Protocol for preliminary, multicenteric validation of "PoCOsteo device": A point of care tool for proteomic and genomic study of osteoporosis.

One of the goals of the HORIZON 2020 project PoCOsteo was to develop a medical device, which would measure and/or quantify proteomic as well as genomic factors as present in whole blood samples collected through finger prick. After validating the tool in the clinical setting, the next step would be its clinical validation based on the existing guidelines. This article presents the protocol of a validation study to be carried out independently at two different centers (Division of Endocrinology and Diabetology at the Medical University of Graz as a clinic-based cohort, and the Endocrinology and Metabolism Research Institute at the Tehran University of Medical Sciences as a population-based cohort). It aims to assess the tool according to the Clinical & Laboratory Standards Institute guidelines, confirming if the proteomics and genomics measurements provided by the tool are accurate and reproducible compared with the existing state-of-the-art tests. This is the first time that such a detailed protocol for lab validation of a medical tool for proteomics and genomic measurement is designed based on the existing guidelines and thus could be used as a template for clinical validation of future point-of-care tools. Moreover, the multicentric cohort design will allow the study of a large number of diverse individuals, which will improve the validity and generalizability of the results for different settings.

The Effect of Metformin on Expression of Long Non-coding RNA H19 in Endometrial Cancer.

Background: Endometrial cancer is the fourth most widespread cancer among females, with a growing prevalence in recent years. Management by combined therapies along with surgery, radiotherapy, and chemotherapy have improved patients' prognoses. Besides, the development of new therapies helps preserve fertility and prognosis in aggressive tumors. The purpose of this research was to identify the efficacy of metformin on the H19 long non-coding RNA expression in endometrial cancer to provide further insight into the pathogenesis and treatment of the disease. Methods: A total of 23 patients with endometrial cancer, diagnosed by biopsy or diagnostic curettage, were recruited and divided into three groups, before and after metformin treatment and placebo. Real-time PCR was used to evaluate the H19 expression in cancer tissue in all patients. Results: : It has been observed that in endometrial tissue of the "after-metformin" treatment group, the H19 expression level was significantly reduced, compared with the "before-metformin" treatment group, but not in comparison with the placebo. These findings indicate that metformin reduced the H19 expression in endometrial cancer. Conclusion: Anti-diabetic drugs, such as metformin, may be beneficial by reducing the H19 expression in endometrial cancer due to the H19 relation to cancer progression.

An in silico approach to identify and prioritize miRNAs target sites polymorphisms in colorectal cancer and obesity.

Colorectal cancer (CRC) and obesity are linked clinical entities with a series of complex processes being engaged in their development. MicroRNAs (miRNAs) participate in these processes through regulating CRC and obesity-related genes. This study aimed to develop an in silico approach to systematically identify and prioritize miRNAs target sites polymorphisms in obesity and CRC. Data from genome-wide association studies (GWASs) were used to retrieve CRC and obesity-associated variants. The polymorphisms that were resided in experimentally verified or computationally predicted miRNA target sites were retrieved and prioritized using a range of bioinformatics analyses. We found 6284 CRC and 38931 obesity unique variants. For CRC 33 haplotypes variants in 134 interactions were in miRNA targetome, while for obesity we found more than 935 unique interactions. Functionally prioritized SNPs revealed that, SNPs in 153 obesity and 50 CRC unique interactions were have disruptive effects on miRNA:mRNA integration by changing on target RNA secondary structure. Structural accessibility of target sites were decreased in 418 and 103 unique interactions and increased in 516 and 79 interactions, for obesity and CRC, respectively. The miRNA:mRNA hybrid stability was increased in 127 and 17 unique interactions and decreased in 33 and 24 interactions for the effect of obesity and CRC SNPs, respectively. In this study, seven SNPs with 15 interactions and three SNPs with four interactions were prioritized for obesity and CRC, respectively. These SNPs could be used for future studies for finding potential biomarkers for diagnoses, prognosis, or treatment of CRC and obesity.

Letter to the Editor: Comments on "Association between the ICAM-1 gene polymorphism and coronary heart disease risk: a meta-analysis".

Yin et al. (Bioscience Reports (2019) 39, BSR20180923) recently published a meta-analysis about the association between the K469E (rs5498) polymorphism and risk of coronary heart disease (CHD). Authors included 14 studies based on their inclusion criteria. They indicated that only studies which their genotyping data were in Hardy-Weinberg equilibrium (HWE) were included in their meta-analysis. They also tested HWE for these studies and found all the control groups in HWE. As their main finding, they concluded that 'K469E polymorphism is associated with CHD risk and the K allele is a more significant risk factor for developing CHD amongst Chinese and Caucasians populations'. However, there seems to be presenting some mistakes in HWE test which strongly affects included studies and the final conclusion. Here we aim to comment on the issue.

Association between epstein barr virus and tongue squamous cell carcinoma in iranian patients.

Detection of Epstein-Barr virus in oral squamous cell carcinoma suggests its involvement in the carcinogenesis of oral cavity. But, there are few studies on the incidence of EBV genome in squamous cell carcinomas at specific locations in the oral cavity like tongue and with different tumor progression. In this study the presence of EBV genome in tongue Squamous Cell Carcinoma (TSCC) in Iranian patients were investigated. Accordingly, a total of 94 cases with TSCC were firstly analyzed for the presence of viral genome through Nested PCR. Patients were divided into different groups based on their gender and the size, nodal involvement, grade and stage of their tumor. Results showed the presence of EBV genome in 72.3% of TSCCs with no significant difference between two genders, although slightly higher in females. Interestingly, PCR products of EBV genome showed a statistically significant higher distribution in TSCCs at IVa stage (p=0.04), while a considerable low involvement of EBV genome was seen in T1-sized tumors. The result of this study further emphasizes the role of EBV in oral SCCs - mainly at tongue. This is the first investigation to clarify the association between EBV genome and different tumor size and stage in TSCCs; however, more studies in different regions and larger populations should be performed to be able to draw a firmed conclusion.

Polymorphisms of Antioxidant Genes as a Target for Diabetes Management.

Diabetes mellitus (DM) is one of the most important health problems with increasing prevalence worldwide. Oxidative stress, a result of imbalance between reactive oxygen species (ROS) generation and antioxidant defense mechanisms has been demonstrated as the main pathology in DM. Hyperglycemia-induced ROS productions can induce oxidative stress through four major molecular mechanisms including the polyol pathway, advanced glycation end- products formation, activation of protein kinase C isoforms, and the hexosamine pathways. In the development of type 2 DM (T2DM) and its complications, genetic and environmental factors play important roles. Therefore, the aim of this review was to focus on the assessment of single-nucleotide polymorphisms within antioxidant enzymes including superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, nitric oxide synthase, and NAD(P)H oxidase and their association with T2DM. The results would be helpful in understanding the mechanisms involved in pathogenesis of disease besides discovering new treatment approaches in management of DM.