A novel mutation in HNF1B promotes ferroptosis-mediated renal mesangial cells fibrosis.

Maturity onset diabetes of the young type 5(MODY5) is typically attributed to mutations in the HNF1B gene, which encodes transcription factors that play a significant role in kidney development and function maintenance. In this study, we identified a novel HNF1B gene mutation (c.445C > A) in a young male MODY5 patient exhibiting elevated serum creatinine levels and albuminuria. Through transfection of wild type and mutant HNF1B plasmids into mouse mesangial cells (MMCs), we investigated the impact on molecular indicators related to proliferation, fibrosis and oxidative stress. The results revealed that the HNF1B novel mutation promoted the expression of fibronectin, type 1 collagen, and CyclinD1, as well as increasing cellular oxidative stress and susceptibility to ferroptosis in MMCs. Our findings established a novel association between HNF1B mutant diseases and mesangial cell proliferation and fibrosis, suggesting that mutations of HNF1B may contribute to the progression of renal function in MODY5 patients. Additionally, our results implicate potential therapeutic targets for restraining fibrosis.

An electrochemical biosensor based on multi-wall carbon nanotube-modified screen-printed electrode immobilized by uricase for the detection of salivary uric acid.

The amounts of uric acid (UA) in non-invasive biological samples, such as saliva, are critical for diagnosis and therapy of gout, hyperuricemia, Lesch-Nyhan syndrome, and several other diseases. Here, disposable UA biosensors were fabricated with the screen printing technique on the substrate of flexible PET. The working electrode was modified with carbon nanotubes followed by uricase for UA detection with excellent selectivity. The biosensor showed good electrocatalytic activity toward UA with high sensitivity, low detection limit, and wide linear range, which covers the full range of UA levels in human saliva. We demonstrate that UA can be directly detected in human saliva with the biosensor and the experimental data were consistent with the clinical analysis. This study indicated that the non-invasive biosensor is an attractive and possible approach for the monitoring of salivary UA. Graphical abstract A disposable uric acid biosensor modified with carbon nanotubes followed by uricase was fabricated on flexible PET and applied for the monitoring of salivary uric acid in human saliva.

Association between systemic iron status and ß-cell function and insulin sensitivity in patients with newly diagnosed type 2 diabetes.

Objective: Abnormal iron metabolism is related to the risk of diabetes, but the underlying mechanism of this association remains uncertain. This study was conducted to evaluate the contributions of systemic iron status to ß-cell function and insulin sensitivity of patients with newly diagnosed T2DM. Methods: A total of 162 patients with newly diagnosed T2DM and 162 healthy controls were enrolled in the study. Basic characteristics, biochemical indicators, and iron metabolism biomarkers, including serum iron (SI), ferritin (SF), transferrin (Trf), and transferrin saturation (TS), were collected. All patients underwent a 75 g oral glucose tolerance test. A series of parameters for assessing ß-cell function and insulin sensitivity were calculated. The multivariate stepwise linear regression model was used to investigate the contributions of iron metabolism to ß-cell function and insulin sensitivity. Results: Compared with healthy controls, patients with newly diagnosed T2DM had significantly higher levels of SF. Among the diabetic patients, the SI and TS levels were higher, and the percentage of Trf levels below normal values was lower in men than in women. In all diabetic patients, SF was the independent risk factor associated with impaired ß-cell function. Further stratification analysis showed that Trf was an independent protective factor for ß-cell function in male patients, while SF was an independent risk factor for impaired ß-cell function in female patients. However, systemic iron status did not affect insulin sensitivity. Conclusion: Elevated SF levels and decreased Trf levels had a profound effect on impaired ß-cell function in Chinese patients with newly diagnosed T2DM.