Pulmonary pharmacology & therapeutics最新文献

{"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":"2023-12-01","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":"Relative bioavailability of budesonide/glycopyrrolate/formoterol fumarate triple therapy delivered using next generation propellants with low global warming potential","authors":"Magnus Aurivillius ,&nbsp;Artur Bednarczyk ,&nbsp;Marek Kokot ,&nbsp;Jonathan Madriaga ,&nbsp;Jie Mei ,&nbsp;Kathryn Collison ,&nbsp;Raulin Surujbally ,&nbsp;James Archbell ,&nbsp;Vidya Joshi ,&nbsp;Michael Gillen","doi":"10.1016/j.pupt.2023.102245","DOIUrl":"10.1016/j.pupt.2023.102245","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;The climate crisis poses an immediate threat to human health and well-being, demanding urgent adaptions across sectors, including healthcare. The development of pressurized metered dose inhalers (MDIs) with greater sensitivity to the climate emergency using novel propellants with lower global warming potentials (GWPs), but comparable pharmacokinetic (PK) parameters to currently marketed MDIs, is a vital step toward reducing the impact of healthcare for respiratory disorders on climate change. This study evaluated the relative bioavailabilities of the individual components of a fixed-dose combination of budesonide/glycopyrrolate/formoterol fumarate (BGF) 160/9/4.8 μg per actuation between three different propellant formulations.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Healthy male participants (aged 18–60 years) were randomized into a single-blind, three-period, single-dose, single-center, crossover study (NCT04600505). The PK and safety and tolerability profiles of BGF MDI formulated with two novel propellants with low GWP (hydrofluoroolefin-1234ze [HFO]; hydrofluorocarbon-152a [HFC]) were compared with BGF MDI formulated with the propellant used in the currently marketed reference product (hydrofluoroalkane-134a [HFA]). The study included a screening period, three treatment periods (with 3- to 7-day washout periods between each dose), and a follow-up. The primary PK parameters assessed were maximum observed plasma concentration (C&lt;sub&gt;max&lt;/sub&gt;), area under the plasma concentration curve (AUC) from time zero extrapolated to infinity (AUC&lt;sub&gt;inf&lt;/sub&gt;), and AUC from time zero to the time of the last quantifiable analyte concentration (AUC&lt;sub&gt;last&lt;/sub&gt;). The study was not powered to statistically demonstrate bioequivalence.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Forty-seven participants completed the study, and 24 participants were evaluable for PK assessments. Systemic exposure, based on geometric mean ratios (90% confidence interval), to each BGF component from the test propellants delivered in a standard MDI was comparable with the reference propellant for AUC&lt;sub&gt;last&lt;/sub&gt; (HFO vs. HFA: budesonide, 107.30 [94.53, 121.90]; glycopyrrolate, 106.10 [86.18, 130.60]; formoterol, 98.13 [86.44, 111.40]; HFC vs. HFA: budesonide, 98.80 [84.59, 115.40]; glycopyrrolate, 99.71 [80.84, 123.00]; formoterol, 107.00 [88.82, 128.90]); AUC&lt;sub&gt;inf&lt;/sub&gt; (where evaluable) and C&lt;sub&gt;max&lt;/sub&gt; followed the same trend. There were no serious adverse events or adverse events leading to treatment discontinuation. No new safety signals were observed.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;Systemic BGF component exposure was similar for both test propellants (HFO and HFC) compared with the HFA reference propellant, with an acceptable safety profile in the studied population. Therefore, both novel low GWP propellants show strong potential as candidates for development of MDIs with greater sensitivity to the climate crisis, a vital step toward amelioratin","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"83 ","pages":"Article 102245"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10226716","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":"Medication use in people with cystic fibrosis before and after modulator therapy","authors":"Louise Lord ,&nbsp;Mark Hew ,&nbsp;Miriam TY. Leung ,&nbsp;Jedidiah I. Morton ,&nbsp;Jenni Ilomaki","doi":"10.1016/j.pupt.2023.102264","DOIUrl":"https://doi.org/10.1016/j.pupt.2023.102264","url":null,"abstract":"<div><h3>Background</h3><p>Long-term changes in medication dispensings post cystic fibrosis transmembrane conductance regulator<span> (CFTR) modulator initiation have not been described. Our study aimed to investigate changes in medication use following the initiation of modulator therapy in people with cystic fibrosis (PwCF) in Australia.</span></p></div><div><h3>Methods</h3><p>Using a 10% sample of the Australian Pharmaceutical Benefits Scheme (PBS) data between 2013 and 2022, linear regression was used to analyse dispensings in PwCF who initiated any modulator (cases) and matched PwCF controls not dispensed a modulator. The difference in mean number of total monthly dispensings pre- and post-modulator initiation was analysed, with separate analyses by medication class.</p></div><div><h3>Results</h3><p>A total of 247 cases were matched 1:1 to controls (case and control median age 21 years (IQR: 13–32), 55.1% male). Immediately after modulator initiation, the mean number of dispensings was 0.9 higher in the modulator group, but then decreased to the level of controls after approximately 5 years. After 7.5 years, cases had decreased opioids compared to the pre-modulator period (β-coefficient: −0.00131, 95% CI: −0.00164, −0.00097) whilst controls did not (β: −0.00014, 95% CI: −0.00042, 0.00014). Over the same time period controls had an increase in psychotropics<span> (β: 0.00389, 95% CI:0.00295, 0.00484) whilst cases remained stable (β: −0.00014, 95% CI: −0.0006, 0.00031). Women's health medications increased in cases (β:0.00026, 95% CI:0.0001, 0.00042) but decreased in controls (β: 0.00044, 95% CI: 0.00063, −0.00025).</span></p></div><div><h3>Conclusions</h3><p>Modulator initiation in PwCF was associated with decreased dispensings of opioids and psychotropics, and increased dispensings of women's health medications, suggesting improved patient outcomes across multiple clinical domains.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"83 ","pages":"Article 102264"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91956640","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":"2023-12-01","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}

{"title":"Nontuberculous mycobacterial (NTM) infections in bronchiectasis patients: A retrospective US registry cohort study","authors":"Myriam Drysdale ,&nbsp;Radmila Choate ,&nbsp;Amanda E. Brunton ,&nbsp;Simon Tiberi ,&nbsp;Iain A. Gillespie ,&nbsp;Noah Lininger ,&nbsp;Susan B. Shrimpton ,&nbsp;Mark Metersky ,&nbsp;Nicole C. Lapinel ,&nbsp;Pamela J. McShane ,&nbsp;Christopher J. Richards ,&nbsp;Colin Swenson ,&nbsp;Hema Sharma ,&nbsp;David Mannino ,&nbsp;Kevin L. Winthrop ,&nbsp;for the Bronchiectasis and NTM Research Registry Investigators","doi":"10.1016/j.pupt.2023.102260","DOIUrl":"10.1016/j.pupt.2023.102260","url":null,"abstract":"<div><h3>Rationale</h3><p>Longitudinal epidemiological and clinical data are needed to improve the management of patients with bronchiectasis<span> developing nontuberculous mycobacterial (NTM) pulmonary disease.</span></p></div><div><h3>Objectives</h3><p><span><span>To describe the epidemiology, patient management, and </span>treatment<span> outcomes of NTM infections </span></span>in patients with bronchiectasis enrolled in the United States Bronchiectasis and NTM Research Registry (US BRR).</p></div><div><h3>Methods</h3><p><span>This was a retrospective cohort study of patients with bronchiectasis and NTM infections enrolled with follow-up in the US BRR in 2008–2019. The study included patients with ≥1 positive NTM respiratory culture in the 24-month baseline period (baseline NTM cohort) and/or during the annual follow-up visits (incident NTM cohort). Incidence, prevalence, baseline </span>patient characteristics, treatment exposure, treatment outcomes, and respiratory clinical outcomes were described in the baseline NTM cohort, incident NTM cohort, and both cohorts combined (prevalent NTM cohort).</p></div><div><h3>Results</h3><p>Between 2008 and 2019, 37.9% (1457/3840) of patients with bronchiectasis in the US BRR met the inclusion criteria for this study and were reported to have <em>Mycobacterium avium</em> complex (MAC) and/or <span><em>Mycobacterium abscessus</em></span><span> complex (MABSC) infections. MAC prevalence increased steadily in the US BRR during 2009–2019; incidence was relatively stable, except for a peak in 2011 followed by a slow decrease. MABSC and mixed MAC/MABSC infections were rare. Most patients with bronchiectasis and NTM infections in the registry were female, White, and aged &gt;65 years. The antibiotics administered most commonly reflected current guidelines. In the prevalent cohort, 44.9% of MAC infections and 37.1% of MABSC infections remained untreated during follow-up, and MAC treatment was initiated with delay (&gt;90 days after positive NTM respiratory culture) twice as frequently as promptly (≤90 days after positive NTM respiratory culture) (68.6% vs 31.4%, respectively). The median time from diagnosis to treatment was shorter for MABSC versus MAC infections (194.0 days [interquartile range (IQR) 8.0, 380.0] vs 296.0 days [IQR 35.0, 705.0], respectively). Among patients with MAC infections who completed treatment, 27.6% were classified as cured and 29.6% as treatment failure during the annual follow-up visit window. For MABSC, these proportions were 25.0% and 28.0%, respectively.</span></p></div><div><h3>Conclusions</h3><p>A considerable proportion of MAC and MABSC infections were untreated or treated after initial delay/observation. MABSC infections were more likely to be treated and start treatment sooner than MAC infections. Further longitudinal studies are warranted to evaluate the monitor-with-delay approach and inform clinical guidelines.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"83 ","pages":"Article 102260"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41149117","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":"Knockdown of HDAC10 inhibits POLE2-mediated DNA damage repair in NSCLC cells by increasing SP1 acetylation levels","authors":"Hua Guo ,&nbsp;Hui Ren ,&nbsp;Kun Han ,&nbsp;Jianying Li ,&nbsp;Yu Dong ,&nbsp;Xuan Zhao ,&nbsp;Chunqi Li","doi":"10.1016/j.pupt.2023.102250","DOIUrl":"10.1016/j.pupt.2023.102250","url":null,"abstract":"<div><p><span><span>HDAC10 has been reported to be associated with poor prognosis </span>in patients with non-small cell lung cancer (NSCLC), however, the regulatory role and mechanisms of HDAC10 in NSCLC have not been investigated. In this study, we found that HDAC10 was increased in NSCLC patients and cell lines. And high expression of HDAC10 is linked to poor survival in NSCLC patients. The results showed that knockdown of HDAC10 triggered DNA damage, </span><em>S</em><span><span>-phase arrest, and proliferation inhibition in A549 and H1299<span> cells. In addition, knockdown of HDAC10 promoted cell ferroptosis<span> by enhancing ROS, </span></span></span>MDA and Fe</span>²⁺<span> levels. Mechanistically, HDAC10 knockdown reduced SP1<span> expression and elevated the acetylation<span> level of SP1, which inhibited the binding of SP1 to the promoter of POLE2, resulting in reduced POLE2 expression. Overexpression of SP1 or POLE2 partially reversed the effects of HDAC10 deletion on NSCLC cell proliferation and ferroptosis. In conclusion, knockdown of HDAC10 inhibited the proliferation of NSCLC cells and promoted their ferroptosis by regulating the SP1/POLE2 axis. HDAC10 might be a promising target for the treatment of NSCLC.</span></span></span></p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"83 ","pages":"Article 102250"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10245137","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":"Dihydroquercetin (DHQ) ameliorates LPS-induced acute lung injury by regulating macrophage M2 polarization through IRF4/miR-132-3p/FBXW7 axis","authors":"Chen Li,&nbsp;Jianhua Liu,&nbsp;Changhong Zhang,&nbsp;Liang Cao,&nbsp;Fang Zou,&nbsp;Zhihua Zhang","doi":"10.1016/j.pupt.2023.102249","DOIUrl":"10.1016/j.pupt.2023.102249","url":null,"abstract":"<div><h3>Background</h3><p><span>Acute lung injury (ALI) is a common complication of </span>sepsis<span>. Dihydroquercetin (DHQ) has been found to attenuate lipopolysaccharide (LPS)-induced inflammation. However, the effect of DHQ on LPS-challenged ALI remains unclear.</span></p></div><div><h3>Methods</h3><p><span>Pulmonary HE and TUNEL staining<span><span> and lung wet/dry ratio were detected in LPS-treated Balb/c mice. IL-1β, IL-6 and TNF-α levels were determined utilizing ELISA assay. RAW264.7 cell </span>apoptosis<span><span> and macrophage markers (CD86, CD206) were tested using flow cytometry. TC-1 viability was analyzed by MTT assay. </span>Western blot<span><span> measured protein expression of macrophage markers. Interactions of miR-132–3p, </span>IRF4 and FBXW7 were explored utilizing </span></span></span></span>ChIP<span>, RNA pull-down and dual luciferase reporter assays.</span></p></div><div><h3>Results</h3><p>DHQ alleviated histopathological change, pulmonary edema<span><span> and apoptosis in LPS-treated mice. DHQ affected LPS-induced M2 macrophage polarization<span> and TC-1 cell injury-related indicators, such as decreased cell activity, decreased LDH levels, and increased apoptosis. </span></span>LPS inhibited IRF4 and miR-132–3p expression, activated Notch pathway and increased FBXW7 level, which were overturned by DHQ. IRF4 transcriptionally activated miR-132–3p expression. FBXW7 was a downstream target of miR-132–3p.</span></p></div><div><h3>Conclusion</h3><p>DHQ alleviated LPS-induced lung injury through promoting macrophage M2 polarization via IRF4/miR-132–3p/FBXW7 axis, which provides a new therapeutic strategy for ALI.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"83 ","pages":"Article 102249"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10199282","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":"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":"2023-12-01","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":"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":"2023-12-01","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}