Deafness or hearing loss is a major issue in human health. Inner ear hair cells are the main sensory receptors responsible for hearing. Defects in hair cells are one of the major causes of deafness. A combination of induced pluripotent stem cell (iPSC) technology with genome-editing technology may provide an attractive cell-based strategy to regenerate hair cells and treat hereditary deafness in humans. Here, we report the generation of iPSCs from members of a Chinese family carrying MYO15A c.4642G>A and c.8374G>A mutations and the induction of hair cell-like cells from those iPSCs. The compound heterozygous MYO15A mutations resulted in abnormal morphology and dysfunction of the derived hair cell-like cells. We used a CRISPR/Cas9 approach to genetically correct the MYO15A mutation in the iPSCs and rescued the morphology and function of the derived hair cell-like cells. Our data demonstrate the feasibility of generating inner ear hair cells from human iPSCs and the functional rescue of gene mutation-based deafness by using genetic correction.
High-fat diet (HFD) induces obesity. This study examined the effects of Shiitake mushroom on the prevention of alterations of plasma lipid profiles, fat deposition, energy efficiency, and body fat index induced by HFD. Rats were given a low, medium, and high (7, 20, 60 g/kg = LD-M, MD-M, HD-M) Shiitake mushroom powder in their high-fat (50% in kcal) diets for 6 weeks. The results showed that the rats on the HD-M diet had the lowest body weight gain compared to MD-M and LD-M groups (P < 0.05). The total fat deposition was significantly lower (−35%, P < 0.05) in rats fed an HD-M diet than that of HFD group. Interestingly, plasma triacylglycerol (TAG) level was significantly lower (−55%, P < 0.05) in rats on HD-M than HFD. This study also revealed the existence of negative correlations between the amount of Shiitake mushroom supplementation and body weight gain, plasma TAG, and total fat masses.
This study characterized CXC chemokine receptor 4 (CXCR4) expression in patients with mitral valve disease and chronic atrial fibrillation (AF). Forty-eight patients with chronic AF formed two groups based on whether they were treated with or without renin-angiotensin system (RAS) blockers (AF + RAS group; n = 25, or AF -RAS group; n = 23). The controls comprised 17 mitral valve disease patients with sinus rhythm (SR group). CXCR4 mRNA and protein levels in the left atria were significantly higher in the AF -RAS and AF + RAS groups than in the SR group. CXCR4 expression was significantly lower in the AF + RAS group than the AF -RAS group. More CD34 + cells expressed CXCR4 in the AF -RAS and AF + RAS groups than in the SR group. Angiotensin II, collagen I and left atrial diameter significantly positively correlated with CXCR4 expression in the AF -RAS group. These results suggest that CXCR4 expression is up-regulated in chronic AF patients with mitral valve disease, is associated with atrial remodelling, and that these effects are attenuated by RAS blockers.
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