Regulation of Autophagy via Carbohydrate and Lipid Metabolism in Cancer

Cancers, Journal Year: 2023, Volume and Issue: 15(8), P. 2195 - 2195

Published: April 7, 2023

Metabolic changes are an important component of tumor cell progression. Tumor cells adapt to environmental stresses via carbohydrate and lipid metabolism. Autophagy, a physiological process in mammalian that digests damaged organelles misfolded proteins lysosomal degradation, is closely associated with metabolism cells, acting as meter cellular ATP levels. In this review, we discuss the glycolytic biosynthetic pathways their impact on carcinogenesis autophagy pathway. addition, these metabolic lung cancer.

Language: Английский

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Fabry Disease: Cardiac Implications and Molecular Mechanisms

Current Heart Failure Reports, Journal Year: 2024, Volume and Issue: 21(2), P. 81 - 100

Published: Jan. 30, 2024

Abstract Purpose of Review This review explores the interplay among metabolic dysfunction, oxidative stress, inflammation, and fibrosis in Fabry disease, focusing on their potential implications for cardiac involvement. We aim to discuss biochemical processes that operate parallel sphingolipid accumulation contribute disease pathogenesis, emphasizing importance a comprehensive understanding these processes. Recent Findings Beyond accumulation, emerging studies have revealed mitochondrial chronic inflammation could be significant contributors These factors promote remodeling may predispose patients conduction disturbances, ventricular arrhythmias, heart failure. While current treatments, such as enzyme replacement therapy pharmacological chaperones, address progression symptoms, effectiveness is limited. Summary Our uncovers relationships disease–related complications. Current findings suggest beyond other mechanisms significantly pathogenesis. prompts exploration innovative therapeutic strategies underscores holistic approach managing disease.

Language: Английский

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Overexpression of VEGFα as a biomarker of endothelial dysfunction in aortic tissue of α-GAL-Tg/KO mice and its upregulation in the serum of patients with Fabry’s disease

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Feb. 5, 2024

Introduction Fabry's disease is an X-linked lysosomal storage disorder caused by reduced activity of α-galactosidase A (GAL), leading to premature death on account renal, cardiac, and vascular organ failure. Accumulation the GAL substrate globotriaosylceramide (Gb3) in endothelial smooth muscle cells associated with early cell damage, suggesting dysfunction as a driver cardiorenal Here, we studied expression key angiogenic factors, VEGFα its antagonist angiostatin, Fabry α-GAL-Tg/KO mice determined circulating angiostatin serum levels patients Fabry’s healthy controls. Methods Cryopreserved aortic vessels from six wild-type (WT) were obtained performing Western blot analysis. was visualized immunohistochemical staining paraffin rings. In addition, measured using enzyme-linked immunosorbent assay 48 genetically verified (50% male) 22 controls correlated severity markers such lyso-Gb3, albuminuria, NTproBNP, high-sensitive troponin T (hsTNT), myocardial wall thickness. Results It found that there significant increase protein (1.66 ± 0.35 vs. 0.62 0.16, p = 0.0009) decrease (0.024 0.007 0.053 0.02, 0.038) lysates compared WT mice. Immunohistochemical revealed adventitial signal mice, whereas no could be detected aortas. No differences between α-GAL-Tg/KO- visualized. The significantly upregulated (708.5 426.3 458.5 181.5 pg/ml, 0.048) positively albuminuria ( r 0.82, < 0.0001) elevated NTproBNP 0.87, hsTNT values 0.41, male disease. For difference (747.6 390.3 858.8 599.3 pg/ml). Discussion conclusion, overexpression downregulation counter player tissue support hypothesis underlying vasculopathy Elevated also observed manifestation males. These findings suggest angiogenetic markers, VEGFα, may potentially useful biomarkers for detection classical

Language: Английский

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Norharmane prevents muscle aging via activation of SKN-1/NRF2 stress response pathways

Redox Biology, Journal Year: 2025, Volume and Issue: 80, P. 103512 - 103512

Published: Jan. 27, 2025

Language: Английский

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Hemodialysis employing molecular hydrogen (H2) enriched dialysis solution may improve dialysis related fatigue through impact on energy metabolism

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 11, 2025

Hemodialysis employing molecular hydrogen (H2)-enriched dialysis solution rendered by water electrolysis (E-HD), has been reported to alleviate dialysis-related fatigue, but its association with metabolic profiles remains unclear. Eighty-one patients undergoing standard HD were classified into 3 groups [Group A (n = 25, 30.9%): fatigue activity reduction—subgroups A1: chronic persistent 11), A2: only on days 14); Group B: without reduction 24, 29.6%); C 32, 39.5%): no fatigue], and their changes in body composition, studied following 12 months of E-HD. There significant differences baseline characteristics among the groups. Over after E-HD initiation, significantly decreased, while Group-B C. Bio-impedance analysis revealed A1, reductions fat increases skeletal muscle mass observed despite weight change A2. Enrichment suggested pathways such as fatty acid metabolism, citric cycle, glycolysis between Groups at baseline, these mitigated could suppress through possible involvement altered energy metabolism patients. may represent a new paradigm for uremia treatment beyond traditional solute removal-based therapies.

Language: Английский

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Cardiac involvement in Fabry disease: Recent advances, unresolved issues, and unmet needs

European Heart Journal Supplements, Journal Year: 2025, Volume and Issue: 27(Supplement_1), P. i51 - i55

Published: Feb. 1, 2025

Fabry disease is an X-linked lysosomal storage disorder caused by deficient activity of the enzyme α-galactosidase A, leading to accumulation globotriaosylceramide in various tissues, including heart. Cardiac involvement a prominent feature and major cause morbidity mortality disease, manifesting as left ventricular hypertrophy, myocardial ischaemia, heart failure, arrhythmias. Secondary mechanisms, triggered storage, contribute damage, particular, inflammation. Early cardiac can be subtle, but with progression, it becomes determinant mortality. Recent progresses diagnostic techniques, such advanced magnetic resonance imaging T1 T2 mapping, have improved early detection Fabry-related disease. Enzyme replacement therapy newer treatments like chaperone shown potential managing manifestations when initiated early, while progression may difficult halt patients diagnosed late course. Gene substrate reduction are emerging treatment modalities that hold promise require further clinical evaluation. The limited efficacy available therapies variability response represent main unresolved issues, together challenges monitoring need for additional therapeutic strategies targeting secondary mechanisms. Unmet needs practice include identification disease-specific cardiac-specific biomarkers detection, staging, damage. Similarly, prognostic stratification better prevention cardiovascular complications essential improve care these patients.

Language: Английский

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Fatigue as hallmark of Fabry disease: role of bioenergetic alterations

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 24, 2024

Fabry disease (FD) is a lysosomal storage disorder due to the impaired activity of α -galactosidase A (GLA) enzyme which induces Gb3 deposition and multiorgan dysfunction. Exercise intolerance fatigue are frequent early findings in FD patients, representing self-standing clinical phenotype with significant impact on patient's quality life. Several determinants can trigger fatigability including psychological factors, cardiopulmonary dysfunctions, primary alterations skeletal muscle. The “metabolic hypothesis” explain muscle symptoms patients growing acknowledged. In this report, we will focus motor system emphasizing role metabolic disarrangement determining altered exercise tolerance patients. We discuss most recent about profile associated offering new insights for diagnosis, management, therapy.

Language: Английский

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Cardiopulmonary determinants of reduced exercise tolerance in Fabry disease

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: May 2, 2024

Fabry disease (FD), also known as Anderson-Fabry disease, is a hereditary disorder of glycosphingolipid metabolism, caused by deficiency the lysosomal alpha-galactosidase A enzyme. This causes progressive accumulation glycosphingolipids in tissues and organs which represents main pathogenetic mechanism FD. The multisystemic characterized early symptoms late complications (renal, cardiac neurological dysfunction). Fatigue exercise intolerance are common FD patients but specific still to be defined. In this narrative review, we deal with contribution pulmonary dysfunctions determining fatigue patients.

Language: Английский

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L-Arginine supplementation as mitochondrial therapy in diabetic cardiomyopathy

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

Published: Dec. 20, 2024

Abstract In patients with type II diabetes, the development of diabetic cardiomyopathy (DC) is associated a high risk mortality. Left ventricular hypertrophy, diastolic dysfunction, and exercise intolerance are first signs DC. The underlying mechanisms not fully elucidated, there an urgent need for specific biomarkers molecular targets early diagnosis treatment. Mitochondrial alterations play key role in DC, microRNAs regulating mitochondrial function emerging as potential metabolic stress L-Arginine (Arg) supplementation has been shown to be effective strategy improving energetics, significant impact on physical performance. aim current study was evaluate effects Arg cardiac function, DC development, relative phenotypes including intolerance. We used db/db mice model chronically treated (1 mg/kg/day) 12 weeks. Arg-treated showed preserved left morphology compared untreated mice. also improved tolerance propensity activity. respiration significantly increased cardiomyocytes isolated from mice, well vitro. improvement + increase PGC-1-alpha levels, biogenesis, recycling, antioxidant capacity. treatment prevented accumulation circulating miR-143 which index activation damage mechanisms. conclusion, preventing preserving by fitness homeostasis. Additionally, could potentially employed monitor diabetes.

Language: Английский

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Signaling through cAMP-Epac1 induces metabolic reprogramming to protect podocytes in glomerulonephritis

Kidney International, Journal Year: 2024, Volume and Issue: 106(3), P. 450 - 469

Published: May 29, 2024

Language: Английский

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