Exosomes derived from mesenchymal stem cells in diabetes and diabetic complications

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)

Published: April 17, 2024

Abstract Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place heavy financial strain on both patients the healthcare establishment. The lack effective treatments contributes to this pessimistic situation negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as most likely new breakthrough advancement in treating diabetes diabetes‐associated complication due capacity intercellular communication, modulating local microenvironment, regulating cellular processes. In present review, we briefly outlined properties MSCs-derived exosomes, provided thorough summary their biological functions potential uses related complications.

Language: Английский

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The Renoprotective Mechanisms of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i)—A Narrative Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7057 - 7057

Published: June 27, 2024

Chronic kidney disease (CKD) is a noncommunicable condition that has become major healthcare burden across the globe, often underdiagnosed and associated with low awareness. The main cause leads to development of renal impairment diabetes mellitus and, in contrast other chronic complications such as retinopathy or neuropathy, it been suggested intensive glycemic control not sufficient preventing diabetic disease. Nevertheless, novel class antidiabetic agents, sodium-glucose cotransporter-2 inhibitors (SGLT2i), have shown multiple renoprotective properties range from metabolic hemodynamic direct effects, impact on reducing risk occurrence progression CKD. Thus, this review aims summarize current knowledge regarding mechanisms SGLT2i offer new perspective innovative antihyperglycemic drugs proven pleiotropic beneficial effects that, after decades no significant progress prevention delaying decline function, start era management patients

Language: Английский

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Lipid homeostasis in diabetic kidney disease

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(10), P. 3710 - 3724

Published: Jan. 1, 2024

Lipid homeostasis is crucial for proper cellular and systemic functions.A growing number of studies confirm the importance lipid in diabetic kidney disease (DKD).Lipotoxicity caused by imbalance renal can further exasperate injury.Large deposits droplet accumulation are present kidneys DKD patients.Autophagy plays a critical role involved regulation content.Inhibition or reduction autophagy lead to accumulation, which turn affects autophagy.Lipophagy selectively recognizes degrades lipids helps regulate metabolism maintain intracellular homeostasis.Therefore, we provide systematic review fatty acid, cholesterol, sphingolipid metabolism, discuss responses different intrinsic cells imbalances homeostasis.Finally, mechanism autophagy, especially lipophagy, maintains support development new drugs targeting homeostasis.

Language: Английский

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Changes in Urinary NGAL, FN, and LN Excretion in Type 2 Diabetic Patients Following Anti-Diabetic Therapy with Metformin

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(4), P. 1088 - 1088

Published: Feb. 8, 2025

Background: Excessive accumulation of glomerular extracellular matrix (ECM) is a key factor in the development and progression diabetic nephropathy (DN). As kidney dysfunction has been reported normoalbuminuric patients, identifying novel diagnostic prognostic markers essential for prevention treatment DN. Methods: Urinary excretion neutrophil gelatinase-associated lipocalin (NGAL) ECM-related glycoproteins, i.e., fibronectin (FN) laminin (LN), was measured obese patients with newly diagnosed type 2 diabetes mellitus (T2DM) before after 6 months metformin therapy. Results: Baseline NGAL (1.27 (0.80–2.36) ng/mg Cr), FN (11.19 (5.31–21.56) Cr) LN (123.17 (54.56–419.28) pg/mg levels did not significantly differ between T2DM controls (1.95 (1.09–2.97) Cr, 11.94 (7.78–18.01) Cr 157.85 (83.75–326.40) respectively). In multivariate regression analysis, body mass index identified as only significant predictor influencing urinary at baseline, β = 0.249, p 0.005 1.068, 0.010, respectively. Metformin increased both ECM proteins, (18.48 (11.64–32.46) (179.51 (106.22–414.68) without any effect on (1.44 (0.81–2.72) Cr). were positively associated (r 0.709 r 0.646, < 0.001, respectively) 0.594 0.479, No correlations found NGAL, FN, LN, albuminuria. However, correlated albumin/creatinine ratio (ACR) 0.323, 0.05) 0.287, therapy, negatively estimated filtration rate (eGFR) pre-treatment diabetics −0.290, 0.05). also ACR 0.384, 0.01 0.470, 0.001), although association limited to untreated 0.422, 0.01). Conclusions: Our results suggest that beneficial turnover increase non-collagenous injury, LN. Additionally, may serve useful tools monitoring early renal injury patients.

Language: Английский

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Diabetic Kidney Disease: Disease Progression Driven by Positive Feedback Loops and Therapeutic Strategies Targeting Pathogenic Pathways

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2025, Volume and Issue: Volume 18, P. 1073 - 1085

Published: April 1, 2025

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus, with its pathogenesis intricately regulated by dynamic feedback mechanisms. This comprehensive review systematically analyzes the hierarchical networks driving DKD progression, spanning from systemic interactions to molecular cross-talks. We reveal that self-amplifying positive loops dominate process, manifested through three key dimensions: (1) The triad hyperglycemia-hypertension-proteinuria establishes vicious cycle accelerating renal dysfunction; (2) Cellular homeostasis collapse cross-amplified cell death modalities (apoptosis, pyroptosis, ferroptosis) and dysregulation; (3) Molecular cascades centered on AGE/RAGE signaling fuel chronic inflammation fibrotic transformation. Collectively, these form loop where PKC activation, oxidative stress propagation, TGF-β-mediated fibrosis induced hyperglycemia lead progressive deterioration fibrosis. Therapeutically, we propose dual intervention strategy targeting both acute phase axis inhibition, coupled via precision modulation pathways. These findings redefine progression as self-reinforcing network disorder, providing roadmap for developing multi-target therapies disrupt pathological while preserving repair

Language: Английский

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Regulation of autophagy by the PI3K-AKT pathway in Astragalus membranaceus -Cornus officinalis to ameliorate diabetic nephropathy

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: May 13, 2025

Aims and background Autophagy plays an increasingly significant role in diabetic nephropathy (DN), but the mechanism by which autophagy participates DN injury is not well understood. Our previous studies have shown that Astragalus membranaceus - Cornus officinalis (AM-CO) improves lipid metabolism disorders, however, exact of also defined. The aim this study was to investigate therapeutic effects AM-CO on action using lipidomic techniques network pharmacological approaches. Experimental methods vivo experiments were carried out KKAy mice model with intervention AM-CO. Analysis kidney serum samples from treated technology obtain biomarkers for treatment identify main targets associated DN; Analyse potential signalling pathways pharmacology methods. In vitro performed PA-induced HK-2 cells results verified protein blotting immunofluorescence. Results Lipidomic analysis revealed 363 differential metabolites 195 tissue, compared analysed find their common belonging phosphatidylethanolamine (PE) classes, respectively. addition, PE a vital functiona process autophagy. And speculated Calycosin (Cal), major component AM-CO, could ameliorate regulating through modulating PI3K-AKT signaling pathway. showed induce autophagy, increase LC3II expression decrease P62 expression. Meanwhile, Cal inhibit levels p62, PI3K, P-AKT AKT. addition PI3K activator resulted reversal Conclusion conclusion, can pathway its regulation key

Language: Английский

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