American Journal of Respiratory Cell and Molecular Biology最新文献_第7页

Integrative Analyses Reveal the Correlation Between the Airway Microbiome and Host Metabolism in Severe Community-acquired Pneumonia. 综合分析揭示严重社区获得性肺炎患者气道微生物组与宿主代谢之间的相关性

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-08-05 DOI: 10.1165/rcmb.2024-0030OC

Siqin Chen, Ping Chen, Minhong Su, Jia Jiang, Xiang Liu, Panxiao Shen, Xi Li, Fu Rong, Shaofeng Zhang, Jiayi Liu, Yaling Zeng, Wei Lei, Junhang Li, Kongqiu Wang, Gongqi Chen, Xiaobin Zheng, Xin Chen, Qiang Xiao

{"title":"Integrative Analyses Reveal the Correlation Between the Airway Microbiome and Host Metabolism in Severe Community-acquired Pneumonia.","authors":"Siqin Chen, Ping Chen, Minhong Su, Jia Jiang, Xiang Liu, Panxiao Shen, Xi Li, Fu Rong, Shaofeng Zhang, Jiayi Liu, Yaling Zeng, Wei Lei, Junhang Li, Kongqiu Wang, Gongqi Chen, Xiaobin Zheng, Xin Chen, Qiang Xiao","doi":"10.1165/rcmb.2024-0030OC","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0030OC","url":null,"abstract":"Community-acquired pneumonia (CAP) is a significant global health concern, responsible for high mortality and morbidity. Recent research has revealed a potential link between disordered microbiome and metabolism in pneumonia, although the precise relationship between these factors and severe CAP remains unclear. To address this knowledge gap, we conducted a comprehensive analysis utilizing 16S sequencing and LC-MS/MS metabolomics data to characterize the microbial profile in sputum and metabolic profile in serum in patients with severe community-acquired pneumonia (sCAP). Our analysis identified 13 genera through LEfSe analysis and 15 metabolites meeting specific criteria (P < 0.05, VIP ≥ 2, and |Log2(FC)| ≥ 2). The findings of this study demonstrate the presence of altered coordination between the microbiome of the lower respiratory tract and host metabolism in patients with sCAP. The observed concentration trends of specific metabolites across different disease stages further support the potential involvement of the serum metabolism in the development of sCAP. These correlations between the airway microbiome and host metabolism in sCAP patients have important implications for optimizing early diagnosis and developing individualized therapeutic strategies.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex-biased Regulation of Extracellular Matrix Genes in COPD. 慢性阻塞性肺病细胞外基质基因的性别差异调控

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-08-05 DOI: 10.1165/rcmb.2024-0226OC

Camila M Lopes-Ramos, Katherine H Shutta, Min Hyung Ryu, Yichen Huang, Enakshi Saha, John Ziniti, Robert Chase, Brian D Hobbs, Jeong H Yun, Peter Castaldi, Craig P Hersh, Kimberly Glass, Edwin K Silverman, John Quackenbush, Dawn L DeMeo

{"title":"Sex-biased Regulation of Extracellular Matrix Genes in COPD.","authors":"Camila M Lopes-Ramos, Katherine H Shutta, Min Hyung Ryu, Yichen Huang, Enakshi Saha, John Ziniti, Robert Chase, Brian D Hobbs, Jeong H Yun, Peter Castaldi, Craig P Hersh, Kimberly Glass, Edwin K Silverman, John Quackenbush, Dawn L DeMeo","doi":"10.1165/rcmb.2024-0226OC","DOIUrl":"10.1165/rcmb.2024-0226OC","url":null,"abstract":"Compared to men, women often develop COPD at an earlier age with worse respiratory symptoms despite lower smoking exposure. However, most preventive, and therapeutic strategies ignore biological sex differences in COPD. Our goal was to better understand sex-specific gene regulatory processes in lung tissue and the molecular basis for sex differences in COPD onset and severity. We analyzed lung tissue gene expression and DNA methylation data from 747 individuals in the Lung Tissue Research Consortium (LTRC), and 85 individuals in an independent dataset. We identified sex differences in COPD-associated gene regulation using gene regulatory networks. We used linear regression to test for sex-biased associations of methylation with lung function, emphysema, smoking, and age. Analyzing gene regulatory networks in the control group, we identified that genes involved in the extracellular matrix (ECM) have higher transcriptional factor targeting in females than in males. However, this pattern is reversed in COPD, with males showing stronger regulatory targeting of ECM-related genes than females. Smoking exposure, age, lung function, and emphysema were all associated with sex-specific differential methylation of ECM-related genes. We identified sex-based gene regulatory patterns of ECM-related genes associated with lung function and emphysema. Multiple factors including epigenetics, smoking, aging, and cell heterogeneity influence sex-specific gene regulation in COPD. Our findings underscore the importance of considering sex as a key factor in disease susceptibility and severity.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Serum Response Factor Expression in Excess Permits a Dual Contractile-Proliferative Phenotype of Airway Smooth Muscle. SRF 过量表达可使气道平滑肌形成收缩-增殖双重表型。

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-08-01 DOI: 10.1165/rcmb.2024-0081OC

Rui Sun, Xingning Pan, Erin Ward, Rafael Intrevado, Arina Morozan, Anne-Marie Lauzon, James G Martin

{"title":"Serum Response Factor Expression in Excess Permits a Dual Contractile-Proliferative Phenotype of Airway Smooth Muscle.","authors":"Rui Sun, Xingning Pan, Erin Ward, Rafael Intrevado, Arina Morozan, Anne-Marie Lauzon, James G Martin","doi":"10.1165/rcmb.2024-0081OC","DOIUrl":"10.1165/rcmb.2024-0081OC","url":null,"abstract":"The transcription factors (TFs) MyoCD (myocardin) and Elk-1 (ETS Like-1 protein) competitively bind to SRF (serum response factor) and control myogenic- and mitogenic-related gene expression in smooth muscle, respectively. Their functions are therefore mutually inhibitory, which results in a contractile-versus-proliferative phenotype dichotomy. Airway smooth muscle cell (ASMC) phenotype alterations occur in various inflammatory airway diseases, promoting pathological remodeling and contributing to airflow obstruction. We characterized MyoCD and Elk-1 interactions and their roles in phenotype determination in human ASMCs. MyoCD overexpression in ASMCs increased smooth muscle gene expression, force generation, and partially restored the loss of smooth muscle protein associated with prolonged culturing while inhibiting Elk-1 transcriptional activities and proliferation induced by EGF (epidermal growth factor). However, MyoCD overexpression failed to suppress these responses induced by FBS, as FBS also upregulated SRF expression to a degree that allowed unopposed function of both TFs. Inhibition of the RhoA pathway reversed said SRF changes, allowing inhibition of Elk-1 by MyoCD overexpression and suppressing FBS-mediated contractile protein gene upregulation. Our study confirmed that MyoCD in increased abundance can competitively inhibit Elk-1 function. However, SRF upregulation permits a dual contractile-proliferative ASMC phenotype that is anticipated to exacerbate pathological alterations, whereas therapies targeting SRF may inhibit pathological ASMC proliferation and contractile protein gene expression.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characteristics and Regulation of Human Eosinophil ETosis In Vitro. 体外人类嗜酸性粒细胞 ETosis 的特征和调控

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-08-01 DOI: 10.1165/rcmb.2023-0438OC

Hiroki Tomizawa, Misaki Arima, Yui Miyabe, Chikako Furutani, Sahoko Kodama, Keisuke Ito, Ken Watanabe, Ryo Hasegawa, Shohei Nishiyama, Keinosuke Hizuka, Takechiyo Yamada, Shigeharu Ueki

{"title":"Characteristics and Regulation of Human Eosinophil ETosis In Vitro.","authors":"Hiroki Tomizawa, Misaki Arima, Yui Miyabe, Chikako Furutani, Sahoko Kodama, Keisuke Ito, Ken Watanabe, Ryo Hasegawa, Shohei Nishiyama, Keinosuke Hizuka, Takechiyo Yamada, Shigeharu Ueki","doi":"10.1165/rcmb.2023-0438OC","DOIUrl":"https://doi.org/10.1165/rcmb.2023-0438OC","url":null,"abstract":"Cytolytic ETosis is a type of programmed cell death distinct from apoptosis and necrosis and plays a major role in the innate immune system and disease progression. Through the process of ETosis, cells release their chromatin with diverse antimicrobial proteins into the extracellular milieu, forming extracellular traps (ETs). Although ETosis has been reported in several leukocyte types, few studies have compared ETosis and the component proteins of ETs in leukocytes. The aim of this study was to better understand the characteristics of eosinophil ETosis (EETosis) compared with other leukocytes. We isolated human blood eosinophils, neutrophils, basophils, monocytes, and lymphocytes and stimulated them with known ETosis inducers, a protein kinase C activator PMA, or a calcium ionophore A23187. Both stimuli induced eosinophil cell death and ET release after 180 minutes of stimulation in a NADPH-oxidase-dependent manner. PMA also induced NADPH-oxidase-dependent ETosis in neutrophils, whereas little or no significant ETosis was observed in basophils, monocytes, or lymphocytes at 180 minutes. Mass spectrometry-based proteomic analysis of eosinophil- and neutrophil-derived ETs identified 997 and 1415 proteins, respectively. Among the physiological stimuli tested, immobilized IgA and IgG induced EETosis. C-C motif chemokine ligand 11 (CCL11) and interleukin 5 (IL-5) were weak inducers of EETosis, but co-stimulation significantly induced rapid EETosis. Under high serum or albumin conditions, co-stimulation with CCL11 and IL-5 paradoxically prolonged cell survival by preventing spontaneous apoptosis. This study provides an in-depth characterization of EETosis and highlights the precise regulation of eosinophil survival and cell death pathways.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Role of TRPV1 in Febrile Seizure Susceptibility: Inflammation, Respiratory Alkalosis, and Seizure Threshold. TRPV1在热性惊厥易感性中的作用：炎症、呼吸性碱中毒与癫痫发作阈值

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-08-01 DOI: 10.1165/rcmb.2024-0182ED

Benjamin W Ackermann, Andreas Merkenschlager

引用次数: 0

August Highlights/Papers by Junior Investigators/NIH News. 八月要闻/初级研究人员的论文/NIH 新闻。

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-08-01 DOI: 10.1165/rcmb.71i2RedAlert

引用次数: 0

E-cad! That's a Big Switch from Epithelial Membrane Protein to Asthma Mediator. E-cad！从上皮细胞膜蛋白到哮喘介质的重大转变

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-08-01 DOI: 10.1165/rcmb.2024-0310ED

Jin-Ah Park

引用次数: 0

Lipids to the Rescue in Pulmonary Fibrosis: Biosynthesis, Bioenergetics, or Epigenetics? 脂质拯救肺纤维化：生物合成、生物能还是表观遗传学？

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-08-01 DOI: 10.1165/rcmb.2024-0187ED

Manas Ranjan Gartia, Victor J Thannickal

引用次数: 0

Senescence in Alveolar Epithelial Type II Cells Promotes Acute Lung Injury and Impairs Regeneration. 肺泡上皮 II 型细胞的衰老促进急性肺损伤并影响再生

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-08-01 DOI: 10.1165/rcmb.2024-0054OC

Merle S Hirsch, Christina B Hildebrand, Florian Geltinger, Andreas Pich, Christian Mühlfeld, Dirk Wedekind, Christina Brandenberger

{"title":"Senescence in Alveolar Epithelial Type II Cells Promotes Acute Lung Injury and Impairs Regeneration.","authors":"Merle S Hirsch, Christina B Hildebrand, Florian Geltinger, Andreas Pich, Christian Mühlfeld, Dirk Wedekind, Christina Brandenberger","doi":"10.1165/rcmb.2024-0054OC","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0054OC","url":null,"abstract":"Mortality of acute lung injury (ALI) increases with age. Alveolar epithelial type 2 cells (AEII) are the progenitor cells of the alveolar epithelium and crucial for repair after injury. We hypothesize that telomere dysfunction-mediated AEII senescence impairs regeneration and promotes the development of ALI. To discriminate between the impact of old age and AEII senescence in ALI, young (3 months) and old (18 months) Sftpc-Ai9 mice and young Sftpc-Ai9-Trf1 mice with inducible Trf1 knockout-mediated senescence in AEII were treated with 1 µg lipopolysaccharide (LPS)/g BW (n=9-11). Control mice received saline (n=7). Mice were sacrificed 4 or 7 days later. Lung mechanics, pulmonary inflammation and proteomes were analyzed and parenchymal injury, AEII proliferation and AEI differentiation rate were quantified using stereology. Old mice showed 55% mortality by day 4, whereas all young mice survived. Pulmonary inflammation was most severe in old mice, followed by Sftpc-Ai9-Trf1 mice. Young Sftpc-Ai9 mice recovered almost completely by day 7, while Sftpc-Ai9-Trf1 mice still showed mild signs of injury. An expansion of AEII was only measured in young Sftpc-Ai9 mice at day 7. Aging and telomere dysfunction-mediated senescence had no impact on AEI differentiation rate in controls, but the reduced number of AEII in Sftpc-Ai9-Trf1 mice also affected de-novo differentiation after injury. In conclusion, telomere dysfunction-mediated AEII senescence promoted parenchymal inflammation in ALI, but did not enhance mortality like old age. While Differentiation rate remained functional with old age and AEII senescence, AEII proliferative capacity was impaired in ALI, affecting the regenerative ability.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A New Methodology for the Oxygen Measurement in Lung Tissue of an Aged Ferret Model Proves Hypoxia during COVID-19. 老年雪貂模型肺组织氧气测量新方法证明 COVID-19 期间缺氧。

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-08-01 DOI: 10.1165/rcmb.2024-0005MA

Katrin Wirz, Claudia Schulz, Franz Söbbeler, Federico Armando, Georg Beythien, Ingo Gerhauser, Nicole de Buhr, Veronika Pilchová, Christian Meyer Zu Natrup, Wolfgang Baumgärtner, Sabine Kästner, Maren von Köckritz-Blickwede

{"title":"A New Methodology for the Oxygen Measurement in Lung Tissue of an Aged Ferret Model Proves Hypoxia during COVID-19.","authors":"Katrin Wirz, Claudia Schulz, Franz Söbbeler, Federico Armando, Georg Beythien, Ingo Gerhauser, Nicole de Buhr, Veronika Pilchová, Christian Meyer Zu Natrup, Wolfgang Baumgärtner, Sabine Kästner, Maren von Köckritz-Blickwede","doi":"10.1165/rcmb.2024-0005MA","DOIUrl":"10.1165/rcmb.2024-0005MA","url":null,"abstract":"Oxygen as a key element has a high impact on cellular processes. Infection with a pathogen such as SARS-CoV-2 and after inflammation may lead to hypoxic conditions in tissue that impact cellular responses. To develop optimized translational in vitro models for a better understanding of physiologic and pathophysiologic oxygen conditions, it is a prerequisite to determine oxygen concentrations generated in vivo. Our study objective was the establishment of an invasive method for oxygen measurements using a luminescence-based microsensor to determine the dissolved oxygen in the lung tissue of ferrets as animal models for SARS-CoV-2 research. By way of analogy to humans, aged ferrets are more likely to show clinical signs after SARS-CoV-2 infection than are young animals. To investigate oxygen concentrations during a respiratory viral infection, we intratracheally infected nine aged (3-yr-old) ferrets with SARS-CoV-2. The aged SARS-CoV-2-infected ferrets showed mild to moderate clinical signs associated with prolonged viral RNA shedding until 14 days postinfection. SARS-CoV-2-infected ferrets showed histopathologic lung lesion scores that significantly negatively correlated with oxygen concentrations in lung tissue. At 4 days postinfection, oxygen concentrations in lung tissue were significantly lower (mean percentage O2, 3.89 ≙ ≈ 27.78 mm Hg) than in the negative control group (mean percentage O2, 8.65 ≙ ≈ 61.4 mm Hg). In summary, we succeeded in determining the pathophysiologic oxygen conditions in the lung tissue of aged SARS-CoV-2-infected ferrets.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0