IntroductionPulmonary fibrosis is a terminal lung disease characterized by fibroblast proliferation, extracellular matrix accumulation, inflammatory damage, and tissue structure destruction. The pathogenesis of this disease, particularly idiopathic pulmonary fibrosis (IPF), remains unknown. Macrophages play major roles in organ fibrosis diseases, including pulmonary fibrosis. The phenotype and polarization of macrophages are closely associated with pulmonary fibrosis. A new direction in research on anti-pulmonary fibrosis is focused on developing drugs that maintain the stability of the pulmonary microenvironment.MethodsWe obtained gene sequencing data and clinical information for patients with IPF from the GEO datasets GSE110147, GSE15197, GSE24988, GSE31934, GSE32537, GSE35145, GSE53845, GSE49072, GSE70864, and GSE90010. We performed GO, KEGG enrichment analysis and GSEA analysis, and conducted weighted gene co-expression network analysis. In addition, we performed proteomic analysis of mouse lung tissue. To verify the results of bioinformatics analysis and proteomic analysis, mice were induced by intratracheal instillation of bleomycin (BLM), and gavaged for 14 days after modeling. Respiratory function of mice in different groups was measured. Lung tissues were retained for histopathological examination, Western Blot and real-time quantitative PCR, etc. In addition, lipopolysaccharide, interferon-γ and interleukin-4 were used to induce RAW264.7 cells for 12h in vitro to establish macrophage inflammation and polarization model. At the same time, HG2 intervention was given. The phenotype transformation and cytokine secretion of macrophages were investigated by Western Blot, RT-qPCR and flow cytometry, etc.ResultsThrough bioinformatics analysis and experiments involving bleomycin-induced pulmonary fibrosis in mice, we confirmed the importance of macrophage polarization in IPF. The analysis revealed that macrophage polarization in IPF involves a change in the phenotypic spectrum. Furthermore, experiments demonstrated high expression of M2-type macrophage-associated biomarkers and inducible nitric oxide synthase, thus indicating an imbalance in M1/M2 polarization of pulmonary macrophages in mice with pulmonary fibrosis.DiscussionOur investigation revealed that the ethyl acetate extract (HG2) obtained from the roots of Prismatomeris connata Y. Z. Ruan exhibits therapeutic efficacy against bleomycin-induced pulmonary fibrosis. HG2 modulates macrophage polarization, alterations in the TGF-β/Smad pathway, and downstream protein expression in the context of pulmonary fibrosis. On the basis of our findings, we believe that HG2 has potential as a novel traditional Chinese medicine component for treating pulmonary fibrosis.

Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treatment of pulmonary fibrosis. Hence, there is an urgent need for developing novel drugs to address such diseases. properties. Our study found for the first time that a natural source of Prismatomeris connate ethyl acetate extract (HG-2) had a significant anti-pulmonary fibrosis effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic (TGF-β1/Smad) pathway. Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation, cellular response to reactive oxygen species, and extracellular matrix disassembly. Moreover, mass spectrometry imaging (MSI) was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-pulmonary fibrosis metabolic mechanism of HG-2, which was related to arginine synthesis, alanine, aspartic acid and glutamate metabolism, the down-regulation of arachidonic acid metabolism, and the up-regulation of glycerophospholipid metabolism. In conclusion, we elaborated on the relationship between metabolite distribution and the progression of PF, constructed the regulatory metabolic network of HG-2, and discovered the multi-target therapeutic effect of HG-2, which might be conducive to the development of new drugs for PF.

Mass spectrometry imaging (MSI) is a powerful molecular imaging technology that can obtain qualitative, quantitative, and location information by simultaneously detecting and mapping endogenous or exogenous molecules in biological tissue slices without specific chemical labeling or complex sample pretreatment. This article reviews the progress made in MSI and its application in drug toxicology research, including the tissue distribution of toxic drugs and their metabolites, the target organs (liver, kidney, lung, eye, and central nervous system) of toxic drugs, the discovery of toxicity-associated biomarkers, and explanations of the mechanisms of drug toxicity when MSI is combined with the cutting-edge omics methodologies. The unique advantages and broad prospects of this technology have been fully demonstrated to further promote its wider use in the field of pharmaceutical toxicology.

Objective To explore the effects of Colla corii asini (CCA) (common name E’jiao) on lung function and pathological injury of the lung tissue in rats with chronic obstructive pulmonary disease (COPD). Methods Twenty-five rats were randomly divided into the control group, COPD model group and treatment group with low, medium and high-doses of CCA (1, 2, 4 g/kg), with 5 rats in each group. The COPD model group and treatment groups were modeled by cigarette smoke exposure with a concentration of (1 100±10)mg/m3 once a day, 90 minutes each time, for 48 consecutive weeks. After the end of the next day, the CCA groups were given by daily oral gavage treatment for 28 days. Lung function was detected by animal lung function instrument and the pathological changes of the lung tissue were assessed by HE staining and microscopy. Results Compared with the control group, TV, EV, Te, RT, EEP and Penh were significantly increased in the COPD model group(P＜0.05), while PEF, PIF, MV, EF50 and f(B) were significantly decreased (P＜0.05). Inflammation and pathological changes of emphysema were observed, and lung tissue lesions were aggravated. Compared with the COPD model group, Te, RT and Penh were significantly reduced in the high-dose CCA group (P＜0.05), while MV, PIF and EF50 were significantly higher (P＜0.05). Less infiltration of inflammatory cells, less alveolar expansion and fewer pulmonary bullae were observed in high-dose CCA-treated rats. The degree of emphysema was reduced, and pathological damage to lung tissue was clearly alleviated. Conclusions CCA improves lung function and alleviates the inflammatory response of the lung tissue in COPD rats.

呼吸系统主要包括上呼吸道(鼻、咽、喉)、下呼吸道(气管、支气管)和肺.呼吸道是传送气体的通道,肺则是气体交换的器官.可吸入颗粒物是指悬浮在空气中,空气动力学直径≤10μm的颗粒物,可以被人体吸入,沉积在呼吸系统,引起各类疾病.在评估颗粒物对机体影响的动物研究中,主要考虑两方面:暴露方式和沉积剂量.

COVID-19的发病特征为发热、干咳、乏力,严重者可进展为急性呼吸窘迫综合征(ARDS)等,甚至危及生命.SARS-CoV-2可通过血管紧张素转化酶2(ACE2)入侵细胞并导致ACE2表达下调.ACE2表达下调会导致肾素-血管紧张素系统(RAS)的失衡,从而引起后续病理状态发生,RAS在ARDS中也发挥重要的作用.本文总结了RAS系统在COVID-19发病过程中可能存在的作用,以及基于RAS对于COVID-19的治疗可能,为优化治疗及后续研究提供参考.

AIM:Excessive exposure to 5-hydroxymethylfurfural (5-HMF), which is a common impurity in various sugar-containing products, induces serious side effects. Our previous study revealed that 5-HMF exerted immune sensitizing potential when injected into rodents. In this study, we explored 5-HMF mediated anaphylactoid reactions and its underlying molecular mechanisms.METHODS:We investigated anaphylactoid reactions in Brown Norway (BN) rats and Institute of Cancer Research (ICR) mice to identify 5-HMF mediated in vivo anaphylactoid reactions. RBL-2H3 and P815 cell degranulation models were also established, and degranulation, enzyme-linked immunosorbent, filamentous actin (F-actin) microfilament staining, and western blot assays were performed in these cells.RESULTS:We showed that 5-HMF induced anaphylactoid reactions by increasing blood vessel permeability in mice, and significantly elevating histamine (His) and glutathione peroxidase-1 (Gpx-1) levels in rat serum. Moreover, after incubation with 5-HMF, β-hexosaminidase (β-Hex), His, IL-4 and IL-6 levels were all significantly increased, thereby inducing cellular degranulation in RBL-2H3 and P815 cells. Finally, 5-HMF also upregulated Lyn, Syk, p38 and JNK protein phosphorylation levels.CONCLUSIONS:Our findings suggest that 5-HMF induces anaphylactoid reactions both in vivo and in vitro, therefore 5-HMF limits in sugar-containing products should receive more regulatory attention.

Polygonum multiflorum Thunb. (PM) is a traditional Chinese medicine, commonly used to treat a variety of diseases. However, the hepatotoxicity associated with PM hampers its clinical application and development. In this study, we refined the zebrafish hepatotoxicity model with regard to the following endpoints: liver size, liver gray value, and the area of yolk sac. The levels of alanine aminotransferase, aspartate transaminase, albumin, and microRNAs-122 were evaluated to verify the model. Subsequently, this model was used to screen different extracts, components, and constituents of PM, including 70 % EtOH extracts of PM, four fractions from macroporous resin (components A, B, C, and D), and 19 compounds from component D. We found that emodin, chrysophanol, emodin-8-O-β-D-glucopyranoside, (cis)-emodin-emodin dianthrones, and (trans)-emodin-emodin dianthrones showed higher hepatotoxicity compared to other components in PM, whereas polyphenols showed lower hepatotoxicity. To the best of our knowledge, this study is the first to identify that dianthrones may account for the hepatotoxicity of PM. We believe that these findings will be helpful in regulating the hepatotoxicity of PM.

Environmental issues pose huge threats to public health, particularly the damage caused by fine particulate matter (PM2.5). However, the mechanisms of injury require further investigation and medical materials that can protect the lungs from PM2.5 are needed. We have found that Colla corii asini, a traditional Chinese medicine that has long been used to treat various ailments, is a good candidate to serve this purpose. To understand the mechanisms of PM2.5-induced lung toxicity and the protective effects of Colla corii asini, we established a rat model of lung injury via intratracheal instillation of artificial PM2.5 (aPM2.5). Our results demonstrated that Colla corii asini significantly protected against lung function decline and pathologic changes. Inflammation was ameliorated by suppression of Arg-1 to adjust the disturbed metabolic pathways induced by aPM2.5, such as arginine and nitrogen metabolism and aminoacyl-tRNA biosynthesis, for 11 weeks. Our work found that metabolomics was a useful tool that contributed to further understanding of PM2.5-induced respiratory system damage and provided useful information for further pharmacological research on Colla corii asini, which may be valuable for therapeutic intervention.