Xiaohai Zhou

INTRODUCTION: Previous studies have demonstrated a correlation between the serum uric acid-to-high-density lipoprotein cholesterol ratio (UHR) and insulin resistance (IR) in individuals with type 2 diabetes mellitus. However, no existing studies have investigated the relationship between IR and UHR in the general population. Therefore, the primary objective of this study was to investigate the correlation between UHR and IR in the general American population. METHODS: A sample of 8,817 participants was selected from the 2013 to 2020 National Health and Nutrition Examination Survey (NHANES). Homeostatic model assessment of insulin resistance (HOMA-IR) was used to assess insulin resistance. Multiple logistic regression, generalized smooth curve fitting, and subgroup analysis were used to assess the association between IR and UHR. RESULTS: Multiple logistic regression analysis indicated a significant correlation between insulin resistance and UHR, with odds ratios (OR) of 1.07 (95% CI = 1.03-1.11) in males and 1.18 (95% CI = 1.13-1.25) in females. A non-linear relationship and saturation effect between IR risk and UHR were observed, characterized by an inverted L-shaped curve and a critical inflection point at 8.82. It was found that the area under the ROC curve (AUC) of UHR was significantly larger (AUC = 0.703 for males and 0.747 for females, all P < 0.01) compared with the use of UA or HDL-C alone. Subgroup analysis showed that this independent association remain consistent regardless of race, age, BMI, diabetes, moderate activities, education level, alcohol drinking, and gender. CONCLUSION: Elevated UHR demonstrates a significant correlation with insulin resistance, so it can be used as a potential indicator of insulin resistance within the American population.

Dual-specificity phosphatase 6 (DUSP6) serves a specific and conserved function on the dephosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). We previously identified Dusp6 as a regenerative repressor during zebrafish heart regeneration, therefore we propose to investigate the role of this repressor in mammalian cardiac repair. Utilizing a rat strain harboring Dusp6 nonsense mutation, rat neutrophil-cardiomyocyte co-culture, bone marrow transplanted rats and neutrophil-specific Dusp6 knockout mice, we find that Dusp6 deficiency improves cardiac outcomes by predominantly attenuating neutrophil-mediated myocardial damage in acute inflammatory phase after myocardial infarction. Mechanistically, Dusp6 is transcriptionally activated by p38-C/EBPβ signaling and acts as an effector for maintaining p-p38 activity by down-regulating pERK and p38-targeting phosphatases DUSP1/DUSP16. Our findings provide robust animal models and novel insights for neutrophil-mediated cardiac damage and demonstrate the potential of DUSP6 as a therapeutic target for post-MI cardiac remodeling and other relevant inflammatory diseases.