Efecto del TNF alfa sobre la síntesis de colágeno y la expresión genética del procolágeno alfa1(I) en lipocitos en cultivo

Tesis de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular II, leída el 22-06-1993El TNFa es una citoquina sintetizada fundamentalmente por macrófagos y neutrófilos. En el presente trabajo se han investigado los efectos que tiene el TNFa sobre la producción y síntesis de colágeno, sobre el metabolismo de esta proteína y sobre la expresión genética del procolágeno a(1)(I). Todo ello se ha determinado en células de ITO cultivadas en DMEM con 10%STF. Los resultados obtenidos indican que el TNFa reduce la producción de colágeno inhibiendo la expresión genética del colágeno. En concreto el TNFa disminuye los niveles de MRNA de procolágeno a(1)(I) a través de una proteína cuya síntesis es inducida por una vía en la que participa una proteína G, una fosfolipasa C, y el calcio libre intracelular, y encuentra su región cisactivadora en el fragmento -2300 a -1700 pb del promotor simultáneamente el TNFa promueve una activación de la ..Fac. de FarmaciaTRUEpu

Efecto del TNF alfa sobre la síntesis de colágeno y la expresión genética del procolágeno alfa1(I) en lipocitos en cultivo

El TNFa es una citoquina sintetizada fundamentalmente por macrófagos y neutrófilos. En el presente trabajo se han investigado los efectos que tiene el TNFa sobre la producción y síntesis de colágeno, sobre el metabolismo de esta proteína y sobre la expresión genética del procolágeno a(1)(I). Todo ello se ha determinado en células de ITO cultivadas en DMEM con 10%STF. Los resultados obtenidos indican que el TNFa reduce la producción de colágeno inhibiendo la expresión genética del colágeno. En concreto el TNFa disminuye los niveles de MRNA de procolágeno a(1)(I) a través de una proteína cuya síntesis es inducida por una vía en la que participa una proteína G, una fosfolipasa C, y el calcio libre intracelular, y encuentra su región cisactivadora en el fragmento -2300 a -1700 pb del promotor simultáneamente el TNFa promueve una activación de la .

Closure Structures as fixed points of some Galois connections.

The starting point of this work is a published paper where the fuzzy powerset of a fuzzy lattice A, the set of isotone mappings on A and the set of isotone total relations on A were proved to be related by three fuzzy Galois connections such that fuzzy closure systems, fuzzy closure operators and the so called strong fuzzy closure relations are fixed points. The final part of that paper studied the commutativity of the diagrams formed by these mappings.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Fuzzy closure structures as formal concepts

Galois connections seem to be ubiquitous in mathematics. They have been used to model solutions for both pure and application-oriented problems. Throughout the paper, the general framework is a complete fuzzy lattice over a complete residuated lattice. The existence of three fuzzy Galois connections (two antitone and one isotone) between three specific ordered sets is proved in this paper. The most interesting part is that fuzzy closure systems, fuzzy closure operators and strong fuzzy closure relations are formal concepts of these fuzzy Galois connections.This research is partially supported by the State Agency of Research (AEI), the Spanish Ministry of Science, Innovation and Universities (MCIU), the European Social Fund (FEDER), the Junta de Andalucía (JA), and the Universidad de Málaga (UMA) through the FPU19/01467 (MCIU) internship and the research projects with reference PGC2018-095869-B-I00, TIN2017-89023-P, PID2021-127870OB-I00 (MCIU/AEI/FEDER, UE) and UMA18-FEDERJA-001 (JA/ UMA/ FEDER, UE). Funding for open access charge: Universidad de Málaga / CBU

Fuzzy Closure Structures as Formal Concepts II

This paper is the natural extension of Fuzzy Closure Structures as Formal Concepts. In this paper we take into consideration the concept of closure system which is not dealt with in the previous one. Hence, a connection must be found between fuzzy ordered sets and a crisp ordered set. This problem is two-fold, the core of the fuzzy orders can be considered in order to complete the ensemble, or the crisp order can be fuzzified. Both ways are studied in the paper. The most interesting result is, similarly to the previous paper, that closure systems are formal concepts of these Galois connections as well.Funding for open access charge: Universidad de Málaga / CBUA This research is partially supported by the State Agency of Research (AEI), the Spanish Ministry of Science, Innovation, and Universities (MCIU), the European Social Fund (FEDER), the Junta de Andalucía (JA), and the Universidad de Málaga (UMA) through the FPU19/01467 (MCIU) internship, the project VALID (PID2022-140630NB-I00 funded by MCIN/ AEI/10.13039/501100011033) and the research projects with reference PGC2018-095869-B-I00, PID2021-127870OB-I00, (MCIU/AEI/FEDER, UE) and UMA18-FEDERJA-001 (JA/ UMA/ FEDER, UE)

A myxoid fibrotic reaction pattern is associated with metastatic risk in cutaneous squamous cell carcinoma

Metastasis; Fibrosis; Cutaneous squamous cell carcinomaMetástasis; Fibrosis; Carcinoma cutáneo de células escamosasMetàstasi; Fibrosi; Carcinoma cutani de cèl·lules escamosesAlthough desmoplasia has been associated with poor prognoses in cutaneous squamous cell carcinoma, little attention has been paid to the patterns of fibrosis. This study aimed to examine the different stromal fibrotic patterns as markers of metastatic risk. We performed a multicenter retrospective study that included 102 cutaneous squamous cell carcinomas (52 non-metastatic and 50 metastatic carcinomas). Clinical and histopa-thological data were registered. The fibrotic reaction pattern was classified as mature, intermediate or immature depending on the presence of keloid-like collagen and myxoid stroma. The immature pattern (areas characterized by myxoid changes with no inflammation) was observed in 18 samples and its presence was significantly associated with immuno-suppression, budding, desmoplasia, perineural invasion, anatomic level, tumoural depth and metastatic risk in the multivariate analysis. Our findings suggest that the presence of an immature myxoid fibrotic pattern, which can be easily identified by routine hematoxylin-eosin staining, is strongly associated with metastatic risk.This work has been supported by grant PI15/00236 from Fondo de Investigación Sanitaria (FIS), Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III, Ministerio de Sanidad, and the ‘‘Xarxa de Bancs de Tumours”

Assessment of non-physical user violence and burnout in primary health Care professionals. The modulating role of job satisfaction

Introduction: Growing concern about workplace violence shows the need for an evaluation in specific contexts in order to identify the particularities of each professional group. The health sector consists of a group of professionals with high exposure to violence, specially from users. There are differences depending on the professional category or unit in which the professional works. In this regard, Primary Health Care (PHC) is characterized by a personalized and continuous patient treatment over time, which is not exempt from cases of violence. Among the commonly studied consequences of these situations are decreases in job satisfaction and burnout. Objective: The main objective of this study is to analyze the modulating role of job satisfaction in the relationship between non-physical user violence and the onset of burnout. Methods: Cross-sectional comparative descriptive design. The sample consisted of 574 professionals from 39 PHC centers of the Murcian Health Service. Data were collected using two-stage cluster sampling. For data analysis, descriptive analysis, correlations and stepwise hierarchical regression were used to analyze the interaction between the variables. Results: Regression analysis draws a model where non-physical violence and low intrinsic and extrinsic job satisfaction act as modulators of non-physical violence, cynicism and emotional exhaustion. Conclusions: This study provides evidence of the psychological consequences of the perception of user violence in the PHC staff. Furthermore, it is evident that the emergence of burnout syndrome in these professionals is related to exposure to verbal or non-physical violence together with low job satisfaction. In this sense, a circular and bidirectional relationship between the variables studied is proposed as a possible explanatory model

RING1B contributes to Ewing sarcoma development by repressing the Na(V)1.6 sodium channel and the NF-kappa B pathway, independently of the fusion oncoprotein

Ewing sarcoma (ES) is an aggressive tumor defined by EWSR1 gene fusions that behave as an oncogene. Here we demonstrate that RING1B is highly expressed in primary ES tumors, and its expression is independent of the fusion oncogene. RING1B-depleted ES cells display an expression profile enriched in genes functionally involved in hematological development but RING1B depletion does not induce cellular differentiation. In ES cells, RING1B directly binds the SCN8A sodium channel promoter and its depletion results in enhanced Nav1.6 expression and function. The signaling pathway most significantly modulated by RING1B is NF-κB. RING1B depletion results in enhanced p105/p50 expression, which sensitizes ES cells to apoptosis by FGFR/SHP2/STAT3 blockade. Reduced NaV1.6 function protects ES cells from apoptotic cell death by maintaining low NF-κB levels. Our findings identify RING1B as a trait of the cell-of-origin and provide a potential targetable vulnerability.Ministerio de Economía y Competitividad SAF2012-31089 and SAF2015-69762-RMEC FEDER RD12/0036/0017, PT13/0010/0056, RTC-2014- 2102-1, ISCIII Sara Borrell CD06/00001, PI12/03102, PI14/01466European FP7 Projects EuroSARC FP7- HEALTH-2011-two-stage, Project 278742 EUROSARCEuroewing FP7-HEALTH.2013.2.4.1-1, Project 60285

Nutritional Supplementation to Increase Influenza Vaccine Response in Children Living With HIV: A Pilot Clinical Trial

Final results of this work have been presented at the following meetings: 36rd Annual Meeting of the European Society for Pediatric Infectious Diseases (ESPID 2018), Malmö, Sweden, 28th May-June 2nd, 2018. (Ref. ESP18-0517).Aims: Vaccine response is poor among children living with HIV. The gut microbiota has been identified as a potential target to improve vaccine immunogenicity, but data are scarce in the context of HIV infection. Methods: Pilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected children were randomized to receive a mixture of symbiotics, omega-3/6 fatty acids, and amino acids or placebo for 4 weeks, each in combination with ART, and were then immunized against influenza. Vaccine response and safety of the nutritional supplementation were the primary outcomes. Results: Eighteen HIV-infected children completed the follow-up period (mean age 11.5 ± 4.14 years, 61% female). The nutritional supplement was safe but did not enhance the response to the influenza vaccine. A 4-fold rise in antibody titers was obtained in only 37.5% of participants in the intervention arm vs. 40% in the placebo. No immunological or inflammatory predictors of vaccine response were identified. Conclusions: In this exploratory study, a 4-week course of symbiotics did not increase influenza vaccine immunogenicity in HIV-infected children. Larger studies are warranted to address the potential of modulating the microbiome in children living with HIV.This work was funded by the Instituto de Salud Carlos III-Fondos FEDER (grant number CB21/17/00025), Acción Estratégica en Salud (PI13/0422, PI17/01283, PI18/00154, and PI18CIII/00009). TS and SS-V have been funded by the Instituto de Salud Carlos III-Fondos FEDER (BA21/00022 and BA21/00017). The funding bodies did not have a role in the design or conduct of the study, the analysis and interpretation of the results, and the writing of the report or the decision to publish. The authors would like to particularly acknowledge all the children and adolescents as well as their families for their participation in this study. They acknowledge the Spanish Pediatric HIV infection Group CORISPE and the Pediatric HIV BioBank integrated in the Spanish AIDS Research Network and collaborating Centers [supported by the Instituto de Salud Carlos III, Spanish Health Ministry (Grant n◦ RD06/0006/0035)] for its collaboration and cession of clinical information and samples used in this work. Nutricion Médica S.L., manufactured and packaged the nutritional product under investigation. Final results of this work have been presented at the following meetings: 36rd Annual Meeting of the European Society for Pediatric Infectious Diseases (ESPID 2018), Malmö, Sweden, 28th May-June 2nd, 2018. (Ref. ESP18-0517).S