214 research outputs found

    Neurolysin knockout mice generation and initial phenotype characterization

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    The oligopeptidase neurolysin (EC 3.4.24.16; Nln) was first identified in rat brain synaptic membranes and shown to ubiquitously participate in the catabolism of bioactive peptides such as neurotensin and bradykinin. Recently, it was suggested that Nln reduction could improve insulin sensitivity. Here, we have shown that Nln knockout mice (KO) have increased glucose tolerance, insulin sensitivity and gluconeogenesis. KO mice have increased liver mRNA for several genes related to gluconeogenesis. Isotopic label semi-quantitative peptidomic analysis suggests increase in specific intracellular peptides in gastrocnemius and epididymal adipose tissue, which likely is involved with the increased glucose tolerance and insulin sensitivity in the KO mice. These results suggest the exciting new possibility that Nln is a key enzyme for energy metabolism and could be a novel therapeutic target to improve glucose uptake and insulin sensitivity

    Laurus nobilis (laurel) aqueous leaf extract's toxicological and anti-tumor activities in HPV16-transgenic mice

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    Cancers induced by human papillomavirus (HPV) infection remain a significant public health threat, fueling the study of new therapies. Laurel (Laurus nobilis) compounds and extracts recently showed in vitro activity against HPV-transformed cell lines. This work aims to evaluate the in vivo efficacy and hepatic toxicity of a laurel extract in a transgenic mouse model of HPV16-induced cancer. The extract was administered in drinking water (20 mg per animal per day) for three consecutive weeks, using four experimental groups (n = 10) (group I: HPV16−/− without treatment, group II: treated HPV16−/−, group III: HPV16+/− without treatment and group IV: treated HPV16+/−). Following the treatment period, animals were sacrificed and skin samples were used to classify skin lesions histologically. Toxicological parameters included hematological and biochemical blood markers, splenic and hepatic histology and hepatic oxidative stress. The extract did not prevent the progression of HPV16-induced cutaneous lesions in this model. The treated wildtype animals showed mild hepatitis, while transgenic animals suffered weight loss. However, there were no changes concerning hematological, biochemical and hepatic oxidative stress markers.This work was supported by: Integrative Research in Environment, Agro-Chains and Technology no. NORTE-01- 0145-FEDER-000017, in its line of research entitled ISAC, cofinanced by the European Regional Development Fund (ERDF) through NORTE 2020 (North Regional Operational Program 2014/2020). European Investment Funds by FEDER/COMPETE/ POCI– Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT - Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013. This study was also funded by Liga Portuguesa Contra o Cancro, by the Research Center of the Portuguese Institute of Oncology of Porto (CI-IPOP 37-2016), by project POCI-01-0145- FEDER-006939 (Laboratory for Process Engineering, Environment, Biotechnology and Energy – LEPABE), project POCI-01-0145-FEDER-006958 and UID/AGR/04033/2013, funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) – and by national funds through FCT – Fundação para a Ciência e a Tecnologia; Rui M. Gil da Costa was funded by grant number SFRH/BPD/85462/2012 from FCT, funded by the Portuguese Government and the Social European Fund. The authors are also grateful to FCT, Portugal and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/ 00690/2013), and to the Interreg España-Portugal for financial support through the project 0377_Iberphenol_6_E.info:eu-repo/semantics/publishedVersio

    Transitions of cardio-metabolic risk factors in the Americas between 1980 and 2014

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    Describing the prevalence and trends of cardiometabolic risk factors that are associated with non-communicable diseases (NCDs) is crucial for monitoring progress, planning prevention, and providing evidence to support policy efforts. We aimed to analyse the transition in body-mass index (BMI), obesity, blood pressure, raised blood pressure, and diabetes in the Americas, between 1980 and 2014
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