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Introduction: As in other countries in the world, the social confinement derived from COVID-19 has led to a significant alteration in the work of higher education institutions in Mexico, this led to the suspension of face-to-face school activities and the development and implementation of new teaching-learning strategies, such as the use of digital teaching resources. Objective: The objective of this work is to present a strategy that favors the teaching-learning process during and after confinement due to COVID-19. Materials and Methods: A search was carried out in the school databases Dialnet, Redalyc, Scielo, Scopus and Google in a time range from 2017 to 2022. Through the following keywords: "digital teaching resources", "podcast of chemical engineering", "Profcast" and "virtual engineering education". Conclusions: Chemical Engineering teachers should consider developing and implementing the Profcast as a viable teaching-learning strategy for the training of human resources.

La arteritis de Takayasu es una vasculitis granulomatosa idiopática de la aorta y sus principales ramas y constituye una de las vasculitis más frecuentes en niños. La inflamación y la proliferación de la íntima conducen al engrosamiento de la pared, lesiones estenóticas u oclusivas y trombosis, mientras que la destrucción de las capas elástica y muscular origina aneurismas y disecciones. Las características clínicas más frecuentes son dolor a la palpación de la arteria carótida, claudicación, alteraciones oculares, anomalías del sistema nervioso central y debilitamiento del pulso. El diagnóstico generalmente se confirma mediante la observación de anomalías en la pared de los vasos grandes: estenosis, aneurismas, oclusión y evidencia de aumento de la circulación colateral en angiografía, MRA o CTA. El propósito de esta revisión es abordar el conocimiento actual sobre patogenia, investigaciones, clasificación

Background Angiomyolipoma is a benign mesenchymal neoplasm of a wide histological heterogeneity belonging to the PEComa “family.” The liver, after the kidney, is their second most frequent location. However, inflammatory hepatic AMLs constitute a rare entity, with only fourteen documented cases until 2020. These neoplasms can overlap morphological features of IgG4-related diseases, being of great diagnostic relevance to demonstrating myomelanocytic-lineage differentiation of the neoplastic cells. Case presentation: we present a new case of an inflammatory hepatic AML resembling an IgG4-related disease in a 35-year-old woman with a subcapsular 5 cm mass confined to segment VII of the right hepatic lobe. Although having reduced its size along the tumor’s natural evolution, complete tumor resection was decided due to its hypermetabolic behavior (max. SUV = 12,6) assessed by PET-CT scan. Finally, the patient underwent a right hepatectomy due to spontaneous rupture and bleeding of the lesion during the intervention. All the diagnostic and therapeutic procedures occurred in the last months of the COVID-19 pandemic. Conclusions: This review aims to describe inflammatory hepatic AML histological and immunohistochemical features. We further sought to establish a clinicopathological contextualization of this tumoral subtype.

La formación universitaria no debe limitarse a una mera instrucción de habilidades profesionales, sino que debe fomentar el desarrollo integral del alumnado. Este planteamiento se hace especialmente necesario en la formación de maestros y maestras, subrayando la necesidad de implementar estrategias metodológicas que lo posibiliten. A través de una aproximación metodológica mixta, se han analizado los efectos producidos por el Aprendizaje-Servicio sobre las habilidades y actitudes cívicas del alumnado (n=117). Los resultados cuantitativos muestran una mejora estadísticamente significativa en el cuestionario en global. Además, la parte cualitativa permite profundizar sobre los aprendizajes relacionados con las dimensiones que presentan mejoras estadísticamente significativas. Los resultados obtenidos sugieren que el Aprendizaje-Servicio se erige como una estrategia idónea para fomentar el desarrollo de las habilidades y actitudes cívicas del futuro profesorado.

La presente investigación basada en el objetivo de dar respuesta a los nuevos requerimientos tecnológicos y sociales, donde todas las empresas se enfrentan a la llamada transformación empresarial. La gestión del cambio es uno de los aspectos sustantivos o métodos utilizados por las organizaciones para frenar la aumento persistente del dinamismo como resultado de cambios en las tecnologías u otros factores. La mayoría del tiempo, los gerentes y/o los líderes están buscando cambios. La gestión como la parte más difícil es una actividad que requiere consideración especial y gran habilidad. Un punto de partida para responder a las demandas cambiantes es mejorar la capacidad de la empresa para operar de manera flexible y, por lo tanto, aumentar su agilidad. Es por ello que, con este documento, se contribuye a la discusión en curso sobre el cambio de las estructuras organizacionales corporativas. Se ha utilizado un diseño de estudio de tres etapas para proporcionar información sobre la cuestión de si la agilidad es un requisito previo o una consecuencia de la transformación empresarial. Además de un análisis de la literatura, se presentan los resultados de entrevistas de grupos focales con gerentes de empresas seleccionadas al sector de la industria del software.

La educación inclusiva es un reto compartido y una necesidad si se pretende avanzar hacia una sociedad más justa. Si bien se ha mejorado sobre la atención a la diversidad funcional en el aula, existe mucho margen de mejora; y la realidad educativa y la literatura nos interpelan a seguir investigando en este sentido. La formación inicial docente es una etapa importante en la que incidir a través de experiencias educativas que posibiliten el desarrollo de aprendizajes, valores y habilidades que faciliten la atención a la diversidad en el futuro profesorado. Esta investigación se centra en analizar un programa de Aprendizaje-Servicio (ApS) atendiendo a cómo afecta en la construcción de la identidad personal y docente del alumnado universitario participante. El grupo de participantes (n=123) está constituido por el grupo-clase de la asignatura obligatoria “Fundamentos de la Expresión Corporal; Juegos Motrices en Educación Infantil” del Grado en Maestro o Maestra de Educación Infantil de la Universitat Jaume I. Esta investigación se ha abordado desde un enfoque cualitativo y el instrumento de recogida de información lo han conformado diarios de seguimiento completados por el alumnado participante. Los resultados refuerzan el estado de la cuestión denotando un cambio en la identidad personal y docente del estudiantado y muestran al ApS como una herramienta adecuada para promover aprendizajes, valores y sentimientos que resultan imprescindibles para avanzar hacia la inclusión educativa. Abstract. Inclusive education is not only a challenge but also a necessity in order to achieve a just society. Although the attention to functional diversity in the classroom has been improved, there are still many aspects to improve; and the educational reality and literature are pushing researchers to continue investigating in this sense. Initial teacher training is a critical stage in which educational experiences may influence through the development of learning, values and skills that facilitate attention to diversity in future teachers. This research aims at analyzing the implications that participating in a Service-Learning (SL) programme may come with regarding the building up of university students’ identity and personality. The participating sample (n = 123) is made up of the group-class of the compulsory subject “Fundamentals of Body Expression; Motor Games in Early Childhood Education”, within the Degree in Early Childhood Education of the Universitat Jaume I. This research has used a qualitative approach. The data collection instrument has been students’ reflective diaries. The results reinforce the state of the art, displaying a rebuilding of the students’ personal and teaching identity. In addition, they show that SL may be an adequate tool to promote learning, values and feelings that are essential to advance towards inclusive education.

Purpose: This research analyzes the effects of a Service-learning program on the development of civic attitudes and skills on preservice teachers (n = 98). They provided a direct service of motor sessions aimed at children with functional diversity. Method: The topic was approached using a mixed methodological approach. A pre- and posttest quantitative analysis was performed on the results obtained after applying the Civic Attitudes and Skills Questionnaire, and a qualitative analysis was performed on the content of follow-up journals. Results: The quantitative results indicated a significant positive posttest, and qualitative analysis explained the civic skills and attitudes that the preservice teachers acquired. Discussion/Conclusion: Service-learning is a useful method for promoting the civic attitudes and skills of preservice teachers. The acquired learning specifically affected the different dimensions involved in achieving meaningful learning, an improvement in the skills and attitudes that are essential characteristics of an inclusive teacher.

Supplementary Figure 1 from A Genetic Screen Identifies Topoisomerase 1 as a Regulator of Senescence

Supplementary Figure Legends 1-3 from A Genetic Screen Identifies Topoisomerase 1 as a Regulator of Senescence

Supplementary Figure 3 from A Genetic Screen Identifies Topoisomerase 1 as a Regulator of Senescence

Supplementary Figure 1 from Immortalization of Primary Human Prostate Epithelial Cells by c-Myc

A significant percentage of prostate tumors have amplifications of the c-Myc gene, but the precise role of c-Myc in prostate cancer is not fully understood. Immortalization of human epithelial cells involves both inactivation of the Rb/p16INK4a pathway and telomere maintenance, and it has been recapitulated in culture by expression of the catalytic subunit of telomerase, hTERT, in combination with viral oncoproteins. Here, we show the immortalization of human prostate epithelial cells (HPrEC) by a single genetic event, the expression of the c-Myc oncogene. Myc stabilizes telomere length in HPrEC through up-regulation of hTERT expression and overrides the accumulation of cell cycle inhibitory proteins, such as p16INK4a. Overall, HPrECs expressing c-Myc retain many characteristics of normal cells, such as the induction of a senescence-like growth arrest in response to oncogenic Ras, an intact p53 response, and an absence of gross karyotypic abnormalities. However, HPrECs expressing c-Myc lack a Rb/p16INK4a checkpoint and can be transformed without the need for additional genetic lesions in that pathway. These results give a partial explanation for the physiologic role of c-Myc overexpression in prostate cancer.

Supplementary Figure 2 from A Genetic Screen Identifies Topoisomerase 1 as a Regulator of Senescence

Supplementary Figure 2 from Immortalization of Primary Human Prostate Epithelial Cells by c-Myc

Epigenetic changes are a driver of senescence and occur during aging. A study in Nature Aging shows how chromatin-mediated loss of transcription fidelity, previously shown in yeast and worms, also occurs in mammalian cells and could constitute a new hallmark of senescence and aging.

Cellular senescence is a stable type of cell cycle arrest triggered by different stresses. As such, senescence drives age-related diseases and curbs cellular replicative potential. Here, we show that 3-deazaadenosine (3DA), an S-adenosyl homocysteinase (AHCY) inhibitor, alleviates replicative and oncogene-induced senescence. 3DA-treated senescent cells showed reduced global Histone H3 Lysine 36 trimethylation (H3K36me3), an epigenetic modification that marks the bodies of actively transcribed genes. By integrating transcriptome and epigenome data, we demonstrate that 3DA treatment affects key factors of the senescence transcriptional program. Remarkably, 3DA treatment alleviated senescence and increased the proliferative and regenerative potential of muscle stem cells from very old mice in vitro and in vivo. Moreover, ex vivo 3DA treatment was sufficient to enhance the engraftment of human umbilical cord blood (UCB) cells in immunocompromised mice. Together, our results identify 3DA as a promising drug enhancing the efficiency of cellular therapies by restraining senescence.

The objective of this study was to evaluate the inclusion of coffee pulp silage (CPS) on the performance and profitability of crossbred cows in the middle tropics. The research took place at the Villa Marina Experimental Farm of the University of Pamplona, Pamplonita, Colombia. Four lactating multiparous bovines with a body weight of 380 ± 10 kg, 6 ± 0.03 years of age and a body condition of 3.8 on a scale of 1 to 5. The animals were distributed in a balanced 4 × 4 Latin square for residual effect. The experiment consisted of four subperiods of 21 days each, being the first 14 days of adaptation to the experimental diet and 7 days for taking samples. The base diet consisted of Pennisetum sp. forage, concentrated in a proportion of 0.2% of body weight, water, and mineralized salt at will. The inclusion of the CPS was included in levels of 4, 8, and 12% of the dry matter (DM) intake. DM intake parameters, nutrient digestibility, milk production and composition, blood parameters, and economic analysis were evaluated. Treatments were compared using orthogonal contrasts; contrasts were constructed in order to evaluate the effects of inclusion of CPS, and the linear and quadratic effects of level inclusion in the DM of the diet. For the variables which did not present inclusion of CPS effect but a linear or quadratic effect was significant, a Dunnett’s test was performed to identify whether a supplemented treatment differed from the control. Significance was considered at P P ≤ 0.10. The inclusion of CPS in the diet increases (P −1 of DM, organic matter (OM), CP, ethereal extract (EE), non-fiber carbohydrates (NFC), digested OM (DM), neutral detergent fiber corrected for ash and protein (NDFap), DNDF and dietary NTD concentration, the total digestibility of DM and OM, and dietary DOM content. The production and chemical composition of milk was not affected (P > 0.10) by the inclusion of EPC in the diet. The inclusion of CPS increased (P

Isoflavonoid composition of freshly harvested soy sprouts of six cultivars grown in Colombia was analyzed. Evaluations on the effect of storage time at 12 °C and exogenous application of the elicitor 2,6-dichloro isonicotinic acid (INA) were carried out to establish their influence in the ability of soy sprouts for synthesizing isoflavonoids. In addition, elicited and non-elicited sprouts of soy cultivar Soy SK-7 was assessed for total phenolic content and antioxidant activity according to the growth stage (VE, VC, and V1) and tissues (cotyledon-epicotyl and hypocotyl-root). Isoflavonoid content and antioxidant capacity were dependent on the cultivar, growth stage, tissue, and storage time at 12 °C. Growth stages VE and V1 and the hypocotyl-root exhibited the highest total phenolic content and antioxidant activity. In general, 6”-O-malonylgenistin, daidzin and genistin were the major constituents in the cultivars. Soy SK-7 and Panorama 358 displayed the highest amounts of 6”-O-malonylgenistin (155.9 µg/g) and daidzin (83.5 µg/g), respectively. Results showed that the isoflavonoids and phenolic contents and antioxidant activity were significantly increased by application of INA. This information can be useful to produce soybean sprouts with increased amounts of bioactive compounds and improved response to abiotic and biotic stresses.

The Uruk Expansion, which took place during various phases throughout the 4th millennium BC, also developed in Northern Mesopotamia. In the area of Birecik, in eastern Turkey, on the edge of the Euphrates, various archaeological sites have been discovered, showing different phases of expansion of the Uruk culture. We focus this study on the Surtepe site, a 8 ha settlement, where we have distinguished a possible Late Calcolithic 5 ritual building, in a phase that we consider Terminal Uruk within the chronology of this Mesopotamian culture

Appearance of dermal matrices has had an incredibly positive impact on the functional and aesthetic aspects in burned patients, and other wounds with loss of subcutaneous tissue. Nevertheless, dermal matrices can be applicable to other reconstructive fields, especially in organs in which the recovery of skin elasticity is essential. From January 2012 to May 2021, all patients with penile wounds treated at our department with dermal matrices were included in the present study. The following aspects of each case were reviewed: patients’ age, wound mechanism, defect location and size, clinical follow-up, and postoperative complications. Four patients were included in this study. Average age was 27.7 years (range: 15-43 years). The mechanism of penile injury was subcutaneous penile paraffin injection (n=2), electrical burn (n=1) and surgical complication (n=1).We used Matriderm® monolayer in all cases. There were no cases of total or partial loss. In all cases, a good functional and aesthetic result was achieved. Use of dermal matrices must be a daily option in our units, both for acute penile wounds and sequelae, and we all must be familiar with their indications, management, and results. A multidisciplinary approach between Plastic Surgery and Urology is highly recommended. Level of evidence: Level V, therapeutic study.

espanolLa prevalencia del trastorno del espectro autista (TEA) ha aumentado en las decadas recientes. Es necesario que el profesorado atienda la diversidad presente en las aulas, teniendo en consideracion las caracteristicas y necesidades que presentan las personas con TEA a la hora de disenar propuestas educativas capaces de motivar la participacion de todo el alumnado. El presente trabajo relata un proceso de investigacion-accion (IA) abordado en el seno de un programa piloto de sesiones de Educacion Fisica (EF) con alumnado con TEA. El objetivo consistio en testar un programa de actividades centrado en ofrecer pautas utiles para el profesorado, aplicables tanto en sesiones ordinarias de EF, como en unidades especificas de comunicacion y lenguaje. Partiendo del compromiso con el enfoque de educacion inclusivo, la propuesta de actividades se hizo teniendo como base de fundamentacion la legislacion vigente y se analizo a traves de la metodologia de IA. Los resultados obtenidos concretan que orientaciones como la utilizacion de pictogramas explicativos de las tareas, el modelaje, la introduccion de tematicas de su interes o el uso de una metodologia directiva, pueden mejorar la participacion y servir como referencia para el diseno de futuras propuestas de EF. EnglishThe prevalence of Autism Spectrum Disorder (ASD) has increased in recent decades. It is necessary for teachers to attend to the diversity present in the classrooms, taking into account the characteristics and needs of people with ASD when designing educational proposals capable of motivating the inclusion of all students. The present work reports an action-research (AR) process approached within a pilot program of Physical Education (PE) sessions with students with ASD. The objective consisted of testing a program of activities focused on offering useful guidelines for teachers, applicable both in ordinary PE sessions, as well as in specific communication and language units. Based on the commitment to the inclusive education approach, the proposal of activities was based on the current legislation and analysed through the AR methodology. The results obtained show that guidelines such as the use of pictograms to explain the tasks, modelling, the introduction of topics of interest, and the use of a directive methodology can improve participation and serve as a reference for the design of future PE proposals. portuguesA prevalencia do transtorno do espectro do autismo (TEA) aumentou nas ultimas decadas. E necessario que o professor atenda a diversidade presente nas salas de aula, levando em consideracao as caracteristicas e necessidades das pessoas com TEA na concepcao de propostas educacionais capazes de motivar a participacao de todos os alunos. O presente trabalho relata um processo de pesquisa-acao (IA) abordado em um programa piloto de sessoes de Educacao Fisica (EF) com alunos com TEA. O objetivo consistia em testar um programa de atividades focado em oferecer orientacoes uteis para os professores, aplicaveis ​​tanto em sessoes ordinarias de EF, como em unidades especificas de comunicacao e linguagem. A partir do compromisso com a abordagem da educacao inclusiva, a proposta de atividades foi feita com base na legislacao vigente e analisada por meio da metodologia de IA. Os resultados obtidos especificam que orientacoes como a utilizacao de pictogramas explicativos das tarefas, modelacao, introducao de temas de interesse ou utilizacao de metodologia diretiva, podem melhorar a participacao e servir de referencia para a concecao de futuras propostas de PE.

Objetivo: Se hizo una evaluación de las características de prescripción y dispensación de antimicrobianos de reserva en la Clínica San Pablo de enero-diciembre del año 2020. Materiales y métodos: Metodológicamente el estudio fue descriptivo, de corte transversal y la recolección de datos de manera retrospectiva, con una muestra de 440 recetas médicas prescritas con antimicrobianos. Resultados: Respecto a los resultados se observó que en su mayoría si cumplió con escribir los datos del paciente. Finalmente se observó que el 100% de las recetas contenían antimicrobianos pertenecientes al PNUME. Conclusión: Siendo la conclusión principal y determinando que la clínica San Pablo tiene altos porcentajes de cumplimientos de las características de prescripción y dispensación de antimicrobianos de reserva, quedando un mínimo porcentaje que podría mejorar.

Covalent drug discovery, in particular targeting reactive cysteines, has undergone a resurgence over the past two decades, demonstrated by recent clinical successes of covalent inhibitors for high-priority cancer targets. Reactive cysteine profiling, first pioneered by the Cravatt lab, has emerged in parallel as a powerful approach for proteome-wide on- and off-target profiling. Thus far however, structural analysis of liganded cysteines has been restricted to experimentally determined protein structures. We combined AlphaFold-predicted amino acid side chain accessibilities for >95% of the human proteome with a meta-analysis of thirteen public cysteine profiling datasets, totalling 40,070 unique cysteine residues, revealing accessibility biases in sampled cysteines primarily dictated by warhead chemistry. Analysis of >3.5 million cysteine-fragment interactions further suggests that exposed cysteine residues are preferentially targeted by elaborated fragments and drug-like compounds. We finally propose a framework for benchmarking coverage of ligandable cysteines in future cysteine profiling approaches, considering both selectivity for high-priority residues and quantitative depth. All analysis and produced resources (freely available atwww.github.com/TateLab) are readily extendable to reactive amino acids beyond cysteine, and related questions in chemical biology.

Atopic dermatitis; Cutaneous lymphocyte antigen; Skin infections Dermatitis atópica; Antígeno cutáneo de linfocitos; Infecciones de la piel Dermatitis atòpica; Antigen limfòcit cutani; Infeccions de la pell Staphylococcus aureus, memory skin-homing cutaneous lymphocyte-associated antigen (CLA)+ T cells and IL-13 constitute relevant play-ers in atopic dermatitis (AD) pathogenesis.1 Since circulating CLA+ T cells reflect cutaneous abnormalities present in human inflammatory skin diseases,2 an ex vivo coculture model made of purified circu-lating CLA+/− effector and central memory T cells and autologous lesional epidermal cells was established. We show a CLA-dependent production of IL-13 upon activation with staphylococcal enterotoxin B (SEB) that allows the differentiation of the Th2 high and Th2 low groups, with distinct clinical correlations between both groups, within a clinically homogeneous population of adult non-treated moderate-to- severe AD patients.

Calluna vulgaris (Ericaceae) is the most widespread and prevalent woody species of the European dry heathland, from the African side of the Strait of Gibraltar to northern Europe. However, previous biogeographic analyses of this species have ignored the western Mediterranean region, despite its preponderant role as a major glacial refugium for European biota. Here, we explore the existence of further Pleistocene glacial refugia for C. vulgaris in the Iberian Peninsula and the Strait of Gibraltar area and provide new insights into the post-glacial colonization of Europe by this emblematic heathland species. We carried out phylogeographical analyses of C. vulgaris samples from 44 locations using four plastid markers (matK, trnH-psbA, trnL-F and rpl16). We built palaeodistribution models using MAXENT to identify possible refugia for C. vulgaris during the mid-Pliocene, Last Interglacial (LIG), Last Glacial Maximum (LGM) and mid-Holocene. Our results identified a genetic lineage exclusive to the Strait of Gibraltar area s.l. (south-western Iberian Peninsula and north-western tip of Africa) as the most probable close to the clade of origin of the species. This lineage also had more private haplotypes than more recent, Eurosiberian clades. The obtained data highlighted two main refugia for C. vulgaris during the LGM, one around the Strait of Gibraltar and another in the north-western Iberian Peninsula. The Strait of Gibraltar area is a major centre of origin or glacial refugium for the heather C. vulgaris. However, the north-western Iberian Peninsula seems to have acted as a secondary glacial refugium for the more recent, Eurosiberian lineage of this species. This study stresses the importance of the Strait of Gibraltar area in the biogeographic history and conservation of the heather and, by extension, the European heathland habitat.

Active and democratic citizenship promotion has become a critical challenge for higher education, and civic engagement is a fundamental axis not only in education but also in fostering democratic systems. Consequently, teacher educators held a prominent role through their own teaching practices to generate contexts promoting critical thinking, skills and attitudes. The aim of this study was to analyze the learning related to the political dimension developed by pre-service teachers (n = 123) after participating in a Service-Learning program through physical education with children at risk or/and student with educational needs. This research followed a qualitative research approach and we based the analysis of reflective diaries on Gorham’s (2005) categories regarding political learning: Critical political thinking, Interest in politics, Deliberation and Political judgment. The findings show a development in learning such as civic attitudes, critical political thinking, awareness of social justice problems, increased civic compromise and responsibility. The Service-Learning program, therefore, may have been an adequate option to develop pre-service teachers’ learning related to a political perspective. Therefore, these findings let us understand how Service-Learning may foster equity and social justice among future teachers., Universitat Jaume I UJI-A2019-01 PREDOC/2016/5 03/UPB/20

Background and purpose Cardiac glycosides (CGs) inhibit the Na+ ,K+ -ATPase and are widely prescribed medicines for chronic heart failure and cardiac arrhythmias. Recently, CGs have been described to induce inflammasome activation and pyroptosis in human macrophages, suggesting a cytotoxicity that remains to be elucidated in tissues. Experimental approach To determine the cell type specificity of CG-mediated cytotoxicity, we used human primary monocyte-derived macrophages (hMDMs) and non-adherent peripheral blood cells isolated from healthy donors. Omental white adipose tissue (WAT) and stromal vascular fraction (SVF)-derived pre-adipocytes and adipocytes were isolated from obese patients undergoing bariatric surgery. All these primary cells/tissues were treated with nanomolar concentrations of ouabain (50nM, 100nM and 500nM) to investigate its degree of cytotoxicity and mechanisms leading to cell death. In WAT, we further explored the consequences of ouabain-mediated cytotoxicity by measuring insulin sensitivity, adipose tissue function and extracellular matrix (ECM) deposition ex vivo. Key results The ouabain-induced cell death is through pyroptosis and apoptosis, and more efficient in hMDMs compared to non-adherent PBMC populations. This selective cytotoxicity is dependent on K+ flux, as ouabain causes an intracellular depletion of K+ , while inducing accumulation of Na+ and Ca2+ levels. Consistently, the cell-death caused by these ion imbalances can be rescued by addition of potassium chloride in hMDMs. Remarkably, when WAT explants from obese patients are cultured with nanomolar concentrations of ouabain, this causes depletion of macrophages, down-regulation of type VI collagen levels, and amelioration of insulin sensitivity ex vivo. Conclusions and implications These results suggest that the usage of nanomolar concentration of CGs can be an attractive therapeutic avenue in metabolic syndrome characterised by pathogenic infiltration and activation of macrophages.

Senescence is a key barrier to neoplastic transformation. To identify senescence regulators relevant to cancer, we screened a genome-wide shRNA library. Here, we describe exportin 7 (XPO7) as a novel regulator of senescence and validate its function in telomere-induced, replicative, and oncogene-induced senescence (OIS). XPO7 is a bidirectional transporter that regulates the nuclear-cytoplasmic shuttling of a broad range of substrates. Depletion of XPO7 results in reduced levels of TCF3 and an impaired induction of the cyclin-dependent kinase inhibitor p21CIP1 during OIS. Deletion of XPO7 correlates with poorer overall survival in several cancer types. Moreover, depletion of XPO7 alleviated OIS and increased tumor formation in a mouse model of liver cancer. Our results suggest that XPO7 is a novel tumor suppressor that regulates p21CIP1 expression to control senescence and tumorigenesis.

BackgroundVedolizumab is a humanized monoclonal antibody targeting the α4β7 integrin used for the treatment of ulcerative colitis. Few biomarkers related to vedolizumab response have been identified. The aim of this work was to assess whether baseline circulating CD4+ and CD8+ memory T-lymphocyte subpopulations could help to identify patients with response to vedolizumab treatment in ulcerative colitis.MethodsProspective pilot study in 15 patients with active ulcerative colitis and previous failure to anti-TNFα starting vedolizumab treatment. Peripheral blood samples were obtained before the first dose of vedolizumab and at week 6 and 14 of treatment. Clinical remission was defined as a Mayo Clinic partial score of ≤2 points without any concomitant dose of steroids. Biochemical remission or endoscopic improvement was defined as fecal calprotectin ResultsAt week 14, nine patients achieved clinical remission and eight patients achieved biochemical remission or endoscopic improvement. Patients in clinical remission presented higher baseline CD8 α4β7+ memory T cells concentration when compared with patients with no remission. In addition, patients with biochemical remission or endoscopic improvement at week 14 presented higher baseline concentration of CD8 α4β7+ memory T cells. No differences were identified according to flare severity, extent of disease or type of anti-TNFα failure. There were no significant differences regarding changes in T cell subsets during vedolizumab induction.ConclusionCD8+ α4β7+ memory T cells before starting vedolizumab therapy could be an early predictor of remission in ulcerative colitis patients and therefore help to select a subset of responders.