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Originally considered to act as a transcriptional co‑factor, Pirin has recently been reported to play a role in tumorigenesis and the malignant progression of many tumors. Here, we have analyzed the diagnostic and prognostic value of Pirin expression in the early stages of melanoma, and its role in the biology of melanocytic cells. Pirin expression was analyzed in a total of 314 melanoma biopsies, correlating this feature with the patient’s clinical course. Moreover, PIR downregulated primary melanocytes were analyzed by RNA sequencing, and the data obtained were validated in human melanoma cell lines overexpressing PIR by functional assays. The immunohistochemistry multivariate analysis revealed that early melanomas with stronger Pirin expression were more than twice as likely to develop metastases during the follow‑up. Transcriptome analysis of PIR downregulated melanocytes showed a dampening of genes involved in the G1/S transition, cell proliferation, and cell migration. In addition, an in silico approach predicted that JARID1B as a potential transcriptional regulator that lies between PIR and its downstream modulated genes, which was corroborated by co‑transfection experiments and functional analysis. Together, the data obtained indicated that Pirin could be a useful marker for the metastatic progression of melanoma and that it participates in the proliferation of melanoma cells by regulating the slow‑cycling JARID1B gene.

[EU] Sarrera: Prozedura kardiako kirurgikoen areagotzeak eta praktika klinikoaren efizientziaren premiak arreta kardiakorako estrategia azkar eta seguruen ezarpena suposatu du. Hori dela eta, gaur egun “fast-track” protokoloak sortu eta erabiltzen dira, pazientearen errekuperazio goiztiarra helburu izanik. Ikusi da protokolo hauek pazienteek bentilazio mekanikoa jasaten igarotzen duten denbora murrizten dutela. Honekin batera, ikerketa berriek extubazio goiztiarrak ebakuntza osteko konplikazioen kopurua nabarmen murrizten duela ondorioztatu dute. Hala ere, protokolo hauek ezberdinak dira osasun zentro bakoitzean eta ondorioz, extubazio goiztiarra aurrera eramateko moduak ezberdinak dira. Hori horrela, prozedura honen estandarizazio eta protokolizazioa ezinbestekoa da. Helburua: Ebakuntza kardiakoak jasan eta gero, extubazio goiztiarraren ondorioz adin nagusiko pazienteek pairatutako konplikazioak eta onurak ezagutzea, eta horrekin batera, extubazio goiztiarra burutzeko denbora-tarte optimoa identifikatzea berrikuspen bibliografiko honen helburuak dira. Metodologia: Berrikuspen bibliografikoa burutzeko, bilaketa bibliografikoa Pubmed eta Web of Science datu baseetan egin zen. Artikuluen aukeraketarako hainbat barneratze- eta kanporatze-irizpide aplikatu ziren. Emaitzak: Bilaketa bibliografikoaren emaitza bezala 12 artikulu berrikusi ziren. Extubazio goiztiarra jasan zuten pazienteek heriotza-tasa, ospitaleratze denbora eta konplikazio-tasa baxuagoa izan zuten. Gainera, onura hauek extubazio-momentua ebakuntza osteko lehenengo 6 ordutan, 8 ordutan eta 12 ordutan burutzean identifikatu ziren. Ondorioak: Pazienteen extubazioa goiztiarra izateak ebakuntza osteko konplikazio orokorrak murriztu zituen. Zehazki, hobekuntza nabarienak, extubazioa ebakuntza osteko lehenengo 6 ordutan jasandako pazienteetan ikusi ziren. Hala ere, pazienteen egoera perioperatorioak ebakuntza osteko jasoeretan eragin zuzena dutenez, hauek kontutan izan beharreko irizpide bezala azpimarratzen dir

[EU] Suizidio tasek gora egiten dute adinak aurrera egin ahala, izan ere, 65 urteko edo gehiagoko pertsonen hilkortasunaren 3. faktore nagusiena bihurtu da. Pubmed datu baseaz baliatuz, hainbat arrisku faktore aurkitu ziren adineko pertsonek buruaz beste egiteko: aurrekari psikiatrikoak, autonomia eta independentziaren gutxitzea, insomnioa, kontrol kognitibo pobrea, sexua, adina, hezkuntza maila baxua, egoera zibila, bakarrik bizitzea eta horrekin batera, bakardadea. Prebentzio foku moduan konexio sozialak sustatzea, psikoterapia, ariketa fisikoa bestelako lanekin konbinatuta, Lehen Mailako Arretan laguntza bilatzea eta profesionalak hezituak izatea azpimarratu ziren.

255 p., Zelulen patroi epigenetikoak haien fisiologia zehazten du, eta organismo baten garapenean zehar zelula bakoitzak duen patroi espezifikoak haren diferentziazioa bideratzen du, organismo osoaren garapen egokia bat koordinatuz. Hala ere, inguruneak eta bizi estiloak eragin kaltegarriak eragin ditzake norbanakoengan, zelulen fisiologia zehazten duen patroi epigenetikoan eraginez. Biomedikuntzak egun duen erronka handienetariko bat inguruneak edota kanpo faktoreek eragindako aldaketa epigenetikoek sortu ditzaketen osasun arazoen edo gaixotasunen atzean dauden mekanismo molekularrak ulertzea da. Bestalde, aldaketa fisiologiko horiek eragiten dituzten marka epigenetikoak denboran zehar mantendu daitezkeela ikusi da. Beraz, kanpo faktore horiekin kontaktu zuzena izan duten bizidunek eragin nabarmenak pairatzeaz gain, denbora zehar mantentzen dituzte memoria zelularra baimentzen duten mekanismoen bidez, eta horrez gain, eragin horien belaunaldiz belaunaldiko herentzia bat ere eman daitekeela ziurtatzen dituzten zantzuak geroz eta ugariagoak dira.Aurrekari horiek kontuan hartuta, doktore-tesi honen helburu nagusia morfinak eragin ditzakeen aldaketa epigenetiko nagusiak identifikatu, eta horiek zelulen edota organismo bizidun konplexuen fisiologian eragin ditzakeen aldaketak aztertzea izan da. Aldaketa fisiologiko horiek eragiten dituzten mekanismo epigenetiko ezberdinak badaude ere, kasu honetan DNAren metilazioan zentratu gara, eta Bigarren Belaunaldiko Sekuentziazio teknikak erabili ditugu metiloma aztertzeko helburuarekin. Ikerketa lan honek, besteak beste, memoria epigenetikoaren atzean dauden mekanismoak aztertzeko aukera eskaini digu. Morfinak asaldurak sortzen ditu birprogramazio epigenetikoan funtsezko prozesua den X kromosomaren inaktibazioan, eta gainera, asaldura horiek mantentzeko eta heredatzeko potentzialtasuna dutenez, morfinak eragindako zelularteko memoriaren azpian dauden mekanismo epigenetikoak ikertu ditugu. Horrez gain, birprogramazioaren helburu nagusia

[EU] Sarrera: COVID-19 gaixotasuna osasun publikoko emergentzia bilakatu da bere ezaugarri klinikoak direla eta. Gertakari honek, inpaktu sozial eta psikologikoa izan du mundu osoko osasun profesionalengan, zeintzuk lehenengo lerroan lan egin duten infektatutako pazienteekin. Honek guztiak, osasun profesionalak infektatzeko arrisku altua izatea eragin du eta ondorioz, langile horietan afekzio mentalak sufritzeko aukerak handitu egin dira. Horregatik, aproposak diren estrategiak erabiltzea funtsezkoa da, pandemiak osasun mentalean duen inpaktu negatiboa saihesteko. Helburua: Lan honetan bi helburu planteatu dira: COVID-19 pandemiak osasun profesionalen (bereziki erizainen) osasun mentalean izan duen inpaktua identifikatzea eta arazo mental horiei aurre egiteko dauden interbentzio edo estrategia posibleak deskribatzea. Metodologia: Berrikuspen bibliografikoa gauzatzeko bilaketa bibliografikoa 2021eko urria eta abendua bitartean eraman zen aurrera PubMed, Scopus eta Biblioteca Virtual de Salud datu baseak erabilita. Barneratze- eta kanporatze-irizpideak ezarri ziren, iragaz filtroekin batera, helburuetara egokitutako artikuluak lortzeko. Emaitzak: Orotara 10 artikulu aukeratu ziren, zeintzuetan erizainek lagin guztien artean %76.7 inguru osatzen zuten. Arazo mentalen prebalentzia totala %65.1 izan zen angustiarentzat, %43.2 depresioarentzat, %40.3 antsietatearentzat, %34.3 estresarentzat eta %29.6 insomnioarentzat. Emaitzek gainera erakutsi zuten emakumeak, erizainak eta lehenengo lerroko profesionalak zirela gaixotasun mentalak garatzeko arrisku gehien zutenak. Bestalde, aztertu ziren interbentzio eta aurre egite estrategiak, baliagarriak izan ziren asaldura mentalen intzidentzia murrizteko (p<0.05), eta konkretuki emaitza interesgarrienak yoga eta musika-terapia saioekin lortu ziren. Ondorioak: COVID-19 pandemiak izan duen inpaktuaren ondorioz osasun langileek, bereziki erizain, emakume eta lehenengo lerroko profesionalek gaixotasun psikologiko desberdinen prebalentz

Sperm fertility ability may be modulated by different molecular systems, such as the renin-angiotensin system (RAS). Although renin is one of its most relevant peptides, the presence and role of the (pro)renin receptor (PRR) is completely unknown. We have proved for the first time the existence of PRR and its transcript in human sperm by western blot and RT-PCR. Immunofluorescence studies showed that this receptor is mainly located in the apical region over the acrosome and in the postacrosomal region of the sperm head and along the sperm tail. In addition, this prospective cohort study also proves that semen samples with higher percentages of PRR-positive spermatozoa are associated with poor sperm motility, worse blastocyst development and no-viable blastocysts. Our results provide insight into how PRR play a negative role in sperm physiology that it may condition human embryo quality and development. An in-depth understanding of the role of PRR in sperm fertility can help elucidate its role in male infertility, as well as establish biomarkers for the diagnosis or selection of sperm to use during assisted reproductive techniques.

Human sperm protein associated with the nucleus on the X chromosome (SPANX) genes encode a protein family (SPANX-A, -B, -C and -D), whose expression is limited to the testis and spermatozoa in normal tissues and various tumour cells. SPANX-A/D proteins have been detected in metastatic melanoma cells, but their contribution to cancer development and the underlying molecular mechanisms of skin tumourigenesis remain unknown. Combining functional and proteomic approaches, the present work describes the presence of SPANX-A/D in primary and metastatic human melanoma cells and how it promotes pro-tumoural processes such as cell proliferation, motility and migration. We provide insights into the molecular features of skin tumourigenesis, describing for the first time a multifunctional role of the SPANX-A/D protein family in nuclear function, energy metabolism and cell survival, considered key hallmarks of cancer. A better comprehension of the SPANX-A/D protein subfamily and its molecular mechanisms will help to describe new aspects of tumour cell biology and develop new therapeutic targets and tumour-directed pharmacological drugs for skin tumours

Background: Environmentally induced epigenetic changes can lead to health problems or disease, but the mechanisms involved remain unclear. Morphine can pass through the placental barrier leading to abnormal embryo development. However, the mechanism by which morphine causes these effects and how they sometimes persist into adulthood is not well known. To unravel the morphine-induced chromatin alterations involved in aberrant embryo development, we explored the role of the H3K27me3/PRC2 repressive complex in gene expression and its transmission across cellular generations in response to morphine. Results: Using mouse embryonic stem cells as a model system, we found that chronic morphine treatment induces a global downregulation of the histone modification H3K27me3. Conversely, ChIP-Seq showed a remarkable increase in H3K27me3 levels at specific genomic sites, particularly promoters, disrupting selective target genes related to embryo development, cell cycle and metabolism. Through a self-regulatory mechanism, morphine downregulated the transcription of PRC2 components responsible for H3K27me3 by enriching high H3K27me3 levels at the promoter region. Downregulation of PRC2 components persisted for at least 48 h (4 cell cycles) following morphine removal, though promoter H3K27me3 levels returned to control levels. Conclusions: Morphine induces targeting of the PRC2 complex to selected promoters, including those of PRC2 components, leading to characteristic changes in gene expression and a global reduction in H3K27me3. Following morphine removal, enhanced promoter H3K27me3 levels revert to normal sooner than global H3K27me3 or PRC2 component transcript levels. We suggest that H3K27me3 is involved in initiating morphine-induced changes in gene expression, but not in their maintenance.

Human sperm protein associated with the nucleus on the X chromosome (SPANX) genes encode a protein family (SPANX-A, -B, -C and -D), whose expression is limited to the testis and spermatozoa in normal tissues and to a wide variety of tumour cells. Present only in hominids, SPANX-A/D is exclusively expressed in post-meiotic spermatids and mature spermatozoa. However, the biological role of the protein family in human spermatozoa is largely unknown. Combining proteomics and molecular approaches, the present work describes the presence of all isoforms of SPANX-A/D in human spermatozoa and novel phosphorylation sites of this protein family. In addition, we identify 307 potential SPANX-A/D interactors related to nuclear envelop, chromatin organisation, metabolism and cilia movement. Specifically, SPANX-A/D interacts with fumarate hydratase and colocalises with both fumarate hydratase and Tektin 1 proteins, involved in meeting energy demands for sperm motility, and with nuclear pore complex nucleoporins. We provide insights into the molecular features of sperm physiology describing for the first time a multifunctional role of SPANX-A/D protein family in nuclear envelope, sperm movement and metabolism, considered key functions for human spermatozoa. SPANX-A/D family members, therefore, might be promising targets for sperm fertility management.

Raf Kinase Inhibitor Protein (RKIP) has been extensively reported as an inhibitor of keysignaling pathways involved in the aggressive tumor phenotype and shows decreased expressionin several types of cancers. However, little is known about RKIP in melanoma or regarding its functionin normal cells. We examined the role of RKIP in both primary melanocytes and malignant melanomacells and evaluated its diagnostic and prognostic value. IHC analysis revealed a significantly higherexpression of RKIP in nevi compared with early-stage (stage I–II, AJCC 8th) melanoma biopsies.Proliferation, wound healing, and collagen-coated transwell assays uncovered the implication ofRKIP on the motility but not on the proliferative capacity of melanoma cells as RKIP protein levelswere inversely correlated with the migration capacity of both primary and metastatic melanoma cellsbut did not alter other parameters. As shown by RNA sequencing, endogenous RKIP knockdownin primary melanocytes triggered the deregulation of cellular differentiation-related processes,including genes (i.e., ZEB1, THY-1) closely related to the EMT. Interestingly, NANOG was identifiedas a putative transcriptional regulator of many of the deregulated genes, and RKIP was able todecrease the activation of the NANOG promoter. As a whole, our data support the utility of RKIPas a diagnostic marker for early-stage melanomas. In addition, these findings indicate its participationin the maintenance of a differentiated state of melanocytic cells by modulating genes intimately linkedto the cellular motility and explain the progressive decrease of RKIP often described in tumors.

296 p., Epigenetikak, kanpo faktoreek edo inguruneak norbanakoan izan dezaketen eragina aztertzen du. Azken urteetan, zenbait ikerketek erakutsi dutenez, inguruneak eragin zuzena izan dezake norbanako helduaren ezaugarri fisiologikoetan. Hala ere, kanpo faktoreek umekian eta garapen goiztiarrean izan dezaketen eraginari buruz, ezer gutxi deskribatu da. Geneen adierazpenarekin duten elkarteratzea dela eta, histonen aldaketak informazio epigenetikoaren eragile nagusien artean aurkitzen ditugu, eta memoria epigenetikoan paper garrantzitsua izan dezaketela iradoki da. Hala ere, naiz eta histonen aldaketa espezifikoek transkripzio egoerekin erlazioa duten, epe luzean zehar mantendu daitekeen herentziaren mekanismoa ez da oraindik ere argitu.Hau guztia aztertzeko eta kanpo estimulu eredu bezala morfina erabiliz, bigarren belaunaldiko sekuentziazio teknikak erabili dira kromatina eta transkriptomika analisiak burutzeko. Bertatik H3K27me3 marka epigenetiko errepresiogilearen desdoitze orokor bat hauteman dugu, epe luzeko geneen adierazpen aldaketak sortuz, saguen ama zelula enbrionikoetan. Zehazki morfinaren tratamendu kronikoak eragindako efektua CpG irletan ugariak diren sustatzaileetan, inpronta genomikodun geneen metilazioaren erregulazio eremuetan, lncRNA-etan eta elementu errepikakorretan aurkitu ditugu. Aipatzekoa da, H3K27me3-ren eta bere erregulazio konplexuaren (Polycomb repressive complex 2 edo PRC2), auto erregulazio mekanismo bat identifikatu dugula morfinaren presentzian. Horrez gain, morfinak eragindako H3K27me3-ko aldaketek bi gene espezifikotan sortzen dituen adierazpen aldaketak sakonago aztertu ditugu, Bmp4 eta Smchd1 hurrenez hurren, hauek parte hartzen duten prozesuak guztiz eraldatzen direla aurkituz. Bmp4 enbrioi goiztiarren garapenean eta jatorrizko hozi zelulen sorreran parte hartzen duen hazkuntza faktorea da eta morfinaren ondorioz, bi prozesu horien azkartzea eragiten dela hauteman dugu. Bestalde, Smchd1, X kromosomaren inaktibazioaren mantentze lanetan

Angiotensin-converting enzyme functions in the male reproductive system, but the extent of its function in reproduction is not fully understood. The primary objective of this work was to investigate the relationship between the testicular isoform of angiotensin-converting enzyme present in human spermatozoa and semen parameters, human embryo quality, and assisted reproduction success. A total of 81 semen samples and 635 embryos from couples undergoing oocyte donation cycles at the IVI Bilbao Clinic were analyzed. Semen parameters, embryos quality, and blastocyst development were examined according to the World Health Organization standards and the Spanish Association of Reproduction Biology Studies criteria. The percentage of testicular angiotensin-converting enzyme-positive spermatozoa and the number of molecules per spermatozoon were analyzed by flow cytometry. Both parameters were inversely correlated with human sperm motility. Higher percentages of testicular angiotensin-converting enzyme-positive spermatozoa together with fewer enzyme molecules per spermatozoon were positively correlated with better embryo quality and development. Our results suggest that embryos with a higher implantation potential come from semen samples with higher percentages of testicular angiotensin-converting enzyme-positive cells and fewer enzyme molecules per spermatozoon. Based on these findings, we propose that testicular angiotensin-converting enzyme could be used to aid embryologists in selecting better semen samples for obtaining high-quality blastocysts during in vitro fertilization procedures.

The presence of endogenous opioid peptides in different testicular cell types has been extensively characterized and provides evidence for the participation of the opioid system in the regulation of testicular function. However, the exact role of the opioid system during the spermatogenesis has remained controversial since the presence of the mu-, delta-and kappa-opioid receptors in spermatogenic cells was yet to be demonstrated. Through a combination of quantitative real-time PCR, immunofluorescence, immunohistochemistry and flow cytometry approaches, we report for the first time the presence of active mu-, deltaand kappa-opioid receptors in mouse male germ cells. They show an exposition time-dependent response to opioid agonist, hence suggesting their active involvement in spermatogenesis. Our results contribute to understanding the role of the opioid receptors in the spermatogenesis and could help to develop new strategies to employ the opioid system as a biochemical tool for the diagnosis and treatment of male infertility.