytes, which improves cell survival rate and reduces cell injury. The underlying mechanism may be related to the activation of PI3K/ Akt / mTOR pathway.

Objective To explore the function and mechanism of interfering long non-coding RNA LINC01133 in cervical cancer cells. Methods TCGA database and qRT-PCR were used to analyze the expression of LINC01133 in cervical cancer tissues and cells. The knockdown efficiency of LINC01133-shRNAs was detected by qRT-PCR. SiHa cells were divided into 3 groups: control group, shRNA-NC group and LINC01133-shRNA1 group. Colony formation assay was used to detect cell proliferation. ELISA assay was used to detect the levels of tumor necrosis factor-α ( TNF-α), interleukin (IL) -6 and IL-1β. The nuclear translocation of P65 in SiHa cells was detected by immunofluorescence. The phosphorylation of P65 was detected by Western blotting. The levels of superoxide dismutase (SOD) and lactate dehydrogenase (LDH) were detected by kits. A nude mouse xenograft model was established to analyze the effect of interfering LINC01133 expression on tumor growth. Results The expression of LINC01133 was significantly up-regulated in cervical cancer tissues and cells (P < 0. 05). The knockdown efficiency of LINC01133-shRNA1 was the best, thus the LINC01133-shRNA1 was selected for the subsequent experiments. The colony formation rate, the levels of inflammatory factors, the phosphorylation level of P65, the proportion of P65 level in nuclear, and the LDH level in the LINC01133-shRNA1 group were significantly increased when compared with those in the control group (P< 0. 05), while the SOD activity was significantly decreased ( P < 0. 05 ) . The volume weight of the tumor tissues, and the SOD activity in the LINC01133-shRNA1 group were significantly decreased when compared with those in the shRNA-NC group (P< 0. 05), while the phosphorylation level of P65 was significantly increased (P< 0. 05). Conclusion Interfering with the LINC01133 shRNA inhibits cervical cancer cell growth, decreases inflammatory factor levels and suppresses the oxidative stress in cervical cancer cells.

Objective To explore the effect of fibroblast growth factor 18 (FGF-18) in colon cancer. Methods The colon cancer cell lines (SW480) were cultured in vitro and divided into 3 groups: control group, shRNA-NC group and sh-FGF-18 group. The cells proliferation was detected by colony formation assay. The apoptosis was detected by flow cytometry. The changes of cells morphology after apoptosis were observed by Hoechst. The cell migration was detected by wound healing assay. The cell invasion was detected by Transwell assay. The metastasis of liver and lung tissues was observed by HE staining. The expression levels of epithelial-mesenchymal transition (EMT) related markers [ E-cadherin ( E-cad ), N-cadherin ( N-cad ), fibronectin ( FN)] were detected by Western blotting. The volume and size of tumors were detected by tumor formation assay in nude mice. The positive expressions of E-cad, N-cad and FN in colon cancer tissues were detected by immunohistochemistry. Results Compared with these in the shRNA-NC group, the relative expression levels of FGF-18 mRNA and protein were decreased in the FGF-18-shRNA group, the number of colonies, migrated cells and invasive cells were reduced, the number of apoptotic cells was increased, the expression level of E-cad was increased, and the expression levels of N-cad and FN were decreased. The positive rate of E-cad expression in colon cancer tissues in the sh-FGF-18 group was higher than that in the shRNA-NC group, while the positive rate of N-cad and FN expressions were lower than those in the shRNA-NC group (P< 0. 05). The tumor weight of primary lesions was lower, and the volume was smaller in the sh-FGF-18 group when compared with those in the shRNA-NC group (P< 0. 05), and there were fewer metastases of liver and lung tissues in the sh-FGF 18 group (P< 0. 05). Conclusion Interfering with FGF-18 can inhibit the proliferation, migration and invasion of colon cancer cells, promote apoptosis and inhibit xenograft growth in nude mice, which may affect tumors metastasis by inhibiting EMT pathway.

Objective To explore the relationship between miR-205 and JAK2 / STAT3 in the development of triple negative breast cancer (TNBC), so as to provide new ideas for the treatment of TNBC. Methods qRT-PCR and Western blotting were used to detect the expression levels of miR-205 and JAK2 in cancer tissues and adjacent tissues. The expression levels of JAK2 pathway related proteins were detected by Western blotting in MDA-MB-231 cell line after cells were transfected with miR-205 mimic, miR NC, pcDNA3. 1 JAK2 or pcDNA3. 1 NC. The migration of MDA-MB-231 cells was detected by wound healing assay, the invasiveness of cells was detected by transwell test, the growth ability of MDA-MB-231 cells was analyzed by colony formation assay, the apoptosis was analyzed by flow cytometry, and the interaction between miR-205 and JAK2 was verified by dual luciferase gene reporter assay. Results In TNBC tissues, the expression level of miR-205 decreased and the expression level of JAK2 increased. After overexpression of miR-205 in MDA-MB-231 cells, the capacity of growth, invasion and metastasis of cells were suppressed, while the apoptosis rate was significantly increased. On the contrary, after overexpression of JAK2 in the MDA-MB-231 cells, the capacity of growth, invasion and metastasis of cells were enhanced, and the apoptosis rate was significantly reduced. The dual luciferase gene reporter assay revealed that miR-205 can target and inhibit JAK2 activity. Conclusion miR-205 can target JAK2 / STAT3 pathway, inhibit the growth, invasion and metastasis of TNBC cells, and promote the apoptosis of TNBC cells.

Objective To investigate the potential molecular mechanism of LncRNA HOTAIR in regulating paclitaxel resistance in breast cancer cells. Methods The breast cancer paclitaxel-resistant cell lines (MCF7 / TR cells) were screened. The expression levels of HOTAIR and paclitaxel resistance indicators (cell proliferation rate, cell apoptosis rate, cell cycle, intracellular paclitaxel concentration) were then examined in the MCF7 / TR cells and the parental cells. Results After knockdown of HOTAIR, paclitaxel significantly inhibited the proliferation of MCF7 / TR cells, induced the cell apoptosis, and arrested the MCF7 / TR cells in the G1 phase. The intracellular concentration of paclitaxel in MCF7 / TR cells was increased after knockdown of HOTAIR. miR-130a-3p was found to be interacted with HOTAIR, and the expression level of miR-130a-3p was elevated after knockdown of HOTAIR. The intracellular paclitaxel concentration was significantly increased in the MCF7 / TR cells upon overexpression of miR-130a-3p. miR-130a-3p targeted the untranslated region at the 3′ end of ABCC5 mRNA, and the intracellular paclitaxel concentration was significantly increased when ABCC5 were overexpressed in MCF7 / TR cells. Conclusion LncRNA HOTAIR reduces the intracellular level of paclitaxel in paclitaxel-resistant cells through the miR-130a-3p / ABCC5 axis, and promotes the resistance of breast cancer cells to paclitaxel.

Objective To investigate the effect of long non-coding RNA bladder cancer-associated transcript 1 (LncRNA BLACAT1) on the proliferation, migration and invasion of human hepatoma cells by regulating miR-324-5p / mitogen-activated protein kinase kinase kinase kinase 3 (MAP4K3) axis. Methods Real-time quantitative PCR (RT-qPCR) was used to detect the expression of BLACAT1, miR-324-5p and MAP4K3 mRNA in the hepatocellular carcinoma tissues, paracancerous tissues, and human normal hepatocytes and hepatoma cell lines ( Huh-7, SMMC7721, MHCC97 L). The liver cancer cells Huh-7 were divided into 5 groups: control group, si-NC group, si-BLACAT1 group, si-BLACAT1 + miR-NC group, and si-BLACAT1 + miR-324-5p inhibitor group. RT-qPCR was used to detect the mRNA expression levels of BLACAT1, miR-324-5p and MAP4K3 in cells of each group. CCK-8 assay was used to detect the cell proliferation. Wound-healing assay and transwell assay was used to detect the cell migration and cell invasion. Western blotting was used to detect the expression levels of MAP4K3, PCNA, MMP2, MMP9, c-Myc and Cyclin D1 in cells. The dual-luciferase reporter assays were used to verify the relationship between BLACAT1 and miR-324-5p, and the relationship between miR-324-5p and MAP4K3. Results The mRNA expression levels of BLACAT1 and MAP4K3 in hepatoma tissues and human hepatoma cell lines were greatly increased, and the expression level of miR-324-5p was greatly decreased (P < 0. 05). When compared with the control group and the si-NC group, the mRNA expression levels of BLACAT1, MAP4K3, the A450 value, the migration and invasion rate, and the expression levels of PCNA, MMP2, MMP9, MAP4K3, c-Myc and Cyclin D1 proteins were greatly decreased in the si-BLACAT1 group (P < 0. 05). The expression level of miR-324-5p was greatly increased ( P < 0. 05). Silencing of miR-324-5p attenuated the inhibitory effect of BASCAT1 knockdown on the proliferation, migration and invasion in Huh-7 cells. BASCAT1 targeted and negatively regulated the expression of miR-324-5p, and miR-324-5p targeted and regulated the MAP4K3. Conclusion Knockdown of BLACAT1 may down-regulate the expression of MAP4K3 by targeting miR-324-5p, thereby inhibiting the proliferation, migration and invasion of liver cancer cells. 

Objective Esophageal cancer is a serious threat to human health, and the metabolic pattern of tumor cells is dominated by glycolysis. This study analyzed the mechanisms regulating glycolysis in esophageal cancer cells. Methods The expression levels of Circular RNA lysophosphatidic acid receptor 3 (CircLPAR3), microRNA-143-5p (miR-143-5p) and ubiquitin-specific protease 14 (USP14) were measured using quantitative real-time (qRT-PCR). The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured using Seahorse XF 24 Extracellular Flux Analyzer. The expression levels of HK2 (a key enzyme of glycolytic pathway) was measured by Western blotting. The target binding site of CircLPAR3 to miR-143-5p and that of miR-143-5p to USP14 were all predicted by the Starbase database and verified through dual luciferase gene reporter assay. Results CircLPAR3 was highly expressed in the esophageal cancer cell lines, especially in the KYSE450 cell lines. At the same time, KYSE450 cells had lower miR-143-5p expression level and higher USP14 expression level. Compared to the Het-1A group, the KYSE450 group showed increased protein expression level of HK2, along with an increased ECAR and a reduced overall glycolytic OCR. Knockdown of CircLPAR3 expression resulted in reduced protein expression levels of cellular HK2, reduced ECAR and increased overall glycolytic OCR. Inhibition of miR-143-5p expression was able to partially reverse the suppression of cellular glycolysis induced by the inhibition of CircLPAR3 expression. The dual luciferase gene reporter assay verified the targeting relationship between CircLPAR3 and miR-143-5p, as well as the targeting relationship between miR-143-5p and USP14. Conclusion Circular RNA LPAR3 regulates the glycolytic pathway in esophageal cancer cells by regulating the miR-143-5p / USP14 pathway.

Objective To study the regulation of BMP9 on P38 MAPK signaling pathway and its effect on autophagy and apoptosis in osteoblasts. Methods The osteoblast cell line MC3T3-E1 was cultured in vitro and was induced to undergo autophagy with rapamycin. The expressions of BMP9, P38 and p-P38 were detected by Western blotting. The MC3T3-E1 cells were divided into 7 groups: pcDNA3. 1-BMP9 group ( pcDNA3. 1-BMP9 ), BMP9 siRNA group ( BMP9 siRNA), P38 activation group ( anisomycin, 10 μmol / L), P38 inhibition group ( SB-202190, 10 μmol / L), pcDNA3. 1-BMP9 + P38 inhibition group ( pcDNA3. 1-BMP9 + SB-202190, 10 μmol / L), BMP9 siRNA + P38 activation group ( BMP9 siRNA + anisomycin, 10 μmol / L) and control group. The expression levels of autophagy-related proteins LC3-Ⅱ, Beclin-1 and P62 were detected by Western blotting, and the cell proliferation and apoptosis were measured by CCK-8 and flow cytometry. Results The expression levels of LC3-Ⅱ, Beclin-1, BMP9 and p-P38 were increased (P< 0. 05) while the expression level of P62 was decreased ( P < 0. 05) after MC3T3-E1 cells were treated with rapamycin. The expression levels of LC3-Ⅱ and Beclin-1 in the pcDNA3. 1-BMP9 group and the P38 activation group were increased (P< 0. 05), and the expression level of P62 in those two groups was decreased (P < 0. 05). The expression levels of LC3-Ⅱ and Beclin-1 in the BMP9 siRNA group and the P38 inhibition group were decreased (P < 0. 05), and the expression level of P62 in those two groups was increased (P< 0. 05). No significant differences in the expression levels of LC3-Ⅱ, Beclin-1 and P62 were found between the pcDNA3. 1-BMP9 + P38 inhibition group, the BMP9 siRNA + P38 activation group and the control group (all P> 0. 05). The cell proliferation rates of the pcDNA 3. 1-BMP9 group and the P38 activation group were increased, and the apoptosis rates of those two groups were decreased (all P< 0. 05). The cell proliferation rates of the BMP9 siRNA group and the P38 inhibition group were decreased, and the apoptosis rates of those two groups were increased (all P< 0. 05). No significant differences in the proliferation and apoptosis rates were found between the pcDNA 3. 1-BMP9 + P38 inhibition group, the BMP9 siRNA + P38 activation group and the control group (all P> 0. 05). Conclusion BMP9 activates the P38 MAPK pathway, induces autophagy and reduces apoptosis in osteoblasts.

Objective To investigate the effect of Compound Shougong powder (CSP) on the pain sensitization in rats with bone cancer pain through tumor necrosis factor-α (TNF-α) signaling pathway. Methods A rat model of lung cancer bone metastases pain was established by injecting Lewis lung cancer cells. Rats were randomly divided into 6 groups: model group, positive control group ( Voltaren, 0. 1 g / kg), CSP low-dose group ( CSP-L, 20 mg / kg), CSP medium-dose group (CSP-M, 40 mg / kg), CSP high-dose group (CSP-H, 80 mg / kg), and the sham operation group, 10 rats in each group. After the intervention, the paw withdrawal mechanical threshold (PWMT) of the rats was detected, and the paw withdrawal thermal latency (PWTL) in rats was detected by the automatic thermal pain tester. The levels of TNF-α, IL-1β and IL-6 in serum were detected by ELISA. Western blotting was performed to detect the expression levels of monocyte chemoattractant protein-1 (MCP-1) and TNF-α in spinal cord tissues of rats in each group. Results The levels of IL-1β, IL-6, TNF-α and MCP-1 in the model group were significantly increased when compared with those in the sham operation group, while the values of PWMT and PWTL were significantly decreased (P<0. 05). The levels of IL-1β, IL-6, TNF-α and MCP-1 in the CSP-L group, CSPM group and CSP-H group were significantly decreased when compared with those in the model group, while the values of PWMT and PWTL were significantly increased (P<0. 05). No obvious differences in the above indexes were found between the CSP-H group and the positive control group (P > 0. 05). Conclusion CSP may alleviate the pain response in rats with lung cancer bone metastases pain and exert analgesic effect by inhibiting the expression of TNF-α and other inflammatory factors.

Objective To investigate the effect of propofol on inflammatory cytokines activation by regulating the nuclear factor kappa-B ( NF-κB ) signaling pathway in BV2 microglial cells. Methods BV2 cells were divided into 5 groups: control group, model group, propofol low-dose group (20 μmol / L), propofol medium-dose group (50 μmol / L), and propofol high-dose group (100 μmol / L). Cell viability was detected by CCK-8 assay. The levels of interleukin-6 (IL6), IL-1β, tumor necrosis factor-α ( TNF-α), nitric oxide synthase (NOS) were detected by ELISA, and the reactive oxygen species (ROS) was detected by ROS assay kit. Western blotting analysis was used to detect the expression levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD ( ASC), Caspase-1, IκB, P65, and p-P65. Immunofluorescence staining was used to observe the nuclear translocation of P65. Results Propofol showed no toxicity to BV3 cells for all three concentrations. The levels of IL-6, IL-1β, TNF-α, ROS, and NOS in the LPS group were significantly increased when compared with those in the control group (P< 0. 01). The expression of IκB was significantly down-regulated, p-P65 / P65 was significantly up-regulated, and P65 nuclear translocation was significantly increased ( P < 0. 01). After treatment with different doses of propofol, the results of above indexes were reversed, IL-6, IL-1β, TNF-α, ROS and NOS levels were significantly reduced (P < 0. 01), the expression of IκB was significantly up-regulated, p-P65 / P65 was significantly down-regulated, and nuclear localized p65 protein was significantly reduced (P< 0. 01). All changes in the above results were dose-dependent. Conclusion Propofol alleviate the activation of inflammatory cytokines in LPS stimulated BV2 cells by regulating the NF-κB signaling pathway. 

Objective To investigate the effect of propofol on the proliferation and invasion of colorectal cancer cells via regulating SFRP1-Wnt signaling pathway. Methods Colorectal cancer cell lines SW620 and HT29 were used, cells were divided into 2 groups: the control group and the propofol group. CCK-8 was used to detect cell proliferation activity. The wound-healing assay and transwell assay were used to analyze cell migration and invasion ability. Reverse transcription real-time fluorescence quantitative PCR was used to detect the expression levels of Wnt signaling pathway related genes. The chromatin immunoprecipitation assay was used to analyze the enrichment of EZH2 and H3K27Me3 in the SFRP1 promoter region. Results The proliferation activity of cells in the propofol group was significantly lower than that of the control group after propofol treatment for 24 hours (P< 0. 01). The wound-healing assay showed that the cell migration in the propofol group was significantly lower than that in the control group (P < 0. 01). The tranwell assay showed that the number of transmembrane cells in the propofol group was significantly less than that in the control group (P < 0. 01 ). qPCR resutls showed that E-cadherin was significantly up-regulated ( P < 0. 01), while N-cadherin was down-regulated (P < 0. 01) in the propofol group when compared with the control group. Wnt signaling pathway target genes β-catenin, c-Myc and Cyclin D1 was significantly down-regulated when compared with the control group (P < 0. 01). In addition, SFRP1, the upstream regulator of Wnt, was also significantly down-regulated in the propofol group ( P < 0. 01). Chromatin immunoprecipitation revealed that the enrichment of EZH2 and H3K27Me3 in the SFRP1 promoter was significantly lower in the propofol group than in the control group (P< 0. 01). Conclusion Propofol can inhibit the proliferation and invasion of colorectal cancer cells. Propofol attenuates the apparent silencing effect of EZH2 on SFRP1 and induces its upregulation, thereby reducing the activity of Wnt signaling pathway.

Objective To explore the effect and mechanism of stearyl coenzyme-A desaturation enzyme 1 (SCD1) on IL-1β induced pancreatic β cell damage. Methods SCD1 gene was inserted into the pEGFP-C1 vector to construct the pEGFP-SCD1 overexpression plasmid. The pancreatic β cell lines INS-1 and βTC-6 were transferred with the pEGFP-SCD1 plasmid and were treated with IL-1β. Western blotting, Tunel staining, and GSIS / KSIS method were used to explore the protective effect of SCD1 on pancreatic β cells. Results IL-1β treatment reduced the expression level of SCD1 in pancreatic β cells. Overexpression of SCD1 reversed the IL-1β induced reduction of insulin synthesis and secretion and the apoptosis in pancreatic β cells. Conclusion SCD1 can protect the pancreatic β cells from cell damage caused by IL-1β.

The renin-angiotensin system ( RAS) is composed of dozens of angiotensin peptides, peptidases and various receptors, which specifically regulates the functions of various tissues and organs and maintain the homeostasis of water and electrolyte. The local RAS components are widely distributed in the tissue structure of human eyes and play a series of physiological and pathological roles. This review makes a summary of the main active factors in the RAS system, and how they maintain the physiological function of trabecular tissues and play roles in the aqueous humor dynamics in the primary open angle glaucoma (POAG). In addition, the prospect of using RAS components as potential targets for anti-glaucoma drugs is also review