Aims/hypothesis: Sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) are antihyperglycaemic drugs that protect the kidneys of individuals with type 2 diabetes mellitus. However, the underlying mechanisms mediating the renal benefits of SGLT2i are not fully understood. Considering the fuel switches that occur during therapeutic SGLT2 inhibition, we hypothesised that SGLT2i induce fasting-like and aestivation-like metabolic patterns, both of which contribute to the regulation of metabolic reprogramming in diabetic kidney disease (DKD).
View Article and Find Full Text PDFImpaired fatty acid oxidation (FAO) is a metabolic hallmark of renal tubular epithelial cells (RTECs) under diabetic conditions. Disturbed FAO may promote cellular oxidative stress and insufficient energy production, leading to ferroptosis subsequently. Canagliflozin, an effective anti-hyperglycemic drug, may exert potential reno-protective effects by upregulating FAO and inhibiting ferroptosis in RTECs.
View Article and Find Full Text PDFDiabetic kidney disease (DKD) develops in ~40% of patients with diabetes and is the leading cause of chronic kidney disease worldwide. We used single-cell RNA-sequencing and spatial transcriptomic analyses of kidney specimens from patients with DKD. Unsupervised clustering revealed distinct cell clusters, including epithelial cells and fibroblasts.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
June 2023
There is increasing evidence that the crosstalk between podocytes and glomerular endothelial cells (GECs) exacerbates the progression of diabetic kidney disease (DKD). Here, we investigated the underlying role of SUMO specific peptidase 6 (SENP6) in this crosstalk. In the diabetic mice, SENP6 was decreased in glomerular tissues and its knockdown further exacerbated glomerular filtration barrier injury.
View Article and Find Full Text PDFBackgroud: Bidirectional communications between the gut microbiota and the brain may play a critical role in diabetes-related cognitive impairment. Compound Danshen Dripping Pills (CDDP) treatment has shown remarkable improvement in cognitive impairment in people with type 2 diabetes mellitus (T2DM) in clinical settings, but the underlying mechanisms remain unknown.
Purpose: An extensive detailed strategy via in vivo functional experiments, transcriptomics, metabolomics, and network pharmacology was adopted to investigate the CDDP-treatment mechanism in diabetic cognitive dysfunction.
Objectives: Elevated thioredoxin-interacting protein (TXNIP)-induced pyroptosis contributes to the pathology of diabetic kidney disease (DKD). However, the molecular mechanisms in dysregulated TXNIP in DKD remain largely unclear.
Materials And Methods: Transcriptomic analysis identified a novel long noncoding RNA-Prader Willi/Angelman region RNA, SNRPN neighbour (PWARSN)-which was highly expressed in a proximal tubular epithelial cell (PTEC) under high glucose conditions.
Objective: The purpose of this study was to elucidate the characteristics of the gut microbiome in patients with Polycystic ovary syndrome (PCOS) and analyze the alterations of fecal fatty acid metabolism, so as to further provide the pathogenesis of PCOS.
Methods: Fecal samples from the PCOS group ( = 31) and healthy control group ( = 27) were analyzed by 16S rRNA gene sequencing and untargeted metabolomics. Peripheral venous blood was collected to measure serum inflammation and intestinal permeability.
Diabetic kidney disease (DKD) is a serious diabetes complication. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel anti-diabetes drugs that confer clinical renal protection. However, the molecular mechanisms involved remain unclear.
View Article and Find Full Text PDFDiabetic kidney disease (DKD) is a severe complication of diabetes mellitus for which there is still no effective treatment. We previously showed that upregulation of thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of thioredoxin (TRX), accelerates the progression of DKD. In this study, we hypothesized whether verapamil, a calcium channel blocker and an established TXNIP inhibitor, might exert a renal-protective effect on DKD by regulating TXNIP expression.
View Article and Find Full Text PDFThe tumor microenvironment (TME) has been reported to have significant value in the diagnosis and prognosis of cancers. This study aimed to identify key biomarkers in the TME of luminal breast cancer (BC). We obtained immune scores (ISs) and stromal scores (SSs) for The Cancer Genome Atlas (TCGA) luminal BC cohort from the online ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) portal.
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