European journal of respiratory medicine最新文献

{"title":"TLR4 Ligation by eNAMPT, a Novel DAMP, is Essential to Sulfur Mustard- Induced Inflammatory Lung Injury and Fibrosis.","authors":"Carrie L Kempf, Jin H Song, Saad Sammani, Tadeo Bermudez, Vivian Reyes Hernon, Lin Tang, Hua Cai, Sara M Camp, Carly A Johnson, Mohamed S Basiouny, Leslie A Bloomquist, Jacqueline S Rioux, Carl W White, Livia A Veress, Joe G N Garcia","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Human and preclinical studies of sulfur mustard (SM)-induced acute and chronic lung injuries highlight the role of unremitting inflammation. We assessed the utility of targeting the novel DAMP and TLR4 ligand, eNAMPT (extracellular nicotinamide phosphoribosyltransferase), utilizing a humanized mAb (ALT-100) in rat models of SM exposure.</p><p><strong>Methods: </strong>Acute (SM 4.2 mg/kg, 24 hrs), subacute (SM 0.8 mg/kg, day 7), subacute (SM 2.1 mg/kg, day 14), and chronic (SM 1.2 mg/kg, day 29) SM models were utilized.</p><p><strong>Results: </strong>Each SM model exhibited significant increases in eNAMPT expression (lung homogenates) and increased levels of phosphorylated NFkB and NOX4. Lung fibrosis (Trichrome staining) was observed in both sub-acute and chronic SM models in conjunction with elevated smooth muscle actin (SMA), TGFβ, and IL-1β expression. SM-exposed rats receiving ALT-100 (1 or 4 mg/kg, weekly) exhibited increased survival, highly significant reductions in histologic/biochemical evidence of lung inflammation and fibrosis (Trichrome staining, decreased pNFkB, SMA, TGFβ, NOX4), decreased airways strictures, and decreased plasma cytokine levels (eNAMPT, IL-6, IL-1β. TNFα).</p><p><strong>Conclusion: </strong>The highly druggable, eNAMPT/TLR4 signaling pathway is a key contributor to SM-induced ROS production, inflammatory lung injury and fibrosis. The ALT-100 mAb is a potential medical countermeasure to address the unmet need to reduce SM-associated lung pathobiology/mortality.</p>","PeriodicalId":72981,"journal":{"name":"European journal of respiratory medicine","volume":"6 1","pages":"389-397"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10883439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examination of eQTL Polymorphisms Associated with Increased Risk of Progressive Complicated Sarcoidosis in European and African Descent Subjects.","authors":"Nancy G Casanova, Sara M Camp, Manuel L Gonzalez-Garay, Ken Batai, Lori Garman, Courtney G Montgomery, Nathan Ellis, Rick Kittles, Christian Bime, Amy P Hsu, Steven Holland, Yves A Lussier, Jason Karnes, Nadera Sweiss, Lisa A Maier, Laura Koth, David R Moller, Naftali Kaminski, Joe G N Garcia","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>A limited pool of SNPs are linked to the development and severity of sarcoidosis, a systemic granulomatous inflammatory disease. By integrating genome-wide association studies (GWAS) data and expression quantitative trait loci (eQTL) single nuclear polymorphisms (SNPs), we aimed to identify novel sarcoidosis SNPs potentially influencing the development of complicated sarcoidosis.</p><p><strong>Methods: </strong>A GWAS (Affymetrix 6.0) involving 209 African-American (AA) and 193 European-American (EA, 75 and 51 complicated cases respectively) and publicly-available GWAS controls (GAIN) was utilized. Annotation of multi-tissue eQTL SNPs present on the GWAS created a pool of ~46,000 eQTL SNPs examined for association with sarcoidosis risk and severity (Logistic Model, Plink). The most significant EA/AA eQTL SNPs were genotyped in a sarcoidosis validation cohort (n=1034) and cross-validated in two independent GWAS cohorts.</p><p><strong>Results: </strong>No single GWAS SNP achieved significance (p<1x10-8), however, analysis of the eQTL/GWAS SNP pool yielded 621 eQTL SNPs (p<10-4) associated with 730 genes that highlighted innate immunity, MHC Class II, and allograft rejection pathways with multiple SNPs validated in an independent sarcoidosis cohort (105 SNPs analyzed) (NOTCH4, IL27RA, BTNL2, ANXA11, HLA-DRB1). These studies confirm significant association of eQTL/GWAS SNPs in EAs and AAs with sarcoidosis risk and severity (complicated sarcoidosis) involving HLA region and innate immunity.</p><p><strong>Conclusion: </strong>Despite the challenge of deciphering the genetic basis for sarcoidosis risk/severity, these results suggest that integrated eQTL/GWAS approaches may identify novel variants/genes and support the contribution of dysregulated innate immune responses to sarcoidosis severity.</p>","PeriodicalId":72981,"journal":{"name":"European journal of respiratory medicine","volume":"5 1","pages":"359-371"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10883688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality in Hospitalized Covid19 Patients during First Wave in a Tertiary Hospital in Northern Patagonia","authors":"","doi":"10.31488/ejrm.128","DOIUrl":"https://doi.org/10.31488/ejrm.128","url":null,"abstract":"","PeriodicalId":72981,"journal":{"name":"European journal of respiratory medicine","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82402119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neo-Adjuvant Therapies in Lung Cancer – Past Present and Future Directions","authors":"","doi":"10.31488/ejrm.131","DOIUrl":"https://doi.org/10.31488/ejrm.131","url":null,"abstract":"","PeriodicalId":72981,"journal":{"name":"European journal of respiratory medicine","volume":"151 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75411832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective, Non-Controlled Pilot Study to Evaluate the Efficacy and Safety of Cefditoren Pivoxil in COVID-19 Patients with Mild to Moderate Pneumonia","authors":"","doi":"10.31488/ejrm.123","DOIUrl":"https://doi.org/10.31488/ejrm.123","url":null,"abstract":"","PeriodicalId":72981,"journal":{"name":"European journal of respiratory medicine","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77787342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Covid-19 based on Risk Features","authors":"","doi":"10.31488/ejrm.127","DOIUrl":"https://doi.org/10.31488/ejrm.127","url":null,"abstract":"","PeriodicalId":72981,"journal":{"name":"European journal of respiratory medicine","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81943672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhaled Sodium Pyruvate Reduces Oxygen Radicals and Inflammatory Cytokines in COPD Patients","authors":"","doi":"10.31488/ejrm.133","DOIUrl":"https://doi.org/10.31488/ejrm.133","url":null,"abstract":"","PeriodicalId":72981,"journal":{"name":"European journal of respiratory medicine","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80249618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Levofloxacin in Outpatient Treatment of Exacerbations of COPD and Bronchiectasis","authors":"","doi":"10.31488/ejrm.125","DOIUrl":"https://doi.org/10.31488/ejrm.125","url":null,"abstract":"","PeriodicalId":72981,"journal":{"name":"European journal of respiratory medicine","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75481131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crizotinib Restored Pembrolizumab Response in Advanced Non-Small Cell Lung Cancer","authors":"","doi":"10.31488/ejrm.126","DOIUrl":"https://doi.org/10.31488/ejrm.126","url":null,"abstract":"","PeriodicalId":72981,"journal":{"name":"European journal of respiratory medicine","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88156875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccine Delivery by Precipitation (VDBP) Lessons from Poison Ivy for Protein Antigens in General and Specifically for SARS Co-V2","authors":"","doi":"10.31488/ejrm.130","DOIUrl":"https://doi.org/10.31488/ejrm.130","url":null,"abstract":"","PeriodicalId":72981,"journal":{"name":"European journal of respiratory medicine","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87405223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}