The rapid emergence of drug-resistant influenza A virus (IAV) strains has severely limited the efficacy of current antiviral therapies, highlighting an urgent need for novel agents with distinct mechanisms of action. In this study, a series of 2-aminoquinoline derivatives were synthesized via a trimethylsilyl trifluoromethanesulfonate (TMSOTf) -catalyzed annulation strategy. Evaluation of their anti-influenza virus activity revealed that derivative 3g exhibited potent antiviral efficacy, low cytotoxicity, and a high selectivity index(SI), making it the most promising candidate in this series. In vitro investigations revealed that 3g primarily acted during the early-to-mid stages of viral replication, significantly suppressing the transcription and translation of viral nucleoprotein (NP) and matrix protein 2 (M2), thereby effectively blocking viral replication and protein synthesis. Furthermore, 3g inhibited virus-induced apoptosis, reduced excessive production of reactive oxygen species (ROS) and nitric oxide (NO) triggered by viral infection, and markedly attenuated cytokine storm responses by suppressing the retinoic acid-inducible gene I (RIG-I)/Toll-like receptor 3 (TLR3)-mediated signaling pathways. In vivo experiments confirmed that 3g significantly reduced viral loads in the lungs of infected mice, alleviated pulmonary histopathological damage, and downregulated inflammatory factor levels, while exhibiting good biosafety. Collectively, these results position derivative 3g as a promising compound for the development of novel anti-influenza therapies.
Jiejie Lu, Longyu Xiao, Chaofan Qi et al.· European journal of medicina...· 0 citations
Regular exercise mediates inter-tissue communication between skeletal muscle and the immune system through skeletal muscle-derived secretory factors, providing an important molecular basis for the beneficial effects of exercise on chronic inflammation, metabolic dysregulation, and impaired tissue repair. As key effector cells of the innate immune system, macrophages do not simply conform to a dichotomous classification of classically activated M1 macrophages and alternatively activated M2 macrophages; rather, their functional states constitute a dynamic spectrum shaped by exercise load, recovery time window, tissue microenvironment, and disease context. This review focuses on recent advances in exercise-induced skeletal muscle secretory factors involved in macrophage functional remodeling. Representative signals, including interleukin-6 (IL-6), irisin, meteorin-like protein (METRNL), fibroblast growth factor 21 (FGF21), oncostatin M (OSM), decorin, myostatin, chemokines, and extracellular vesicles, are systematically summarized in terms of their exercise responsiveness, evidence for skeletal muscle origin, and evidence supporting macrophage regulation. Based on these dimensions, an evidence-strength grading framework is further proposed. Moreover, this review integrates key signaling axes, including glycoprotein 130 (gp130)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT), signal transducer and activator of transcription 6 (STAT6)/peroxisome proliferator-activated receptor gamma (PPARγ), AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/nuclear factor kappa B (NF-κB), transforming growth factor beta (TGF-β)/Smad, and chemokine receptor pathways, to explain how exercise-induced secretory networks participate in the dynamic regulation of the macrophage functional spectrum through immune cell recruitment, inflammatory clearance, immunometabolic reprogramming, matrix remodeling, and repair-niche formation. Current evidence indicates the translational potential of exercise-induced skeletal muscle secretory factors in skeletal muscle repair, metabolic inflammation, aging-related functional decline, and cancer rehabilitation. However, this field still faces several major challenges, including insufficient tracing of skeletal muscle-derived signals, limited direct causal validation, a lack of human tissue-level evidence, and unclear exercise dose–response relationships. Future studies should combine tissue-specific genetic interventions, receptor blockade, single-cell and spatial omics, metabolic flux analysis, and standardized human exercise interventions to further clarify the mechanistic basis and application boundaries of exercise-induced skeletal muscle–macrophage communication, thereby providing a theoretical foundation for precision exercise prescription and chronic inflammation intervention.
Ziyang Li, Chen-Yu Lin, Lin-Tao Tang et al.· International Journal of Mol...· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
