Cancer remains one of the leading causes of death globally. The enhanced glycolytic activity of tumor cells drives malignant progression, making glycolysis inhibition a promising therapeutic strategy. The glycolysis-associated gene stanniocalcin 1 (STC1) has been shown to influence glycolytic capacity and promote tumor growth in several cancers, yet its role remains poorly understood. In particular, whether STC1 regulates glycolytic capacity in gastric cancer (GC) has not been explored. In this study, we investigated the role of STC1 across cancer types using multiple online databases. We analyzed STC1 expression patterns and their associations with patient survival and prognosis. We further examined the immunological role of STC1 by correlating its expression with immune checkpoints, tumor stemness, immunomodulators, and immune cell infiltration. Additionally, we used small interfering RNA (siRNA) to assess the effects of STC1 on glycolysis and malignant progression in GC cells. Our analysis revealed that STC1 is highly expressed across multiple tumor types and that this elevated expression correlates with poor prognosis. In addition, STC1 expression was positively associated with immune cell infiltration, suggesting a potential role in remodeling the tumor microenvironment (TME). In GC, high STC1 expression was also linked to reduced survival. Knockdown of STC1 in GC cells reduced PI3K/Akt phosphorylation, downregulated the glycolytic enzymes HK2 and LDHA, decreased glycolytic capacity, and inhibited proliferation, invasion, and migration. These findings suggest that STC1 may regulate glycolysis in GC and could serve as both a prognostic biomarker and a therapeutic target, acting through its involvement in glucose metabolism and immune modulation. Targeting STC1 to suppress glycolysis may therefore represent a novel approach for GC therapy.

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.

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.

The environmental pollutant benzo[a]pyrene (BaP) can induce cytochrome P450 family 1 subfamily A (CYP1A) or generate metabolic products that disrupt the balance of oxidative stress, triggering inflammatory responses in the lungs and leading to tissue damage. Flavonoids, known for their natural anti-inflammatory and antioxidant properties, are potential targets for intervention. This study used phenacetin, a specific substrate probe for CYP1A, to evaluate the inhibitory effects of 40 flavonoids on CYP1A. Structure-activity relationship analysis revealed that introducing hydroxyl groups at positions 3- and 6-enhances CYP1A inhibition. Notably, 3,6-dihydroxyflavone (DHF) emerged as a significant inhibitor of CYP1A. In vitro experiments confirmed that DHF effectively inhibits BaP-induced cytochrome P450 family 1 subfamily A member 1 (CYP1A1) in airway epithelial cells and shows dose-dependent inhibition of intracellular and mitochondrial reactive oxygen species (ROS) production. In summary, DHF is a promising CYP1A inhibitor and a potential anti-inflammatory candidate for preventing and treating CYP1A-mediated lung diseases.

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.

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.

Microwave ablation (MWA) is a key alternative therapy to conventional surgery for the treatment of lung cancer. In addition to eliminating local tumors, MWA may promote antitumor immunological responses, such as abscopal effects in distant lesions. However, the intensity of MWA is limited and the underlying mechanisms are not well-defined. The present study assessed the impact of MWA on immune cell subsets and cytokines in patients with lung cancer. A total of 45 patients with lung cancer who underwent percutaneous lung tumor MWA were enrolled. Peripheral blood samples were collected before and 24 h after MWA and changes in immune cell subsets [lymphocytes, CD3+, CD4+ and CD8+ T cells, B cells and natural killer (NK) cells] and serum cytokine levels (IL-1 beta, IL-2, IL-4-6, IL-8, IL-10, IL-12p70, IL-17A and F, IL-22, TNF-alpha, TNF-beta and IFN-gamma) were assessed by flow cytometry and ELISA. The number of total lymphocytes, CD4+ T and NK cells in the peripheral blood significantly decreased 24 h after MWA, while number of CD8+ T cells remained stable, leading to a higher proportion of CD8+ T cells. In addition, the serum levels of IL-2, IL-1 beta, IL-6, IL-12p70, IL-22, TNF-alpha and IFN-gamma were significantly increased 24 h after MWA, indicating a T helper 1 type immune response. The immune response in patients with advanced stage disease was comparable with patients in the early stage group; however, the number of total lymphocytes and CD3+ T cells significantly decreased and the ratio of CD4/CD8 and IL-2 levels significantly increased. The early immune response after MWA may contribute to systemic antitumor immunity in patients with both early and advanced disease. Thus, MWA may exhibit potential as a local therapy and trigger abscopal effects in distant lesions in patients with lung cancer.

Butyrylcholinesterase (BChE) is widely expressed in multiple tissues and has a vital role in several key human disorders, such as Alzheimer's disease and tumorigenesis. However, the role of BChE in human disorders has not been investigated. Thus, to quantitatively detect and visualize dynamical variations in BChE activity is essential for exploring the biological roles of BChE in the progression of a number of human disorders. Herein, based on the substrate characteristics of BChE, we customized and synthesized three near-infrared (NIR) fluorescent probe substrates with cyanine-skeleton, and finally selected a NIR fluorescence probe substrate named CYBA. The CYBA demonstrated a significant increase in fluorescence when interacting with BChE, but mainly avoided AChE. Upon the addition of BChE, CYBA could be specifically hydrolyzed to TBO, resulting in a significant NIR fluorescence signal enhancement at 710 nm. Systematic evaluation revealed that CYBA exhibited exceptional chemical stability in complex biosamples and possessed remarkable selectivity and sensitivity towards BChE. Moreover, CYBA was successfully applied for real-time imaging of endogenous BChE activity in two types of nerve-related living cells. Additionally, CYBA demonstrated exceptional stability in the detection of complex biological samples in plasma recovery studies (97.51%-104.01%). Furthermore, CYBA was used to construct a high-throughput screening (HTS) method for BChE inhibitors using human plasma as the enzyme source. We evaluated inhibitory effects of a series of natural products and four flavonoids were identified as potent inhibitors of BChE. Collectively, CYBA can serve as a practical tool to track the changes of BChE activity in complicated biological environments due to its excellent capabilities.

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.

The study aimed to investigate the immunomodulatory effect of Qixian Decoction (QXT) in an asthmatic model. In this study, ovalbumin (OVA)-induced asthma in female SPF BALB/c mice was established. Mice were randomly divided into four groups (n = 8): a control group, an OVA model group, a low-dose Qixian Granules (KLL) group, and a high-dose Qixian Granules (KLH) group. Mice in the KLL and KLH groups were given the Qixian Granules at a dose of 8 and 16 g/kg, respectively. After the treatment, the lung pathology was evaluated. The expression of inflammatory factors was determined. Serum metabolomics was used to investigate the overall regulation of QXT on the metabolism of asthmatic mice. Our data showed that QXT significantly increased the expression levels of Th1-related interferon-γ, Treg-related interleukin (IL)-10, and transforming growth factor-β1 while decreasing Th1-related tumor necrosis factor α levels in bronchoalveolar lavage fluid, and Th2-related IL-4 and IL-5 levels in serum when compared with the model group (all p < 0.05). Serum metabolomics revealed 28 potential biomarkers associated with nine pathways. Compared with the control group, 19 different metabolites in the KLL group and 18 different metabolites in the KLH were reversed. QXT's therapeutic effect against asthma might be related to glycerophospholipid metabolism and arachidonic acid metabolism. In conclusion, QXT could ameliorate inflammation of the OVA-induced asthmatic mice, mainly by regulating the expression of immune-related factors, probably through regulating the Th1/Th2 immune balance and promoting the proliferation of Treg.

PURPOSE:The aim of this study was to observe the expression of interleukin (IL)-17 and intercellular adhesion molecule (ICAM)-1 in conjunctivochalasis (CCH) and to analyze the correlations between cytokines and the severity of CCH. METHODS:Serum samples were collected from 22 patients with CCH and 18 normal controls (NCs). The Ocular Surface Disease Index, tear film break-up time, Schirmer I test, and corneal fluorescein staining were used to evaluate the ocular surface signs and symptoms. The concentrations of IL-17, IL-23, and ICAM-1 in serum and cellular supernatants were measured by enzyme-linked immunosorbent assays, and the gene expression levels of cytokines were measured by a quantitative real-time polymerase chain reaction. The relationships between serum concentrations of IL-17, IL-23, and ICAM-1 with clinical ocular surface parameters in CCH were analyzed using the Spearman correlation analysis. RESULTS:The concentrations of IL-17 and ICAM-1 in serum and cellular supernatants of CCH were significantly higher than those of NCs (all P < 0.001). The concentrations of IL-23 in serum and cellular supernatants of CCH showed no significant difference from those of NCs ( P > 0.05). The mRNA expression levels of IL-17 and ICAM-1 in conjunctival fibroblasts of CCH were significantly higher than those of NCs (all P < 0.001). The mRNA expression of IL-23 in conjunctival fibroblasts of CCH was higher than that of NCs, without a significant difference ( P > 0.05). Furthermore, the serum concentrations of IL-17 and ICAM-1 were positively correlated with Ocular Surface Disease Index and fluorescein staining (all P < 0.05), and negatively correlated with break-up time and Schirmer I test of CCH (all P < 0.05). CONCLUSIONS:The expression levels of IL-17 and ICAM-1 were significantly increased in CCH serum and associated with the disease severity. We postulate that IL-17 and ICAM-1 may play a role in the pathogenesis of CCH. IL-17 and ICAM-1 antagonists may be a potential treatment option for CCH in the future.

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.

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.