Maternal hyperglycemia potentially inhibits the development of the fetal heart by suppressing cardiomyocyte proliferation and promoting apoptosis. Different studies have indicated that miRNAs are key regulators of cardiomyocyte proliferation, differentiation, and apoptosis and play a protective role in a variety of cardiovascular diseases. However, the biological function of miRNA-23a in hyperglycemia-related cardiomyocyte injury is not fully understood. The present study investigated the effect of miRNA-23a-3p on cell proliferation and apoptosis in a myocardial injury model induced by high glucose. H9c2 cardiomyocytes were exposed to high glucose to establish an in vitro myocardial injury model and then transfected with miRNA-23a-3p mimics. After miRNA-23a-3p transfection, lens-free microscopy was used to dynamically monitor cell numbers and confluence and calculate the cell cycle duration. CCK-8 and EdU incorporation assays were performed to detect cell proliferation. Flow cytometry was used to measured cell apoptosis. Upregulation of miRNA-23a-3p significantly alleviated high glucose-induced cell apoptosis and cell proliferation inhibition (p < 0.01 and p < 0.0001, respectively). The cell cycle of the miRNA-23a-3p mimics group was significantly shorter than that of the negative control group (p < 0.01). The expression of cell cycle–activating and apoptosis inhibition-associated factors Ccna2, Ccne1, and Bcl-2 was downregulated by high glucose and upregulated by miRNA-23a-3p overexpression in high glucose-injured H9c2 cells. miRNA-23a-3p mimics transfection before high glucose treatment had a significantly greater benefit than transfection after high glucose treatment (p < 0.0001), and the rescue effect of miRNA-23a-3p increased as the concentration increased. This study suggests that miRNA-23a-3p exerted a dose- and time-dependent protective effect on high glucose-induced H9c2 cardiomyocyte injury.
Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and Alpha B-crystallin (CRYAB) protein has been identified as a prognostic biomarker for CRC. We evaluated CRYAB C-802G (rs14133)polymorphism in association with CRC risk and survival in Chinese population. We genotyped for CRYAB C-802G (rs14133), A-1215G (rs2228387) and intron 2 (rs2070894), and assessed their associations with CRC in a case-control study of 441 CRC cases and 500 healthy controls. We also analyzed this polymorphism in relation to overall survival in CRC patients. A significantly different frequency distribution was found in CRYAB C-802G genotypes, but not in A-1215G and intron2 genotypes, between the cases and the controls. Under multivariable logistic regression adjusted for age and gender, CG/GG genotype carriers were associated with increased risk of CRC (OR 1.754, 95% CI 1.338–2.301, P < 0.001) when compared with CC genotype carriers. Multivariate Cox proportional hazards model showed that patients with CG/GG genotype had significant shorter survival time than those with CC genotype, after adjustment for gender and TNM stage (HR 2.347, 95% CI 1.719–3.204, P < 0.001), and after adjustment for gender and tumor grade (HR 2.871, 95% CI 2.121–3.887, P < 0.001), respectively. Our results demonstrated that CG/GG at CRYAB C-802G is correlated with CRC susceptibility and this polymorphism may be an useful marker for clinical outcome of CRC.
Objectives: Melatonin has been reported to be an appropriate candidate for mitigating various cardiovascular injuries, owing to its versatility. This study aimed to explore the role of melatonin in Kawasaki disease (KD)-associated vasculitis and its underlying mechanisms.
Material and Methods: The role of melatonin was evaluated in human coronary artery endothelial cells (HCAECs), peripheral blood mononuclear cells from KD patients, human THP1 cell line in vitro, and a Candida albicans water-soluble fraction (CAWS)-induced KD mouse model in vivo. Cell proliferation assay, cell apoptosis assay, cell co-culture, RNA extraction, RNA sequencing, reverse transcription quantitative PCR, enzyme-linked immunosorbent assay (ELISA), transwell assay, western blot, dual-luciferase reporter assay, and autophagic flux assay were performed to investigate the function and regulatory mechanisms of melatonin in vitro, while haematoxylin and eosin staining, Verhoeff's van Gieson staining, ELISA, and immunohistochemical analysis were performed to detect the effect of melatonin in vivo. Results: Melatonin suppressed cell apoptosis directly reduced the expression of endothelial cell damage markers in HCAECs, and alleviated vasculitis in the CAWSinduced KD mouse model. Mechanistically, melatonin promoted autophagy by activating the melatonin/ melatonin receptor (MT)/cAMP-response element binding protein (CREB) pathway and upregulating the expression of autophagy-related gene-3, thereby suppressing cell apoptosis in an autophagy-dependent manner. Additionally, melatonin decreased the production of pro-inflammatory cytokines in macrophages and indirectly reduced the immunopathological damage of HCAECs.Conclusions: This study revealed that melatonin protects vascular endothelial cells in KD, by suppressing cell apoptosis in an autophagy-dependent manner and reducing the immunopathological damage mediated by macrophages.
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