SMAD signaling pathway is disrupted by BPA via the AMH receptor in bovine granulosa cells†.

Significant events that determine oocyte competence occur during follicular growth and oocyte maturation. The anti-Mullerian hormone, a positive predictor of fertility, has been shown to be affected by exposure to endocrine disrupting compounds, such as bisphenol A and S. However, the interaction between bisphenols and SMAD proteins, mediators of the anti-Mullerian hormone pathway, has not yet been elucidated. AMH receptor (AMHRII) and downstream SMAD expression was investigated in bovine granulosa cells treated with bisphenol A, bisphenol S, and then competitively with the anti-Mullerian hormone. Here, we show that 24-h bisphenol A exposure in granulosa cells significantly increased SMAD1, SMAD4, and SMAD5 mRNA expression. No significant changes were observed in AMHRII or SMADs protein expression after 24-h treatment. Following 12-h treatments with bisphenol A (alone or with the anti-Mullerian hormone), a significant increase in SMAD1 and SMAD4 mRNA expression was observed, while a significant decrease in SMAD1 and phosphorylated SMAD1 was detected at the protein level. To establish a functional link between bisphenols and the anti-Mullerian hormone signaling pathway, antisense oligonucleotides were utilized to suppress AMHRII expression with or without bisphenol exposure. Initially, transfection conditions were optimized and validated with a 70% knockdown achieved. Our findings show that bisphenol S exerts its effects independently of the anti-Mullerian hormone receptor, while bisphenol A may act directly through the anti-Mullerian hormone signaling pathway providing a potential mechanism by which bisphenols may exert their actions to disrupt follicular development and decrease oocyte competence.

Exploring the Prognostic Significance of the C-reactive Protein/Albumin Ratio in Assessing the Severity of Acute Pancreatitis: A Prospective Observational Study in the Indian Population.

Background The present study aimed to evaluate the predictive utility of the C-reactive protein (CRP)/albumin (CRP/Alb) ratio in predicting outcomes of acute pancreatitis in Indian patients. Methods This prospective observational study included 150 patients admitted within 24 hours of symptom onset. Serum CRP and albumin levels were measured to calculate the CRP/Alb ratio. Atlanta criteria classified severity as mild, moderate, or severe. The primary outcome was persistent organ failure. Results The mean age was 45±15 years, and 63% were males. The median C-reactive protein was 120 mg/L, Alb 3.2 g/dL, and CRP/Alb ratio 0.28. Severe acute pancreatitis patients (n = 50) had higher CRP/Alb ratios than mild cases (0.45 vs. 0.20, p<0.001). At a cut-off of 0.25, the CRP/Alb ratio demonstrated 85% sensitivity, 80% specificity, and an AUROC of 0.82 for predicting organ failure. This was significantly higher than the CRP (area under the receiver operating characteristic (AUROC) curve 0.72, p = 0.03) and Ranson score (AUROC 0.76, p = 0.04). On multivariate regression, CRP/Alb ratio >0.25 independently predicted severe acute pancreatitis after adjusting for age, gender, and CT severity index (adjusted OR 5.2, 95% CI 2.8-9.6). Conclusion The CRP/Alb ratio calculated within 24 hours reliably predicts persistent organ dysfunction in Indian acute pancreatitis patients. Incorporating this inexpensive biomarker into clinical prediction tools could significantly improve early risk stratification and streamline healthcare delivery in resource-limited settings.