Bu-Fei-Huo-Xue capsule alleviates bleomycin-induced pulmonary fibrosis in mice through modulating gut microbiota.

Introduction: Bu-Fei-Huo-Xue capsule (BFHX) has been used to treat pulmonary fibrosis (PF) in clinic. However, the mechanism of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis remains unclear. Recent studies have shown that the changes in gut microbiota were closely related to the progression of pulmonary fibrosis. Modulating gut microbiota provides new thoughts in the treatment of pulmonary fibrosis. Methods: In this study,a mouse model of pulmonary fibrosis was induced using bleomycin (BLM) and treated with Bu-Fei-Huo-Xue capsule. We firstly evaluated the therapeutic effects of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis model mice. Besides,the anti-inflammatory and anti- oxidative effects of Bu-Fei-Huo-Xue capsule were evaluated. Furthermore, 16S rRNA sequencing was used to observe the changes in gut microbiota in pulmonary fibrosis model mice after Bu-Fei-Huo-Xue capsule treatment. Results: Our results showed that Bu-Fei-Huo-Xue capsule significantly reduced the collagen deposition in pulmonary fibrosis model mice. Bu-Fei-Huo-Xue capsule treatment also reduced the levels and mRNA expression of pro-inflammatory cytokines and inhibited the oxidative stress in lung. 16S rRNA sequencing showed that Bu-Fei-Huo-Xue capsule affected the diversity of gut microbiota and the relative abundances of gut microbiota such as Lactobacillus, Lachnospiraceae_NK4A136_group, and Romboutsia. Conclusion: Our study demonstrated the therapeutic effects of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis. The mechanisms of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis may be associated with regulating gut microbiota.

Study on the Mechanism of Qing-Fei-Shen-Shi Decoction on Asthma Based on Integrated 16S rRNA Sequencing and Untargeted Metabolomics.

Qing-Fei-Shen-Shi decoction (QFSS) consists of Prunus armeniaca L., Gypsum Fibrosum, Smilax glabra Roxb., Coix lacryma-jobi L., Benincasa hispida (Thunb.) Cogn., Plantago asiatica L., Pyrrosia lingua (Thunb.) Farw., Houttuynia cordata Thunb., Fritillaria thunbergii Miq., Cicadae Periostracum, and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle. QFSS shows significant clinical efficacy in the treatment of asthma. However, the specific mechanism of QFSS on asthma remains unclear. Recently, multiomics techniques are widely used in elucidating the mechanisms of Chinese herbal formulas. The use of multiomics techniques can better illuminate the multicomponents and multitargets of Chinese herbal formulas. In this study, ovalbumin (OVA) was first employed to induce an asthmatic mouse model, followed by a gavage of QFSS. First, we evaluated the therapeutic effects of QFSS on the asthmatic model mice. Second, we investigated the mechanism of QFSS in treating asthma by using an integrated 16S rRNA sequencing technology and untargeted metabolomics. Our results showed that QFSS treatment ameliorated asthma in mice. In addition, QFSS treatment affected the relative abundances of gut microbiota including Lactobacillus, Dubosiella, Lachnospiraceae_NK4A136_group, and Helicobacter. Untargeted metabolomics results showed that QFSS treatment regulated the metabolites such as 2-(acetylamino)-3-[4-(acetylamino) phenyl] acrylic acid, D-raffinose, LysoPC (15 : 1), methyl 10-undecenoate, PE (18 : 1/20 : 4), and D-glucose6-phosphate. These metabolites are associated with arginine and proline metabolism, arginine biosynthesis, pyrimidine metabolism, and glycerophospholipid metabolism. Correlation analysis indicated that arginine and proline metabolism and pyrimidine metabolism metabolic pathways were identified as the common metabolic pathways of 16s rRNA sequencing and untargeted metabolomics. In conclusion, our results showed that QFSS could ameliorate asthma in mice. The possible mechanism of QFSS on asthma may be associated with regulating the gut microbiota and arginine and proline metabolism and pyrimidine metabolism. Our study may be useful for researchers to study the integrative mechanisms of Chinese herbal formulas based on modulating gut microbiota and metabolism.

Mechanistic study of salidroside on ovalbumin-induced asthmatic model mice based on untargeted metabolomics analysis.

Salidroside (SAL) is a natural component derived from Rhodiola rosea and is well known for its wide range of biological activities such as its anti-inflammatory and anti-oxidative properties. However, its effects and mechanisms of action related to asthma have not been well explored yet. Recent studies have found that changes in host metabolism are closely related to the progression of asthma. Many natural components can ameliorate asthma by affecting host metabolism. The use of untargeted metabolomics can allow for a better understanding of the metabolic regulatory mechanisms of herbs on asthma. This study aimed to demonstrate the anti-asthmatic effects and metabolic regulatory mechanisms of SAL. In this study, the therapeutic effects of SAL on asthmatic mice were tested at first. Secondly, the effects of SAL on the airway inflammatory reaction, oxidative stress, and airway remodeling were investigated. Finally, untargeted metabolomics analysis was used to explore the influence of SAL on lung metabolites. The results showed that SAL had a significant therapeutic effect on asthmatic model mice. Moreover, SAL treatment lowered interleukin (IL)-4, IL-5, and IL-13 levels but elevated interferon gamma (IFN-γ) and IL-10 levels in bronchoalveolar lavage fluid (BALF). Additionally, it also increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and decreased methane dicarboxylic aldehyde (MDA) levels in the lungs. Besides, SAL-treated mice showed decreased expression of smooth muscle actin (α-SMA), matrix metallopeptidase 2 (MMP2), matrix metallopeptidase 9 (MMP9), and transforming growth factor-beta 1 (TGF-ß1) in the lung. Untargeted metabolomics analysis showed 31 metabolites in the lungs that were influenced by SAL. These metabolites were related to pyrimidine metabolism, steroid hormone biosynthesis, and tricarboxylic acid (TCA) cycle. In conclusion, SAL treatment can reduce the inflammatory response, oxidative stress, and airway remodeling in asthmatic model mice. The mechanism of SAL in the treatment of asthma may be related to the regulation of pyrimidine metabolism, steroid hormone biosynthesis, and the TCA cycle. Further studies can be carried out using targeted metabolomics and in vitro models to deeply elucidate the anti-inflammatory and anti-oxidative mechanisms of SAL on asthma based on regulating metabolism.

Papillary squamous cell carcinoma successfully treated with bronchoscopic intratumoral injections of cisplatin and Endostar: a case report.

Squamous cell carcinoma (SCC) is a malignant epithelial tumor originating from the bronchial epithelium that shows keratosis and/or intercellular bridges. Papillary squamous cell carcinoma (PSCC) is an extremely rare subtype of SCC that manifests with a unique intrabronchial papillary growth pattern. Surgical resection is still the first recommendation for localized noninvasive SCC. However, some patients are not candidates for surgical resection. With the development of interventional pulmonology, bronchoscopic interventional therapy has played a key role in the treatment of central airway tumors. Here, we report a case of noninvasive PSCC in the airway treated with an electric snare, argon plasma coagulation (APC), and cryotherapy. After removing the tumor by electrotomy, cryotherapy, and APC, the tumor was injected with Endostar 15 mg (3 ml) and cisplatin 20 mg (diluted to 3 ml with 0.9% normal saline) in six separate sites, once every 21 days. The tumor was eliminated, and the treatment was stopped after four treatment cycles. During the 1-year follow-up, there was no recurrence of PSCC in the airway. In this case, submucosal injections of Endostar combined with cisplatin was a feasible and effective endoscopic method for treating a low-grade intratracheal malignant tumor.

Long non-coding RNA-ZNF281 upregulates PTEN expression via downregulation of microRNA-221 in non-small cell lung cancer.

A recent study reported that zinc finger protein (ZNF)281 is a tumor-suppressive long non-coding (lnc)RNA in glioma. The present study investigated the role of ZNF281 in non-small cell lung cancer (NSCLC). ZNF281 expression in paired cancer and non-cancerous tissues from patients with NSCLCs was analyzed by RNA extraction and reverse transcription-quantitative-PCR. A 5-year follow up on patients was performed to analyze the prognostic value of ZNF281 for NSCLC. Cell transfections of ZNF281 or phosphatase and tensin homolog (PTEN) expression vector and microRNA (miR)-221 mimic were performed to analyze the relationship between ZNF281, miR-221 and PTEN. Cell apoptosis and proliferation were analyzed using Cell Counting Kit-8 and flow cytometry, respectively. In patients with NSCLC, expression levels of ZNF281 were significantly lower in cancer tissues compared with in non-cancerous tissues, and lower levels of ZNF281 expression in cancerous tissues predicted poor survival. In NSCLC cells, ZNF281 overexpression resulted in upregulated PTEN and downregulated miR-221 expression, whereas cells with miR-221 overexpression exhibited downregulated PTEN expression and unaffected ZNF281 expression. In addition, ZNF281 and PTEN overexpression resulted in accelerated cell apoptosis and inhibited the cell proliferation of NSCLC cells. Notably, miR-221 overexpression exhibited an opposite effect and attenuated the functions of ZNF281 and PTEN overexpression. Therefore, ZNF281 may upregulate PTEN via downregulation of miR-221 in NSCLC, resulting in inhibition of cancer cell proliferation and the promotion of apoptosis.