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Chronic inflammation of white adipose tissue is a key link between obesity and the associated metabolic syndrome. Transient receptor potential melastatin-like 7 (TRPM7) is known to be related to inflammation; however, the role of TRPM7 in adipocyte phenotype and function in obesity remains unclear. Here, we observe that the activation of adipocyte TRPM7 plays an essential role in pro-inflammatory responses. Adult male mice are used in our experiments. Adipocyte-specific deficiency in TRPM7 attenuates the pro-inflammatory phenotype, improves glucose homeostasis, and suppresses weight gain in mice fed a high-fat diet. Mechanistically, the pro-inflammatory effect of TRPM7 is dependent on Ca2+ signaling. Ca2+ influx initiated by TRPM7 enhances transforming growth factor-β activated kinase 1 activation via the co-regulation of calcium/calmodulin-dependent protein kinase II and tumor necrosis factor receptor-associated factor 6, leading to exacerbated nuclear factor kappa B signaling. Additionally, obese mice treated with TRPM7 inhibitor are protected against obesity and insulin resistance. Our results demonstrate TRPM7 as a factor in the development of adipose inflammation that regulates insulin sensitivity in obesity.Adipose tissue inflammation contributes to the pathogenesis of obesity-related metabolic disorders. Here the authors report that adipocyte-specific genetic deficiency or pharmacological inhibition of TRPM7, a cation channel, attenuates adipose tissue inflammation, improves glucose homeostasis, and suppresses weight gain in obese male mice. [ABSTRACT FROM AUTHOR]

Metabolite alteration has been associated with the pathogenesis of inflammatory bowel disease (IBD), including colitis. Mannose, a natural bioactive monosaccharide that is involved in metabolism and synthesis of glycoproteins, exhibits anti-inflammatory and anti-oxidative activities. We show here that the circulating level of mannose is increased in patients with IBD and mice with experimental colitis. Mannose treatment attenuates intestinal barrier damage in two mouse colitis models, dextran sodium sulfate (DSS)-induced colitis and spontaneous colitis in IL-10-deficient mice. We demonstrate that mannose treatment enhanced lysosomal integrity and limited the release of cathepsin B, preventing mitochondrial dysfunction and myosin light chain kinase (MLCK)-induced tight junction disruption in the context of intestinal epithelial damage. Mannose exerts a synergistic therapeutic effect with mesalamine on mouse colitis. Cumulatively, the results indicate that mannose supplementation may be an optional approach to the treatment of colitis and other diseases associated with intestinal barrier dysfunction. New potential therapies for inflammatory bowel disease are needed as not all patients respond to or maintain a response to conventional therapies. Here the authors report that mannose supplementation ameliorates experimental colitis in male mice, potentially via effects on intestinal epithelium lysosomal integrity. [ABSTRACT FROM AUTHOR]

Most colorectal cancer (CRC) patients are diagnosed with advanced stages and low prognosis. We aimed to identify potential diagnostic and prognostic biomarkers, as well as active small molecules of CRC. Microarray data (GSE9348, GSE35279, and GSE106582) were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by the GEO2R platform. Common DEGs were selected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Cytoscape software was used to construct protein-protein interaction networks and identify hub genes. Hub genes were evaluated by Kaplan-Meier survival analysis in the GEPIA database and validated in two independent microarray data (GSE74602 and GSE83889). Common DEGs were used to select active small molecules by the connectivity map database. A total of 166 DEGs were identified as common DEGs. GO analysis demonstrated that common DEGs were significantly enriched in the apoptotic process, cell proliferation, and cell adhesion. KEGG analysis indicated that the most enriched pathways were the PI3K-Akt signaling pathway and extracellular matrix-receptor interaction. COL1A2, THBS2, TIMP1, and CXCL8 significantly upregulated in colorectal tumor. High expressions of COL1A2, THBS2, and TIMP1 were associated with poor survival, while high expressions of CXCL8 were associated with better survival. We selected 11 small molecules for CRC therapy. In conclusion, we found key dysregulated genes associated with CRC and potential small molecules to reverse them. COL1A2, THBS2, TIMP1, and CXCL8 may act as diagnostic and prognostic biomarkers of CRC. [ABSTRACT FROM AUTHOR]

A novel nanomaterial of two-dimensional holey CuCo2O4 (2D HCCO) nanosheets was synthesized via a general template-directed method and employed for the first time to construct an effective electrochemical platform for H2O2 sensing with the combination of cerium oxide (CeO2). During the electrocatalytic reduction of H2O2, the synergetic catalysis of CeO2/HCCO/MWCNTs/GCE owing to the naturally holey frameworks and the mediator of CeO2 results in the ultra-sensitive detection of H2O2. The current was greatly enhanced owing to the unique holey structure that can minimize the charge transfer distance and provide more active sites to boost the signals, and the dual oxidation state of Ce3+/Ce4+ on the surface of 2D HCCO nanosheets can promote the in situ production of Cu2+/Cu+ and Cu+/Cu and further amplify the detection signal. The CeO2/HCCO/MWCNTs/GCE showed a wide linear range from 1 μM to 7.31 mM using chronoamperometry at the potential of − 0.25 V and a relatively low detection limit of 0.16 μM in physiological environment, which was also utilized for tracking the trace H2O2 released from Hela cells. This study shows great promise for the emerging application of holey HCCO-based biosensors in bioanalysis and early cancer diagnosis. [ABSTRACT FROM AUTHOR]