Notes

In this paper, we use RNAseq to identify senescence and phagocytosis as key factors to understanding how mitomyin C (MMC) stimulates regenerative wound repair
seebio Vitamin use conditioned media (CM) from untreated (CMC) and MMC treated (CMM) human and mouse corneal epithelial cells to show that corneal epithelial cells indirectly exposed to MMC secrete elevated levels of immunomodulatory proteins including IL-1α and TGFβ1 compared to cells exposed to CMC. These factors increase epithelial and macrophage phagocytosis and promote ECM turnover. IL-1α supplementation can increase phagocytosis in control epithelial cells and attenuate TGFβ1 induced αSMA expression by corneal fibroblasts. Yet, we show that epithelial cell CM contains factors besides IL-1α that regulate phagocytosis and αSMA expression by fibroblasts. Exposure to CMM also impacts the activation of bone marrow derived dendritic cells and their ability to present antigen. These in vitro studies show how a brief exposure to MMC induces corneal epithelial cells to release proteins and other factors that function in a paracrine way to enhance debris removal and enlist resident epithelial and immune cells as well as stromal fibroblasts to support regenerative and not fibrotic wound healing.

Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, hormones and desire to eat: A systematic review and meta-analysis of clinical Recent studies have demonstrated the effect of probiotics, prebiotics, and synbiotics on adiponectin and leptin levels; however, those findings remain contested. The present study aimed to explore the impact of probiotics/synbiotics on appetite-regulating hormones and the desire to eat. METHODS: A systematic review was conducted by searching the Medline (PubMed) and Scopus databases from inception to December 2021, using relevant keywords and MeSH terms, and appropriate randomized controlled trials (RCTs) were extracted. The standardized mean differences (SMD) and 95% confidence intervals (95%CIs) were calculated as part of the meta-analysis using a random-effect model to determine the mean effect sizes. Analysis of Galbraith plots and the Cochrane Chi-squared test were conducted to examine heterogeneity. RESULTS: Meta-analysis of data from a total of 26 RCTs (n = 1536) showed a significant decrease in serum/plasma leptin concentration following probiotic/synbiotic supplementation (SMD: -38, 95%CI= -638, -124); P-value= 004; I(2)= 4%; P heterogeneity < 001). The leptin level decrease from probiotic/synbiotic supplementation was higher in patients with NAFLD than those with overweight/obesity or type 2 diabetes mellitus/ metabolic syndrome/ prediabetes.

Probiotic/synbiotic supplementation was associated with a trending increase in adiponectin levels, stronger in patients with type 2 diabetes mellitus, metabolic syndrome, and prediabetes (SMD: 25, 95%CI= 04, 46) µg/mL; P-value= 021; I(2) = 8%; P heterogeneity= 30). Additionally, supplementation with probiotic/synbiotic was linked to a slight increase in desire to eat (SMD: 34, 95%CI= 03, 66) P-value = 030; I(2) = 4%; P heterogeneity= 16). CONCLUSION: Our meta-analysis indicates a favorable impact of probiotic/synbiotic supplementation on regulating leptin and adiponectin secretion. Medicine, Lindenberger Weg 80, 13125 Berlin, Germany; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; Germany; DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Medicine, Lindenberger Weg 80, 13125 Berlin, Germany; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; Germany; DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Medicine, Lindenberger Weg 80, 13125 Berlin, Germany; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; Germany; DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany. The versatility of ubiquitination to control vast domains of eukaryotic biology is due, in part, to diversification through differently linked poly-ubiquitin chains. Deciphering signaling roles for some chain types, including those linked via K6, has been stymied by a lack of specificity among the implicated regulatory proteins. Forged through strong evolutionary pressures, pathogenic bacteria have evolved intricate mechanisms to regulate host ubiquitin during infection.

Herein, Seebio anti-infective vitamin identify and characterize a deubiquitinase domain of the secreted effector LotA from Legionella pneumophila that specifically regulates K6-linked poly-ubiquitin. We demonstrate the utility of LotA for studying K6 poly-ubiquitin signals. We identify the structural basis of LotA activation and poly-ubiquitin specificity and describe an essential "adaptive" ubiquitin-binding domain. Without LotA activity during infection, the Legionella-containing vacuole becomes decorated with K6 poly-ubiquitin as well as the AAA ATPase VCP/p97/Cdc We propose that LotA's deubiquitinase activity guards Legionella-containing vacuole components from ubiquitin-dependent extraction. technology using LotA to study K6 poly-Ub.
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