Proteomics analyses of acute kidney injury biomarkers in a rat exertional heat stroke model.

The frequency of exertional heat stroke (EHS) increases with the gradual elevation of global temperatures during summer. Acute kidney injury (AKI) is a common complication of EHS, and its occurrence often indicates the worsening of a patient's condition or a poor prognosis. In this study, a rat model of AKI caused by EHS was established, and the reliability of the model was evaluated by HE staining and biochemical assays. The expression of kidney tissue proteins in the EHS rats was analyzed using label-free liquid chromatography-tandem mass spectrometry. A total of 3,129 differentially expressed proteins (DEPs) were obtained, and 10 key proteins were finally identified, which included three upregulated proteins (Ahsg, Bpgm, and Litaf) and seven downregulated proteins (medium-chain acyl-CoA synthetase 2 (Acsm2), Hadha, Keg1, Sh3glb1, Eif3d, Ambp, and Ddah2). The qPCR technique was used to validate these 10 potential biomarkers in rat kidney and urine. In addition, Acsm2 and Ahsg were double-validated by Western blotting. Overall, this study identified 10 reliable biomarkers that may provide potential targets for the treatment of AKI caused by EHS.

Impacts of Mercury Exposure Levels and Sources on the Demethylation of Methylmercury Through Human Gut Microbiota.

This study aims to investigate methylmercury (MeHg) demethylation processes in human gut. Here, we determined the compositions and MeHg demethylation rates of gut microbiota in residents from different Hg exposure levels (Wanshan (WS) town and Yangtou (YT) town) and different Hg exposure sources (Zhuchang (ZC) town and YT town) regions. MeHg and inorganic Hg exposure levels in residents of WS town were significantly higher than those of YT and ZC town. Desulfovibrio and Methanogens, which related to Hg methylation/demethylation, showed significantly higher abundance in WS and ZC, comparing with YT. In vitro experiments demonstrated that human intestinal microbiota could degrade MeHg directly. Besides, gut microbiota in WS and ZC exhibited significantly higher demethylation rates than YT, suggesting Desulfovibrio and Methanogens may play important roles in intestinal MeHg demethylation. This study highlights Hg exposure levels and sources may affect demethylation efficiency of gut microbiota, which provides new insights for MeHg demethylation processes in human body.

Revealing Potential Diagnostic Gene Biomarkers Associated with Immune Infiltration in Patients with Renal Fibrosis Based on Machine Learning Analysis.

Chronic kidney disease is characterized by the development of renal fibrosis. The basic mechanisms of renal fibrosis have not yet been fully investigated despite significant progress in understanding the etiology of the disease. In this work, the researchers sought to identify potential diagnostic indicators for renal fibrosis. From the GEO database, we were able to acquire two gene expression profiles with publically available data (GSE22459 and GSE76882, respectively) from human renal fibrosis and control samples. 215 renal fibrosis specimens and 124 normal specimens were examined for differentially expressed genes (DEGs). The SVM-RFE and LASSO regression models were used to discover potential markers. CIBERSORT was applied to estimate the combined cohorts' immune cell fraction compositional trends in renal fibrosis. RT-PCR was used to examine the expression of ISG20 in renal fibrosis and healthy samples. In vitro experiments were applied to examine the function of ISG20 knockdown on the progression of renal fibrosis. In this study, we identified 24 DEGs. The result of LASSO and SVM-RFE identified nine critical genes. ROC assays confirmed the diagnostic value of the above nine genes for renal fibrosis. Immune cell infiltration analysis revealed that ISG20 and SERPINA3 were both found to be correlated with T cell follicular helper, neutrophils, T cell CD4 memory activated, eosinophils, T cell CD8, dendritic cell activated, B cell memory, monocytes, macrophage M2, plasma cells, T cell CD4 naïve, mast cell resting, B cell naïve, T cell regulatory, and NK cell activated. Finally, we observed that the expression of ISG20 and SERPINA3 was distinctly increased in renal fibrosis samples compared with normal samples. ISG20 siRNA significantly suppressed the progression of renal fibrosis in vitro. Overall, this study identified nine diagnostic biomarkers for renal fibrosis. ISG20 may be a novel therapeutic target of renal fibrosis.

Two New C19-Diterpenoid Alkaloids from Aconitum nagarum var. lasiandrum.

Continuous investigations of the roots of Aconitum nagarum var. lasiandrum led to the isolation of two new C19-diterpenoid alkaloids, lasiandrine (1) and lasiandroline (2). Their structures were elucidated on the basis of extensive interpretation of spectroscopic and mass spectrometric data.