Pulmonary pharmacology & therapeutics最新文献

{"title":"Evaluation of high dose N- Acetylcysteine on airway inflammation and quality of life outcomes in adults with bronchiectasis: A randomised placebo-controlled pilot study","authors":"L. Jayaram, P.T. King, J. Hunt, M. Lim, C. Park, E. Hu, L. Dousha, P. Ha, J.B. Bartlett, Southcott Am, S. Muruganandan, S. Vogrin, M.A. Rees, O.M. Dean, C.A. Wong","doi":"10.1016/j.pupt.2023.102283","DOIUrl":"https://doi.org/10.1016/j.pupt.2023.102283","url":null,"abstract":"<h3>Background</h3><p>High dose N acetylcysteine (NAC), a mucolytic, anti-inflammatory and antioxidant agent has been shown to significantly reduce exacerbations, and improve quality of life in placebo controlled, double blind randomised (RCT) studies in patients with COPD, and in an open, randomised study in bronchiectasis. In this pilot, randomised, double-blind, placebo-controlled study, we wished to investigate the feasibility of a larger clinical trial, and the anti-inflammatory and clinical benefits of high dose NAC in bronchiectasis.</p><h3>Aims</h3><p>Primary outcome: to assess the efficacy of NAC 2400 mg/day at 6 weeks on sputum neutrophil elastase (NE), a surrogate marker for exacerbations. Secondary aims included assessing the efficacy of NAC on sputum MUC5B, IL-8, lung function, quality of life, and adverse effects.</p><h3>Methods</h3><p>Participants were randomised to receive 2400 mg or placebo for 6 weeks. They underwent 3 visits: at baseline, week 3 and week 6 where clinical and sputum measurements were assessed.</p><h3>Results</h3><p>The study was stopped early due to the COVID pandemic. In total 24/30 patients were recruited, of which 17 completed all aspects of the study. Given this, a per protocol analysis was undertaken: NAC (n = 9) vs placebo (n = 8): mean age 72 vs 62 years; male gender: 44% vs 50%; baseline median FEV₁1.56 L (mean 71.5 % predicted) vs 2.29L (mean 82.2% predicted). At 6 weeks, sputum NE fell by 47% in the NAC group relative to placebo (mean fold difference (95%CI: 0.53 (0.12,2.42); MUC5B increased by 48% with NAC compared with placebo. Lung function, FVC improved significantly with NAC compared with placebo at 6 weeks (mean fold difference (95%CI): 1.10 (1.00, 1.20), p = 0.045. Bronchiectasis Quality of life measures within the respiratory and social functioning domains demonstrated clinically meaningful improvements, with social functioning reaching statistical significance. Adverse effects were similar in both groups.</p><h3>Conclusion</h3><p>High dose NAC exhibits anti-inflammatory benefits, and improvements in aspects of quality of life and lung function measures. It is safe and well tolerated. Further larger placebo controlled RCT's are now warranted examining its role in reducing exacerbations.</p>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"88 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139022393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of nirmatrelvir/ritonavir on tacrolimus levels in lung transplant recipients: A single-center study","authors":"Xiaoxing Wang ,&nbsp;Wenwen Du ,&nbsp;Dan Zhang ,&nbsp;Wenhui Chen ,&nbsp;Xianbo Zuo","doi":"10.1016/j.pupt.2023.102280","DOIUrl":"10.1016/j.pupt.2023.102280","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Lung transplant recipients (LTRs) have a higher risk of hospitalization and mortality due to COVID-19 compared with the immunocompetent population. The use of nirmatrelvir/ritonavir (NR), an effective oral treatment for COVID-19, is quite challenging due to its potent drug-drug interactions with </span>immunosuppressants<span><span> and azole </span>antifungals<span>. As there are few clinical reports of the use of NR in LTRs, we measured tacrolimus levels </span></span></span>in patients receiving NR in our hospital to improve safety when prescribing NR.</p></div><div><h3>Methods</h3><p><span>In total, 48 adult LTRs who received NR between November 19, 2022, and January 19, 2023, at China-Japan Friendship Hospital were retrospectively included and followed for 20 days after initiating NR. Tacrolimus was held at least 12 h before initiating NR and re-administered based on the trough levels after completing NR treatment. All concomitant medications, </span>drug concentrations, laboratory results, and genotypes were recorded and analyzed.</p></div><div><h3>Results</h3><p>Most patients showed stable tacrolimus trough levels despite high individual variability. Four patients exhibited supratherapeutic trough levels of tacrolimus (more than 15 ng/mL). Two patients who received 0.5 mg of tacrolimus during NR treatment had trough levels below 3.0 ng/mL. In addition, we found that in 13 patients, the trough levels were 130% of baseline after cessation of tacrolimus, and logistic regression revealed that increased trough level was significantly associated with age more than 60 years.</p></div><div><h3>Conclusions</h3><p>NR can be safely used in LTRs with close monitoring of tacrolimus levels and appropriate dose adjustments. However, more attention should be paid to elderly patients, as NR may more severely affect their drug metabolism. Due to the limited sample size, further studies are needed to guide the optimal use of tacrolimus following treatment with NR and explore the risk factors significantly affecting the interactions between NR and tacrolimus.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"84 ","pages":"Article 102280"},"PeriodicalIF":3.2,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138547215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can single-inhaler Beclometasone Dipropionate/Formoterol Fumarate/Glycopyrronium therapy postpone or save biologics for severe asthma?","authors":"Silvano Dragonieri,&nbsp;Vitaliano Nicola Quaranta,&nbsp;Andrea Portacci,&nbsp;Giovanna Elisiana Carpagnano","doi":"10.1016/j.pupt.2023.102270","DOIUrl":"10.1016/j.pupt.2023.102270","url":null,"abstract":"<div><p><span>Inhaled corticosteroids, along with beta2-agonists and anti-muscarinics, represent the cornerstone of asthma treatment<span><span>. Although the advent of monoclonal antibodies has dramatically changed </span>severe asthma management, there are still patients ineligible or with poor response to biologics. Moreover, high costs associated with monoclonal antibodies prescription are still an open issue, leading clinicians to carefully assess cost-benefit ratio before their administration. From this perspective, the use of single-inhaler Beclometasone Dipropionate/Formoterol Fumarate/Glycopyrronium </span></span>in patients with severe asthma could not only improve their clinical and functional performance, but also postpone biologic prescription, with positive repercussions on healthcare costs.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"83 ","pages":"Article 102270"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement of asthma control in adult patients using extrafine inhaled beclomethasone/formoterol fixed combination as maintenance therapy as well as maintenance and reliever therapy – CONTROL study","authors":"Tomasz Dębowski ,&nbsp;Monika Marko ,&nbsp;Barbara Rogala ,&nbsp;Paweł Majak ,&nbsp;Rafał Pawliczak","doi":"10.1016/j.pupt.2023.102272","DOIUrl":"10.1016/j.pupt.2023.102272","url":null,"abstract":"<div><h3>Introduction</h3><p>Extrafine formulation of beclomethasone/formoterol fixed combination (BDP/F pMDI HFA) is approved for both fixed maintenance and maintenance and reliever therapy (MART) of asthma, and recent data has proven that BDP/F pMDI HFA maintenance and reliever therapy is an effective alternative to other regimens.</p></div><div><h3>Objective</h3><p>This study aimed to assess the level of asthma control in a real-life setting in adult patients using extrafine BDP/F pMDI HFA fixed combination in a pressurized metered-dose inhaler (pMDI) as fixed maintenance dosing as well as maintenance and maintenance and reliever therapy. Additionally, we examined patients’ satisfaction with the inhaler device and compliance with therapy as essential factors determining asthma control.</p></div><div><h3>Methods</h3><p>This multicenter prospective non-interventional observational study lasted 4 months with 3 patient visits. We used the Asthma Control Questionnaire 7 (ACQ-7) to evaluate the degree of asthma control and Morisky Medication Adherence Scale (MMAS-4) to assess compliance. A self-developed questionnaire was used to assess satisfaction with the inhaler device.</p></div><div><h3>Results</h3><p>2179 patients using BDP/F pMDI HFA fixed combination as maintenance and reliever therapy or BDP/F pMDI HFA as maintenance therapy and SABA (short-acting beta₂-agonist) as a reliever for at least 2 months were included. During the prospective follow-up, we observed an upward trend in the FEV1% (forced expiratory volume in 1 s) predicted values, improvement in the control of symptoms as indicated by a decline in the mean ACQ-7 score was noted (1.62 at Visit 1 vs. 1.21 at Visit 2 vs. 0.94 at Visit 3, p &lt; 0.001) and increase in patients’ compliance (the number of patients that reported forgetting at times to take their medication was reduced from 49.7 % to 27.1 %, p &lt; 0.001). At the same time, we noted a reduction in the number of as-needed doses used for symptom relief (p &lt; 0.001). Most patients were satisfied with the pMDI, considered it easy and convenient to use, and preferred it to a dry powder inhaler (p &lt; 0.001).</p></div><div><h3>Conclusions</h3><p>The use of extrafine BDP/F pMDI HFA as maintenance as well as reliever therapy seems to be associated with increased asthma control and better compliance to therapy.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"84 ","pages":"Article 102272"},"PeriodicalIF":3.2,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1094553923000846/pdfft?md5=8a220b559f944d45e1562736287df2a3&pid=1-s2.0-S1094553923000846-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cefepime pharmacokinetics in adult extracorporeal membrane oxygenation patients","authors":"Lily Zheng ,&nbsp;Mohammad H. Alshaer ,&nbsp;Charles Peloquin ,&nbsp;Veena Venugopalan ,&nbsp;Hassan M. Alnuaimat ,&nbsp;Maureen Converse","doi":"10.1016/j.pupt.2023.102271","DOIUrl":"10.1016/j.pupt.2023.102271","url":null,"abstract":"<div><h3>Background</h3><p>The impact of extracorporeal membrane oxygenation<span><span> (ECMO) on the pharmacokinetics/dynamics (PK/PD) of beta-lactam antibiotics have not been well studied in general, but cefepime specifically has the least amount of data. We aimed to investigate whether ECMO alters the PK of cefepime in adult </span>intensive care unit (ICU) patients.</span></p></div><div><h3>Methods</h3><p>This single-center, retrospective case-control study evaluated cefepime therapeutic drug<span><span><span> monitoring (TDM) results from ECMO patients that were matched 1:1 with TDM results in non-ECMO patients for drug regimen and renal function. The primary outcome was the difference in PK/PD of cefepime in ECMO compared with non-ECMO ICU patients. Secondary outcomes included hospital length of stay, treatment failure, </span>superinfection, </span>bacterial resistance, and survival to discharge.</span></p></div><div><h3>Results</h3><p><span>Eighty-two patients were included with 44 matched cefepime concentrations in each group. ECMO patients had higher free maximum concentrations (fCmax) (p = 0.003), lower free minimum concentration (fCmin)/1x minimum inhibitory concentration (MIC) ratios (</span><em>p</em> = 0.040), and lower attainment of free Cmin/4x MIC (<em>p</em><span> = 0.010). There were no differences between the groups for free Cmin, time above 1xMIC or 4x MIC, and pharmacokinetic parameters (ke, half-life, and Vd). Of those who survived to discharge, hospital length of stay was longer in the ECMO group (</span><em>p</em> &lt; 0.001). Patients on ECMO were more likely to experience treatment failure (<em>p</em> = 0.036). The incidence of bacterial resistance, superinfection, or survival were similar among the groups.</p></div><div><h3>Conclusion</h3><p>These data suggest that more aggressive empiric dosing may be warranted in patients on ECMO. Therapeutic drug monitoring and future prospective studies would provide more evidence to guide decision making regarding dose adjustments.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"84 ","pages":"Article 102271"},"PeriodicalIF":3.2,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-fibrotic effects of nintedanib on lung fibroblasts derived from patients with Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs)","authors":"Audrey Joannes ,&nbsp;Tom Voisin ,&nbsp;Claudie Morzadec ,&nbsp;Alice Letellier ,&nbsp;Francisco Llamas Gutierrez ,&nbsp;Dan Cristian Chiforeanu ,&nbsp;Cécile Le Naoures ,&nbsp;Stéphanie Guillot ,&nbsp;Bertrand Richard De Latour ,&nbsp;Simon Rouze ,&nbsp;Madeleine Jaillet ,&nbsp;Bruno Crestani ,&nbsp;Lutz Wollin ,&nbsp;Stéphane Jouneau ,&nbsp;Laurent Vernhet","doi":"10.1016/j.pupt.2023.102267","DOIUrl":"10.1016/j.pupt.2023.102267","url":null,"abstract":"<div><p><span><span><span>The tyrosine kinase inhibitor </span>nintedanib has been recently approved for the treatment of </span>Interstitial Lung Diseases<span> (ILDs) that manifest a progressive fibrosis phenotype other than </span></span>Idiopathic pulmonary Fibrosis (IPF).</p><p><span>Nintedanib reduces the development of lung fibrosis in various animal models resembling features of PF-ILD and </span><em>in vitro</em><span><span>, it inhibits the fibrosing phenotype of human lung fibroblasts (HLFs) isolated from patients with IPF. To get insight on the cellular and molecular mechanisms that drive the clinical efficiency of nintedanib </span>in patients with non-IPF PF-ILD, we investigated its effects on the fibrosing functions of HLFs derived from patients with PF-hypersensitivity pneumonitis (PF-HP, n = 7), PF-sarcoidosis (n = 5) and pleuroparenchymal fibroelastosis (PPFE, n = 4).</span></p><p>HLFs were treated with nintedanib (10 nM-1 μM) and then stimulated with PDGF-BB (25–50 ng/ml) or TGF-β1 (1 ng/ml) for 24–72 h to assess proliferation and migration or differentiation.</p><p><span>At nanomolar concentrations, nintedanib reduced the levels of PDGF receptor and ERK1/2 phosphorylation, the proliferation and the migration of PF-HP, PF-sarcoidosis and PPFE HLFs stimulated with PDGF-BB. Moreover, nintedanib also attenuates the myofibroblastic differentiation driven by TGF-β1 but only when it is used at 1 μM. The </span>drug<span> reduced the phosphorylation of SMAD2/3 and decreased the induction of collagen, fibronectin and α-smooth muscle actin expression induced by TGF-β1.</span></p><p>In conclusion, our results demonstrate that nintedanib counteracts fundamental fibrosing functions of lung fibroblasts derived from patients with PF-HP, PF-sarcoidosis and PPFE, at concentrations previously reported to inhibit control and IPF HLFs. Such effects may contribute to its clinical benefit in patients suffering from these irreversible ILDs.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"83 ","pages":"Article 102267"},"PeriodicalIF":3.2,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136398962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tyvaso DPI: Drug-device characteristics and patient clinical considerations","authors":"Colleen McEvoy ,&nbsp;Rahul Argula ,&nbsp;Sandeep Sahay ,&nbsp;Shelley Shapiro ,&nbsp;Christina Eagan ,&nbsp;Anthony J. Hickey ,&nbsp;Chad Smutney ,&nbsp;Chris Dillon ,&nbsp;Thomas Winkler ,&nbsp;Brittany N. Davis ,&nbsp;Meredith Broderick ,&nbsp;Charles Burger","doi":"10.1016/j.pupt.2023.102266","DOIUrl":"10.1016/j.pupt.2023.102266","url":null,"abstract":"<div><p>Tyvaso DPI is a drug-device combination therapy comprised of a small, portable, reusable, breath-powered, dry powder inhaler (DPI) for the delivery of treprostinil. It is approved for the treatment of pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease. Tyvaso DPI utilizes single-use prefilled cartridges to ensure proper dosing. Unlike nebulizer devices, administration of Tyvaso DPI is passive and does not require coordination with the device. The low-flow rate design results in targeted delivery to the peripheral lungs due to minimal drug loss from impaction in the oropharynx. The inert fumaryl diketopiperazine (FDKP) excipient forms microparticles that carry treprostinil into the airways, with a high fraction of the particles in the respirable range. In a clinical study in patients with pulmonary arterial hypertension, Tyvaso DPI had similar exposure and pharmacokinetics, low incidence of adverse events, and high patient satisfaction compared with nebulized treprostinil solution. Tyvaso DPI may be considered as a first prostacyclin agent or for those that do not tolerate other prostacyclin formulations, patients with pulmonary comorbidities, patients with mixed Group 1 and Group 3 pulmonary hypertension, or those that prefer an active lifestyle and need a portable, non-invasive treatment. Tyvaso DPI is a patient-preferred, maintenance-free, safe delivery option that may improve patient compliance and adherence.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"83 ","pages":"Article 102266"},"PeriodicalIF":3.2,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1094553923000780/pdfft?md5=a2533bc287439f9ecc193b026c7bf7fd&pid=1-s2.0-S1094553923000780-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134649629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The compound artemisinin-hydroxychloroquine ameliorates bleomycin-induced pulmonary fibrosis in rats by inhibiting TGF-β1/Smad2/3 signaling pathway","authors":"Zhaojia Wang ,&nbsp;Min Liu ,&nbsp;Ying Ai ,&nbsp;Shaoqin Zheng ,&nbsp;Yingyi Chen ,&nbsp;Hujun Du ,&nbsp;Shijia Yuan ,&nbsp;Xueying Guo ,&nbsp;Yueming Yuan ,&nbsp;Guoming Li ,&nbsp;Jianping Song ,&nbsp;Changsheng Deng","doi":"10.1016/j.pupt.2023.102268","DOIUrl":"10.1016/j.pupt.2023.102268","url":null,"abstract":"<div><p><span>Pulmonary fibrosis<span><span><span> (PF) is a lethal disease characterized by a progressive decline in lung function. Currently, lung transplantation remains the only available </span>treatment for PF. However, both </span>artemisinin<span><span> (ART) and hydroxychloroquine (HCQ) possess potential antifibrotic properties. This study aimed to investigate the effects and mechanisms of a compound known as Artemisinin-Hydroxychloroquine (AH) in treating PF, specifically by targeting the TGF-β1/Smad2/3 pathway. To do this, we utilized an animal model of PF induced by a single tracheal drip of </span>bleomycin<span><span><span> (BLM) in Sprague-Dawley (SD) rats. The PF animal models were administered various doses of AH, and the efficacy and safety of AH were evaluated through pulmonary function testing<span>, blood routine tests, serum biochemistry tests, organ index measurements, and pathological examinations. Additionally, Elisa, </span></span>western blotting, and qPCR techniques were employed to explore the potential molecular mechanisms of AH in treating PF. Our findings reveal that AH effectively and safely alleviate PF by inhibiting BLM-induced specific inflammation, reducing </span>extracellular matrix<span> (ECM) deposition, and interfering with the TGF-β1/Smad2/3 signaling pathway. Notably, the windfall for this study is that the inhibition of ECM may initiate self-healing in the BLM-induced PF animal model. In conclusion, AH shows promise as a potential therapeutic </span></span></span></span></span>drug<span> for PF, as it inhibits disease progression through the TGF-β1/Smad2/3 signaling pathway.</span></p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"83 ","pages":"Article 102268"},"PeriodicalIF":3.2,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134649579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The wonders of stem cells therapeutic application towards chronic obstructive pulmonary disease","authors":"Akram Tayanloo-Beik ,&nbsp;Shayesteh Kokabi Hamidpour ,&nbsp;Mohaddese chaharbor ,&nbsp;Mostafa Rezaei-Tavirani ,&nbsp;Rasta Arjmand ,&nbsp;Hossein Adibi ,&nbsp;Hamid Ojagh ,&nbsp;Bagher Larijani ,&nbsp;Babak Arjmand","doi":"10.1016/j.pupt.2023.102269","DOIUrl":"10.1016/j.pupt.2023.102269","url":null,"abstract":"<div><p><span>Chronic obstructive pulmonary disease (COPD) is a respiratory condition characterized by its heterogeneous nature, progressive course, and significant impact on individuals' </span>quality of life<span>. It is a prevalent global health issue affecting a substantial number of individuals and can pose life-threatening complications if left unmanaged. The development and course of COPD can be influenced by a range of risk factors, including genetic predisposition<span> and environmental exposures. Nevertheless, as researchers adopt a more comprehensive and expansive viewpoint of therapeutic techniques, the associated obstacles become more apparent. Indeed, a definitive medication for COPD that reliably leads to symptom alleviation has not yet been discovered. Therefore, the limitations of conventional therapy methods prompted researchers to focus on the advancement of novel procedures, potentially leading to significant outcomes. In contemporary times, the field of regenerative medicine and cell therapy has presented unprecedented opportunities for the exploration of innovative treatments for COPD, owing to the distinctive attributes exhibited by stem cells. Hence, it is imperative to provide due consideration to preclinical investigations and notable characteristics of stem cells as they serve as a means to comprehensively comprehend the fundamental mechanisms of COPD and uncover novel therapeutic strategies with enhanced efficacy for patients.</span></span></p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"83 ","pages":"Article 102269"},"PeriodicalIF":3.2,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134649628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IRE1α/XBP-1 promotes β-catenin signaling activation of airway epithelium in lipopolysaccharide-induced acute lung injury","authors":"Hailing Zhang ,&nbsp;Jiehong Li ,&nbsp;Xilong Wang ,&nbsp;Kai Wang ,&nbsp;JianPeng Xie ,&nbsp;Guanjin Chen ,&nbsp;Yijian Li ,&nbsp;Kai Zhong ,&nbsp;Jiahui Li ,&nbsp;Xin Chen","doi":"10.1016/j.pupt.2023.102263","DOIUrl":"10.1016/j.pupt.2023.102263","url":null,"abstract":"<div><h3>Background</h3><p>Acute lung injury (ALI), along with the more severe condition--acute respiratory distress syndrome (ARDS), is a major cause of respiratory failure in critically ill patients with high morbidity and mortality. Inositol-requiring protein 1α (IRE1α)/X box protein-1 (XBP1) pathway was proved to regulate lipopolysaccharide (LPS)-induced lung injury and inflammation. Yet, its role on epithelial β-catenin in LPS-induced ALI remains to be elucidated.</p></div><div><h3>Methods</h3><p>LPS-induced models were generated in mice (5 mg/kg) and Beas-2B cells (200 μg/mL). Two selective antagonists of IRE1α (4μ8c and STF-083010) were respectively given to LPS-exposed mice and cultured cells.</p></div><div><h3>Results</h3><p>Up-regulated expression of endoplasmic reticulum (ER) stress markers immunoglobulin-binding protein (BIP) and spliced X box protein-1(XBP-1s) was detected after LPS<span> exposure. Besides, LPS also led to a down-regulated total β-catenin level in the lung and Beas-2B cells, with decreased membrane distribution as well as increased cytoplasmic and nuclear accumulation, paralleled by extensively up-regulated downstream targets of the Wnt/β-catenin signaling. Treatment with either 4μ8c or STF-083010 not only significantly attenuated LPS-induced lung injury and inflammation, but also recovered β-catenin expression in airway epithelia, preserving the adhesive function of β-catenin while blunting its signaling activity.</span></p></div><div><h3>Conclusion</h3><p>These results illustrated that IRE1α/XBP1 pathway promoted the activation of airway epithelial β-catenin signaling in LPS-induced ALI.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"83 ","pages":"Article 102263"},"PeriodicalIF":3.2,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71485359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}