Unraveling the molecular complexity: Wtap/Ythdf1 and Lcn2 in novel traumatic brain injury secondary injury mechanisms

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: Aug. 7, 2024

The primary aim of this research was to explore the functions Wtap and Ythdf1 in regulating neuronal Lipocalin-2 (Lcn2) through m6A modification traumatic brain injury (TBI). By employing transcriptome sequencing enrichment analysis, we identified Wtap/Ythdf1-mediated Lcn2 pathway as crucial TBI. In our vitro experiments using cortical neurons, knockout led inhibition modification, resulting reduced death inflammation. Furthermore, overexpression neurons induced activation reactive astrocytes M1-like microglial cells, causing apoptosis. vivo confirmed cells TBI importantly demonstrated that knockdown improved neuroinflammation functional impairment. These findings underscore significance regulation secondary suggest potential therapeutic implications for combating TBI-induced damage.

Language: Английский

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The genetic advantage of healthy centenarians: unraveling the central role of NLRP3 in exceptional healthspan

Frontiers in Aging, Journal Year: 2024, Volume and Issue: 5

Published: Sept. 5, 2024

Despite extensive research into extending human healthspan (HS) and compressing morbidity, the mechanisms underlying aging remain elusive. However, a better understanding of genetic advantages responsible for exceptional HS healthy centenarians (HC), who live in good physical mental health one hundred or more years, could lead to innovative health-extending strategies. This review explores role NLRP3, critical component innate immunity that significantly impacts aging. It is activated by pathogen-associated signals self-derived increase with age, leading low-grade inflammation implicated age-related diseases. Furthermore, NLRP3 functions upstream several molecular pathways, regulates cellular senescence, may underlie robust observed HC. By targeting mice exhibit phenotype akin HC, monkeys extended, symptoms are reversed humans. Thus, offer promising approach extend HS. Additionally, paradigm shift proposed. Given broader population 30 years shorter than it postulated they suffer from form accelerated The term 'auto-aging' suggested describe driven NLRP3.

Language: Английский

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LCN2 aggravates diabetic cataracts by promoting ferroptosis in lens epithelial cells

Frigid Zone Medicine, Journal Year: 2024, Volume and Issue: 4(3), P. 177 - 192

Published: Sept. 1, 2024

Abstract Background Cataracts are the leading cause of reversible blindness worldwide. Diabetic cataract (DC), a prevalent complication diabetes mellitus, is characterized by its high occurrence, rapid progression, and severe impact. The prevalence varies greatly between northern southern regions, with higher rates observed among residents. DC-induced lens opacity mainly attributed to oxidative stress. However, it remains unclear whether ferroptosis, form regulated cell death, occurs in crystalline epithelial cells during pathogenesis, which may represent novel mechanism contributing DC. Methods Transmission electron microscopy, quantitative assays for iron levels reactive oxygen species (ROS), real-time polymerase chain reaction (RT-qPCR), western blotting, immunofluorescence, immunohistochemistry were used detect ferroptosis. Gene editing techniques utilized study regulatory relationships lipocalin 2 (LCN2), glutathione peroxidase 4 (GPX4), ferritin heavy (FTH). Local knockdown LCN2 gene B-3 eyes Sprague Dawley (SD) rats was performed verify further explore role mechanisms DC-associated Results An vitro model using glucose an vivo streptozotocin-induced SD successfully established. Ferroptosis both experiments. protein normally expressed human rat cells, but expression significantly increased ferroptosis inhibitor, ferrostatin-1 (Fer-1) effectively inhibited reduced expression. Notably, local via protected from slowed progression DC . Conclusion Our findings underscore significant pathogenesis DC, suggesting that selectively targeting activation enhancing resistance offer therapeutic approach treating

Language: Английский

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Lipocalin-2 and intestinal diseases

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(46), P. 4864 - 4879

Published: Nov. 19, 2024

Dysfunction of the intestinal barrier is a prevalent phenomenon observed across spectrum diseases, encompassing conditions such as mesenteric artery dissection, inflammatory bowel disease, cirrhosis, and sepsis. In these pathological states, integrity barrier, which normally serves to regulate selective passage substances between gut lumen bloodstream, becomes compromised. This compromised function can lead range adverse consequences, including increased permeability harmful substances, translocation bacteria their products into systemic circulation, heightened responses within beyond. Understanding mechanisms underlying dysfunction in diverse disease contexts crucial for development targeted therapeutic interventions aimed at restoring ameliorating progression. Lipocalin-2 (LCN2) expression significantly upregulated during episodes inflammation, making it pivotal indicator gauging extent processes. Notably, however, LCN2 derived from distinct cellular sources, whether epithelial cells or immune cells, exhibits notably divergent functional characteristics. Furthermore, multifaceted nature underscored by its varying roles different sometimes even demonstrating contradictory effects.

Language: Английский

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Diverse Cytokines Secreted by Adipocyte in Linking Cardio-Metabolic Disorder and SLE

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(11)

Published: Oct. 31, 2024

Systemic lupus erythematosus (SLE) is a multi-factorial autoimmune-mediated disease with hyper-stimulation of immune cells especially the T lymphocytes. By this method, it might facilitate systematic damages in multiple tissues and organs. Otherwise, SLE also correlated diverse cardio-metabolic comorbidities, including dyslipidemia, insulin resistance, hypertension. It worth-noting that risk disorders significantly higher compared healthy patients which was reported as approximately one-third were proved obesity. Notably, current focus shifting to implementing protective strategies well elucidating underlying mechanisms lupus-mediated obese status. On other hand, adipocyte, most abundant endocrine cell fat tissue, are dysfunctional individuals aberrant secretion adipokines. proposing adipokine link pathology SLE, whereas related mechanism complicated. In review, functions potential by listed. Furthermore, recommendations, identify therapeutic targets for treatment summarized.

Language: Английский

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