Phytomedicine, Journal Year: 2024, Volume and Issue: 129, P. 155673 - 155673
Published: April 22, 2024
Language: Английский
Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(18)
Published: Sept. 1, 2024
Abstract Despite extensive progress in the knowledge and understanding of cardiovascular diseases significant advances pharmacological treatments procedural interventions, (CVD) remain leading cause death globally. Mitochondrial dynamics refers to repetitive cycle fission fusion mitochondrial network. Fission balance regulate shape influence physiology, quality homeostasis. Mitophagy is a process that eliminates aberrant mitochondria. Melatonin (Mel) pineal‐synthesized hormone with range properties. Numerous nonclinical trials have demonstrated Mel provides cardioprotection against ischemia/reperfusion, cardiomyopathies, atherosclerosis cardiotoxicity. Recently, interest has grown how contribute melatonin cardioprotective effects. This review assesses literature on protective effects CVD via regulation mitophagy both in‐vivo in‐vitro studies. The signalling pathways underlying its were reviewed. modulated proteins by upregulation mitofusin, inhibition DRP1 mitophagy‐related proteins. evidence supports role control CVD.
Language: Английский
Citations
10
Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)
Published: Jan. 3, 2024
Abstract Background The management of myocardial ischemia–reperfusion injury (MIRI) presents continuous therapeutic challenges. NAD-dependent deacetylase Sirtuin 6 (Sirt6) plays distinct roles in various disease contexts and is hence investigated for potential applications MIRI. This study aimed to examine the impact Sirt6-overexpressing exosomes derived from adipose stem cells (S-ASC-Exo) on MIRI, focusing their influence AIM2-pyroptosis mitophagy processes. sirtuin family proteins, particularly (Sirt6), play a pivotal role these explore effects Sirt6-enriched regulating Results Bioinformatic analysis revealed significant downregulation Sirt6 MIRI subjected control group, causing consequential increase pyroptosis regulator expressions. Therefore, our that influenced progression through regulation target proteins AIM2 GSDMD, associated with pyroptosis, p62 Beclin-1, related mitophagy. introduction S-ASC-Exo inhibited while enhancing Consequently, this led reduction GSDMD cleavage endothelial cells, catalyzing deceleration atherosclerosis. Extensive vivo vitro assays were performed validate expressions specific genes which affirmed dynamic modulation by exosomes. Furthermore, treatment drastically ameliorated cardiac functions limited infarct size, underlining cardioprotective attributes. Conclusions Our underscores managing We demonstrated profound effect, evident enhanced function attenuated tissue damage, strategic Given intricate interplay between aforementioned processes, comprehensive understanding pathways essential fully exploit Sirt6. Altogether, findings indicate promise as novel strategy treating injuries cardiovascular diseases at large. Future research needs underscore optimizing balance during ischemia avoid loss normal myocytes.
Language: Английский
Citations
9
Molecules, Journal Year: 2020, Volume and Issue: 25(19), P. 4410 - 4410
Published: Sept. 25, 2020
Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting host are different strategies, but with an identical purpose, i.e., to curb pathogen’s spreading and cure illness. It appears that increase tolerance against can be of substantial advantage strategy used in evolution. Practically, it has broader protective spectrum than only specific pathogens, which differ terms susceptibility. Methods applied one pandemic even effective upcoming pandemics pathogens. This more urgent if we consider possible concomitance two respiratory diseases potential multi-organ afflictions such as Coronavirus disease 2019 (COVID-19) seasonal flu. Melatonin molecule enhance host’s pathogen invasions. Due its antioxidant, anti-inflammatory, immunoregulatory activities, melatonin capacity reduce severity mortality deadly virus infections including COVID-19. synthesized functions mitochondria, play critical role infections. Not surprisingly, synthesis become target strategies manipulate mitochondrial status. For example, infection switch energy metabolism from respiration widely anaerobic glycolysis plenty oxygen available (the Warburg effect) when cell cannot generate acetyl-coenzyme A, metabolite required biosynthesis. Under some conditions, aging, gender, predisposed health already compromised exposed further challenges, lose their producing sufficient amounts melatonin. leads reduced support makes these individuals vulnerable diseases. Thus, maintenance function by supplementation expected beneficial effects on outcome
Language: Английский
Citations
55
Cells, Journal Year: 2022, Volume and Issue: 11(2), P. 199 - 199
Published: Jan. 7, 2022
Mitophagy, which mediates the selective elimination of dysfunctional mitochondria, is essential for cardiac homeostasis. Mitophagy regulated mainly by PTEN-induced putative kinase protein-1 (PINK1)/parkin pathway but also FUN14 domain-containing 1 (FUNDC1) or Bcl2 interacting protein 3 (BNIP3) and BNIP3-like (BNIP3L/NIX) pathways. Several studies have shown that dysregulated mitophagy involved in dysfunction induced aging, aortic stenosis, myocardial infarction diabetes. The cardioprotective role well described, whereas excessive could contribute to cell death dysfunction. In this review, we summarize mechanisms regulation its physiological condition. We focused on during following highlighting PI NK1/parkin-; FUNDC1-; BNIP3- BNIP3L/NIX-induced ischemia reperfusion.
Language: Английский
Citations
38
Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 8
Published: Jan. 18, 2022
Cytokine storm is closely related to the initiation and progression of sepsis, level IL-6 positively correlated with mortality organ dysfunction. Sepsis-induced myocardial dysfunction (SIMD) one major complications. However, role IL-6/STAT3 signaling in SIMD remains unclear.Septic mice were induced by intraperitoneal injection LPS (10 mg/kg). Echocardiography, cytokines detection, histologic examination showed that sepsis developed cardiac systolic diastolic dysfunction, increase inflammatory serum, activated STAT3 TLR4/NFκB pathway heart, raised apoptosis, which attenuated inhibitor, Bazedoxifene. In vitro, we found decreased cell viability a concentration-dependent manner STAT3. Western blot immunofluorescence results indicated phosphorylation was inhibited Bazedoxifene also suppressed LPS-induced transcription. sIL-6R caused p-STAT3 firstly then significantly increased. More importantly, STAT3-knockdown expression FUNDC1, protein located mitochondria-associated endoplasmic reticulum membranes (MAMs). Overexpression led an FUNDC1 expression. Dual-luciferase reporter assay used confirm potential transcription factor for FUNDC1. Moreover, increased MAMs formation intracellular Ca2+ levels, enhanced Cav1.2 RyR2, mitochondrial membrane ATP promoted fragmentation, mitophagy proteins ROS production H9c2 cells, reversed knockdown inhibitor including Stattic.IL-6/STAT3 plays key through regulating FUNDC1-associated interfering function ER mitochondria. IL-6/STAT3/FUNDC1 could be new therapeutic target SIMD.
Language: Английский
Citations
30
Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 116004 - 116004
Published: Dec. 11, 2023
Dysregulation of mitochondrial homeostasis is common to all types cardiovascular diseases. SIRT3 regulates apoptosis and autophagy, material energy metabolism, oxidative stress, inflammation, fibrosis. As an important mediator node in the network mechanisms, essential many activities. This review explains how tricarboxylic acid cycle treat A novel description impact lifestyle factors on expression from angles nutrition, exercise, temperature provided.
Language: Английский
Citations
19
Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(4)
Published: March 20, 2023
Language: Английский
Citations
18
Aging, Journal Year: 2021, Volume and Issue: 13(12), P. 16105 - 16123
Published: June 11, 2021
Diabetic patients are more vulnerable to cerebral ischemia-reperfusion (CIR) injury and have a worse prognosis higher mortality after ischemic stroke than non-diabetic counterparts. Melatonin can exert neuroprotective effects against CIR in nondiabetic animal models. However, its on diabetic the underlying mechanisms remain unclarified. Herein, we found that melatonin administration improved neurological deficit, infarct volume, brain edema, cell viability, reduced mitochondrial swelling, reactive oxygen species generation, cytoplasmic cytochrome C release, increased antioxidant enzymes activities, adenosine triphosphate production, membrane potential both streptozotocin-induced mice high glucose-treated HT22 cells. Importantly, also activated protein kinase B (Akt) sirtuin 3 (SIRT3)/superoxide dismutase 2 (SOD2) signaling upregulated biogenesis-related transcription factors. these were largely attenuated by LY294002 (a specific Akt blocker) administration. Additionally, 3-TYP selective SIRT3 inhibitor) siRNA inhibited above protective of as well upregulation decrease SOD2 acetylation but did not affect p-Akt/Akt ratio. Overall, demonstrate alleviate activating Akt-SIRT3-SOD2 subsequently improving damage.
Language: Английский
Citations
38
Toxicology and Applied Pharmacology, Journal Year: 2022, Volume and Issue: 452, P. 116179 - 116179
Published: July 30, 2022
Language: Английский
Citations
27
Pharmacological Research, Journal Year: 2022, Volume and Issue: 176, P. 106072 - 106072
Published: Jan. 8, 2022
Language: Английский
Citations
26