Chronic inflammation and the hallmarks of aging

Molecular Metabolism, Год журнала: 2023, Номер 74, С. 101755 - 101755

Опубликована: Июнь 16, 2023

Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, low-grade inflammation during aging, without overt infection, is defined as "inflammaging," which associated with increased morbidity mortality in population. Emerging evidence suggests a bidirectional cyclical relationship between development age-related conditions, such cardiovascular diseases, neurodegeneration, cancer, frailty. How crosstalk other underlies biological mechanisms disease thus particular interest current geroscience research.

Язык: Английский

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4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to promote cuproptosis in colorectal cancer

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 159, С. 114301 - 114301

Опубликована: Янв. 25, 2023

Cuproptosis, a novel copper-induced cell death pathway, is linked to mitochondrial respiration and mediated by protein lipoylation. The discovery of cuproptosis unfolds new areas investigation, particularly in cancers. present study aimed explore the role colorectal cancer progression. genetic alterations colon were evaluated using database. MTT assays, colony formation, flow cytometry used examine effect elesclomol-Cu 4-Octyl itaconate (4-OI) on oxaliplatin-resistant viability. anti-tumor elesclomol with 4-OI was verified vivo assay. results showed that FDX1, SDHB, DLAT, DLST genes more highly expressed normal tissues than those primary tumor tissues. Patients high expressions these had better prognosis. Using assay formation analysis, pulse treatment significant inhibition viability HCT116, LoVo, HCT116-R cells. In addition, revealed significantly promoted apoptosis. Tetrathiomolybdate, copper chelator, markedly inhibited cuproptosis. Subsequently, we found 2-deoxy-D-glucose, glucose metabolism inhibitor, sensitized Furthermore, galactose further Interestingly, enhanced which irrelevant ROS production, apoptosis, necroptosis, or pyroptosis pathways. Aerobic glycolysis through GAPDH, one key enzymes glycolysis, sensitizing Meanwhile, FDX1 knockdown weakened ability promote experiments, effects. These indicated rapidly halted growth cells line. Importantly, aerobic targeting GAPDH

Язык: Английский

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Targeting macrophage polarization as a promising therapeutic strategy for the treatment of osteoarthritis

International Immunopharmacology, Год журнала: 2023, Номер 116, С. 109790 - 109790

Опубликована: Фев. 1, 2023

Язык: Английский

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The Role of Regulated Programmed Cell Death in Osteoarthritis: From Pathogenesis to Therapy

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5364 - 5364

Опубликована: Март 10, 2023

Osteoarthritis (OA) is a worldwide chronic disease that can cause severe inflammation to damage the surrounding tissue and cartilage. There are many different factors lead osteoarthritis, but abnormally progressed programmed cell death one of most important risk induce osteoarthritis. Prior studies have demonstrated death, including apoptosis, pyroptosis, necroptosis, ferroptosis, autophagy, cuproptosis, has great connection with In this paper, we review role types in generation development OA how signal pathways modulate regulate OA. Additionally, provides new insights into radical treatment osteoarthritis rather than conservative treatment, such as anti-inflammation drugs or surgical operation.

Язык: Английский

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Macrophage plasticity: signaling pathways, tissue repair, and regeneration

MedComm, Год журнала: 2024, Номер 5(8)

Опубликована: Авг. 1, 2024

Abstract Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) alternatively (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay signaling pathways, transcriptional regulators, epigenetic modifications orchestrates polarization, allowing respond stimuli dynamically. Here, we provide comprehensive overview the cascades governing focusing on roles Toll‐like receptors, signal transducer activator transcription proteins, nuclear microRNAs. We also discuss emerging concepts metabolic reprogramming trained immunity, contributing their functional adaptability. Macrophage plasticity plays pivotal role in repair regeneration, macrophages coordinating inflammation, angiogenesis, matrix remodeling restore homeostasis. By harnessing potential novel therapeutic strategies targeting polarization could be developed for diseases, including chronic wounds, fibrotic disorders, inflammatory conditions. Ultimately, deeper understanding molecular mechanisms underpinning will pave way innovative regenerative medicine engineering approaches.

Язык: Английский

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Regulation of immunomodulatory networks by Nrf2-activation in immune cells: Redox control and therapeutic potential in inflammatory diseases

Redox Biology, Год журнала: 2024, Номер 70, С. 103077 - 103077

Опубликована: Фев. 11, 2024

Inflammatory diseases present a serious health challenge due to their widespread prevalence and the severe impact on patients' lives. In quest alleviate burden of these diseases, nuclear factor erythroid 2-related 2 (Nrf2) has emerged as pivotal player. As transcription intimately involved in cellular defense against metabolic oxidative stress, Nrf2's role modulating inflammatory responses immune cells garnered significant attention. Recent findings suggest that ability alter redox status underlies its regulatory effects responses. Our review delves into preclinical clinical evidence underscores complex influence Nrf2 activators cell phenotypes, particularly milieu. By offering detailed analysis different populations, we cast light potential shaping response towards more regulated state, mitigating adverse inflammation through modeling cells. Furthermore, explore innovative use nanoencapsulation techniques enhance delivery efficacy activators, potentially advancing treatment strategies for ailments. We hope this will stimulate development expansion Nrf2-targeted treatments could substantially improve outcomes patients suffering from broad range diseases.

Язык: Английский

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TREM2 promotes macrophage polarization from M1 to M2 and suppresses osteoarthritis through the NF-κB/CXCL3 axis

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(6), С. 1992 - 2007

Опубликована: Янв. 1, 2024

Objective: Osteoarthritis (OA) is the most prominent chronic arthritic disease, affecting over 3 billion people globally.Synovial macrophages, as immune cells, play an essential role in cartilage damage OA.Therefore, regulating macrophages crucial for controlling pathological changes OA.Triggering receptor expressed on myeloid cells 2 (TREM2), cell surfaces, such and dendritic has suppressed inflammation regulated M2 macrophage polarization but demonstrated unknown synovial OA.This study aimed to investigate TREM2 expression downregulation OA mice macrophages.Furthermore, trend of was associated with polarization-related molecule mice.Results: We used knockout (TREM2-KO) observe that deficiency significantly exacerbated joint response mice, thereby accelerating disease progression.Separating chondrocytes from TREM2-KO co-cultivating them increased chondrocyte apoptosis inhibited proliferation.Further, also enhanced phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway activation, increasing nuclear factor kappa light chain enhancer activated B (NF-κB) C-X-C Motif Chemokine Ligand (CXCL3) expression.Furthermore, NF-κB inhibition arthritis effectively alleviating deficiency-related adverse effects chondrocytes.Notably, knocking down CXCL3 inhibits inflammatory promotes proliferation.Intravenous recombinant protein (soluble TREM2, sTREM2) injection markedly M1 improves tissue pathology OA.Conclusion: Our reveals during by NF-κB/CXCL3 axis regulation, improving state OA.

Язык: Английский

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Hydroxytyrosol downregulates inflammatory responses via Nrf2/HO-1 axis during fungal keratitis and exerts antifungal effects

International Immunopharmacology, Год журнала: 2025, Номер 149, С. 114202 - 114202

Опубликована: Фев. 6, 2025

Язык: Английский

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Antioxidant-Rich Functional Foods and Exercise: Unlocking Metabolic Health Through Nrf2 and Related Pathways

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1098 - 1098

Опубликована: Янв. 27, 2025

This article reviews the synergistic effects of antioxidant-enriched functional foods and exercise in improving metabolic health, focusing on underlying molecular mechanisms. The review incorporates evidence from PubMed, SCOPUS, Web Science, PsycINFO, reference lists relevant up to 20 December 2024, highlighting central role Nrf2 pathway. As a critical regulator oxidative stress adaptation, mediates benefits these interventions. presents an innovative approach understanding regulation inflammation, its potential prevention treatment various diseases, including cancer, neurodegenerative disorders, cardiovascular pulmonary diabetes, inflammatory conditions, ageing, infections such as COVID-19. novelty this study is investigate bioactive compounds found (such polyphenols, flavonoids, vitamins) exercise-induced activation combined reveals their improve insulin sensitivity lipid metabolism reduce offering promising strategy for management chronic diseases. However, there are significant gaps current research, particularly regarding mechanisms interaction between diet, physical activity, activation, well long-term different populations, those with In addition, interactions other signalling pathways, AMPK, NF-κB, PI3K/Akt, collective contributions health explored. Furthermore, novel biomarkers presented assess impact strategies, NAD+/NADH ratio, GSH markers mitochondrial health. findings provide valuable insights into how integration antioxidant-rich diet regular can by activating related pathways represent strategies disorders. Further studies needed fully understand therapeutic interventions diseases stress, disease, cancer.

Язык: Английский

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The potential roles of JAK/STAT signaling in the progression of osteoarthritis

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Ноя. 24, 2022

Osteoarthritis (OA) is an age-related chronic progressive degenerative disease that induces persistent pain and disabilities. The development of OA a complex process, the risk factors are various, including aging, genetics, trauma altered biomechanics. Inflammation immunity play important role in pathogenesis OA. JAK/STAT pathway one most prominent intracellular signaling pathways, regulating cell proliferation, differentiation, apoptosis. Inflammatory can act as initiators pathway, which implicated pathophysiological activity chondrocyte. In this article, we provide review on importance pathological Potentially, becomes therapeutic target for managing

Язык: Английский

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