Diabetic nephropathy (DN) is a severe complication of diabetes lethal for end-stage renal disease, with less treatment methodologies and uncertain pathogenesis. In the current study, we determined the role of mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) containing microRNA (miR)-15b-5p in DN. After extraction and identification of MSC-derived EVs, mouse podocyte line MPC5 was selected to establish an in vitro high-glucose (HG) cell model, where expression of miR-15b-5p, pyruvate dehydrogenase kinase 4 (PDK4) and VEGFA expression in tissues and cells were determined. The loss- and gain- function assays were conducted to determine the roles of miR-15b-5p, PDK4 and VEGFA. MPC5 cells were then co-cultured with MSC-derived EVs and their biological behaviors were detected by Western blot, CCK-8 assay, and flow cytometry. The binding relationship between miR-15b-5p and PDK43 by dual luciferase reporter gene assay. The expression of miR-15b-5p was downregulated in podocytes under HG environment, but highly expressed in mouse MSCs-derived EVs. EVs-derived miR-15b-5p could protect MPC5 cell apoptosis and inflammation. miR-15b-5p inhibited the expression of PDK4 by directly bound to the 3'UTR region of PDK4 gene. miR-15b-5p inhibits VEGF expression by binding to PDK4. Inhibition of PDK4 decreased VEGFA expression and reduced apoptosis and inflammation. Collectively, miR-15b-5p shuttled by MSC-derived EV can play protective roles in HG-induced mouse podocyte injury, possibly by targeting PDK4 and decreasing the VEGFA expression.
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http://dx.doi.org/10.1007/s10863-021-09919-y | DOI Listing |
Asian Pac J Cancer Prev
January 2025
Adhiparasakthi Dental College and Hospital, Melmaruvathur, India.
Background: Angiogenesis, the formation of new blood vessels from preexisting ones via capillary sprouting, is a crucial process in tumor growth and metastasis. As a tumor's angiogenic capacity increases, its microvasculature, measured by micro vessel density (MVD), also increases. This study aims to evaluate the expression of Vascular Endothelial Growth Factor (VEGF) and CD34 in oral epithelial dysplasia and oral squamous cell carcinoma through immunohistochemical methods.
View Article and Find Full Text PDFBiol Reprod
January 2025
Department of Animal Sciences, University of Florida, Gainesville, FL 32611-0910, USA.
Optimal embryonic development depends upon cell-signaling molecules released by the maternal reproductive tract called embryokines. Identity of specific embryokines that enhance competence of the embryo for sustained survival is largely lacking. The current objective was to evaluate effects of three putative embryokines in cattle on embryonic development to the blastocyst stage.
View Article and Find Full Text PDFAnn Med
December 2025
Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China.
Background And Aims: Hepatocellular carcinoma (HCC) recurrence was previously characterized into four types, and patients with progression/hyper-progression recurrence (type III-IV) have an extremely poor prognosis. However, the immune background of resectable HCC, particularly in patients who experience recurrence, remains underexplored. Therefore, this study aimed to describe the immune landscape of resectable HCC, especially postoperative type III-IV recurrent HCC, and explore potential immune-targeted anti-relapse strategies for treated populations.
View Article and Find Full Text PDFFitoterapia
January 2025
College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China; Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Medicine, Zhengzhou 450046, China. Electronic address:
Tripterygium wilfordii (TW), which has severe hepatotoxicity, is commonly used as anti-rheumatism. Using the juice of auxiliary herbs in concocting poisonous herbs is a conventional method for toxicity reduction or efficacy enhancement. Traditional Chinese Pharmacy textbooks record that Spatholobi Caulis (SC) can alleviate the side effects caused by TW and also possesses excellent hepatoprotective effect.
View Article and Find Full Text PDFPlacenta
January 2025
Magee-Women's Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, 15213, USA. Electronic address:
Introduction: Fusion of mononucleated cytotrophoblasts into syncytium leads to trophoblast senescence. Yet, premature senescence is associated with preeclampsia, fetal growth restriction (FGR), and related obstetrical syndromes. A set of 28 transcripts that comprise senescence-associated secretory phenotype (SASP) was recently described in placentas from women with preeclampsia.
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