Ethnopharmacological relevance: The combined prescription of two classical decoctions (Ma-Xing-Shi-Gan decoction with Xiao-Chai-Hu decoction), named as San-Yang-He-Zhi (SYHZ) decoction, has been widely used for the treatment of influenza virus (IFV) infections for decades.Aim of the study: This study aimed to evaluate the anti-influenza effect of SYHZ decoction and explore the un-derlying mechanism. Materials and methods: The ingredients of SYHZ decoction were analyzed by mass spectrometry. An animal model of IFV infection was established by challenging C57BL/6J mice with PR8 virus. Three groups of mice were infected with lethal or non-lethal doses of IFV, then followed by oral administration of phosphate-buffered saline (PBS), or SYHZ, or oseltamir; blank control mice (without IFV infection) were treated with PBS. Survival rate, Lung index, colon length, body weight loss and IFV viral load were measured 7 days post infection; histology and electron-microscopy examinations of lung tissue were performed; cytokine and chemokine levels in lung and serum were measured; and the intestinal metagenome, the cecum metabolome, and the lung transcriptome were analyzed. Results: SYHZ treatment significantly improved survival rate compared with PBS (40% vs 0%); improved lung index, colon length, and body weight loss; and alleviated lung histological damage and viral load. SYHZ-treated mice had significantly lower levels of IL-1 beta, TNF-alpha, IL-6, CCL2, CXCL10 in lung and serum, and increased levels of multiple bioactive components in cecum. Pro-inflammatory cytokines, Toll-and NOD-like receptors, pro-apoptosis molecules, and lung-injury-related proteins were downregulated in SYHZ mice, whereas surfactant protein and mucin were upregulated. The NOD-like receptor pathway, Toll-like receptor pathway, and NF-kappa B pathway were downregulated by SYHZ treatment.Conclusions: SYHZ decoction alleviated IFV infection in a mouse model. Multiple bioactive ingredients of SYHZ may inhibit replication of IFV and suppress excessive immune response.

Objective:To explore the mechanism of Ma-Xing Shi-Gan decoction combined with Xiao-Chai-Hu decoction (hereinafter referred to as " Sanyang combined treatment" ) in alleviating colon injury in mice infected with influenza virus by transcriptome sequencing technique.Methods:The mouse model of colonic injury caused by influenza virus was induced by intranasal drip of influenza A virus H1N1 suspension. The mice were divided into Control group, Model group, and Sanyang combined treatment (SCT) group. Model group and SCT group were fed with PBS and Ma-Xing Shi-Gan decoction combined with Xiao-Chai-Hu decoction respectively. Seven days later, the colon tissues of each group were taken, the colon length and pathological damage were observed, and the transcriptome was sequenced to screen the significantly different genes between the SCT group and model group for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis(GSEA).Results:After the therapy with SCT, the length of the colon of mice was significantly improved and the pathological injury of the colon was reduced. There are 92 differentially expressed genes between the SCT group and the model group. GO analysis indicated that the differential genes were enriched in biological processes such as regulation of cytokine and chemokine production, inflammatory response, defense response, immune response, regulation of NF-κB inducing kinase(NIK)/Nuclear factor-κB(NF-κB) signal and Mitogen-activated protein kinase(MAPK) cascade, as well as cell components related to intestinal barrier such as brush border membrane, brush border and microvilli. KEGG analysis indicated that the differential genes were enriched in Toll-like receptor signaling pathway, intestinal immune network for IgA production, complement and coagulation cascade, and Peroxisome proliferator-activated receptor(PPAR) signaling pathway. GSEA indicated that the intestinal immune network for IgA production, PPAR signaling pathway, propionic acid metabolism and butyrate metabolism were significantly up-regulated after the intervention with SCT, while apoptosis and MAPK signaling pathway were significantly down-regulated.Conclusions:Sanyang combined therapy can protect the intestinal tract of mice infected with influenza virus mainly through immunity, inflammation and metabolism pathways.

Introduction:Hyperuricemia (HUA) is a common metabolic disease, and its prevalence has been increasing worldwide. Pharmaceutical drugs have been used for controlling HUA but they all have certain side effects, which thus calls for discovering alternative options including using treatment of probiotics to prevent the development of HUA.Methods:We established HUA mice model induced by potassium oxonate and adenine and performed in vivo experiments to verify the ability to lower serum uric acid of Lactiplantibacillus pentosus P2020 (LPP), a probiotics stain extracted from Chinese pickle. We also tried to discussed the underlying mechanisms.Results:Oral administration with LPP significantly decreased serum uric acid and reduced renal inflammatory response by downregulating multiple inflammation pathways including NK-kB, MAPK, and TNFα. We also found that LPP administration significantly promoted uric acid excretion by regulating expression of transporters in the kidney and ileum. In addition, LPP intake improved intestinal barrier function and modulated the composition of gut microbiota.Discussion:These results suggest that probiotics LPP may have a promising potential to protect against development of HUA and HUA-related renal damage, and its working mechanisms involve regulation of inflammation pathways and expression of transporters in the kidney and ileum.

目的 预测基于千金三黄汤加减的"麻黄-黄芩-黄芪-鱼腥草"配伍治疗甲型流感病毒感染的潜在作用靶点及作用机制,以期丰富抗流感病毒的复方配伍.方法 通过中药系统药理学分析平台数据库(TCMSP)、PubChem数据库、Swiss Target Prediction数据库筛选麻黄、黄芩、黄芪、鱼腥草的活性成分与潜在靶点.使用GeneCards数据库筛选流感病毒感染的疾病相关靶点,利用微生信平台中"集合运算Venn图"获得药物与甲型流感病毒的交集靶点.通过Cytoscape 3.8.2 软件构建"药物-活性成分-作用靶点"网络并进行拓扑分析.利用String数据库构建蛋白质-蛋白质互作(PPI)网络,并通过Cytoscape 3.8.2 软件进行拓扑分析,获得核心靶点.并应用Metascape数据库进行GO及KEGG富集分析.流感病毒PR8 构建C57BL/6J小鼠感染模型,观察小鼠一般状态、肺指数、肺组织病理,ELISA及RT-PCR对部分核心靶点及抑炎因子表达进行检测.结果 得到"麻黄-黄芩-黄芪-鱼腥草"配伍的活性成分 86 个,潜在靶点 505 个.甲型流感病毒相关的疾病靶点 1531 个.药物与疾病的交集靶点 175 个.GO富集获得424 个条目,KEGG通路富集获得 202 个条目,涉及PI3K-Akt信号通路、流感通路、COVID-19 通路、C型凝集素受体信号通路、TNF信号通路、IL-17 信号通路、凋亡通路、Th17 分化等多个流感相关的通路.实验结果表明,中药干预后可以改善感染小鼠一般状态及感染诱发的结肠缩短,减轻肺指数与肺组织病理损伤,下调核心靶点中促炎因子 TNF-α、IL-6、MAPK3、IL-1βmRNA 的表达、上调抑炎因子IL-10的表达.结论 基于千金三黄汤加减的"麻黄-黄芩-黄芪-鱼腥草"配伍可以多成分、多途径发挥抗甲型流感病毒的作用,可能通过TNF-α、IL-6、MAPK3、IL-1β、Akt1 等核心靶点调控PI3K-Akt信号通路、TNF信号通路、IL-17 信号通路等减轻甲型流感病毒所致的肺组织免疫炎性损伤,初步证实了该配伍治疗甲型流感病毒感染的部分作用靶点及对感染小鼠的保护作用.

ObjectiveProbiotics can modulate immune responses to resist influenza infection. This study aims to evaluate the anti-viral efficacy of B. dorei.MethodsC57BL/6J mice were infected with influenza virus together with treatment of PBS vehicle, B. dorei, or oseltamivir respectively. Anti-influenza potency of B. dorei and the underlying mechanism were determined by measuring survival rate, lung viral load and pathology, gene expression and production of cytokines and chemokines, and analysis of gut microbiota.ResultsAdministration of B. dorei increased (by 30%) the survival of influenza-infected mice, and improved their weight loss, lung pathology, lung index, and colon length compared to the vehicle control group. B. dorei treatment reduced (by 61%) the viral load of lung tissue and increased expression of type 1 interferon more rapidly at day 3 postinfection. At day 7 postinfection, B. dorei-treated mice showed lower local (lung) and systemic (serum) levels of interferon and several proinflammatory cytokines or chemokines (IL-1β, IL-6, TNF-α, IL-10, MCP-1 and IP-10) with a efficacy comparable to oseltamivi treatment. B. dorei treatment also altered gut microbiota as indicated by increased levels of Bacteroides, Prevotella, and Lactobacillus and decreased levels of Escherichia, Shigella, and Parabacteroides.ConclusionB. dorei has anti-influenza effect. Its working mechanisms involve promoting earlier interferon expression and down-regulating both local and systemic inflammatory response. B. dorei changes the composition of gut microbiota, which may also contribute to its beneficial effects.

Purpose Many studies have shown that chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is associated with asthma. The purpose of this meta-analysis was to evaluate the role of serum YKL-40 in the diagnosis and differential diagnosis of asthma, severity grading, and determination of disease state. Methods The PubMed, Ovid, and Cochrane databases were searched. A total of 17 articles involving 5696 subjects were included in this meta-analysis. Results The results showed that the level of YKL-40 was significantly higher in asthmatic patients than in the normal group regardless of age and residential location, and increased with severity and acute exacerbation (p < 0.05). YKL-40 levels were significantly different between chronic obstructive pulmonary disease (COPD) and asthma, and also between asthma-COPD overlap syndrome (ACO) and asthma (p < 0.05). Conclusion YKL-40 may act as a potential serological marker for the diagnosis of asthma, assessment of severity, indicator of the disease state, and differential diagnosis of COPD, ACO, and asthma.