Sijia Li

Our results indicate that SARM1-mediated prodegenerative pathway and neuroinflammation promotes the pathological progress of SCI and anti-SARM1 therapeutics are viable and promising approaches for preserving neuronal function after SCI.

Abstract The loss of functional insulin-producing β-cells is a hallmark of diabetes. Mammalian sterile 20-like kinase 1 (MST1) is a key regulator of pancreatic β-cell death and dysfunction; its deficiency restores functional β-cells and normoglycemia. The identification of MST1 inhibitors represents a promising approach for a β-cell-protective diabetes therapy. Here, we identify neratinib, an FDA-approved drug targeting HER2/EGFR dual kinases, as a potent MST1 inhibitor, which improves β-cell survival under multiple diabetogenic conditions in human islets and INS-1E cells. In a pre-clinical study, neratinib attenuates hyperglycemia and improves β-cell function, survival and β-cell mass in type 1 (streptozotocin) and type 2 (obese Lepr db/db ) diabetic mouse models. In summary, neratinib is a previously unrecognized inhibitor of MST1 and represents a potential β-cell-protective drug with proof-of-concept in vitro in human islets and in vivo in rodent models of both type 1 and type 2 diabetes.

BACKGROUND: Stress hyperglycemia is a common condition in patients suffering from critical illness such as spontaneous intracerebral hemorrhage (ICH). Our study aimed to use glucose-to-glycated hemoglobin (HbA1c) ratio to investigate the impact of stress hyperglycemia on clinical outcomes in patients with ICH. METHODS: A sample of eligible 586 patients with spontaneous intracerebral hemorrhage from a multicenter, hospital-based cohort between 2014 and 2016 were recruited in our study. Stress hyperglycemia was evaluated by the index of the glucose-to-HbA1c ratio that was calculated by fasting blood glucose (mmol/L) divided by HbA1c (%). Patients were divided into two groups based on the median of the glucose-to-HbA1c ratio. The main outcomes were poor functional outcomes (modified Rankin Scale score of 3-6) at discharge and 90 days. Multivariable logistic regression and stratified analyses were performed to explore the association of stress hyperglycemia with poor prognosis of ICH. RESULTS: On multivariable analysis, higher glucose-to-HbA1c ratio (≥1.02) was independently correlated with poor functional outcomes at discharge (adjusted OR = 3.52, 95%CI: 1.98-6.23) and 90 days (adjusted OR = 2.27, 95%CI: 1.38-3.73) after adjusting for potential confounding factors. The correlation between glucose-to-HbA1c ratio and worse functional outcomes still retained in patients with or without diabetes mellitus. CONCLUSIONS: Stress hyperglycemia, calculated by glucose-to-HbA1c ratio, was independently correlated with worse functional outcomes at discharge and 90 days in patients with ICH. Moreover, glucose-to-HbA1c ratio, might not only be used as a simple and readily available index to predict clinical outcomes of ICH but also provide meaningful insight into future analysis to investigate the optimal range of glucose levels among ICH patients and develop tailored glucose-lowering strategies.