Regulação molecular do ritmo circadiano e transtornos psiquiátricos: uma revisão sistemática / Molecular regulation of circadian rhythm and psychiatric disorders: a systematic review

RESUMO Objetivo O artigo possui como objetivo investigar os genes relógio que estão mais associados com os transtornos psiquiátricos, as funções e localizações desses genes, assim como investigar o principal transtorno, método e modelo considerados nas análises. O trabalho busca resumir os achados e discutir o impacto dessas pesquisas no conhecimento científico. Métodos Esta revisão utilizou-se de uma metodologia sistemática (Prospero; ID 152031) e seguiu as diretrizes PRISMA. A busca dos estudos foi realizada nas bases de dados PubMed/MEDLINE e Scientific Eletronic Library Online e foram utilizados os termos do Medical Subject Headings Terms . Foram selecionados estudos quantitativos com resultados conclusivos referentes à associação de transtornos psiquiátricos com a regulação molecular do ritmo circadiano. As informações úteis foram extraídas e utilizadas para a elaboração de gráficos e tabelas. Resultados Foram incluídos 24 artigos em nosso estudo. Observou-se que o transtorno bipolar consistiu no transtorno psiquiátrico mais abordado (40% dos estudos); a nacionalidade polonesa dos participantes também se destacou em 39% dos trabalhos. Adicionalmente, o gene PER foi o mais estudado (25%) e o córtex cerebral foi a principal região em que os genes relógio avaliados se expressam (34%). A PCR comum mostrou ser o método mais utilizado (38%) e o metabolismo da serotonina mostrou ser a principal função desempenhada pelos produtos gênicos (16%). Conclusões Em conjunto, os resultados sugerem que o transtorno bipolar consiste no distúrbio psiquiátrico mais prevalente entre as pesquisas relacionadas aos genes circadianos, expressos principalmente no córtex cerebral de humanos, em especial o gene PER .

ABSTRACT Objective The article aims to investigate the clock genes that are most associated with psychiatric disorders, the functions, and locations of these genes, as well as to investigate the main disorder, method and model in the analyzes. The paper seeks to summarize the findings and discuss the impact of this research on scientific knowledge. Methods This review used a systematic methodology (Prospero; ID 152031) and followed the PRISMA guidelines. The studies were searched in the PubMed/MEDLINE and Scientific Electronic Library Online databases and the terms of the Medical Subject Headings Terms were used. Quantitative studies with conclusive results regarding the association of psychiatric disorders with the molecular regulation of circadian rhythm were selected. The useful information was extracted and used for the elaboration of graphs and tables. Results We included 24 articles in our study. Bipolar disorder was the most commonly addressed psychiatric disorder (40% of studies); The participants' Polish nationality also stood out in 39% of the works. Additionally, the PER gene was the most studied (25%) and the cerebral cortex was the main region in which the evaluated clock genes express themselves (34%). Finally, common PCR was the most used method (38%) and serotonin metabolism was the main function performed by gene products (16%). Conclusions Taken together, the results suggest that bipolar disorder is the most prevalent psychiatric disorder among research related to circadian genes, expressed mainly in the cerebral cortex of humans, especially the PER gene.

Study of the relationship between vitamin D deficiency, sunlight incidence and skeletal/extra skeletaldiseases

It is estimated that more than 1 billion people worldwide have vitamin D insufficiency or deficiency. Vitamin D participates in bone mineralization, and is therefore important in osteoporosis, osteomalacia and rickets prevention. However, vitamin D deficiency could also be associated with several other pathologies. The present study aimed to investigate the relationships between vitamin D deficiency and vitamin D deficiency-related disorders in patients. In addition, this study aims to verify if countries with low solar incidence have higher extraskeletal disease death rates when compared to countries with high solar incidence. The vitamin D concentrations were obtained from the Heart Hospital database (Natal/Brazil). The relationship between solar incidenceand death rate for vitamin D deficiency-related disorders was verified. Death rate data were extracted from the 'World Life Expectancy' repository and data about solar incidence were obtained from NASA's Surface Meteorology and Solar Energy project. Thesedata were statistically processed with IBM SPSS v23.0 software and R programming language. Our results showed that patients with vitamin D insufficiency/deficiency showed significantly more bone diseases, thyroid diseases, hypercholesterolemy, hypertriglyceridemia, cancers, diabetes, hepatobiliary diseases, and urinary system diseases. Moreover, countries with high solar incidence have low cancer and multiple sclerosis death rates. This work suggests the participation of vitamin D and sunlight incidence inseveral diseases.

Study of comparative proteome between normal and inverted karyotypes of human mesenchymal stem cells

Multipotent mesenchymal stem cells have been expanded in vitro for cellular therapy in numerous clinical settings without standardized culture conditions or quality-control schemes. The in vitro expansion is necessary to obtain sufficient cells for clinical applications. However, the expansion may induce genetic and functional abnormalities which may affect the safety and functionality of MSC, especially the chromosomal stability. This study aimed to investigate the protein profile of umbilical cord-derived MSC with normal and inverted karyotypes after expansion in the laboratory. Mass spectrometry analysis was performed and the Bradford method, Scaffold software, String and Cytoscape databases were employed to measure and characterize the protein content of umbilical cord-derived MSC. Networks of protein interactions, hub and bottleneck proteins were identified by proteomics and systems biology approaches. We found that proteins related to cellular stress were super expressed in inverted karyotype cells. Moreover, a high expression of Serpine 1, RHOA, and CTSB was found in these cells, which are proteins related to cancer. The albumin and ubiquitin proteins have been associated with a positive prognosis in cancer and cellular stress, and were up- and down-regulated in normal karyotype cells, respectively. The results suggests that the paracentric inversion inv(3)(p25p13) induced some type of cellular stress and genetic instability in human mesenchymal stem cells. These analyses showed the importance of carrying out studies related to the genetic instability of human mesenchymal stem cells using the protein expression profile as a parameter.

Receptores neurais e a doença de Alzheimer: uma revisão sistemática da literatura sobre as famílias de receptores mais associadas a doença, suas funções e áreas de expressão / Neural receptors and Alzheimer's disease: a systematic review of the literature on receptor families most associated with the disease, their functions and expression areas

RESUMO Objetivo O artigo tem como objetivo determinar as famílias de receptores mais estudadas, envolvidas com a doença de Alzheimer, assim como determinar a região do sistema nervoso na qual mais tipos de receptores são expressos e quais funções dos receptores estão predominantemente associadas com a patologia em questão. O artigo busca mostrar os modelos e métodos mais utilizados nessas pesquisas, resumindo alguns achados e discutindo o impacto desses estudos no conhecimento científico. Métodos Esta revisão utilizou-se de uma metodologia sistemática (Prospero; ID 141957). Resultados Pode-se constatar que os receptores de transcrição nuclear foram os mais estudados. A maior parte desses receptores se expressa no córtex cerebral e hipocampo. Adicionalmente, a maioria das pesquisas avaliou os receptores relacionados com os efeitos benéficos na doença. A eliminação da proteína amiloide ou o bloqueio de vias relacionadas à síntese dessa proteína foram as principais funções desempenhadas por esses receptores. Por fim, as técnicas de imunoistoquímica e reação em cadeia de polimerase em tempo real (RT-PCR), respectivamente, foram as mais utilizadas, e os roedores consistiram no principal modelo de estudo. Conclusões Os receptores de transcrição nuclear, o córtex cerebral, o hipocampo, a micróglia e a proteína beta-amiloide mostraram importância na patogênese da doença de Alzheimer neste estudo.

ABSTRACT Objective The article aims to find the receptors family involved with Alzheimer's disease most studied as well as the tissue that most receptors are expressed. This study also aims to determine the functions predominantly associated with the pathology. In addition, the work seeks to show the models and techniques most used, as well as summarize the findings and discuss the impact of these studies on scientific knowledge. Methods This review addressed a systematic methodology (Prospero; ID 141957). Results It can be seen that nuclear transcription receptors were the most studied. Most of these receptors are expressed in the cerebral cortex and hippocampus. Additionally, a great number of studies evaluated the receptors related to beneficial effects in the disease. The depletion of amyloid protein or the blockade of pathways related to its synthesis were the main functions performed by these receptors. Finally, immunohistochemistry and RT-PCR techniques, respectively, were the most used and the rodents were the main study model. Conclusions Nuclear transcription receptors, cerebral cortex and hippocampus, microglia, and amyloid beta protein have shown significant importance in the pathogenesis of Alzheimer's disease in this study.