Role of hypoxia in cellular senescence

Pharmacological Research, Journal Year: 2023, Volume and Issue: 194, P. 106841 - 106841

Published: June 28, 2023

Senescent cells persist and continuously secrete proinflammatory tissue-remodeling molecules that poison surrounding cells, leading to various age-related diseases, including diabetes, atherosclerosis, Alzheimer's disease. The underlying mechanism of cellular senescence has not yet been fully explored. Emerging evidence indicates hypoxia is involved in the regulation senescence. Hypoxia-inducible factor (HIF)- 1α accumulates under hypoxic conditions regulates by modulating levels markers p16, p53, lamin B1, cyclin D1. Hypoxia a critical condition for maintaining tumor immune evasion, which promoted driving expression genetic factors (such as p53 CD47) while triggering immunosenescence. Under conditions, autophagy activated targeting BCL-2/adenovirus E1B 19-kDa interacting protein 3, subsequently induces p21WAF1/CIP1 well p16Ink4a increases β-galactosidase (β-gal) activity, thereby inducing Deletion p21 gene activity response regulator poly (ADP-ribose) polymerase-1 (PARP-1) level nonhomologous end joining (NHEJ) proteins, repairs DNA double-strand breaks, alleviates Moreover, associated with intestinal dysbiosis an accumulation D-galactose derived from gut microbiota. Chronic leads striking reduction amount Lactobacillus D-galactose-degrading enzymes gut, producing excess reactive oxygen species (ROS) bone marrow mesenchymal stem cells. Exosomal microRNAs (miRNAs) long noncoding RNAs (lncRNAs) play important roles miR-424-5p are decreased hypoxia, whereas lncRNA-MALAT1 increased, both induce present review focuses on recent advances understanding role effects HIFs, PARP-1, microbiota, exosomal mRNA hypoxia-mediated cell specifically discussed. This our provides new clues anti-aging processes treatment aging-related diseases.

Language: Английский

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Bee Pollen Phytochemicals and Nutrients as Unequaled Pool of Epigenetic Regulators: Implications for Age-Related Diseases

Foods, Journal Year: 2025, Volume and Issue: 14(3), P. 347 - 347

Published: Jan. 21, 2025

Bee pollen is characterized by an exceptional diversity and abundance of micronutrients bioactive phytochemicals. This richness remains very sparsely investigated, but accumulating evidence strongly supports a promising future for bee in human nutrition medicine. Epigenetic regulation among the most compelling biomedical topics that remain completely untapped derivative research. In our current research, we identified numerous ubiquitous compounds are consistently present this matrix, regardless its botanical geographical origins, have been well studied documented as epigenetic regulators recent years. Given relative newness both research studies within nutritional, pharmaceutical, medical sciences, review aims to bridge these valuable fields advance related experimental investigations. To best knowledge, first work has aimed comprehensively investigate modulatory potential compounds. Our findings also unveiled several intriguing phenomena, such dual effect same compound depending on cellular context or some cross-generational heritability traits. Although whole extract still lacking, study clearly indicates avenue worth further We hope constitutes foundational cornerstone investigations

Language: Английский

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Silica Nanoparticles Induce SH-SY5Y Cells Death Via PARP and Caspase Signaling Pathways

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Language: Английский

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MSLN Correlates With Immune Infiltration and Chemoresistance as a Prognostic Biomarker in Ovarian Cancer

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: May 25, 2022

Mesothelin (MSLN) is a glycoprotein with various expression degrees in different tumors including mesothelioma, ovarian cancer, pancreatic etc. MSLN considered to play an important role cell survival, proliferation, and tumor progression. Although the of makes it potential therapeutic target, its mechanism action still unclear, especially correlation immune cells infiltration microenvironment has not been investigated. In this study, we detected overexpression cancer using database analysis tissue-array staining. We further evaluated diagnostic value found was associated poor overall survival cancer. addition, high significantly related immune-related genes chemoresistant genes. confirmed lines. Our research suggests that participates variety pathways suppression activation promotion chemoresistance, leading prognosis

Language: Английский

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Baicalin attenuates lipopolysaccharide-induced intestinal inflammatory injury via suppressing PARP1-mediated NF-κB and NLRP3 signalling pathway

Toxicon, Journal Year: 2024, Volume and Issue: 239, P. 107612 - 107612

Published: Jan. 10, 2024

Language: Английский

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The General Principle of the Warburg Effect as a Possible Approach for Cancer Immunotherapy: The Regulatory Effect of Plant Extracts Could Change the Game

Molecules, Journal Year: 2025, Volume and Issue: 30(2), P. 393 - 393

Published: Jan. 18, 2025

The interpretation of the biochemistry immune metabolism could be considered an attractive scientific field biomedicine research. In this review, role glycolysis in macrophage polarization is discussed together with mitochondrial cancer cells. first part, focus on Warburg effect and redox during polarization, development, management response by second part addresses possibility impacts through targeting peroxisome proliferator-activated receptors (PPARs). This activator native responses. Because reported serious adverse effects using synthetic ligands for PPARs combination chemotherapeutics, searches less toxic more active PPAR inhibitors, as well blocking undesirable cellular PPAR-dependent processes, are progress. On other hand, recent research modern immunotherapy has focused search gentle immune-modulating natural compounds harmless synergistic chemotherapeutic efficacy that can used adjuvant. It a well-known fact plant kingdom source important therapeutic agents multifaceted effectiveness. One these known association activities. regard, secondary metabolites extracted from plants change game.

Language: Английский

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IONPs-induced neurotoxicity via cascade of neuro-oxidative stress, parthanatos-mediated cell death, neuro-inflammation and neurodegenerative changes: Ameliorating effect of rosemary methanolic extract

Toxicology Reports, Journal Year: 2025, Volume and Issue: 14, P. 101935 - 101935

Published: Jan. 31, 2025

Language: Английский

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Perfluorooctane sulfonic acid: a possible risk factor of endothelial dysfunction based on in silico and in vitro studies

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Language: Английский

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Green Cancer Prevention and Beyond

Cancer Prevention Research, Journal Year: 2024, Volume and Issue: 17(3), P. 107 - 118

Published: Jan. 19, 2024

Abstract The concept of green chemoprevention was introduced in 2012 by Drs. Jed Fahey and Thomas Kensler as whole-plant foods and/or extract-based interventions demonstrating cancer prevention activity. Refining concepts research proof-of-principle approaches are highlighted within this review. Early included extensively investigated whole foods, including broccoli sprouts black raspberries showing dose–responsive effects across a range activities both animals humans with minimal or no apparent toxicity. A recent randomized crossover trial evaluating the detoxification tobacco carcinogens seed sprout extract high-risk cohort current smokers highlights use dietary supplement potential next-generation approach. Challenges addressed, selection dose, duration mode delivery, choice control group, standardization plant food extract. Identification characterization molecular targets careful cohorts for study additional important considerations when designing studies. Goals precision include acquiring robust evidence from carefully controlled human studies linking extracts, compounds to modulation risk reduction individual types.

Language: Английский

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Human PARP1 Facilitates Transcription through a Nucleosome and Histone Displacement by Pol II In Vitro

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 7107 - 7107

Published: June 26, 2022

Human poly(ADP)-ribose polymerase-1 (PARP1) is a global regulator of various cellular processes, from DNA repair to gene expression. The underlying mechanism PARP1 action during transcription remains unclear. Herein, we have studied the role human through nucleosomes by RNA polymerase II (Pol II) in vitro. strongly facilitates mononucleosomes Pol and displacement core histones presence NAD+ transcription, its NAD+-dependent catalytic activity essential for this process. Kinetic analysis suggests that formation “open” complexes containing nucleosomal partially uncoiled octamer allowing progression along DNA. Anti-cancer drug inhibitor olaparib represses PARP1-dependent transcription. data suggest negative charge on protein(s) poly(ADP)-ribosylated interact with positively charged DNA-binding surfaces transiently exposed facilitating chromatin transcription-dependent histone displacement/exchange.

Language: Английский

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