المؤلفون: Sergio Garcia-Segura, Javier del Rey, Laia Closa, Iris Garcia-Martínez, Carlos Hobeich, Ana Belén Castel, Francisco Vidal, Jordi Benet, Maria Oliver-Bonet

المساهمون: Institut Català de la Salut, [Garcia-Segura S, Del Rey J] Unit of Cell Biology and Medical Genetics, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Closa L] Histocompatibility and Immunogenetics Laboratory, Banc de Sang i Teixits (BST), Barcelona, Spain. Medicina Transfusional, Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. [Garcia-Martínez I, Hobeich C] Grup de Recerca de Medicina Transfusional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Grup de Coagulopaties Congènites, Banc de Sang i Teixits (BST), Barcelona, Spain. [Castel AB] Instituto de Fertilidad, Palma de Mallorca, Spain. [Vidal F] Grup de Recerca de Medicina Transfusional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Grup de Coagulopaties Congènites, Banc de Sang i Teixits (BST), Barcelona, Spain. CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain, Vall d'Hebron Barcelona Hospital Campus

المصدر: International Journal of Molecular Sciences; Volume 24; Issue 9; Pages: 7867
Scientia

مصطلحات موضوعية: Otros calificadores::Otros calificadores::/genética [Otros calificadores], Organic Chemistry, General Medicine, Male Urogenital Diseases::Genital Diseases, Male::Infertility [DISEASES], Esterilitat, Bacteris, Catalysis, Computer Science Applications, Inorganic Chemistry, fenómenos microbiológicos::microbiota [FENÓMENOS Y PROCESOS], Other subheadings::Other subheadings::/genetics [Other subheadings], Physical and Theoretical Chemistry, Microbiological Phenomena::Microbiota [PHENOMENA AND PROCESSES], enfermedades urogenitales masculinas::enfermedades de los genitales masculinos::infertilidad [ENFERMEDADES], Molecular Biology, seminal microbiota, MinION, nanopore sequencing, Illumina, male fertility, Genètica, Spectroscopy

الوصف: Male fertility; Nanopore sequencing; Seminal microbiota Fertilitat masculina; Seqüenciació de nanopors; Microbiota seminal Fertilidad masculina; Secuenciación de nanoporos; Microbiota seminal Since the first description of a commensal seminal microbiome using sequencing, less than a decade ago, interest in the composition of this microbiome and its relationship with fertility has been growing. Articles using next-generation sequencing techniques agree on the identification of the most abundant bacterial phyla. However, at the genus level, there is still no consensus on which bacteria are most abundant in human seminal plasma. This discrepancy may be due to methodological variability such as sample collection, bacterial DNA extraction methodology, which hypervariable regions of 16S rRNA gene have been amplified, or bioinformatic analysis. In the present work, seminal microbiota of 14 control samples and 42 samples of idiopathic infertile patients were characterized based on full-length sequencing of the 16S rRNA gene using MinION platform from Oxford Nanopore. These same samples had been analyzed previously using Illumina’s MiSeq sequencing platform. Comparison between the results obtained with the two platforms has been used to analyze the impact of sequencing method on the study of the seminal microbiome’s composition. Seminal microbiota observed with MinION were mainly composed of the phyla Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria, with the most abundant genera being Peptoniphilus, Finegoldia, Staphylococcus, Anaerococcus, Campylobacter, Prevotella, Streptococcus, Lactobacillus, Ezakiella and Enterococcus. This composition was similar to that found by the Illumina platform, since these 10 most abundant genera were also among the most abundant genera detected by the Nanopore platform. In both cases, the top 10 genera represented more than 70% of the classified reads. However, relative abundance of each bacterium did not correlate between these two platforms, with intraindividual variations of up to 50 percentage points in some cases. Results suggest that the effect of the sequencing platform on the characterization of seminal microbiota is not very large at the phylum level, with slightly variances in Firmicutes and Actinobacteria, but presents differences at the genus level. These differences could alter the composition and diversity of bacterial profiles or posterior analyses. This indicates the importance of conducting multi-platform studies to better characterize seminal microbioma. This research was funded by the European Regional Development Fund and Instituto de Salud Carlos III (Economy, Industry and Competitiveness Ministry, Madrid, Spain; Project PI14/00119) and Generalitat de Catalunya (2017SGR1796 and 2021SGR00122).

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ed9f3a585131ea430cb120cab6e0ecc7Test

المؤلفون: Ian Y. Luk, Laura J. Jenkins, Kael L. Schoffer, Irvin Ng, Janson W. T. Tse, Dmitri Mouradov, Stanislaw Kaczmarczyk, Rebecca Nightingale, Allan D. Burrows, Robin L. Anderson, Diego Arango, Higinio Dopeso, Larry Croft, Mark F. Richardson, Oliver M. Sieber, Yang Liao, Jennifer K. Mooi, Natalia Vukelic, Camilla M. Reehorst, Shoukat Afshar-Sterle, Vicki L. J. Whitehall, Lochlan Fennell, Helen E. Abud, Niall C. Tebbutt, Wayne A. Phillips, David S. Williams, Wei Shi, Lisa A. Mielke, Matthias Ernst, Amardeep S. Dhillon, Nicholas J. Clemons, John M. Mariadason

المساهمون: Institut Català de la Salut, [Luk IY, Tse JWT] Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia. La Trobe University School of Cancer Medicine, Melbourne, VIC, Australia. Department of Medicine, University of Melbourne, Melbourne, VIC, Australia. [Jenkins LJ, Schoffer KL, Ng I] Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia. La Trobe University School of Cancer Medicine, Melbourne, VIC, Australia. [Mouradov D] Personalised Oncology Division, The Walter and Eliza Hall Institute of Medial Research, Parkville, VIC, Australia. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia. [Arango D] Grup de Recerca Biomèdica en Tumors de l'Aparell Digestiu, CIBBIM-Nanomedicina, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Group of Molecular Oncology, Biomedical Research institute of Lleida (IRBLleida), Lleida, Spain. [Dopeso H] Grup de Recerca Biomèdica en Tumors de l'Aparell Digestiu, CIBBIM-Nanomedicina, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus

المصدر: Scientia

مصطلحات موضوعية: Homeodomain Proteins, fenómenos genéticos::regulación de la expresión génica::epigénesis genética [FENÓMENOS Y PROCESOS], Recte - Càncer - Aspectes genètics, Otros calificadores::Otros calificadores::/genética [Otros calificadores], FOS: Clinical medicine, Còlon - Càncer - Aspectes genètics, Cell Biology, Epigenètica, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES], Epigenesis, Genetic, Mice, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES], Genetic Phenomena::Gene Expression Regulation::Epigenesis, Genetic [PHENOMENA AND PROCESSES], Other subheadings::Other subheadings::/genetics [Other subheadings], Animals, Colorectal Neoplasms, Molecular Biology, Transcription Factors, Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors [CHEMICALS AND DRUGS], aminoácidos, péptidos y proteínas::proteínas::factores de transcripción [COMPUESTOS QUÍMICOS Y DROGAS], 111299 Oncology and Carcinogenesis not elsewhere classified

الوصف: Epigenetics; Tumour-suppressor proteins Epigenética; Proteínas supresoras de tumores Epigenètica; Proteïnes supresores de tumors Colorectal cancers (CRCs) often display histological features indicative of aberrant differentiation but the molecular underpinnings of this trait and whether it directly drives disease progression is unclear. Here, we identify co-ordinate epigenetic inactivation of two epithelial-specific transcription factors, EHF and CDX1, as a mechanism driving differentiation loss in CRCs. Re-expression of EHF and CDX1 in poorly-differentiated CRC cells induced extensive chromatin remodelling, transcriptional re-programming, and differentiation along the enterocytic lineage, leading to reduced growth and metastasis. Strikingly, EHF and CDX1 were also able to reprogramme non-colonic epithelial cells to express colonic differentiation markers. By contrast, inactivation of EHF and CDX1 in well-differentiated CRC cells triggered tumour de-differentiation. Mechanistically, we demonstrate that EHF physically interacts with CDX1 via its PNT domain, and that these transcription factors co-operatively drive transcription of the colonic differentiation marker, VIL1. Compound genetic deletion of Ehf and Cdx1 in the mouse colon disrupted normal colonic differentiation and significantly enhanced colorectal tumour progression. These findings thus reveal a novel mechanism driving epithelial de-differentiation and tumour progression in CRC. This project was supported by NHMRC project grant (1107831), a Cancer Council Victoria Grant (1164674) and the Operational Infrastructure Support Programme, Victorian Government, Australia. JMM was supported by a NHMRC Senior Research Fellowship (1046092). IYL was supported by F J Fletcher Research Scholarship and Randal and Louisa Alcock Scholarship from the University of Melbourne. LJJ was supported by La Trobe University Australian Postgraduate Awards. IN was supported by La Trobe University Postgraduate Research Scholarship. JWTT was supported by the University of Melbourne Australian Postgraduate Awards. OMS is a National Health and Medical Research Council (NHMRC) Senior Research Fellow (APP1136119). Open Access funding enabled and organized by CAUL and its Member Institutions.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c1771def1a2b343893e5c103bb2bd76Test

المؤلفون: Esther Clavero, José Manuel Sanchez-Maldonado, Angelica Macauda, Rob Ter Horst, Belém Sampaio-Marques, Artur Jurczyszyn, Alyssa Clay-Gilmour, Angelika Stein, Michelle A. T. Hildebrandt, Niels Weinhold, Gabriele Buda, Ramón García-Sanz, Waldemar Tomczak, Ulla Vogel, Andrés Jerez, Daria Zawirska, Marzena Wątek, Jonathan N. Hofmann, Stefano Landi, John J. Spinelli, Aleksandra Butrym, Abhishek Kumar, Joaquín Martínez-López, Sara Galimberti, María Eugenia Sarasquete, Edyta Subocz, Elzbieta Iskierka-Jażdżewska, Graham G. Giles, Malwina Rybicka-Ramos, Marcin Kruszewski, Niels Abildgaard, Francisco García Verdejo, Pedro Sánchez Rovira, Miguel Inacio da Silva Filho, Katalin Kadar, Małgorzata Razny, Wendy Cozen, Matteo Pelosini, Manuel Jurado, Parveen Bhatti, Marek Dudzinski, Agnieszka Druzd-Sitek, Enrico Orciuolo, Yang Li, Aaron D. Norman, Jan Maciej Zaucha, Rui Manuel Reis, Miroslaw Markiewicz, Juan José Rodríguez Sevilla, Vibeke Andersen, Krzysztof Jamroziak, Kari Hemminki, Sonja I. Berndt, Vicent Rajkumar, Grzegorz Mazur, Shaji K. Kumar, Paula Ludovico, Arnon Nagler, Stephen J. Chanock, Charles Dumontet, Mitchell J. Machiela, Judit Varkonyi, Nicola J. Camp, Elad Ziv, Annette Juul Vangsted, Elizabeth E. Brown, Daniele Campa, Celine M. Vachon, Mihai G. Netea, Federico Canzian, Asta Försti, Juan Sainz

المساهمون: Institut Català de la Salut, [Clavero E] Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain. [Sanchez-Maldonado JM] Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, Spain. Instituto de Investigación Biosanataria IBs, Granada, Granada, Spain. [Macauda A] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Ter Horst R] Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, GA Nijmegen, The Netherlands. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. [Sampaio-Marques B] Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. [Jurczyszyn A] Plasma Cell Dyscrasias Center, Department of Hematology, Jagiellonian University Medical College, Kraków, Poland. [Jerez A] Experimental Hematology Unit, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus

المصدر: International Journal of Molecular Sciences, 24, 10
International Journal of Molecular Sciences; Volume 24; Issue 10; Pages: 8500
Scientia
International Journal of Molecular Sciences, 24

مصطلحات موضوعية: fenómenos fisiológicos celulares::muerte celular::autofagia [FENÓMENOS Y PROCESOS], Cell Physiological Phenomena::Cell Death::Autophagy [PHENOMENA AND PROCESSES], Otros calificadores::Otros calificadores::/genética [Otros calificadores], Organic Chemistry, Hemic and Lymphatic Diseases::Hematologic Diseases::Blood Protein Disorders::Paraproteinemias::Hemic and Lymphatic Diseases::Hematologic Diseases::Multiple Myeloma [DISEASES], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Mieloma múltiple - Aspectes genètics, General Medicine, Biological Factors::Biomarkers [CHEMICALS AND DRUGS], Catalysis, factores biológicos::biomarcadores [COMPUESTOS QUÍMICOS Y DROGAS], Computer Science Applications, multiple myeloma, autophagy, genetic variants, genetic susceptibility, Inorganic Chemistry, All institutes and research themes of the Radboud University Medical Center, Autofàgia, Marcadors bioquímics, Other subheadings::Other subheadings::/genetics [Other subheadings], Physical and Theoretical Chemistry, enfermedades hematológicas y linfáticas::enfermedades hematológicas::trastornos de las proteínas sanguíneas::paraproteinemias::enfermedades hematológicas y linfáticas::enfermedades hematológicas::mieloma múltiple [ENFERMEDADES], Molecular Biology, Spectroscopy

الوصف: Autophagy; Genetic variants; Multiple myeloma Autofagia; Variantes genéticas; Mieloma múltiple Autofàgia; Variants genètiques; Mieloma múltiple Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+IgD− cells, IgM− cells, IgD−IgM− cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27− cells (p = 9.3 × 10−4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3−, MCP-2−, and IL20-dependent pathways. This work was supported by the European Union’s Horizon 2020 research and innovation program, N° 856620 and by grants from the Instituto de Salud Carlos III and FEDER (Madrid, Spain; PI17/02256 and PI20/01845), Consejería de Transformación Económica, Industria, Conocimiento y Universidades and FEDER (PY20/01282), from the CRIS foundation against cancer, from the Cancer Network of Excellence (RD12/10 Red de Cáncer), from the Dietmar Hopp Foundation and the German Ministry of Education and Science (BMBF: CLIOMMICS [01ZX1309]), and from National Cancer Institute of the National Institutes of Health under award numbers: R01CA186646, U01CA249955 (EEB). This work was also funded d by Portuguese National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020 and by the project NORTE-01-0145-FEDER-000055, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).

وصف الملف: application/pdf; application/vnd.openxmlformats-officedocument.spreadsheetml.sheet

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b9418026976c50e18561c5d0878d524cTest
https://repository.ubn.ru.nl/handle/2066/293432Test

المؤلفون: Kerick, Martin, Acosta-Herrera, Marialbert, Simeón-Aznar, Carmen Pilar, Callejas, José Luis, Assassi, Shervin, International SSc Group, Proudman, Susanna M, Nikpour, Mandana, Australian Scleroderma Interest Group (ASIG), PRECISESADS Clinical Consortium, Hunzelmann, Nicolas, Moroncini, Gianluca, de Vries-Bouwstra, Jeska K, Orozco, Gisela, Barton, Anne, Herrick, Ariane L, Terao, Chikashi, Allanore, Yannick, Fonseca, Carmen, Alarcón-Riquelme, Marta Eugenia, Radstake, Timothy R D J, Beretta, Lorenzo, Denton, Christopher P, Mayes, Maureen D, Martin, Javier

المساهمون: Institut Català de la Salut, [Kerick M] Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain. [Acosta-Herrera M] Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain. Systemic Autoimmune Disease Unit, Hospital Clínico San Cecilio, Instituto de Investigación Biosanitaria Ibs. GRANADA, Granada, Spain. [Simeón-Aznar CP] Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Callejas JL] Department of Internal Medicine, Hospital San Cecilio, Granada, Spain. [Assassi S] Department of Rheumatology, The University of Texas Health Science Center at Houston, Houston, TX, USA, Vall d'Hebron Barcelona Hospital Campus, Rheumatology, AII - Inflammatory diseases

المصدر: NPJ Genomic Medicine, 7, 1
International SSc Group, Australian Scleroderma Interest Group (ASIG) & PRECISESADS Clinical Consortium 2022, ' Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis ', NPJ GENOMIC MEDICINE, vol. 7, no. 1, 57 . https://doi.org/10.1038/s41525-022-00327-8Test
Scientia
NPJ Genomic Medicine, 7
NPJ GENOMIC MEDICINE, 7(1):57. Nature Publishing Group

مصطلحات موضوعية: Otros calificadores::Otros calificadores::/genética [Otros calificadores], Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic [DISEASES], Genetics, Other subheadings::Other subheadings::/genetics [Other subheadings], Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Esclerosi sistemàtica progressiva - Aspectes genètics, Genetic Phenomena::Genetic Phenomena::Genetic Structures::Transcriptome [PHENOMENA AND PROCESSES], Molecular Biology, Expressió gènica, enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::esclerodermia sistémica [ENFERMEDADES], Genetics (clinical), fenómenos genéticos::expresión génica [FENÓMENOS Y PROCESOS]

الوصف: Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals.
MCIN/AEI by "ERDF A way of making Europe" RTI2018101332-B-100
Red de Investigacion en Inflamacion y Enfermedades Reumaticas (RIER) from Instituto de Salud Carlos III RD16/0012/0013
Innovative Medicines Initiative 1 & 2 Joint Undertaking (JU) 115565 831434
European Union's FP7 and Horizon 2020 research and innovation programs
EFPIA
Juan de la Cierva Incorporacion program - MCIN/AEI IJC2018-035131-I

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b8c515a057db2ca1f215e35ef1d803d2Test
https://hdl.handle.net/10481/77756Test

المؤلفون: Nora Diéguez-Martínez, Sergio Espinosa-Gil, Guillermo Yoldi, Elisabet Megías-Roda, Idoia Bolinaga-Ayala, Maria Viñas-Casas, Gokhan Gorgisen, Inés Domingo-Ortí, Héctor Pérez-Montoyo, Jose R. Bayascas, Eva Colas, Xavier Dolcet, Jose M. Lizcano

المساهمون: Institut Català de la Salut, [Diéguez-Martínez N, Espinosa-Gil S, Bolinaga-Ayala I, Viñas-Casas M, Lizcano JM] Departament de Bioquímica i Biologia Molecular, Unitat de Medicina, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. Grup de Recerca en Proteïnes Kinases i Càncer, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Yoldi G] Departament de Bioquímica i Biologia Molecular, Unitat de Medicina, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Megías-Roda E] Grup de Recerca en Proteïnes Kinases i Càncer, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Ability Pharmaceuticals, SL. Cerdanyola del Vallès, 08290 Barcelona, Spain. [Colas E] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBERONC, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus

المصدر: Scientia
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona

مصطلحات موضوعية: Paclitaxel, MAP Kinase Signaling System, Mice, Nude, Medicaments antineoplàstics - Ús terapèutic, Apoptosis, MAP Kinase Kinase 5, Map kinase, Endometri - Càncer - Tractament, Carboplatin, Mice, Cellular and Molecular Neuroscience, fenómenos fisiológicos celulares::procesos de crecimiento celular::proliferación celular [FENÓMENOS Y PROCESOS], Endometrial cancer, Other subheadings::Other subheadings::/genetics [Other subheadings], Animals, Humans, NF-kB, Molecular Biology, Cell Proliferation, Pharmacology, Cell Physiological Phenomena::Cell Growth Processes::Cell Proliferation [PHENOMENA AND PROCESSES], Epidermal Growth Factor, Otros calificadores::Otros calificadores::/genética [Otros calificadores], NF-kappa B, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS], Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Endometrial Neoplasms [DISEASES], Cell Biology, Anticancer drug, Endometrial Neoplasms, ERK5, Cytokines, Molecular Medicine, Female, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS], neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales femeninos::neoplasias uterinas::neoplasias endometriales [ENFERMEDADES], Endometri - Càncer - Aspectes genètics

الوصف: Apoptosis; Endometrial cancer; Map kinase Apoptosis; Cáncer endometrial; Mapa quinasa Apoptosi; Càncer d'endometri; Mapa quinasa Endometrial cancer (EC) is the most common type of gynecologic cancer in women of developed countries. Despite surgery combined with chemo-/radiotherapy regimens, overall survival of patients with high-risk EC tumors is poor, indicating a need for novel therapies. The MEK5-ERK5 pathway is activated in response to growth factors and to different stressors, including oxidative stress and cytokines. Previous evidence supports a role for the MEK5-ERK5 pathway in the pathology of several cancers. We investigated the role of ERK5 in EC. In silico analysis of the PanCancer Atlas dataset showed alterations in components of the MEK5-ERK5 pathway in 48% of EC patients. Here, we show that ERK5 inhibition or silencing decreased EGF-induced EC cell proliferation, and that genetic deletion of MEK5 resulted in EC impaired proliferation and reduced tumor growth capacity in nude mice. Pharmacologic inhibition or ERK5 silencing impaired NF-kB pathway in EC cells and xenografts. Furthermore, we found a positive correlation between ERK5 and p65/RELA protein levels in human EC tumor samples. Mechanistically, genetic or pharmacologic impairment of ERK5 resulted in downregulation of NEMO/IKKγ expression, leading to impaired p65/RELA activity and to apoptosis in EC cells and xenografts, which was rescued by NEMO/IKKγ overexpression. Notably, ERK5 inhibition, MEK5 deletion or NF-kB inhibition sensitized EC cells to standard EC chemotherapy (paclitaxel/carboplatin) toxicity, whereas ERK5 inhibition synergized with paclitaxel to reduce tumor xenograft growth in mice. Together, our results suggest that the ERK5-NEMO-NF-κB pathway mediates EC cell proliferation and survival. We propose the ERK5/NF-κB axis as new target for EC treatment. Open Access Funding provided by Universitat Autonoma de Barcelona. The JM Lizcano research group was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO, grant SAF2015-64237-R), and the Spanish Ministry of Science and Innovation (grant PID2019-107561RB-I00), and co-funded by the European Regional Development Fund (ERDF).

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7ee209282eb349c6036150295fb11f1bTest
https://hdl.handle.net/11351/8468Test

المؤلفون: Luca Bosco, Daniela Leone, Laura Costa Comellas, Mauro Monforte, Marika Pane, Eugenio Mercuri, Enrico Bertini, Adele D’Amico, Fabiana Fattori

المساهمون: Institut Català de la Salut, [Bosco L] Genetics and Rare Diseases Research Division, Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy. Department of Science, University 'Roma Tre', Rome, Italy. [Leone D] Centro Clinico Nemo, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Roma, Italy. [Costa Comellas L] Servei de Neurologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Monforte M] UOC di Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. [Pane M, Mercuri E] Centro Clinico Nemo, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Roma, Italy. Pediatric Neurology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Rome, Italy, Vall d'Hebron Barcelona Hospital Campus

المصدر: Scientia

مصطلحات موضوعية: Otros calificadores::Otros calificadores::/genética [Otros calificadores], Organic Chemistry, enfermedades musculoesqueléticas::enfermedades musculares::miopatías estructurales congénitas [ENFERMEDADES], Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES], General Medicine, Musculoskeletal Diseases::Muscular Diseases::Myopathies, Structural, Congenital [DISEASES], Catalysis, Computer Science Applications, Inorganic Chemistry, Anomalies cromosòmiques, Músculs - Malalties - Aspectes genètics, Other subheadings::Other subheadings::/genetics [Other subheadings], Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS]

الوصف: Myotubular myopathy; Novel mutation; Splicing Miopatía miotubular; Nueva mutación; Empalme Miopatia miotubular; Nova mutació; Empalmament X-linked myotubular myopathy (XLMTM) is a severe form of centronuclear myopathy, characterized by generalized weakness and respiratory insufficiency, associated with pathogenic variants in the MTM1 gene. NGS targeted sequencing on the DNA of a three-month-old child affected by XLMTM identified the novel hemizygous MTM1 c.1261-5T>G intronic variant, which interferes with the normal splicing process, generating two different abnormal transcripts simultaneously expressed in the patient’s muscular cells. The first aberrant transcript, induced by the activation of a cryptic splice site in intron 11, includes four intronic nucleotides upstream of exon 12, resulting in a shift in the transcript reading frame and introducing a new premature stop codon in the catalytic domain of the protein (p.Arg421SerfsTer7). The second aberrant MTM1 transcript, due to the lack of recognition of the 3′ acceptor splice site of intron 11 from the spliceosome complex, leads to the complete skipping of exon 12. We expanded the genotypic spectrum of XLMTM underlying the importance of intron–exons boundaries sequencing in male patients affected by XLMTM.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da1b8331fd30da6eb0a5138914868503Test
https://hdl.handle.net/11351/8474Test

المؤلفون: Beatriz Villafranca-Magdalena, Carina Masferrer-Ferragutcasas, Carlos Lopez-Gil, Eva Coll-de la Rubia, Marta Rebull, Genis Parra, Ángel García, Armando Reques, Silvia Cabrera, Eva Colas, Antonio Gil-Moreno, Cristian P. Moiola

المساهمون: Institut Català de la Salut, [Villafranca-Magdalena B, Masferrer-Ferragutcasas C, Lopez-Gil C, Rebull M, Moiola CP] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Escola de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Coll-de la Rubia E, Colas E] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Escola de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Biomedical Research Center Network (CIBERONC), Madrid, Spain. [Parra G] National Center for Genomic Analysis—Genomic Regulation Center (CNAG-CRG), Scientific Park of Barcelona, Barcelona, Spain. [García A, Reques A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Cabrera S, Gil-Moreno A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Escola de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Biomedical Research Center Network (CIBERONC), Madrid, Spain. Servei de Ginecologia Oncològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus

المصدر: International Journal of Molecular Sciences; Volume 23; Issue 11; Pages: 6266
Scientia

مصطلحات موضوعية: Otros calificadores::Otros calificadores::/genética [Otros calificadores], Organic Chemistry, Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Endometrial Neoplasms [DISEASES], endometrial cancer, preclinical model, PDXs, personalized medicine, translational research, genomics, bioinformatics, molecular marker, TCGA, General Medicine, Genomics, Xenograft Model Antitumor Assays, Catalysis, Computer Science Applications, Endometrial Neoplasms, Inorganic Chemistry, Disease Models, Animal, Genòmica, Other subheadings::Other subheadings::/genetics [Other subheadings], Animals, Heterografts, Humans, Female, Endometri - Càncer, Physical and Theoretical Chemistry, Neoplasm Recurrence, Local, neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales femeninos::neoplasias uterinas::neoplasias endometriales [ENFERMEDADES], Molecular Biology, Spectroscopy

الوصف: Bioinformatics; Endometrial cancer; Molecular marker Bioinformática; Cáncer endometrial; Marcador molecular Bioinformàtica; Càncer d'endometri; Marcador molecular Endometrial cancer (EC) is the second most frequent gynecological cancer worldwide. Although improvements in EC classification have enabled an accurate establishment of disease prognosis, women with a high-risk or recurrent EC face a dramatic situation due to limited further treatment options. Therefore, new strategies that closely mimic the disease are required to maximize drug development success. Patient-derived xenografts (PDXs) are widely recognized as a physiologically relevant preclinical model. Hence, we propose to molecularly and histologically validate EC PDX models. To reveal the molecular landscape of PDXs generated from 13 EC patients, we performed histological characterization and whole-exome sequencing analysis of tumor samples. We assessed the similarity between PDXs and their corresponding patient’s tumor and, additionally, to an extended cohort of EC patients obtained from The Cancer Genome Atlas (TCGA). Finally, we performed functional enrichment analysis to reveal differences in molecular pathway activation in PDX models. We demonstrated that the PDX models had a well-defined and differentiated molecular profile that matched the genomic profile described by the TCGA for each EC subtype. Thus, we validated EC PDX’s potential to reliably recapitulate the majority of histologic and molecular EC features. This work highlights the importance of a thorough characterization of preclinical models for the improvement of the success rate of drug-screening assays for personalized medicine. This research was funded by grants from the Instituto de Salud Carlos III (ISCIII) grant number PI17/02071, PI20/01566, and from the Ministerio de ciencia, Innovación y Universidades through a RETOS Colaboración (RTC-2017-6261-1), both co-financed by the European Regional Development Fund (FEDER); from Fundación Científica Asociación Española Contra el Cáncer (AECC) grant number GCTRA1804MATI, Biomedical Research Center Network (CIBERONC) grant number CB16/12/00328 and Generalitat de Catalunya, grant number 2017SGR1661. B.V.-M. is supported by a predoctoral fellowship (PERIS-SLT017/20/000183) from Generalitat de Catalunya. E.C. is supported by an Investigator Grant from AECC (INVES20051COLA).

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7540405cab123be7843b3463a6fa6979Test

المؤلفون: Dolores Martínez-Rubio, Ángela Rodríguez-Prieto, Paula Sancho, Carmen Navarro-González, Nerea Gorría-Redondo, Javier Miquel-Leal, Clara Marco-Marín, Alison Jenkins, Mario Soriano-Navarro, Alberto Hernández, Belén Pérez-Dueñas, Pietro Fazzari, Sergio Aguilera-Albesa, Carmen Espinós

المساهمون: Instituto de Salud Carlos III, European Commission, Ministerio de Economía y Competitividad (España), Fundació La Marató de TV3, Generalitat Valenciana, Ministerio de Ciencia e Innovación (España), Marco-Marín, Clara, Institut Català de la Salut, [Martínez-Rubio D] Rare Neurodegenerative Diseases Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain. Joint Unit CIPF-IIS La Fe Rare Diseases, Valencia, Spain. [Rodríguez-Prieto Á, Navarro-González C, Miquel-Leal J] Cortical Circuits in Health and Disease Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain. [Sancho P] Rare Neurodegenerative Diseases Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain. [Gorría-Redondo N] Pediatric Neurology Unit, Department of Pediatrics, Complejo Hospitalario de Navarra, Navarrabiomed, Pamplona, Spain. [Pérez-Dueñas B] Servei de Neurologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus

المصدر: HUMAN MOLECULAR GENETICS
r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
instname
r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
Scientia

مصطلحات موضوعية: Pediatria, Peroxiredoxin III, Cerebel - Degeneració, Cerebellar Ataxia, Otros calificadores::Otros calificadores::/genética [Otros calificadores], aminoácidos, péptidos y proteínas::proteínas::proteínas mitocondriales [COMPUESTOS QUÍMICOS Y DROGAS], General Medicine, Atàxia - Aspectes genètics, Mitochondrial Proteins, Mice, enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades cerebelosas::degeneraciones espinocerebelosas [ENFERMEDADES], enfermedades del sistema nervioso::manifestaciones neurológicas::discinesias::ataxia [ENFERMEDADES], Amino Acids, Peptides, and Proteins::Proteins::Mitochondrial Proteins [CHEMICALS AND DRUGS], Mutation, Other subheadings::Other subheadings::/genetics [Other subheadings], Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebellar Diseases::Spinocerebellar Degenerations [DISEASES], Genetics, Humans, Animals, Ataxia, Molecular Biology, Genetics (clinical), Nervous System Diseases::Neurologic Manifestations::Dyskinesias::Ataxia [DISEASES], HeLa Cells, Spinocerebellar Degenerations

الوصف: 17 páginas, 8 figuras
Peroxiredoxin 3 (PRDX3) encodes a mitochondrial antioxidant protein, which is essential for the control of reactive oxygen species homeostasis. So far, PRDX3 mutations are involved in mild-to-moderate progressive juvenile onset cerebellar ataxia. We aimed to unravel the molecular bases underlying the disease in an infant suffering from cerebellar ataxia that started at 19 months old and presented severe cerebellar atrophy and peripheral neuropathy early in the course of disease. By whole exome sequencing, we identified a novel homozygous mutation, PRDX3 p.D163E, which impaired the mitochondrial ROS defense system. In mouse primary cortical neurons, the exogenous expression of PRDX3 p.D163E was reduced and triggered alterations in neurite morphology and in mitochondria. Mitochondrial computational parameters showed that p.D163E led to serious mitochondrial alterations. In transfected HeLa cells expressing the mutation, mitochondria accumulation was detected by correlative light electron microscopy. Mitochondrial morphology showed severe changes, including extremely damaged outer and inner membranes with a notable cristae disorganization. Moreover, spherical structures compatible with lipid droplets were identified, which can be associated with a generalized response to stress and can be involved in the removal of unfolded proteins. In the patient's fibroblasts, PRDX3 expression was nearly absent. The biochemical analysis suggested that the mutation p.D163E would result in an unstable structure tending to form aggregates that trigger unfolded protein responses via mitochondria and endoplasmic reticulum. Altogether, our findings broaden the clinical spectrum of the recently described PRDX3-associated neurodegeneration and provide new insight into the pathological mechanisms underlying this new form of cerebellar ataxia.
The Instituto de Salud Carlos III (ISCIII)—Subdirección General de Evaluación y Fomento de la Investigación within the framework of the National R + D + I Plan cofunded with European Regional Development Funds (ERDF) (grants PI18/00147 and PI21/00103 to C.E.); the Spanish Ministry of Economy and Competitiveness (grant SAF2017-89020-R to P.F.); the Fundació La Marató TV3 (grants 20143130 and 20143131 to B.P.-D. and C.E.) and the Generalitat Valenciana (grant PROMETEO/2018/135 to C.E.). Part of the equipment employed in this work was funded by Generalitat Valenciana and co-financed with ERDF (OP ERDF of Comunitat Valenciana 2014-2020). P.F. and A.R.-P. are supported by the Spanish Ministry of Science and Innovation (grants RyC-2014-16410 to P.F. and PRE2018-083562 to A.R.-P.).

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3cdcc3ce146164c11fcb0a4936001ae4Test
https://pubmed.ncbi.nlm.nih.gov/35766882Test

المؤلفون: Inés García-Consuegra, Sara Asensio-Peña, Rocío Garrido-Moraga, Tomàs Pinós, Cristina Domínguez-González, Alfredo Santalla, Gisela Nogales-Gadea, Pablo Serrano-Lorenzo, Antoni L. Andreu, Joaquín Arenas, José L. Zugaza, Alejandro Lucia, Miguel A. Martín

المساهمون: Institut Català de la Salut, [García-Consuegra I, Domínguez-González C] Mitochondrial and Neuromuscular Disorders Group, Hospital 12 de Octubre Health Research Institute (imas12), Madrid, Spain. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain. [Asensio-Peña S, Garrido-Moraga R] Mitochondrial and Neuromuscular Disorders Group, Hospital 12 de Octubre Health Research Institute (imas12), Madrid, Spain. [Pinós T] Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain. Grup de Recerca de Patologia Neuromuscular i Mitocondrial, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Santalla A] Department of Computer and Sport Sciences, Universidad Pablo de Olavide, Sevilla, Spain, Vall d'Hebron Barcelona Hospital Campus

المصدر: International Journal of Molecular Sciences
r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol
instname
ABACUS. Repositorio de Producción Científica
Universidad Europea (UEM)
Addi. Archivo Digital para la Docencia y la Investigación
Universidad de Alicante (UA)
International Journal of Molecular Sciences; Volume 23; Issue 9; Pages: 4650
Scientia

مصطلحات موضوعية: McArdle disease, Proteome, Múscul estriat - Patogènesi, Enfermedad del almacenamiento de glucógeno tipo V, Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Carbohydrate Metabolism, Inborn Errors::Glycogen Storage Disease::Glycogen Storage Disease Type V [DISEASES], Enfermedad cardiovascular, Genética humana, Biological Factors::Biomarkers [CHEMICALS AND DRUGS], Catalysis, factores biológicos::biomarcadores [COMPUESTOS QUÍMICOS Y DROGAS], PYGM, Inorganic Chemistry, enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::alteraciones congénitas del metabolismo::trastornos congénitos del metabolismo de los carbohidratos::enfermedad por almacenamiento de glucógeno::enfermedad por almacenamiento de glucógeno tipo V [ENFERMEDADES], proteomics, myophosphorylase, Other subheadings::Other subheadings::/genetics [Other subheadings], Humans, Protein Isoforms, Physical and Theoretical Chemistry, skeletal muscle, Muscle, Skeletal, aminoácidos, péptidos y proteínas::proteínas::proteoma [COMPUESTOS QUÍMICOS Y DROGAS], Molecular Biology, Spectroscopy, GSDV, iTRAQ, metabolic myopathy, protein biomarkers, Metabolismo, Otros calificadores::Otros calificadores::/genética [Otros calificadores], Organic Chemistry, General Medicine, Computer Science Applications, Glicogen, Marcadors bioquímics, Glycogen Storage Disease Type V, Metabolisme, Errors congènits del, Amino Acids, Peptides, and Proteins::Proteins::Proteome [CHEMICALS AND DRUGS], Biomarkers, Glycogen

الوصف: McArdle disease; Proteomics; Skeletal muscle Enfermedad de McArdle; Proteómica; Músculo esquelético Malaltia de McArdle; Proteòmica; Múscul esquelètic Glycogen storage disease type V (GSDV, McArdle disease) is a rare genetic myopathy caused by deficiency of the muscle isoform of glycogen phosphorylase (PYGM). This results in a block in the use of muscle glycogen as an energetic substrate, with subsequent exercise intolerance. The pathobiology of GSDV is still not fully understood, especially with regard to some features such as persistent muscle damage (i.e., even without prior exercise). We aimed at identifying potential muscle protein biomarkers of GSDV by analyzing the muscle proteome and the molecular networks associated with muscle dysfunction in these patients. Muscle biopsies from eight patients and eight healthy controls showing none of the features of McArdle disease, such as frequent contractures and persistent muscle damage, were studied by quantitative protein expression using isobaric tags for relative and absolute quantitation (iTRAQ) followed by artificial neuronal networks (ANNs) and topology analysis. Protein candidate validation was performed by Western blot. Several proteins predominantly involved in the process of muscle contraction and/or calcium homeostasis, such as myosin, sarcoplasmic/endoplasmic reticulum calcium ATPase 1, tropomyosin alpha-1 chain, troponin isoforms, and alpha-actinin-3, showed significantly lower expression levels in the muscle of GSDV patients. These proteins could be potential biomarkers of the persistent muscle damage in the absence of prior exertion reported in GSDV patients. Further studies are needed to elucidate the molecular mechanisms by which PYGM controls the expression of these proteins. This research was funded by Instituto de Salud Carlos III (ISCIII) y FEDER (ERDF) funds “a way to construct Europe”; Ministerio de Ciencia e Innovación (Madrid, Spain), grant numbers (PI17/02052 and PI19/01313). G.N.-G is supported by a ISCIII contract CPII19/00021. P.S.-L. is supported by a ISCIII-CIBERER contract.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::244b932b2fd543f5a5ec25d294df5ba0Test
https://fundanet.igtp.cat/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2574Test

المؤلفون: Alejandro Cruz-Utrilla, Natalia Gallego-Zazo, Jair Antonio Tenorio-Castaño, Inmaculada Guillén, Alba Torrent-Vernetta, Amparo Moya-Bonora, Carlos Labrandero, María Elvira Garrido-Lestache Rodríguez-Monte, Alejandro Rodríguez-Ogando, María del Mar Rodríguez Vázquez Del Rey, Juana Espín, Beatriz Plata-Izquierdo, María Álvarez-Fuente, Antonio Moreno-Galdó, Pilar Escribano-Subias, María Jesús Del Cerro Marín

المساهمون: Institut Català de la Salut, [Cruz-Utrilla A] Pulmonary Hypertension Unit, ERN-Lung, Cardiology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. [Gallego-Zazo N, Tenorio-Castaño JA] Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, Madrid, Spain. CIBERER, Centro de Investigación en Red de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain. ITHACA, European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability, Brussels, Belgium. [Guillén I] Pediatric Cardiology Unit, Department of Pediatrics, Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Torrent-Vernetta A, Moreno-Galdó A] CIBERER, Centro de Investigación en Red de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain. Unitat de Pneumologia Pediàtrica i Fibrosi Quística, Servei de Pediatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Moya-Bonora A] Pediatric Cardiology, Department of Pediatrics, Hospital Universitari i Politècnic La Fe, Valencia, Spain, Vall d'Hebron Barcelona Hospital Campus

المصدر: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
instname
International Journal of Molecular Sciences; Volume 23; Issue 18; Pages: 10433
Scientia

مصطلحات موضوعية: enfermedades respiratorias::enfermedades pulmonares::hipertensión pulmonar [ENFERMEDADES], Catalysis, técnicas de investigación::métodos epidemiológicos::recopilación de datos::registros [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Inorganic Chemistry, Respiratory Tract Diseases::Lung Diseases::Hypertension, Pulmonary [DISEASES], Hipertensió pulmonar - Aspectes genètics, Other subheadings::Other subheadings::/genetics [Other subheadings], Humans, genetics, Familial Primary Pulmonary Hypertension, Registries, Physical and Theoretical Chemistry, Child, Molecular Biology, Spectroscopy, Pulmonary Arterial Hypertension, Otros calificadores::Otros calificadores::/genética [Otros calificadores], Organic Chemistry, heritable pulmonary arterial hypertension, General Medicine, Investigative Techniques::Epidemiologic Methods::Data Collection::Registries [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Computer Science Applications, Registres mèdics, pediatric pulmonary hypertension, pulmonary veno-occlusive disease, Pulmonary Veno-Occlusive Disease, Genetic Background

الوصف: Genetics; Heritable pulmonary arterial hypertension; Pediatric pulmonary hypertension Genética; Hipertensión arterial pulmonar hereditaria; Hipertensión pulmonar pediátrica Genètica; Hipertensió arterial pulmonar hereditària; Hipertensió pulmonar pediàtrica Background: Pulmonary arterial hypertension (PAH) is a severe and rare disease with an important genetic background. The influence of genetic testing in the clinical classification of pediatric PAH is not well known and genetics could influence management and prognosis. Objectives: The aim of this work was to identify the molecular fingerprint of PH children in the REgistro de pacientes con HIpertensión Pulmonar PEDiátrica (REHIPED), and to investigate if genetics could have an impact in clinical reclassification and prognosis. Methods: We included pediatric patients with a genetic analysis from REHIPED. From 2011 onward, successive genetic techniques have been carried out. Before genetic diagnosis, patients were classified according to their clinical and hemodynamic data in five groups. After genetic analysis, the patients were reclassified. The impact of genetics in survival free of lung transplantation was estimated by Kaplan–Meier curves. Results: Ninety-eight patients were included for the analysis. Before the genetic diagnoses, there were idiopathic PAH forms in 53.1%, PAH associated with congenital heart disease in 30.6%, pulmonary veno-occlusive disease—PVOD—in 6.1%, familial PAH in 5.1%, and associated forms with multisystemic disorders—MSD—in 5.1% of the patients. Pathogenic or likely pathogenic variants were found in 44 patients (44.9%). After a genetic analysis, 28.6% of the cohort was “reclassified”, with the groups of heritable PAH, heritable PVOD, TBX4, and MSD increasing up to 18.4%, 8.2%, 4.1%, and 12.2%, respectively. The MSD forms had the worst survival rates, followed by PVOD. Conclusions: Genetic testing changed the clinical classification of a significant proportion of patients. This reclassification showed relevant prognostic implications. This project was funded by project “Bases Genético-Moleculares de la Medicina de Precisión en la Hipertensión Arterial Pulmonar”. Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Gobierno de España. Co-funded by “Fondo Europeo de Desarrollo Regional, Programa Operativo Crecimiento Inteligente 2014–2020” (Award number: PI 18/01233). A.C.-U. holds a research-training contract “Rio Hortega” (CM20/00164) from the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III). REHIPED is supported by unrestricted grants of Janssen and Ferrer.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::613716f6ee6d3ab322b0a53bad57ada4Test
https://fundanet.iislafe.san.gva.es/publicaciones/ProdCientif/PublicacionFrw.aspx?id=17137Test