Chronic inorganic nitrate supplementation does not improve metabolic health and worsens disease progression in mice with diet-induced obesity. DOI
Alice P. Sowton, Lorenz M.W. Holzner, Fynn N. Krause

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 8, 2024

Abstract Inorganic nitrate (NO 3 - ) has been proposed to be of therapeutic use as a dietary supplement in obesity and related conditions including the Metabolic Syndrome (MetS), type-II diabetes metabolic dysfunction associated steatotic liver disease (MASLD). Administration NO endothelial nitric oxide synthase-deficient mice reversed aspects MetS, however impact supplementation diet-induced is not well understood. Here we investigated whole-body phenotype cardiac hepatic metabolism fed high-fat high-sucrose (HFHS) diet for up 12-months age, supplemented with 1 mM NaNO (or NaCl) their drinking water. HFHS-feeding was progressive obesogenic diabetogenic phenotype, which ameliorated by . Furthermore, HFHS-fed showed elevated levels fibrosis, accelerated progression MASLD development hepatocellular carcinoma comparison NaCl-supplemented mice. did enhance mitochondrial β-oxidation capacity any tissue assayed suppress lipid accumulation, suggesting it does prevent lipotoxicity. We conclude that ineffective preventing consequences an may instead detrimental health against background HFHS-feeding. This first report unfavorable effect long-term context challenges overfeeding, warranting urgent further investigation into mechanism this interaction. New & Noteworthy suggested benefit obesity-related increases bioavailability, enhances reverses eNOS -/- However, here show over 12 months, mice, worsened health, impairing cholesterol handling, increasing exacerbating progression, acceleration carcinoma.

Language: Английский

Discovery of Titin and Its Role in Heart Function and Disease DOI
Henk Granzier, Siegfried Labeit

Circulation Research, Journal Year: 2025, Volume and Issue: 136(1), P. 135 - 157

Published: Jan. 2, 2025

This review examines the giant elastic protein titin and its critical roles in heart function, both health disease, as discovered since identification nearly 50 years ago. Encoded by TTN (titin gene), has emerged a major disease locus for cardiac disorders. Functionally, acts third myofilament type, connecting sarcomeric Z-disks M-bands, regulating myocardial passive stiffness stretch sensing. Its I-band segment, which includes N2B element PEVK (proline, glutamate, valine, lysine-rich regions), serves viscoelastic spring, adjusting sarcomere length force response to stretch. The details how alternative splicing of pre-mRNA produces different isoforms that greatly impact tension under physiological pathological conditions. Key posttranslational modifications, especially phosphorylation, play crucial titin’s stiffness, allowing rapid adaptation changing hemodynamic demands. Abnormal modifications dysregulation are linked diseases such failure with preserved ejection fraction, where increased impairs diastolic function. In addition, discusses importance A-band region setting thick filament enhancing Ca² + sensitivity, contributing Frank-Starling Mechanism heart. truncating variants frequently associated dilated cardiomyopathy, outlines potential mechanisms, including haploinsufficiency, disarray, altered regulation. Variants have also been conditions peripartum cardiomyopathy chemotherapy-induced cardiomyopathy. Therapeutic avenues explored, targeting factors RBM20 (RNA binding motif 20) adjust isoform ratios or using engineered tissues study mechanisms. Advances genetic engineering, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), offer promise modifying treat titin-related cardiomyopathies. comprehensive highlights structural, mechanical, signaling function mutations on diseases.

Language: Английский

Citations

1
SLC31A1 loss depletes mitochondrial copper and promotes cardiac fibrosis DOI

Bin Tu,

Kai Song, Ze‐Yu Zhou

et al.

European Heart Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Metals serve as co-factors for a host of metalloenzymes involved in mitochondrial metabolic reprogramming. Modifications metal homeostasis are linked to epigenetic mechanisms. However, the mechanisms through which affects cardiac fibrosis (CF) remain poorly understood. The content mouse heart samples was measured using inductively coupled plasma mass spectrometry. Cardiac fibroblast-specific MeCP2-deficient mice and control were treated with isoprenaline/angiotensin II induce CF. AAV9 carrying POSTN promoter-driven small hairpin RNA targeting MeCP2, YTHDF1, or SLC31A1 copper-chelating agent tetrathiomolybdate administered investigate their vital roles Histological biochemical analyses performed determine how YTHDF1/MeCP2 regulated expression reconstitution YTHDF1/MeCP2-deficient fibroblasts hearts study its effect on copper depletion fibrosis. Human tissues from atrial fibrillation patients used validate findings. Lower concentrations accompanied by down-regulation Fibroblast-specific deficiency enhances depletion, augments glycolysis, promotes fibroblast proliferation triggers inhibition due increased MeCP2-recognized methylating CpG islands promoter region restrains transcription. Conversely, MeCP2 knockdown rescued expression, resulting contradictory effects. up-regulation is associated elevated m6A mRNA levels. Mechanistically, YTHDF1 recognizes target induces translation. In human patients, reduced along levels observed. These changes enhanced A novel mechanism demonstrated increases impairs Findings provide new insights development preventive measures

Language: Английский

Citations

1
Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis DOI Creative Commons
Cong Chen, Jie Wang,

Shan Zhang

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 76, P. 103321 - 103321

Published: Aug. 19, 2024

Cell death constitutes a critical component of the pathophysiology cardiovascular diseases. A growing array non-apoptotic forms regulated cell (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified is intimately linked to various conditions. These RCD are governed by genetically programmed mechanisms within cell, with epigenetic modifications being common crucial regulatory method. Such include DNA methylation, RNA histone acetylation, non-coding RNAs. This review recaps roles modifications, RNAs in diseases, well which regulate key proteins involved death. Furthermore, we systematically catalog existing pharmacological agents targeting novel their action article aims underscore pivotal role precisely regulating specific pathways thus offering potential new therapeutic avenues that may prove more effective safer than traditional treatments.

Language: Английский

Citations

8
Enzyme memory-driven Ce-enhanced carbon dots from vegetable moss enable rapid treatment of traumatic spinal cord injury DOI
Baofeng Zhao, Fan Wang,

Huicong Feng

et al.

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: 505, P. 159097 - 159097

Published: Jan. 7, 2025

Language: Английский

Citations

0
The molecular and cellular landscape of hypertrophic cardiomyopathy phenotypes: transition from obstructive to end-stage heart failure DOI
Jude Taylor, Sean Lal, Filip Braet

et al.

Journal of Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Language: Английский

Citations

0
Recent research progress on metal ions and metal-based nanomaterials in tumor therapy DOI Creative Commons

Yongcheng Xu,

Aikebaier Reheman,

Wenhua Feng

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 7, 2025

Tumors, as a disease that seriously threatens human health, have always been major challenge in the field of medicine. Currently, main methods tumor treatment include surgery, radiotherapy, chemotherapy, etc., but these traditional often certain limitations. In addition, recurrence and metastasis are also difficult problems faced clinical treatment. this context, importance metal-based nanomaterials therapy is increasingly highlighted. Metal-based possess unique physical, chemical, biological properties, providing new ideas for can achieve targeted tumors through various mechanisms, reducing damage to normal tissues; they serve drug carriers, improving stability bioavailability drugs; at same time, some photothermal, photodynamic, other characteristics, which be used phototherapy tumors. This review examines latest advances application within past 5 years, presents prospective insights into future applications.

Language: Английский

Citations

0
The Role of Hypoxia in Longevity DOI Creative Commons
Ayesha Nisar,

Sawar Khan,

Yongzhang Pan

et al.

Aging and Disease, Journal Year: 2025, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2025

Aging is marked by a progressive decrease in physiological function and reserve capacity, which results increased susceptibility to diseases. Understanding the mechanisms of driving aging crucial for extending health span promoting human longevity. Hypoxia, reduced oxygen availability, has emerged as promising area study within research. This review explores recent findings on potential restriction promote healthy extend lifespan. While role hypoxia-inducible factor 1 (HIF-1) cellular responses hypoxia well-established, its impact lifespan remains complex context-dependent. Investigations invertebrate models suggest HIF-1 longevity, while evidence mammalian limited. Hypoxia extends independent dietary (DR), known intervention underlying However, both DR converge common downstream effectors, such forkhead box O (FOXO) flavin-containing monooxygenase (FMOs) modulate Further work required elucidate molecular hypoxia-induced longevity optimize clinical applications. crosstalk between other longevity-associated pathways developing interventions enhance healthspan. Future studies may uncover novel therapeutic strategies populations.

Language: Английский

Citations

0
Oxidative Stress and Redox Signaling in Gastric Cancer: From Mechanisms to Therapeutic Implications DOI Creative Commons
Zehua Chen,

Jiawu Fan,

Xiao‐Long Chen

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 258 - 258

Published: Feb. 24, 2025

Oxidative stress, which is characterized by an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, has critical roles in the initiation, progression, treatment of gastric cancer. On one hand, excessive ROS accumulation induces oxidative damage cancer cell death. other moderate levels cause genetic mutations dysregulation signaling pathways to promote proliferation, inflammation, angiogenesis, metastasis Notably, emerging evidence revealed that also mediate post-translational modifications (oxPTMs) redox-sensitive proteins, can directly affect protein functions regulate redox cells. Therefore, elucidating regulatory mechanisms stress holds great promise identify novel therapeutic targets or redox-targeting strategies. This review will summarize regulating hallmarks highlight ROS-mediated oxPTMs In addition, we discuss strategies targeting for cancer, with emphasis on use bioactive natural products nanomaterials.

Language: Английский

Citations

0
Novel Epitranscriptomic and Epigenetic Therapeutic Strategies and Targets for Ferroptosis in Liver Fibrosis DOI
Minghui Li, Yang Yang,

Qi-Qi Dong

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 996, P. 177344 - 177344

Published: Feb. 25, 2025

Language: Английский

Citations

0
Novel impact of metal ion-induced cell death on diabetic cardiomyopathy pathogenesis and therapy DOI

Jingjing Jiang,

Shengnan Hu, Kaibo Hu

et al.

APOPTOSIS, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Language: Английский

Citations

0