OBJECTIVE:To investigate the protective effect of N-acetylcysteine (NAC) against benzo[a]pyrene (BaP)-aggravated lung injury in asthma and to elucidate whether it is mediated through the ROS/CREB/ERK signaling pathway. METHODS:Twenty-four BALB/c mice were randomly divided into Control, Model (OVA + BaP), and Intervention (OVA + BaP + NAC) groups. An aggravated asthma model was established by ovalbumin (OVA) sensitization/challenge combined with intratracheal instillation of BaP. The NAC group received NAC via gavage. Airway inflammation and mucus secretion were assessed by H&E and PAS staining. Serum IgE levels were measured by ELISA. SOD activity and MDA content were detected using commercial kits. ROS levels in lung tissue were observed by fluorescence staining. The mRNA expression of mucin genes (MUC5AC, MUC5B, MUC16, etc.) was detected by qPCR. The protein expression of apoptosis-related markers (Bax, Bcl-2) and signaling pathway components (p-ERK1/2, p-CREB) was measured by Western Blot. RESULTS:Compared with the Model group, NAC intervention significantly alleviated airway inflammatory cell infiltration, mucus hypersecretion, and epithelial damage, and reduced serum IgE levels. Meanwhile, NAC effectively decreased ROS and MDA levels, increased SOD activity in lung tissue, reversed the BaP-induced upregulation of MUC5AC, MUC5B, and MUC16 genes, and modulated the Bax/Bcl-2 ratio to inhibit apoptosis. Mechanistically, NAC significantly inhibited BaP-induced phosphorylation of ERK1/2 and CREB. CONCLUSION:NAC can mitigate BaP-induced airway mucus hypersecretion and apoptosis, thereby alleviating asthma lung injury, by scavenging ROS and inhibiting the overactivation of the ROS/CREB/ERK signaling pathway. This study provides experimental evidence supporting NAC as a potential therapeutic strategy for preventing and treating air pollution-associated asthma.

Asthma is a heterogeneous airway disease in which chronic inflammation, epithelial barrier injury, immune-cell imbalance and airway remodeling interact to shape variable clinical phenotypes. N6-methyladenosine (m6A), the most abundant internal modification of eukaryotic mRNA, has emerged as a dynamic epitranscriptomic layer that regulates RNA splicing, export, stability, translation and decay. Recent profiling studies and mechanistic experiments indicate that m6A patterns and m6A regulators are altered in lung tissue, airway epithelial cells, airway smooth muscle cells and immune cells in asthma. These changes influence type 2 inflammation, the balance between T helper 1 (Th1) and T helper 2 (Th2) cells, the balance between T helper 17 (Th17) and regulatory T (Treg) cells, macrophage polarization, epithelial ferroptosis, ciliary function, mitochondrial stress, pollutant responses and structural remodeling. This Review synthesizes current evidence linking m6A writers, erasers and readers to asthma pathobiology, highlights context-dependent and sometimes opposing functions of key regulators such as METTL3, FTO and ALKBH5, and discusses how m6A signatures may inform biomarker discovery and therapeutic development. We also outline major translational barriers, including cell-type specificity, target validation, assay standardization and safety of pharmacologic m6A modulation.

ETHNOPHARMACOLOGICAL RELEVANCE:Qufeng Xuanbi Formula (QFXBF), a traditional Chinese medicine prescription used for asthma-like respiratory disorders, has shown anti-asthmatic activity. However, whether it attenuates allergic airway remodeling through innate immune-metabolic regulation remains unknown. AIM OF THE STUDY:This study aimed to determine whether QFXBF alleviates house dust mite (HDM)-induced allergic airway inflammation and remodeling through targeting the STING/HIF-1α/glycolysis axis, and to evaluate the specific inhibitory potential of its constituent tectorigenin on STING-mediated immunometabolic signaling. MATERIALS AND METHODS:An HDM-induced allergic asthma model was established in male C57BL/6 mice by intranasal sensitization and challenge, followed by oral administration of QFXBF at 12.5, 25, and 50 g/kg/day or dexamethasone at 2 mg/kg/day. Airway hyperresponsiveness, lung histopathology, mucus secretion, collagen deposition, α-SMA expression, inflammatory mediators in BALF and serum, and glycolytic metabolic indices were evaluated. BSMCs were stimulated with IL-4 and LPS, both at 5 ng/mL, and treated with QFXBF at 2, 4, and 8 mg/mL. Cell proliferation, migration, glucose consumption, lactate production, RT-qPCR, Western blotting, and immunofluorescence were performed to assess airway smooth muscle activation and metabolic reprogramming. Transcriptomic analysis of lung tissue, STING overexpression, HIF-1α pharmacological inhibition, LC-MS/MS-based identification of tectorigenin, molecular docking, and molecular dynamics simulations were further used to investigate the STING/HIF-1α/glycolysis axis and the potential STING-targeting activity of tectorigenin. RESULTS:QFXBF markedly reduced airway hyperresponsiveness, inflammatory infiltration, and collagen deposition in HDM-challenged mice, accompanied by decreased asthma-related markers in bronchoalveolar lavage fluid and serum. QFXBF also downregulated STING, HIF-1α, and key glycolytic enzymes at both mRNA and protein levels in lung tissue. In IL-4+LPS-stimulated BSMCs, QFXBF dose-dependently suppressed proliferation and migration, reduced glucose utilization and lactate accumulation, and concurrently inhibited STING/HIF-1α and glycolysis-associated factors. Mechanistically, QFXBF attenuated HIF-1α activity and glycolytic flux through suppression of STING. Liquid chromatography-based analysis identified tectorigenin as a bioavailable constituent of QFXBF. In STING-overexpressing BSMCs, tectorigenin significantly reduced STING expression, proliferative activity, and lactate metabolism, supporting STING inhibition as a key pharmacological basis of QFXBF. CONCLUSION:QFXBF can alleviate allergic remodeling by suppressing the STING/HIF-1α-mediated glycolytic program. Tectorigenin may act as a potential STING inhibitor that disrupts innate immune-metabolic signaling, providing mechanistic support for QFXBF-derived therapeutic strategies in asthma.

ETHNOPHARMACOLOGICAL RELEVANCE:COPD, marked by coughing, sputum production, and wheezing, is categorized as "Lung Distension" in Traditional Chinese Medicine (TCM). The combined use of Suzi Jiangqi Decoction and Sanzi Yangqin Decoction, known as Jia Wei Su Zi Jiang Qi Formula (JWSZJQF), is a common treatment for Lung Distension with phlegm accumulation in the lungs. It is particularly effective for symptoms like excessive phlegm and chest tightness. However, the specific active components of JWSZJQF and their molecular mechanisms in addressing mucus hypersecretion in COPD remain unclear, requiring further investigation and validation. AIM OF THE STUDY:This study aims to identify the potential targets and signaling pathways of JWSZJQF in treating COPD-associated mucus hypersecretion using UHPLC-Q-Orbitrap MS/MS, network pharmacology, and in vitro experimental verification. MATERIALS AND METHODS:All plant names were verified through WorldFloraOnline (www.worldFloraonline.org) and MPNs (http://mpns.kew.org). First, the effective components of JWSZJQF were identified and analyzed using UHPLC-Q-Orbitrap MS/MS, supplemented by data from TCMSP. Network pharmacology analysis was used to determine the potential targets and pathways of JWSZJQF in COPD treatment. A mucus hypersecretion cell model was created using IL-17 cytokine, and the effectiveness of JWSZJQF in reducing mucus hypersecretion was assessed through immunofluorescence assay, Western blotting, and quantitative real-time polymerase chain reaction (qPCR). Lastly, a prospective study was conducted to collect data from 30 inpatients with AECOPD between September 2023 and July 2024. Serum samples before and after treatment were analyzed to validate the findings. RESULTS:A total of 864 active components were identified, with 79 potential COPD therapeutic targets confirmed based on the top 30 active components, including TNF, IL-6, and AKT1. The involved KEGG pathways included the IL-17 and NF-κB signaling pathways. In vitro experiments showed that JWSZJQF inhibited mucin (MUC5AC) secretion at both mRNA and protein levels. Additionally, JWSZJQF modulated i-κBα and p65 expression in the NF-κB pathway. Compared to the control group, patients treated with JWSZJQF exhibited lower levels of IL-17 and MUC5AC in their serum. CONCLUSION:This study preliminarily explored the mechanisms of JWSZJQF in treating COPD-associated mucus hypersecretion through UHPLC-Q-Orbitrap MS/MS, network pharmacology, in vitro experiments, and clinical observation. The main active components and potential targets were identified, laying a scientific foundation for further research.

Objective: To evaluate the effects of Fu Tu Sheng Jin Rehabilitation Formula (FTSJRF) on airway inflammation, mucus secretion, and immunoreaction in a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-induced mouse model. Methods: Forty-two mice were randomly divided into seven groups: normal, D1, D3, D10, D10H, D10M and D10L, according to the days of modeling and different dosages of FTSJRF. D1, D3, D10, D10H, D10M and D10L group mice were intratracheally administered with 15 mu g SARS-CoV-2 spike protein; mice in the D10H, D10M, and D10L groups were intragastrically administered FTSJRF (46, 23 and 11.5 g/kg, respectively). Observe the pathological changes in lung tissues, expression of inflammatory factors, and mucins in different groups of mice using HE and PAS staining methods, as well as ELISA and RT-qPCR. Flow cytometry was used to detect T helper 17 (Th17)/regulatory T (Treg) cells and T helper 1(Th1)/T helper 2 (Th2) lymphocyte ratios and the proportions of conventional myeloid dendritic cells (cDCs), plasma cell-like DCs, CD80 and CD86 cells in mouse spleens. Results: HE and PAS staining showed that, compared to that in the normal group, the lung tissue of the D1 group mice showed a significant inflammatory damage response, whereas the D3 and D10 groups showed a gradual recovery trend. Groups D1 and D3 showed mild mucus secretion, whereas the D10 group had excessive mucus secretion. The D10 group of mice displayed increased levels of IL-4, TNF-alpha, IL-33 and mucin genes such as MUC1, MUC4, etc, and FTSJRF inhibited the expression of these molecules, mucus secretion and lung damage in SARS-CoV-2 spike protein-induced mouse model. Flow cytometry results showed a decrease in the number of cDCs and an abnormal recovery of DC mature cells in the D10 group. FTSJRF increased the number of cDCs and promoted DC maturation. A higher Th17/Treg ratio was observed in the D3 and D10 groups than in the normal group, whereas this ratio decreases under the effect of FTSJRF. D10 had significantly lower Th1/Th2 ratio than normal, D1 and D3 groups, and high doses of FTSJRF increased it. Conclusion: FTSJRF mitigates airway inflammation and mucus secretion induced by SARS-CoV-2 spike protein. Additionally, FTSJRF regulates immune functions by promoting DC maturation and Th17/Treg and Th1/Th2 cell homeostasis.

Air pollutants contribute to the occurrence and development of asthma by impairing the airway epithelial barrier. However, underlying molecular mechanisms remain unknown. The present study investigated whether co‑exposure to the air pollutant benzo[a]pyrene (BaP) and ovalbumin (OVA) enhanced OVA‑induced epithelial tight junction disruption and explored the potential mechanisms involved. Asthma mouse and airway epithelial cell models were established and exposed to BaP. Lung pathology, immunoglobulin E (IgE), tight junction proteins zonula occludens‑1 (ZO‑1) and occludin, reactive oxygen species (ROS), NOD‑like receptor protein 3 (NLRP3), apoptosis‑associated speck‑like protein containing a CARD, caspase‑1, interleukin (IL)‑18 and IL‑1β were assessed by hematoxylin‑eosin staining, enzyme‑linked immunosorbent assay, western blotting, immunohistochemistry and immunofluorescence. Inhibitors of ROS and NLRP3 were used to assess their effect on ZO‑1 and occludin and downstream signaling pathways to clarify BaP‑induced damage. Lung tissue damage was exacerbated by BaP, the IgE level increased and the ZO‑1 and occludin expression reduced in both models, thereby disrupting airway epithelial tight junctions. Additionally, BaP increased ROS levels and activated the NLRP3/caspase‑1 signaling pathway. However, reducing ROS and NLRP3 restored the ZO‑1 and occludin expression and improved epithelial integrity. Airway tight junction disruption was promoted by BaP by activating the ROS‑driven NLRP3/caspase‑1 signaling pathway.

OBJECTIVE:Previous clinical studies have demonstrated that Wumei Pill (WP), a traditional Chinese medicine formula, can effectively alleviate nocturnal asthma-related anxiety and improve nighttime symptoms. The therapeutic mechanism of WP may involve the regulation of inflammatory chemokines in peripheral blood. This mechanism is potentially linked to modulation of the circadian clock gene ARNT-like protein-1 (Bmal1), but precise pathways underlying this interaction remain unclear, requiring further investigation. METHODS:Bmal1 knockout and wild-type mice were utilized to establish asthma models. Techniques such as flow cytometry, RT-PCR, and ELISA were employed to measure the levels of serum inflammatory mediators, specifically IFN-γ, CXCL16, I-TAC, and PARC. Furthermore, the pathological alterations in airway thickness were assessed. Additionally, we investigated the regulation of the Bmal1 gene and its influence on the circadian rhythm-related recruitment of leukocytes, as well as the expression patterns of downstream mediators. RESULTS:Compared to the wild-type (WT) group, the model group showed significantly higher levels of CXCL16, I-TAC, and PARC (p < 0.05), as well as a notable decrease in IFN-γ expression. WP treatment effectively normalized the levels of these inflammatory factors in the model group, indicating a regulatory effect of WP on inflammatory chemokines. CONCLUSION:The knockout of the Bmal1 gene, a crucial regulator of circadian rhythms, disrupts the circadian expression of inflammatory chemokines. Treatment with WP modulated Bmal1 expression, influencing the release of these mediators, offering a promising strategy for managing nocturnal asthma. Notably, wild-type nocturnal asthma mice exhibited significantly better control of airway inflammation compared to their Bmal1-deficient counterparts, highlighting the importance of circadian regulation in the pathophysiology of asthma.

Benzo [a]pyrene (BaP), a toxic pollutant, increases the incidence and severity of asthma. However, the molecular mechanisms underlying the effects of BaP in asthma remain unclear. In terms of research methods, we used BaP to intervene in the animal model of asthma and the human bronchial epithelial (16HBE) cells, and the involved mechanisms were found from the injury, inflammation, and airway epithelial to mesenchymal transition (EMT) in asthma. We also constructed small interfering RNAs and overexpression plasmids to knockdown/overexpress IL-6R and FOXA2 in 16HBE cells and a serotype 9 adeno-associated viral vector for lung tissue overexpression of FOXA2 in mice to determine the mechanism of action of BaP-exacerbated asthma airway EMT. We observed that BaP aggravated inflammatory cell infiltration into the lungs, reduced the Penh value, increased collagen fibres in the lung tissue, and increased serum IgE levels in asthmatic mice. After BaP intervention, the expression of FOXA2 in the lung tissue of asthmatic mice decreased, the production and secretion of IL-6 were stimulated, and STAT3 phosphorylation and nuclear translocation increased, leading to changes in EMT markers. However, EMT decreased after increasing FOXA2 expression and decreasing that of IL-6R and was further enhanced after low FOXA2 expression. Our results revealed that BaP exacerbated airway epithelial cell injury and interfered with FOXA2, activating the IL-6/IL-6R/STAT3 signaling pathway to promote airway EMT in asthma. These findings provide toxicological evidence for the mechanism underlying the contribution of BaP to the increased incidence of asthma and its exacerbations.

Objective: Mume fructus is commonly used in traditional Chinese medicine to treat nocturnal asthma symptoms. However, the molecular mechanisms underlying its effects on nocturnal asthma have not yet been established. This study evaluated the therapeutic mechanisms of Mume fructus in treating nocturnal asthma. Materials and Methods: Network pharmacology was used to investigate the chemical composition, critical targets, and potential mechanisms of action of Mume fructus in treating nocturnal asthma. “ Mume fructus ” and “nocturnal asthma” were used as keywords to search the relevant databases. The 16HBE and RAW264.7 cells were treated with various concentrations of Mume fructus and lipopolysaccharides (LPSs). Data provided included analyses of cell viability detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, cell proliferation and apoptosis detected by 5-ethynyl-2’-deoxyuridine and Hoechst 33342, messenger ribonucleic acid (mRNA) levels obtained by real-time polymerase chain reaction, and protein expression detected by Western blotting. Additionally, immunofluorescence was used to detect nuclear translocation. Results: Network pharmacology analyses were mainly enriched in nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK) pathway, and interleukin (IL)-6. Mume fructus and LPS had no effect on viability, proliferation, and apoptosis in 16HBE and RAW264.7 cells under certain concentration conditions. Mume fructus counteracted LPS-stimulated mRNA and protein expression of IL-6. In addition, Mume fructus treatment prevented the LPS-induced phosphorylation of NF-κB and MAPK pathways, as well as the nuclear translocation of NF-κB p-p65 in the 16HBE and RAW264.7 cells. Conclusions: Mume fructus can treat nocturnal asthma by regulating the NF-κB and MAPK pathways and counteracting IL-6 expression. These findings provide a scientific basis for the use of Mume fructus in the treatment of nocturnal asthma.

Ethnopharmacological relevance: Excessive secretion of airway mucus may be an important pathological factor of air pollution-induced acute asthma attacks. Treatment of airway mucus hypersecretion improves asthma aggravated by air pollutants. Qufeng Xuanbi Formula (QFXBF) has been used to treat asthma for more than 30 years. However, whether QFXBF inhibits asthmatic mucus secretion exacerbated by air pollutants has not yet been established.Aim of the study: This study aimed to evaluate the effect of QFXBF on airway mucus secretion and the mechanism of action in an air pollutant benzo[a]pyrene (BaP)-induced mouse model of aggravated asthma.Materials and methods: Ovalbumin (OVA) and BaP co-exposure were used to establish the aggravated asthma model. The average enhanced pause (Penh), serum OVA-specific IgE, and changes in lung histopathology were determined. 16HBE cells exposed to BaP, treatment with QFXBF, arylhydrocarbon receptor (AhR) signal antagonist SR1, reactive oxygen species (ROS) antagonist NAC, or extracellular signal-regulated kinase (ERK1/2) signal antagonist U0126 were established to investigate the effect of QFXBF on BaP-induced mucus secretion and its target. The mRNA and protein expression levels of MUC5AC in the lung tissue and 16HBE cells were examined. We also studied the effect of QFXBF on ROS production. Finally, the protein expression of AhR, phospho-extracellular signal-regulated kinases (p-ERK1/2), and ERK1/2 in 16HBE cells and lung tissues was determined by western blotting.Results: Administration of QFXBF significantly alleviated the pathological symptoms, including Penh, serum OVA-specific IgE, and changes in lung histopathology in a BaP-induced mouse model of aggravated asthma. QFXBF inhibited MUC5AC expression in asthmatic mice and 16HBE cells exposed to BaP. ROS production, AhR expression, and ERK1/2 phosphorylation were significantly increased in BaP-induced asthmatic mice and 16HBE cells. Signaling pathway inhibitors StemRegenin 1 (SR1), NAC, and U0126 significantly inhibitedBaP-induced MUC5AC expression in 16HBE cells. SR1 reversed Bap-induced ROS production and ERK activation, and NAC inhibited Bap-induced ERK activation. In addition, QFXBF regulated AhR signaling, inhibited ROS production, reversed ERK activation , downregulated mucus secretion to improve asthma aggravated by air pollutant BaP.Conclusions: QFXBF can ameliorate mucus secretion in BaP-induced aggravated asthmatic mice , 16HBE cells, and the specific mechanism may be related to the inhibition of the AhR/ROS/ERK signaling pathway.

目的:探究祛风宣痹方对气道上皮细胞氧化损伤的保护作用.方法:体内研究采用OVA诱导哮喘小鼠模型,体外研究采用不同浓度的H2 O2及祛风宣痹方干预人气道上皮细胞系16HBE 48 h.DCFH-DA活性氧探针检测细胞中活性氧(ROS)的生成水平;MTT(噻唑蓝)法检测细胞活力;Western blot法检测凋亡相关蛋白Bcl-2、Bax的表达水平;Annexin V-FITC/PI双染法检测细胞凋亡水平.结果:ROS结果显示,H2 O2作用后细胞内ROS生成明显增加,祛风宣痹方提取物可降低ROS水平.MTT结果显示,H2O2作用后对气道上皮细胞的抑制率随浓度增加而增大(P<0.01),祛风宣痹方水提取物和祛风宣痹方醇提取物均可减少H2O2诱导的气道上皮细胞损伤(P<0.01).Western blot结果提示,H2O2刺激后气道上皮细胞Bcl-2蛋白表达水平显著降低,Bax蛋白表达水平增高(P<0.05,P<0.01),祛风宣痹方提取物作用后可以回调H2 O2诱导的Bcl-2蛋白表达水平降低,抑制H2 O2诱导的Bax蛋白表达水平增加(P<0.05).Annexin V-FITC/PI双染法结果显示,H2 O2作用后细胞凋亡和坏死水平增高,祛风宣痹方提取物可减少细胞发生凋亡和坏死的比例.结论:祛风宣痹方可以抗氧化,减少哮喘气道上皮细胞凋亡.

目的 观察祛风宣痹方对哮喘大鼠气道炎症及MEK/ERK信号通路的影响,探讨其改善哮喘的作用机制.方法 将18只SD大鼠随机分为对照组、哮喘组和祛风宣痹方组,每组6只,采用卵清蛋白诱导哮喘模型,祛风宣痹方组予祛风宣痹方灌胃,对照组和哮喘组予等量生理盐水,连续14 d.HE染色观察大鼠肺组织病理变化,ELISA检测血清IgE、白细胞介素(IL)-6和肺泡灌洗液IL-6含量,Western blot检测肺组织MEK/ERK信号通路相关蛋白表达.将巨噬细胞RAW264.7分为对照组、脂多糖(LPS)组、祛风宣痹方组和U0126组,以LPS诱导细胞炎症反应,同时祛风宣痹方组和U0126组分别予祛风宣痹方或MEK通路抑制剂U0126干预,ELISA检测细胞培养液IL-6含量,Western blot检测细胞MEK/ERK信号通路相关蛋白表达.结果 与对照组比较,哮喘组大鼠气道壁增厚,支气管周围炎症细胞增多,血清IgE、IL-6和肺泡灌洗液IL-6含量显著增加(P<0.01),肺组织p-MEK1/2、p-ERK1/2蛋白表达显著升高(P<0.05);与哮喘组比较,祛风宣痹方组大鼠气道炎症细胞浸润减少,血清IgE、IL-6和肺泡灌洗液IL-6含量显著减少(P<0.01),肺组织p-MEK1/2、p-ERK1/2蛋白表达显著降低(P<0.05).细胞实验结果显示,与对照组比较,LPS组细胞培养液IL-6含量显著增加(P<0.01),细胞p-MEK1/2、p-ERK1/2蛋白表达显著升高(P<0.01);与LPS组比较,祛风宣痹方组细胞培养液IL-6含量显著减少(P<0.05),p-MEK1/2、p-ERK1/2蛋白表达显著降低(P<0.01).结论 祛风宣痹方能够缓解哮喘气道炎症,抑制MEK/ERK信号通路可能是其作用机制之一.

Asthma often presents with a daily rhythm; however, the underlying mechanisms remain unclear. Circadian rhythm genes have been proposed to regulate inflammation and mucin expression. Here, ovalbumin (OVA)-induced mice and serum shock human bronchial epidermal cells (16HBE) were used in in vivo and in vitro models, respectively. We constructed a brain and muscle ARNT-like 1 (BMAL1) knockdown 16HBE cell line to analyze the effects of rhythmic fluctuations on mucin expression. Serum immunoglobulin E (IgE) and circadian rhythm genes in asthmatic mice showed rhythmic fluctuation amplitude. Mucin (MUC) 1 and MUC5AC expression was increased in the lung tissue of the asthmatic mice. MUC1 expression was negatively correlated with that of the circadian rhythm genes, particularly BMAL1 (r = -0.546, P = 0.006). There was also a negative correlation between BMAL1 and MUC1 expression (r = -0.507, P = 0.002) in the serum shock 16HBE cells. BMAL1 knockdown negated the rhythmic fluctuation amplitude of MUC1 expression and upregulated MUC1 expression in the 16HBE cells. These results indicate that the key circadian rhythm gene, BMAL1, causes periodic changes in airway MUC1 expression in OVA-induced asthmatic mice. Targeting BMAL1 to regulate periodic changes in MUC1 expression may, therefore, improve asthma treatments.

Asthma is a common chronic respiratory disease. The Qufeng Xuanbi formula (QFXBF), a Chinese herbal decoction, has shown efficacy in the management of asthma. The purpose of this study was to investigate the potential therapeutic effects of QFXBF in the treatment of asthma both in vitro and in vivo. Platelet-derived growth factor (PDGF)-induced airway smooth muscle cell (ASMC) proliferation and MTT assays were used to explore the effects of QFXBF on the proliferation of ASMCs. Moreover, 40 female BALB/c mice were randomly divided into five groups: control group, ovalbumin (OVA) group, high QFXBF group, low QFXBF group, and dexamethasone (DEX) group (n = 8 per group). A mouse allergic asthma model was established using the intranasally administered OVA sensitization method. Morphological changes in the lung tissue were examined by hematoxylin and eosin (H&E) staining and Masson's trichrome staining. Finally, the protein expression of alpha-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), phospho-mitogen-activated protein kinase (p-MEK1/2), mitogen-activated protein kinase (MEK1/2), phospho-extracellular signal-regulated kinases (p-ERK1/2), and extracellular signal-regulated kinases (ERK1/2) in ASMCs and lung tissue were determined by western blotting and immunofluorescent staining assays. PDGF significantly increased the viability of ASMCs. Compared with mice in the control group, the airway walls and airway smooth muscle of mice in the OVA group were thickened, and the number of inflammatory cells around the bronchus significantly increased. Moreover, the administration of QFXBF markedly inhibited the proliferation of ASMCs and alleviated the pathological changes induced by OVA. Furthermore, the protein expressions of p-ERK1/2, p-MEK1/2, PCNA, and α-SMA were significantly increased in OVA-treated mice and PDGF-treated ASMCs. Finally, treatment with QFXBF also significantly decreased the protein expression of p-ERK1/2, p-MEK1/2, α-SMA, and PCNA. QFXBF inhibited the proliferation of ASMCs by suppressing MEK/ERK signaling in PDGF-induced ASMCs and OVA-induced mice.

Background: Many studies have assessed the potential link between interleukin-6 polymorphisms and susceptibility to allergic diseases. However, the results are still conflicting. Therefore, a comprehensive meta-analysis can not only resolve differences but also provide clues for future projects. Methods: A systematic electronic search was conducted on the databases of Web of Science, PubMed, and Cochrane Library to retrieve all published studies. Revman and Stata software were used for statistical analysis. Results: This meta-analysis included 11 studies. The results revealed that there was a statistically significant association between IL-6 rs1800795 polymorphism and the risk of asthma and allergic rhinitis in the general population. Subgroup analyses demonstrated that rs1800795 affected allergic diseases risk in different populations. Conclusion: Our findings suggested that IL-6 rs1800795 was associated with allergic diseases susceptibility among Asians and Caucasians in opposite trends, and it might influence the risk of asthma and allergic rhinitis. None of the IL-6 polymorphisms were shared risk variants of allergic diseases.

The circadian clock is closely associated with inflammatory reactions. Increased inflammatory cytokine levels have been detected in the airways of nocturnal asthma. However, the mechanisms that contribute to the nocturnal increase in inflammatory responses and the relationship with circadian clock remain unknown. Methods Inflammatory cytokine levels were measured in asthma patients with and without nocturnal symptoms. Allergic airway disease was induced in mice by ovalbumin (OVA), and different periods of light/dark cycles were used to induce circadian rhythm disorders. Serum shock was used to stimulate the rhythmic expression in human bronchial epidermal cells (16HBE). The expression and oscillation of circadian clock genes and inflammatory cytokines in 16HBE cells subjected to brain and muscle ARNT-like protein-1 (BMAL1) and Forkhead Box A2 (FOXA2) knockdown and treatment with a FOXA2 overexpression plasmid were assessed. Results Serum IL-6 was found to be significantly higher in asthmatic patients with nocturnal symptoms than those without nocturnal symptoms. The OVA-induced asthma model with a circadian rhythm disorder and 16HBE cells treated with serum shock showed an increase in IL-6 levels and a negative correlation with BMAL1 and FOXA2. The knockdown of BMAL1 resulted in a lower correlation between IL-6 and other rhythm clock genes. Furthermore, knockdown of the BMAL1 and FOXA2 in 16HBE cells reduced the expression and rhythmic fluctuations of IL-6. Conclusions Our findings suggest that there are increased IL-6 levels in nocturnal asthma resulting from inhibition of the BMAL1/FOXA2 signalling pathway in airway epithelial cells.

Abstract Purpose Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important event in the course of chronic obstructive pulmonary disease that negatively affects patients’ quality of life and leads to higher socioeconomic costs. While previous studies have demonstrated a significant association between urban air pollution and hospitalization for AECOPD, there is a lack of research on the impact of particulate matter (PM) on inflammation and coagulation in AECOPD inpatients. Therefore, this study investigated the association of changes in coagulation function and C-reactive protein (CRP) with PM levels in the days preceding hospitalization. Patients and methods We reviewed the medical records of AECOPD patients admitted to Putuo Hospital, Shanghai University of Traditional Chinese Medicine, between March 2017 and September 2019. We analyzed the association of coagulation function and CRP level in AECOPD patients with PM levels in the days before hospitalization. Multivariate unconditional logistic regression analyses were used to evaluate the adjusted odds ratio (OR) and 95% confidence interval (CI) for the association of CRP data with hospitalization day. Kruskal–Wallis tests were used to evaluate mean aerodynamic diameter of ≥ 2.5 μm (PM2.5) exposure on the day before hospitalization; we assessed its association with changes in prothrombin time (PT) in AECOPD inpatients with different Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes. Results The peripheral blood PT of AECOPD patients with PM2.5 ≥ 25 mg/L on the day before hospitalization were lower than those of patients with PM2.5 < 25 mg/L (t = 2.052, p = 0.041). Patients with severe GOLD class exposed to greater than 25 mg/L of PM2.5on the day before hospitalization showed significant differences in PT (F = 9.683, p = 0.008). Peripheral blood CRP levels of AECOPD patients exposed to PM2.5 ≥ 25 mg/L and PM10 ≥ 50 mg/L on the day before hospitalization were higher than those of patients exposed to PM2.5 < 25 mg/L and PM10 < 50 mg/L (t = 2.008, p = 0.046; t = 2.637, p = 0.009). Exposure to < 25 mg/L of PM2.5 on the day before hospitalization was significantly associated with CRP levels (adjusted OR 1.91; 95% CI 1.101, 3.315; p = 0.024). Conclusion Exposure of patients with AECOPD to high PM levels on the day before hospitalization was associated with an increased CRP level and shortened PT. Moreover, PM2.5 had a greater effect on CRP level and PT than mean aerodynamic diameter of ≥ 10 μm (PM10). AECOPD patients with severe GOLD class were more sensitive to PM2.5-induced shortening of PT than those with other GOLD classes.