Asthma is a complex and heterogeneous disease presenting with a wide range of phenotypes. While prior studies have highlighted the importance of gut microbiota in asthma development, the extent of their influence varies. The exact causal links between gut microbiota and asthma remain to be fully understood, and the role of blood cell perturbation responses as potential mediators in this relationship remains unclear. To elucidate the connections between gut microbiota, blood cell perturbation responses, and asthma, we utilized data from comprehensive genome-wide association studies (GWAS). Our investigation covered six distinct asthma phenotypes: unspecified asthma, eosinophilic asthma, allergic asthma, childhood asthma, non-allergic asthma, and obesity-related asthma. Employing Mendelian randomization (MR) techniques, we evaluated the causal associations among gut microbiota, blood cell perturbation responses, and these asthma phenotypes, primarily using inverse variance weighting (IVW) for statistical analysis. Furthermore, we examined the potential mediating effects of blood cell perturbation responses on the relationship between gut microbiota and asthma. Our comprehensive analysis uncovered significant interactions among gut microbiota, blood cell perturbation responses, and asthma. We pinpointed five specific blood cell perturbation responses that play a crucial role in modulating the progression of three distinct asthma phenotypes. Our investigation yields compelling evidence of causal connections between gut microbiota and asthma, with blood cell perturbation responses serving as pivotal mediators in this pathway.

BACKGROUND:Polygonum cuspidatum is a Chinese medicine commonly used to treat phlegm-heat asthma. However, its anti-asthmatic active ingredients and mechanism are still unknown. The aim of this study was to predict the active ingredients and pathways of Polygonum cuspidatum and to further explore the potential molecular mechanism in asthma by using network pharmacology.METHODS:The active ingredients and their targets related to Polygonum cuspidatum were seeked out with the TCM systematic pharmacology analysis platform (TCMSP), and the ingredient-target network was constructed. The GeneCards, DrugBank and OMIM databases were used to collect and screen asthma targets, and then the drug-target-disease interaction network was constructed with Cytoscape software. A target protein-protein interaction (PPI) network was constructed using the STRING database to screen key targets. Finally, GO and KEGG analyses were used to identify biological processes and signaling pathways. The anti-asthmatic effects of Polygonum cuspidatum and its active ingredients were tested in vitro for regulating airway smooth muscle (ASM) cells proliferation and MUC5AC expression, two main symptoms of asthma, by using Real-time PCR, Western blotting, CCK-8 assays and annexin V-FITC staining.RESULTS:Twelve active ingredients in Polygonum cuspidatum and 479 related target proteins were screened in the relevant databases. Among these target proteins, 191 genes had been found to be differentially expressed in asthma. PPI network analysis and KEGG pathway enrichment analysis predicted that the Polygonum cuspidatum could regulate the AKT, MAPK and apoptosis signaling pathways. Consistently, further in vitro experiments demonstrated that Polygonum cuspidatum and resveratrol (one active ingredient of Polygonum cuspidatum) were shown to inhibit ASM cells proliferation and promoted apoptosis of ASM cells. Furthermore, Polygonum cuspidatum and resveratrol inhibited PDGF-induced AKT/mTOR activation in ASM cells. In addition, Polygonum cuspidatum decreased H2O2 induced MUC5AC overexpression in airway epithelial NCI-H292 cells.CONCLUSION:Polygonum cuspidatum could alleviate the symptoms of asthma including ASM cells proliferation and MUC5AC expression through the mechanisms predicted by network pharmacology, which provides a basis for further understanding of Polygonum cuspidatum in the treatment of asthma.

Objectives: Benzo(a)pyrene (BaP) is a ubiquitous air pollutants, and BaP exposure leads to a risk of respiratory diseases. The oversecretion of airway mucus and high expression of mucin 5AC (MUC5AC) are associated with common respiratory disorders caused by air pollution. We aimed to investigate the effect of BaP on MUC5AC expression, especially the mechanisms by which BaP induces MUC5AC gene expression. Methods: The human airway epithelial cell NCI-H292 was used to test the effects of BaP on the expression of MUC5AC in vitro. MUC5AC mRNA and protein expression were assessed with real-time quantitative PCR, immunochemistry, and western blotting. A luciferase assay was conducted to detect the activity of the promoter. The total cellular ROS and mitochondrial ROS were measured by corresponding probes. Small-interfering RNAs were used for gene silencing. AhR-overexpressing cell lines were constructed by transfection with AhR overexpression lentivirus. Results: We found that BaP stimulation upregulated the MUC5AC mRNA and protein levels and activated the ERK pathway. Suppressing ERK with U0126 (an ERK inhibitor) or knocking down ERK with siRNA decreased BaP-induced MUC5AC expression. The luciferase activity transfected with the MUC5AC promoter and cAMP-response element (CRE) was increased after BaP treatment, whereas CREB siRNA suppressed the BaP-induced overexpression of MUC5AC. In addition, BaP increased mitochondrial ROS production, and Mito-TEMP, a mitochondrial ROS inhibitor, inhibited BaP-induced MUC5AC expression and ERK activation. BaP increased the mRNA levels of CYP1A1 and CYP1B1, while Alizarin, a CYP1s inhibitor, suppressed the effects of BaP, including the MUC5AC overexpression, ERK activation and mitochondrial ROS generation. BaP induced the translocation of aryl hydrocarbon receptor (AhR) from the cytoplasm to the nucleus. SiRNA-mediated knockdown or chemical inhibition of AhR decreased the BaP-induced expression of MUC5AC, while the overexpression of AhR significantly enhanced the BaP-induced expression of MUC5AC. ITE, an endogenous AhR ligand, also upregulated the mRNA and protein expression of MUC5AC. Furthermore, resveratrol treatment inhibited the BaP-induced MUC5AC overexpression, AhR translocation, mitochondrial ROS production and ERK pathway activation. Conclusion: Here, we highlighted the crucial role of AhR/mitochondrial ROS/ERK pathway activation in BaP-induced MUC5AC overexpression and identified resveratrol as a promising drug to reduce BaP-induced MUC5AC overexpression.

目的 探讨芪仙汤提取物对苯并芘(BaP)诱导的气道上皮细胞黏蛋白(MUC)5AC的抑制作用及其可能的机制.方法 以人支气管黏液上皮细胞NCI-H292细胞株为研究对象,用BaP刺激细胞构建MUC5AC升高模型(模型组),分别用芪仙汤提取物240 μg/mL(低浓度组)和480 μg/mL(高浓度组)处理细胞株,空白组予二甲基亚砜(DMSO)处理.采用CCK-8法检测芪仙汤提取物处理后细胞活性的变化,实时荧光定量PCR检测MUC5AC和细胞色素P450 1A1(CYP1A1)mRNA水平,免疫印迹法检测MUC5AC、CYP1A1、细胞外信号调节激酶(ERK)1/2、磷酸化ERK(p-ERK)1/2、相对分子质量为90 000核糖体S6激酶(RSK)和磷酸化p90 RSK(p-p90 RSK)蛋白质表达水平,荧光探针检测细胞内活性氧(ROS)水平.结果 浓度≤480 μg/mL的芪仙汤提取物对NCI-H292细胞株活力无显著影响.与模型组相比,芪仙汤低、高浓度组MUC5AC蛋白质和MUC5AC mRNA水平均显著降低(P＜0.05或0.01),ROS荧光强度值均显著降低(P＜0.05或0.01),CYP1A1 mRNA水平均显著降低(P值均＜0.01),p-ERK 1/2和p-p90 RSK蛋白质水平亦显著降低(P值均＜0.01).结论 芪仙汤可下调BaP诱导的人气道上皮细胞MUC5AC基因和蛋白质高水平表达,其机制与抑制芳香烃受体活化介导的ROS和ERK通路激活相关.

Background: MUC5AC was recently identified to play important roles in the proliferation and metastasis of malignant mucinous lung tumor cells. Resveratrol (Res), a natural compound with anticancer effects in lung cancer cells, has been reported to inhibit mucin production in airway epithelial cells. This study aimed to investigate the inhibitory effect of Res on MUC5AC expression in lung mucinous adenocarcinoma cells and the potential mechanisms. Methods: Mucus-producing A549 human lung carcinoma cells were used to test the effects of Res on SPDEF and MUC5AC expression. Gene and protein expression was assessed by real-time quantitative PCR (qPCR), immunofluorescence and western blotting assays. SPDEF lentivirus was used to upregulate SPDEF expression levels in mucus-producing A549 human lung carcinoma cells. Cell proliferation was assessed by Cell Counting Kit-8 (CCK8) assay. Results: Res decreased MUC5AC expression in an SPDEF-dependent manner in mucus-producing A549 human lung carcinoma cells, and this change was accompanied by decreased ERK expression and AKT pathway activation. Moreover, SPDEF was found to be overexpressed in lung adenocarcinoma (LUAD), especially in mucinous adenocarcinoma. In-vitro functional assays showed that overexpression of SPDEF reduced the chemosensitivity of A549 cells to cisplatin (DDP). In addition, Res treatment increased A549 cell chemosensitivity to DDP by inhibiting the SPDEF-MUC5AC axis. Conclusion: Our results indicate that the SPDEF-MUC5AC axis is associated with DDP sensitivity, and that Res decreases SPDEF and MUC5AC expression by inhibiting ERK and AKT signaling in A549 cells, which provides a potential pharmacotherapy for the prevention and therapeutic management of mucinous adenocarcinoma.

最近几年研究发现,一种固有免疫细胞——2型ILC(ILC2),它能够在早期即参与哮喘气道炎症反应及固有免疫应答,对组织重塑、修复也起重要作用.目前认为,ILC2可作为Th2的"镜像细胞",能分泌大量的IL-13、IL-5、IL-4及IL-9等细胞因子,并与哮喘不同效应细胞相互作用,从而影响哮喘的发生与发展.因此,文章将从不同效应细胞与ILC2之间的相互作用为切入点,探讨ILC2与哮喘发病机制的联系.

总结虎杖的化学成分及其治疗呼吸系统疾病的研究进展.虎杖的主要入药部位为根和根茎,主要通过止咳化痰的功效治疗呼吸系统疾病.虎杖治疗呼吸系统疾病的现代药理研究主要集中于白藜芦醇和大黄素2种成分.目前对于虎杖的功效研究主要包括抑菌,抗菌,抗病毒,抑制气道炎症、重塑,抗氧化,抑制平滑肌增殖,改善肺血管重构,抑制肺纤维化.此外,虎杖具有抗寄生虫、减轻放射性肺损伤的作用.

The aim of the study was to evaluate the significance of hypomagnesemia in patients with coronavirus disease 2019 (COVID-19) and clarify its possible pathogenesis. A retrospective cohort study was conducted by reviewing 83 patients hospitalized in Guanggu district, Wuhan Third Hospital, China. Clinical histories, laboratory findings and outcome data were collected. Eighteen patients had hypomagnesemia during hospitalization. Fourteen patients were in the critical group and six died. In the critical group, serum magnesium (0.72 ± 0.15 mmol/L) was much lower than that in the moderate and severe groups. At the same time, we also found that several indicators are correlated with the level of magnesium. The level of magnesium was positively associated with the lymphocyte count (r = 0.203, P = 0.004) and platelet count (r = 0.217, P = 0.002) but negatively related to the levels of CRP (r = -0.277, P = 0.000), LDH (r = -0.185, P = 0.011) and α-hydroxybutyrate dehydrogenase (r = -0.198, P = 0.008) in the critical group. Hypomagnesemia might increase symptoms and may be associated with mortality in COVID-19 by affecting enzyme activity and activating the inflammatory response. Thus, magnesium might play a key role in the pathogenesis of COVID-19.

Background Pulmonary rehabilitation is a crucial part of the nonpharmacological treatment of stable chronic obstructive pulmonary disease (COPD), but management remains problematic. WeChat could serve as a useful tool in patient management. Baduanjin is a popular exercise in China that is usually applied in pulmonary rehabilitation, which has been confirmed to be effective in improving lung function and life quality. Objective This study aimed to explore the efficiency of WeChat in the management of Baduanjin exercise in COPD patients. Methods A total of 200 patients from the respiratory department of Putuo Hospital participated in the Baduanjin rehabilitation project from September 2018 to October 2019, and were randomly assigned to the WeChat and control groups and followed up using the WeChat platform or telephone for 12 weeks. The frequency of Baduanjin exercise, lung function (percentage of forced expiratory volume in 1 second predicted, FEV1% predicted), and COPD assessment test (CAT) scores were collected and compared between the two groups. The number of message exchanges and a satisfaction survey on the WeChat platform were used to assess the feasibility of WeChat management outside the hospital. Results The Baduanjin exercise frequency significantly differed between the control group and WeChat group (F=33.82, P<.001) and across various time points (F=214.87, P<.001). After the follow-up on WeChat, there were fewer patients not performing Baduanjin exercise. The FEV1% predicted value significantly differed before and after Baduanjin exercise in the control group (Z=−3.686, P<.001) and the WeChat group (Z=−6.985, P<.001). A significant difference in the FEV1% predicted value was observed after Baduanjin exercise between the two groups (Z=−3.679, P<.001). The CAT score significantly differed before and after Baduanjin exercise in the control group (Z=−4.937, P<.001) and the WeChat group (Z=−5.246, P<.001). A significant difference in the CAT score was observed after Baduanjin exercise between the two groups (Z=−5.246, P<.001). The number of completed Baduanjin exercises, lung function, and CAT scores in active patients were higher than those in nonactive patients. All satisfaction survey items were scored with more than 4 points. Among the items, the highest score (mean 4.54, SD 0.77) was for continued WeChat management, followed by the effective management of Baduanjin exercise (mean 4.46, SD 0.87). The patients in the WeChat group showed much higher enthusiasm for and compliance with Baduanjin exercise, resulting in better life quality and lung function. The patients were very satisfied with the WeChat management because of the obvious curative effect and home feeling. Conclusions The WeChat platform provided a feasible, effective, and sustainable management plan for Baduanjin rehabilitation. Trial Registration Chinese Clinical Trial Registry ChiCTR1900028248; http://www.chictr.org.cn/showprojen.aspx?proj=46995

含SAM尖端结构域的E26转化特异性因子(SAM pointed domain cintaining Ets transcription factor,SPDEF)是Ets转录因子家族的成员之一.SPDEF又称为前列腺源性Ets因子(Prostate-derived Ets factor,PDEF),最初在前列腺癌中发现,在前列腺癌进展过程中发挥重要作用,作为前列腺特异性抗原基因(PSA)启动子的非雄激素依赖性转录激活因子.目前研究发现SPDEF在前列腺癌、乳腺癌和肺癌等不同组织中发挥抑制肿瘤或促进肿瘤的作用,但其具体机制仍未完全阐明.本文主要介绍SPDEF的结构和SPDEF在不同肿瘤中的调控机制,预期SPDEF在肿瘤中的重要作用,为相关肿瘤的防治提供了新思路.

目的:评价芪仙清鸣颗粒治疗支气管哮喘缓解期的疗效和安全性.方法:采用随机、双盲、对照、多中心的临床研究方法.将200例支气管哮喘缓解期患者按照1:1的比例随机分为对照组和试验组.在两组均在使用沙美特罗替卡松粉吸入剂(舒利迭)50μg/250μg治疗的基础上,试验组给予芪仙清鸣颗粒,对照组给予模拟颗粒,疗程6个月.评价两组治疗前后疗效及安全性.结果:两组治疗后中医证候疗效评分、呼出气一氧化氮水平及1年内急性发作次数均较治疗前显著下降(P＜0.01,P＜0.05),一秒率、第1秒用力呼气量、第1秒用力呼气量占预计值百分比、哮喘控制测试评分均显著升高(P＜0.01),且试验组治疗前后差值优于对照组(P＜0.01,P＜0.05).本研究中不良反应共发生9次(5.1％),均为胃肠道反应.结论:芪仙清鸣颗粒治疗哮喘缓解期的临床疗效显著,安全无严重不良反应,值得临床推广.

目的 探讨羟基喜树碱(HCPT)对肺癌A549细胞增殖、凋亡的影响及其机制.方法 以肺癌A549细胞为研究对象,分别用0、5、10μmol/L的HCPT处理细胞,将细胞分为对照组、HCPT-5组、HCPT-10组.采用CCK-8法检测细胞增殖能力,采用流式细胞术检测细胞凋亡情况,采用生物荧光法检测Caspase-8活性,采用Western blotting法检测Bcl-2、Bcl-xl和β-catenin蛋白表达.结果 与对照组相比,HCPT-5组和HCPT-10组的细胞生存率降低,且HCPT-10组细胞生存率低于HCPT-5组(P均<0.01).HCPT-5组和HCPT-10组细胞凋亡率均高于对照组,且HCPT-10组细胞凋亡率高于HCPT-5组(P均<0.01).与对照组相比,HCPT-10组的Bcl-2蛋白表达均下降(P<0.01);HCPT-5组和HCPT-10组的Bcl-xl蛋白表达下降(P<0.05或0.01).HCPT-5组和HCPT-10组的Caspase-8活性均高于对照组(P均<0.01).HCPT-5组和HCPT-10组的β-catenin蛋白表达均低于对照组(P均<0.05).结论 HCPT可抑制A549肺癌细胞的增殖、促进其凋亡,其机制可能与抑制β-catenin的表达有关.

Objective This study aimed to investigate the relationship between CLPTM1L gene and lung cancer 95-D cells sensitivity to gemcitabine,and to explore its potential mechanism of action. Methods Overexpression of lentivirus against CLPTM1L gene was constructed and infected with lung cancer 95-D cells;Cells were divided into the CLPTM1L overexpression group and con-trol group;The proliferation of cells in the overexpressing and control groups after gemcitabine treatment was detected by CCK-8;The changes of CLPTM1L gene and protein were detected by real-time PCR,Western blot and immunochemiluminescence;The changes of caspase-3/7 and caspase-9 activities were detected by bioluminescence;Western blot was used to detect the changes of p-4E-BP1 protein. Results The expression of CLPTM1L gene( P =0. 036) and its protein ( P <0. 01) was significantly increased after CLPTM1L overexpressed lentivirus-infected 95 -D cells;Compared with the control group,the proliferation of CLPTM1L overex-pressing group after gemcitabine treatment was increased(P <0. 01);The activity of caspase activity showed that the activities of caspase-3/7 and caspase-9 in the CLPTM1L overexpression group were significantly lower than those in the control group(P<0. 01);The phosphorylated level of 4E-BP1 protein in the CLPTM1L overexpression group was significantly higher than that in the control group. Conclusion Overexpression of CLPTM1L can reduce the sensitivity of lung cancer cells to gemcitabine. Its mechanism may be to increase the phosphorylation level of 4E-BP1.