INTRODUCTION/OBJECTIVE:Psoriasis is associated with an increased risk of Ischemic Stroke (IS), but the underlying mechanisms remain unclear. This study aims to identify shared associated genes and explore potential mechanisms underlying psoriasis and IS. METHODS:Gene expression datasets from the GEO database were analyzed to identify common Differentially Expressed Genes (co-DEGs). Integrative bioinformatics analyses, machine-learning algorithms, single-cell RNA sequencing, molecular docking, and molecular dynamics simulations were employed to identify candidate shared genes and investigate the potential molecular mechanisms. RESULTS:We identified 57 co-DEGs shared between psoriasis and IS. Enrichment analyses indicated that these genes were mainly associated with immune and inflammatory pathways, including NET formation, NF-κB, TLR, and IL-17 signaling pathways. TLR2 and TNFSF10 were identified as shared associated genes and remained significant across leave-one-out sensitivity analyses, demonstrating the robustness of their differential expression. Single-cell analysis revealed that TLR2 and TNFSF10 were mainly expressed in macrophages, NK cells, and smooth muscle cells. Epigallocatechin gallate was identified as a candidate compound for further investigation. DISCUSSION:Our integrative analysis highlights TLR2 and TNFSF10 as potential mechanistic candidates associated with persistent immune activation, endothelial dysfunction, and vascular injury. These genes may participate in interconnected inflammatory processes involving TLR, IL-17, NF-κB, and NET-related pathways, providing a potential molecular link between psoriasis and IS. CONCLUSION:Chronic inflammation and immune dysregulation may contribute to psoriasis and IS comorbidity. TLR2 and TNFSF10 were identified as shared associated genes. These findings provide exploratory insights into the immunoinflammatory mechanistic association between psoriasis and IS.

PM2.5 exposure is harmful to health. The related mechanisms by which PM2.5 induced acute lung injury remain to be investigated. Herein, we found PM2.5 compromised lung function, disrupted lung tissue histology, and elevated inflammatory cytokines. Transcriptome sequencing data showed that ferroptosis-mediated oxidative stress plays a critical role in both cellular and murine models. In airway epithelial cells, a dose-dependent decrease in junction proteins was observed following PM2.5 induction, which was subsequently ameliorated by the ferroptosis inhibitor Fer-1 treatment. In alveolar macrophages, continuous exposure to PM2.5 for 6 h resulted in diminished phagocytic capacity, which was also reversed upon the addition of Fer-1. Moreover, network analysis identified FTH1 as a central node in regulating PM2.5-induced lung injury. These findings suggest that enhanced pulmonary uptake and retention of PM2.5 correlate with more severe lung injuries, with the number of barriers encountered by PM2.5 during its transit potentially playing a crucial role. The underlying mechanism is partially through disrupting pulmonary barriers via promoting FTH1-mediated ferroptosis.

OBJECTIVE:The aim of the study was to study maternal exposure to PM2.5 components and preterm birth. METHODS:Counts of hospitalizations due to preterm birth at the Fourth Hospital of Shijiazhuang City were collected from 2014 to 2019. The daily number of hospitalizations and short-term exposure to five types of PM2.5 components were examined using a time-stratified case-crossover method. The overall mixture of PM2.5 components and its relationship with preterm birth were analyzed via Bayesian kernel regression. RESULTS:In the single-pollutant analyses, maternal exposed to components of PM2.5 had an increased risks per interquartile increase in concentration during lag 0-2 days. The mixed component analysis revealed exposure to a mixture of PM2.5 components increased the risk of preterm birth. BCs are the main factors affecting the overall effects. CONCLUSIONS:PM2.5 components may have a potential influence of preterm birth.

BACKGROUND:Fine particulate matter (PM2.5) exposure significantly contributes to the development of chronic obstructive pulmonary disease (COPD). However, the underlying mechanisms remain inadequately elucidated, and there is a lack of effective clinical treatments. A combination of five bioactive ingredients derived from the traditional Chinese prescription Bufei Yishen formula (BYF) that is widely accepted for COPD treatment, exhibits bioequivalence with BYF and has been shown to alleviate COPD exacerbation in rat models induced by PM2.5 exposure. PURPOSE:To investigate the underlying mechanisms of the effective compound combination (ECC) attenuating mitochondrial oxidative stress in COPD progression induced by PM2.5 exposure. METHODS:The COPD rats were induced by cigarette smoke inhalation and bacterial infection, then exposed to real-time PM2.5 by a whole-body exposure system. The therapeutic efficacy of ECC was assessed by evaluating lung function, pathological changes, levels of oxidative stress, and inflammation. In vitro, the PM2.5-induced human bronchial and alveolar epithelial cells (BEAS-2B and HPAEpiC) were used to explore the underlying mechanisms of ECC against mitochondrial oxidative stress. RESULTS:Initially, based on the successful establishment of a PM2.5-aggravated COPD rat model, we demonstrated the protective effects of ECC on COPD progression induced by PM2.5 exposure by improving lung function, alleviating pathological injury, and reducing oxidative stress and inflammation. Subsequently, we identified that the inhibitory effects of ECC on mitochondrial oxidative damage, respiratory dysfunction, and fission/fusion imbalance induced by PM2.5 are primarily mediated through SIRT3 activation, both in vivo and in vitro. Mechanically, the deacetylation of FOXO3 at lysine residues 271 and 290 by SIRT3 is crucial for ECC to mitigate mitochondrial oxidative stress during the progression of COPD in response to PM2.5. CONCLUSION:This study reveals a previously unrecognized mechanism by which ECC acts as an agonist of SIRT3, offering potential therapeutic benefits for patients with COPD who are exposed to PM2.5.

Background:Chronic obstructive pulmonary disease (COPD) has emerged as a very consequential issue threatening human life and health; therefore, research on its pathogenesis is urgently needed. A prior investigation discovered a significant elevation in the phosphoglycerate mutase 5 (PGAM5) expression in the lung tissue of COPD smoking patients. This rise in expression is closely associated with COPD severity. Nevertheless, the precise molecular processes by which PGAM5 influences the COPD initiation and advancement remain unknown. Materials and Methods:A COPD model was created using murine alveolar macrophages (MH-S). Flow cytometry, enzyme-linked immunosorbent assay, Western blotting, and other methods were used to detect macrophage polarization, inflammatory factor secretion levels, and changes in PGAM5 and the nuclear factor-κB (NF-κB) pathway. Results:PGAM5 stimulated macrophage M1 polarization and secretion of the proinflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). PGAM5 bound and activated apoptotic signaling-regulated kinase 1 (ASK1), further activating the NF-κB pathway. These implications were reversed when PGAM5 expression was silenced. Conclusion:PGAM5 can cause an increase in p-ASK1T838, trigger the NF-κB pathway activation, and stimulate the M1 macrophage polarization and production of proinflammatory factors. This finding has significant implications for preventing and treating COPD.

Background Multiple sclerosis (MS) and psoriasis are both immune-mediated inflammatory diseases. Previous studies have reported comorbidity between MS and psoriasis, but the underlying mechanisms remain unclear. This study aims to elucidate the shared pathogenesis and core genes underlying MS and psoriasis. Methods Microarray data for MS and psoriasis were downloaded from the GEO database. Differentially expressed genes (DEGs) were analyzed using “limma” package. Functional enrichment analyses were conducted to elucidate biological functions of common DEGs. PPI analysis and machine learning were used to select core genes, and the diagnostic efficacy was evaluated using nomograms. Single-cell analysis and CeRNA network construction were performed. Immune cell infiltration was assessed by single-sample gene set enrichment. Drug prediction, molecular docking and molecular dynamics (MD) simulations identified potential therapeutic drugs. Results 89 DEGs identified in MS and psoriasis datasets were enriched in the NOD-like receptor, NF-κB, and JAK-STAT signaling pathways. IL7R and IRF8 were determined as core genes with good diagnostic performance (AUC >0.7). Immune infiltration analysis showed dysregulation of activated CD4 T cells, activated dendritic cells, and gamma delta T cells in both diseases. Single-cell analysis suggested that IL7R and IRF8 were mainly expressed in immune cells. Molecular docking and MD simulations revealed that parthenolide is a potential therapeutic agent. Conclusion This study highlights the critical role of immune dysregulation and chronic inflammation in MS and psoriasis comorbidity. IL7R and IRF8 were identified as core genes and novel intervention targets for both diseases. These findings provide new insights for future research.

Investigating comorbidities of ischemic stroke (IS) enhances understanding of its intricate mechanisms. Crohn’s disease (CD) is associated with an increased risk of IS, but the underlying mechanisms remain unclear. This study aims to identify shared diagnostic genes and explore the mechanisms underlying CD-IS comorbidity using bioinformatics and machine learning approaches. Gene expression data for CD and IS were obtained from the Gene Expression Omnibus. Shared genes were identified through differential expression and weighted gene co-expression network analyses (WGCNA). Functional enrichment analyses highlighted key biological pathways. Core genes were screened via machine learning algorithms and protein-protein interaction networks. Diagnostic nomograms were constructed, and single-cell RNA sequencing was used to characterize expression patterns of core genes. Immune cell infiltration was quantified using CIBERSORT, and a competing endogenous RNA network was built based on TarBase and SpongeScan databases. Mendelian randomization was performed to assess causal associations between core genes and disease risk. Candidate drugs were predicted using the Drug-Gene Interaction Database and validated through molecular docking. Twenty shared genes were identified through differential expression analysis and WGCNA. The toll-like receptor (TLR) signaling pathway was identified as a key pathway in CD-IS comorbidity. TLR2 and TLR8 were identified as core genes, with strong diagnostic performance (AUC > 0.80). The polymorphism of rs73221365 was associated with both CD and IS. Resveratrol hexanoic acid was a potential therapeutic candidate for CD-IS comorbidity. This study highlights the critical role of TLR-mediated inflammatory responses in CD-IS comorbidity. TLR2 and TLR8 may serve as promising diagnostic biomarkers. These findings advance understanding of the shared pathophysiology in CD-IS comorbidity and provide a foundation for developing precise diagnostics and targeted therapies.

Chronic obstructive pulmonary disease (COPD) continues to be a leading cause of mortality worldwide. Emerging evidence increasingly identifies exposure to fine particulate matter (PM2.5) as a significant risk factor, in addition to cigarette smoking, highlighting a critical gap in available treatment options. This review synthesizes epidemiological and experimental data that documents the correlation between airborne PM2.5 and the incidence and exacerbations of COPD. Numerous studies have demonstrated that PM2.5 exposure exacerbates COPD, manifesting in reduced lung function, lung and systemic inflammation, oxidative stress, mitochondrial dysfunction, cell death, emphysema, and small airway remodeling, all of which involve complex molecular pathways. Understanding the cellular and molecular mechanisms underlying these effects may inform the development of potential therapeutic interventions, mainly including reactive oxygen species scavengers, anti-inflammatory agents, specific pathway regulators, and traditional Chinese medicine. Future research should prioritize longitudinal exposure assessments and the development of personalized mitigation strategies to address the increasing burden of COPD in regions with high-pollution levels. This review serves as a stark reminder of the urgent necessity for substantive measures to combat air pollution, with the aim of reducing the associated health burden on our expanding global population.

Long-term exposure to particulate matter is a known risk factor for chronic obstructive pulmonary disease (COPD), yet the impact of ultrafine particles (UFPs) remains poorly understood. As COPD is an age-related disease, the potential modifying role of biological age acceleration in UFP-induced respiratory effects warrants investigation. We conducted a longitudinal panel study of 47 COPD patients with three repeated clinic visits in Beijing, China. Annual exposure levels to UFPs were estimated using a land use regression model. Lung function and respiratory inflammation were assessed at each visit. Biological age was quantified using the Klemera-Doubal method (KDM-BA) and PhenoAge algorithms. Associations were estimated using linear mixed-effects models. Overall, each IQR increase in UFPs exposure was associated with a 3.0-year increase in both KDM-BA (95 % CI: 0.2-5.8) and PhenoAge acceleration (95 % CI: 0.1-5.8). Accelerated biological age was associated with reductions in large and small airway function and lung volume. Stratified analysis indicated that individuals with faster biological aging were more susceptible to UFP-related lung injury. Our study provides novel evidence linking long-term UFP exposure to accelerated biological aging and impaired respiratory function in COPD patients. Biological age may serve as a modifier in assessing air pollution-related health risks.

ETHNOPHARMACOLOGICAL RELEVANCE:Bufei Yishen formula (BYF) is clinically used to treat chronic obstructive pulmonary disease (COPD). Effective-component compatibility (ECC) is a combination of five active components derived from BYF, which has an equal effect on COPD to BYF. Our previous study has also demonstrated that ECC can protect COPD rats against PM2.5 exposure. However, the precise mechanisms remain to be elucidated.AIM OF THE STUDY:To explore the mechanism underlying the anti-inflammatory effects of ECC-BYF against PM2.5-accelerated COPD.MATERIALS AND METHODS:MH-S macrophages were stimulated by PM2.5 suspension to establish an in vitro model. Western blotting and immunofluorescent staining were used to measure the protein levels of autophagy markers. ELISA and quantitative PCR were used to detect the levels of inflammatory cytokines. In vivo, an established PM2.5-accelerated COPD rat model was used to determine the protective effect of ECC-BYF. Lung function, pathology, autophagy, and inflammatory mediators were detected.RESULTS:Firstly, we observed a significantly increased number of macrophages in the lungs upon PM2.5 exposure. Then, decreased autophagy flux while elevated inflammation was detected in PM2.5-exposed rats and MH-S cells. In MH-S cells, ECC-BYF significantly suppressed the PM2.5-increased inflammatory cytokines production, which was accompanied by the enhancement of autophagy flux. An autophagy inhibitor counteracted the anti-inflammatory effect elicited by ECC-BYF. In addition, ECC-BYF stimulated Foxo3 nuclear translocation and upregulated Foxo3 expression, whereas Foxo3 knockdown abrogated the inhibitory effect of ECC-BYF on inflammation. In PM2.5-accelerated COPD rats, ECC-BYF also attenuated the autophagy disruption and increased Foxo3 in the lungs, finally resulting in a suppression of pulmonary inflammation and an enhancement of lung function.CONCLUSION:ECC-BYF can ameliorate PM2.5-aggravated inflammation in COPD, which might be associated with the enhancement of autophagy flux in alveolar macrophages through the activation of Foxo3 signals.

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive, and lethal lung disease with few treatments. Formononetin (FMN) is a clinical preparation extract with extensive pharmacological actions. However, its effect on COPD remains unknown. This study aimed to explore the effect and underlying mechanisms of FMN on COPD. A mouse model of COPD was established by exposure to cigarette smoke (CS) for 24 weeks. In addition, bronchial epithelial BEAS-2B cells were treated with CS extract (CSE) for 24 h to explore the in vitro effect of FMN. FMN significantly improved lung function and attenuated pathological lung damage. FMN treatment reduced inflammatory cell infiltration and pro-inflammatory cytokines secretion. FMN also suppressed apoptosis by regulating apoptosis-associated proteins. Moreover, FMN relieved CS-induced endoplasmic reticulum (ER) stress in the mouse lungs. In BEAS-2B cells, FMN treatment reduced CSE-induced inflammation, ER stress, and apoptosis. Mechanistically, FMN downregulated the CS-activated AhR/CYP1A1 and AKT/mTOR signaling pathways in vivo and in vitro. FMN can attenuate CS-induced COPD in mice by suppressing inflammation, ER stress, and apoptosis in bronchial epithelial cells via the inhibition of AhR/CYP1A1 and AKT/mTOR signaling pathways, suggesting a new therapeutic potential for COPD treatment.

Background: As a fibrinolytic enzyme from fermented soybean, nattokinase has been shown to be potentially beneficial for cardiovascular health, but current clinical evidences regarding the nattokinase supplementation on cardiovascular risk factors are various. This study aims to evaluate the cardiovascular efficacy of nattokinase. Methods: Four electronic databases were systematically searched to collect eligible randomized controlled trials. Data were extracted and summarized in a pre-designed form by two independent reviewers. Review Manager 5.4 software (Cochrane Library Software, Oxford, U.K.) was used for meta-analysis and bias risk assessment. Results: Six studies were eligible for quantitative analysis with 546 participants. The overall methodological quality of included studies was high. Relatively low total dosage of nattokinase had a negative effect on blood total cholesterol (MD [mean difference] = 5.27, 95% CI [confidence intervals]: 3.74 to 6.81, p < 0.00001), high-density lipoprotein cholesterol (MD = –2.76, 95% CI: –3.88 to –1.64, p < 0.00001), and low-density lipoprotein cholesterol (MD = 6.49, 95% CI: 0.83 to 12.15, p = 0.02). Nattokinase supplementation significantly reduced systolic blood pressure (MD = –3.45, 95% CI: –4.37 to –2.18, p < 0.00001) and diastolic blood pressure (MD = –2.32, 95% CI: –2.72 to –1.92, p < 0.00001), and led a slight increase in blood glucose (MD = 0.40, 95% CI: 0.20 to 0.60, p < 0.0001) as compared to placebo. Nattokinase group with relatively high total dosage also had a higher total cholesterol (MD = 3.18, 95% CI: 2.29 to 4.06, p < 0.00001) than control interventions, but no significant differences were found in levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. No significant correlation was found between nattokinase supplementation and triglyceride (p = 0.71). No notable adverse events were reported in all studies due to intake of nattokinase. Conclusions: This study further supports that nattokinase can be used as an effective adjunctive therapy for hypertension, but relatively low-dose supplementation of nattokinase may have no significant lipid-lowering effect. More work will need to be done to determine whether the positive efficacy of nattokinase on cardiovascular risk factors is dose-dependent. Systematic Review Registration: This work has been registered on PROSPERO (CRD42022315020).

BACKGROUND:The urban ambient air quality has been largely improved in the past decade. It is unknown whether childhood asthma prevalence is still increasing in ever top-ranking city of Shanghai, whether the improved air quality is beneficial for children's asthma and what time window of exposure plays critical roles. METHODS:Using a repeat cross-sectional design, we analyzed the association between early life exposure to particles and wheezing/asthma in each individual and combined surveys in 2011 and 2019, respectively, in 11,825 preschool children in Shanghai. RESULTS:A significantly lower prevalence of doctor-diagnosed asthma (DDA) (6.6% vs. 10.5%, p < 0.001) and wheezing (10.5% vs. 23.2%, p < 0.001) was observed in 2019 compared to 2011. Exposure to fine particulate matter (PM2.5), coarse particles (PM2.5-10) and inhalable particles (PM10) was decreased in 2019 by 6.3%, 35.4%, and 44.7% in uterus and 24.3%, 20.2%, and 31.8% in infancy, respectively. Multilevel log-binomial regression analysis showed exposure in infancy had independent association with wheezing/DDA adjusting for exposure in uterus. For each interquartile range (IQR) increase of infancy PM2.5, PM2.5-10 and PM10 exposure, the odds ratios were 1.39 (95% confidence interval (CI): 1.24-1.56), 1.51 (95% CI:1.15-1.98) and 1.53 (95% CI:1.27-1.85) for DDA, respectively. The distributed lag non-linear model showed the sensitive exposure window (SEW) was 5.5-11 months after birth. Stratified analysis showed the SEWs were at or shortly after weaning, but only in those with <6 months of exclusive breastfeeding. CONCLUSIONS:Improved ambient PM benefits in decreasing childhood asthma prevalence. We firstly reported the finding of SEW to PM at or closely after weaning on childhood asthma.

Yindan Xinnaotong soft capsule (YDXNT), a traditional Chinese medicine preparation, has shown a promising effect in the treatment of acute ischemic stroke (AIS). The goal of this study was to investigate the therapeutic effects and pharmacological mechanisms of YDXNT on AIS. Randomized controlled trials were searched and screened. Review Manager 5.4 was used for a meta-analysis. Active ingredients and targets of YDXNT were extracted from the Traditional Chinese Medicine Systems Pharmacology Database, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, and Encyclopaedia of Traditional Chinese Medicine. AIS-related targets were retrieved from GeneCards, OMIM, and DrugBank databases. We constructed PPI and ingredient-target networks, performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and conducted molecular docking. The YDXNT group had a higher total effective rate and a higher Barthel Index score. YDXNT reduced the low-density lipoprotein cholesterol and the whole blood viscosity at high and shear rates. Our study identified 313 ingredients and 1196 common targets. The key ingredients were mainly quercetin, neocryptotanshinone II, miltionone I, neotanshinone C, and tanshiquinone B, and the key targets were mainly SRC, MAPK3, AKT1, MAPK1, and JUN. GO analysis showed that the core targets mainly involved in atherosclerosis and neural apoptosis. The core pathways were lipid and atherosclerosis, PI3K-Akt, MAPK, and other pathways. Key ingredients exhibited robust binding interactions with core targets. YDXNT could effectively improve the total effective rate, ability of daily life, blood lipids, and blood viscosity. Antiatherosclerotic and neuroprotective effects are the main pharmacological mechanisms. Registration number: CRD42023400127.

Objective To observe the effect of PM2.5 and the effective-component compatibility of Bufei Yishen Formula（ECC-BYF）on the epithelial–mesenchymal transition（EMT）of chronic obstructive pulmonary diseases（COPD） rats and its possible involved mechanism. Methods Fifty rats were randomly divided into control group,COPD group,PM2.5 group,ECC-BYF and aminophylline group,10 rats in each group. Except for the control group,the COPD rat model was established by repeated cigarette smoke inhalations and bacterial infections,then rats in all groups except for the control and COPD groups were exposed to real-time atmospheric concentrated PM2.5. Meanwhile,rats in the ECC-BYF group and aminophylline group were given ECC-BYF（6.48 mg · kg-1· d-1） and aminophylline(54 mg·kg -1 ·d -1 ) by gavage,respectively,while rats in other groups were given normal saline once daily,the course was 8 weeks. The maximum expiratory flow（MMEF） and functional residual capacity（FRC） were measured.The expression levels of alpha-smooth muscle actin（α-SMA）,collagen（COL） Ⅰ and COL Ⅲ in lung tissues were examined by immumohistochemical. Evaluation of the expressions of E-cadherin（E-cad）,N-cadherin（N-cad）,α-SMA,COL Ⅰ,Smad4,p-Smad2/3 in lung tissues were conducted via Western Blot,and TGF-β1 in the serum and lung tissue homogenate were detected by ELISA. Results Compared with the control group, MMEF and E-cad protein expression decreased, FRC,TGF-β1,α-SMA,COL Ⅰ,COL Ⅲ,p-Smad3,Smad4 protein expression increased in the COPD group（P＜0.05,P＜0.01）. Compared with the control group,MMEF and E-cad protein expression dcreased,FRC,TGF-β1 content,and α-SMA,COL Ⅰ,COL Ⅲ,N-cad,p-Smad2,p-Smad3 and Smad4 protein expression increased in the PM2.5 group（P＜0.05,P＜0.01）. Compared with the COPD group, FRC and TGF-β1 content,and α-SMA,COL Ⅰ and COL Ⅲ protein expression increased in the PM2.5 group（P＜0.05,P＜0.01）. Compared with the PM2.5 group, MMEF and E-cad protein expression increased,FRC,TGF-β1 content,α-SMA,COL Ⅰ,COL Ⅲ,N-cad,p-Smad2,p-Smad3,and Smad4 protein expression decreased in ECC-BYF group（P＜0.05,P＜0.01）. FRC,TGF-β1 content,α-SMA,COL Ⅰ,COL Ⅲ,p-Smad2 and Smad4 protein expression decreased in aminophylline group（P＜0.05,P＜0.01）. Conclusions PM2.5 exposure promotes EMT in the lung tissue of COPD rats,which markedly aggravated lung injury. ECC-BYF could alleviate the EMT of COPD rats caused by PM2.5 exposure,and the mechanism may be related to the regulation of TGF β1/Smad pathway.

Ligustilide (LIG) is the main active ingredient of Angelica sinensis (Oliv.) Diels, which could promote focal angiogenesis to exert neuroprotection. However, there was no report that verified the exact effects of LIG on endometrial angiogenesis and the pregnancy outcomes. To explore the effects of LIG on low endometrial receptivity (LER) and angiogenesis, pregnancy rats were assigned into Control (saline treatment), LER (hydroxyurea-adrenaline treatment), LIG 20 mg/kg and LIG 40 mg/kg groups. Hematoxylin and eosin (H E) staining was performed to evaluate endometrial morphology. Quantitative real-time PCR, immunofluorescence staining, western blot and immunohistochemistry staining were employed to assess the expression of endometrial receptivity factors and angiogenesis-related gene/protein, respectively. RNA sequencing was used to analyze the effects of LIG on LER caused by Kidney deficiency and blood stasis. We found that endometrial thickness and the implanted embryo number were substantially reduced in the hydroxyurea-adrenaline-treated pregnancy rats. At the same time, the gene and protein expressions of ERα, LIF, VEGFA and CD31 in the endometrium were markedly reduced, while the expressions of MUC1, E-cadherin were increased in the LER group. Administration of LIG raised the endometrial thickness and implanted embryos, as well as reversed the expressions of these factors. Collectively, our findings revealed that LIG could facilitate embryo implantation via recovery of the endometrium receptivity and promotion of endometrial angiogenesis.

Background. Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality and poor prognosis. The prognostic signatures related to conventional therapy response remain limited. The Wenfei Buqi Tongluo (WBT) formula, a traditional Chinese medicine (TCM) formula, has been widely utilized to treat respiratory diseases in China, which is particularly effective in promoting inflammatory absorption. In this study, we aim to explore the mechanism of the WBT formula in the inhibition of inflammatory response during IPF, based on network pharmacology and in vivo experiments. Methods. Network pharmacology was applied to predict the changes of biological processes and potential pathways for the WBT formula against IPF. Histopathological changes, inflammatory factors (IL-6, IL-1β, and TNF-α), and the proteins of the TLR4/MyD88/NF-κB pathway in bleomycin- (BLM-) induced mice model were examined by hematoxylin-eosin (H&E), Masson or immunohistochemistry staining, Western blot, and enzyme-linked immunosorbent assay analysis. Results. A total of 163 possible components and 167 potential targets between the WBT formula and IPF were obtained. The enrichments of network pharmacology showed that inflammation response, TNF, and NF-κB pathways were involved in the treatment of WBT against IPF. The in vivo experiments indicated that the WBT formula could ameliorate inflammatory exudation and collagen deposition at a histopathology level in the BLM-induced mice model. The levels of IL-6, IL-1β, and TNF-α were reduced after the WBT formula treatment. Moreover, the expressions of phosphorylated-NF-κB p65, TLR4, and MyD88 were significantly downregulated by the WBT formula, compared with the BLM-induced group. Conclusion. These results indicated that the WBT formula can suppress BLM-induced IPF in a mouse model by inhibiting the inflammation via the TLR4/MyD88/NF-κB pathway. This study provides a new insight into the molecular mechanisms of the WBT formula in the application at the clinic.

目的:通过代谢组学技术评价当归芍药散对PM2.5致雄性生殖损伤大鼠睾丸组织的影响.方法:18只雄性SD大鼠分为对照组、PM2.5组和当归芍药散组,每组6只.除对照组外的大鼠进行为期12周的PM2.5实时浓缩暴露.自暴露第9周起,对照组、PM2.5组予以生理盐水(2 mL/只)灌胃,当归芍药散组给予当归芍药散[2 g/(kg·d)]灌胃.第12周结束后取材,光镜下观察肺组织及睾丸组织病理改变,采用代谢组学技术分析大鼠睾丸组织代谢物的变化.结果:与对照组相比,PM2.5组大鼠肺组织出现肺泡壁断裂、炎症细胞浸润等病理表现;睾丸组织生精细胞层次减少,排列紊乱,精子及精子细胞减少;代谢组学分析结果显示,PM2.5组大鼠睾丸组织中磷脂酰乙醇胺、磷脂酰胆碱等代谢物含量降低,当归芍药散组上述代谢物含量较PM2.5组回调(P<0.05),3组差异代谢产物主要涉及甘油磷脂代谢、亚油酸代谢、α-亚麻酸代谢等5条代谢通路,其中甘油磷脂类代谢产物的改变较为显著.结论:PM2.5暴露可引起大鼠睾丸组织代谢紊乱,当归芍药散对其具有良好的保护作用,其机制可能与调控甘油磷脂代谢有关.

This panel study attempted to assess the effects of ambient fine particulate matter (PM 2.5 ) exposure on oxidative stress, inflammation, and janus kinase (JAK)/signal transducer and activator of transcription (STAT) signal molecules. Twenty-nine nonsmoking adults with asthma were followed up for three seasons. Lung function was measured four times and peripheral blood was collected one time per season. The markers of oxidative stress, inflammation, and JAK/STAT were detected. Daily concentration of ambient PM 2.5 was recorded from the China National Environmental Monitoring Center. Linear mixed-effects regression models were used to investigate the relationships of ambient PM 2.5 with the index of lung function, oxidative stress, inflammation, and JAK/STAT. Mediation analyses were used to explore the mediation effect of JAK. The concentration of PM 2.5 was the highest in spring, with a median of 151 μg/m 3 . In the analyses of oxidative stress, the malonaldehyde (MDA) increased by 3.80% (95% CI: 2.43 to 5.17%; p <0.001) for each 10 μg/m 3 increase in lag4 PM 2.5 exposure. Furthermore, we detected a significant association in cytokines. Lag4 PM 2.5 exposure was associated with an increased interleukin-4 (IL-4) by 3.00% (95% CI: 0.26 to 5.74%; p <0.05). Besides, we found mediation of JAK2 in the associations between superoxide dismutase (SOD)/IL-12 and STAT4, JAK3 in the association between MDA and STAT6. The injury of pulmonary function in asthmatic adults induced by ambient PM 2.5 exposure is most likely to occur at lag 4 days. Ambient PM 2.5 aggravates asthma by systemic oxidative stress and inflammation, in which JAK/STAT signal molecules may be involved. Graphical abstract