Opioide-hartzaileen deskribapena saguen gametoetan: morfinak obozitoen in vitro heltzean duen eragina

Gaur egun, ugarkotasun ezaren arazoa dela eta, geroz eta gehiago dira haurdunaldia lortzearren lagunduriko ugalketa tekniketara (ART, assisted reproductive technology) jo behar duten pertsonak; baina, oraindik, teknika horien arrakasta ez da oso handia eta batez beste, %50eko arrakasta duela esan ohi da(SEF erregistroa 2013). ART guztien artean, obozitoen in vitro heltzea (IVM, in vitro maturation) oso teknika berria da baina duen arrakasta txikiagatik, gutxien erabiliena da. Hala ere, in vitro ernalketaren (IVF, in vitro fertilization) hasieran eragingo litekeenez, ARTen arrakasta asko igoko litzateke

Extracellular Vesicles in NAFLD/ALD:From Pathobiology to Therapy

In recent years, knowledge on the biology and pathobiology of extracellular vesicles (EVs) has exploded. EVs are submicron membrane-bound structures secreted from different cell types containing a wide variety of bioactive molecules (e.g., proteins, lipids, and nucleic acids (coding and non-coding RNA) and mitochondrial DNA). EVs have important functions in cell-to-cell communication and are found in a wide variety of tissues and body fluids. Better delineation of EV structures and advances in the isolation and characterization of their cargo have allowed the diagnostic and therapeutic implications of these particles to be explored. In the field of liver diseases, EVs are emerging as key players in the pathogenesis of both nonalcoholic liver disease (NAFLD) and alcoholic liver disease (ALD), the most prevalent liver diseases worldwide, and their complications, including development of hepatocellular carcinoma. In these diseases, stressed/damaged hepatocytes release large quantities of EVs that contribute to the occurrence of inflammation, fibrogenesis, and angiogenesis, which are key pathobiological processes in liver disease progression. Moreover, the specific molecular signatures of released EVs in biofluids have allowed EVs to be considered as promising candidates to serve as disease biomarkers. Additionally, different experimental studies have shown that EVs may have potential for therapeutic use as a liver-specific delivery method of different agents, taking advantage of their hepatocellular uptake through interactions with specific receptors. In this review, we focused on the most recent findings concerning the role of EVs as new structures mediating autocrine and paracrine intercellular communication in both ALD and NAFLD, as well as their potential use as biomarkers of disease severity and progression. Emerging therapeutic applications of EVs in these liver diseases were also examined, along with the potential for successful transition from bench to clinic

Extracellular Vesicles in Hepatobiliary Malignancies

Primary hepatobiliary malignancies include a heterogeneous group of cancers with dismal prognosis, among which hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatoblastoma (HB) stand out. These tumors mainly arise from the malignant transformation of hepatocytes, cholangiocytes (bile duct epithelial cells) or hepatoblasts (embryonic liver progenitor cells), respectively. Early diagnosis, prognosis prediction and effective therapies are still a utopia for these diseases. Extracellular vesicles (EVs) are small membrane-enclosed spheres secreted by cells and present in biological fluids. They contain multiple types of biomolecules, such as proteins, RNA, DNA, metabolites and lipids, which make them a potential source of biomarkers as well as regulators of human pathobiology. In this review, the role of EVs in the pathogenesis of hepatobiliary cancers and their potential usefulness as disease biomarkers are highlighted. Moreover, the therapeutic value of EV regulation is discussed and future directions on basic and clinical research are indicated.Spanish Ministries of Economy and Competitiveness [JB (FIS PI12/00380, FIS PI15/01132 and Miguel Servet Programme CON14/00129); MP (FIS PI14/00399, FIS PI17/00022) and Ramon y Cajal Programme RYC-2015-17755] cofinanced by Fondo Europeo de Desarrollo Regional (FEDER); ISCIII [CIBERehd: JB, LB, and MP], Spain; Diputacion Foral Gipuzkoa (JB: DFG15/010, DFG16/004), BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD to JB); Department of Health of the Basque Country (JB: 2013111173 and 2017111010; MP: 2015111100), and AECC Scientific Foundation (JB). AL and PO were funded by the Basque Government

Extracellular Vesicles in Hepatobiliary Malignancies

Primary hepatobiliary malignancies include a heterogeneous group of cancers with dismal prognosis, among which hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatoblastoma (HB) stand out. These tumors mainly arise from the malignant transformation of hepatocytes, cholangiocytes (bile duct epithelial cells) or hepatoblasts (embryonic liver progenitor cells), respectively. Early diagnosis, prognosis prediction and effective therapies are still a utopia for these diseases. Extracellular vesicles (EVs) are small membrane-enclosed spheres secreted by cells and present in biological fluids. They contain multiple types of biomolecules, such as proteins, RNA, DNA, metabolites and lipids, which make them a potential source of biomarkers as well as regulators of human pathobiology. In this review, the role of EVs in the pathogenesis of hepatobiliary cancers and their potential usefulness as disease biomarkers are highlighted. Moreover, the therapeutic value of EV regulation is discussed and future directions on basic and clinical research are indicated

Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis

Cholangiocarcinoma (CCA) comprises a group of heterogeneous biliary cancers with dismal prognosis. The etiologies of most CCAs are unknown, but primary sclerosing cholangitis (PSC) is a risk factor. Non-invasive diagnosis of CCA is challenging and accurate biomarkers are lacking. We aimed to characterize the transcriptomic profile of serum and urine extracellular vesicles (EVs) from patients with CCA, PSC, ulcerative colitis (UC), and healthy individuals. Serum and urine EVs were isolated by serial ultracentrifugations and characterized by nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting. EVs transcriptome was determined by Illumina gene expression array [messenger RNAs (mRNA) and non-coding RNAs (ncRNAs)]. Differential RNA profiles were found in serum and urine EVs from patients with CCA compared to control groups (disease and healthy), showing high diagnostic capacity. The comparison of the mRNA profiles of serum or urine EVs from patients with CCA with the transcriptome of tumor tissues from two cohorts of patients, CCA cells in vitro, and CCA cellsderived EVs, identified 105 and 39 commonly-altered transcripts, respectively. Gene ontology analysis indicated that most commonly-altered mRNAs participate in carcinogenic steps. Overall, patients with CCA present specific RNA profiles in EVs mirroring the tumor, and constituting novel promising liquid biopsy biomarkers

Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids

[Background and Aims] Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with a dismal prognosis. We investigated if lipid metabolism is disrupted in CCA and its role in tumor proliferation.[Approach and Results] The in vitro and in vivo tumorigenic capacity of five human CCA cell lines was analyzed. Proteome, lipid content, and metabolic fluxes were evaluated in CCA cells and compared with normal human cholangiocytes (NHC). The Akt1/NOTCH1 intracellular cytoplasmic domain (Nicd1)-driven CCA mouse model was also evaluated. The proteome of CCA cells was enriched in pathways involved in lipid and lipoprotein metabolism. The EGI1 CCA cell line presented the highest tumorigenic capacity. Metabolic studies in high (EGI1) versus low (HUCCT1) proliferative CCA cells in vitro showed that both EGI1 and HUCCT1 incorporated more fatty acids (FA) than NHC, leading to increased triglyceride storage, also observed in Akt1/Nicd1-driven CCA mouse model. The highly proliferative EGI1 CCA cells showed greater uptake of very-low-density and HDLs than NHC and HUCCT1 CCA cells and increased cholesteryl ester content. The FA oxidation (FAO) and related proteome enrichment were specifically up-regulated in EGI1, and consequently, pharmacological blockade of FAO induced more pronounced inhibition of their tumorigenic capacity compared with HUCCT1. The expression of acyl-CoA dehydrogenase ACADM, the first enzyme involved in FAO, was increased in human CCA tissues and correlated with the proliferation marker PCNA.[Conclusions] Highly proliferative human CCA cells rely on lipid and lipoprotein uptake to fuel FA catabolism, suggesting that inhibition of FAO and/or lipid uptake could represent a therapeutic strategy for this CCA subclass.This work was supported by “Ayudas para apoyar grupos de investigación del sistema Universitario Vasco” (IT971‐16 to PA), MCIU/AEI/FEDER, UE (2018‐095134‐B‐100 to PA and by the University of Basque Country COLAB20/01 to PA; Spanish Carlos III Health Institute (ISCIII) (FIS PI15/01132, PI18/01075, PI21/00922, and Miguel Servet Program CON14/00129 and CPII19/00008 to JMB; FIS PI14/00399, PI17/00022 and PI20/00186 to MJP; Sara Borrell [CD19/00254 to PMR]) cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER); CIBERehd (ISCIII) to JMB, MJP, PMR, PA and LB); “Diputación Foral Gipuzkoa” (DFG15/010, DFG16/004 to JMB and 2020‐CIEN‐000067‐01 to PMR), Department of Health of the Basque Country (2019111024 to MJP, 2017111010 to JMB, and 2020111077 to JMB and PA), “Euskadi RIS3” (2016222001, 2017222014, 2018222029, 2019222054, 2020333010 to JMB), BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD to JMB) and Department of Industry of the Basque Country (Elkartek: KK‐2020/00008 to JMB); La Caixa Scientific Foundation (HR17‐00601 to JMB). “Fundación Científica de la Asociación Española Contra el Cáncer” (AECC Scientific Foundation, to JMB). AMMF‐The Cholangiocarcinoma Charity (EU/2019/AMMFt/001, to JMB and PMR). MRDG was funded by “Fundación Científica de la Asociación Española Contra el Cáncer” (AECC de Bizkaia), MJP was funded by the Spanish Ministry of Economy and Competitiveness (MINECO: “Ramón y Cajal” Program RYC‐2015‐17755), IL, AL and FG‐R by the Basque Government (PRE_2016_1_0152, PRE_2018_2_0195 and PRE 2020 2 02500, respectively), AN‐Z and BG‐S by the UPV/EHU, AB‐V by “Programa de especialización de Personal Investigador Doctor” at the UPV/EHU (2019‐2020) and MA by the MCIU/AEI/FEDER

Cholangiocarcinoma biomarkers in biofluid extracellular vesicles: a new liquid biopsy strategy

220 p.b+oDonosti

Berdinen arteko harremanak Lehen Hezkuntzan: Kasu baten azterketa

46 p. : il. -- Bibliogr.: p. 35-37[EUS] Ikerketa honek hiru helburu nagusi ditu: (1) berdinen arteko harremanetan oinarrituriko unitate didaktiko bat diseinatzea; (2) diseinaturiko unitate didaktikoa aurrera eramatea; (3) eta tailerraren ostean ikasleen arteko harremanak deskribatzea. Lana aurrera eramateko, 5. mailako 20 ikaslek parte hartu dute (9 mutil eta 11 neska). Parte hartzaileak, Lapurdi probintzian kokatzen den Urruña herriko ikastolakoak dira. Emaitzei dagokienez, (1) Harremanak sendotzen: elkar ezagutu, sentitu eta entzun unitate didaktikoa diseinatu da; (2) hortik, denboralizazioan eta haurren arteko elkarrekintza gatazkatsuak eman direla ikusi da; eta bukatzeko, (3) argi geratu da beraien arteko harreman dinamikak zeintzuk diren. Lan honetan ere emaitza horiek baloratu dira eta etorkizunerako hobekuntza proposamenak egin dira.[ES] Esta investigación ha tenido tres objetivos principales: (1) diseñar una unidad de enseñanza que promueve las relaciones entre iguales; (2) llevar a cabo la unidad didáctica diseñada; (3) y describir la relación entre los alumnos después del taller. Para llevar a cabo el trabajo, participaron 20 estudiantes de 5º de primaria (9 niños y 11 niñas). Las personas participantes son alumnos y alumnas de Educación Primaria de Urruña, un pueblo ubicado en la provincia de Lapurdi. Con respecto a los resultados, (1) se ha diseñado una unidad didáctica llamada Harremanak sendotzen: elkar ezagutu, sentitu eta entzun [Fortaleciendo relaciones: conocer, sentir y escuchar]; (2) se ha visto que han habido interacciones conflictivas entre el alumnado y que se han encontrado dificultades para gestionar el tiempo durante los talleres; y para concluir, (3) ha quedado claro cuáles son las dinámicas de relación que se dan en el grupo. En este trabajo también se evalúan los resultados y se llevan a cabo propuestas de mejora en el futuro.[FRE] Cette recherche a trois objectifs principaux: (1) concevoir une unité d’enseignement basée sur l’enseignement mutuel; (2) réaliser l'unité didactique conçue; (3) et décrire la relation entre les élèves après l’atelier. Pour effectuer ce travail, 20 élèves du CM2 ont participé (9 garçons et 11 filles). Les participants viennent de l'Ikastola d'Urrugne, située dans la province de Lapurdi. En ce qui concerne les résultats, (1) l'unité d'enseignement Harremanak sendotzen: elkar ezagutu, sentitu eta entzun [Améliorer les relations: se connaître, se sentir, s'écouter] a été conçue; (2) À partir de là, on a constaté des interactions conflictuelles entre les élèves et des difficultés ont été rencontrées dans la gestion du temps pendant les ateliers; et pour conclure (3), il est évident que leur dynamique relationnelle est restée la même. Dans ce travail, les résultats ont également été évalués et des propositions d’amélioration ont été réalisées à l’avenir.[EN] The main objectives of this study are (1) to design a teaching unit that promotes relationships among peers; (2) to carry out the designed teaching unit; (3) and to describe the relationship among pupils after the workshop. To begin with, 20 pupils in a 5th grade class participated (9 boys and 11 girls). Participants are from a Primary school in Urruña, located in the province of Lapurdi. In regards to the results, (1) the teaching unit Harremanak sendotzen: elkar ezagutu, sentitu eta entzun [Strengthening relationships: to know, feel and listen to each other] was designed; (2) conflicting interactions were found among children, as well as difficulties in time management during the workshop; finally, (3) it was obvious the relationship dynamics among the group stayed the same. In this work, results are discussed and evaluated with suggestions for future improvement

Opioide-hartzaileen deskribapena saguen gametoetan: morfinak obozitoen in vitro heltzean duen eragina

Gaur egun, ugarkotasun ezaren arazoa dela eta, geroz eta gehiago dira haurdunaldia lortzearren lagunduriko ugalketa tekniketara (ART, assisted reproductive technology) jo behar duten pertsonak; baina, oraindik, teknika horien arrakasta ez da oso handia eta batez beste, %50eko arrakasta duela esan ohi da(SEF erregistroa 2013). ART guztien artean, obozitoen in vitro heltzea (IVM, in vitro maturation) oso teknika berria da baina duen arrakasta txikiagatik, gutxien erabiliena da. Hala ere, in vitro ernalketaren (IVF, in vitro fertilization) hasieran eragingo litekeenez, ARTen arrakasta asko igoko litzateke