BackgroundHepatocellular 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/MethodsIn 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 β-catenin and p-β-catenin.ResultsPirfenidone inhibited proliferation and promoted HepG2 cell apoptosis. In addition, Western blot results indicated that pirfenidone suppressed β-catenin expression in HepG2 cells. To assess the mechanism, we treated HepG2 cells with pirfenidone, and pirfenidone plus the β-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 β-catenin expression in HepG2 cells treated with pirfenidone.ConclusionsIn conclusions, pirfenidone may be a potential drug for HCC treatment.

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.

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 α 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.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated 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 miR-23b in HCC remains unclear. The present study revealed a negative correlation between miR-23b expression in HCC tissues and progression of carcinomas. Compared to normal tissues, miR-23b expression was significantly downregulated in HCC tissues, whereas the expression of interleukin (IL)-11 and IL-11 receptor α (IL-11Rα) was significantly upregulated, indicating that miR-23b expression is negatively correlated with IL-11 and IL-11Rα expression. In addition, miR-23b inhibited proliferation and promoted apoptosis of SMMC-7721 cells. This effect was mediated by IL-11, which was found to be the direct target of miR-23b in this study. These results indicated that miR-23b regulates IL-11 and IL-11Rα expression, and might act as an anti-oncogenic agent in the progression of HCC by directly downregulating IL-11 expression.

Background To investigate the correlation between single nucleotide polymorphism (SNP) of human Apolipoprotein E (ApoE) gene and essential hypertension (EH) in Han, Miao, and Buyi populations in Guizhou. Methods A case–control study was conducted. A total of 343 patients with EH and 335 healthy controls were selected from Leishan Miao, Libo Buyi, and Guiyang Han populations in Guizhou. The clinical data and biochemical indicators including age, gender, height, weight, fasting blood glucose, cholesterol, and triglyceride were collected. The t test or chi-square test was used to compare the differences of clinical data and biochemical indexes between the 2 groups. Sequenom MassARRAY was used to detect genotype of 5 SNP (rs7259620, rs440446, rs769449, rs1065853, and rs439401) and kompetitive allele-specific PCR (KASP) was used to detect 2 SNP (rs429358 and rs7412) of ApoE gene. Logistic regression was used to analyze the genetic relationship between ApoE gene polymorphisms and EH in Guizhou populations. Results Age, overweight, and obesity were independent risk factors for EH in Guizhou populations. Fasting blood glucose and triacylglycerol are independent risk factors for EH in Guizhou Han population. In the Miao and Buyi populations in Guizhou, the correlation between EH and the studied SNP was not statistically significant. In the Han population, the distribution of rs439401 allele and genotype between EH group and control group was significantly different (χ2 = 6.438, P = 0.011; χ2 = 6.389, P = 0.041). Compared with the TT or TC genotype, the genotype CC increased the risk of EH (OR = 2.164, 95% CI 1.035–4.526, P = 0.040). Compared with haplotype G-G-T (rs7259620–rs1065853–rs439401), haplotype G-G-C reduced the risk of EH in Han population (OR = 0.465, 95% CI 0.263–0.824, P = 0.008). Multifactor dimensionality reduction analysis results showed that rs440446, rs429358, and rs7412 had an interaction effect on the occurrence of EH in Miao population (χ2 = 10.012, P = 0.002); rs7259620, rs1065853, and rs439401 had an interaction effect on the occurrence of EH in Buyi population (χ2 = 3.972, P = 0.046); rs7259620, rs440446, and rs439401 had an interaction effect on the occurrence of EH in Han population (χ2 = 10.155, P = 0.001). Conclusions The rs439401 of ApoE gene and the haplotype GGC (rs7259620–rs1065853–rs439401) may be associated with the occurrence of EH in Guizhou Han population.