Shijun Xu

Influenza virus-induced pneumonia (IVP) is a contagious lung disease marked by severe lung inflammation following viral infection and remains a significant public health concern due to its high mortality rate. G protein-coupled receptor 84 (GPR84) has been implicated in various inflammatory diseases, however, its role in influenza virus-induced lung inflammation remains poorly understood. In this study, using high-throughput screening, we found that Influenza A virus (IAV) infection markedly upregulates the expression of several G protein-coupled receptors, with GPR84 mRNA and protein levels being highly induced in the lungs of animal models during pneumonia. Mechanistically, GPR84 enhances ZBP1-PANoptosome mediated PANoptosis and exacerbates the release of inflammatory chemokines and danger associated molecular patterns (DAMPs). Notably, deletion of GPR84 attenuates influenza virus-induced PANoptosis, indicating that GPR84 participates in regulating lung inflammation and the pathogenesis of pneumonia during influenza infection. Overall, these findings demonstrate that GPR84 plays a central role in influenza virus–induced lung inflammation by promoting PANoptosis and the release of inflammatory mediators. Targeting GPR84 attenuates IAV-induced PANoptosis, highlighting its potential as a therapeutic target to mitigate the pathogenesis of influenza virus-induced pneumonia.

Alzheimer’s disease (AD) remains a major, intractable neurodegenerative disorder and a serious threat to human health, characterized by a protracted clinical course, gradual progression, and irreversible cognitive decline. The current therapeutic landscape is characterized by a lack of disease-modifying agents, making the pursuit of early, effective interventions a global priority. Endoplasmic reticulum–mitochondria contact sites (ERMCs), also termed mitochondria-associated ER membranes (MAMs), constitute critical platforms for interorganellar communication, enabling material exchange and signal transduction. Key functions regulated at these junctions include calcium (Ca²⁺) homeostasis, mitochondrial dynamics, and lipid synthesis/transfer. Growing evidence implicates dysregulated ERMCs in the pathogenesis of neurodegenerative diseases, including AD and Parkinson’s disease (PD). Recent advances in understanding the physiological and pathological roles of ERMCs have further illuminated their multifaceted contribution to AD, spanning amyloid-β (Aβ) production, Ca²⁺ signaling, energy and lipid metabolism, mitochondrial integrity, and endoplasmic reticulum stress (ERs). This review synthesizes current knowledge on ERMCs as a pivotal communication hub in AD and underscores their promising potential as targets for novel therapeutic strategies. Deeper insights into this axis may inform future approaches to improve clinical outcomes.

Background: Influenza A virus (IAV) infection poses a significant global health burden, contributing to high morbidity and mortality in both humans and animals through rapid viral transmission and dysregulated inflammatory responses. Fangqin Qinggan Decoction (FQ-01), a traditional Chinese medicine (TCM) formula, has demonstrated clinical efficacy in treating viral upper respiratory infections, however, its underlying therapeutic mechanisms remain poorly understood. Methods: The therapeutic efficacy and mechanisms of FQ-01 against IAV infection were comprehensively investigated using a multidisciplinary approach, including in vivo murine models, histopathological (H&E staining), RT-qPCR, immunohistochemistry (IHC), network pharmacology, weighted gene co-expression network analysis (WGCNA), machine learning (LASSO), transcriptomics, metabolomics, molecular docking and molecular dynamics (MD) simulation. Results: FQ-01 significantly improved survival rates, reduced clinical mortality, and mitigated pulmonary inflammation in an IAV-infected mice while suppressing viral replication. Integrated bioinformatics and LASSO regression analyses identified 20 genes associated with FQ-01’s antiviral effects, with Myd88 and Ccl5 emerging as key targets. Transcriptomic profiling of murine lung tissues further validated these genes as critical mediators of FQ-01’s therapeutic action. Spearman correlation analysis revealed strong associations between Myd88/Ccl5 expression and serum/lung metabolites, particularly 3-indolyl sulfate and inosine. Subsequent in vivo RT-qPCR and IHC validation, molecular docking, and MD simulations confirmed that FQ-01 exerts its anti-IAV effects by inhibiting Myd88 and Ccl5 expression. Conclusions: Our findings elucidate the molecular mechanisms underlying FQ-01’s therapeutic potential against IAV infection, highlighting Myd88 and Ccl5 as promising targets for antiviral and anti-inflammatory interventions. This study provides a foundation for further exploration of TCM-based strategies in combating influenza and related respiratory infections. Graphical

Background: Perihematomal neuroinflammation serves as a pivotal pathogenic driver of secondary brain injury during the acute stage of intracerebral hemorrhage (ICH). The traditional Chinese medicine Zhongfeng Xingnao Liquid exhibits anti-neuroinflammatory effects. This study aims to elucidate the optimal timing for ZFXN administration within hours of symptom onset and its underlying mechanisms, focusing on NF-κB/NLRP3-mediated neuroinflammation. Methods: ICH was induced by injection of autologous arterial blood into the left caudal nucleus. Neurological deficits scores, hematoma volume, cerebral blood flow (CBF), H&E and Nissl staining were conducted at 24 hours following ICH. The levels of neuroinflammation response and NF-κB/NLRP3 axis surrounding the hematoma were measured using immunofluorescent staining and Western blot. The inhibition of ZFXN on NF-κB/NLRP3 axis was further confirmed in Lipopolysaccharide (LPS)-induced BV-2 cells. Results: Post-ICH pathology was characterized by progressive hematoma expansion, elevated neurological deficit scores, neuronal damage, and reduced CBF, accompanied by neuroinflammatory. Early ZFXN intervention within 6 hours post-ICH significantly reduced hematoma volume and improved neurological scores (mNSS, Bederson, Zea Longa) at 24 hours, while markedly alleviating perihematomal neuronal damage and enhancing CBF, with optimal efficacy observed following one-hour administration. The treatment also effectively suppressed IL-1β/TNF-α release and microglial activation through NF-κB/NLRP3 pathway inhibition. Consistently, ZFXN diminished NF-κB-p65 nuclear translocation and downregulated NLRP3 inflammasome components (ASC, Cleaved Caspase-1) in LPS-stimulated BV-2 cells. Conclusion: ZFXN emerges as a promising neuroprotective agent for ICH through targeted inhibition of the NF-κB/NLRP3 inflammatory axis, demonstrating optimal efficacy within the critical 6-hour hyperacute phase by mitigating secondary neuroinflammation and addressing current therapeutic gaps in ICH management.