Oxaliplatin resistance is a key challenge in gastric cancer therapy. This study explored how bufalin, an active component of Chansu, reverses this resistance. We found that bufalin targets the transcription factor YBX1, which is upregulated in resistant cells. YBX1 activates STC1 expression, leading to PI3K/Akt pathway activation, increased HK2 levels, and enhanced glycolysis—all contributing to resistance. Bufalin inhibits this YBX1/STC1/glycolysis axis. Using in vitro assays (proliferation, apoptosis, glycolysis measurement) and in vivo models, we demonstrated that bufalin suppresses glycolysis and restores oxaliplatin sensitivity. Mechanistic studies (RNA-seq, ChIP, SPR, etc.) confirmed the direct YBX1-bufalin interaction. Our work reveals YBX1/STC1-mediated glycolysis as a novel resistance mechanism and identifies bufalin as a promising therapeutic agent to overcome it.

BACKGROUND:Elevated palmitic acid (PA) levels have been associated with increased asthma risk, but its pathogenic role remains unclear. This study aims to investigate the relationship between serum PA levels and asthma severity and explores the pro-inflammatory effects of PA on airway epithelial cells and the underlying mechanism. METHODS:Serum samples were collected from asthmatic patients, and the concentrations of PA were quantified by ELISA. An HDM-induced mouse model of asthma was established and treated with PA. RNA sequencing and metabolomic profiling were used to identify PA-responsive genes and metabolites in airway epithelial cells, and key targets were validated by qPCR, Western blot, and ELISA. RESULTS:We found that elevated serum PA levels correlated with worse lung function, higher blood neutrophil percentages, and increased steroid needs in asthma patients. In a murine asthma model, PA exacerbated airway inflammation, hyperresponsiveness, and neutrophil infiltration. In vitro, PA stimulated airway epithelial cells to express high levels of neutrophil chemokines (CXCL2/CXCL8) via Src-ERK pathway activation. In addition, metabolomic analyses revealed that PA triggered pro-inflammatory metabolic reprogramming in airway epithelial cells, characterized by dysregulation of acylcarnitine/fatty acid β-oxidation, sphingolipid signaling, and arachidonic acid metabolism. Using of CD36 inhibitors significantly suppressed pro-inflammatory chemokines expression, Src/ERK signaling activation, and metabolic reprogramming in airway epithelial cells, as well as in the asthma mouse model. CONCLUSIONS:our study demonstrated elevated PA exacerbates airway inflammation in asthma by inducing neutrophil chemokine expression and metabolic reprogramming in airway epithelial cells, providing novel insights into the pathophysiology of metabolically dysregulated asthma.

INTRODUCTION:Qixian Decoction (QXT), a traditional Chinese medicine formula, exerts favorable therapeutic effects on asthma, but its underlying mechanisms remain incompletely elucidated. MATERIALS AND METHODS:This study combined network pharmacology and experimental validation. Employing the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), we screened active compounds of QXT and their targets. A herbcompound- target network was constructed. DEGs were recognized from the GSE161245 asthma dataset. Molecular docking was utilized to validate the interaction of key compounds with selected core targets. The effects of QXT on the Potential Vanilloid 1 (TRPV1)/Phosphatidylinositol 3-Kinase-Protein Kinase B (PI3K-Akt)/Hypoxia-Inducible Factor-1α (HIF-1α) axis and Epithelial- Mesenchymal Transition (EMT) were evaluated using in vivo (asthmatic mice) and in vitro (TGF-β-stimulated 16HBE cells) models. RESULTS:A total of 83 active compounds and 308 potential targets were identified, with significant enrichment observed in the PI3K-Akt pathway. Key targets (IGF1R, CDK6, and EGFR) were positively correlated with TRPV1. Luteolin, quercetin, and EGCG stably bind to their targets. QXT suppressed TRPV1, p-AKT, and HIF-1α, and ameliorated airway hyperresponsiveness and EMT in vivo and in vitro. DISCUSSION:QXT could alleviate asthma airway hyperresponsiveness and remodeling by inhibiting the TRPV1/PI3K-Akt/HIF-1α axis and EMT. The active compounds potentially exerted their therapeutic effects through multi-target mechanisms. CONCLUSION:QXT alleviated asthma airway remodeling and hyperresponsiveness via suppressing the TRPV1/PI3K-Akt/HIF-1α signaling axis and EMT, providing a scientific basis for its clinical application.

RATIONALE:Eosinophilic granulomatosis with polyangiitis (EGPA) is a small- to medium-vessel vasculitis commonly associated with asthma and eosinophilia. Misdiagnosis as isolated asthma may delay recognition and treatment. PATIENT CONCERNS:A patient with a long history of asthma presented with persistent respiratory symptoms and a pulmonary mass initially presumed to be asthma-related pathology. DIAGNOSIS:Clinical evaluation, laboratory findings of eosinophilia, and imaging supported the diagnosis of EGPA rather than isolated asthma. INTERVENTIONS:The patient received glucocorticoid therapy (methylprednisolone) combined with mepolizumab. OUTCOMES:Treatment resulted in rapid symptomatic improvement and radiological resolution of the pulmonary mass within 1 month. LESSONS:This case highlights the diagnostic challenge of distinguishing EGPA from long-standing asthma and supports the role of targeted biologic therapy in achieving effective disease control.

BACKGROUND AND PURPOSE:Microwave ablation (MWA) has demonstrated promising potential in instigating an anti-tumor immune response, potentially resulting in the regression of distant tumors. Nevertheless, the observed abscopal effect remains modest, and its underlying mechanism remains poorly elucidated. This study aims to systematically examine the utilization of α-PD-L1 to enhance the abscopal effect induced by MWA and to comprehensively investigate the associated mechanisms. METHODS:The Lewis lung cancer model was employed to investigate the abscopal effect of MWA and α-PD-L1 co-treatment. The maturation status of bone marrow-derived dendritic cells (BMDCs) was observed after stimulating with the fragments of tumor cells harvested by microwave treatment. Flow cytometry analysis was employed to scrutinize the ratio of T cells and dendritic cells, along with the quantification of IFN-γ and GzmB expression levels. The expression of CXCL9 or PD-L1 was detected by immunofluorescence. RESULTS:Local MWA treatment on one site of tumor did not yield a significant reduction in the volume of distant tumors. However, when combined with intraperitoneal α-PD-L1 injection, a notable abscopal effect was induced, resulting in decreased distant tumor volume and prolonged survival in mice. Flow cytometry analysis revealed an increase in infiltrating and activated CD8+ T cells in distant tumors, with up-regulation of IFN-γ and GzmB expression. Notably, the expression of CXCR3 was increased in CD8+ T cells. The mRNA and protein levels of CXCL9 were elevated within distant tumors, concomitant with increased infiltration of macrophages. Moreover, dendritic cells (DCs) in tumor-draining lymph nodes (TDLNs) exhibited enhanced maturation. Additionally, in vitro experiments showed enhanced maturation of BMDCs following stimulation with fragments of Lewis cells harvested via microwave treatment. CONCLUSIONS:MWA exhibited the potential to stimulate systemic immune responses, it did not lead to a significant abscopal effect. However, the combination of MWA with α-PD-L1 treatment effectively induced the occurrence of the abscopal effect. This phenomenon appears to be linked to the activation of cytotoxic T lymphocytes (CTLs), phagocytosis by macrophages, and the maturation of DCs, facilitated by a cytokine network involving IFN-γ and CXCL9.

Airway remodeling, involving fibroblast activation and collagen deposition, is a hallmark of asthma. The pollutant Benzo(a)pyrene (BaP), an aryl hydrocarbon receptor (AhR) activator, is associated with increased asthma severity, but its role in remodeling remains unclear. This study investigates whether BaP exacerbates remodeling by enhancing epithelial-fibroblast crosstalk through an AhR-mediated pathway and identifies key mediators. We found BaP exposure significantly upregulated growth differentiation factor 15 (GDF15) expression and secretion from airway epithelial cells in an AhR-dependent manner, as AhR directly bound to the GDF15 promoter. Consequently, conditioned media from BaP-treated epithelial cells promoted fibroblast activation, marked by elevated α-smooth muscle actin (α-SMA) and type I collagen (COL1A1) levels, which were reduced by GDF15 knockdown. In vivo, BaP co-exposure worsened allergen-induced airway remodeling, with greater collagen deposition and higher GDF15, α-SMA, and COL1A1 expression. Consistently, recombinant GDF15 directly activated lung fibroblasts and stimulated collagen production. Critically, inhibition of AhR by epigallocatechin gallate (EGCG) attenuated BaP-induced GDF15 expression and remodeling in vivo, a effect associated with reduced AhR expression. In conclusion, these findings demonstrate that BaP aggravates airway remodeling via epithelial-fibroblast crosstalk mediated by the AhR-GDF15 axis, highlighting a potential target for treating pollutant-exacerbated asthma.

Traditional Chinese medicine (TCM) establishes that the kidney serves vital systemic functions and its deficiency represents a fundamental factor influencing various diseases, including asthma. The kidney-tonifying method represents a widely implemented clinical approach in TCM to address kidney deficiency. This study hypothesized that bone marrow mesenchymal stem cells (BMSCs) function as key contributors to the kidney-tonifying method. An ovalbumin (OVA)-induced asthma mouse model received treatment with the traditional kidney-tonifying formula, Qi-Xian decoction (QXD). QXD demonstrated significant therapeutic efficacy, enhanced BMSC proliferation in mouse bone marrow, and facilitated their migration to lung tissues. Inhibition of the CXCL12/CXCR4 axis diminished the QXD-induced migration of endogenous BMSCs and reduced QXD’s efficacy in asthma treatment. QXD-containing serum enhanced BMSC proliferation and promoted CXCL12-induced BMSC migration in vitro. These findings indicate that endogenous BMSCs may serve as a crucial mediator in the therapeutic effects of the kidney-tonifying method. Furthermore, the mild and sustained stimulation of production and enhanced homing of endogenous BMSCs presents a potential novel approach for effective asthma treatment.

BACKGROUND:Obstructive sleep apnea (OSA) is a prevalent disorder posing significant health hazards. Studies have suggested an association between trace elements and OSA; however, the causal relationship of this association remains unclear. METHODS:This study investigated the potential causal relationship between magnesium and OSA, with magnesium status evaluated through magnesium-related single nucleotide polymorphisms (SNPs) and magnesium depletion score (MDS). Mendelian Randomization (MR) and the National Health and Nutrition Examination Survey (NHANES) were used to mitigate confounders and ensure a more robust assessment. RESULTS:MR analysis indicated a significant protective effect of magnesium against OSA (odds ratio [OR]<1, P < 0.05). A reverse MR analysis of OSA on magnesium did not show significant causal effects (P > 0.05). NHANES analysis further demonstrated a strong positive correlation between MDS and OSA, with participants scoring above 1 exhibiting a 64 % increased likelihood of developing OSA (OR = 1.64, 95 % confidence interval [CI]: 1.32-2.05, P < 0.001). Adjusted multivariable logistic regression models confirmed the robustness of this association (Model II: OR = 1.36, 95 % CI: 1.08-1.72, P = 0.018; Model III: OR = 1.30, 95 % CI: 1.03-1.63, P = 0.045). Subgroup and interaction analysis revealed no statistically significant interactions (P > 0.05). CONCLUSION:We confirmed the causal relationship between magnesium and OSA, underscoring magnesium's role in OSA pathogenesis and suggesting that MDS may serve as a promising biomarker for identifying high-risk populations. Further studies on the biological mechanisms linking magnesium deficiency to OSA may contribute to its treatment.

BACKGROUND:Despite promising individual benefits, the combined efficacy of Baduanjin and Tri-Ball Breath training as a home-based pulmonary rehabilitation in Chronic Obstructive Pulmonary Disease (COPD) subjects remains unexplored. OBJECTIVE:The aim of the study was to evaluate the effect of combining Baduanjin (a traditional Chinese exercise) and Tri-Ball Breath training into a home-based pulmonary rehabilitation regimen for COPD patients. METHODS:A multicenter randomized controlled trial was conducted, enrolling 240 moderate COPD patients from 10 hospitals. Participants were randomly assigned to four groups: Baduanjin group, Tri-Ball Breath training group, Combination training group, and control group. The intervention lasted 12 weeks. Data were collected at baseline, 4 weeks, 8 weeks, 12 weeks, and 24 weeks post-intervention. RESULTS:After 12 weeks, the 6-Minute Walk Distance (6MWD) significantly improved in the Baduanjin group and the Tri-Ball Breath training group ( p <0 .05), with the most significant improvement observed in the Combination training group ( p <0 .01) compared to the control group. FEV1% increased in the Baduanjin group and the Tri-Ball Breath training group ( p <0 .05) and markedly improved in the Combination training group ( p <0 .01). No significant differences were observed in the COPD Assessment Test (CAT), the Modified British Medical Research Council Scale (mMRC), or the Traditional Chinese Medicine symptom scores at 4-week and 8-week. The mMRC scores improved significantly in the Baduanjin group and the Combination training group at 24-week ( p <0 .05). The vital signs of all participants were stable from the baseline, and no statistic difference was observed among the four groups at all visits. CONCLUSION:Our findings underscore the significance of incorporating Baduanjin and respiratory muscle training into the long-term management of COPD patients. By fostering continuous improvements in pulmonary function (FEV1%) and exercise capacity (6MWD), these interventions may help to mitigate disease progression and enhance patients' quality of life.

The overexpression of mucin 5AC (MUC5AC) induced by interferon-beta (IFN-β) plays a critical role in airway mucus hypersecretion and contributes to the mortality associated with coronavirus disease 2019 (COVID-19) patients. Epigallocatechin gallate (EGCG), a polyphenol derived from green tea, has demonstrated potential as a therapeutic agent for the treatment of coronavirus-related diseases. This study aimed to investigate the regulatory effects of EGCG on IFN-β-induced MUC5AC overexpression and to elucidate its underlying molecular mechanisms. We found that IFN-β-induced MUC5AC overexpression was associated with the activation of the signal transducer and activator of transcription 1 (STAT1) and extracellular signal-regulated kinase (ERK) signaling pathways. The use of STAT1 or ERK inhibitors significantly attenuated IFN-β-induced MUC5AC overexpression. EGCG treatment markedly inhibited IFN-β-induced MUC5AC overexpression and suppressed activation of the STAT1 and ERK signaling pathways. Subsequent research revealed that EGCG binds to Janus kinase 1 (JAK1) and inhibits its kinase activity, leading to reduced phosphorylation of STAT1 and ERK. The use of JAK1 inhibitors reproduced the effects observed with EGCG treatment. Structural analysis indicated that the methyl gallate of the EGCG molecule was crucial for its inhibitory activity. In vivo studies demonstrated that EGCG effectively suppressed IFN-β-induced mucus hypersecretion and MUC5AC overexpression, along with inhibition of the associated signaling pathways. In conclusion, EGCG inhibits IFN-β-induced MUC5AC overexpression by suppressing JAK1 kinase activity, thereby blocking activation of the STAT1 and ERK signaling pathways.

Asthma is a common disease that affects millions of people but has no cure. Resveratrol (Res) has been confirmed to be effective against asthma; however, in vivo experiments had shown that Res administration by either oral or intraperitoneal injection had low absorption, leading to a bad efficacy. Aerosol therapy is widely used in asthma treatment, which can achieve effective concentrations locally. The efficacy of atomized Res for asthma has not been evaluated yet. Therefore, this article aimed to evaluate the effects of Res aerosol inhalation on asthma and explore the mechanisms involved. Ovalbumin (OVA) was used to construct an asthma mouse model. Different concentrations of Res solution were atomized with an ultrasonic nebulizer, and the asthmatic mice were treated. Hematoxylin and eosin (HE) staining was used to evaluate the degree of airway inflammation and airway remodeling in the mice. Serum from each group of mice was collected for IgE and total antioxidant capacity (T-AOC) detection. Real-time quantitative PCR, immunohistochemistry, and western blotting were used to detect the expression levels of the target genes and proteins. Compared with the asthma group, the airway inflammation scores were significantly decreased in the low- or high-dose Res group. The airway remodeling parameters of the WAm/Pbm, WAmuc/Pbm, and WAi/Pbm ratios were significantly reduced. The expression of serum IgE, IL-5 mRNA, and p-STAT6 protein was significantly decreased, and serum T-AOC was increased in the Res group. Consistently, Res treatment significantly inhibited p-STAT6 expression induced by recombinant human IL-13 in 16HBE cells. Results suggest that Res nebulization therapy can improve airway inflammation, airway remodeling, airway allergy, and antioxidant capacity in asthmatic mice, which may be mediated by a STAT6-related pathway.

Background: The pathogenesis of COVID-19, including thrombocytopenia, has not been fully clarified. The lungs are a major organ of platelet production and thrombocytopenia induced by severe COVID-19 was proposed. Methods: the change of platelet level was analysed with clinical parameters in 95 hospitalized COVID-19 patients in Wuhan Third Hospital. The production of platelets in the lungs was explored in an ARDS rat model. Results: The level of platelets was negatively correlated with disease severity and was recovered with disease improvement. The non-survivors were accompanied by lower levels of platelet. The odds ratio (OR) of the valley level of the platelet count (PLTlow) was greater than 1, suggesting that PLTlow could be a death exposure factor. The platelet/lymphocyte ratio (PLR) was positively associated with severity of COVID-19, and the platelet/lymphocyte ratio threshold of 248.5 was best correlated with death risk (sensitivity 0.641 and specificity 0.815). To demonstrate the possible biogenesis aberration of platelet in lungs, an LPS-induced ARDS rat model was applied. Lower level of platelet in peripheral and less production of platelet from lungs in ARDS were demonstrated. Though megakaryocyte (MK) number in ARDS lungs is higher than controls, the immature platelet fraction (IPF) in postpulmonary blood is still at the same level as prepulmonary in ARDS rat, indicating that ARDS rats generated fewer platelets in lungs. Conclusion: Our data suggested that COVID-19-induced severe lung inflammation may impair platelet production in the lung. Thrombocytopenia may be mainly caused by platelet consumption for multiorgan thrombosis; however, biogenesis aberration of platelet in the lung induced by diffuse interstitial pulmonary damage cannot be ruled out.

Colorectal adenoma (CRA) is a premalignant lesion of colorectal cancer. The current treatment is surgical resection, but CRA is prone to recurrence, and there is no safe and effective drug to prevent adenoma recurrence and canceration. Recent studies have shown that natural compounds in plants have favorable antitumor effects. According to preclinical studies, natural polyphenols can regulate different signal pathways and targets to play a role in the treatment of CRA, which is closely related to its inhibition of proliferation, induction of apoptosis, inhibition of inflammation and oxidative stress, and regulation of intestinal flora. Natural polyphenols are potential candidates for CRA therapy due to their remarkable efficacy and safety. In the present review, attention was paid to the experimental research progress of natural polyphenols extracted from numerous plants in the treatment of CRA in the last 10 years. The present review provided new guidance for the study of CRA, clarified the therapeutic role of polyphenols in CRA, and evaluated for the first time, to the best of our knowledge, the therapeutic potential of natural polyphenols to treat CRA by targeting multiple genes and signal pathways and epigenetic modification.

Introduction: Qi-Xian Decoction (QXD), a traditional Chinese medicine (TCM) formula consisting of eight herbs, has been clinically used to treat asthma. However, the underlying mechanisms have not been completely elucidated. This study aimed to combine metabolomics and network pharmacology to reveal the mechanism of action of QXD in asthma treatment.Methods: An ovalbumin (OVA)-induced asthma mouse model was constructed to evaluate the therapeutic effects of QXD. Serum metabolomics and network pharmacology were combined to study the mechanism of anti-asthma action as well as the potential target, and related biological functions were validated.Results: The QXD treatment has demonstrated significant protective effects in OVA-induced asthmatic mice, as evidenced by its ability to inhibit inflammation, IgE, mucus overproduction, and airway hyperreactivity (AHR). Metabolomic analysis has revealed a total of 140 differential metabolites associated with QXD treatment. In addition, network pharmacology has identified 126 genes that are linked to the effects of QXD, including TNF, IL-6, IL1β, STAT3, MMP9, EGFR, JUN, CCL2, TLR4, MAPK3 and MAPK8. Through comprehensive gene-metabolite interaction network analysis, seven key metabolites have been identified and associated with the potential anti-asthmatic effect of QXD, with palmitic acid (PA) being the most notable among them. In vitro validation studies have confirmed the gene-metabolite interaction involving PA, IL-6, and MAPK8. Furthermore, our research has demonstrated that QXD treatment can effectively inhibit PA-promoted IL-6 expression in MH-S cells and reduce PA concentration in OVA-induced asthmatic mice.Conclusion: The regulation of metabolic pathways by QXD was found to be associated with its anti-asthmatic action, which provides insight into the mechanism of QXD in treating asthma.

Background Asthma is a chronic airway inflammatory disease characterized by airway inflammation, mucus hypersecretion, airway hyper-reactivity. Sanzi Yangqin Decoction (SZYQD) is widely prescribed for asthma treatment. Its anti-asthma activities have been reported in animal model, but the exact mechanism and targets of SZYQD in asthma treatment have not been fully elucidated. Methods A network pharmacological approach was used to predict the active components, targets, and signalling pathways of SZYQD in asthma, including potential target prediction, protein‒protein interaction (PPI) network construction and analysis, and Gene Ont (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The active ingredients were identified from the SZYQD, and were molecular docked according to the results of network pharmacology. A mouse model of asthma induced by ovalbumin (OVA) and lipopolysaccharide (LPS) was constructed to evaluate the therapeutic effect of SZYQD. Furthermore, the effects of SZYQD and its active ingredients were tested in vitro for regulating inflammation and MUC5AC expression (two main pathophysiologic abnormalities of asthma) in macrophages and airway epithelial cells by using Real-time PCR and western blotting. Results A total of 28 active ingredients and 111 HUB genes were screened in the relevant databases, including three key ingredients (luteolin, β-carotene, and Sinapine) and nine core target genes (JUN, CTNNB1, IL10, TP53, AKT1, STAT3, TNF, IL6 and EGFR). KEGG and GO analysis indicated that the potential anti-asthmatic mechanisms of SZYQD were related to PI3K-Akt signalling pathway and response to lipopolysaccharide, etc. In the in vivo asthmatic model, our findings demonstrated that SZYQD exerted a protective effect against asthmatic mice induced by OVA and LPS through the inhibition of inflammation and mucus overproduction. Consistently, cell experiments showed that the SZYQD extract or the key active ingredients luteolin significantly decreased lipopolysaccharide (LPS)-induced IL-6 expression and activation of the NF-κB pathway in macrophages. In addition, SZYQD extract or luteolin inhibited activation of the AKT pathway and expression of MUC5AC induced by EGF in airway epithelial cells. Conclusion The anti-asthmatic mechanism of SZYQD might be associated with inhibiting inflammation and airway mucus hypersecretion by regulating the NF-κB and AKT signalling pathways as predicted by network pharmacology, which provides more evidence for the application of SZYQD in asthma treatment.

电子烟可导致急性肺损伤，其诊断需排除其他病因后根据电子烟吸食史及弥漫性肺泡损伤的影像特征来确诊，类固醇皮质激素治疗有效。本病例在患者及家属拒绝有创检查的情况下，依据吸食电子烟病史及肺泡弥漫性损伤的影像特征，排除其他病因后确诊，及时使用皮质类固醇药物治疗后，取得了较好的治疗效果。

Objective To observe the effects of Qixian Decoction（composed of Astragali Radix,Herba Epimedii,Morindae Officinalis Radix,etc.） on airway inflammation and mucus secretion in asthmatic mice exposed to the atmospheric pollutant benzopyrene（BaP）,and to explore the molecular mechanisms.Methods Female BALB/c mice were randomly divided into blank group,asthma group[ovalbumin（OVA）sensitization],BaP group（OVA+BaP）and Qixian Decoction group(OVA+BaP+Qixian Decoction 37.5 g·kg -1 ),with 10 mice in each group.The mouse asthma model was replicated using the OVA sensitization method,and exposed to atmospheric pollution was simulated by BaP nasal drip method.The levels of lung inflammation and mucus secretion were detected by HE and AB-PAS staining;the mRNA expressions of interleukin 4（IL-4）and interleukin 13（IL-13）in lung tissue were detected by qRT-PCR,and the protein expressions of mucin 5AC（MUC5AC）and phosphorylated ERK（p-ERK）in lung tissue were detected by immunohistochemistry;the lung tissue reactive oxygen species（ROS）levels were measured by the DCFH-DA probe method.Results Compared with the blank group,the inflammatory cells around airway and blood vessels in asthma group were significantly increased;the airway mucosa was interrupted and discontinuous,and the inflammation score was significantly increased（P＜0.01）;the mRNA expressions of IL-4 and IL-13 in mice lung tissue were significantly up-regulated（P＜0.05）;the airway mucus secretion of mice was significantly increased（P＜0.01）;the protein expressions of MUC5AC and p-ERK in airway of mice were significantly up-regulated（P＜0.01）;the ROS level in mouse lung tissue was significantly increased（P＜0.05）.Compared with the asthma group,the inflammatory cell infiltration in BaP group was further aggravated,the alveolar septum was significantly broken,and the inflammatory score was significantly increased（P＜0.01）;the mRNA expressions of IL-4 and IL-13 in mouse lung tissue were significantly up-regulated（P＜0.01）;the airway mucus in mice was significantly increased（P＜0.01）;the protein expressions of MUC5AC and p-ERK in mice airway were significantly up-regulated（P＜0.05,P＜0.01）;and the ROS level in mice lung tissue was significantly increased（P＜0.01）.Compared with the BaP group,the inflammatory cell infiltration and airway mucosal continuity in the mice in the Qixian Decoction group were significantly improved,and the inflammation score was significantly reduced（P＜0.01）;the mRNA expressions of IL-4 and IL-13 in mice lung tissue were significantly down-regulated（P＜0.01）;the airway mucus secretion in mice was significantly reduced（P＜0.01）;the protein expressions of MUC5AC and p-ERK in mice airway were significantly down-regulated（P＜0.05,P＜0.01）;the ROS level in mice lung tissue was significantly reduced（P＜0.01）.Conclusion Qixian Decoction has effects in relieving airway inflammation and mucus secretion in mice with asthma exacerbated by atmospheric pollutants BaP and the anti-lung damage effects were possibly related to its inhibition of ROS and ERK pathways.

Benzo[a]pyrene (BaP) is a common air pollutant that has been reported to cause oxidative stress and carcinogenesis. Wogonin, a flavonoid compound extracted from the roots of Scutellaria baicalensis, has been found to possess a variety of pharmacological activities, including anti-inflammatory and anti-cancer effects. The purpose of this study was to examine the ability of wogonin to alleviate the cytotoxicity induced by BaP in human airway epithelial cells and explore the corresponding mechanism. Our study found that wogonin treatment inhibited DNA damage and reactive oxygen species overproduction induced by BaP in human airway epithelial cells. In vitro enzyme assays showed that wogonin significantly inhibited the enzymatic activity of CYP1A1. In addition, wogonin decreased the basal level of CYP1A1 and inhibited the CYP1A1 overexpression induced by BaP, whereas overexpression of CYP1A1 partially reversed the effect of wogonin on BaP-induced DNA damage. Meanwhile, a CYP1A1 inhibitor and CYP1A1 knockdown also showed these same effects. Further studies showed that wogonin regulates CYP1A1 expression by inhibiting CDK7 and CDK9 activity. The use of CDK7 or CDK9 inhibitors decreased BaP-induced cytotoxicity and CYP1A1 expression. Finally, we found that the methoxy group of wogonin was crucial for its inhibitory activity. In conclusion, our data indicated that wogonin could effectively relieve BaP induced cytotoxicity, and its mechanism was related to the dual inhibition of CYP1A1 activity and expression.

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.