Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA189544 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:QUANTitative Chest Computed Tomography UnMasking Emphysema Progression in Alpha-1 Antitrypsin Deficiency - RLDC 5701
| PRJNA189543 | ENA
Project description:Gene expression profiling of lung tissue from undiseased (NML), 'usual' emphysema (EML), and Alpha-1 Antitrypsin Deficiency-related emphysema (ADL). Keywords = Emphysema Keywords = COPD Keywords = Alpha-1 Antitrypsin Deficiency Keywords: ordered
2004-06-01 | GSE1122 | GEO
Project description:Gene expression profiling of lung tissue from undiseased (NML), 'usual' emphysema (EML), and Alpha-1 Antitrypsin Deficiency-related emphysema (ADL).
2007-07-19 | E-GEOD-1122 | biostudies-arrayexpress
Project description:Chymotrypsin-like elastase 1 (CELA1) is a serine protease that is neutralized by alpha-1 antitrypsin (AAT) and prevents emphysema in a murine antisense oligonucleotide model of AAT-deficient emphysema. We tested the role of CELA1 in emphysema development in this genetic model of AAT-deficiency following tracheal lipopolysaccharide (LPS), 10 months of cigarette smoke (CS) exposure, aging, and a low-dose tracheal porcine pancreatic elastase (LD-PPE) model we developed. In this last model, we performed proteomic analysis to understand differences in lung protein composition. We were unable to show that AAT-deficient mice developed more emphysema than wild type with escalating doses of LPS.
2023-02-20 | MSV000091330 | MassIVE
Project description:In this study, we sought to thoroughly characterize the liver pathophysiology of a human transgenic mouse model for alpha-1 antitrypsin deficiency (AATD) with a strong manifestation of AATD-mediated liver disease. Male and female transgenic mice for normal variant human alpha-1 antitrypsin (Pi*M) and mutant human alpha-1 antitrypsin (Pi*Z) at 3 and 6 months of age with a C57BL/6J background were subjected to study. The progression of hepatic accumulation of mutant alpha-1 antitrypsin (ZAAT), hepatocyte injury, steatosis, liver inflammation and fibrotic features of this mouse model were monitored by performing an in vivo study.
2023-03-19 | GSE206619 | GEO
Project description:Whole genome mRNA and microRNA profiling of bronchoalveolar lavage (BAL) and peripheral blood mononuclear cell (PBMC) in Alpha-1 Antitrypsin Deficiency patients with PiZZ or PiMZ alpha-1 antitrypsin genotypes
2020-11-03 | GSE109515 | GEO
Project description:We conducted a small cross-sectional proteomic study aiming to identify potential biomarkers of emphysema, as well as to identify COPD- and smoking-related biomarkers. This study was approved by the University Hospital Dubrava's Institutional Ethics Committee (approval no. 2022/2908‐05), as well as by the School of Medicine, University of Zagreb's Institutional Ethics Committee (approval no. 251-59-10106-24-111/119). This study included a total of 40 participants, divided into four equal age and gender-matched groups (N=10 participants per group): 1.) patients with COPD and radiologically verified emphysema on chest CT (CE group), confirmed by a radiologist, 2.) patients with COPD without radiological signs of emphysema on chest CT (CN group), confirmed by a radiologist, 3) healthy smokers (active smokers (>20 pack-years) without respiratory symptoms and normal spirometry) (HS group), 4) healthy never-smokers (without respiratory symptoms and with normal spirometry) (HN group). A graphic study outline is shown in Figure 1. Participants were included in the study in a non-probabilistic manner (in order to be age, gender, comorbidity and body mass index matched – so group homogeneity in these regards could be achieved). Patients with COPD (CE and CN groups) were GOLD 2B patients as defined by GOLD 2023, active smokers (>20 pack-years), on dual inhalation therapy (combination of long-acting β2 agonist (LABA) and long-acting muscarinic antagonist (LAMA)). Exclusion criteria were: reversible airflow limitation, positive bronchodilator test (either by the GINA criteria or by the ERS/ATS technical standard 2022; acute exacerbation of COPD in the last 6 months, concomitant malignancy, autoimmune disease or concomitant asthma, as well as alpha-1-antitrypsin deficiency. Patients that consumed tobacco products other than classical cigarettes (including e-cigarettes, heat not-burn tobacco products, vape, cigars and cigarillos) were also excluded from the study. None of the participants were taking glucocorticoids or other immunosuppressive medications. All subjects in the study signed an informed consent form. Comorbidities were assessed using the Charlson's comorbidity index and also a modified Charlson's comorbidity index in which “chronic pulmonary disease“ was excluded. The participants underwent spirometry testing and all COPD patients had a chest CT no older than 3 months prior to inclusion. Spirometry with a subsequent bronchodilator test (with 400mcg of salbutamol) was performed according to the international standards, using the Global Lung Initiative (GLI) reference values. Expiratory airflow limitation was determined using the proposed GOLD criteria with a fixed FEV1/FVC ratio of 0.7.
2026-04-06 | PXD074107 | Pride
Project description:<p>AAT deficiency is a genetic disorder associated with emphysema. Spirometry, the lung function test that measures how well the lungs exhale air, is used to diagnose and track the progression of emphysema. Some studies have suggested that forced expiratory volume in 1 second (FEV1) measurements, a type of spirometry test, may lack accuracy in detecting disease progression in cases of severe AAT deficiency. Another method, high resolution chest CT scans, may be more accurate at measuring the progression of emphysema. The purpose of this study is to determine if high resolution CT scans are better at detecting the progression of emphysema than lung function tests. Results from this study may lead to the development of a more accurate way to assess lung tissue loss and may improve the understanding of lung destruction in AAT deficiency.</p> <p>This study will last 4 years and will enroll people with AAT deficiency who have nearly normal lung function test results. Study visits, each lasting about 4 hours, will occur at baseline and months 6, 12, 18, 24, and 36. At each visit, participants will undergo lung function tests, a CT scan, blood collection, and a physical exam. Female participants will have urine collected for a pregnancy test. All participants will also complete questionnaires to assess health status and lung function. Study researchers will call participants every 2 months to collect information on lung disease symptoms and medication changes.</p>
| phs000698 | dbGaP
Project description:Non-emphysematous COPD, which is defined based on chest computed tomography (CT) findings, may present different transcriptome features of peripheral blood mononuclear cells (PBMCs) derived from bone marrow (BM). In obstructive disorder-fixed COPD, including the airway-dominant phenotype, the upregulated differentially expressed genes (DEGs) were mainly related to Th2 inflammation, suppression of pulmonary vascular remodeling, and the function of BM-derived progenitor cells. Airway-dominant phenotypes are associated with less obstructive impairment. The upregulated DEGs in emphysematous COPD could be associated with airway inflammation and remodeling, suggesting an asthmatic component. Upregulated XCL1, PRKCZ, TMEM102, CD200R1, and AQP1 levels are associated with the activation of T lymphocytes and eosinophils. The upregulation of keratan sulfate biosynthesis and metabolic processes is associated with protection against destruction of the distal airways. The upregulation of ITGA3 could augment interactions with extracellular matrix proteins. COL6A1 may augment the profibrotic mast cell phenotype during the deposition of alveolar collagen VI. The upregulated HSPG2, PDGFRB and PAK4 may contribute to airway wall thickening. The upregulated SERPINF1 could explain the better preserved vascular bed, and the upregulation of SERPINF1 and ISM1 seem to protect against emphysema formation. These patterns in PBMCs may be related to the pathogenesis of nonemphysematous COPD.
2023-12-18 | GSE248493 | GEO
Project description:Protein misfolding diseases, including alpha-1 antitrypsin deficiency (AATD), pose significant health challenges, yet their progression at the cellular level remains poorly understood. Here, we employ spatial proteomics by mass spectrometry and machine learning to map the molecular landscape of AATD in human liver tissue at high resolution. Our approach, combining Deep Visual Proteomics with single-cell analysis in a patient cohort, characterized early and late responses to protein aggregation across fibrosis stages. We achieved a remarkable quantitative depth of 2,800 proteins per single hepatocyte shape, providing detailed insights into cellular heterogeneity. This comprehensive biological dataset revealed an unexpected early integrated peroxisomal upregulation, preceding the canonical unfolded protein response. Our single-cell data demonstrate that alpha-1 antitrypsin accumulation is largely cell-intrinsic, with minimal stress propagation between neighboring hepatocytes. By integrating proteomic data with AI-guided image analysis across multiple disease stages, we identify a terminal hepatocyte phenotype, marked by globular protein aggregates and distinct proteomic signatures including elevated TNFSF10/TRAIL expression. This phenotype may represent a critical stage in disease progression. Our study unveils novel insights into AATD pathogenesis and introduces a powerful methodology for high-resolution, in situ proteomic analysis of complex tissues. This approach holds potential to unravel molecular mechanisms in various protein misfolding disorders and beyond, setting a new standard for understanding disease progression at the single-cell level in human tissue.
2025-02-19 | PXD054440 | Pride