INPP4B protects from metabolic syndrome and associated disorders

A high fat diet and obesity have been linked to the development of metabolic dysfunction and the promotion of multiple cancers. The causative cellular signals are multifactorial and not yet completely understood. In this report, we show that Inositol Polyphosphate-4-Phosphatase Type II B (INPP4B) signaling protects mice from diet-induced metabolic dysfunction. INPP4B suppresses AKT and PKC signaling in the liver thereby improving insulin sensitivity. INPP4B loss results in the proteolytic cleavage and activation of a key regulator in de novo lipogenesis and lipid storage, SREBP1. In mice fed with the high fat diet, SREBP1 increases expression and activity of PPARG and other lipogenic pathways, leading to obesity and non-alcoholic fatty liver disease (NAFLD). Inpp4b−/− male mice have reduced energy expenditure and respiratory exchange ratio leading to increased adiposity and insulin resistance. When treated with high fat diet, Inpp4b−/− males develop type II diabetes and inflammation of adipose tissue and prostate. In turn, inflammation drives the development of high-grade prostatic intraepithelial neoplasia (PIN). Thus, INPP4B plays a crucial role in maintenance of overall metabolic health and protects from prostate neoplasms associated with metabolic dysfunction.

Predicting MiRNA-disease associations by multiple meta-paths fusion graph embedding model

Background Many studies prove that miRNAs have significant roles in diagnosing and treating complex human diseases. However, conventional biological experiments are too costly and time-consuming to identify unconfirmed miRNA-disease associations. Thus, computational models predicting unidentified miRNA-disease pairs in an efficient way are becoming promising research topics. Although existing methods have performed well to reveal unidentified miRNA-disease associations, more work is still needed to improve prediction performance. Results In this work, we present a novel multiple meta-paths fusion graph embedding model to predict unidentified miRNA-disease associations (M2GMDA). Our method takes full advantage of the complex structure and rich semantic information of miRNA-disease interactions in a self-learning way. First, a miRNA-disease heterogeneous network was derived from verified miRNA-disease pairs, miRNA similarity and disease similarity. All meta-path instances connecting miRNAs with diseases were extracted to describe intrinsic information about miRNA-disease interactions. Then, we developed a graph embedding model to predict miRNA-disease associations. The model is composed of linear transformations of miRNAs and diseases, the means encoder of a single meta-path instance, the attention-aware encoder of meta-path type and attention-aware multiple meta-path fusion. We innovatively integrated meta-path instances, meta-path based neighbours, intermediate nodes in meta-paths and more information to strengthen the prediction in our model. In particular, distinct contributions of different meta-path instances and meta-path types were combined with attention mechanisms. The data sets and source code that support the findings of this study are available at https://github.com/dangdangzhang/M2GMDA. Conclusions M2GMDA achieved AUCs of 0.9323 and 0.9182 in global leave-one-out cross validation and fivefold cross validation with HDMM V2.0. The results showed that our method outperforms other prediction methods. Three kinds of case studies with lung neoplasms, breast neoplasms, prostate neoplasms, pancreatic neoplasms, lymphoma and colorectal neoplasms demonstrated that 47, 50, 49, 48, 50 and 50 out of the top 50 candidate miRNAs predicted by M2GMDA were validated by biological experiments. Therefore, it further confirms the prediction performance of our method.

Fusing multiple biological networks to effectively predict miRNA-disease associations

Background: MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs with about 22 nucleotides and they play a significant role in a variety of complex biological processes. Many researches have shown that miRNAs are closely related to human diseases. Although the biological experiments are reliable in identifying miRNA-disease associations, they are time-consuming and costly. Objective: Thus, computational methods are urgently needed to effectively predict miRNA-disease associations. Method: In this paper, we proposed a novel method, BIRWMDA based on a bi-random walk model to predict miRNAdisease associations. Specifically, in BIRWMDA, the similarity network fusion algorithm is used to combine the multiple similarity matrices to obtain a miRNA-miRNA similarity matrix and a disease-disease similarity matrix, then the miRNAdisease associations were predicted by the bi-random walk model. Results: To evaluate the performance of BIRWMDA, we ran the leave-one-out cross validation and 5-fold cross validation, and their corresponding AUCs were 0.9303 and 0.9223 ± 0.00067, respectively. To further demonstrate the effectiveness of the BIRWMDA, from the perspective of exploring disease-related miRNAs, we conducted three case studies of breast neoplasms, prostate neoplasms and gastric neoplasms, where 48, 50 and 50 out of the top 50 predicted miRNAs were confirmed by literatures, respectively. From the perspective of exploring miRNA-related diseases, we conducted two case studies of hsa-mir-21 and hsa-mir-155, where 7 and 5 out of the top 10 predicted diseases were confirmed by literatures, respectively. Conclusion: Fusion of multiple biological networks could effectively predict miRNA-diseases associations. We expected BIRWMDA to severe as a biological tool for mining potential miRNA-disease associations.

The Panel of 12 Cell-Free MicroRNAs as Potential Biomarkers in Prostate Neoplasms

Prostate cancer is a global biological, medical, and social issue aggravated by the lack of reliable, highly specific, and sensitive non-invasive tests for diagnosis and staging of prostate cancer. One prospective source of biomarkers are the cell-free miRNAs present in various biological fluids. In the present study, we validated the diagnostic potential of cell-free miRNAs: miR-19b, miR-22, miR-92a, miR-378, miR-425, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375, and miR-660; we estimated the required sample size and the minimal miRNA set for a subsequent large-scale validation study. Relative expression of 12 miRNA combined in 31 ratios was investigated in three fractions of biological fluids (urine extracellular vesicles, clarified urine, and plasma) obtained from patients with prostate cancer (n = 10), benign prostate hyperplasia (n = 8), and healthy volunteers (n = 11). Eight of the miRNAs found in urine vesicles (miR-19b, miR-30e, miR-31, miR-92a, miR-125, miR-200, miR-205, and miR-660) showed great promise and when combined into six ratios (miR-125b/miR-30e, miR-200/miR-30e, miR-205/miR-30e, miR-31/miR-30e, miR-660/miR-30e, and miR-19b/miR-92a) could classify patients with prostate cancer, benign prostate hyperplasia, and healthy donors with 100% specificity, 100% sensitivity, and with a high degree of reliability for most donors.

Masculinities of prostate cancer survivors: a qualitative metasynthesis

ABSTRACT Objective: To identify the production of knowledge in the health literature about masculinities in the context of prostate cancer survivors and to analyze the implications of this relationship for the maintenance of health care. Method: Metasynthesis of 21 qualitative studies, performed in the LILACS, MEDLINE and CINAHL databases, with the scientific descriptors of DeCS and MeSH terms masculinity, prostate neoplasms. Results: Illness due to prostate cancer imposes numerous changes in male relationships, especially the non-dominance of the body and vulnerability to treatments and their consequences. The cultural values surrounding the disease and the hegemonic behaviors have implications for the health care of men. Conclusion: It has been shown that this relationship makes it difficult to communicate about the disease, marital relationships and family support, mainly influencing neglect of health. The knowledge produced is useful to promote the engagement of men in strengthening care.

A Novel Approach Based on a Weighted Interactive Network to Predict Associations of MiRNAs and Diseases

Accumulating evidence progressively indicated that microRNAs (miRNAs) play a significant role in the pathogenesis of diseases through many experimental studies; therefore, developing powerful computational models to identify potential human miRNA–disease associations is vital for an understanding of the disease etiology and pathogenesis. In this paper, a weighted interactive network was firstly constructed by combining known miRNA–disease associations, as well as the integrated similarity between diseases and the integrated similarity between miRNAs. Then, a new computational method implementing the newly weighted interactive network was developed for discovering potential miRNA–disease associations (WINMDA) by integrating the T most similar neighbors and the shortest path algorithm. Simulation results show that WINMDA can achieve reliable area under the receiver operating characteristics (ROC) curve (AUC) results of 0.9183 ± 0.0007 in 5-fold cross-validation, 0.9200 ± 0.0004 in 10-fold cross-validation, 0.9243 in global leave-one-out cross-validation (LOOCV), and 0.8856 in local LOOCV. Furthermore, case studies of colon neoplasms, gastric neoplasms, and prostate neoplasms based on the Human microRNA Disease Database (HMDD) database were implemented, for which 94% (colon neoplasms), 96% (gastric neoplasms), and 96% (prostate neoplasms) of the top 50 predicting miRNAs were confirmed by recent experimental reports, which also demonstrates that WINMDA can effectively uncover potential miRNA–disease associations.

CONHECIMENTOS, ATITUDES E CRENÇAS DE HOMENS RESIDENTES EM ARAXÁ-MG QUANTO AO CÂNCER DE PRÓSTATA

O câncer de próstata é o mais incidente entre os homens em todas as regiões brasileiras, e tende a aumentar o número de casos, em resposta ao envelhecimento populacional, pois tem como principal fator de risco a idade do homem. O exame do toque retal, embora eficaz quando combinado com o exame de sangue na detecção precoce das neoplasias da próstata, ainda não é amplamente realizado, pois frequentemente é visto como contrário a masculinidade. O objetivo do estudo foi avaliar conhecimentos, atitudes e crenças de homens acima de 40 anos residentes em Araxá-MG quanto ao câncer de próstata. A pesquisa foi exploratória, quantitativa, realizada através de questionário aplicado para homens acima de 40 anos, na estratégia de saúde da família Vila Estância da cidade de Araxá-MG. Os resultados mostraram que, em geral, os homens entrevistados têm conhecimentos quanto ao câncer de próstata, exames de rastreio e importância do diagnóstico precoce. Entretanto, notou-se que, as ações efetivas, com realização dos dois exames de rotina periodicamente, ainda não são amplamente realidade entre os participantes, pois parcela significativa da amostra nunca realizou os exames preconizados. Ações educativas devem ser intensificadas com intuito de divulgar a importância dos exames de rastreio, bem como, do estilo de vida na prevenção do câncer de próstata.Palavras-chave: Câncer de Próstata. Exame de Toque Retal. PSA. Knowledge, attitudes and beliefs of resident men in Araxá-MG regarding prostate cancer ABSTRACT: Prostate cancer is the most frequent among men in all Brazilian regions, and it tends to increase the number of cases, in response to the aging population, since its main risk factor is the age of the man. Rectal examination, although effective when combined with a blood test for the early detection of prostate neoplasms, is still not widely performed because it is often seen as contrary to masculinity. The objective of the study was to evaluate the knowledge, attitudes and beliefs of men over 40 years living in Araxá-MG regarding prostate cancer. The research was exploratory, quantitative, performed through a questionnaire applied to men over 40 years old, in the health strategy of the Vila Estância family of the city of Araxá-MG. The results showed that, in general, the men interviewed had knowledge about prostate cancer, screening tests and the importance of early diagnosis. However, it was noted that the effective actions, with the two routine exams being performed periodically, are not yet widely realized among the participants, since a significant portion of the sample never performed the recommended tests. Educational actions should be intensified in order to publicize the importance of screening exams as well as lifestyle in the prevention of prostate cancer.Keywords: Prostate Cancer. Rectal Touch Exam. PSA.

Spinal cord compression with manifestation primary of spinal metastasis

Introduction: Spinal compression from unknown primary neoplasms occurs in 5 to 14% in cancer patients. The most common metastasis is secondary to lung, breast and prostate neoplasms. The objective of this study is to describe the clinical characteristics and to evaluate outcomes in patients with spinal compression from unknown primary neoplasms. Methods: We developed a retrospective, observational and descriptive study. Six patients were analyzed according to gender, age, location of injury, treatment and prognosis. These patients were analyzed from January 2008 and July 2011 at Emergency Hospital of Sergipe. Results: Six patients were identified. The median age was 52 years. Male gender was the most affected. The main complaint was pain, followed by motor deficit and sphincter disturbances. The thoracic region was involved in four cases, one cervical and one lumbar. The primary source was lung in three patients, thyroid in one, prostate in one and unknown in one. The CT and MRI were gold standard exams to the diagnosis. Four patients were undergoing decompressive laminectomy, a radiotherapy combined with chemotherapy was performed in three patients and only chemotherapy in two cases. There was death in four cases. Conclusions: Spinal compression can be a late manifestation of primary cancer metastasis. The prognosis of these patients is reserved in several cases due to advanced stage of the primary lesion when the diagnosis is made.