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关键词： DECMs   Decellularized extracellular matrices   ECM   Extracellular matrix   EDTA   Ethylene diamine tetraacetic acid   EGTA   Ethylene glycol tetraacetic acid   GAGs   Glycosaminoglycans   MHC   Major Histocompatibility Complex   MMPs   Matrix Metalloproteinases   PGP   Proline–Glycine–Proline   SDS   Sodium dodecyl sulfate   SD   Sodium deoxycholate   SEM   Scanning Electron Microscopy   TEM   Transmission electron microscopy   PNGase-F   Peptide N-Glycosidase F   Extracellular matrix   Decellularization   Immune response   Compatibility  

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关键词： IL-17A pathway   Lcn2   Necrotizing enterocolitis   Pyroptosis  

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关键词： CCDC25   Chrysophanein   IL-22   ILC3s   UC  

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关键词： IL-6/CD73 axis   MDSCs   Non-small cell lung cancer   Tumor immune microenvironment   Wu-Wei-Zi decoction  

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关键词： Aging   Zhenqi Buxu oral liquid   TNF-alpha   Chronic inflammation   Senescence   SASP  

摘要： Ethnopharmacological relevance: Aging is associated with a persistent, low-grade inflammatory state termed "inflammaging", driven by the accumulation of senescent cells and their senescence-associated secretory phenotype (SASP). Zhenqi Buxu Oral Liquid (ZQBX) is a widely used traditional Chinese medicine formula known to treat human weakness and have potential anti-aging effects. Aim of study: To explore the geroprotective effects of ZQBX and its underlying mechanisms. Methods: We used a natural aging mouse model to evaluate the effects of ZQBX intervention on aging. Tissue staining, serum ELISA assays, physical function analysis, network pharmacological analysis and molecular docking analysis were employed to describe the phenotypic and mechanistic effects of ZQBX. Results: ZQBX treatment protected against age-related declines in liver function and hepatic steatosis, mitigated chronic inflammation, and improved insulin sensitivity and glucose metabolism in aged mice. Mechanically, ZQBX reduced SASP in senescent hepatic cells to delay liver aging through inhibiting the TNF-alpha signaling pathway. Conclusion: The pharmacological significance of ZQBX in modulating senescence-associated phenotypes implies its potential benefits in regulating the activities of senescent cells, suggesting possible contributions to future geriatric medicine.

关键词： Andrographolide   Inflammation   TNF-alpha   IL-6   DAS   iNOS   Succinate  

摘要： The succinate derivatives of 14-deoxy-11,12-didehydroandrographolide (14-DDA) were synthesized and screened for anti-inflammatory activity. Cell viability assay results indicated that all synthesized compounds maintained healthy cell viability above 90 % at 10 mu M and were further evaluated for their nitric oxide (NO) inhibition potential. Among these, compound 5 exhibited the strongest NO suppression, with an IC50 value of 8.6 mu M, compared to andrographolide (IC50 = 12.2 mu M). The inhibitory effects of compound 5 on pro-inflammatory cytokines TNF-alpha and IL-6 were also studied in comparison to the parent compound. Compound 5 significantly reduced the production of TNF-alpha and IL-6 in LPS-stimulated macrophage cells, with IC50 values of 13.06 mu M and 9.1 mu M, respectively. Molecular docking studies of compound 5 revealed substantial hydrogen and alkyl bonding interactions with TNF-alpha, indicating greater binding affinity than IL-6. Further analysis demonstrated that compound 5 had stronger binding affinity for iNOS and TNF-alpha, with iNOS showing the highest docking score of -9.5 kcal/mol. These results highlight compound 5 as a promising lead candidate for the development of novel antiinflammatory therapies.

关键词： Diospyros melanoxylon   LC-MS   In silico study   Ursolic acid   Paracetamol   Hepatoprotective  

摘要： Ethnopharmacological relevance Diospyros melanoxylon, Roxb., (Ebenaceae), native to South and Southeast Asia, has been traditionally used to treat liver disorders, jaundice, tuberculosis, and chronic wounds and inflammatory conditions. Aim of the study To evaluate the hepatoprotective effect of D. melanoxylon leaf methanolic extract (MDML) in paracetamol (PCM)-induced liver toxicity in rats. Material and method Phytoconstituents in the MDML were identified via LC-MS. Molecular docking and dynamics simulations evaluated the binding stability of ursolic acid (UA) with IL-6, COX-2, and LOX. In vitro COX-2 and 5-LOX inhibition assays assessed anti-inflammatory potential. Hepatoprotective efficacy was examined in PCM-intoxicated rats treated with MDML (200, 300, 400 mg/kg). Biochemical markers, serum enzymes (ALT, AST, ALP, GGT, LDH), protein profile (TP, ALB, GLB, TB), antioxidant enzymes (SOD, CAT, GSH), oxidative stress marker (MDA), and cytokines (IL-6, IL-10, IL-1 beta, TNF-alpha) were analyzed. Histopathological examination of liver tissues further validated the findings. Result Nineteen compounds were identified by LC-MS. UA showed strong docking affinities with IL-6 (-7.0 kcal/mol), COX-2 (-8.5 kcal/mol), and LOX, with MD simulations confirming stable interactions. MDML (400 mu g/mL) inhibited COX-2 and 5-LOX by 78.45 % and 85.45 %, respectively. In vivo, MDML (400 mg/kg) significantly (p < 0.01, p < 0.001) reduced liver enzymes and oxidative stress markers, while improving antioxidant levels and cytokine balance. Significant reductions in TB and GLB, with corresponding increases in TP and TLB, were observed. Histology revealed dose-dependent restoration of hepatic architecture comparable to controls. Conclusion MDML shows dose-dependent hepatoprotection against PCM-induced toxicity, likely due to the presence of UA, supporting its traditional use in liver disorders.

关键词： High-altitude cerebral edema (HACE)   Musk   TNF-alpha/RIPK1 signaling   Necroptosis   Hypobaric hypoxia (HH)  

摘要： Ethnopharmacological relevance: Musk (Moschus Moschiferus) is regarded as a key drug for treating brain injury-related nerve damage in both traditional Chinese medicine and Tibetan medicine. According to the theory of traditional Chinese medicine, musk has the characteristics of being pungent and warm, and acts on the heart and spleen meridians, with the effects of awakening the brain and opening the orifices, as well as promoting blood circulation and removing blood stasis. This makes it an important drug for treating acute brain injuries such as closed coma and stroke with phlegm obstruction. Modern research has revealed that musk has multiple neuroprotective mechanisms and anti-inflammatory/antioxidant effects. These findings support its therapeutic potential in targeting neuronal injury pathways in the prevention and treatment of HACE, and further translational research is warranted. Aim of the study: This study aimed to investigate the neuroprotective properties of musk and uncovering the mechanisms through which it may exert its beneficial effects against HACE. Materials and methods: The constituents of musk were analyzed using Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS). Additionally, network pharmacology and proteomic profiling were applied to identify possible molecular targets and associated signaling pathways. In vivo experiments were carried out using a rat model simulating an altitude of 6000 m over a 48-h period, while in vitro investigations involved exposing cultured microglial cells to hypoxia for 6h. The effectiveness and mode of action of musk were evaluated using a range of experimental techniques, including brain water content analysis via brain water content (BWC), histopathological examination (HE), Enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), transmission electron microscopy (TEM), and flow cytometry (FCM). Results: The UPLC-MS analysis identified 117 active compounds within musk. The tumor necrosi

摘要： Herpes simplex encephalitis (HSE) is a devastating disease with high mortality and serious sequelae. Genetic defects in the IFN-I pathway predispose individuals to HSE, but underlying mechanisms remain unclear. Using transgenic mice with the IRF3 R278Q mutation, ortholog to HSE-associated IRF3 R285Q, and iPSC-derived CNS cells from a pediatric patient carrying the variant, we investigated mechanisms in HSE. IRF3 R278Q transgenic mice exhibited aggravated HSV-1 brain disease and elevated CNS viral loads. Accordingly, microglia from the IRF3 R278Q mice showed reduced HSV-1-induced IFN-I expression. Surprisingly, unaltered Ifnb levels along with elevated levels of inflammatory cytokines were detected in infected transgenic mouse brains, correlating with higher viral load. This was successfully modeled in patient microglia. Multiomics-based immune profiling revealed an inflammatory monocyte population in the infected IRF3 R278Q mouse brain, which was enriched for NF-κB activation. NF-κB inhibition improved disease outcomes, surpassing the effect of acyclovir. These findings suggest that IFN-I defects lead to elevated levels of HSV-1 replication in the brain, which subsequently enables NF-κB-driven immunopathology, offering insights with therapeutic potential.

摘要： Respiratory viral infections establish tissue-resident memory T cells (TRM) in the lung, which provide optimal protection against subsequent infections, though the underlying mechanisms are incompletely understood. Here, we demonstrate in a mouse model of heterosubtypic influenza infection that lung TRM attenuate inflammation by macrophages during secondary versus primary responses, in part, through production of the immunoregulatory cytokine IL-10. During secondary infections, lung TRM were the predominant producers of early IL-10; inhibiting early IL-10 signaling resulted in increased macrophage-mediated inflammation, morbidity, and lung pathology. Moreover, lung TRM were shown to directly modulate lung macrophage responses and polarization in depletion experiments. Finally, IL-10 enhanced IFN-γ production by lung memory CD8+ T cells. Human influenza-specific TRM isolated from lungs recapitulated robust IL-10 expression associated with augmented effector responses of murine TRM. These data support a dual role of TRM in coordinating in situ secondary responses-augmenting effector responses for robust viral clearance while dampening inflammation to limit tissue damage.