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Adipose Tissue-Derived Mesenchymal Stem Cells Protect Against Amiodarone-Induced Lung Injury in Rats.


  • 影响因子:2.17
  • DOI:10.1007/s12010-020-03227-8
  • 作者列表:"Radwan SM","Ghoneim D","Salem M","Saeed M","Saleh Y","Elhamy M","Wael K","Shokair O","Wahdan SA
  • 发表时间:2020-01-17

:Pulmonary fibrosis (PF) is a progressive and irreversible lung disease, characterized by poor prognosis with limited treatment options. Mesenchymal stem cells (MSCs) are multi-potent cells having the ability to self-renew and differentiate into multiple tissues, thus considered a novel treatment option. The present study aimed to investigate the possible antifibrotic effect of undifferentiated adipose tissue-derived mesenchymal stem cell (AD-MSC) therapy on PF experimentally induced in rats using amiodarone (AMD). AMD (30 mg/kg) was given orally, once daily for 12 consecutive weeks to induce lung fibrosis. Following the confirmation of lung damage with histopathological examination, AD-MSCs (2 × 106 and 4 × 106 undifferentiated MSCs) were injected once intravenously, followed by 2 months for treatment. AMD induced focal fibroblastic cells proliferation in the peribronchiolar tissue, as well as in between the collapsed emphysematous alveoli. Also, AMD significantly increased serum and lung homogenate fibroblast growth factor-7 (FGF7), Clara cell protein-16 (CC16), and cytokeratin -19 (CK19) levels, as well as the expression of both iNOS and NFкB in the lung alveoli. Moreover, AMD caused excessive collagen deposition and increased alpha smooth muscle actin (α-SMA) expression. All findings significantly regressed on stem cell therapy in both doses, with superior effect of the high dose, providing evidence that adipose tissue-derived MSCs could be a promising approach for the treatment of PF. Graphical Abstract.


: 肺纤维化 (PF) 是一种进行性和不可逆的肺部疾病,其特点是预后不良,治疗选择有限。间充质干细胞 (MSCs) 是多能细胞,具有自我更新和分化为多个组织的能力,因此被认为是一种新的治疗选择。本研究旨在探讨未分化脂肪组织来源的间充质干细胞 (AD-MSC) 治疗胺碘酮 (AMD) 诱导的大鼠 PF 的可能抗纤维化作用。给予 AMD (30 mg/kg) 口服,每日 1 次,连续 12 周诱导肺纤维化。经组织病理学检查证实为肺损伤后,静脉注射 AD-MSCs (2 × 106 和 4 × 106 未分化 MSCs) 1 次,然后治疗 2 个月。AMD 在细支气管周围组织以及塌陷的肺气肿肺泡之间诱导局灶性成纤维细胞增殖。同样,AMD 显著增加血清和肺匀浆成纤维细胞生长因子-7 (FGF7) 、克拉拉细胞蛋白-16 (CC16) 和细胞角蛋白-19 (CK19) 水平, 以及肺泡中 iNOS 和 nf к b 的表达。此外,AMD 引起胶原过度沉积,α 平滑肌肌动蛋白 (α-SMA) 表达增加。所有结果在两种剂量的干细胞治疗中均显著消退,具有高剂量的优越效果,提供了脂肪组织来源的 MSCs 可能是治疗 PF 的一种有前途的方法的证据。图形摘要。



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
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
来源期刊:New biotechnology
作者列表:["Sousa SA","Soares-Castro P","Seixas AMM","Feliciano JR","Balugas B","Barreto C","Pereira L","Santos PM","Leitão JH"]

METHODS::Bacteria of the Burkholderia cepacia complex (Bcc) are ubiquitous multidrug resistant organisms and opportunistic pathogens capable of causing life threatening lung infections among cystic fibrosis (CF) patients. No effective therapies are currently available to eradicate Bcc bacteria from CF patients, as these organisms are inherently resistant to the majority of clinically available antimicrobials. An immunoproteomics approach was used to identify Bcc proteins that stimulate the humoral immune response of the CF host, using bacterial cells grown under conditions mimicking the CF lung environment and serum samples from CF patients with a clinical record of Bcc infection. 24 proteins of the Bcc strain B. cenocepacia J2315 were identified as immunoreactive, 19 here reported as immunogenic for the first time. Ten proteins were predicted as extracytoplasmic, 9 of them being conserved in Bcc genomes. The immunogenic Bcc extracytoplasmic proteins are potential targets for development of novel therapeutic strategies and diagnostic tools to protect patients against the onset of chronic Bcc lung infections.