Serum metabolomics analysis of patients with chronic obstructive pulmonary disease and 'frequent exacerbator' phenotype.

Chronic obstructive pulmonary disease (COPD) exacerbations accelerate loss of lung function and increased mortality. The complex nature of COPD presents challenges in accurately predicting and understanding frequent exacerbations. The present study aimed to assess the metabolic characteristics of the frequent exacerbation of COPD (COPD­FE) phenotype, identify potential metabolic biomarkers associated with COPD­FE risk and evaluate the underlying pathogenic mechanisms. An internal cohort of 30 stable patients with COPD was recruited. A widely targeted metabolomics approach was used to detect and compare serum metabolite expression profiles between patients with COPD­FE and patients with non­frequent exacerbation of COPD (COPD­NE). Bioinformatics analysis was used for pathway enrichment analysis of the identified metabolites. Spearman's correlation analysis assessed the associations between metabolites and clinical indicators, while receiver operating characteristic (ROC) analysis evaluated the ability of metabolites to distinguish between two groups. An external cohort of 20 patients with COPD validated findings from the internal cohort. Out of the 484 detected metabolites, 25 exhibited significant differences between COPD­FE and COPD­NE. Metabolomic analysis revealed differences in lipid, energy, amino acid and immunity pathways. Spearman's correlation analysis demonstrated associations between metabolites and clinical indicators of acute exacerbation risk. ROC analysis demonstrated that the area under the curve (AUC) values for D­fructose 1,6­bisphosphate (AUC=0.871), arginine (AUC=0.836), L­2­hydroxyglutarate (L­2HG; AUC=0.849), diacylglycerol (DG) (16:0/20:5) (AUC=0.827), DG (16:0/20:4) (AUC=0.818) and carnitine­C18:2 (AUC=0.804) were >0.8, highlighting their discriminative capacity between the two groups. External validation results demonstrated that DG (16:0/20:5), DG (16:0/20:4), carnitine­C18:2 and L­2HG were significantly different between patients with COPD­FE and those with COPD­NE. In conclusion, the present study offers insights into early identification, mechanistic understanding and personalized management of the COPD­FE phenotype.

Rapid identification of chemical constituents and dynamic metabolic profile of Shenqi-Tiaoshen formula in rat plasma based on UPLC-Q-TOF/MSE.

Shenqi-Tiaoshen formula (SQTSF) is a traditional Chinese medicine (TCM) prescription that has been employed in the treatment of chronic obstructive pulmonary disease (COPD). Clinical practice has demonstrated that SQTSF is an effective prescription for stable COPD. However, owing to the complexity of TCM prescription, there is a lack of in-depth understanding of the chemical components of SQTSF and its in vivo metabolism studies. In this study, a comprehensive analytical strategy based on ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was established to identify the chemical components, the absorbed components, and the metabolites of SQTSF given by gavage in rats, and analyze their dynamic changes. As a result, 86 chemical components of SQTSF were characterized, which were mainly categorized into flavonoids, saponins, organic acids, terpenoids, etc. Among them, 13 compounds were confirmed unambiguously by reference standards. Furthermore, 20 prototype components and 46 metabolites were detected in rat plasma at different time points. It was found that one prototype component and thirteen metabolites could be detected during the entire 24 h, indicating that these compounds were slowly eliminated and thus accumulated in vivo over a prolonged duration. Interestingly, the phenomenon that three prototype components and fourteen metabolites reappeared after a period of disappearance from the plasma was found. It was also observed that different prototype components may generate the same metabolite. The metabolic processes of SQTSF in rats mainly included oxidation, reduction, hydration, demethylation, deglycosylation, methylation, acetylation, glucuronidation, glutathionylation, and associated combination reactions. Overall, the present study identified the chemical components of SQTSF and their dynamic metabolic profile in rat plasma, which provided a systematic and applicable strategy for screening and characterization of the prototype components and metabolites of TCM compound preparations.

Pingchuanning Decotion Alleviates Bronchial Asthma Airway Inflammation Through ROS/HMGB1/Beclin-1 Mediated Cell Autophagy.

Objective: Bronchial asthma is a prevalent respiratory disorder characterized by airway inflammation. This study aimed to investigate the protective effect of Pingchuanning decoction (PCN) on airway inflammation in bronchial asthma, focusing on the role of autophagy and its underlying molecular mechanism. Methods: Using an in vitro lipopolysaccharide (LPS)-induced inflammatory damage model of human airway epithelial cells (16HBE), we assessed the effect of PCN. Various experiments were performed to evaluate the expression of autophagy-related genes, autophagosome and vesicle counts, and reactive oxygen species (ROS) levels. Results: First, PCN reduced LPS-induced cellular inflammation. Second, PCN decreased the number of autophagosomes and autophagic vesicles. And third, PCN significantly reduced reactive oxygen species (ROS) levels. Most importantly, PCN also down-regulated LPS-induced expression of HMGB1, Beclin-1, and autophagy-related gene 5 (ATG5) while enhancing the expression of B-cell lymphoma 2 (Bcl-2), which further reduced the LC3II/I ratio. Conclusion: PCN reduces the 16HBE inflammatory response by inhibiting the overexpression of ROS/HMGB1/Beclin-1 mediated cell autophagy. Therefore, it may serve as a potential drug for treating bronchial asthma.

Integration of metabolomics and network pharmacology to reveal the protective mechanism underlying Qibai Pingfei capsule on chronic obstructive pulmonary disease.

In this study, we have employed metabolomics technology in combination with network pharmacology to ascertain the key metabolites and hub genes. The objective was to explore the pathway of Qibai Pingfei Capsule (QBPF) in treating COPD through metabolomics. We identified 96 differential metabolites in the lung tissues of rats belonging to control and model groups, out of which 47 were observed to be critical (VIP >2, p < 0.05). Furthermore, 16 important differential metabolites were reversed after QBPF treatment. Using network pharmacology, we identified 176 core targets of 81 drug-active ingredients. Our comprehensive analysis of network pharmacology and metabolomics enabled us to identify a core target, prostaglandin-endoperoxide synthase 2 (PTGS2), and a core metabolic pathway for glutathione metabolism. Finally, the result of molecular docking showed that PTGS2 had strong binding activity to 18 compounds including Fumarine and Kaempferol, etc.. PTGS2 is a marker of ferroptosis, so we wanted to explore whether QBPF could inhibit ferroptosis in COPD. The results showed that ferroptosis was involved in the pathogenesis of COPD, and QBPF could inhibit the occurrence of ferroptosis. In conclusion, the mechanism of QBPF for treating COPD may be related to PTGS2 expression, glutathione metabolism and ferroptosis.

Identification of ACHE as the hub gene targeting solasonine associated with non-small cell lung cancer (NSCLC) using integrated bioinformatics analysis.

Background: Solasonine, as a major biological component of Solanum nigrum L., has demonstrated anticancer effects against several malignancies. However, little is understood regarding its biological target and mechanism in non-small cell lung cancer (NSCLC). Methods: We conducted an analysis on transcriptomic data to identify differentially expressed genes (DEGs), and employed an artificial intelligence (AI) strategy to predict the target protein for solasonine. Subsequently, genetic dependency analysis and molecular docking were performed, with Acetylcholinesterase (ACHE) selected as a pivotal marker for solasonine. We then employed a range of bioinformatic approaches to explore the relationship between ACHE and solasonine. Furthermore, we investigated the impact of solasonine on A549 cells, a human lung cancer cell line. Cell inhibition of A549 cells following solasonine treatment was analyzed using the CCK8 assay. Additionally, we assessed the protein expression of ACHE, as well as markers associated with apoptosis and inflammation, using western blotting. To investigate their functions, we employed a plasmid-based ACHE overexpression system. Finally, we performed dynamics simulations to simulate the interaction mode between solasonine and ACHE. Results: The results of the genetic dependency analysis revealed that ACHE could be identified as the pivotal target with the highest docking affinity. The cell experiments yielded significant findings, as evidenced by the negative regulatory effect of solasonine treatment on tumor cells, as demonstrated by the CCK8 assay. Western blotting analysis revealed that solasonine treatment resulted in the downregulation of the Bcl-2/Bax ratio and upregulation of cleaved caspase-3 protein expression levels. Moreover, we observed that ACHE overexpression promoted the expression of the Bcl-2/Bax ratio and decreased cleaved caspase-3 expression in the OE-ACHE group. Notably, solasonine treatment rescued the Bcl-2/Bax ratio and cleaved caspase-3 expression in OE-ACHE cells compared to OE-ACHE cells without solasonine treatment, suggesting that solasonine induces apoptosis. Besides, solasonine exhibited its anti-inflammatory effects by inhibiting P38 MAPK. This was supported by the decline in protein levels of IL-1ß and TNF-α, as well as the phosphorylated forms of JNK and P38 MAPK. The results from the molecular docking and dynamics simulations further confirmed the potent binding affinity and effective inhibitory action between solasonine and ACHE. Conclusions: The findings of the current investigation show that solasonine exerts its pro-apoptosis and anti-inflammatory effects by suppressing the expression of ACHE.

Metabolic profiling of Qi-Yu-San-Long decoction in rat feces by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry combined with a post-targeted screening strategy.

Research into traditional Chinese medicine metabolism in feces is one of the key avenues to understanding the fate of traditional Chinese medicines in vivo. In this study, we used ultraperformance liquid chromatography-quadrupole time-of-flight MS in combination with a post-targeted screening strategy to identify the prototype components and metabolites in rat feces after oral administration. Based on our group's previous research, the component database of Qi-Yu-San-Long decoction (QYSLD) was established. Prototype components were screened from the fecal samples based on summarized chromatographic and MS behaviors. According to the chemical structure characteristics of related compounds, the possible metabolic pathways were inferred, and the metabolites related to QYSLD were predicted. We extracted ion chromatograms by predicting the m/z values of metabolite excimer ions and identified related metabolites based on their retention time and fragmentation behavior. A total of 93 QYSLD-related xenobiotics were confirmed or tentatively identified in rat fecal samples, and the results indicated that the main metabolic pathways of QYSLD were hydrolysis, deglycosylation, oxidation, reduction, decarboxylation, methylation and acetylation. This study presents a rapid method for identifying the prototype components and metabolites, and offers valuable insights into the biotransformation profiling of QYSLD in rat feces.

Correlation of Coagulation Dysfunction with Infection and Hypercapnia in Acute Exacerbation of COPD Patients.

Background: This study aims to explore the factors influencing the coagulation function of patients with chronic obstructive pulmonary disease (COPD) and its effects on thrombosis. Methods: A total of 155 COPD patients, including 118 patients with acute exacerbation of COPD (AECOPD) and 37 patients with stable COPD (SCOPD), were enrolled in this study. Meanwhile, 50 patients with gastrointestinal polyps found during physical examination and treated with surgery in the same period were enrolled as the control group. The basic data, routine blood tests, C-reactive protein (CRP), procalcitonin (PCT), and coagulation indexes of the three groups were collected, as well as arterial blood gas indexes of AECOPD patients. Results: The differences in erythrocyte count and hemoglobin among groups were not statistically significant. Compared with the SCOPD group and control group, white blood cell (WBC), neutrophil percentage, PCT, CRP, prothrombin time (PT), and fibrinogen (FIB) in the AECOPD group increased significantly, while the international normalized ratio (INR) decreased (P < 0.05). The differences in activated partial thromboplastin time (APTT) and D-dimer among groups were not statistically significant (P > 0.05). Thrombin time (TT) in the AECOPD group was shorter than that of the control group, and PT was longer than that of the SCOPD group (P < 0.05). Five patients with AECOPD and one patient with SCOPD had venous thrombosis. Conclusion: The abnormal coagulation function in AECOPD patients is related to the degree of infection and hypercapnia, which may be a risk factor for thrombosis.

EPHX1 and GSTP1 polymorphisms are associated with COPD risk: a systematic review and meta-analysis.

Background: Chronic obstructive pulmonary disease (COPD) affects approximately 400 million people worldwide and is associated with high mortality and morbidity. The effect of EPHX1 and GSTP1 gene polymorphisms on COPD risk has not been fully characterized. Objective: To investigate the association of EPHX1 and GSTP1 gene polymorphisms with COPD risk. Methods: A systematic search was conducted on 9 databases to identify studies published in English and Chinese. The analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines (PRISMA). The pooled OR and 95% CI were calculated to evaluate the association of EPHX1 and GSTP1 gene polymorphisms with COPD risk. The I2 test, Q test, Egger's test, and Begg's test were conducted to determine the level of heterogeneity and publication bias of the included studies. Results: In total, 857 articles were retrieved, among which 59 met the inclusion criteria. The EPHX1 rs1051740 polymorphism (homozygote, heterozygote, dominant, recessives, and allele model) was significantly associated with high risk of COPD risk. Subgroup analysis revealed that the EPHX1 rs1051740 polymorphism was significantly associated with COPD risk among Asians (homozygote, heterozygote, dominant, and allele model) and Caucasians (homozygote, dominant, recessives, and allele model). The EPHX1 rs2234922 polymorphism (heterozygote, dominant, and allele model) was significantly associated with a low risk of COPD. Subgroup analysis showed that the EPHX1 rs2234922 polymorphism (heterozygote, dominant, and allele model) was significantly associated with COPD risk among Asians. The GSTP1 rs1695 polymorphism (homozygote and recessives model) was significantly associated with COPD risk. Subgroup analysis showed that the GSTP1 rs1695 polymorphism (homozygote and recessives model) was significantly associated with COPD risk among Caucasians. The GSTP1 rs1138272 polymorphism (heterozygote and dominant model) was significantly associated with COPD risk. Subgroup analysis suggested that the GSTP1 rs1138272 polymorphism (heterozygote, dominant, and allele model) was significantly associated with COPD risk among Caucasians. Conclusion: The C allele in EPHX1 rs1051740 among Asians and the CC genotype among Caucasians may be risk factors for COPD. However, the GA genotype in EPHX1 rs2234922 may be a protective factor against COPD in Asians. The GG genotype in GSTP1 rs1695 and the TC genotype in GSTP1 rs1138272 may be risk factors for COPD, especially among Caucasians.

An ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry method based on a four-step analysis strategy to investigate metabolites of Qi-Yu-San-Long decoction in rat plasma.

Metabolism is undoubtedly significantly correlated with the efficacy and safety of traditional Chinese medicine. In clinic, Qi-Yu-San-Long decoction (QYSLD) has achieved good results in the treatment of non-small-cell lung cancer (NSCLC). Nevertheless, a detailed understanding of the compounds (prototypes and metabolites) of QYSLD and its dynamic metabolic profile in plasma has not been revealed. METHODS: In this study, a rapid and sensitive method based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF/MSE ), combined with a four-step analysis strategy, was established to investigate QYSLD metabolic profile in rat plasma. RESULTS: In all, 101 xenobiotics (41 prototypes and 60 QYSLD-related metabolites) were identified in rat plasma. The research uncovered metabolic profiles of alkaloids, saponins, flavonoids, iridoids, anthraquinones, and phenylpropanoids of QYSLD in rat plasma. The dynamic changes in these xenobiotics were also observed at different time intervals. At 0.5 h after oral administration, only 15 prototypes and 11 metabolites were detected. Within 24 h, 4 prototypes and 20 metabolites can still be detected. Four prototypes and 10 metabolites had the phenomenon of emergence-disappearance-reappearance in vivo. CONCLUSION: In rat plasma, 101 xenobiotics of QYSLD were identified and their dynamic metabolic profiles were systematically delineated, which laid a material basis for further research of the pharmacodynamic substances of QYSLD inhibiting NSCLC.

The causal relationship between risk of developing bronchial asthma and frailty: a bidirectional two-sample Mendelian randomization study.

Background: A potential link between asthma and frailty has been suggested in previous studies. However, the nature of the causal relationship between these two conditions warrants further investigation. Therefore, this study assessed the bidirectional causality between asthma and frailty risk using two-sample Mendelian randomization (MR). Methods: The study data were obtained from the genome-wide association study (GWAS) dataset, with 337,159 samples representing asthma data and 175,226 samples representing frailty. The causal relationship between the two disorders was assessed by selecting the single nucleotide polymorphisms (SNPs), significantly associated with both asthma and frailty. The inverse variance weighting (IVW) method was used as the main analytical method to estimate the possible influence of causality. Sensitivity analysis was also performed using Mr-Egger intercept, funnel plot, "leave-one-out," and Cochran Q test. In addition, potential mediators were investigated by risk factor analysis. Result: The IVW method showed an increased risk of frailty due to increased genetic susceptibility factors and the number of to asthma (OR = 2.325, 95%CI:1.958-2.761; p = 6.527498e-22), while no horizontal pleiotropy was observed for the Mr-Egger intercept (p = 0.609) and the funnel plot. The Cochran Q value was 72.858, p = 0.024, and there was heterogeneity in the Cochran Q-value. No single SNP was observed for "leave-one-out" that had a biasing effect on the instrumental variables. In addition, genetic susceptibility to frailty was associated with asthma (OR = 1.088, 95%CI:1.058-1.119; p = 4.815589e-09). In the causal relationship described above, several risk factors for frailty are complex, with asthma leading to a significant reduction in physical activity endurance. Conclusion: Our findings suggest a probable positive causal effect of asthma on the risk of developing frailty, potentially mediated by reduced physical activity endurance. At the same time, a causal relationship exists between frailty and asthma. Therefore, assessment strategies for frailty should include asthma and vice versa.

The dynamic metabolic profile of Qi-Yu-San-Long decoction in rat urine using UPLC-QTOF-MSE coupled with a post-targeted screening strategy.

Qi-Yu-San-Long decoction (QYSLD) is a traditional Chinese medicine that has been clinically used in the treatment of non-small-cell lung cancer (NSCLC) for more than 20 years. However, to date, metabolic-related studies on QYSLD have not been performed. In this study, a post-targeted screening strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight full information tandem mass spectrometry (UPLC-QTOF-MSE) was developed to identify QYSLD-related xenobiotics in rat urine. The chemical compound database of QYSLD constituents was established from previous research, and metabolites related to these compounds were predicted in combination with their possible metabolic pathways. The metabolites were identified by extracted ion chromatograms using predicted m/z values as well as retention time, excimer ions, and fragmentation behavior. Overall, 85 QYSLD-related xenobiotics (20 prototype compounds and 65 metabolites) were characterized from rat urine. The main metabolic reactions and elimination features of QYSLD included oxidation, reduction, decarboxylation, hydrolysis, demethylation, glucuronidation, sulfation, methylation, deglycosylation, acetylation, and associated combination reactions. Of the identified molecules, 14 prototype compounds and 58 metabolites were slowly eliminated, thus accumulating in vivo over an extended period, while five prototypes and two metabolites were present in vivo for a short duration. Furthermore, one prototype and five metabolites underwent the process of "appearing-disappearing-reappearing" in vivo. Overall, the metabolic profile and characteristics of QYSLD in rat urine were determined, which is useful in elucidating the active components of the decoction in vivo, thus providing the basis for studying its mechanism of action.

[Bioinformatics analysis of the molecular mechanism of Qibaipingfei Capsule in the regulation of chronic obstructive pulmonary disease related immune cells].

Objective To investigate the mechanism of the Qibaipingfei Capsule regulating chronic obstructive pulmonary (COPD) related immune cells by analyzing the single-cell transcriptome sequencing (scRNA-seq) data of COPD lung tissue and the pharmacology of Qibaipingfei Capsule. Methods The scRNA-seq data of COPD lung tissue downloaded from the gene expression omnibus (GEO) was used to obtain the COPD related immune cells and the differentially expressed RNA, and the primary active molecular and target genes of Qibaipingfei Capsule were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The "active molecules-immune cells-target genes" network was constructed by mapping the target genes of Qibaipingfei Capsules to the differentially expressed RNA of COPD related immune cells, and the Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the protein-protein interaction (PPI) were administrated to analyze the molecular mechanisms of target genes. Results Twelve active molecules including quercetin, kaempferol, and formononetin of Qibaipingfei Capsule targeted multiple COPD related immune cells like macrophages, alveolar macrophages, and T cells, and genes like PPARG, JUN, HMOX1, and HIF1A which were primarily collected in pathways such as interleukin 17 signaling pathway, nuclear factor-κB (NF-κB) signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway. Conclusions The Qibaipingfei Capsule may target multiple immune cells and intervene in inflammation and immune-related pathways to regulate the inflammation and immune response of COPD.

Discovering the potential active ingredients of Qi-Yu-San-Long decoction for anti-oxidation, inhibition of non-small cell lung cancer based on the spectrum-effect relationship combined with chemometric methods.

Qi-Yu-San-Long decoction (QYSLD), a traditional Chinese medicine (TCM) prescription, consisting of ten types of herbal medicine which has significant clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). However, the bioactive ingredients of QYSLD remain unclear, due to their "multi-ingredients" and "multi-targets" features. This study aimed to construct a spectrum-effect correlation analysis model and screen the potential active components of QYSLD. A fingerprint method based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was developed and validated to obtain seventy common peaks of ten batches of QYSLD. The results of methodological evaluation, including precision, repeatability and stability, were less than 8.19%. In terms of linearity, eleven common components did not reach the linear standard (R2 < 0.99), they were removed before spectrum-effect relationship analysis. After treated with ten batches of QYSLD, the results of DPPH and FRAP assays ranged from 1.59 to 5.50 mg mL-1 and 143.83-873.83 µmol L-1, respectively. Meanwhile, the cell viabilities of A549 cells treated with QYSLD samples ranged from 21.73% to 85.71%. The relative healing rates ranged from 21.50% to 44.46%. The number of migrated and invaded cells ranged from 12.00 to 68.67 and 7.67 to 27.00, respectively. Then, the potential active components of QYSLD were screened through spectrum-effect relationship constructed by grey correlation analysis (GRA), partial least squares regression (PLSR) and backpropagation neural network (BP-ANN). The results were as follow: 1) eight ingredients of QYSLD were relevant to DPPH free radical scavenging ability; 2) nine ingredients were relevant to FRAP; 3) six ingredients were relevant to inhibit the proliferation ability of A549 cells; 4) twenty-two ingredients were relevant to inhibit the horizontal migration ability; 5) five ingredients were relevant to inhibit the vertical migration ability; 6) twelve ingredients were relevant to inhibit the invasion ability. Confirmatory experiments showed that compared with the unscreened ingredients, the potential active ingredients screened by the spectrum-effect relationship had better antioxidant and anti-NSCLC effects. In general, this study found the potential active ingredients in QYSLD. Meanwhile, the established method provided a valuable reference model for the potential active ingredients of TCM.

Targeting non-coding RNA H19: A potential therapeutic approach in pulmonary diseases.

Non-coding RNA is still one of the most popular fields in biology research. In recent years, people paid more attention to the roles of H19 in lung diseases, which expressed abnormally in various pathological process. Therefore, this review focus on the regulatory role of H19 in asthma, pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), lung injury, pneumonia, lung cancer, etc. And the potential therapeutic agents and molecular treatments of H19 are collected. The aim is to demonstrate its underlying mechanism in pulmonary diseases and to guide the basic research targeting H19 into clinical drug translation.

Antioxidant Biodegradable Covalent Cyclodextrin Frameworks as Particulate Carriers for Inhalation Therapy against Acute Lung Injury.

Drug therapies for acute lung injury (ALI) are far from satisfactory, primarily because drugs cannot specifically target the lungs. Direct delivery of drugs to the deep alveolar regions by inhalation administration is crucial for the treatment of ALI. However, conventional inhalable carriers such as lactose and mannitol are generally inactive. Therefore, the use of a novel pharmacologically active carrier for pulmonary delivery may produce synergetic effects in treating ALI. Considering the pathophysiological environment of ALI, which typically featured excessive reactive oxygen species (ROS) and acute inflammation, we synthesized a novel kind of biodegradable and ROS-sensitive cross-linked covalent cyclodextrin frameworks (OC-COF) with uniform inhalable particle size to treat ALI. OC-COF was devised to incorporate H2O2-scavenging peroxalate ester linkages, which could hydrolyze and eliminate ROS generated in inflammatory sites. Ligustrazine (LIG), an antioxidant and anti-inflammatory natural compound, was loaded into OC-COF and evaluated as a dry powder inhaler (LIG@OC-COF) in vitro and in vivo, showing favorable aerodynamic properties and prominent antioxidant and anti-inflammatory capacities for the synergistic effects of OC-COF and LIG. In ALI rats, inhalation of LIG@OC-COF with a one-fifth LIG dose significantly alleviated the inflammation, oxidant stress, and lung damage. Western blot analysis demonstrated that LIG@OC-COF protected the lungs by regulating the Nrf2/NF-κB signaling pathway. In summary, this study provides a novel ROS-responsive material as an inhalable particulate carrier for the improved treatment of ALI and other medical conditions.

The treatment of Qibai Pingfei Capsule on chronic obstructive pulmonary disease may be mediated by Th17/Treg balance and gut-lung axis microbiota.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), a prevalent, progressive respiratory disease, has become the third leading cause of death globally. Increasing evidence suggests that intestinal and pulmonary microbiota dysbiosis is associated with COPD. Researchers have shown that T helper (Th) 17/regulatory T (Treg) imbalance is involved in COPD. Qibai Pingfei Capsule (QBPF) is a traditional Chinese medicine used to treat COPD clinically in China. However, the effects of QBPF intervention on the Th17/Treg balance and microbiota in the gut and lung are still poorly understood. METHODS: This study divided the rats into three groups (n = 8): control, model, and QBPF group. After establishing the model of COPD for four weeks and administering of QBPF for two weeks, Th17 cells, Treg cells, their associated cytokines, transcription factors, and intestinal and pulmonary microbiota of rats were analyzed. Furthermore, the correlations between intestinal and pulmonary microbiota and between bacterial genera and pulmonary function and immune function were measured. RESULTS: The results revealed that QBPF could improve pulmonary function and contribute to the new balance of Th17/Treg in COPD rats. Meanwhile, QBPF treatment could regulate the composition of intestinal and pulmonary microbiota and improve community structure in COPD rats, suppressing the relative abundance of Coprococcus_2, Prevotella_9, and Blautia in the gut and Mycoplasma in the lung, but accumulating the relative abundance of Prevotellaceae_UCG_003 in the gut and Rikenellaceae_RC9_gut_group in the lung. Additionally, gut-lung axis was confirmed by the significant correlations between the intestinal and pulmonary microbiota. Functional analysis of microbiota showed amino acid metabolism was altered in COPD rats in the gut and lung. Spearman correlation analysis further enriched the relationship between the microbiota in the gut and lung and pulmonary function and immune function in COPD model rats. CONCLUSIONS: Our study indicated that the therapeutic effects of QBPF may be achieved by maintaining the immune cell balance and regulating the gut-lung axis microbiota, providing references to explore the potential biomarkers of COPD and the possible mechanism of QBPF to treat COPD.

Ligustrazine Inhibits Lung Phosphodiesterase Activity in a Rat Model of Allergic Asthma.

OBJECTIVES: This study sought to examine whether ligustrazine was capable of inhibiting phosphodiesterase (PDE) activity and improving lung function in a rat model of asthma. METHODS: Rats were initially sensitized using ovalbumin (OVA) and then were challenged daily with aerosolized OVA beginning 14 days later (30 min/day) to generate a rat model of asthma. Changes in airway function following methacholine (MCh) injection were evaluated by monitoring lung resistance (R L) and dynamic lung compliance (C dyn) values using an AniRes2005 analytic system. In addition, serum IgE was measured via ELISA, while PDE expression was evaluated via qPCR and western blotting. Key Findings. Ligustrazine significantly impaired allergen-induced lung hyperresponsivity and inflammation in this asthma model system. Ligustrazine treatment was also associated with reduced expression of PDEs including PDE4 in the lungs of these rats. CONCLUSIONS: Ligustrazine suppresses airway inflammation and bronchial hyperresponsivity in this rat model system, and these changes are associated with decreased PDE expression at the protein and mRNA levels.

The Link between Circadian Clock Genes and Autophagy in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD), a progressive respiratory disease, is characterized by the alveolar epithelium injury and persistent airway inflammation. It is documented that oscillation and dysregulated expression of circadian clock genes, like Bmal1, Per1, and Per2, involved in COPD pathogenies, including chronic inflammation and imbalanced autophagy level, and targeting the associations of circadian rhythm and autophagy is promising strategies in the management and treatment of COPD. Herein, we reviewed the mechanisms of the circadian clock and the unbalance of the autophagic level in COPD, as well as the link between the two, so as to provide further theoretical bases for the study on the pathogenesis of COPD.

[Rapid identification of chemical components in Qi-Yu-San-Long decoction by ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry].

Qi-Yu-San-Long decoction (QYSLD) is a classic traditional Chinese medicine prescription consisting of ten types of herbal medicines, including Astragali Radix, Polygonati Odorati Rhizoma, Scolopendra, Pheretima, Solanum nigrum L., Hedyotis diffusa Willd., Coicis Semen, Euphorbia helioscopia L., Curcumae Rhizoma, and Fritillariae Cirrhosae Bulbus, combined in a ratio of 15∶5∶3∶3∶10∶10∶10∶3∶5∶3 by weight. QYSLD has been used to treat non-small cell lung cancer (NSCLC) for over 20 years in clinical practice, and its curative effect is considered credible. However, the chemical constituents of QYSLD have not been revealed because of their complexity, which has significantly hindered the systematic clarification of the efficacy of the materials and quality evaluation. In this study, a reliable strategy based on the data-independent acquisition (DIA) technology of ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) combined with a targeted screening method was established to investigate the chemical components of QYSLD. A 2-µL aliquot from each vial was injected into a Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm) to separate complex components. The temperature of the column was 35 ℃, and the flow rate was set at 0.2 mL/min. The mobile phase consisted of 0.1% formic acid aqueous solution and acetonitrile. Detection was conducted using an Xevo G2-XS QTOF-MS with a LockSpray capable-electrospray interface. The data for complex components in QYSLD were collected by full-information tandem mass spectrometry (MS E) in the positive and negative ion modes. In the MSE mode, data acquisition was performed using a mass spectrometer by rapidly switching from a low-collision-energy (CE) scan to a high-CE scan during a single LC run. Thus, accurate precursor and fragment ions were collected in a single run, which was helpful for the structural elucidation of multiple components in QYSLD. In addition, systematic information on isolated chemical compounds was collected and distinguished from the ten individual herbs in QYSLD using databases such as China Academic Journals Full-text database (CNKI), PubMed, Web of Science, Medline, and ChemSpider. Accordingly, a self-building library of QYSLD, including the component name, molecular formula, and structure of the components from the herbs, was established. Subsequently, the raw MSE data of the collected samples and the self-building chemical composition library were imported into a natural product post-processing screening (UNIFI) platform for targeted screening of the chemical components in QYSLD. The parameters for UNIFI platform were as follows: the retention time deviation was ±0.1 min; an error margin of no more than 5×10 -6 for the identified compounds was allowed; positive adducts, including [M+H]+and [M+Na]+, were selected; and negative adducts, including [M-H]- and [M+HCOO]-, were selected. The results showed that a total of 166 compounds were initially identified, including 22 saponins, 13 alkaloids, 27 flavonoids, 32 terpenes, 20 amino acids, 16 phenylpropanoids, 9 organic acids, 6 sterols, 6 anthraquinones, and 15 other components. Among them, sixteen components were confirmed unambiguously with the reference substances. To better understand the chemical contribution of individual herbs to the entire decoction, the attributes of each component were summarized. This study provides a foundation for exploring the pharmacodynamic substances of QYSLD.