Phytic acid promotes high glucose-mediated bone marrow mesenchymal stem cells osteogenesis via modulating circEIF4B that sponges miR-186-5p and complexes with IGF2BP3.

Diabetes-related hyperglycemia inhibits bone marrow mesenchymal stem cell (BMSC) function, thereby disrupting osteoblast capacity and bone regeneration. Dietary supplementation with phytic acid (PA), a natural inositol phosphate, has shown promise in preventing osteoporosis and diabetes-related complications. Emerging evidence has suggested that circular (circ)RNAs implicate in the regulation of bone diseases, but their specific regulatory roles in BMSC osteogenesis in hyperglycemic environments remain elucidated. In this study, in virto experiments demonstrated that PA treatment effectively improved the osteogenic capability of high glucose-mediated BMSCs. Differentially expressed circRNAs in PA-induced BMSCs were identified using circRNA microarray analysis. Here, our findings highlight an upregulation of circEIF4B expression in BMSCs stimulated with PA under a high-glucose microenvironment. Further investigations demonstrated that circEIF4B overexpression promoted high glucose-mediated BMSC osteogenesis. In contrast, circEIF4B knockdown exerted the opposite effect. Mechanistically, circEIF4B sequestered microRNA miR-186-5p and triggered osteogenesis enhancement in BMSCs by targeting FOXO1 directly. Furthermore, circEIF4B inhibited the ubiquitin-mediated degradation of IGF2BP3, thereby stabilizing ITGA5 mRNA and promoting BMSC osteogenic differentiation. In vivo experiments, circEIF4B inhibition attenuated the effectiveness of PA treatment in diabetic rats with cranial defects. Collectively, our study identifies PA as a novel positive regulator of BMSC osteogenic differentiation through the circEIF4B/miR-186-5p/FOXO1 and circEIF4B/IGF2BP3/ITGA5 axes, which offers a new strategy for treating high glucose-mediatedBMSCosteogenic dysfunction and delayed bone regeneration in diabetes.

[Study on inhibitory effect of EGCG on Calcium oxalate nephrolithiasis in rats and its related mechanism].

In the study, the inhibitory effect of epigallocatechin gallate (EGCG) on Calcium oxalate nephrolithiasis and its possible mechanism were investigated. The rat Calcium oxalate nephrolithiasis model was induced through the combined oral administration of ethylene glycol and ammonium chloride, which was intervened with EGCG. Rat blood samples were collected to detect blood creatinine (Cr), blood urea nitrogen (BUN) and blood calcium. Rat urine samples were collected to observe and compare 24-hour urine volume, oxalic acid (Ox) and calcium in urine. Renal samples were collected to prepare tissue slices and observe the pathological changes in Calcium oxalate nephrolithiasis. The expression of osteopontin (OPN) in renal tissues was evaluated by Real-time PCR and Western blot. According to the results, compared with normal rats, rats in the nephrolithiasis model showed significant increases in Cr, BUN, urine Calcium, urine Ox and renal OPN expression (P < 0.05), but obvious decrease in 24-hour urine volume (P < 0.05); Compared with rats with nephrolithiasis, those processed with EGCG revealed remarkable declines in Cr, BUN, urine Calcium and urine Ox (P < 0.05), with significant rise in 24-hour urine volume (P < 0.05) in a concentration-dependent manner. Additionally, compared with the control group, nephrolithiasis rats showed significant pathological changes in Calcium oxalate calculus. After ECCG treatment, the renal pathological changes and OPN expression attenuated significantly in a concentration-dependent manner. The results showed that EGCG inhibits the formation of calcium oxalate nephrolithiasis in rats and shows a notable protective effect on renal functions.