Association of APP gene polymorphisms and promoter methylation with essential hypertension in Guizhou: a case-control study.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) and DNA methylation are crucial regulators of essential hypertension (EH). Amyloid precursor protein (APP) mutations are implicated in hypertension development. Nonetheless, studies on the association of APP gene polymorphism and promoter methylation with hypertension are limited. Therefore, this case-control aims to evaluate the genetic association of APP gene polymorphism and promoter methylation with EH in Guizhou populations. OBJECTIVE AND METHODS: We conducted a case-control study on 343 EH patients and 335 healthy controls (including Miao, Buyi, and Han populations) in the Guizhou province of China to analyze 11 single-nucleotide polymorphisms (rs2040273, rs63750921, rs2211772, rs2830077, rs467021, rs368196, rs466433, rs364048, rs364051, rs438031, rs463946) in the APP gene via MassARRAY SNP. The MassARRAY EpiTYPER was employed to detect the methylation levels of the promoters. RESULTS: In the Han population, the rs2211772 genotype distribution was significantly different between disease and control groups (χ2 = 6.343, P = 0.039). The CC genotype reduced the risk of hypertension compared to the TT or TC genotype (OR 0.105, 95%CI 0.012-0.914, P = 0.041). For rs2040273 in the Miao population, AG or GG genotype reduced the hypertension risk compared with the AA genotype (OR 0.533, 95%CI 0.294-0.965, P = 0.038). Haplotype TCC (rs364051-rs438031-rs463946) increased the risk of EH in Guizhou (OR 1.427, 95%CI 1.020-1.996, P = 0.037). Each 1% increase in CpG_19 (- 613 bp) methylation level was associated with a 4.1% increase in hypertension risk (OR 1.041, 95%CI 1.002-1.081, P = 0.039). Each 1% increase in CpG_1 (- 296 bp) methylation level was associated with an 8% decrease in hypertension risk in women (OR 0.920, 95%CI 0.860-0.984, P = 0.015). CpG_19 significantly correlated with systolic blood pressure (r = 0.2, P = 0.03). The methylation levels of CpG_19 in hypertensive patients with rs466433, rs364048, and rs364051 minor alleles were lower than that with wild-type alleles (P < 0.05). Moreover, rs467021 and rs364051 showed strong synergistic interaction with EH (χ2 = 7.633, P = 0.006). CpG_11, CpG_19, and rs364051 showed weak synergistic interaction with EH (χ2 = 19.874, P < 0.001). CONCLUSION: In summary, rs2211772 polymorphism and promoter methylation level of APP gene may be linked to EH in Guizhou populations. Our findings will provide novel insights for genetic research of hypertension and Alzheimer's disease.

Polymorphism of NOS3 gene and its association with essential hypertension in Guizhou populations of China.

OBJECTIVE: A case-control study was conducted to evaluate the relationship between endothelial nitric oxide synthase (NOS3) gene polymorphism and essential hypertension in the Han, Miao, and Buyi populations in Guizhou China. METHODS: DNA was collected from the blood samples of 353 essential hypertension patients and 342 healthy controls from Guizhou province of China. Eight polymorphisms of the NOS3 gene were genotyped using the Sequenom MassARRAY platform. For genetic analysis, SPSS 26.0, Haploview, SNPStats, SHEsis, and MDR were utilized. RESULTS: All SNPs (rs11771443, rs1808593, rs753482, rs3918186, rs3918188, rs3918227, rs7830, and rs891512) satisfied the Hardy-Weinberg equilibrium test (P > 0.05). The allele and genotype frequencies of rs7830 and rs1808593 in case-control groups demonstrated significant differences (P < 0.05). Compared to the TT genotype of rs1808593, the TG or GG genotype reduced the risk of hypertension in the Miao population (OR = 0.410, 95% CI: 0.218-0.770, P = 0.006). Compared to the GG or GT genotype of rs7830, the TT genotype increased the risk of hypertension in the overall populations (OR = 1.716, 95%CI: 1.139-2.586, P = 0.010). The CATT (rs3918227-rs391818186-rs1808593-rs7830) haplotype was a risk factor for hypertension in the Miao and Han populations (OR = 1.471, 95%CI: 1.010-2.143, P = 0.044 and OR = 1.692, 95%CI: 1.124-2.545, P = 0.011). The CAGG haplotype in the Miao population was a protective factor against hypertension (OR = 0.555, 95%CI: 0.330-0.934, P = 0.025). The rs3918188, rs1808593, and rs7830 in the Miao population showed an interaction effect on hypertension (P < 0.001). The rs11771443, rs3918188, and rs7830 in the Buyi and Han populations showed an interaction effect on hypertension (P = 0.013 and P < 0.001). CONCLUSION: The single nucleotide polymorphisms rs1808593 and rs7830 of NOS3 gene are associated with essential hypertension in Guizhou ethnic populations.

miR-29b affects neurocyte apoptosis by targeting MCL-1 during cerebral ischemia/reperfusion injury.

The present study aimed to determine whether an miRNA (miR)-29b inhibitor protected against cerebral ischemia/reperfusion (I/R) injury in vitro and to investigate the underlying mechanisms. As a model for induced cerebral IR injury, N2a cells were exposed to an oxygen-glucose deprivation/reoxygenation (OGD/R) environment. Using this model, it was demonstrated that miR-29b was significantly upregulated compared with cells in a normal environment. The interactions between miR-29b and myeloid cell leukemia sequence (MCL)-1 were then investigated using dual-luciferase assays, revealing a strong regulation of MCL-1 through the 3'untranslated region. Using the OGD/R model, the present study additionally examined the effects of miR-29b and miR-29b inhibitor on cell viability and apoptosis using Cell Counting kit 8 and flow cytometry assays, respectively. miR-29b transfection led to increased N2a cell apoptosis and reduced cell viability under an OGD/R environment. However, this effect was reversed by the miR-29b inhibitor. Finally, the effects of miR-29b on the expression of several Wnt-associating proteins were examined. It was observed that B cell lymphoma-2 was inhibited by miR-29b, as was MCL-1, whereas caspase-3 expression was promoted. The miR-29b inhibitor demonstrated the opposite effect. Overall, miR-29b promoted neurocyte apoptosis by targeting MCL-1 during cerebral I/R injury. The results of the present study suggest a potential novel therapeutic target for the treatment of ischemic stroke.

miR­23b inhibits proliferation of SMMC­7721 cells by directly targeting IL­11.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer­associated mortality in the 21st century. microRNA (miR)­23b has been shown to be involved in the pathogenesis of many cancers, including breast and prostate cancer. However, the role of miR­23b in HCC remains unclear. The present study revealed a negative correlation between miR­23b expression in HCC tissues and progression of carcinomas. Compared to normal tissues, miR­23b expression was significantly downregulated in HCC tissues, whereas the expression of interleukin (IL)­11 and IL­11 receptor α (IL­11Rα) was significantly upregulated, indicating that miR­23b expression is negatively correlated with IL­11 and IL­11Rα expression. In addition, miR­23b inhibited proliferation and promoted apoptosis of SMMC­7721 cells. This effect was mediated by IL­11, which was found to be the direct target of miR­23b in this study. These results indicated that miR­23b regulates IL­11 and IL­11Rα expression, and might act as an anti­oncogenic agent in the progression of HCC by directly downregulating IL­11 expression.

MiR-29b expression is associated with a dexmedetomidine-mediated protective effect against oxygen-glucose deprivation-induced injury to SK-N-SH cells in vitro.

Ischemic cerebral stroke is a leading cause of death and long-term disability world-wide. Neuronal injury following cerebral ischemia initiates a complex series of signaling cascades that lead to neuronal cell death. MicroRNA 29b (miR-29b) has reported involvement in the pathogenic process of ischemic brain injury. Dexmedetomidine (Dex) is a highly selective α2 adrenergic receptor stimulant that exerts a protective effect on brain tissue. To determine whether Dex might directly influence miR-29b expression after an ischemic injury, human neuroblastoma SK-N-SH cells were subjected to oxygen-glucose deprivation (OGD) for the purpose of creating a neuronal injury model that mimics the effects of brain ischemia in vitro. Next, the association of miR-29b with the protective effect of Dex against ischemic brain injury was studied through the enhancement or inhibition of miR-29b expression by transfection with an miR-29b mimic or inhibitor. We demonstrated that Dex treatment could reduce miR-29b expression, increase cell viability, and inhibit cell apoptosis in the OGD-induced neuronal injury model in vitro. Furthermore, down-regulation of miR-29b expression produced effects on OGD-induced neuronal injuries that were similar to those produced by Dex treatment. Moreover, up-regulation of miR-29b reversed the protective effect of Dex treatment against OGD-induced neuronal injury. Therefore, down-regulation of miR-29b expression might play a role in anti-apoptotic signaling similar to that played by Dex. Elucidation of the role played by miR-29b in ischemia, and identification of a definite association between Dex and miR-29b may lead to the development of new strategies for treating ischemic brain injuries.

Pirfenidone Inhibits Proliferation and Promotes Apoptosis of Hepatocellular Carcinoma Cells by Inhibiting the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND Hepatocellular carcinoma (HCC) is the most important cause of cancer-related deaths worldwide. Pirfenidone is an orally available small molecule with therapeutic potential for fibrotic diseases. MATERIAL AND METHODS In this study, we analyzed the effects of different pirfenidone concentrations on the proliferation of HepG2 HCC cells using Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was performed to measure the apoptotic effects of pirfenidone on HepG2 cells. Western blot analysis was performed to detect the expression of ß-catenin and p-ß-catenin. RESULTS Pirfenidone inhibited proliferation and promoted HepG2 cell apoptosis. In addition, Western blot results indicated that pirfenidone suppressed b-catenin expression in HepG2 cells. To assess the mechanism, we treated HepG2 cells with pirfenidone, and pirfenidone plus the ß-catenin activator, SB-216763. The results revealed that SB-216763 accelerated proliferation and inhibited apoptosis in HepG2 cells treated with pirfenidone. Western blot results showed that SB-216763 upregulated ß-catenin expression in HepG2 cells treated with pirfenidone. CONCLUSIONS In conclusions, pirfenidone may be a potential drug for HCC treatment.