Ecotoxicology and Environmental Safety, Год журнала: 2025, Номер 297, С. 118225 - 118225
Опубликована: Апрель 23, 2025
Язык: Английский
Frontiers in Endocrinology, Год журнала: 2025, Номер 15
Опубликована: Янв. 17, 2025
Obesity is a major modifiable risk factor leading to neuroinflammation and neurodegeneration. Excessive fat storage in obesity promotes the progressive infiltration of immune cells into adipose tissue, resulting release pro-inflammatory factors such as cytokines adipokines. These inflammatory mediators circulate through bloodstream, propagating inflammation both periphery central nervous system. Gut dysbiosis, which results leaky intestinal barrier, exacerbates plays significant role linking pathogenesis neurodegeneration gut-brain/gut-brain-liver axis. Inflammatory states within brain can lead insulin resistance, mitochondrial dysfunction, autolysosomal increased oxidative stress. disruptions impair normal neuronal function subsequently cognitive decline motor deficits, similar pathologies observed neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, Parkinson's disease. Understanding underlying disease mechanisms crucial for developing therapeutic strategies address defects these metabolic pathways. In this review, we summarize provide insights different strategies, methods alter gut lifestyle changes, dietary supplementation, well pharmacological agents derived from natural sources, that target obesity-induced
Язык: Английский
Процитировано
2
Frontiers in Endocrinology, Год журнала: 2025, Номер 16
Опубликована: Фев. 11, 2025
Editorial: Lipid Metabolism Dysregulation in Obesity-Related Diseases and Neurodegeneration Provisionally accepted
Язык: Английский
Процитировано
1
Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13
Опубликована: Фев. 27, 2025
Periodontitis is a chronic inflammatory disease affecting the supporting tissues of teeth and has emerged as global public health issue. Current therapies primarily address pathogenic factors alleviate symptoms, with limited options available for complete restoration reconstruction already absorbed periodontal bone tissue. In this study, we developed nanotherapeutic strategy utilizing fusion nanovesicles (FVs) to modulate microenvironment create regenerative niche ligament stem cells (PDLSCs), which play crucial role in tissue repair. The FVs are composed Scutellaria baicalensis (SBNVs) anti-Porphyromonas gingivalis (P. gingivalis) anti-inflammatory properties, combined PDLSC membrane-derived genetically engineered express TNFR1. These preserved biological activity SBNVs immunomodulatory function PDLSCs. Additionally, effectively captured cleared TNF-α from through Moreover, alleviated response PDLSCs induced by P. gingivalis-LPS (Pg-LPS) TNF-α, restoring their proliferation, migration, osteogenic differentiation capabilities. Hence, holds great potential treating periodontitis.
Язык: Английский
Процитировано
0
Hereditas, Год журнала: 2025, Номер 162(1)
Опубликована: Фев. 27, 2025
Abstract Background Non-small cell lung cancer (NSCLC) is a common subtype of that has received considerable attention for its potential association with rheumatoid arthritis (RA). However, current understanding the relationship between RA and NSCLC risk remains limited in-depth studies molecular mechanisms are lacking. Methods We obtained transcriptomic data from Gene Expression Omnibus (GEO) database performed Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analyses differential genes. then used Mendelian randomisation (MR) analysis to explore causal NSCLC, but results showed no direct NSCLC. In light this finding, we shifted our research focus investigate effect therapeutics on risk. A drug-targeted MR drugs available treatment was by searching target genes associated RA. Results found several corresponding treat By drugs, some do have an developing increasing Conclusion This study employed drug targets elucidate correlation The identification differentially expressed their provided new perspectives pathogenesis Furthermore, additional immune infiltration demonstrated that, in tissues, levels specific subpopulations, including regulatory T cells (Tregs), activated natural killer (NK cells) unpolarised macrophages (M0), exhibited notable differences. These findings emphasise significant role interactions may play disease progression. through validation histology, further confirmed development expression these differences samples, providing basis possible future therapeutic biomarkers.
Язык: Английский
Процитировано
0
Computational and Structural Biotechnology Journal, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Tumor necrosis factor (TNF) receptor 1 (TNFR1) plays a central role in signal transduction mediating inflammation and cell death associated with autoimmune neurodegenerative disorders. Inhibition of TNFR1 signaling is highly sought-after strategy to target these diseases. forms pre-ligand dimers held together by the assembly domain (PLAD), which essential for signaling. form crucial points interaction entire complex connecting TNF ligand bound trimeric receptors. While previous studies have shown feasibility disrupting dimeric interactions through competitive mechanism that targets PLAD, our recent demonstrated small molecules could also bind PLAD modulate an allosteric mechanism. Importantly, modulators alter dynamics propagate long-range conformational perturbation involves reshuffling receptors cytosolic domains without receptor-receptor or receptor-ligand interactions. In this study, we perform molecular docking previously reported on extracellular understand their binding sites interacting residues. We identify inter-monomeric space between as novel pocket modulators. further conduct pharmacological analyses bioactivity compounds residues properties. then provide insights into structure-activity relationship targeting dynamics. This paves way developing new therapeutic strategies designing chemical scaffolds
Язык: Английский
Процитировано
0
Biomedicines, Год журнала: 2025, Номер 13(4), С. 852 - 852
Опубликована: Апрель 2, 2025
Introduction: Immunosenescence alters TNF receptor expression (TNFR1 and TNFR2), contributing to chronic inflammation (inflamm-aging) age-related diseases. Polymorphisms in TNFRSF1A TNFRSF1B may influence expression; however, their role age-dependent modulation remains unclear. This study examines TNFR1/TNFR2 dynamics on T cells, B monocytes across different ages evaluates the impact of genetic polymorphisms. Methods: PBMCs from 150 donors (18–60 years) were isolated via density-gradient centrifugation cultured under spontaneous LPS-stimulated conditions. TNFR1 TNFR2 immune cell subsets was quantified using flow cytometry with BD QuantiBRITE PE beads. SNP genotyping performed PCR restriction analysis. Nonlinear trends assessed polynomial approximation inflection point analysis (Tukey’s method). Results: Among 23 analyzed system parameters, proportion TNFR2+CD3+ cells increased age, whereas TNFR1+ TNFR2+ monocyte populations showed significant negative correlations (p < 0.05). Inflection points (~27, 34–36, 44–45 indicated nonlinear TNFRs during aging. gradually stabilized at later ages, followed distinct declining trajectories. Genetic polymorphisms influenced correlation strength, but did not alter direction, demonstrating a conserved pattern shifts. Conclusions: TNFR exhibits nonlinear, alterations shaped by immunosenescence variability. The identified critical age intervals represent key phases remodeling, where assessing provide insights into inflamm-aging mechanisms potential targets for modulation.
Язык: Английский
Процитировано
0
Bioorganic & Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 118197 - 118197
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0
Ecotoxicology and Environmental Safety, Год журнала: 2025, Номер 297, С. 118225 - 118225
Опубликована: Апрель 23, 2025
Язык: Английский
Процитировано
0