Int J Med Sci
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Cultured human skeletal-muscle satellite cells have properties of mesenchymal stem cells (skeletal muscle satellite cell-derived mesenchymal stem cells, SkMSCs) and play anti-inflammatory roles by secreting prostaglandin E2 and hepatocyte growth factor (HGF). To evaluate the utility of SkMSCs in treating liver diseases, we determined whether SkMSCs could ameliorate acute liver and gut inflammation induced by binge ethanol administration. Binge drinking of ethanol led to weight loss in the body and spleen, liver inflammation and steatosis, and increased serum ALT and AST levels (markers of liver injury), along with increased IL-1β, TNF-α, and iNOS expression levels in mice. ⋯ SkMSCs also reduced the leakage of blood albumin, an indicator of leaky gut, in the stool of ethanol-exposed mice. Alcohol-induced damage to human colonic Caco-2/tc7 cells was also alleviated by HGF. Therefore, a single treatment with SkMSCs can attenuate alcoholic liver damage by reducing inflammatory responses in the liver and gut, suggesting that SkMSCs could be used in cell therapy to treat alcoholic liver diseases.
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Background: Oxidative stress-related apoptosis is considered as the key mechanism implicated in the pathophysiology of nephrotoxicity with vancomycin (VCM) therapy. We evaluated the possible effects of N-acetylcysteine (NAC) on VCM-induced nephrotoxicity and the underlying mechanism. Methods: VCM-induced nephrotoxicity was established using HK-2 cells and SD rats and observed by measuring cell survival, kidney histological changes, renal function and kidney injury related markers (KIM-1 and NGAL). ⋯ NAC inhibited ROS production, decreased cell apoptosis by decreasing the Bax/Bcl-2 ratio and caspase-3 expression in HK-2 cells and regulated oxidative stress indicators in the kidney by decreasing GSH, SOD and CAT activity and increasing MDA levels. Furthermore, NAC could effectively reverse VCM-associated increased P38 MAPK/JNK phosphorylation. Conclusions: The results demonstrated that NAC had a protective effect against nephrotoxicity from VCM by inhibiting oxidative stress and apoptosis via P38 MAPK/JNK.
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Background and Aims: MicroRNAs (miRNAs) play important roles in hepatocyte differentiation from human bone marrow mesenchymal stem cells (hBMSCs) and the therapeutic application in vivo. However, the mechanisms of miRNA regulation are still unknown. This study aimed to profile the miRNA basis for improving the function of hBMSC-differentiated hepatocyte-like cells (hBMSC-Heps). ⋯ Functional experiments with these miRNAs showed that activators of hsa-miR-26b-5p and hsa-miR-148a-3p and an inhibitor of hsa-miR-423-3p were sufficient to improve the differentiation of hBMSCs into hepatocyte-like cells. Conclusions: Transcriptome profiles of miRNA revealed the basis of the differentiation and development of hBMSC-Heps. Manipulation of three miRNAs (hsa-miR-26b-5p, hsa-miR-148a-3p and hsa-miR-423-3p) significantly improved hepatocyte generation and liver regeneration, indicating the potential of these miRNAs for future clinical applications.
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Uterine corpus endometrial carcinoma (UCEC) is one of the most common types of cancer in women, and the incidence is rapidly increasing. Studies have shown that various signaling pathways serve crucial roles in the tumorigenesis of UCEC, amongst which the Wnt/β-catenin pathway is of great interest due to its crucial role in cell proliferation and the huge potential as a therapeutic target. ⋯ Besides, the results suggested that FBXO17 may inhibit the Wnt/β-catenin signaling pathway and influence the expression of adhesion molecules, such as E-cadherin and N-cadherin in Ishikawa cells. In conclusion, these findings indicate that FBXO17 is a novel inhibitor of endometrial tumor development and it likely exerts effects via regulation of the Wnt signaling pathway.
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Background: Lipid metabolism plays a pivotal role in cancer progression and metastasis. This study aimed to investigate the prognostic value of lipid metabolism-related genes (LMRGs) in early-stage lung adenocarcinoma (LUAD) and develop a lipid metabolism-related gene prognostic index (LMRGPI) to predict their overall survival (OS) and treatment response. Methods: A total of 774 early-stage LUAD patients were identified from The Cancer Genome Atlas (TCGA, 403 patients) database and Gene Expression Omnibus (GEO, 371 patients) database. ⋯ The opposite results were observed in the low-LMRGPI group. Conclusions: We comprehensively investigated the prognostic value of LMRGs in early-stage LUAD. Given its good prognostic ability, LMRGPI could serve as a promising biomarker to predict the OS and treatment response of these patients.