Article
Biochemistry & Molecular Biology
Jan C. Kamp, Naomi N. Kappe, Carlos Fernandez Moro, Jan Fuge, Mark P. Kuehnel, Sabine Wrenger, Tobias Welte, Bart van Hoek, Danny D. Jonigk, Padmini P. S. J. Khedoe, Pavel Strnad, Mikael Bjornstedt, Jan Stolk, Sabina Janciauskiene, Antal Nemeth
Summary: PiZZ (Glu342Lys) alpha 1-antitrypsin deficiency (AATD) is a risk factor for liver disease development in children, characterized by intrahepatic AAT polymerization. The presence of Z-AAT polymers in hepatocytes is common among PiZZ children, but the clinical outcomes vary, with some developing neonatal cholestasis and cirrhosis. The expression of genes related to liver fibrosis/cirrhosis and lipid, aldehyde/ketone, and bile acid metabolism differ between groups, suggesting that changes in specific genes and pathways may reflect the degree of liver injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Judith E. Carroll, Richard Olmstead, Reina Haque, Michael R. Irwin
Summary: Depression history and the number of depressive episodes are associated with accelerated biological aging in breast cancer survivors.
Article
Biochemistry & Molecular Biology
Juan Luis Rodriguez Hermosa, Gianna Vargas Centanaro, Maria Estela Gonzalez Castro, Marc Miravitlles, Lourdes Lazaro-Asegurado, Beatriz Maria Jimenez-Rodriguez, Rosanel Amaro Rodriguez, Rosaly Moreno Mendez, Maria Torres-Duran, Jose Maria Hernandez-Perez, Ana Maria Humanes-Navarro, Myriam Calle Rubio
Summary: This study found that patients with allelic variants of SERPINA1 gene, which is associated with severe cases of COVID-19, were more likely to have alpha-1 antitrypsin deficiency (AATD), making them more susceptible to severe COVID-19. Therefore, increased precautionary measures are recommended for AATD patients.
Article
Cell Biology
Adriana Ordonez, Heather P. Harding, Stefan J. Marciniak, David Ron
Summary: The study explored the cellular factors affecting the secretion of circulating polymers of alpha 1-antitrypsin, finding that cargo receptors LMAN1 and SURF4 are crucial for polymer secretion. Disruption of these receptors leads to a defect in alpha 1-antitrypsin secretion, particularly polymers, indicating their important role in regulating the process.
Article
Medicine, Research & Experimental
Maximilian Ebert, Uwe Jerke, Claudia Eulenberg-Gustavus, Lovis Kling, Dieter Jenne, Marieluise Kirchner, Philipp Mertins, Markus Bieringer, Saban Elitok, Kai-Uwe Eckardt, Adrian Schreiber, Alan D. Salama, Ralph Kettritz
Summary: The levels of PR3 and AAT were significantly increased in patients with both PR3-AAV and MPO-AAV, but only in PR3-AAV did the level of PR3 correlate with the ANCA titer, inflammatory response, and disease severity. Mechanistically, AAT prevented PR3 from binding to CD177, reducing the binding of PR3-ANCA to neutrophil surface antigens. Active patients with PR3-AAV showed methionine oxidation in plasma AAT, which was replicated by ANCA-activated neutrophils. The protective effects of PR3-related AAT were compromised by oxidation in the AAT reactive center loop, but preserved with valine and leucine substitution for critical methionines.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Immunology
Xiyuan Bai, An Bai, Michele Tomasicchio, James R. Hagman, Ashley M. Buckle, Arnav Gupta, Vineela Kadiyala, Shaun Bevers, Karina A. Serban, Kevin Kim, Zhihong Feng, Kathrin Spendier, Guy Hagen, Lorelenn Fornis, David E. Griffith, Monika Dzieciatkowska, Robert A. Sandhaus, Anthony N. Gerber, Edward D. Chan
Summary: This study identifies a new mechanism for the gene regulation, anti-inflammatory, and host-defense properties of AAT. AAT binds to the cytoplasmic glucocorticoid receptor (GR) in human macrophages, leading to inhibition of NF-kB activation and IL-8 production, as well as induction of angiopoietin-like 4 protein. This AAT-GR interaction contributes to a host-protective role against mycobacteria in macrophages.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Lela Lackey, Aaztli Coria, Auyon J. Ghosh, Phil Grayeski, Luke Hatfield, Vijay Shankar, John Platig, Zhonghui Xu, Silvia B. Ramos, Edwin K. Silverman, Victor E. Ortega, Michael H. Cho, Craig P. Hersh, Brian D. Hobbs, Peter Castaldi, Alain Laederach
Summary: The study identifies a novel alternative polyadenylation event that regulates A1AT protein expression in COPD, involving two polyadenylation sites in the SERPINA1 mRNA. Additionally, differences in SERPINA1 distal ratio distribution among cell types in the liver and lung were observed in single-cell RNA-seq analysis.
Article
Hematology
Julie Riis, Borge G. Nordestgaard, Shoaib Afzal
Summary: The study revealed an association between the alpha(1)-antitrypsin Z genetic variant and an increased risk of venous thromboembolism, with hazard ratios of 2.2 for homozygotes and 1.1 for heterozygotes. The absolute risk of venous thromboembolism associated with alpha(1)-antitrypsin ZZ homozygosity was 7.8%.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Respiratory System
Sine V. Winther, Eskild M. Landt, Borge G. Nordestgaard, Niels Seersholm, Morten Dahl
Summary: Individuals with alpha(1)-antitrypsin deficiency have an increased risk of heart failure hospitalization and heart failure-specific mortality in the Danish population.
Review
Medicine, General & Internal
Andrea Vianello, Gabriella Guarnieri, Fausto Braccioni, Beatrice Molena, Sara Lococo, Alessia Achille, Federico Lionello, Leonardo Salviati, Marco Caminati, Gianenrico Senna
Summary: This review examines the correlation between alpha 1-antitrypsin deficiency, SARS-CoV-2 infection, and COVID-19 mortality rates, suggesting that ethnic differences in SERPINA1 allele frequencies may partially explain the geographic disparities. Shared pathogenetic pathways are also discussed as theoretical basis for the epidemiological findings, along with the potential use of AAT augmentation therapy in patients with COVID-19.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Psychiatry
L. Spano, B. Etain, M. Meyrel, V. Hennion, G. Gross, J-l. Laplanche, F. Bellivier, C. Marie-Claire
Summary: The accelerated cellular aging in individuals with bipolar disorder (BD) is associated with decreased telomere length (TL) and mitochondrial DNA copy number (mtDNAcn). In this study, it was found that both TL and mtDNAcn were significantly lower in individuals with BD compared to healthy controls (HC), and these markers could effectively distinguish between the two groups. Furthermore, a subgroup of young individuals with accelerated cellular aging, characterized by shorter TL and lower mtDNAcn, was identified, primarily consisting of individuals with BD. This subgroup was not associated with specific clinical variables related to the course of BD or childhood maltreatment, but these patients were more frequently treated with anticonvulsants.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Biotechnology & Applied Microbiology
Jonathan B. Rosenberg, P. De Bishnu, Alessandria Greco, Nicholas Gorman, Vikrum Kooner, Alvin Chen, Melissa Yost-Bido, Carlos Munoz-Zuluaga, Stephen M. Kaminsky, Mahboubeh Rostami, Sebastien Monette, Ronald G. Crystal, Dolan Sondhi
Summary: Alpha 1-antitrypsin (AAT) deficiency is a common hereditary disorder with a risk of early-onset emphysema. AAT, produced in the liver, protects the lungs from protease damage, but deficiency leads to lung tissue destruction. Oxidative damage to AAT prevents it from inhibiting target proteases. In this study, the safety of intravenous administration of an engineered AAT variant, AAV8hAAT(AVL), was evaluated in mice. The study showed that AAV8hAAT(AVL) is safe with no significant adverse effects, demonstrating its potential for further clinical studies.
HUMAN GENE THERAPY
(2023)
Article
Pathology
Josiah D. Murray, Maria A. Willrich, Michael J. Krowka, Aleh Bobr, David L. Murray, Kevin C. Halling, Rondell P. Graham, Melissa R. Snyder
Summary: The study evaluated the effectiveness of a LC-MSIMS-based algorithm in detecting AAT deficiency, showing high sensitivity and cost-effectiveness with a significant reduction in IEF testing. The algorithm demonstrated a 99.9% sensitivity for detecting deficiency-associated phenotypes and was particularly successful in identifying heterozygous patients with specific allele pairings.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2021)
Article
Gastroenterology & Hepatology
Christina Louise Winther, Sofie Nyrann, Rasmus Gaardskaer Nielsen, Morten Duno, Klaus Birkelund Johansen, Thora Wesenberg Helt, Vibeke Brix Christensen
Summary: The aim of this study was to assess the state of disease at the time of diagnosis in Danish children with alpha(1)-antitrypsin deficiency. The results showed that homozygous children had higher concentrations of liver enzymes and conjugated bilirubin, but lower concentrations of S-AAT compared to heterozygotes at diagnosis.
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
(2022)
Article
Biochemistry & Molecular Biology
Varinderpal S. Dhillon, Permal Deo, Philip Thomas, Michael Fenech
Summary: The study investigates the relationship between sleep, micronutrients (including magnesium), and telomere length in elderly individuals. The findings suggest that low levels of magnesium are associated with shorter sleep duration and telomere length. Additionally, plasma homocysteine levels were negatively correlated with magnesium, and there was an interaction effect between magnesium and homocysteine on sleep duration and telomere length. These results highlight the importance of adequate magnesium levels and the potential impact of vitamin B-12 and folate levels on sleep and telomere attrition rate in elderly individuals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Ana Reula, Daniel Pellicer, Silvia Castillo, Maria Magallon, Miguel Armengot, Guadalupe Herrera, Jose-Enrique O'Connor, Lucia Banuls, Maria Mercedes Navarro-Garcia, Amparo Escribano, Francisco Dasi
Summary: This study established a new method based on flow cytometry to evaluate the oxidative profile of human nasal epithelial cells, which could be useful in research on respiratory diseases. The method allows for the measurement of a comprehensive set of oxidative stress parameters using small amounts of sample and a non-invasive sampling technique.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Medicine, General & Internal
Maria Magallon, Ana Esther Carrion, Lucia Banuls, Daniel Pellicer, Silvia Castillo, Sergio Bondia, Maria Mercedes Navarro-Garcia, Cruz Gonzalez, Francisco Dasi
Summary: Rare respiratory diseases like AATD, IPF, CF, and PCD have been shown to exhibit oxidative stress and endoplasmic reticulum stress. This review discusses their involvement in the pathologies and the potential use of antioxidants as therapeutic agents to mitigate the effects of oxidative stress.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Respiratory System
Alba Torrent-Vernetta, Mirella Gaboli, Silvia Castillo-Corullon, Pedro Mondejar-Lopez, Veronica Sanz Santiago, Jordi Costa-Colomer, Borja Osona, Javier Torres-Borrego, Olga De la Serna-Blazquez, Sara Bellon Alonso, Pilar Caro Aguilera, Alvaro Gimeno-Diaz De Atauri, Alfredo Valenzuela Soria, Roser Ayats, Carlos Martin de Vicente, Valle Velasco Gonzalez, Jose Domingo Moure Gonzalez, Elisa Maria Canino Calderin, Maria Dolores Pastor-Vivero, Maria Angeles Villar Alvarez, Sandra Rovira-Amigo, Ignacio Iglesias Serrano, Ana Diez Izquierdo, Ines de Mir Messa, Silvia Gartner, Alexandra Navarro, Noelia Baz-Redon, Rosario Carmona, Nuria Camats-Tarruella, Monica Fernandez-Cancio, Christina Rapp, Joaquin Dopazo, Matthias Griese, Antonio Moreno-Galdo
Summary: This study analyzed the incidence and prevalence of children's diffuse lung disease (chILD) in Spain. The results showed a higher incidence and prevalence of chILD than previously described, probably due to greater understanding and increased clinician awareness of these rare diseases.
ARCHIVOS DE BRONCONEUMOLOGIA
(2022)
Article
Gastroenterology & Hepatology
David Perez Solis, Ma Luz Cilleruelo Pascual, Carlos Ochoa Sangrador, Jose Ignacio Garcia Burriel, Felix Sanchez-Valverde Visus, Francisco Javier Eizaguirre Arocena, Salvador Garcia Calatayud, Eva Martinez-Ojinaga Nodal, Ester Donat Aliaga, Josefa Barrio Torres, Gemma Castillejo de Villasante, Ma del Carmen Miranda Cid, Ricardo Torres Peral, Raquel Vecino Lopez, Mercedes Juste Ruiz, Honorio Armas Ramos, Patricia Barros Garcia, Rosaura Leis, Rosa Solaguren Alberdi, Jose Carlos Salazar Quero, Ruth Garcia Romero, Luis Ortigosa del Clastillo, Luis Pena Quintana, Pedro Urruzuno Telleria, Pilar Codoner Franch, Zurine Garcia Casales, Maria Lluisa Masiques Mas, Gonzalo Galicia Poblet, Cecilia Martinez Costa, Elena Balmaseda Serrano, Isabel Polanco Allue, Carmen Ribes Koninck, Enriqueta Roman Riechmann
Summary: There has been a trend towards less symptomatic forms of paediatric coeliac disease (CD) and an increase in the age at diagnosis in Spain. The most common clinical presentation is the classical form, but there is an increasing proportion of asymptomatic cases. The use of serological markers and HLA typing for diagnosis is increasing, while the proportion of patients undergoing biopsies is decreasing.
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
(2022)
Article
Gastroenterology & Hepatology
Alan Codoner-Alejos, Joaquin Carrasco-Luna, Alvaro Carrasco-Garcia, Pilar Codoner-Franch
Summary: The expression levels of FFAR4 gene are associated with childhood obesity and its comorbidities, suggesting a potential role in the pathogenesis of obesity-related conditions.
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
(2022)
Article
Nutrition & Dietetics
Marie Gombert, Vanessa Martin-Carbonell, Gonzalo Pin-Arboledas, Joaquin Carrasco-Luna, Alvaro Carrasco-Garcia, Pilar Codoner-Franch
Summary: The study found that melatonin levels in children with obesity significantly increased after sleep compared to controls, and were related to fat mass. Additionally, children with obesity had shorter sleep duration and earlier waking times. Melatonin in children with obesity appears to be involved in the global metabolic and inflammatory alteration of this condition.
Article
Chemistry, Applied
Elias Arilla, Javier Martinez-Monzo, Pilar Codoner-Franch, Purificacion Garcia-Segovia, Marta Igual
Summary: Adding resistant maltodextrin (RMD) to pasteurised orange juice can help preserve the bioactive compounds and antioxidant capacity, with the highest effectiveness seen in samples with 5% RMD.
FOOD SCIENCE AND TECHNOLOGY INTERNATIONAL
(2022)
Article
Gastroenterology & Hepatology
Ester Donat, Maria Roca, Gemma Castillejo, Felix Sanchez-Valverde, Jose Ignacio Garcia-Burriel, Eva Martinez-Ojinaga, Francisco Javier Eizaguirre, Josefa Barrio, Ma Luz Cilleruelo, David Perez-Solis, Carlos Ochoa-Sangrador, Raquel Vecino-Lopez, Ma Del Carmen Miranda-Cid, Salvador Garcia-Calatayud, Ricardo Torres-Peral, Mercedes Juste, Honorio Armas, Patricia Barros-Garcia, Rosaura Leis, Rosa Solaguren, Jose Carlos Salazar, Ruth Garcia-Romero, Luis Ortigosa, Luis Pena-Quintana, Pedro Urruzuno, Pilar Codoner-Franch, Zurine Garcia-Casales, Maria Lluisa Masiques, Gonzalo Galicia-Poblet, Elena Crehua-Gaudiza, Elena Balmaseda, Javier Rubio-Santiago, Isabel Polanco-Allue, Enriqueta Roman-Riechmann, Carmen Ribes-Koninckx
Summary: This study assessed the association between serological markers and changes in the intestinal mucosa in children with celiac disease. The results showed a positive correlation between t-TGA IgA levels and the severity of mucosal damage. Age was negatively associated with intestinal mucosal changes. In IgA-deficient patients, there was no correlation found between t-TGA IgG levels and intestinal mucosal changes.
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
(2022)
Correction
Medicine, General & Internal
Maria Magallon, Sara Pastor, Ana Esther Carrion, Lucia Banuls, Daniel Pellicer, Silvia Castillo, Sergio Bondia, Maria Mercedes Navarro-Garcia, Cruz Gonzalez, Francisco Dasi
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Immunology
Felix Sanchez-Valverde, Eva Martinez-Ojinaga, Ester Donat, Andres Bodas, Eva Bandres, Ricardo Torres, Berta Ibanez, Ma Luz Cilleruelo, Gemma Castillejo, David Perez-Solis, Carlos Ochoa, Francisco Javier Eizaguirre, Salvador Garcia, Jose Ignacio Garcia, Josefa Barrio, Raquel Vecino, Maria del Carmen Miranda, Mercedes Juste, Jose Carlos Salazar, Honorio Armas, Luis Ortigosa, Pedro Urruzuno, Zurine Garcia, Elena Balmaseda, Cecilia Martinez-Costa, Enrique La Orden, Pilar Codoner, Amadeu Roca, Carlos Trillo, Mercedes Sebastian, Ruth Garcia, Luis Pena-Quintana, Patricia Barros, Marta Soria, Roger Garcia, Begona Perez-Moneo, Isabel Polanco, Carmen Ribes, Enriqueta Roman, Margarita Pich, Ana Arevalo, Sonia Fernandez, David Gil, Pablo Oliver, Juan Manuel Bartolome, Jose Vicente Arcos, Francisco Perez, Haydee Exposito, Juana M. Rizo, Victor Manuel Navas, Rafael Gonzalez de Caldas, Maria Jesus Balboa, Cristina Molinos, Laura Alonso, Helena Lorenzo, Jose Bernardo Gonzalez, Maria Lluisa Masiques, Ana Isabel Ruiz, Jose Ignacio Olazabal
Summary: Celiac disease is strongly associated with HLA-DQ, specifically with haplotypes DRB1*03-DQA1*05:01/DQB1*02:01 (DQ2.5), DRB1*07-DQA1*02:01/DQB1*02:02 (DQ2.2), DRB1*11-DQA1*05:05/DQB1*03:01 (DQ7.5), and DRB1*04-DQA1*03:01/DQB1*03:02 (DQ8). The distribution of these risk haplotypes in patients with celiac disease varies in different geographical areas.
Review
Biochemistry & Molecular Biology
Pilar Codoner-Franch, Marie Gombert, Jose Martinez-Raga, Maria Carmen Cenit
Summary: Mental illness is increasing alarmingly, and the disruptions in circadian rhythms caused by modern lifestyle may be the main explanation for this trend. Impaired circadian rhythms are associated with mental disorders, and evening chronotype is a risk factor for severe psychiatric symptoms and metabolic comorbidities. Resynchronization of circadian rhythms improves psychiatric symptoms, and preventing circadian misalignment may reduce the risk and impact of psychiatric disorders. The gut microbiota, regulated by meal timing, exhibits diurnal rhythmicity and can aid in preventing circadian misalignment and resynchronizing circadian rhythms, making it a potential therapeutic strategy for mental illnesses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Maria Magallon, Silvia Castillo-Corullon, Lucia Banuls, Daniel Pellicer, Teresa Romero, Carlos Martinez-Ferraro, Maria Mercedes Navarro-Garcia, Alberto Herrejon, Cruz Gonzalez, Francisco Dasi
Summary: This study aims to determine the impact of hypoxia on neutrophil oxidative stress profile in AATD patients. Our results indicate that ZZ-AATD neutrophils produce higher amounts of hydrogen peroxide, peroxynitrite, and nitric oxide and decreased levels of the antioxidant enzymes. Likewise, our results show a decrease in mitochondrial membrane potential, indicating that this organelle could be involved in the production of the reactive species observed.
Article
Respiratory System
Maria Torres-Duran, Jose Luis Lopez-Campos, Myriam Calle Rubio, Carmen Montero-Martinez, Ana Priegue Carrera, Rosanel Amaro Rodriguez, Miriam Barrecheguren, Maria Angeles Barrio Guirado, Francisco Javier Callejas-Gonzalez, Francisco Casas-Maldonado, Layla Diab-Caceres, Pilar Garcia-Meseguer, Jose Maria Hernandez-Perez, Lourdes Lazaro-Asegurado, Cristina Martinez-Gonzalez, Carlos Martinez Rivera, Francisco Javier Michel, Jose-Bruno Montoro-Ronsano, Raquel Sanchez, Marta Ortiz-Pica, Isabel Parra, Jose Pablo Quintero Garcia, Maria del Rosario Ruiz-Serrano-de la Espada, Begona Tortajada-Goitia, Marc Miravitlles
Summary: This study provides recommendations for the implementation of a self-administration program for patients with AAT deficiency, including patient selection criteria, roles of healthcare professionals, training, and logistic issues. The proposal aims to increase awareness and facilitate the implementation of self-administration programs for AAT therapy, with the potential for improving patient experience and outcomes.
INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
(2023)