A multifunctional injectable hydrogel for boosted diabetic wound healing assisted by Quercetin-ZIF system

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 495, P. 153425 - 153425

Published: June 22, 2024

Language: Английский

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ERK1/2 Inhibition Alleviates Diabetic Cardiomyopathy by Suppressing Fatty Acid Metabolism

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 22, 2025

Background: Diabetes mellitus is associated with morphological and functional impairment of the heart primarily due to lipid toxicity caused by increased fatty acid metabolism. Extracellular signal-regulated protein kinases 1 2 (ERK1/2) have been implicated in metabolism acids liver skeletal muscles. However, their role diabetes remains unclear. In this study, we tested our hypothesis that pharmacological inhibition ERK1/2 alleviates cardiac remodeling diabetic mice through a reduction Methods: phosphorylation was determined both vitro vivo. H9C2 cells were subjected high glucose, palmitic acid, or glucose acid. db/db streptozotocin (STZ)-induced analyzed for levels as well effects U0126 treatment on remodeling. Administration STZ performed via intraperitoneal injection. Blood measured using glucometer. Mouse total RNAs purified reverse transcription. Real-time polymerase chain reaction (PCR) analysis messenger ribonucleic (mRNA) expression hypertrophy (ANF, BNP, βMHC), fibrosis (Col3α1), genes (PPARα, CPT1A, FACS). Interstitial myocardium Masson’s trichrome staining paraffin-embedded tissues. Results: significantly conditions. Inhibition streptozotocin-induced resulted significant fibrosis. contrast, elevated Dusp6/8 knockout (DKO) Mechanistically, activation enhanced PPARα, FACS heart, which reversed treatment. Conclusion: are potential therapeutic targets cardiomyopathy modulating heart.

Language: Английский

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The SGLT2 inhibitor Empagliflozin promotes post-stroke functional recovery in diabetic mice

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Feb. 29, 2024

Abstract Type-2 diabetes (T2D) worsens stroke recovery, amplifying post-stroke disabilities. Currently, there are no therapies targeting this important clinical problem. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) potent anti-diabetic drugs that also efficiently reduce cardiovascular death and heart failure. In addition, SGLT2i facilitate several processes implicated in recovery. However, the potential efficacy of to improve recovery T2D has not been investigated. Therefore, we determined whether a intervention with Empagliflozin could mice. was induced C57BL6J mice by 8 months high-fat diet feeding. Hereafter, animals were subjected transient middle cerebral artery occlusion treated vehicle or SGLTi (10 mg/kg/day) starting from 3 days after stroke. A similar study non diabetic conducted. Stroke assessed using forepaw grip strength test. To identify mechanisms involved Empagliflozin-mediated effects, metabolic parameters assessed. Additionally, neuronal survival, neuroinflammation, neurogenesis vascularization analyzed immunohistochemistry/quantitative microscopy. significantly improved but non-diabetic Improvement functional associated lowered glycemia, increased serum levels fibroblast growth factor-21 (FGF-21), normalization T2D-induced aberration parenchymal pericyte density. The global T2D-epidemic fact is major risk factor for drastically increasing number people need efficacious Our data provide strong incentive use treatment sequelae T2D.

Language: Английский

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Melatonin attenuates diabetic cardiomyopathy by increasing autophagy of cardiomyocytes via regulation of VEGF-B/GRP78/PERK signaling pathway

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 9, 2024

Abstract Aims Diabetic cardiomyopathy (DCM) is a major cause of mortality in patients with diabetes, and the potential strategies for treating DCM are insufficient. Melatonin (Mel) has been shown to attenuate DCM, however, underlying mechanism remains unclear. The role vascular endothelial growth factor-B (VEGF-B) little known. In present study, we aimed investigate whether Mel alleviated via regulation VEGF-B explored its mechanisms. Methods results We found that significantly cardiac dysfunction improved autophagy cardiomyocytes type 1 diabetes mellitus (T1DM) induced mice. was highly expressed mice comparison normal mice, expression markedly reduced after treatment. treatment diminished interaction Glucose-regulated protein 78 (GRP78) GRP78 kinase RNA -like ER (PERK). Furthermore, increased phosphorylation PERK eIF2α, then up-regulated ATF4. −/− imitated effect on wild diabetic Interestingly, injection Recombinant adeno-associated virus serotype 9 (AAV9)-VEGF-B or administration GSK2656157 (GSK), an inhibitor phosphorylated abolished protective DCM. rapamycin, agonist displayed similar treatment; while 3-Methyladenine (3-MA), neutralized high glucose-treated neonatal rat ventricular myocytes. Conclusions These demonstrated attenuated increasing cardiomyocytes, this cardio-protective dependent VEGF-B/GRP78/PERK signaling pathway.

Language: Английский

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Autophagy in High-Fat Diet and Streptozotocin-Induced Metabolic Cardiomyopathy: Mechanisms and Therapeutic Implications

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1668 - 1668

Published: Feb. 15, 2025

Metabolic cardiomyopathy, encompassing diabetic and obese is an escalating global health concern, driven by the rising prevalence of metabolic disorders such as insulin resistance, type 1 2 diabetes, obesity. These conditions induce structural functional alterations in heart, including left ventricular dysfunction, fibrosis, ultimately heart failure, particularly presence coronary artery disease or hypertension. Autophagy, a critical cellular process for maintaining cardiac homeostasis, frequently disrupted cardiomyopathy. This review explores role autophagy pathogenesis high-fat diet (HFD) streptozotocin (STZ)-induced focusing on non-selective selective pathways, mitophagy, ER-phagy, ferritinophagy. Key proteins genes PINK1, Parkin, ULK1, AMPK, mTOR, ATG7, ATG5, Beclin-1, miR-34a are central to regulation Dysregulated autophagic flux impairs mitochondrial function, promotes oxidative stress, drives fibrosis heart. Additionally, processes lipophagy, regulated PNPLA8, ferritinophagy, modulated NCOA4, play pivotal roles lipid metabolism iron homeostasis. Emerging therapeutic strategies targeting autophagy, plant extracts (e.g., curcumin, dihydromyricetin), endogenous compounds sirtuin 3, LC3), lipid/glucose-lowering drugs, offer promising avenues mitigating effects Despite recent advances, precise mechanisms underlying this context remain poorly understood. A deeper understanding autophagy's regulatory networks, involving these proteins, may lead novel approaches treating

Language: Английский

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Impact of gliflozins on cardiac remodeling in patients with type 2 diabetes mellitus & reduced ejection fraction heart failure: A pilot prospective study. GLISCAR study

Diabetes Research and Clinical Practice, Journal Year: 2023, Volume and Issue: 200, P. 110686 - 110686

Published: April 25, 2023

Language: Английский

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Modulation of diabetic wound healing using carbon monoxide gas-entrapping materials

Device, Journal Year: 2024, Volume and Issue: 2(5), P. 100320 - 100320

Published: March 12, 2024

Diabetic wound healing is uniquely challenging to manage due chronic inflammation and heightened microbial growth from elevated interstitial glucose. Carbon monoxide (CO), widely acknowledged as a toxic gas, also known provide unique therapeutic immune-modulating effects. To facilitate delivery of CO, we have designed hyaluronic-acid-based CO gas-entrapping materials (CO-GEMs) for topical prolonged gas the bed. We demonstrate that CO-GEMs promote response in murine diabetic models (full-thickness wounds pressure ulcers) compared N2-GEMs untreated controls.

Language: Английский

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Endothelial Cells Promote Pseudo-islet Function Through BTC-EGFR-JAK/STAT Signaling Pathways

Annals of Biomedical Engineering, Journal Year: 2024, Volume and Issue: 52(9), P. 2610 - 2626

Published: June 3, 2024

Language: Английский

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Aberration of CA3 functionally mediates the pathogenesis of Cardiomyocyte hypertrophy in a miR-138–5p dependent manner

Acta Histochemica, Journal Year: 2025, Volume and Issue: 127(1), P. 152233 - 152233

Published: Feb. 8, 2025

Language: Английский

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Exercise in Diabetic Cardiomyopathy: Its Protective Effects and Molecular Mechanism

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1465 - 1465

Published: Feb. 10, 2025

Diabetic cardiomyopathy (DCM) is one of the cardiovascular complications diabetes, characterized by development ventricular systolic and diastolic dysfunction due to factors such as inflammation, oxidative stress, fibrosis, disordered glucose metabolism. As a sustainable therapeutic approach, exercise has been reported in numerous studies regulate blood improve abnormal energy metabolism through various mechanisms, thereby ameliorating left mitigating DCM. This review summarizes positive impacts on DCM explores its underlying molecular providing new insights paving way for tailored programs prophylaxis therapy

Language: Английский

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