Non-coding RNA as a key regulator and novel target of apoptosis in diabetic cardiomyopathy: Current status and future prospects

Cellular Signalling, Journal Year: 2025, Volume and Issue: 128, P. 111632 - 111632

Published: Feb. 6, 2025

Language: Английский

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Curcumol ameliorates diabetic retinopathy via modulating fat mass and obesity-associated protein-demethylated MAF transcription factor G antisense RNA 1

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

Published: Feb. 28, 2025

Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus, leading to significant visual impairment and blindness among adults. Current treatment options are limited, making it essential explore novel therapeutic strategies. Curcumol, sesquiterpenoid derived from traditional Chinese medicine, has shown anti-inflammatory anti-cancer properties, but its potential role in DR remains unclear. To investigate the effects curcumol on progression elucidate underlying molecular mechanisms, particularly impact fat mass obesity-associated (FTO) protein long non-coding RNA (lncRNA) MAF transcription factor G antisense 1 (MAFG-AS1). A streptozotocin-induced mouse model was established, followed by with curcumol. Retinal damage inflammation were evaluated through histological analysis assays. Human retinal vascular endothelial cells exposed high glucose conditions simulate diabetic environments vitro. Cell proliferation, migration, markers assessed curcumol-treated cells. LncRNA microarray identified key molecules regulated curcumol, further experiments conducted confirm involvement FTO MAFG-AS1 DR. Curcumol significantly reduced blood levels alleviated models. In high-glucose-treated human cells, inhibited cell inflammatory responses. as most upregulated lncRNA following treatment. Mechanistically, demethylated MAFG-AS1, stabilizing expression. Rescue demonstrated that protective against mediated FTO/MAFG-AS1 signaling pathway. ameliorates modulating axis, providing pathway for These findings suggest curcumol-based therapies could offer promising alternative managing this debilitating diabetes.

Language: Английский

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RNA-based diagnostic innovations: A new frontier in diabetes diagnosis and management

Diabetes and Vascular Disease Research, Journal Year: 2025, Volume and Issue: 22(2)

Published: March 1, 2025

Background/Objective: Diabetes mellitus (DM) remains a major global health challenge due to its chronic nature and associated complications. Traditional diagnostic approaches, though effective, often lack the sensitivity required for early-stage detection. Recent advancements in molecular biology have identified RNA molecules, particularly non-coding RNAs such as microRNAs (miRNAs), long (lncRNAs), circular (circRNAs), promising biomarkers diabetes. This review aims explore role of RNA-based diagnosis, prognosis, management diabetes, highlighting their potential revolutionize diabetes care. Method: A comprehensive literature was conducted using electronic databases including PubMed, Scopus, Web Science. Articles published up 2024 were screened analyzed extract relevant findings related diagnostics Emphasis placed on studies demonstrating clinical utility, mechanistic insights, translational molecules. Results: Numerous species, miRNAs miR-375, miR-29, lncRNAs like H19 MEG3, exhibit altered expression patterns diabetic patients. These molecules are involved key regulatory pathways glucose metabolism, insulin resistance, β-cell function. Circulating detectable various biofluids, enabling non-invasive approaches. Emerging technologies, sequencing liquid biopsy platforms, enhanced specificity detection, fostering development novel tools personalized therapeutic strategies. Conclusion: hold significant promise advancing early risk stratification, monitoring Despite current challenges standardization validation, integration into routine practice could transform management, paving way precision medicine Further research multi-center trials essential validate these facilitate approval implementation.

Language: Английский

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Peptides based on the interface of hnRNPA2B1-transthyretin complex repress retinal angiogenesis in diabetic retinopathy

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 19, 2025

Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) plays a vital role in angiogenesis, when its nucleic acid-binding domain is occupied by transthyretin (TTR), the neovascularization of human retinal microvascular endothelial cells (hRECs) repressed under hyperglycemic conditions. HnRNPA2B1-targeting peptides (THIPs) were designed based on core fragments at TTR-hnRNPA2B1 interface. Biacore, Langmuir equilibrium adsorption, and co-immunoprecipitation (co-IP) assays performed to determine association between THIPs hnRNPA2B1. Proliferation DNA synthesis hRECs detected using CCK-8 EdU assays. Transwell, wound healing, tube formation used evaluate migratory angiogenic capacity hRECs. Related RNA protein expression levels tested quantitative PCR western blot assays, respectively. Streptozotocin (STZ)-induced diabetic retinopathy (DR) model rats intravitreally injected with 5 μL AAV9 virus (1 × 1012 vg/mL) every 8 weeks, sterile saline as control. After 16 retinas extracted subjected Evans blue leakage trypsin digestion Retinal paraffin sections prepared stained hematoxylin eosin (H&E) or immunohistochemical immunofluorescence co-IP analyses demonstrated that four specifically recognized labeling showed inhibited proliferation hyperglycemia. healing Quantitative suggested exerted their effects via STAT4/miR-223-3p/FBXW7 downstream Notch1/Akt/mTOR axes. In vivo studies DR rat revealed intravitreal administration THIP-4 significantly mitigated leakage, capillary decellularization, pericyte loss, fibrosis, gliosis during progression. Our findings hyperglycemia, suppressed progression axes both vitro vivo. These results indicated has strong potential for clinical application other angiogenesis associated diseases.

Language: Английский

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STAT3-induced upregulation of lncRNA TTN-AS1 aggravates podocyte injury in diabetic nephropathy by promoting oxidative stress

Toxicology Research, Journal Year: 2024, Volume and Issue: 13(3)

Published: May 1, 2024

Abstract Background Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus (DM), being second cause end-stage renal disease globally. Podocyte injury closely associated with DN developmen. Our study aimed to investigate role long non-coding RNA (lncRNA) TTN-AS1 in DN-associated podocyte injury. Methods The mouse cell line (MPC5) and human primary podocytes were stimulated by high glucose (HG; 30 nM glucose) establish cellular model DN. Before HG stimulation, both transfected sh-TTN-AS1#1/2 or pcDNA3.1/STAT3 evaluate influence knockdown STAT3 overexpression on HG-induced expression was examined RT-qPCR. Cell viability death assessed CCK-8 LDH release assay. ELISA adopted for testing IL-6 TNF-α contents supernatants. levels oxidative stress markers (ROS, MDA, SOD, GSH) supernatants determined commercial kits. Western blotting used measuring fibrosis (fibronectin α-SMA function (podocin nephrin) podocytes. Results stimulation led decreased viability, increased death, fibrosis, inflammation, dysfunction However, ameliorated Mechanically, transcription factor interacted promoter upregulated expression. offset protective effect silencing damage. Conclusion Overall, STAT3-mediated upregulation lncRNA could exacerbate through suppressing inflammation stress.

Language: Английский

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Preliminary research on LncRNA ATP2B2-IT2 in neovascularization of diabetic retinopathy

BMC Ophthalmology, Journal Year: 2024, Volume and Issue: 24(1)

Published: June 21, 2024

Abstract Objective Diabetic retinopathy (DR) is a common complication of diabetes, and recent findings have shown that long noncoding RNAs (lncRNAs) may be involved in its pathogenesis. Through bioinformatics analysis, we found lncRNA ATP2B2-IT2 this process. This study primarily investigated the expression human retinal microvascular endothelial cells (HRMECs) under high-glucose conditions effects on HRMEC proliferation, migration, neovascularization. Methods We used RT‒PCR to assess levels vascular growth factor (VEGF) HRMECs normal glucose (5.5 mmol/L) high (30 conditions. were subsequently divided into four groups: (NG), (HG), with silencing (HG + si-lncRNA ATP2B2-IT2), control si-NC) groups. The VEGF each group determined using RT‒PCR. Thereafter, cell neovascularization assessed CCK-8, Transwell, tube formation assays, respectively. Results revealed greater HG than NG ( P < 0.05). After ATP2B2-IT2, decreased significantly Subsequent assays demonstrated compared those group, exhibited increased However, after Conclusion LncRNA promote migration

Language: Английский

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The m6A-ncRNAs axis in diabetes complications: novel mechanism and therapeutic potential

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: June 24, 2024

Diabetes, a multifaceted metabolic disorder, poses significant global health burden with its increasing prevalence and associated complications, such as diabetic nephropathy, retinopathy, cardiomyopathy, angiopathy. Recent studies have highlighted the intricate interplay between N 6 -methyladenosine (m A) non-coding RNAs (ncRNAs) in key pathways implicated these diabetes like cell apoptosis, oxidative stress, inflammation. Thus, understanding mechanistic insights into how m A dysregulation impacts expression function of ncRNAs opens new avenues for therapeutic interventions targeting A-ncRNAs axis complications. This review explores regulatory roles modifications ncRNAs, stresses role A-ncRNA providing potential diseases.

Language: Английский

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LncRNA-Mediated Regulation of Cisplatin Response in Breast Cancer

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 264, P. 155716 - 155716

Published: Nov. 7, 2024

Language: Английский

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