Unraveling IGFBP3-mediated m6A modification in fracture healing.

BACKGROUND: This study investigates the role of IGFBP3-mediated m6A modification in regulating the miR-23a-3p/SMAD5 axis and its impact on fracture healing, aiming to provide insights into potential therapeutic targets. METHODS: Utilizing fracture-related datasets, we identified m6A modification-related mRNA and predicted miR-23a-3p as a regulator of SMAD5. We established a mouse fracture healing model and conducted experiments, including Micro-CT, RT-qPCR, Alizarin Red staining, and Alkaline phosphatase (ALP) staining, to assess gene expression and osteogenic differentiation. RESULTS: IGFBP3 emerged as a crucial player in fracture healing, stabilizing miR-23a-3p through m6A modification, leading to SMAD5 downregulation. This, in turn, inhibited osteogenic differentiation and delayed fracture healing. Inhibition of IGFBP3 partially reversed through SMAD5 inhibition, restoring osteogenic differentiation and fracture healing in vivo. CONCLUSION: The IGFBP3/miR-23a-3p/SMAD5 axis plays a pivotal role in fracture healing, highlighting the relevance of m6A modification. IGFBP3's role in stabilizing miR-23a-3p expression through m6A modification offers a potential therapeutic target for enhancing fracture healing outcomes.

Effects of fasting hyperglycemia in men on pregnancy outcomes of singleton pregnant women with cryo-thawed embryo transfer.

BACKGROUND: The relationship of metabolic issues to pregnancy outcomes during assisted reproductive technology (ART) is gaining much attention. Fasting Plasma Glucose (FPG) is one of the most common metabolic indicators. Abnormal FPG not only affects the quality of life of human body, but also has a bearing on reproductive health. However, most attentions are paid on women's physical health and reproductive assessment, the health status of the male partner on pregnancy outcomes during ART treatment is often neglected. This study investigated whether male fasting hyperglycemia (FH, FPG > 6.1 mmol/L) can affect live birth rates (LBR) in singleton intrauterine clinical pregnancy women with cryo-thawed embryo transfer (CET) cycles. MATERIAL AND METHODS: A retrospective cohort study (370 CET cycles with first singleton clinical intrauterine pregnancy and grouped by male FPG) was conducted to analyze the relationship between male FH and clinical pregnancy outcomes using binary logistic regression; the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated as a measure of relevancy. Live birth rate was the main outcome measure. RESULTS: The live birth rate (LBR) was significantly lower [58.6% vs. 81.8%, P = 0.007, adjusted OR 0.635, 95% CI 0.456-0.884] and miscarriage rate (MR) was significantly higher [41.4% vs. 18.2%, P = 0.007, adjusted OR 1.575, 95% CI 1.131-2.195] in the FH group when compared with the Con group. There was no difference in healthy baby rate [88.2% vs. 89.6%, P = 0.058, adjusted OR 2.143, 95% CI 0.974-4.716] or abnormal birth weight rate (23.5% vs. 11.8%, P = 0.238, adjusted OR 2.859, 95% CI 0.777-10.460] between the FH and control group. No birth defects were observed in the present study. CONCLUSION: Male FH is an independent risk factor for lower LBR and higher MR in singleton intrauterine pregnancy women with CET cycles.