Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion. Global gene expression profile of normal dermal lymphatic endothelial cells (ndLECs) compared to dermal lymphatic endothelial cells derived from type 2 diabetic patients (dLECs).Quadruplicate biological samples were analyzed from human lymphatic endothelial cells (4 x diabetic; 4 x non-diabetic). subsets: 1 disease state set (dLECs), 1 control set (ndLECs)
Project description:Hepatocellular carcinoma is one of the most prevalent malignancies worldwide, and the role of stress in hepatocellular carcinoma progression remains incompletely understood. In this study, we integrated clinical and preclinical models to investigate how stress-associated gut microbiota remodeling contributes to hepatocellular carcinoma progression. Stress profoundly altered the gut microbiota, with Phocaeicola vulgatus significantly reduced. Restoration of Phocaeicola vulgatus or administration of its tryptophan-derived metabolite indole-3-propionic acid attenuated hepatocellular carcinoma progression in vivo. Single-cell RNA sequencing was performed to characterize changes in the hepatocellular carcinoma tumor microenvironment. Indole-3-propionic acid treatment reduced endothelial JAM2 expression and was associated with reduced JAM2-F11R-mediated endothelial-macrophage crosstalk. These findings support a role for the stress-gut microbiota-metabolite-tumor microenvironment axis in hepatocellular carcinoma progression and suggest potential translational targets for microbiome-based therapeutic strategies.