Protective Effects of Exogenous Melatonin Administration on White Fat Metabolism Disruption Induced by Aging and a High-Fat Diet in Mice DOI Creative Commons

Dongying Lv,

Yujie Ren,

Jiayan Chen

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(12), P. 1500 - 1500

Published: Dec. 9, 2024

Obesity has emerged as a major risk factor for human health, exacerbated by aging and changes in dietary habits. It represents significant health challenge, particularly older people. While numerous studies have examined the effects of obesity on fat metabolism independently, research their combined is limited. In present study, protective action against white accumulation after high-fat diet (HFD) exerted exogenous melatonin, circadian hormone endowed with antioxidant properties also involved metabolism, was investigated mouse model. For this purpose, battery tests applied before melatonin treatments animals, including epididymal adipose tissue (eWAT) histological evaluations, transcriptomic lipidomic analyses, real-time PCR tests, immunofluorescence staining, Western blot, appraisal serum levels, transmission electron microscopy. This study found that aged mice showed increased lipid deposition, inflammation, reduced glutathione (GSH) levels compared to younger mice. Lipidomic analyses revealed elevated triglycerides, diglycerides, ceramides, cholesterol, along decreased sphingomyelin fatty acids eWAT. The genes linked NF-κB signaling, autophagy, pathways, were significantly altered. HFD exhibited Melatonin supplementation GSH upregulated AANAT MTNR1A expression eWAT, suggesting alleviates eWAT damage via pathway. suppressed inflammatory markers (e.g., TNF-α, NLRP3, NF-κB, IL-1β, CEBPB) preserved mitochondrial function through enhanced mitophagy. highlights how affect gene expression, offering potential intervention strategies. These findings provide important insights into mechanisms deposition associated diet,

Language: Английский

PTEN: a new dawn in Parkinson’s disease treatment DOI Creative Commons
Xiuna Yang, Tianqi Liu, Hong Cheng

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: March 10, 2025

In recent years, the study of phosphatase and tension homolog (PTEN) has gradually become a research hotspot. As an important oncogene, role PTEN in cancer long been widely recognized intensively studied, but it relatively less studied other diseases. Parkinson’s disease (PD) is neurodegenerative refractory commonly observed middle-aged elderly individuals. The etiology pathogenesis PD are numerous, complex, incompletely understood. With continuous deepening research, numerous studies have proven that related to occurrence PD. this review, we discuss relationship between through phosphorylation ubiquitination possible regulatory mechanisms, including RNA molecules, exosomes, transcriptional regulation, chemical modification, subtype variation, with aim clarifying better elucidating its pathogenesis. Finally, summarize shortcomings highlight great potential future application clinical treatment. These findings provide ideas new perspectives for use as therapeutic target targeted drug development future.

Language: Английский

Citations

0
AMBRA1 performs a balancing act in β-thalassemia DOI Open Access
Christophe Lechauve, Mitchell J. Weiss

Blood, Journal Year: 2025, Volume and Issue: 145(10), P. 1001 - 1003

Published: March 6, 2025

Language: Английский

Citations

0
Effect of knockdown LncRNA SNHG1 on autophagic function in SH-SY5Y cells: a model of Alzheimer’s disease (AD) DOI

Xiaoxu Li,

Xu-Sheng Yan,

Chunjie Zhang

et al.

Journal of Toxicology and Environmental Health, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 9

Published: March 5, 2025

Alzheimer 's disease, a neurodegenerative is considered serious global type of dementia affecting predominantly elderly associated with progressive memory loss. disease exhibits typical pathological manifestations including neuronal loss, β-amyloid deposition, and tau protein neurofibrillary tangles. Significantly increased expression long-non -coding transcript RNA, LncRNA SNHG1, was detected in the brain AD patients. However, it not clear whether knockdown SNHG1 might improve autophagy function SH-SY5Y cells reduce number apoptotic cells. The aim this study to (1) examine role on autophagic following induction by Aβ1-42 (2) elucidate underlying mechanisms. were transfected lentiviral vectors construct cell line stable genetic ability knock down compared control empty vector line. Following for 24 hr, an model constructed. Downregulation significantly viability lowered Concomitantly downregulation induced significant decrease p-tau caspase3 elevated Beclin1 AMBRA1. Our results showed that reduced enhancing Data suggest knocking may be potential target compounds treat AD.

Language: Английский

Citations

0
Aconiti Lateralis Radix Praeparata ameliorates heart failure via PI3K/AKT/Bnip3 pathway DOI Creative Commons
Wenxiu Liu,

Xingju Zou,

Yang Zheng

et al.

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

Published: March 26, 2025

Background Chronic heart failure (CHF) is one of the leading causes high mortality worldwide. It characterized by pathological hypertrophy and poses a major threat to human health. Aconiti Lateralis Radix Praeparata widely used in ancient China treat CHF. However, pathology obscured, necessitating further exploration. Methods Prospective targets were predicted network analysis. A transverse aortic constriction (TAC) mice model was subsequently constructed determine effects aqueous extract (AEA) on The echocardiography performed investigate cardiac function. Histopathological analysis tissue conducted assess myocardial fibrosis. Nontargeted metabolomics analyze serum metabolites. phosphorylation level PI3K AKT, downstream such as Bnip3, p62, Atg5, LC3II measured Western blotting. In vitro , norepinephrine (NE) stimulate hypertrophy. Parameters reactive oxygen species levels, mitochondrial membrane potential, ATP concentration, CK/MB content detected H9c2 cells. Results AEA significantly alleviated Network indicated participation AKT CHF, modulated Praeparata. vivo administration effectively ameliorated performance, evidenced elevation ejection fraction. displayed diminishment collagen fiber. Metabolomics showed that several metabolites tetrahydroxycorticosterone, decylubiquinone taurocholic acid increased TAC serum. Additionally, levels expression Drp1, Opa1, Atg5 altered group. NE stimulation cell surface area deteriorated functions partially reversed results, mechanism associated with mitophagy. Conclusion This study revealed improved function via PI3K/AKT/Bnip3 pathway.

Language: Английский

Citations

0
Artemisinin and Its Derivatives: Promising Therapeutic Agents for Age-Related Macular Degeneration DOI Creative Commons
Chun Liu, Xiao‐Qin Liu, Junguo Duan

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 535 - 535

Published: April 6, 2025

Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in older adults. Its pathogenesis involves multiple factors, including aging, environmental influences, genetic predisposition, oxidative stress, metabolic dysfunction, immune dysregulation. Currently, AMD treatment focuses primarily on wet AMD, managed through repeated intravitreal injections anti-vascular endothelial growth factor (VEGF) therapies. While anti-VEGF agents represent major breakthrough care, may lead to incomplete responses or resistance some patients, carry risk progressive fibrosis. Artemisinin (ART) its derivatives, originally developed as antimalarial drugs, exhibit broad spectrum pleiotropic activities beyond their established use, anti-inflammatory, anti-angiogenic, antioxidant, anti-fibrotic, mitochondrial regulatory, lipid metabolic, immunosuppressive effects. These properties position ART promising therapeutic candidate for AMD. A growing interest ART-based therapies has emerged recent years, with numerous studies demonstrating potential benefits. However, no comprehensive review systematically summarized the specific roles derivatives treatment. This paper aims fill knowledge gap by synthesizing efficacy molecular mechanisms thereby providing foundation future investigations.

Language: Английский

Citations

0
Mitochondrial connection to Alzheimer's disease and heart failure DOI Creative Commons

Anupriya Sinha,

Natasha Jaiswal, Pooja Jadiya

et al.

Current Opinion in Physiology, Journal Year: 2025, Volume and Issue: unknown, P. 100830 - 100830

Published: May 1, 2025

Language: Английский

Citations

0
Niclosamide: CRL4AMBRA1 mediated degradation of cyclin D1 following mitochondrial membrane depolarization DOI Creative Commons
Seemon Coomar,

Jessica A. Gasser,

Mikołaj Słabicki

et al.

RSC Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Niclosamide, an FDA-approved anthelmintic drug, known to uncouple the mitochondria induces cyclin D1 degradation via CRL4 AMBRA1 . We find a striking correlation between two processes and that it is observed amongst various compounds.

Language: Английский

Citations

0
Dysregulation of autophagy during photoaging reduce oxidative stress and inflammatory damage caused by UV DOI Creative Commons

Zhongsong Zhang,

Ru Yu Tan, Zhengang Xiong

et al.

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

Published: May 12, 2025

Photoaging, the premature aging of skin due to chronic ultraviolet (UV) exposure, is a growing concern in dermatology and cosmetic science. While UV radiation known induce DNA damage, oxidative stress, inflammation cells, recent research unveils promising countermeasure: autophagy. This review explores intricate relationship between autophagy photoaging, highlighting how this cellular recycling process can mitigate UV-induced damage. We begin by examining differential impacts UVA UVB on cells role stress accelerating photoaging. Next, we delve into molecular mechanisms autophagy, including its various forms regulatory pathways. Central discussion autophagy’s protective functions, such as clearance damaged organelles proteins, maintaining genomic integrity. Furthermore, address current challenges harnessing for therapeutic purposes, need selective inducers deeper understanding context-dependent effects. By synthesizing advancements proposing future directions, underscores potential modulation novel strategy prevent treat comprehensive analysis aims inspire further investigation autophagy-based interventions, offering new hope preserving health face environmental stressors.

Language: Английский

Citations

0
Rab40 GTPases regulate AMBRA1-mediated transcription and cell migration DOI Creative Commons

Revathi Sampath,

Katherine F. Vaeth, Valeryia Mikalayeva

et al.

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

Published: Nov. 7, 2024

ABSTRACT The Rab40 subfamily are unique small monomeric GTPases that form CRL5-based ubiquitin E3 ligase complex and regulate ubiquitylation of specific target proteins. Recent studies have shown Rab40s play an important role in regulating cell migration, but the underlying mechanisms Rab40/CRL5 function still not fully understood. In this study we identified AMBRA1 as a novel binding partner showed interaction mediates bi-directional crosstalk between CRL4 CRL5 ligases. Importantly, found ubiquitylates AMBRA1, which does result degradation, instead it seems to induce AMBRA1-dependent regulation gene transcription. global transcriptional profiles by RNA-seq regulates transcription genes related adhesion migration. Additionally, require enzymatic activity AMBRA1/CRL4, Rab40-induced leads dissociation AMBRA1/CRL4 complex. Taken together, our findings reveal regulator for involved

Language: Английский

Citations

0
Protective Effects of Exogenous Melatonin Administration on White Fat Metabolism Disruption Induced by Aging and a High-Fat Diet in Mice DOI Creative Commons

Dongying Lv,

Yujie Ren,

Jiayan Chen

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(12), P. 1500 - 1500

Published: Dec. 9, 2024

Obesity has emerged as a major risk factor for human health, exacerbated by aging and changes in dietary habits. It represents significant health challenge, particularly older people. While numerous studies have examined the effects of obesity on fat metabolism independently, research their combined is limited. In present study, protective action against white accumulation after high-fat diet (HFD) exerted exogenous melatonin, circadian hormone endowed with antioxidant properties also involved metabolism, was investigated mouse model. For this purpose, battery tests applied before melatonin treatments animals, including epididymal adipose tissue (eWAT) histological evaluations, transcriptomic lipidomic analyses, real-time PCR tests, immunofluorescence staining, Western blot, appraisal serum levels, transmission electron microscopy. This study found that aged mice showed increased lipid deposition, inflammation, reduced glutathione (GSH) levels compared to younger mice. Lipidomic analyses revealed elevated triglycerides, diglycerides, ceramides, cholesterol, along decreased sphingomyelin fatty acids eWAT. The genes linked NF-κB signaling, autophagy, pathways, were significantly altered. HFD exhibited Melatonin supplementation GSH upregulated AANAT MTNR1A expression eWAT, suggesting alleviates eWAT damage via pathway. suppressed inflammatory markers (e.g., TNF-α, NLRP3, NF-κB, IL-1β, CEBPB) preserved mitochondrial function through enhanced mitophagy. highlights how affect gene expression, offering potential intervention strategies. These findings provide important insights into mechanisms deposition associated diet,

Language: Английский

Citations

0