Mapping research in the obesity, adipose tissue, and microRNA field: a bibliometric analysis

Recent studies have investigated the control of adipose tissue expansion and inflammatory process by microRNAs (miRNAs). These two processes are of great interest because both are associated with obesity and metabolic syndrome. However, despite the great relevance of the role of miRNAs in obesity and adipose tissue, no qualitative and quantitative analysis on the subject has been performed. Thus, we aimed to examine global research activity and current trends with respect to the interaction between obesity, adipose tissue and miRNAs through a bibliometric analysis. This research was performed on the Scopus database for publications containing miRNA, obesity, and adipose tissue keyword combinations. In total, 898 articles were analyzed and the most frequently occurring keywords were selected and clustered into three well-defined groups. As a result, first group of keywords pointed to the research area on miRNAs expressed in obesity-associated diseases. The second group demonstrated the regulation of the adipogenesis process by miRNAs, while the third group highlighted brown adipose tissue and thermogenesis as one of the latest global research trends related to the theme. The studies selected in this paper describe the expression and performance of different miRNAs in obesity and comorbidities. Most studies have focused on identifying miRNAs and signaling pathways associated with obesity, type 2 diabetes mellitus, and cardiovascular disease. Thus, the miRNA profile for these diseases may be used as biomarkers and therapeutic targets in the prevention and treatment of obesity-associated diseases812CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP132365/2018-9sem informação17/09602-4; 2017/19504-

Advances in Breast Cancer Management and Extracellular Vesicle Research, a Bibliometric Analysis

Extracellular vesicles transport variable content and have crucial functions in cell–cell communication. The role of extracellular vesicles in cancer is a current hot topic, and no bibliometric study has ever analyzed research production regarding their role in breast cancer and indicated the trends in the field. In this way, we aimed to investigate the trends in breast cancer management involved with extracellular vesicle research. Articles were retrieved from Scopus, including all the documents published concerning breast cancer and extracellular vesicles. We analyzed authors, journals, citations, affiliations, and keywords, besides other bibliometric analyses, using R Studio version 3.6.2. and VOSviewer version 1.6.0. A total of 1151 articles were retrieved, and as the main result, our analysis revealed trending topics on biomarkers of liquid biopsy, drug delivery, chemotherapy, autophagy, and microRNA. Additionally, research related to extracellular vesicles in breast cancer has been focused on diagnosis, treatment, and mechanisms of action of breast tumor-derived vesicles. Future studies are expected to explore the role of extracellular vesicles on autophagy and microRNA, besides investigating the application of extracellular vesicles from liquid biopsies for biomarkers and drug delivery, enabling the development and validation of therapeutic strategies for specific cancers

Effects of copper metal complexes on triple negative breast cancer

Breast cancer is the second most common type in the world and can be considered a disease with good prognosis if diagnosed early and treated timely. The treatment of breast cancer aims to increase survival and improve the quality of life of women. Chemotherapy drugs cause DNA damage to both tumor and normal cells. Cisplatin is considered one of the best drugs in the treatment of various cancers in the world, but it has several side effects. Research into replacing platinum with another metal center, such as copper and ruthenium, shows advantages mainly in its ability to lessen side effects. In this sense, the objective of the present study was to evaluate the effect of copper complexes in in vitro experimental models on different tumor and non-tumoral breast cell lines. For this, different in vitro experiments were performed using the non-tumor human breast cell lines MCF-10A, the human tumoral cell lines MDA-MB-231, MCF-7, SK-BR3, mouse fibroblast L929 and mouse tumor 4t1.The results demonstrated that the copper [Cu(sdmx-)2(phen)].H2O complex was the most effective in inducing toxicity in triple negative subtype breast tumor cells (MDA-MB-231) compared to non-tumoral breast cell line MCF-10A, which was slightly more resistant to the same complex. Furthermore, it was able to decrease the number and size of colonies, modify the structure of the cytoskeleton, and inhibit cell migration. The importance of copper transporter protein 1, CTR1, was also verified by cell transfection, in which after this process, gene expression was increased approximately ten-fold in transfected MDA-MB-231 cells, and that the complex [CuCl2(-impy)] was more cytotoxic in these cells compared to non-transfected cells. This can be attributed to the presence of vacant points in copper through the loss of chloride ions, which allows their interaction with CTR1 and greater uptake through it. In summary, the results show that the [Cu(sdmx-)2(phen)].H2O and [CuCl2(-impy)] complexes were cytotoxic to tumor cell line MDA-MB-231 and that increased expression of CTR1 caused sensitization in transfected cells upon treatment with the [CuCl2(-impy)] complex. Further studies should be performed with the [Cu(sdmx-)2(phen)].H2O and [CuCl2(-impy)] complexes for understanding of the mechanisms of action and the influence of CTR1 in this process. In addition, considering CTR1 as a target in tumor cells supports the development of strategies that use rational drug design to improve therapeutic efficacy through greater specificity and consecutive reduction of side effects.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)O câncer de mama é o segundo tipo mais comum no mundo e pode ser considerado uma doença com bom prognóstico se diagnosticado precocemente e tratado oportunamente. O tratamento do câncer de mama tem como objetivos principais aumentar a sobrevida e melhorar a qualidade de vida da mulher. Os fármacos utilizados na quimioterapia causam danos ao DNA, tanto das células tumorais, como também das normais. O cisplatina é considerado um dos melhores medicamentos no tratamento de vários tipos de câncer no mundo, contudo apresenta diversos efeitos colaterais. Pesquisas realizando a substituição da platina por outro centro metálico, como o cobre e rutênio, mostram vantagens principalmente na capacidade de diminuir efeitos colaterais. Neste sentido, o objetivo do presente trabalho foi avaliar o efeito de complexos de cobre em modelos experimentais in vitro em diferentes linhagens celulares tumorais e não tumorais de mama. Para isso, diferentes experimentos in vitro foram realizados utilizando as linhagens celulares não-tumoral de mama humana MCF-10A, as células tumorais humanas MDA-MB-231, MCF-7, SK-BR3, fibroblasto de camundongo L929 e tumoral de camundongo 4t1. Os resultados demonstram que o complexo de cobre [Cu(sdmx-)2(phen)].H2O foi o mais eficaz em induzir a toxicidade em células tumorais de mama do subtipo triplo negativo (MDA-MB-231), em comparação com a linhagem não tumoral de mama MCF-10A, que se mostrou ligeiramente mais resistente ao mesmo complexo. Ainda, este foi capaz de diminuir o número e tamanho de colônias, modificar a estrutura do citoesqueleto, e inibir a migração celular. Também foi constatado a importância do transportador de cobre 1, CTR1, por meio de transfecção celular. Após este processo, observou-se aumento da expressão gênica de CTR1 em aproximadamente dez vezes nas células MDA-MB-231 transfectadas, e que o complexo [CuCl2(-impy)] mostrou-se mais citotóxico nestas células em comparação às células não transfectadas, podendo isto ser atribuído à presença de pontos vacantes no cobre por meio da perda dos íons cloretos, o que permite sua interação com o CTR1 e maior captação por meio deste. Em suma, os resultados mostram que os complexos [Cu(sdmx-)2(phen)].H2O e [CuCl2(-impy)] foram citotóxicos para as células tumorais da linhagem MDA-MB-231 e que o aumento da expressão de CTR1 provocou sensibilização nas células transfectadas frente ao tratamento com o complexo [CuCl2(-impy]. Mais estudos devem ser realizados com os complexos [Cu(sdmx-)2(phen)].H2O e [CuCl2(-impy)] visando a compreensão dos mecanismos de ação e a influência do CTR1 neste processo. Além disso, considerar o CTR1 como alvo em células tumorais embasa o desenvolvimento de estratégias que se utilizem do desenho racional de fármacos visando melhorar a eficácia terapêutica, por meio de maior especificidade e consecutiva redução de efeitos colaterais.FAPESP: 17/19504-0FAPESP: 18/17170-0CAPES: Código de Financiamento 00

Advances in breast cancer management and extracellular vesicle research, a bibliometric analysis

Extracellular vesicles transport variable content and have crucial functions in cell–cell communication. The role of extracellular vesicles in cancer is a current hot topic, and no bibliometric study has ever analyzed research production regarding their role in breast cancer and indicated the trends in the field. In this way, we aimed to investigate the trends in breast cancer management involved with extracellular vesicle research. Articles were retrieved from Scopus, including all the documents published concerning breast cancer and extracellular vesicles. We analyzed authors, journals, citations, affiliations, and keywords, besides other bibliometric analyses, using R Studio version 3.6.2. and VOSviewer version 1.6.0. A total of 1151 articles were retrieved, and as the main result, our analysis revealed trending topics on biomarkers of liquid biopsy, drug delivery, chemotherapy, autophagy, and microRNA. Additionally, research related to extracellular vesicles in breast cancer has been focused on diagnosis, treatment, and mechanisms of action of breast tumor-derived vesicles. Future studies are expected to explore the role of extracellular vesicles on autophagy and microRNA, besides investigating the application of extracellular vesicles from liquid biopsies for biomarkers and drug delivery, enabling the development and validation of therapeutic strategies for specific cancers

Copper transporter 1 affinity as a delivery strategy to improve the cytotoxic profile of rationally designed copper(II) complexes for cancer treatment

Cisplatin is widely used to treat different types of cancer, but its severe side effects are the major disadvantage of this treatment. Therefore, other metals are currently the subject of research in the rational development of anticancer drugs, such as copper, that has been demonstrated to be promising in this scenario. Here, we evaluated the effects of two novel copper complexes against breast cancer cell lines, and also examined the influence of overexpressing copper transporter 1 (CTR1) on the cytotoxicity of these complexes. Complex (1) [Cu(sdmx−)2(phen)] showed low IC50 values, induced intense cell morphological changes and arrested the cell cycle at the sub-G1 phase in cancer cells. Complex (1) was tested in transfected cells overexpressing the CTR1 receptor in order to compare its steric effects with a less bulky ligand and more labile complex (2) [CuCl2(impy)]. A significant reduction of IC50 value was observed in CTR1 overexpressing cells for complex (2) (32 μM to 20 μM) as compared to (1) (2.78 μM to 3.41 μM), evidencing a possible uptake through copper reduction (Cu+2 → Cu+1) mediated by CTR1. Thus, considering that CTR1 is a mediator of metallodrugs uptake, the development of strategies that use rational drug design is important in order to improve the therapeutic efficacy through greater specificity and consecutive reduction of side effects. Here we show the example for the case of copper(II) complexes67FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2015/20882-3; 2017/19504-0; 2018/17170-0; 2013/07600-3; 2018/12062-

The Role Of Community Physical Therapy In The Functional Independence And Quality Of Life Of Elderly Women

Introduction: The elderly population demands special and specific measures focused on the promotion of health and quality of life. The Family Health Support Centers  seek to increase the operational scope of the Family Health Strategy through the inclusion of different professionals, including physiotherapists, who develop their activities with the elderly by focusing on educational measures and preventive and health promoting corporal practices.Objectives: Evaluate the importance of Physical Therapy in the Family Health Support Centers for the functional independence and quality of life of elderly women.Methodology: Descriptive research with a case control epidemiological base performed in the Family Health Support Centers of the city of Parnaíba/PI. 88 individuals participated  in this study, all of them female, of which 46  participated in the Physical Therapy activities (G1) and 42 didn't (G2). Quality of life was measured according to the Health-Related Quality of Life (HRQOL) profile for independent elderly, and functionality was analyzed according to the Katz scale. The project was approved by the Ethics Committee for Research of the Universidade Federal do Piauí under the number: 1.087.464. The statistical analyses were performed using the unpaired Student's t test in samples of normal distribution, and using the Mann-Whitney test in samples of non-normal distribution. The normality of groups was analyzed using the Shapiro-Wilk test. The considered level of significance was p≤0,05.Results: According to the Katz index, a better performance could be observed for G1, where 91.3% (n=42) obtained a score of 6, which means a greater level of independence, when compared to G2, where 61.9% (n=26) obtained a score of 6 and 38.1% (n=16) scores between 5 and 3, indicating moderate dependency. According to the HRQOL questionnaire, G1 had a better perception of health.CONCLUSION: The elderly who participated in the activities proposed by the physical therapists of the Family Health Support Centers had better functionality and health perception indicators