RESUMO
From chemistry design to clinical application, several approaches have been developed to overcome platinum drawbacks in antitumoral therapies. An in-depth understanding of intracellular signaling may hold the key to the relationship of both conventional drugs and nanoparticles. Within these strategies, first, nanotechnology has become an essential tool in oncotherapy, improving biopharmaceutical properties and providing new immunomodulatory profiles to conventional drugs mediated by activation of endoplasmic reticulum (ER) stress. Secondly, functional proteomics techniques based on microarrays have proven to be a successful method for high throughput screening of proteins and profiling of biomolecule mechanisms of action. Here, we conducted a systematic characterization of the antitumor profile of a platinum compound conjugated with iron oxide nanoparticles (IONPs). As a result of the nano-conjugation, cytotoxic and proteomics profiles revealed a significant improvement in the antitumor properties of the starting material, providing selectivity in certain tumor cell lines tested. Moreover, cell death patterns associated with immunogenic cell death (ICD) response have also been identified when ER signaling pathways have been triggered. The evaluation in several tumor cell lines and the analysis by functional proteomics techniques have shown novel perspectives on the design of new cisplatin-derived conjugates, the high value of IONPs as drug delivery systems and ICD as a rewarding approach for targeted oncotherapy and onco-immunotherapies.
RESUMO
Objetivo: evaluar si en la literatura científica se describe una relación entre obesidad y dislipidemia con progresión a deterioro cognitivo leve (DCL) y demencia en adultos mayores de 65 años. Métodos: búsqueda en la literatura científica publicada en PubMed, EbscoHost, ScienceDirect, ClinicalKey y Registro Cochrane entre 2009 y 2017, de estudios prospectivos de cohortes, casos y controles de sujetos adultos con diagnóstico de obesidad o dislipidemia y con valoraciones de la función cognitiva a través del tiempo, con el fin de determinar la incidencia de DCL y demencia, y su relación con los factores de riesgo mencionados. Resultados: la revisión sistemática arrojó un total de 13 artículos de alta calidad según SIGN que cumplieron con los criterios de selección. De estos 7 incluyen la obesidad como factor de riesgo y 6 la dislipidemia. En los diferentes artículos relacionados con obesidad en adultos mayores no existió relación directa entre obesidad y deterioro cognitivo, de igual forma en los relacionados con dislipidemia no se reportó relación directa con deterioro cognitivo. Conclusión: los pacientes adultos mayores con obesidad podrían tener un factor protector frente al desarrollo de deterioro cognoscitivo, lo que no ocurre con adultos jóvenes. Por su parte, la fisiopatología descrita en la dislipidemia sugiere que el colesterol alto o bajo pueden llevar a DCL y a demencia.
Objective: to evaluate if the scientific literature describes a relationship between obesity and dyslipidemia with a risk of mild cognitive decline and dementia in people aged 65-years or older. Methods: a search of case-control and cohort prospective studies in the scientific literature published in PubMed, EbscoHost, ScienceDirect ClinicalKey and Cochrane databases between 2009 and 2017, on elderly adults diagnosed with obesity or dyslipidemia undergoing cognitive function assessment over time to identify the incidence of mild cognitive decline and dementia and its relationship with said risk factors. Results: the systematic review provided 13 high-quality articles according to the SIGN scale, which met the inclusion criteria. Seven included obesity as risk factor and six dyslipidemia. In articles on obesity in adults there was no direct relationship between obesity and cognitive impairment, with similar results observed for dyslipidemia. Conclusion: obesity in elderly individuals may have a protective effect against cognitive decline, not present in young adults. As to dyslipidemia, its physiopathology suggests that high or low cholesterol values may lead to mild cognitive decline and dementia.