FSH exacerbates bone loss by promoting osteoclast energy metabolism through the CREB-MDH2-NAD+ axis

Metabolism, Journal Year: 2025, Volume and Issue: unknown, P. 156147 - 156147

Published: Jan. 1, 2025

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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Ferroptosis: mechanism and role in diabetes-related cardiovascular diseases

Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 7, 2025

Cardiovascular diseases represent the principal cause of death and comorbidity among people with diabetes. Ferroptosis, an iron-dependent non-apoptotic regulated cellular characterized by lipid peroxidation, is involved in pathogenesis diabetic cardiovascular diseases. The susceptibility to ferroptosis hearts possibly related myocardial iron accumulation, abnormal metabolism excess oxidative stress under hyperglycemia conditions. Accumulating evidence suggests can be therapeutic target for This review summarizes ferroptosis-related mechanisms novel choices targeting pathways. Further study on ferroptosis-mediated cardiac injury enhance our understanding pathophysiology provide more potential choices.

Language: Английский

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Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects

Bone Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 25, 2025

Abstract The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and activities of digestive organs. Additionally, muscle tissues serve an endocrine function secreting myogenic cytokines, thereby regulating metabolism throughout entire body. Maintaining requires iron homeostasis. Recent studies suggest that disruptions ferroptosis, form iron-dependent cell death, are essential contributors to progression wide range diseases disorders, including sarcopenia, cardiomyopathy, amyotrophic lateral sclerosis. Thus, comprehensive overview mechanisms ferroptosis these conditions is crucial for identifying potential therapeutic targets developing new strategies disease treatment and/or prevention. This review aims summarize recent advances understanding molecular underlying context injury, as well associated disorders. Moreover, we discuss within pathway possible managing Finally, shed light on current limitations future prospects interventions targeting ferroptosis.

Language: Английский

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JAK/STAT signaling as a key regulator of ferroptosis: mechanisms and therapeutic potentials in cancer and diseases

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 7, 2025

Ferroptosis is a distinct form of regulated cell death characterized by iron-dependent lipid peroxidation, playing critical role in various diseases, including cancer, neurodegeneration, and tissue damage. This study reviews the intricate relationship between ferroptosis Janus kinase/signal transducer activator transcription (JAK/STAT) signaling pathway, highlighting its regulatory functions across multiple biological processes. Dysregulation JAK/STAT pathway implicated promoting or inhibiting ferroptosis, depending on context. JAK2 promotes activating STAT proteins, modulating expression key regulators like SLC7A11 GPX4, influencing iron homeostasis through pathways such as ferritinophagy hepcidin regulation. STAT1 activation primarily enhances suppression cystine-glutamate antiporter (System Xc-), leading to glutathione depletion contributing conditions Sjogren's syndrome age-related macular degeneration. In contrast, STAT3 plays protective upregulating which inhibits survival, particularly cancers hepatocellular carcinoma, prostate renal carcinoma. also discusses STAT6's involvement diseases asthma lung injury regulating antioxidant defenses. Furthermore, review explores potential therapeutic strategies targeting manipulate for disease treatment. cancer therapy, this can enhance effectiveness inducers, offering promising avenues overcome drug resistance. Additionally, interplay immune responses, oxidative stress, metabolism underscores significance progression intervention. By exploring these mechanisms, provides insights into development novel treatments modulation, with implications inflammatory neurodegenerative conditions.

Language: Английский

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Leucine‐Rich Repeat‐Containing G Protein‐Coupled Receptor 6 Ameliorates Pressure Overload‐Induced Cardiac Hypertrophy by Regulating Cardiomyocyte Metabolic Reprogramming

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Abstract Metabolic reprogramming is a pivotal mechanism in the pathogenesis of pathological cardiac hypertrophy. Leucine‐rich repeat‐containing G protein‐coupled receptor 6 (Lgr6) has emerged as significant player cardiovascular diseases. In this study, potential Lgr6 to counteract pressure overload (PO)‐induced hypertrophy investigated, and underlying mechanisms involved are elucidated. Transverse aortic constriction (TAC) induced establish an vivo model. Adeno‐associated virus 9 adenovirus vectors utilized knock down overexpress cardiomyocytes, respectively. The effects its downstream molecules subsequently determined using RNA sequencing chromatin immunoprecipitation. Significant downregulation expression observed heart after TAC cardiomyocytes treated with phenylephrine. deficiency accelerated overexpression inhibits dysfunction TAC. Mechanistically, vitro experiments suggest that regulates ubiquitin specific protease 4 (USP4) peroxisome proliferator‐activated alpha (PPARα) by activating cGMP/PKG/CREB1 signalling pathway, thereby regulating cardiomyocyte metabolic PO. Targeting can be therapeutic strategy treat

Language: Английский

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Exploring the key target molecules of angiogenesis in diabetic cardiomyopathy based on bioinformatics analysis

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

Published: April 17, 2025

Backgrounds Diabetic cardiomyopathy has a very high incidence and serious clinical consequences, making it an urgent problem to be solved. Angiogenesis is significant phenotype in the occurrence development of diabetic cardiomyopathy, especially damage angiogenesis cardiac microvessels, which inextricably linked risk patients. In current basic research, there still lack treatment methods that directly target cardiomyopathy. This study hopes discover key molecules related damage, provide ideas for possible interventions. Methods Sequencing data animals cells were obtained from GEO database, differentially expressed genes analyzed. Subsequently, angiogenesis-related clustered functional pathway analysis. Then, microangiogenesis mice changes glucose-stimulated HUVECs verified, top three verified using western blot. Results 24 associated with found GSE241565(human) GSE215979(mice). Among them, 11 showed same trend two databases. Then CD31 staining hearts microvascular was impaired, decreased tube formation, wound healing migration weakened. Finally, 3 most no difference between Edn1 Lepr. At time, Efnb2 significantly increased under glucose stimulation. Conclusion Combined sequencing animal cell models differential screened. These findings not only elucidate novel molecular axis linking but also highlight as potential therapeutic target.

Language: Английский

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Natural products and ferroptosis: A novel approach for heart failure management

Phytomedicine, Journal Year: 2025, Volume and Issue: 142, P. 156783 - 156783

Published: April 18, 2025

Language: Английский

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LGR6 protects against myocardial ischemia-reperfusion injury via suppressing necroptosis

Redox Biology, Journal Year: 2024, Volume and Issue: 78, P. 103400 - 103400

Published: Oct. 17, 2024

Language: Английский

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Ferrostatin-1 improves acute sepsis-induced cardiomyopathy via inhibiting neutrophil infiltration through impaired chemokine axis

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Dec. 12, 2024

Introduction Sepsis-induced cardiomyopathy is a common complication of sepsis and associated with higher mortality. To date, effective diagnostic management strategies are still lacking. Recent studies suggest that ferroptosis plays critical role in sepsis-induced inhibitor Ferrostatin-1 (Fer-1) improved cardiac dysfunction survival lipopolysaccharide (LPS) induced endotoxemia. However, the effects Fer-1 early stages cecal ligation puncture (CLP) remains unclear. Our study aims to elucidate acute phase peritonitis injury. Methods Results CLP was used induce mice. Pretreatment ferrostatin-1 vivo models. Survival monitored for 48h. Cardiac function histology were analyzed 6h after surgery. We found ejection fraction (EF) remained normal at CLP, but contractility detected by muscle strain analysis significantly reduced, along increased immune cell infiltration. Pretreating mice 5 mg/kg reduced At key regulator Gpx4, iron malonaldehyde (MDA) did not change, marker gene expression increased. treatment showed beneficial function, less myocardial inflammatory cytokine inhibited cells, especially neutrophil infiltration heart. Consistently, chemokines (Ccrl2, Cxcl2, Cxcl3 Cxcl5) as well extracellular matrix (ECM) degradation enzymes (Adamts1, Adamts4, Adamts9 Mmp8) decreased pre-treated Conclusion Discussion findings inhibits disrupting chemokine axis, highlighting its potential therapeutic option manage overactivation cardiomyopathy.

Language: Английский

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