Doxorubicin-Induced Cardiac Senescence Is Alleviated Following Treatment with Combined Polyphenols and Micronutrients through Enhancement in Mitophagy DOI Creative Commons
Eleonora Foglio,

Erica D’Avorio,

Laura Vitiello

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(22), P. 2605 - 2605

Published: Nov. 10, 2023

Oxidative stress and impaired mitophagy are the hallmarks of cardiomyocyte senescence. Specifically, a decrease in mitophagic flux leads to accumulation damaged mitochondria development senescence through increased ROS other mediators. In this study, we describe preventive role A5+, mix polyphenols micronutrients, doxorubicin (DOXO)-induced H9C2 cells. cells exposed DOXO showed an increase protein expression proteins senescence-associated genes, p21 p16, telomere binding factors TRF1 TRF2, indicative induction. Nevertheless, A5+ pre-treatment attenuated senescent-like cell phenotype, as evidenced by inhibition all senescent markers SA-β-gal staining DOXO-treated Importantly, restored LC3 II/LC3 I ratio, Parkin BNIP3 expression, therefore rescuing mitophagy, decreased production. Further, determined ripolarization mitochondrial membrane improved basal respiration. A5+-mediated protective effects might be related its ability activate SIRT3 synergy with but contrast SIRT4 activation. Accordingly, knockdown further MnSOD activity, enhanced reduced generation following exposure compared WT Indeed, demonstrated that protects from DOXO-induced senescence, establishing new specific for controlling quality control restoring activity which provided molecular basis therapeutic strategies against

Language: Английский

CMPK2 promotes NLRP3 inflammasome activation via mtDNA‐STING pathway in house dust mite‐induced allergic rhinitis DOI Creative Commons
Yaoming Zheng, Y. Xie, Jiaying Li

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Abstract Background House dust mite (HDM) is the leading allergen for allergic rhinitis (AR). Although sensitisation by inhaled allergens renders susceptible individuals prone to developing AR, molecular mechanisms driving this process remain incompletely elucidated. Objective This study aimed elucidate underlying HDM‐induced AR. Methods We examined expression of cytidine/uridine monophosphate kinase 2 (CMPK2), STING and NLRP3 inflammasome in both AR patients mice. Additionally, we investigated role CMPK2 activation Results The CMPK2, was significantly increased nasal mucosa compared non‐AR controls. A positive correlation found between levels STING, NLRP3, ASC, CASP1 IL‐1β. HDM treatment up‐regulated overexpression enhanced human epithelial cells (HNEPCs). mitochondrial reactive oxygen species (mtROS) production following exposure contributed dysfunction release DNA (mtDNA), which activated cyclic GMP‐AMP synthase (cGAS)‐STING pathway. Remarkably, depletion mtDNA or inhibition signalling reduced HNEPCs. In vivo, genetic knockout alleviated ameliorated clinical symptoms Conclusions Our results suggest that promotes through up‐regulation ensuing mtDNA‐STING pathway, hence revealing additional therapeutic target Key points Cytidine/uridine (CMPK2) mice with caused via (mtDNA)‐STING Blocking house (HDM)‐challenged

Language: Английский

Citations

1
Network pharmacology mechanisms and experimental verification of licorice in the treatment of ulcerative colitis DOI
Jinrong Kong,

Qingzhen Xiang,

Wanyue Ge

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 117691 - 117691

Published: Jan. 1, 2024

Language: Английский

Citations

8
The role of polyphenols in modulating mitophagy: Implications for therapeutic interventions DOI Creative Commons
Xinyu Lin, Wenkai Liu, Xizhuo Hu

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 207, P. 107324 - 107324

Published: July 24, 2024

This review rigorously assesses the burgeoning research into role of polyphenols in modulating mitophagy, an essential cellular mechanism for targeted removal impaired mitochondria. These natural compounds, known their low toxicity, are underscored potential therapeutic strategies against a diverse array diseases, such as neurodegenerative, cardiovascular, and musculoskeletal disorders. The analysis penetrates deeply molecular mechanisms whereby promote particularly by influencing crucial signaling pathways transcriptional regulators, including phosphatase tensin homolog (PTEN) induced putative kinase 1 (PINK1)/parkin forkhead box O3 (FOXO3a) pathways. Noteworthy discoveries include neuroprotective properties resveratrol curcumin, which affect both autophagic mitochondrial dynamics, pioneering integration with other substances to amplify effectiveness. Furthermore, confronts issue polyphenol bioavailability emphasizes imperative clinical trials corroborate viability. By delivering exhaustive synthesis contemporary insights recent advancements mitophagy research, this endeavors catalyze additional foster creation innovative modalities that exploit distinctive attributes manage prevent disease.

Language: Английский

Citations

7
NLRP3 Inflammasome Deficiency Alleviates Inflammation and Oxidative Stress by Promoting PINK1/Parkin-Mediated Mitophagy in Allergic Rhinitis Mice and Nasal Epithelial Cells DOI Creative Commons
Hong Ding,

Xiaofan Lu,

Huimin Wang

et al.

Journal of Asthma and Allergy, Journal Year: 2024, Volume and Issue: Volume 17, P. 717 - 731

Published: Aug. 1, 2024

Accumulating evidence indicates that oxidative stress and inflammation are the pathological basis of allergic diseases. Inhibition NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome could ameliorate rhinitis (AR). Here, we explored effects mechanisms underlie NLRP3 inhibition on in AR.

Language: Английский

Citations

5
Exploring Advances in Natural Plant Molecules for Allergic Rhinitis Immunomodulation in Vivo and in Vitro DOI Creative Commons

Bingquan Li,

Boyang Dong,

Liangzhen Xie

et al.

International Journal of General Medicine, Journal Year: 2025, Volume and Issue: Volume 18, P. 529 - 565

Published: Feb. 1, 2025

Abstract: Allergic rhinitis (AR) is a prevalent allergic disease that imposes significant economic burdens and life pressures on individuals, families, society, particularly in the context of accelerating globalization increasing pathogenic factors. Current clinical therapies for AR include antihistamines, glucocorticoids administered via various routes, leukotriene receptor antagonists, immunotherapy, several decongestants. These treatments have demonstrated efficacy alleviating symptoms pathological states. However, with growing awareness rising expectations improvements quality life, these become associated higher incidence side effects an elevated risk drug resistance. Furthermore, development intricately dysregulation immune system, yet underlying pathogenetic mechanisms remain incompletely understood. In contrast, widely available natural plant molecules offer multiple targeting pathways uniquely modify typical pathophysiology through immunomodulatory processes. This review presents comprehensive analysis both vivo vitro studies modulate immunity treating AR. Additionally, we examine their specific action animal models to provide new insights developing safe effective targeted while guiding experimental applications against Keywords: molecules, rhinitis, immunomodulation, therapeutic mechanism, research progress

Language: Английский

Citations

0
Potential of Polydatin Against Ischemia-Reperfusion Injury: New Insights from Pharmacological-Pathological Mechanism Associations DOI Creative Commons
Zhicheng Sun, Xiyang Wang, Xiaoyang Pang

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 1585 - 1594

Published: March 1, 2025

Ischemia-reperfusion injury is a multi-tissue/organ susceptible and highly destructive disease. The complex pathological mechanisms of ischemia-reperfusion make its prevention treatment challenging, the development novel drugs with pharmacological pleiotropy that can target multiple has become focus current drug research. Polydatin traditional Chinese medicine monomer pleiotropic effects, existing research evidence suggests polydatin strong protective potential against injury. However, mechanism still unclear. In this review, extensive pharmacological-pathological associations between have been described from perspectives inflammatory response, oxidative stress, apoptosis, autophagy, ferroptosis, cellular pyroptosis, which will provide references to basic applied in field

Language: Английский

Citations

0
Inhibition of PINK1 senses ROS signaling to facilitate neuroblastoma cell pyroptosis DOI

Yuyuan Zhu,

Min Cao,

Yancheng Tang

et al.

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

Published: March 31, 2025

Mitochondria serve as the primary source of intracellular reactive oxygen species (ROS), which play a critical role in orchestrating cell death pathways such pyroptosis various types cancers. PINK1-mediated mitophagy effectively removes damaged mitochondria and reduces detrimental ROS levels, thereby promoting survival. However, regulation by PINK1 neuroblastoma remains unclear. In this study, we demonstrate that inhibition or deficiency sensitizes signaling promotes cells via BAX-caspase-GSDME pathway. Specifically, AC220 knockout impairs enhances production, leading to oxidation oligomerization TOMM20, followed mitochondrial recruitment activation BAX. Activated BAX facilitates release CYCS (cytochrome c, somatic) from into cytosol, activating CASP3 (caspase 3). Subsequently, activated cleaves activates GSDME, inducing pyroptosis. Furthermore, potentiates anti-tumor effects clinical ROS-inducing drug ethacrynic acid (EA) inhibit progression vivo. Therefore, our study provides promising intervention strategy for through induction

Language: Английский

Citations

0
Arctiin Inhibits Hyperglycemia‐Induced Oxidative Stress by Activating the Nrf2/HO‐1 Signaling Pathway to Treat Type 2 Diabetic Osteoporosis DOI

Weipeng Sun,

Minying Li, Qing Lin

et al.

Molecular Nutrition & Food Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Arctiin (ARC), a primary component of burdock (Arctium lappa L.), is widely recognized as traditional herb and nutritional supplement in Asia. This study set out to explore its potential impact on type 2 diabetic osteoporosis (T2DOP). MC3T3-E1 cells were exposed high-glucose environment simulate conditions. Treatment with ARC increased the expression crucial osteogenic transcription factor genes, such RUNX2, Osterix, COL1A1. Moreover, mitigated production ROS induced by high glucose levels. For vivo experimentation, db/db mice used models for T2DOP. supplementation decreased bone loss improved structural integrity. Collectively, our findings indicate that holds promise intervention treatment By activating Nrf2/HO-1 signaling pathway, could help counteract oxidative stress impaired differentiation associated diabetes, thus offering dietary strategy support health. Incorporating ARC-containing foods or supplements into diet be beneficial approach enhance overall quality potentially reduce risk fractures other bone-related problems patients highlighting importance considering natural compounds management chronic diseases.

Language: Английский

Citations

0
Role of Mitochondria in the Chronification of Inflammation: Focus on Dysfunctional Mitophagy and Mitochondrial DNA Mutations DOI Creative Commons
Alexander N. Orekhov, Volha I. Summerhill, Victoria A. Khotina

et al.

Gene Expression, Journal Year: 2023, Volume and Issue: 22(4), P. 329 - 344

Published: Nov. 30, 2023

Inflammation is a natural reaction of the innate immune system that evolved primarily to protect human body from invading pathogens and heal injuries. There are two different types inflammation, acute chronic differing in duration, underlying causes, characteristics. The acute-to-chronic transition can be determined by several pathomechanisms, including dysregulation response failure eliminate cause. Moreover, epigenetic changes refer modifications gene expression heritable but do not involve DNA sequence also contribute prolonged inflammation. Emerging evidence suggests dysfunctional mitochondria promote development In this respect, mechanisms triggering defective mitophagy, selective form autophagy exterminates maintain cellular homeostasis, attracted special attention. hypothesis on pivotal role mutations mitochondrial causing mitophagy stimulated area research applies editing genome. mitoCAS9 vector single guide RNAs G15059A mutation were used macrophage-like cells. normal activity initially was restored intact cells, confirming causal disruption process. unraveling inflammation will help develop targeted therapeutic approaches aimed at restoring health alleviating for treatment wide range inflammatory diseases.

Language: Английский

Citations

7
Notch1 hyperactivity drives ubiquitination of NOX2 and dysfunction of CD8+ regulatory T cells in patients with systemic lupus erythematosus DOI

Zixin Yuan,

Mengdi Liu, Lei Zhang

et al.

Lara D. Veeken, Journal Year: 2024, Volume and Issue: unknown

Published: April 21, 2024

Patients with systemic lupus erythematosus (SLE) display heightened immune activation and elevated IgG autoantibody levels, indicating compromised regulatory T cell (Tregs) function. Our recent findings pinpoint CD8+ Tregs as crucial regulators within secondary lymphoid organs, operating in a NOX2-dependent mechanism. However, the specific involvement of SLE pathogenesis mechanisms underlying their role remain uncertain.

Language: Английский

Citations

2