Search results for "Wester"

Gestión del agua subterránea de uso agrícola: Los retos de la sostenibilidad socio-ambiental y la equidad

2018

The combination of PDE4 and PDE5 inhibitors reduces YAP expression in IPF

2017

Background: Pathological fibrosis is associated with repeated episodes of injury to alveolar epithelial cells of largely. Yes-associated protein (YAP) is prominently expressed in fibrotic lung. Roflumilast has demonstrated to exhibit anti-fibrosis effects, while PDE5 inhibitors (sildenafil) combinated with PDE4 inhibitors reduce fibrotic-effects secondary to TGFs1. Apparently, no studies of PDE4 and PDE5 inhibitors on YAP expression there are. Objectives: To study the effects from adding a sildenafil to Roflumilast N- oxide (RNO) on TGF-β/SMAD3/YAP pathway in IPF in vitro models. Methods: A549 cells were pre-incubated with therapeutical concentrations of RNO (2nM) and/or sildenafil (10nM) a…

Statins and the squalene synthase inhibitor zaragozic acid stimulate the non-amyloidogenic pathway of amyloid-beta protein precursor processing by su…

2010

Cholesterol-lowering drugs such as statins influence the proteolytic processing of the amyloid-beta protein precursor (AbetaPP) and are reported to stimulate the activity of alpha-secretase, the major preventive secretase of Alzheimer's disease. Statins can increase the alpha-secretase activity by their cholesterol-lowering properties as well as by impairment of isoprenoids synthesis. In the present study, we elucidate the contribution of these pathways in alpha-secretase activation. We demonstrate that zaragozic acid, a potent inhibitor of squalene synthase which blocks cholesterol synthesis but allows synthesis of isoprenoids, also stimulates alpha-secretase activity. Treatment of human n…

Putative molecular determinants mediating sensitivity or resistance towards carnosic acid tumor cell responses.

2020

Abstract Background Carnosic acid (CA) is one of the main constituents in rosemary extract. It possesses valuable pharmacological properties, including anti-oxidant, anti-inflammatory, anti-microbial and anti-cancer activities. Numerous in vitro and in vivo studies investigated the anticancer profile of CA and emphasized its potentiality for cancer treatment. Nevertheless, the role of multidrug-resistance (MDR) related mechanisms for CA's anticancer effect is not yet known. Purpose We investigated the cytotoxicity of CA against known mechanisms of anticancer drug resistance (P-gp, ABCB5, BCRP, EGFR and p53) and determined novel putative molecular factors associated with cellular response to…

Un nuevo suido con dientes yugales tubulidentados e hipselorrizos del Mioceno inferior de Córcoles, España

2018

[EN] Excavations at Córcoles, Guadalajara, Spain (MN 4) in October 1987, yielded a mandible and several isolated teeth of a strange suiform with tubulidentate cheek teeth, initially interpreted to be the remains of Tubulidentata. The specimens are complete enough to remove any doubt about which Order (Artiodactyla) and Superfamily (Suoidea) they belong to. They are here attributed to the Family Doliochoeridae, being related to the genera Bransatochoerus (MP 30) and Lorancahyus (MN 2) both of which have hypsorhizic cheek teeth, the latter with tubules in the teeth, but not to the fully-expressed extent seen in the fossils from Córcoles and the molars retain a distinct and large pulp cavity, …

60KDa chaperonin (HSP60) is over-expressed during colorectal carcinogenesis

2003

The aim of the present study was to evaluate the expression of the heat shock protein 60 (HSP60), a mitochondrial matrix-associated protein belonging to the chaperonin family, in colorectal adenomas and cancers, comparing them to normal colonic tissues and hyperplastic polyps. We performed both immunohistochemistry and Western blot analysis for HSP60. Immunohistochemistry resulted positive in all tubular adenomas and infiltrating adenocarcinomas. By contrast, normal tissues and hyperplastic polyps were negative. Quantitative analysis showed that tubular adenomas with different levels of dysplasia did not present statistical differences concerning HSP60 positivity. In addition, carcinomas al…

Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations.

2010

Hofer D, Paul K, Fantur K, Beck M, Roubergue A, Vellodi A, Poorthuis BJ, Michelakakis H, Plecko B, Paschke E. Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations. GM1 gangliosidosis manifests with progressive psychomotor deterioration and dysostosis of infantile, juvenile, or adult onset, caused by alterations in the structural gene coding for lysosomal acid s-galactosidase (GLB1). In addition, allelic variants of this gene can result in Morquio B disease (MBD), a phenotype with dysostosis multiplex and entire lack of neurologic involvement. More than 100 sequence alterations in the GLB1 gene have been identified so far, but only few could be proven to …

Azathioprine suppresses ezrin-radixin-moesin-dependent T cell-APC conjugation through inhibition of Vav guanosine exchange activity on rac proteins

2006

Abstract We have shown recently that the azathioprine metabolite 6-Thio-GTP causes immunosuppression by blockade of GTPase activation in T lymphocytes. In the present study, we describe a new molecular mechanism by which 6-Thio-GTP blocks GTPase activation. Although 6-Thio-GTP could bind to various small GTPases, it specifically blocked activation of Rac1 and Rac2 but not of closely related Rho family members such as Cdc42 and RhoA in primary T cells upon stimulation with αCD28 or fibronectin. Binding of 6-Thio-GTP to Rac1 did not suppress Rac effector coupling directly but blocked Vav1 exchange activity upon 6-Thio-GTP hydrolysis, suggesting that 6-Thio-GTP loading leads to accumulation of…

X-Linked Dilated Cardiomyopathy.

1995

We report on a family with a severe form of X-linked dilated cardiomyopathy (DCM). Two brothers, the elder requiring heart transplantation, and a maternal cousin presented elevated creatine kinase levels, increased right ventricular diameters and electrocardiographic abnormalities. All complained of exertional cramping myalgia, but none had muscle weakness or a pathological electromyogram. Muscle biopsies of these individuals revealed a mild myopathic picture with atrophic type I and hypertrophic type II fibers. Immunofluorescence using N- and C-terminal antibodies (dys-2, dys-3) against the dystrophin protein showed preserved, but reduced intensity of staining of the sarcolemmal membranes.…

Testing the Cross-Cultural Robustness of the Minority Stress Model in Gay and Bisexual Men

2017

The study tests the cross-cultural robustness of the minority stress model using a most different systems approach. Data from Western European, Eastern European (including Russian), Indian, Philippine, and Thai gay and bisexual men was obtained online. The final sample consisted of N = 90,467 participants who reported their level of satisfaction with life, victimization, felt stigma, and internalized homonegativity, as well as their disclosure status and sociodemographic details. Stepwise linear regressions were conducted on reported levels of satisfaction with life. Higher levels of victimization, felt stigma, and internalized homonegativity predicted lower satisfaction with life in all gr…