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Protective effect of rutin against bleomycin induced lung fibrosis: Involvement of TGF-β1/α-SMA/Col I and III pathway.

芦丁对博莱霉素诱导的肺纤维化的保护作用: tgf-β 1/α-SMA/Col I 和 III 通路的参与。

  • 影响因子:3.52
  • DOI:10.1002/biof.1629
  • 作者列表:"Bai L","Li A","Gong C","Ning X","Wang Z
  • 发表时间:2020-03-31
Abstract

:Lung fibrosis is a progressive fatal lung disorder with significantly high mortality rates. Bleomycin (BLM) is one of the most commonly used chemotherapeutic agents for the treatment of several carcinomas. The most severe adverse effect of BLM is lung toxicity; therefore, BLM has been repeatedly reported to be considered amongst the most widely used agents for the induction of experimental lung fibrosis. In the current study, rutin has been investigated for its ability to ameliorate BLM-induced pulmonary fibrosis. BLM was instilled intratracheally and rutin was administered orally (50 and 100 mg/kg) for 3 weeks. Rutin significantly decreased lung/body weight index, bronchoalveolar lavage fluid lactate dehydrogenase activity, total cell count, macrophages, and lymphocyte counts. Rutin significantly decreased lung malondialdehyde content, increased lung glutathione content, superoxide dismutase activity, serum total antioxidant capacity, and decreased lung nitric oxide content. Moreover, rutin reduced expressions of transforming growth factor beta 1 and other fibrosis-related biomarkers (Col I, Col III, and α-SMA). In addition, rutin significantly ameliorated histological changes and prevented collagen deposition with the paralleled decrease in lung hydroxyproline content. In conclusion, rutin can be proposed to be a potential therapeutic agent for the management of lung fibrosis.

摘要

: 肺纤维化是一种进行性致死性肺疾病,死亡率显著增高。博莱霉素 (BLM) 是治疗多种癌症最常用的化疗药物之一。BLM 最严重的不良反应是肺毒性; 因此,BLM 被反复报道为诱导实验性肺纤维化最广泛使用的药物之一。在目前的研究中,芦丁已经研究了其改善 BLM 诱导的肺纤维化的能力。气管内滴注 BLM,口服芦丁 (50 和 100 mg/kg) 3 周。芦丁显著降低肺/体重指数、支气管肺泡灌洗液乳酸脱氢酶活性、总细胞计数、巨噬细胞和淋巴细胞计数。芦丁显著降低肺丙二醛含量,增加肺谷胱甘肽含量、超氧化物歧化酶活性、血清总抗氧化能力,降低肺一氧化氮含量。此外,芦丁降低转化生长因子 β 1 和其他纤维化相关生物标志物 (Col I 、 Col III 和 α-SMA) 的表达。此外,芦丁可明显改善肺组织病理改变,防止胶原沉积,同时降低肺羟脯氨酸含量。总之,芦丁可被认为是一种潜在的治疗肺纤维化的药物。

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DOI:10.1093/rheumatology/kez673
作者列表:["Vadillo C","Nieto MA","Romero-Bueno F","Leon L","Sanchez-Pernaute O","Rodriguez-Nieto MJ","Freites D","Jover JA","Álvarez-Sala JL","Abasolo L"]

METHODS:OBJECTIVES:To asses the clinical course in RA-related interstitial lung disease (RA-ILD) patients with and without rituximab (RTX). The influence of other variables was also evaluated. METHODS:A longitudinal multicentre study was conducted in RA diagnosed with ILD from 2007 until 2018 in Madrid. Patients were included in a registry [pNEumology RhEumatology Autoinmune diseases (NEREA)] from the time of ILD diagnosis. The main endpoint was functional respiratory impairment (FI), when there was a decline ≥5% in the predicted forced vital capacity compared with the previous one. Pulmonary function was measured at baseline and in follow-up visits every 6-12 months. The independent variable was therapy with RTX. Covariables included sociodemographic, clinical, radiological and other therapies. Survival techniques were used to estimate the incidence rate (IR) and 95% CI of functional impairment, expressed per 100 patient-semesters. Cox multivariate regression models were run to examine the influence of RTX and other covariates on FI. Results were expressed as the hazard ratio (HR) and CI. RESULTS:A total of 68 patients were included. FI occurred in 42 patients [IR 23.5 (95% CI 19, 29.1)] and 50% of them had FI within 1.75 years of an ILD diagnosis. A multivariate analysis showed that RTX exposure resulted in a lower risk of FI compared with non-exposure [HR 0.51 (95% CI 0.31, 0.85)]. Interstitial pneumonia, glucocorticoids, disease activity and duration also influenced FI. CONCLUSION:RA-ILD patients deteriorate over time, with the median time free of impairment being <2 years. Patients exposed to RTX had a higher probability of remaining free of FI compared with other therapies. Other factors have also been identified. Key words: rheumatoid arthritis, interstitial lung disease, observational study, rituximab and prognosis

翻译标题与摘要 下载文献
影响因子:4.40
发表时间:2020-01-01
DOI:10.1007/s00262-019-02431-8
作者列表:["Shibaki, Ryota","Murakami, Shuji","Matsumoto, Yuji","Yoshida, Tatsuya","Goto, Yasushi","Kanda, Shintaro","Horinouchi, Hidehito","Fujiwara, Yutaka","Yamamoto, Nobuyuki","Kusumoto, Masahiko","Yamamoto, Noboru","Ohe, Yuichiro"]

METHODS:The safety of anti-programmed cell death 1 (PD-1) antibody for patients with preexisting interstitial lung disease (ILD) remains unknown. The aim of this study was to evaluate the dependence of preexisting ILD on anti-PD-1 antibody-induced pneumonitis in non-small cell lung cancer (NSCLC) patients. We retrospectively reviewed the association of preexisting ILD with the incidence, radiographic pattern, and outcome of pneumonitis in NSCLC patients receiving anti-PD-1 antibody. A total of 331 patients were included in this study. Of these patients, 17 had preexisting ILD. The incidence of pneumonitis was higher among the patients with preexisting ILD than among those without preexisting ILD (29% vs. 10%, P  = 0.027). The distributions of the CT appearances at the onset of anti-PD-1 antibody-induced pneumonitis were as follows: for the patients with preexisting ILD, two patients (40%) had diffuse alveolar damage (DAD), one patient each with organizing pneumonia-like (OP), hypersensitivity pneumonitis (HP), and other patterns (20% each); for the patients without preexisting ILD, 19 patients (61%) had OP, 8 (26%) had HP, 3 (10%) had DAD, and 1 (3.2%) had other patterns. The median onset time from the initiation of anti-PD-1 antibody treatment until the development of pneumonitis was 1.3 months (range 0.3–2.1 months) for the patients with preexisting ILD and 2.3 months (range 0.2–14.6 months) for the patients without preexisting ILD. Careful attention to the development of pneumonitis is needed, especially within the first 3 months after the start of anti-PD-1 antibody treatment, when using anti-PD-1 antibody to treat patients with preexisting ILD.

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翻译标题与摘要 下载文献
影响因子:4.04
发表时间:2020-01-25
来源期刊:New biotechnology
DOI:10.1016/j.nbt.2019.08.006
作者列表:["Sousa SA","Soares-Castro P","Seixas AMM","Feliciano JR","Balugas B","Barreto C","Pereira L","Santos PM","Leitão JH"]

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