Polydatin alleviates bleomycin-induced pulmonary fibrosis and alters the gut microbiota in a mouse model.

To investigate the effect and mechanism of polydatin on bleomycin (BLM)-induced pulmonary fibrosis in a mouse model. The lung fibrosis model was induced by BLM. The contents of TNF-α, LPS, IL-6 and IL-1ß in lung tissue, intestine and serum were detected by ELISA. Gut microbiota diversity was detected by 16S rDNA sequencing; R language was used to analyse species composition, α-diversity, ß-diversity, species differences and marker species. Mice were fed drinking water mixed with four antibiotics (ampicillin, neomycin, metronidazole, vancomycin; antibiotics, ABx) to build a mouse model of ABx-induced bacterial depletion; and faecal microbiota from different groups were transplanted into BLM-treated or untreated ABx mice. The histopathological changes and collagen I and α-SMA expression were determined. Polydatin effectively reduced the degree of fibrosis in a BLM-induced pulmonary fibrosis mouse model; BLM and/or polydatin affected the abundance of the dominant gut microbiota in mice. Moreover, faecal microbiota transplantation (FMT) from polydatin-treated BLM mice effectively alleviated lung fibrosis in BLM-treated ABx mice compared with FMT from BLM mice. Polydatin can reduce fibrosis and inflammation in a BLM-induced mouse pulmonary fibrosis model. The alteration of gut microbiota by polydatin may be involved in the therapeutic effect.

Effect of Liuzijue on pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: study protocol for a multicenter, non-randomized, prospective study.

BACKGROUND: Traditional Chinese exercise as a new pulmonary rehabilitation technique has been increasingly used and achieved good results in pulmonary rehabilitation of chronic obstructive pulmonary disease (COPD). The aim of this study is to investigate the protective effects of Liuzijue on exercise tolerance, lung function, and quality of life in patients with COPD. METHODS: This study is a multicenter, non-randomized, prospective study. Patients will be divided into a control group (CG) and a Liuzijue group (LG) based on their willingness to learn Liuzijue. None of the outcome assessors will know the grouping of patients. Participants in this study will be collected from stable COPD patients who are outpatients or inpatients in 3 centers in China since September 2021. Patients will meet the diagnostic criteria for GOLD stage I-II COPD (FEV1% ≥ 0.5 and FEV1/FVC < 0.7) and be aged 40 years or older. Patients voluntarily will take part in the clinical study and sign an informed consent form. All participants will follow their existing medication. For LG patients, Liuzijue training has been added. Patients will practice Liuzijue for more than 30 minutes a day, more than 5 days a week, and adhere to the training for 3 months. Outcome indicators are 6-minute walk test (6MWT), lung function (FEV1%, FEV1/FVC, MMEF, PEF), modified British Medical Research Council (mMRC) score, COPD assessment test score (CAT), acute exacerbations and changes in drug treatment. DISCUSSION: This study quantified the effect of Liuzijue on the pulmonary rehabilitation of COPD patients in the stable phase of the disease, and provided a basis for the use of Liuzijue in COPD patients. TRIAL REGISTRATION: Chinese clinical trial registry, ChiCTR2100048945. Date: 2021-07-19. http://www.chictr.org.cn/showproj.aspx?proj=129094.

Intralobular pulmonary sequestration in the middle lobe supplied by a right internal mammary artery: a case report.

BACKGROUND: Pulmonary sequestration (PS) is a rare congenital malformation that is more common in the left lower lobe, and the thoracic aorta is the most common arterial supply. CASE PRESENTATION: We describe a case of a 67-year-old man with a chief complaint of intermittent cough and hemoptysis who had been diagnosed by multidetector computed tomography angiography with right middle lobe intralobular pulmonary sequestration supplied by a right internal mammary artery. Finally, he underwent middle pulmonary lobectomy with normal postoperative recovery. DISCUSSION: This is a rare intralobular pulmonary sequestration case for a feeding artery from the right internal mammary. Multidetector computed tomography angiography should be performed for diagnosis and preoperative evaluation once pulmonary sequestration is suspected.

Emodin inhibiting neutrophil elastase-induced epithelial-mesenchymal transition through Notch1 signalling in alveolar epithelial cells.

The transition of alveolar type II epithelial cells into fibroblasts has been reported to cause and/or aggravate pulmonary fibrosis (PF), which is characterized by fibroblast proliferation, an enhanced production and accumulation of ECM (extracellular matrix), alveolar wall damage and functional capillary unit loss. Traditional Chinese medicine Emodin has been reported to inhibit TGF-ß-induced epithelial-mesenchymal transition (EMT) in alveolar epithelial cells through Notch signalling. In the present study, neutrophil elastase (NE, also known as ELA2) treatment promoted EMT, Notch1 cleavage (NICD/Notch1 ratio increase) and NICD nuclear translocation in RLE-6TN cells and A549 cells. The promotive roles of NE treatment in these events were significantly reversed by Notch1 knockdown. Traditional Chinese medicine Emodin treatment remarkably inhibited the enzyme activity of NE, suppressed EMT, Notch1 cleavage and NICD nuclear translocation within RLE-6TN and A549 cells, while NE treatment significantly reversed the effects of Emodin. Moreover, in RLE-6TN, the effects of NE on EMT, Notch1 cleavage and NICD nuclear translocation were remarkably attenuated by Emodin treatment and more attenuated by the combination of Emodin and neutrophil elastase inhibitor Sivelestat or notch signal pathway inhibitor DAPT. In conclusion, we revealed the involvement of NE-induced Notch1 cleavage in the functions of Emodin suppressing NE-caused EMT in RLE-6TN cells and A549 cells. This novel mechanism of Emodin inhibiting EMT might extend the application of Emodin in PF treatment.

Emodin suppresses TGF-ß1-induced epithelial-mesenchymal transition in alveolar epithelial cells through Notch signaling pathway.

Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-ß1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway. Emodin inhibits the proliferation of Rat alveolar type II epithelial cells RLE-6TN in a concentration-dependent manner; reduces the expression of Collagen I, α-SMA and Vimentin, promotes the expression of E-cadherin. Moreover, Emodin could regulate the expression patterns of the Notch signaling pathway-related factors and reduce the Notch-1 nucleus translocation. Knockdown of Notch-1 enhances the inhibitory effect of Emodin on TGF-ß1-induced EMT in RLE-6TN cells. In conclusion, the data of the present study suggests that Emodin suppresses TGF-ß1-induced EMT in alveolar epithelial cells through Notch signaling pathway and shows the potential to be effective in the treatment of pulmonary fibrosis.

[Effect of Polydatin on Epithelial-Mesenchymal Transition of Human Alveolar Epithelium A549 Cells Induced by TGF-ß1].

OBJECTIVE: To explore the effect of polydatin on the growth of TGF-ß1induced humanalveolar epithelium A549 cells and the mechanism of polydatin for inhibiting the process of epithelial-mesenchymal transition (EMT). METHODS: A549 cells in vitro cultured were randomly divided into five groups, i.e., the blank group, the control group, the low dose polydatin group, the middle dose polydatin group, the high dose polydatin group. Common culture fluid was added in A549 cells of the blank group. Five ng/mLTGF-ß1contained culture fluid was added in A549 cells of the control group. 50, 100, and 150 µmol/mL of polydatin plus 5 ng/mL TGF-ß1contained culture fluid was added in A549 cells of low, middle, and high dosepolydatin groups, respectively. Morphological changes were observed and recorded at different time points. The optimal concentration of polydatin was determined by MTT method. Protein and mRNA expressions of E-cad epithelial cell marker) and Vimentin (mesenchymal cell marker) were detected by Western blot and Real-time PCR. RESULTS: Under inverted phase contrast microscope, A549 cells turned from previous pebble shape to fusiform shape after intervened by polydatin and TGF-ß1. The intercellular space was enlargedand the intercellular connection became loose. These phenomena were more obviously seen in the control group. A549 cells were more satiated in low, middle, and high dose polydatin groups than in the control group. The EMT inhibition was most obviously seen in the middle dose polydatin group at 48 h. Protein and mRNA expressions of E-cad showed an overall descending tendency after intervened by polydatin and TGF-ß1 (P < 0.05). But compared with the control group, protein and mRNA expressions of E-cad were down-regulated in a lesser amplitude in each intervened group. Besides, the tendency was more obviously seen at 48 h than at 24 h. Protein and mRNA expressions of Vimentin showed an overall up-regulating tendency. But compared with the control group, protein and mRNA expressions of Vimentin were down-regulated in a lesser amplitude in each intervened group. Besides, the tendency was more obviously seen at 48 h than at 24 h (P < 0.05). CONCLUSIONS Polydatin could inhibit TGF-ß1 induced EMT process of A549 cells time- and dose-dependently. It also played roles in inhibiting pulmonary fibrosis.

IL-17A, but not IL-17F, is indispensable for airway vascular remodeling induced by exaggerated Th17 cell responses in prolonged ovalbumin-challenged mice.

We previously demonstrated an essential role of Th17 cells in excessive mucous secretion and airway smooth muscle proliferation in a prolonged OVA-challenged C57BL/6 mouse model. However, the impact of Th17 cells in vascular remodeling, another characteristic feature of airway remodeling in asthma, remains elusive. This issue was further investigated in this study. The time-course experiments showed that progressively increasing levels of Th17 cells and IL-17A (not IL-17F) in the lungs of prolonged allergen-challenged mice were positively correlated with microvessel density in peribronchial tissues. In addition, exaggerated airway vascular remodeling in this mouse model was exacerbated by airway administration of IL-17A or adoptive transfer of Th17 cells. This effect was dramatically alleviated by the administration of anti-IL-17A Ab, but not anti-IL-17F Ab. Boyden chamber assays indicated that IL-17A accelerates endothelial progenitor cell (EPC) migration. Furthermore, EPC accumulation in the airways of allergen-exposed mice after adoptive transfer of Th17 cells was eliminated by blockade of IL-17A. We found that IL-17A promoted tubule-like formation rather than proliferation of pulmonary microvascular endothelia cells (PMVECs) in vitro. In addition, IL-17A induced PMVEC tube formation via the PI3K/AKT1 pathway, and suppression of the PI3K pathway markedly reduced the formation of tubule-like structures. Collectively, our results indicate that Th17 cells contribute to the airway vascular remodeling in asthma by mediating EPC chemotaxis, as well as PMVEC tube formation, via IL-17A rather than IL-17F.