Hallmarks of aging: An expanding universe

Cell, Год журнала: 2023, Номер 186(2), С. 243 - 278

Опубликована: Янв. 1, 2023

Язык: Английский

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Hypoxia signaling in human health and diseases: implications and prospects for therapeutics

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июль 7, 2022

Abstract Molecular oxygen (O 2 ) is essential for most biological reactions in mammalian cells. When the intracellular content decreases, it called hypoxia. The process of hypoxia linked to several processes, including pathogenic microbe infection, metabolic adaptation, cancer, acute and chronic diseases, other stress responses. mechanism underlying cells respond changes mediate subsequent signal response central question during Hypoxia-inducible factors (HIFs) sense regulate expressions a series downstream genes expression, which participate multiple processes cell metabolism, growth/death, proliferation, glycolysis, immune response, tumorigenesis, metastasis. Importantly, signaling also interacts with cellular pathways, such as phosphoinositide 3-kinase (PI3K)-mammalian target rapamycin (mTOR) signaling, nuclear factor kappa-B (NF-κB) pathway, extracellular signal-regulated kinases (ERK) endoplasmic reticulum (ER) stress. This paper systematically reviews mechanisms activation, control HIF function human health diseases. In addition, therapeutic targets involved balance diseases are summarized highlighted, would provide novel strategies design development drugs.

Язык: Английский

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Reshaping endoplasmic reticulum quality control through the unfolded protein response

Molecular Cell, Год журнала: 2022, Номер 82(8), С. 1477 - 1491

Опубликована: Апрель 1, 2022

Язык: Английский

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Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 25, 2023

Abstract Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in which the airways narrow or collapse during sleep, causing obstructive apnea. The prevalence of OSAS continues to rise worldwide, particularly middle-aged and elderly individuals. mechanism upper airway incompletely understood but associated with several factors, including obesity, craniofacial changes, altered muscle function airway, pharyngeal neuropathy, fluid shifts neck. main characteristics are recurrent pauses respiration, lead intermittent hypoxia (IH) hypercapnia, accompanied by blood oxygen desaturation arousal sharply increases risk diseases. This paper first briefly describes epidemiology, incidence, pathophysiological mechanisms OSAS. Next, alterations relevant signaling pathways induced IH systematically reviewed discussed. For example, can induce gut microbiota (GM) dysbiosis, impair intestinal barrier, alter metabolites. These ultimately secondary oxidative stress, systemic inflammation, sympathetic activation. We then summarize effects on disease pathogenesis, cardiocerebrovascular disorders, neurological metabolic diseases, cancer, reproductive COVID-19. Finally, different therapeutic strategies for caused causes proposed. Multidisciplinary approaches shared decision-making necessary successful treatment future, more randomized controlled trials needed further evaluation define what treatments best specific patients.

Язык: Английский

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Melatonin Engineering M2 Macrophage‐Derived Exosomes Mediate Endoplasmic Reticulum Stress and Immune Reprogramming for Periodontitis Therapy

Advanced Science, Год журнала: 2023, Номер 10(27)

Опубликована: Июль 14, 2023

Periodontitis is a chronic infectious disease caused by bacterial irritation. As an essential component of the host immunity, macrophages are highly plastic and play crucial role in inflammatory response. An appropriate timely transition from proinflammatory (M1) to anti-inflammatory (M2) indispensable for treating periodontitis. M2 macrophage-derived exosomes (M2-exos) can actively target sites modulate immune microenvironments, M2-exos effectively treat Excessive endoplasmic reticulum stress (ER stress) unfolded protein response (UPR) destructive pathological characteristics during periodontal bone loss. Although melatonin has antioxidant effects, studies focusing on ER modulation remain limited. This study fabricates engineered loading with (Mel@M2-exos) result, drive macrophage reprogramming M1 type, which resolves inflammation accelerated healing. Melatonin released Mel@M2-exos rescues osteogenic cementogenic differentiation capacity human ligament cells (hPDLCs) reducing excessive UPR. Injectable gelatin methacryloyl (GelMA) hydrogels sustained-release accelerate regeneration rats ligation-induced Taken together, engineering promising candidates tissue regeneration.

Язык: Английский

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Reactive oxygen species and ovarian diseases: Antioxidant strategies

Redox Biology, Год журнала: 2023, Номер 62, С. 102659 - 102659

Опубликована: Март 7, 2023

Reactive oxygen species (ROS) are mainly produced in mitochondria and involved various physiological activities of the ovary through signaling critical for regulating ovarian cycle. Notably, imbalance between ROS generation antioxidant defense system contributes to development diseases. These contradictory effects have implications potential strategies that aim scavenge excessive ROS. However, much remains be learned about how causes diseases application therapy Here, we review mechanisms maintenance homeostasis its associated effects. Additionally, highlighted pathological treatment.

Язык: Английский

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Endoplasmic Reticulum (ER) Stress and Its Role in Pancreatic β-Cell Dysfunction and Senescence in Type 2 Diabetes

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(9), С. 4843 - 4843

Опубликована: Апрель 27, 2022

An increased life span and accompanying nutritional affluency have led to a rapid increase in diseases associated with aging, such as obesity type 2 diabetes, imposing tremendous economic health burden on society. Pancreatic β-cells are crucial for controlling glucose homeostasis by properly producing secreting the glucose-lowering hormone insulin, dysfunction of determines outcomes both 1 diabetes. As native structure insulin is formed within endoplasmic reticulum (ER), ER should be appropriately maintained allow proper metabolic functioning β-cells. Recent studies found that cellular senescence critically linked stresses, including stress, oxidative mitochondrial stress. These implied β-cell caused stress other stresses contributes β-cells’ impairment homeostasis. This review documents discusses current understanding senescence, function, its signaling mechanism (unfolded protein response), effect dysfunction.

Язык: Английский

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Polystyrene nanoplastics-induced lung apoptosis and ferroptosis via ROS-dependent endoplasmic reticulum stress

The Science of The Total Environment, Год журнала: 2023, Номер 912, С. 169260 - 169260

Опубликована: Дек. 10, 2023

Язык: Английский

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The role of oxidative stress in intervertebral disc degeneration: Mechanisms and therapeutic implications

Ageing Research Reviews, Год журнала: 2024, Номер 98, С. 102323 - 102323

Опубликована: Май 9, 2024

Oxidative stress is one of the main driving mechanisms intervertebral disc degeneration(IDD). has been associated with inflammation in disc, cellular senescence, autophagy, and epigenetics cells. It above pathological are closely linked through common hub reactive oxygen species(ROS), promote each other process degeneration development disease. This reveals important role oxidative IDD, importance great potential IDD therapy targeting stress. The efficacy traditional unstable or cannot be maintained. In recent years, due to rise materials science, many bioactive functional have applied treatment combination drugs, satisfactory achieved. At present, research review antioxidant not complete. Based on existing studies, mechanism were summarized this paper, strategies based emerging reviewed.

Язык: Английский

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Mechanism of Decision Making between Autophagy and Apoptosis Induction upon Endoplasmic Reticulum Stress

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(8), С. 4368 - 4368

Опубликована: Апрель 15, 2024

Dynamic regulation of the cellular proteome is mainly controlled in endoplasmic reticulum (ER). Accumulation misfolded proteins due to ER stress leads activation unfolded protein response (UPR). The primary role UPR reduce bulk damages and try drive back system former or a new homeostatic state by autophagy, while an excessive level results apoptosis. It has already been proven that proper order characteristic features both surviving self-killing mechanisms are negative positive feedback loops, respectively. suggest these loops found not only within but also between branches UPR, fine-tuning stress. In this review, we summarize recent knowledge dynamical mechanism using theoretical molecular biological techniques. addition, review pays special attention describing action controlling life-and-death decision upon Since appears diseases common worldwide, more detailed understanding behaviour medical importance.

Язык: Английский

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