Hakai reduces cell-substratum adhesion and increases epithelial cell invasion

BACKGROUND: The dynamic regulation of cell-cell adhesions is crucial for developmental processes, including tissue formation, differentiation and motility. Adherens junctions are important components of the junctional complex between cells and are necessary for maintaining cell homeostasis and normal tissue architecture. E-cadherin is the prototype and best-characterized protein member of adherens junctions in mammalian epithelial cells. Regarded as a tumour suppressor, E-cadherin loss is associated with poor prognosis in carcinoma. The E3 ubiquitin-ligase Hakai was the first reported posttranslational regulator of the E-cadherin complex. Hakai specifically targetted E-cadherin for internalization and degradation and thereby lowered epithelial cell-cell contact. Hakai was also implicated in controlling proliferation, and promoted cancer-related gene expression by increasing the binding of RNA-binding protein PSF to RNAs encoding oncogenic proteins. We sought to investigate the possible implication of Hakai in cell-substratum adhesions and invasion in epithelial cells. METHODS: Parental MDCK cells and MDCK cells stably overexpressing Hakai were used to analyse cell-substratum adhesion and invasion capabilities. Western blot and immunofluoresecence analyses were performed to assess the roles of Paxillin, FAK and Vinculin in cell-substratum adhesion. The role of the proteasome in controlling cell-substratum adhesion was studied using two proteasome inhibitors, lactacystin and MG132. To study the molecular mechanisms controlling Paxillin expression, MDCK cells expressing E-cadherin shRNA in a tetracycline-inducible manner was employed. RESULTS: Here, we present evidence that implicate Hakai in reducing cell-substratum adhesion and increasing epithelial cell invasion, two hallmark features of cancer progression and metastasis. Paxillin, an important protein component of the cell-matrix adhesion, was completely absent from focal adhesions and focal contacts in Hakai-overexpressing MDCK cells. The expression of Paxillin was found to be regulated by a proteasome-independent mechanism, possibly due to the decreased abundance of E-cadherin. CONCLUSIONS: Taken together, these results suggest that Hakai may be involved in two hallmark aspects of tumour progression, the lowering cell-substratum adhesion and the enhancement of cell invasion

Sol-gel coatings for protection and bioactivation of metals used in orthopaedic devices

The aim of this work is the production and characterisation of sol-gel coatings for protection and bioactivation of metals used as standard surgical implant materials, such as stainless steel 316 L (ASTM F138), Co based alloys (ASTM F75) and titanium alloy Ti-6A1-4V (ASTM F67). These films should both prevent degradation of the substrates by wear or corrosion, and bioactivate the material for inducing the formation of a hydroxyapatite (HA) rich layer onto the material surface, thereby permitting a natural bonding to living tissues. Formation of HA layers can be observed on performing in vitro tests by soaking the material in simulated body solutions. The work describes the development of coatings containing bioactive glass and glass-ceramic particles in hybrid methyl-triethoxysilane (MTES) and tetraethylorthosilicate (TEOS) acidic sol, applied by dip-coating to surgical alloys, AISI 316 L, ASTM F75 and ASTM 67, with the aim of accomplishing both high corrosion resistance of the metal in the body environment and adhesion of the implant to the surrounding tissue. The performance of the coated metal was evaluated in vitro by electrochemical techniques including potentiodynamic polarisation curves and electrochemical impedance spectroscopy, to follow the formation of hydroxyapatite on the surface, as well as the in vitro release of ions by plasma atomic emission spectroscopy (ICP-MS) after up to one year of immersion. In vivo behaviour was evaluated by subcutaneous tests and endomedullar implantation in Hokaido rats to study possible rejection reactions and natural bonding to living tissue.Peer Reviewe

Efficacy of a cognitive training and domotic control program (BCI) to prevent cognitive impairment

p. 6Con el tiempo, el envejecimiento puede causar un estado de discapacidad y dependencia. Este estudio tiene como objetivo evaluar la eficacia de entrenamiento cognitivo y control domótico con una computadora programa (Brain Computer Interface, BCI). Con el fin de hacer entonces, el rendimiento neuropsicológico estimado de los sujetos han sido evaluados con el ADN de Luria batería neuropsicológica antes y después del entrenamientoS

Proyecto de emprendimiento para la producción y comercialización de batidos “FRUTPAN” elaborados a base de la fruta de pan, ubicado en el municipio de Diriamba, departamento de Carazo, durante el segundo semestre del año 2020

El presente proyecto de emprendimiento se realizó con el fin de elaborar un producto innovador que cumpla con los estándares de calidad enfocada al cuido de la salud de los consumidores con un batido natural elaborado a base de la fruta de pan, mejorando la calidad de vida de las personas con enfermedades cardiovasculares y así determinar la factibilidad de la creación de la micro empresa batidos FRUTPAN dedicada al procesamiento y comercialización de batidos naturales ubicada en el municipio de Diriamba -Carazo. El estudio de mercado es el conjunto de acciones, el cual hemos ejecutado para conocer la respuesta del mercado potencial del producto nuevo, este nos ha permitido analizar la oferta, demanda, competencia y proveedores. así como el precio y los canales de distribución para la comercialización del producto batidos FRUTPAN conociendo la distribución geográfica adecuada de la ubicación para la micro empresa. El plan de producción es una herramienta en el cual se han definido los aspectos técnicos y organizativos para la elaboración del producto, esto es una parte relevante donde se describe cada uno de los procesos de elaboración del batido natural. En el plan de organización se construye cada una de las funciones y estructura de la micro empresa batidos FRUTPAN analizando cada uno del conjunto de relaciones estables de objetos y sujetos de la administracion en la organización implementado de forma organizativa y específicas. Por último, se presenta el plan financiero el cual es una herramienta donde se realizó el análisis de la viabilidad económica y financiera de la micro empresa batidos FRUTPAN en distintas perspectivas de su inversión de capital y en el cómo se apertura en sus proyecciones anuales que le permitirán la rentabilidad del negocio, iniciando con una inversión de C$ 234,804.41 en su operatividad de la micro empresa batidos FRUTPAN

Efficacy of a cognitive training and domotic control program (BCI) to prevent cognitive impairment

Over time, ageing can cause a state of disability and dependency. This study aims to evaluate the efficacy of cognitive training and domotic control with a computer program (Brain Computer Interface, BCI). In order to do so, estimated neuropsychological performance of the subjects has been evaluated with the Luria-DNA neuropsychological battery before and after training. A quasi-experimental design of repeated measures is defined where five areas are evaluated: visuospatial, spoken language, memory, intellectual processes and an attention test. Said study was carried out at The State Reference Centre for Disability and Dependency (CRE Spanish initials), San Andrés del Rabanedo, León (Spain). 63 people took part, 31 subjects in the experimental group and 32 in the control group. The results showed an improvement in almost all of the measured variables, revealing a significant increase in the cognitive capacity of the experimental group when compared with the control group. It can be concluded that with appropriate cognitive training, elderly people can delay cognitive impairment and enjoy an active ageing process which can have an effect on their life in terms of improving their independence

A novel procedure for protein extraction from formalin-fixed paraffin-embedded tissues

Most of the archived pathological specimens in hospitals are kept as formalin-fixed paraffin-embedded tissues (FFPE) for long-term preservation. Up to now, these samples are only used for immunohistochemistry in a clinical routine as it is difficult to recover intact protein from these FFPE tissues. Here, we report a novel, short time-consuming and cost-effective method to extract full-length, non-degraded proteins from FFPE tissues. This procedure is combined with an effective and non-toxic deparaffinisation process and an extraction method based on antigen-retrieval, high concentration of SDS and high temperature. We have obtained enough intact protein to be detected by Western blotting analysis. This technique will allow utilising these stored FFPE tissues in several applications for protein analysis helping to advance the translational studies in cancer and other diseases

Increased risk of MAFLD and liver fibrosis in inflammatory bowel disease independent of classic metabolic risk factors

ackground & Aims There is conflicting evidence regarding the prevalence of and risk factors for metabolic-associated fatty liver disease (MAFLD) in patients with inflammatory bowel disease (IBD). We aimed to determine MAFLD prevalence and risk factors in IBD patients. Methods Cross-sectional, case-control study included all consecutive IBD patients treated at 2 different university hospitals. Controls were subjects randomly selected from the general population and matched by age, sex, type 2 diabetes status, and body mass index in a 1:2 ratio. MAFLD was confirmed by controlled attenuation parameter. Liver biopsies were collected when MAFLD with significant liver fibrosis was suspected. In addition, age- and fibrosis stage-paired non-IBD patients with biopsy-proven MAFLD served as a secondary control group. Results Eight hundred thirty-one IBD patients and 1718 controls were included. The prevalence of MAFLD and advanced liver fibrosis (transient elastography ≥9.7 kPa) was 42.00% and 9.50%, respectively, in IBD patients and 32.77% and 2.31%, respectively, in the general population (P < .001). A diagnosis of IBD was an independent predictor of MAFLD (adjusted odds ratio, 1.99; P < .001) and an independent risk factor for advanced liver fibrosis (adjusted odds ratio, 5.55; P < .001). Liver biopsies were obtained from 40 IBD patients; MAFLD was confirmed in all cases, and fibrosis of any degree was confirmed in 25 of 40 cases (62.5%). Body mass index and type 2 diabetes prevalence were significantly lower in IBD-MAFLD patients than in severity-paired patients with biopsy-proven MAFLD. Conclusions MAFLD and liver fibrosis are particularly prevalent in IBD patients, regardless of the influence of classic metabolic risk factors.Acknowledgements: The authors report funding support from the Spanish Instituto de Salud Carlos III-FEDER Grant (FIS - PI18/01304) related to this manuscript

Effectiveness of rotavirus vaccination in Spain

With the aim of determining rotavirus vaccine effectiveness (RVVE) in Spain, from Oct-2008/Jun-2009, 467 consecutive children below 2 years old with acute gastroenteritis (AGE) were recruited using a pediatric research network (ReGALIP-www.regalip.org) that includes primary, emergency and hospital care settings. Of 467 enrolled children, 32.3% were rotavirus positive and 35.0% had received at least one dose of any rotavirus vaccine. RRVE to prevent any episode of rotavirus AGE was 91.5% (95% CI: 83.7%-95.6%). RVVE to prevent hospitalization by rotavirus AGE was 95.6% (85.6-98.6%). No differences in RVVE were found regarding the vaccine used. Rotavirus vaccines have showed an outstanding effectiveness in Spain