Povezanost slike o vlastitu tijelu s tjelesnom aktivnošću, zadovoljstvom životom i mediteranskom prehranom španjolskih adolescenata

The aim of this study was to examine the association between physical self-concept and physical activity, the intention to be physically active, life satisfaction, and adherence to the Mediterranean diet in adolescents. A total of 1,808 Spanish adolescents (12-16 years of age) participated in this cross-sectional study. Physical Self Questionnaire, Moderate-to-Vigorous Physical Activity Screening Measure, Intention to be Physically Active Scale, Satisfaction with Life Scale, and Mediterranean Diet Quality Index were administered. The boys with a lower physical self-concept showed higher odd ratios of being inactive, having low intentions of being physically active, poor life satisfaction and low adherence to the Mediterranean diet. Similarly, most of the associations were also statistically significant in girls as well. In conclusion, the study reveals that having a low level of physical self-concept increases the risk of being inactive and of having a low level of intention to be physically active, life satisfaction and adherence to the Mediterranean diet in adolescents.Cilj je ovog istraživanja bio utvrditi povezanost između samopoimanja tijela i tjelesne aktivnosti, namjere da se bude tjelesno aktivan, zadovoljstva životom i pridržavanja mediteranske prehrane kod adolescenata. U ovo transverzalno istraživanje bilo je uključeno ukupno 1.808 španjolskih adolescenata (u dobi od 12 do 16 godina). U istraživanju su korišteni sljedeći mjerni instrumenti: Physical Self Questionnaire, Moderate-to-Vigorous Physical Activity Screening Measure, Intention to be Physically Active Scale, Satisfaction with Life Scale, i Mediterranean Diet Quality Index. Dječaci s nižom razinom zadovoljstva vlastitim tijelom, u bilo kojoj njegovoj dimenziji, pokazali su veću sklonost tjelesnoj neaktivnosti, nižu odlučnost da budu tjelesno aktivni, manifestirali su nisku razinu zadovoljstva životom i slabo pridržavanje načela mediteranske prehrane. Slično kao i kod dječaka, većina relacija bila je statistički značajna i kod djevojčica. Zaključno, istraživanje je ukazalo na činjenicu da niska razina samopoimanja povećava rizik za neaktivnost i za nisku razinu namjere za kasniju tjelesnu aktivnost te da je povezano sa slabijim zadovoljstvom životom i slabijim pridržavanjem načela mediteranske prehrane kod adolescenata

Identifying SARS-CoV-2 'memory' NK cells from COVID-19 convalescent donors for adoptive cell therapy

COVID-19 disease is the manifestation of syndrome coronavirus 2 (SARS-CoV-2) infection, which is causing a worldwide pandemic. This disease can lead to multiple and different symptoms, being lymphopenia associated with severity one of the most persistent. Natural killer cells (NK cells) are part of the innate immune system, being fighting against virus-infected cells one of their key roles. In this study, we determined the phenotype of NK cells after COVID-19 and the main characteristic of SARS-CoV-2-specific-like NK population in the blood of convalescent donors. CD57+ NKG2C+ phenotype in SARS-CoV-2 convalescent donors indicates the presence of 'memory'/activated NK cells as it has been shown for cytomegalovirus infections. Although the existence of this population is donor dependent, its expression may be crucial for the specific response against SARS-CoV-2, so that, it gives us a tool for selecting the best donors to produce off-the-shelf living drug for cell therapy to treat COVID-19 patients under the RELEASE clinical trial (NCT04578210)

Partial order label decomposition approaches for melanoma diagnosis

Melanoma is a type of cancer that develops from the pigment-containing cells known as melanocytes. Usually occurring on the skin, early detection and diagnosis is strongly related to survival rates. Melanoma recognition is a challenging task that nowadays is performed by well trained dermatologists who may produce varying diagnosis due to the task complexity. This motivates the development of automated diagnosis tools, in spite of the inherent difficulties (intra-class variation, visual similarity between melanoma and non-melanoma lesions, among others). In the present work, we propose a system combining image analysis and machine learning to detect melanoma presence and severity. The severity is assessed in terms of melanoma thickness, which is measured by the Breslow index. Previous works mainly focus on the binary problem of detecting the presence of the melanoma. However, the system proposed in this paper goes a step further by also considering the stage of the lesion in the classification task. To do so, we extract 100 features that consider the shape, colour, pigment network and texture of the benign and malignant lesions. The problem is tackled as a five-class classification problem, where the first class represents benign lesions, and the remaining four classes represent the different stages of the melanoma (via the Breslow index). Based on the problem definition, we identify the learning setting as a partial order problem, in which the patterns belonging to the different melanoma stages present an order relationship, but where there is no order arrangement with respect to the benign lesions. Under this assumption about the class topology, we design several proposals to exploit this structure and improve data preprocessing. In this sense, we experimentally demonstrate that those proposals exploiting the partial order assumption achieve better performance than 12 baseline nominal and ordinal classifiers (including a deep learning model) which do not consider this partial order. To deal with class imbalance, we additionally propose specific over-sampling techniques that consider the structure of the problem for the creation of synthetic patterns. The experimental study is carried out with clinician-curated images from the Interactive Atlas of Dermoscopy, which eases reproducibility of experiments. Concerning the results obtained, in spite of having augmented the complexity of the classification problem with more classes, the performance of our proposals in the binary problem is similar to the one reported in the literature

Dietary supplementation with vitamins C and E prevents downregulation of endothelial NOS expression in hypercholesterolemia in vivo and in vitro

Impaired endothelium-dependent vasodilation has been associated with decreased NO bioavailability in hypercholesterolemia. This study aimed to determine whether antioxidant vitamins C and E could improve hypercholesterolemia-derived endothelial dysfunction in the porcine model, and whether observed in vivo results could be reproduced in vitro by incubation of coronary endothelial cells (EC) in the presence of native low-density lipoproteins (LDL). Adult mini-pigs were fed standard (C), cholesterol rich (HC) or cholesterol rich diet supplemented with vitamins C and E (HCV). Endothelium-dependent blood flow increase in response to acetylcholine was determined. Endothelial nitric oxide synthase (eNOS) expression was measured in arterial samples and in EC incubated with LDL isolated from porcine plasma. Vasomotor response to acetylcholine in HC was significantly lower (P<0.05) than control and HCV. There was a significant (P<0.05) decrease in eNOS immunoreactivity in HC, compared with HCV and control. Native LDL from HC, but not from HCV, induced a significant decrease in eNOS expression. Vitamins C and E treatment improved the endothelium-dependent vasomotor capacity and prevented decreased expression of eNOS in hypercholesterolemic pigs. A similar effect could be demonstrated in vitro, by incubation of EC with native LDL, suggesting that the effect of physiologically-modified LDL on eNOS could have a role in recovering vascular function

Effect of ABCB1 and ABCC3 Polymorphisms on Osteosarcoma Survival after Chemotherapy: A Pharmacogenetic Study

Standard treatment for osteosarcoma patients consists of a combination of cisplatin, adriamycin, and methotrexate before surgical resection of the primary tumour, followed by postoperative chemotherapy including vincristine and cyclophosphamide. Unfortunately, many patients still relapse or suffer adverse events. We examined whether common germline polymorphisms in chemotherapeutic transporter and metabolic pathway genes of the drugs used in standard osteosarcoma treatment may predict treatment response. METHODOLOGY/PRINCIPAL FINDINGS: In this study we screened 102 osteosarcoma patients for 346 Single Nucleotide Polymorphisms (SNPs) and 2 Copy Number Variants (CNVs) in 24 genes involved in the metabolism or transport of cisplatin, adriamycin, methotrexate, vincristine, and cyclophosphamide. We studied the association of the genotypes with tumour response and overall survival. We found that four SNPs in two ATP-binding cassette genes were significantly associated with overall survival: rs4148416 in ABCC3 (per-allele HR = 8.14, 95%CI = 2.73-20.2, p-value = 5.1x10(-)(5)), and three SNPs in ABCB1, rs4148737 (per-allele HR = 3.66, 95%CI = 1.85-6.11, p-value = 6.9x10(-)(5)), rs1128503 and rs10276036 (r(2) = 1, per-allele HR = 0.24, 95%CI = 0.11-0.47 p-value = 7.9x10(-)(5)). Associations with these SNPs remained statistically significant after correction for multiple testing (all corrected p-values [permutation test] </= 0.03). CONCLUSIONS: Our findings suggest that these polymorphisms may affect osteosarcoma treatment efficacy. If these associations are independently validated, these variants could be used as genetic predictors of clinical outcome in the treatment of osteosarcoma, helping in the design of individualized therapy

Inmunoterapia con células CAR-T en hematooncología pediátrica

Resumen A pesar de ser una enfermedad rara, el cáncer es la primera causa de mortalidad por enfermedad durante la edad pediátrica en los países desarrollados. En este momento, la irrupción de nuevos tratamientos como la inmunoterapia constituye un nuevo paradigma clínico y regulatorio. Uno de estos tipos de inmunoterapia es la inmunoterapia celular. En particular, los medicamentos de terapia avanzada con receptores antigénicos quiméricos en los linfocitos T (CAR-T), y en concreto las células CAR-T19, han supuesto un nuevo escenario en el abordaje de los tumores hematológicos, como la leucemia aguda linfoblástica y los linfomas de células tipo B. La aprobación por las autoridades regulatorias de tisagenlecleucel y axicabtagene ciloleucel, ha impulsado la puesta en marcha del Plan Nacional de Terapias Avanzadas-Medicamentos CART en Espana, ˜ evidenciándose no solo la conveniencia de identificar los centros más adecuados para su administración, sino la necesidad de que estos sufran una profunda transformación para que su actividad asistencial se extienda en algunos casos a la capacidad de fabricación propia de este tipo de terapias. Los hospitales especializados en hematooncología pediátrica tienen por tanto el reto de evolucionar hacia un modelo asistencial que integre la inmunoterapia celular, dotándose de capacidad propia para gestionar todos los aspectos relativos al uso, fabricación y administración de estos nuevos tratamientos.Abstract Despite being a rare disease, cancer is the first cause of mortality due to disease during the paediatric age in the developed countries. The current, great increase in new treatments, such as immunotherapy, constitutes a new clinical and regulatory paradigm. Cellular immunotherapy is one of these types of immunotherapy. In particular, the advanced therapy drugs with chimeric antigen receptors in the T-lymphocytes (CAR-T), and particularly the CART19 cells, has opened up a new scenario in the approach to haematology tumours like acute lymphoblastic leukaemia and the B-Cell lymphomas. The approval of tisagenlecleucel and axicabtagene ciloleucel by the regulatory authorities has led to the setting up of the National Plan for Advanced Therapies-CAR-T drugs in Spain. There is evidence of, not only the advantage of identifying the centres most suitable for their administration, but also the need for these to undergo a profound change in order that their healthcare activity is extended, in some cases, to the ability for the in-house manufacture of these types of therapies. The hospitals specialised in paediatric haematology-oncology thus have the challenge of progressing towards a healthcare model that integrates cellular immunotherapy, having the appropriate capacity to manage all aspects relative to their use, manufacture, and administration of these new treatments

Regulation of mammalian liver methionine adenosyltransferase

S-adenosylmethionine (SAM) is an essential metabolite in all cells. SAM is the most important biological methyl group donor and is a precursor in the synthesis of polyamines. Methionine adenosyltransferase (MAT; EC 2.5.1.6) catalyzes the only known SAM biosynthetic reaction from methionine and ATP. In mammalian tissues, three different forms of MAT (MAT I, MAT III and MAT II) have been identified that are the product of two different genes (MAT1A and MAT2A). Although MAT2A is expressed in all mammalian tissues, the expression of MAT1A is primarily restricted to adult liver. In mammals, up to 85% of all methylation reactions and as much as 48% of methionine metabolism occurs in the liver, which indicates the important role of this organ in the regulation of blood methionine. Recent evidence indicates that not only is SAM the main biological methyl group donor and an intermediate metabolite in methionine catabolism, but it is also an intracellular control switch that regulates essential hepatic functions such as liver regeneration and differentiation as well as the sensitivity of this organ to injury. Therefore, knowledge of factors that regulate the activity of MAT I/III, the specific liver enzyme, is essential to understand how cellular SAM levels are controlled

EZH2 endorses cell plasticity to non-small cell lung cancer cells facilitating mesenchymal to epithelial transition and tumour colonization

CGL was funded by the Consejería de Salud y Familias, Junta de Andalucía (RH-0139-2020) and SG-P is funded by Instituto de Salud Carlos III (CP19/00029, PI15/00336, PI19/01533). JAM is supported by RTI2018.101309B-C22 funded by MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” and by the Chair “Doctors Galera-Requena in cancer stem cell research”. PCS is funded by Ministerio de Ciencia e Innovación (grant PID2020-119032RB-I00) and FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades (grants P20_00335 and B‐CTS‐40‐UGR20). The Landeira lab is supported by the Spanish ministry of science and innovation (PID2019-108108-100, EUR2021-122005), the Andalusian regional government (PC-0246-2017, PIER-0211-2019, PY20_00681) and the University of Granada (A-BIO-6-UGR20) grants.Reversible transition between the epithelial and mesenchymal states are key aspects of carcinoma cell dissemination and the metastatic disease, and thus, characterizing the molecular basis of the epithelial to mesenchymal transition (EMT) is crucial to find druggable targets and more effective therapeutic approaches in cancer. Emerging studies suggest that epigenetic regulators might endorse cancer cells with the cell plasticity required to conduct dynamic changes in cell state during EMT. However, epigenetic mechanisms involved remain mostly unknown. Polycomb Repressive Complexes (PRCs) proteins are well-established epigenetic regulators of development and stem cell differentiation, but their role in different cancer systems is inconsistent and sometimes paradoxical. In this study, we have analysed the role of the PRC2 protein EZH2 in lung carcinoma cells. We found that besides its described role in CDKN2A-dependent cell proliferation, EZH2 upholds the epithelial state of cancer cells by repressing the transcription of hundreds of mesenchymal genes. Chemical inhibition or genetic removal of EZH2 promotes the residence of cancer cells in the mesenchymal state during reversible epithelial–mesenchymal transition. In fitting, analysis of human patient samples and tumour xenograft models indicate that EZH2 is required to efficiently repress mesenchymal genes and facilitate tumour colonization in vivo. Overall, this study discloses a novel role of PRC2 as a master regulator of EMT in carcinoma cells. This finding has important implications for the design of therapies based on EZH2 inhibitors in human cancer patients.Junta de Andalucía (RH-0139-2020)Instituto de Salud Carlos III (CP19/00029, PI15/00336, PI19/01533)MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” RTI2018.101309B-C22Chair “Doctors Galera-Requena in cancer stem cell research”Ministerio de Ciencia e Innovación (grant PID2020-119032RB-I00)FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades (grants P20_00335 and B‐CTS‐40‐UGR20)Spanish ministry of science and innovation (PID2019-108108-100, EUR2021-122005)Andalusian regional government (PC-0246-2017, PIER-0211-2019, PY20_00681)University of Granada (A-BIO-6-UGR20