Project description:To further explore the overall development and progression of hepatic steatosis induced by HiAlc Kpn, we examined liver transcriptional profiles derived HiAlc Kpn-fed, pair-fed, or ethanol-fed mice for the 4th, 6th and 8th week post gavage. The liver gene expressions in mice both with HiAlc Kpn-fed and ethanol-fed have been showed large diversities to pair-fed mice. These results clearly illustrated a process of chronic liver injury, which is consistent with previous “two-hits” insulin hypothesis, and suggested that endogenous ethanol produced by HiAlc Kpn play important roles in the steatohepatitis, as well as alcohol intake.
Project description:The emergence and spread of carbapenem-resistant Klebsiella pneumoniae (CR-KPN) infections have worsened the current situation worldwide. Clinically, cotrimoxazole (CTX) and amikacin (AMI) are considered to be the preferred drugs in the treatment of (CR-KPN). But for now, the extensive use of cotrimoxazole (CTX) and amikacin (AMI) During the course of treatment leads to the emergence of cotrimoxazole- and amikacin-resistant infections, which is of great clinical concern. Previous evidence has shown that bacteria with reduced metabolism tend to be resistant to antibiotics, however, the mechanism remains unclear. In the present study, proteomics was performed on the sensitive, cotrimoxazole-resistant, amikacin-resistant and cotrimoxazole/amikacin-both-resistant KPN clinical isolates, and 2266 proteins were identified in total by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) analysis. Further bioinformatic analysis showed down-regulation of tricarboxylic acid cycle pathway and up-regulation of alcohol metabolic or glutathione metabolism processes, which may contribute to ROS clearance and cell survival, in drug-resistant isolates. Finally, combined with minimum inhibitory concentration (MIC) of Amikacin and Cotrimoxazole on different KPN isolates, we identified nine proteins contributed mostly to such an alteration and the survival of bacteria under drug pressure, which could reveal novel mechanisms or pathways involved in drug resistance. These proteins and their pathways might be used as targets for the development of novel therapeutics against antimicrobial-resistant (AMR) infections.
Project description:We aimed to investigate gene expression changes in intestinal organoids from different mouse genotypes after treatment with interferon-gamma. Wild-type, villinCreER;KrasG12D/+;Trp53fl/flRosa26N1icd/+ (KPN), and villinCreER;Apcfl/fl;KrasG12D/+;Trp53fl/flTgfbrIfl/fl (AKPT) intestinal organoids were plated, and the media was supplemented with 1 ng/mL of recombinant mouse interferon-gamma protein on Day 3. RNA was collected 24h later and processed for RNA sequencing.
Project description:We aimed to investigate gene expression changes in intestinal organoids from different mouse genotypes after treatment with TGF-beta. Wild-type, villinCreER;KrasG12D/+;Trp53fl/flRosa26N1icd/+ (KPN), and villinCreER;Apcfl/fl;KrasG12D/+;Trp53fl/flTgfbrIfl/fl (AKPT) intestinal organoids were plated, and the media was supplemented with 5ng/mL of recombinant mouse TGFß1 protein on Day 3. RNA was collected 24h later and processed for RNA sequencing.