- COVID-19's impact on care practice for alpha-1-antitrypsin deficiency patients. [Journal Article]BMC Health Serv Res. 2023 Jan 30; 23(1):98.BH
- CONCLUSIONS: The study advances knowledge by highlighting the challenges faced by health professionals and changes in AATD patient management in the context of the COVID-19 pandemic. It also proposes experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. This work could serve as a reference study for physicians on their daily clinical practice with AATD patients and may also provide guidance on the changes to be put in place for the post-pandemic situation.
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- Differential Plasma Proteins Identified via iTRAQ-Based Analysis Serve as Diagnostic Markers of Pancreatic Ductal Adenocarcinoma. [Journal Article]
- CONCLUSIONS: AAT, RAB2B, and IGFBP2 could serve as effective biomarkers to facilitate the early diagnosis of pancreatic cancer.
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- Alpha1-Antitrypsin Inherited Variants in Patients With Bronchiectasis. [Case Reports]Arch Bronconeumol. 2023 Jan 18 [Online ahead of print]AB
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- The impact of diagnostic delay on survival in alpha-1-antitrypsin deficiency: results from the Austrian Alpha-1 Lung Registry. [Journal Article]
- CONCLUSIONS: A delayed diagnosis was associated with significantly worse OS and TS. Screening should be improved and efforts to ensure early AATD diagnosis should be intensified.
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- Alpha-1 antitrypsin limits neutrophil extracellular trap disruption of airway epithelial barrier function. [Journal Article]
- Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought to understand the impact of human NETs on barrier function in primary human bronchial epithelial and a human airway epithelial cell line. We demonstrate that NETs disrupt airway epithelial barrier function by decreasing transepithelial electrical resistance a…
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- COVID-19 Pathology Sheds Further Light on Balance between Neutrophil Proteases and Their Inhibitors. [Review]
- Excessive neutrophil influx and activation in lungs during infections, such as manifest during the ongoing SARS CoV-2 pandemic, have brought neutrophil extracellular traps (NETs) and the concomitant release of granule contents that damage surrounding tissues into sharp focus. Neutrophil proteases, which are known to participate in NET release, also enable the binding of the viral spike protein to…
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- Human Alpha-1 Antitrypsin Attenuates ENaC and MARCKS and Lowers Blood Pressure in Hypertensive Diabetic db/db Mice. [Journal Article]
- Hypertension may develop before or after the onset of diabetes and it is known to increase the risk of developing diabetic nephropathy. Alpha-1 antitrypsin (AAT) is a multi-functional protein with beneficial effects in various diseases but its role in reducing blood pressure in the diabetic kidney has not been thoroughly studied. Like blood pressure, epithelial sodium channels (ENaC) and its adap…
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- Low-Dose Colchicine Attenuates Sepsis-Induced Liver Injury: A Novel Method for Alleviating Systemic Inflammation. [Journal Article]Inflammation. 2023 Jan 19 [Online ahead of print]I
- Sepsis is a significant public health challenge. The immune system underlies the pathogenesis of the disease. The liver is both an active player and a target organ in sepsis. Targeting the gut immune system using low-dose colchicine is an attractive method for alleviating systemic inflammation in sepsis without inducing immunosuppression. The present study aimed to determine the use of low-dose c…
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- Long Non-Coding RNA Expression in Alpha-1 Antitrypsin Deficient Monocytes Pre- and Post-AAT Augmentation Therapy. [Journal Article]
- Long non-coding RNAs (lncRNAs) regulate gene expression. Their expression in alpha-1 antitrypsin (AAT) deficiency has not been investigated. Treatment of AAT deficiency involves infusion of plasma-purified AAT and this augmentation therapy has previously been shown to alter microRNA expression in monocytes of AAT-deficient (ZZ) individuals. Here, we assess the effect of AAT augmentation therapy o…
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- Capturing the conversion of the pathogenic alpha-1-antitrypsin fold by ATF6 enhanced proteostasis. [Journal Article]Cell Chem Biol. 2023 Jan 19; 30(1):22-42.e5.CC
- Genetic variation in alpha-1 antitrypsin (AAT) causes AAT deficiency (AATD) through liver aggregation-associated gain-of-toxic pathology and/or insufficient AAT activity in the lung manifesting as chronic obstructive pulmonary disease (COPD). Here, we utilize 71 AATD-associated variants as input through Gaussian process (GP)-based machine learning to study the correction of AAT folding and functi…
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- Association of Alpha-1 Antitrypsin Pi*Z Allele Frequency and Progressive Liver Fibrosis in Two Chronic Hepatitis C Cohorts. [Journal Article]
- (1) Background: The inherited alpha-1 antitrypsin (A1AT) deficiency variant 'Pi*Z' emerged as a genetic modifier of chronic liver disease. Controversial data exist on the relevance of heterozygous Pi*Z carriage ('Pi*MZ' genotype) as an additional risk factor in patients with chronic viral hepatitis C to develop progressive liver fibrosis. (2) Methods: Two prospectively recruited cohorts totaling …
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- Modeling bile duct ischemia and reoxygenation injury in human cholangiocyte organoids for screening of novel cholangio-protective agents. [Journal Article]
- CONCLUSIONS: These findings demonstrate that ICOs recapitulate ischemic cholangiopathy in vitro and enable drug assessment studies for the discovery of new therapeutics for ischemic cholangiopathies.
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- Quantitative Proteomic Analysis of Non-Tobacco Associated Oral Squamous Cell Carcinoma Reveals Deregulation of Cytoskeletal and Apoptotic Proteins. [Journal Article]Asian Pac J Cancer Prev. 2022 Dec 01; 23(12):4285-4292.AP
- CONCLUSIONS: The differentially expressed proteins are found to be involved in apoptotic signalling pathways, cytoskeletal dynamics and are known to play a critical role in oral tumorigenesis. Put together, the results provide available baseline information for understanding the development and progression of NT-OSCC. These identified proteins on further validation may be used as potential biomarkers in future for early detection and predicting therapeutic outcome of patients with NT-OSCC.
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- Corroboration of cross-reactivity between Mycobacterium leprae and hosts' salivary and cutaneous proteins: A hope for prognostic biomarkers for the pathogenesis of reactions in leprosy. [Journal Article]
- Immunological reactions are frequent complications that may occur either before, during, or after treatment and affect 30-50% of leprosy patients. The presence of autoantibodies like rheumatoid factor, antinuclear factor, and antibodies to host collagen, keratin, actin, myosin, endothelial cells, and myelin basic protein (MBP) has been earlier reported in leprosy patients. The purpose of this stu…
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- Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept. [Journal Article]
- Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder associated with pulmonary emphysema and bronchiectasis. Its management currently consists of weekly infusions of plasma-purified human AAT, which poses several issues regarding plasma supplies, possible pathogen transmission, purification costs, and parenteral administration. Here, we investigated an alternative administration strategy fo…
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- Abnormal Alpha-1 Antitrypsin Levels and Other Risk Factors Associated with Lung Function Impairment at 6 and 12 Months after Hospitalization Due to COVID-19: A Cohort Study. [Journal Article]
- Respiratory function deficits are common sequelae for COVID-19. In this study, we aimed to identify the medical conditions that may influence lung function impairment at 12 months after SARS-CoV2 infection and to analyze the role of alpha-1 antytripsin (AAT) deficiciency (AATD). A cohort study was conducted on hospitalized COVID-19 pneumonia patients in Granada (Spain) during the first infection …
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- Genetic and Serum Screening for Alpha-1-Antitrypsin Deficiency in Adult Patients with Cystic Fibrosis: A Single-Center Experience. [Journal Article]
- Cystic fibrosis (CF) and alpha-1 antitrypsin (AAT) deficiency are two of the commonest genetic diseases affecting the Caucasian population. Neutrophil-mediated inflammation due to protease-antiprotease imbalance leads to progressive pulmonary involvement in both diseases. The aim of this study was to investigate the prevalence of AAT deficiency in CF adults. A prospective study enrolling CF adult…
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- Influence of Protein Carbonylation on Human Adipose Tissue Dysfunction in Obesity and Insulin Resistance. [Journal Article]
- CONCLUSIONS: The adipose tissue carbonylome contributes to understanding the molecular mechanism driving adipocyte dysfunction and identifies possible adipose tissue carbonylated targets in obesity-associated insulin resistance.
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- Registry-based cohort study of alpha-1 antitrypsin deficiency prevalence, incidence and mortality in Denmark 2000-2018. [Journal Article]
- CONCLUSIONS: Diagnosed AATD was associated with increased mortality, especially for children. The finding for children was based on few deaths and had very wide 95% CIs.
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- Bronchoscopic Lung Volume Reduction in Patients with Emphysema due to Alpha-1 Antitrypsin Deficiency. [Journal Article]Respiration. 2022 Dec 22 [Online ahead of print]R
- CONCLUSIONS: EBV treatment in patients with emphysema and AATD or a reduced AAT level is feasible and results in significant improvements in pulmonary function, exercise capacity, and quality of life and has an acceptable safety profile.
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- Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells. [Journal Article]Histochem Cell Biol. 2022 Dec 19 [Online ahead of print]HC
- Identification of the signature molecular profiles involved in therapy resistance is of vital importance in developing new strategies for treatments and disease monitoring. Protein alpha-1 antitrypsin (AAT, encoded by SERPINA1 gene) is an acute-phase protein, and its high expression has been linked with unfavorable clinical outcome in different types of cancer; however, data on its involvement in…
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- Basilar Predominant Emphysema: Thinking beyond Alpha-1-Antitrypsin Deficiency. [Case Reports]
- Basilar predominant emphysema, or disproportionate emphysematous involvement of the lung bases compared to the apices, is an uncommon radiographic pattern of emphysema traditionally associated with alpha-1-antitrypsin deficiency (AATD). We present a case of a 59-year-old female with 41 pack-year tobacco use, Stage IV COPD with supplemental oxygen, and bibasilar predominant emphysema who successfu…
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- Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry. [Journal Article]
- CONCLUSIONS: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www.
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- Role and mechanism of alpa1-antitrypsin in polycystic ovary syndrome. [Journal Article]Saudi Med J. 2022 Dec; 43(12):1309-1316.SM
- CONCLUSIONS: Alpha1-antitrypsin is closely associated with NE, IL-1β, and IL-8. Therefore, we speculate that A1AT might ameliorate PCOS symptoms by inhibiting pro-inflammatory factors: NE, IL-1β, and IL-8.
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- Alpha-1-Antitrypsin Pi*MZ variant increases risk of developing hepatic events in nonalcoholic fatty liver disease patients. [Journal Article]Clin Res Hepatol Gastroenterol. 2022 Dec 09; 47(2):102066.CR
- CONCLUSIONS: Patients with NAFLD and A1AT Pi*MZ variant are at increased risk for developing hepatic decompensation. NAFLD patients should be offered A1AT genotyping for risk stratification, counseling, and multidisciplinary intervention for NAFLD.
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- Discovering new peripheral plasma biomarkers to identify cognitive decline in type 2 diabetes. [Journal Article]
- Type 2 diabetes mellitus (T2DM) is an independent risk factor of Alzheimer's disease (AD), and thus identifying who among the increasing T2DM populations may develop into AD is important for early intervention. By using TMT-labeling coupled high-throughput mass spectrometry, we conducted a comprehensive plasma proteomic analysis in none-T2DM people (Ctrl, n = 30), and the age-/sex-matched T2DM pa…
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- Giant Bullous Emphysema Mimicking Spontaneous Pneumothorax. [Case Reports]
- Emphysema is a progressive and degenerative lung disease that most commonly occurs due to many years of smoking or exposure to smoke and irritants. It is also seen in the congenital absence of the alpha-1-antitrypsin enzyme. Bullous emphysema is an advanced stage of the disease where strictures of the bronchi permit the inspired air to enter the bronchi but close on expiration, causing air retent…
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- Structural characterization and conformational dynamics of alpha-1 antitrypsin pathogenic variants causing alpha-1-antitrypsin deficiency. [Journal Article]
- Background: Alpha-1 antitrypsin deficiency (A1ATD) is a progressive lung disease caused by inherited pathogenic variants in the SERPINA1 gene. However, their actual role in maintenance of structural and functional characteristics of the corresponding α-1 anti-trypsin (A1AT) protein is not well characterized. Methods: The A1ATD causative SERPINA1 missense variants were initially collected from var…
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- New variants of alpha-1-antitrypsin: structural simulations and clinical expression. [Journal Article]
- CONCLUSIONS: The results characterize five variants, four of them previously unknown, of the SERPINA1 gene, which define new alleles contributing to the deficiency of AAT. Rare variants might be more frequent than expected, and therefore, in discordant cases, standardized screening of the S and Z alleles needs complementation with gene sequencing and structural approaches. The utility of computational modelling for providing supporting evidence of the pathogenicity of rare single nucleotide variations is discussed.
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- Seronegative MSM at high risk of HIV-1 acquisition show an immune quiescent profile with a normal immune response against common antigens. [Journal Article]
- Human immunodeficiency virus (HIV) infection still represents a major public health problem worldwide, and its vaccine remains elusive. The study of HIV-exposed seronegative individuals (HESN) brings important information about the natural resistance to HIV, allows a better understanding of the infection, and opens doors for new preventive and therapeutic strategies. Among HESN groups, there are …
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