MiR-448-5p/VEGFA Axis Protects Cardiomyocytes from Hypoxia Through Regulating the FAS/FAS-L Signaling Pathway.

Bioinformatics analysis showed that miR-448-5p expression in the myocardial tissue of rats with myocardial infarction significantly increased, suggesting that it may participate in myocardial cell apoptosis in myocardial infarction. This study aimed to explore the protective effects of miR-448-5p on hypoxic myocardial cells.H9C2 cells were cultured and subjected to anoxia for 2, 4, and 8 hours to establish a hypoxia model. MiR-448-5p mimic and inhibitor were transfected into the cells; then, a dual-luciferase experiment was conducted to verify the targeting relationship between miR-448-5p and VEGFA. Cell viability and apoptosis was detected by cell counting kit-8 and flow cytometry, respectively. The expressions of apoptosis-related proteins, miR-448-5p, FAS, and FAS-L were measured using western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Hypoxia-reduced H9C2 cell viability and promoted apoptosis. MiR-448-5p expression was increased after H9C2 cell hypoxia. MiR-448-5p mimic significantly inhibited the viability and promoted the apoptosis of hypoxia-induced model cells. Hypoxia promoted the expression of apoptosis-related protein B-cell lymphoma-2 (Bcl-2) and inhibited the expressions of Bcl-2-associated x protein (Bax), cleaved caspase-3, and caspase-3, whereas the effect of inhibitor on hypoxia-reduced H9C2 cell and apoptotic protein expression were opposite to miR-448-5p mimic. MiR-448-5p targeted VEGFA and regulated its expression. Silenced VEGFA expression significantly inhibited inhibitor effect on increasing cell viability and promoted apoptosis. In addition, miR-448-5p mimic inhibited the effect of hypoxia on promoting the expressions of FAS and FAS-L of H9C2 cells. Inhibitors had the opposite effect on cell hypoxia model.The miR-448-5p/VEGFA axis could protect cardiomyocytes from hypoxia through inhibiting the FAS/FAS-L signaling pathway.

Inhibitory Effect of Paeonol on Apoptosis, Oxidative Stress, and Inflammatory Response in Human Umbilical Vein Endothelial Cells Induced by High Glucose and Palmitic Acid Induced Through Regulating SIRT1/FOXO3a/NF-κB Pathway.

Reactive oxygen species (ROS) induced by high glucose and high fat of diabetes mellitus (DM) finally caused the occurrence and progression of atherosclerosis and other macrovascular complications. Paeonol (Pae) exhibits anti-inflammation, antioxidation, and antiatherosclerosis activities. However, the role of Pae in diabetic cardiopathy has not been fully understood. Therefore, we aimed to investigate the role of Pae in diabetic cardiovascular diseases. Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose and palmitic acid (HG/HP), a model DM environment and different doses of Pae. The viability and apoptotic rate of HUVECs were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assay, respectively. Oxidative indicators (ROS, malondiadehyde [MDA], superoxide dismutase [SOD]), and inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß, and interleukin-6) were detected by 2,7-dichlorodihydrofluorescein diacetate, colorimetry, and enzyme-linked immunosorbent assay. The protein levels of Sirtuin type 1 (SIRT1), Bcl-2, Bax, Cleaved caspase-3, p-p65, and p-65 were detected by Western blot. The mRNA levels of Bcl-2 and Bax were detected by quantitative real-time polymerase chain reaction. The acetylation and protein levels of forkhead box O3a (FOXO3a) were detected by immunoprecipitation assay. SIRT1 silencing was used to confirm the role of Pae in the resistance to apoptosis, oxidative stress, and inflammatory response. Pae increased SIRT1 expression, cell viability, and SOD activity and suppressed apoptosis, the levels of p-p65/p-65, ROS, MDA, and inflammatory cytokines, and the expression of acetylated-FOXO3a induced by HG/HP in HUVECs. SIRT1 silencing abrogated the effect of Pae on HG/HP-mediated HUVECs. Inhibitory effect of Pae on apoptosis, oxidative stress, and inflammatory response in HUVECs induced by HG/HP induced through regulating SIRT1/FOXO3a/NF-κB pathway.

Relationship between the matrix metalloproteinase-9 gene polymorphisms and ischemic stroke.

BACKGROUND: In recent years, with the further research of human genome scanning, the relationship between matrix metalloproteinase-9 (MMP-9) gene polymorphisms and many diseases has aroused increased attention. But there is little research on the relationship between MMP-9 gene polymorphisms and ischemic stroke (IS). This study was conducted to evaluate the relationships between the rs3918242 and rs17577 polymorphisms in the MMP-9 gene and IS in a Chinese population. METHODS: 152 cases of IS patients and 152 healthy controls were enrolled in this study. All subjects were genotyped for the MMP-9 rs3918242 and rs17577 polymorphisms by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP) and restriction analysis. RESULTS: Rs3918242 showed genotypes TT, TC, and CC, and rs17577 exhibited genotypes AA, AG, and GG. The MMP-9 polymorphisms rs3918242 and rs17577 exhibited complete linkage. Our study found there was no significant difference in genotype and allele between rs3918242 and rs17577 between patients and controls. The MMP-9 gene rs3918242 and rs17577 polymorphisms are not significantly correlated with IS risk. Genetic polymorphisms vary among ethnic and regional populations. CONCLUSION: Our results suggest that MMP-9 rs3918242 is completely linked to rs17577, while the rs3918242 and rs17577 polymorphisms are not significantly associated with the risk of IS. Genetic polymorphisms vary among ethnic and regional populations.

Effect of Zhuang Jing Decoction on Learning and Memory Ability in Aging Rats.

With the average life span of humans on the rise, aging in the world has drawn considerable attentions. The monoamine neurotransmitters and neurotrophic factors in brain areas are involved in learning and memory processes and are an essential part of normal synaptic neurotransmission and plasticity. In the present study, the effect of Zhuang Jing Decoction (ZJD) on the learning and memory ability in aging rats was examined in vivo using Morris water maze. Furthermore, the levels of monoamine neurotransmitters and neurotrophic factors in brain were detected by high-performance liquid chromatography with a fluorescence detector and enzyme-linked immunosorbent assay, respectively. These data showed that oral administration with ZJD at the dose of 30 g·kg(-1) exerted an improved effect on learning and memory ability in aging rats. The results revealed that ZJD could effectively adjust the monoamine neurotransmitters and neurotrophic factors, restore the balance of the level of monoamine neurotransmitters and neurotrophic factors in brain, and finally attenuate the degeneration of learning and memory ability. These findings suggested that ZJD might be a potential agent as cognitive-enhancing drug in improving learning and memory ability. It may exert through regulating the levels of monoamine neurotransmitters and neurotrophic factors in brain, which demonstrated that ZJD had certain antiaging effects.

XRCC7 rs#7003908 Polymorphism and Helicobacter pylori Infection-Related Gastric Antrum Adenocarcinoma.

The X-ray repair cross-complementing group 7 (XRCC7) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. To determine whether XRCC7 rs#7003908 polymorphism (XRCC7P) is associated with Helicobacter pylori (H. pylori) infection-related gastric antrum adenocarcinoma (GAA) risk, we conducted a hospital-based case-control study, including 642 patients with pathologically confirmed GAA and 927 individually matched controls without any evidence of tumours or precancerous lesions, among Guangxi population. Increased risks of GAA were observed for individuals with cagA positive (odds ratio (OR) 6.38; 95% confidence interval (CI) 5.03-8.09). We also found that these individuals with the genotypes of XRCC7 rs#7003908 G alleles (XRCC7-TG or -GG) featured increasing risk of GAA (ORs 2.80 and 5.13, resp.), compared with the homozygote of XRCC7 rs#7003908 T alleles (XRCC7-TT). GAA risk, moreover, did appear to differ more significantly among individuals featuring cagA-positive status, whose adjusted ORs (95% CIs) were 15.74 (10.89-22.77) for XRCC7-TG and 38.49 (22.82-64.93) for XRCC7-GG, respectively. Additionally, this polymorphism multiplicatively interacted with XRCC3 codon 241 polymorphism with respect to HCC risk (ORinteraction = 1.49). These results suggest that XRCC7P may be associated with the risk of Guangxiese GAA related to cagA.