Imbalances in lipid storage and secretion lead to the accumulation of hepatocyte lipid droplets (LDs) (i.e., hepatic steatosis).
View Article and Find Full Text PDFUnlabelled: Islet transplantation can cure type 1 diabetes, but peri-transplant beta cell death limits this procedure to those with low insulin requirements. Improving human beta cell survival or proliferation may make islet transplantation a possibility for more type 1 patients. To identify novel regulators of beta cell survival and proliferation, we conducted a pooled small hairpin RNA (shRNA) screen in primary human beta cells transplanted into immunocompromised mice.
View Article and Find Full Text PDFUnderstanding the interactions between SARS-CoV-2 and host cell machinery may reveal new targets to treat COVID-19. We focused on an interaction between the SARS-CoV-2 ORF3A accessory protein and the CLIC-like chloride channel-1 (CLCC1). We found that ORF3A partially co-localized with CLCC1 and that ORF3A and CLCC1 could be co-immunoprecipitated.
View Article and Find Full Text PDFThough the concentration of chloride has been measured in the cytoplasm and in secretory granules of live cells, it cannot be measured within the endoplasmic reticulum (ER) due to poor fluorescence of existing biosensors. We developed a fluorescent biosensor composed of a chloride-sensitive superfolder GFP and long Stokes-shifted mKate2 for simultaneous chloride and pH measurements that retained fluorescence in the ER lumen. Using this sensor, we showed that the chloride concentration in the ER is significantly lower than that in the cytosol.
View Article and Find Full Text PDFGpr27 is a highly conserved, orphan G protein coupled receptor (GPCR) previously implicated in pancreatic beta cell insulin transcription and glucose-stimulated insulin secretion in vitro. Here, we characterize a whole-body mouse knockout of Gpr27. Gpr27 knockout mice were born at expected Mendelian ratios and exhibited no gross abnormalities.
View Article and Find Full Text PDFCancer is one of the most fatal threatens to human health throughout the world. The major challenges in the control and eradication of cancers are the continuous emergency of drug-resistant cancer and the low specificity of anticancer agents, creating an urgent need to develop novel anticancer agents. Organometallic compounds especially ferrocene derivatives possess remarkable structural and mechanistic diversity, inherent stability towards air, heat and light, low toxicity, low cost, reversible redox, ligand exchange, and catalytic properties, making them promising drug candidates for cancer therapy.
View Article and Find Full Text PDFTwelve novel propylene-tethered ciprofloxacin-isatin hybrids 3a-f and 4a-f were designed, synthesized and characterized by MS, HRMS, H NMR and C NMR. All hybrids were evaluated for their in vitro antimicrobial activities against representative Gram-positive, Gram-negative and mycobacterial pathogens, cytotoxicity in VERO cell line as well as metabolic stability and in vivo pharmacokinetic (PK) properties. The preliminary results indicated that all mono-isatin-ciprofloxacin hybrids exhibited excellent antibacterial activities with MIC ranging from ≤0.
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