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American Journal of Transplantation :... Nov 2022Ischemia-reperfusion injury is a major cause of acute kidney injury. Many cytokines are involved in the pathogenesis of renal ischemia-reperfusion injury. IL24 is a...
Ischemia-reperfusion injury is a major cause of acute kidney injury. Many cytokines are involved in the pathogenesis of renal ischemia-reperfusion injury. IL24 is a member of the IL10 family and has gained importance because of its apoptosis-inducing effects in tumor disease besides its immunoregulative function. Littles is known about the role of IL24 in kidney disease. Using a mouse model, we found that IL24 is upregulated in the kidney after renal ischemia-reperfusion injury and that tubular epithelial cells and infiltrating inflammatory cells are the source of IL24. Mice lacking IL24 are protected from renal injury and inflammation. Cell culture studies showed that IL24 induces apoptosis in renal tubular epithelial cells, which is accompanied by an increased endoplasmatic reticulum stress response. Moreover, IL24 induces robust expression of endogenous IL24 in tubular cells, fostering ER-stress and apoptosis. In kidney transplant recipients with delayed graft function and patients at high risk to develop acute kidney injury after cardiac surgery IL24 is upregulated in the kidney and serum. Taken together, IL24 can serve as a biomarker, plays an important mechanistic role involving both extracellular and intracellular targets, and is a promising therapeutic target in patients at risk of or with ischemia-induced acute kidney injury.
Topics: Animals; Mice; Mice, Inbred C57BL; Acute Kidney Injury; Reperfusion Injury; Kidney; Apoptosis; Interleukins; Epithelial Cells
PubMed: 35801504
DOI: 10.1111/ajt.17143 -
Frontiers in Microbiology 2023Liver cirrhosis is commonly accompanied by intestinal dysbiosis and metabolic defects. Many clinical trials have shown microbiota-targeting strategies represent...
BACKGROUND
Liver cirrhosis is commonly accompanied by intestinal dysbiosis and metabolic defects. Many clinical trials have shown microbiota-targeting strategies represent promising interventions for managing cirrhosis and its complications. However, the influences of the intestinal metagenomes and metabolic profiles of patients have not been fully elucidated.
METHODS
We administered lactulose, , and as a synbiotic and used shotgun metagenomics and non-targeted metabolomics to characterize the results.
RESULTS
Patients treated with the synbiotic for 12 weeks had lower dysbiosis index (DI) scores than placebo-treated patients and patients at baseline (NIP group). We identified 48 bacterial taxa enriched in the various groups, 66 differentially expressed genes, 18 differentially expressed virulence factor genes, 10 differentially expressed carbohydrate-active enzyme genes, and 173 metabolites present at differing concentrations in the Synbiotic versus Placebo group, and the Synbiotic versus NIP group. And species, especially , showed positive associations with many differentially expressed genes in synbiotic-treated patients. Metabolites pathway enrichment analysis showed that synbiotic significantly affected purine metabolism and aminoacyl-tRNA biosynthesis. And the purine metabolism and aminoacyl-tRNA biosynthesis were no longer significant differences in the Synbiotic group versus the healthy controls group. In conclusion, although littles influence on clinical parameters in the early intervention, the synbiotic showed a potential benefit to patients by ameliorating intestinal dysbiosis and metabolic defects; and the DI of intestinal microbiota is useful for the evaluation of the effect of clinical microbiota-targeting strategies on cirrhotic patients.
CLINICAL TRIAL REGISTRATION
https://www.clinicaltrials.gov, identifiers NCT05687409.
PubMed: 37180228
DOI: 10.3389/fmicb.2023.1169811