MicroRNA-122-5p is upregulated in diabetic foot ulcers and decelerates the transition from the inflammatory to the proliferative stage

World Journal of Diabetes, Journal Year: 2025, Volume and Issue: 16(4)

Published: Feb. 28, 2025

Shifting from the inflammatory to proliferative phase represents a pivotal step during managing diabetic foot ulcers (DFUs); however, existing medical interventions remain insufficient. MicroRNAs (miRs) highlight notable capacity for accelerating repair process of DFUs. Previous research has demonstrated which miR-122-5p regulates matrix metalloproteinases under conditions, thereby influencing extracellular dynamics. To investigate impact on transition stage in DFU. Analysis expression skin tissues ulcer patients and mice was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). A wound healing model induced by streptozotocin used, with receiving intradermal injections adeno-associated virus -DJ encoding empty vector or miR-122. Skin were retrieved at 3, 7, 14 days after injury gene analysis, histology, immunohistochemistry, network studies. The study explored miR-122-5p's role macrophage-fibroblast interactions its effect transitioning inflammation proliferation DFU healing. High-throughput sequencing revealed as crucial qRT-PCR showed significant upregulation within among individuals mice. Western blot, along immunohistochemical enzyme-linked immunosorbent assay, demonstrating mediators (hypoxia inducible factor-1α, metalloproteinase 9, tumor necrosis factor-α) reduced fibrosis markers (fibronectin 1, α-smooth muscle actin) targeting vascular endothelial growth factor. Fluorescence situ hybridization indicated localized epidermal keratinocytes fibroblasts Immunofluorescence enhanced increased presence M1 macrophages M2 polarization, highlighting inflammation. MiR-122-5p elevated cytokine levels while suppressing fibrotic activity exposed macrophage-derived media, regulating impedes cutaneous via enhancing inhibiting fibrosis, offering insights into miR roles human repair.

Language: Английский

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MiRNA-122-5p is Upregulated in Diabetic Foot Ulcers and Decelerates the Transition from the Inflammatory to the Proliferative Stage

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

Transitioning from the inflammatory to proliferative stage is critical in treating diabetic foot ulcers (DFUs), yet current treatment options are limited. MicroRNAs (miRNAs) hold significant potential enhancing DFU healing. Previous studies have shown that miR-122-5p targets regulation of metalloproteinases, impacting extracellular matrix. We hypothesize plays a crucial role healing DFU. MiR-122-5p levels skin tissue samples both patients with and mice were evaluated using quantitative real-time PCR (qRT-PCR). The streptozotocin-induced diabetes mouse model for wound was utilized. Animals randomized receive intradermal injections either an AAVDJ empty vector (AAVDJ-EV, control) or AAVDJ-miR-122 upregulation vector. Mice euthanized at different intervals (3, 7, 14 days post-injury), tissues collected gene marker analysis, histological evaluation, immunohistochemistry, network analysis. study focused on proteins involved transition during Additionally, mediating interactions between macrophages fibroblasts analyzed. FISH qRT-PCR results indicated significantly upregulated skin, individuals mice, compared controls. Western blot, IHC, ELISA vitro, increased MMP9 expression mediators such as TNF-α HIF-1α, while concurrently decreasing VEGF markers associated fibrosis FN1 α-SMA.Our findings confirmed increases cytokines reduces cultured macrophage-conditioned media.MiR-122-5p inflammation reduce slowing stage. These open door understanding how miRNAs functionally contribute human

Language: Английский

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The Mag-Click-Capture-Release Technology for Selective Capture and Release of Hepatocyte-Derived Extracellular Vesicles as Biomarkers for Liver Disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Abstract Chronic liver diseases, such as cirrhosis and hepatocellular carcinoma (HCC), present major global health challenges, often diagnosed late. Circulating extracellular vesicles (EVs), which carry disease-specific biomolecular cargo, is emerging an early diagnostic prognostic biomarker for several diseases including cancer. However, current EV purification methods ultracentrifugation size exclusion chromatography limitations. Here, we the Mag-Click-Capture-Release Technology selective capture release of EVs that combines mag netic beads, trans-cyclooctene (TCO) tetrazine (Tz) click chemistry, immuno(antibody)-based disulfide-driven EVs. Importantly, customizable, whereby using specific antibodies conjugated to TCO antibodies, different subtypes can be selectively captured released further analysis. With our Technology, successfully isolated hepatocyte-derived from human serum with good recovery, high specificity purity when compared standard ultracentrifugation. Validation in samples obtained HCC patients alcohol-associated disease evidenced increasing trend hepatocyte-EV levels correlating severity, suggesting potential diagnosis prognosis. In conclusion, here a customizable efficient approach isolation organ-, cell-specific, disease-relevant biological subsequently downstream molecular analysis EV-related functional assays.

Language: Английский

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Lnc_CXADR/miR-421/ATG7 as promising biomarkers relevant to hepatocellular carcinoma

Gene Reports, Journal Year: 2024, Volume and Issue: 38, P. 102114 - 102114

Published: Dec. 10, 2024

Language: Английский

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