Non-alcoholic fatty liver disease is not independent risk factor for cardiovascular disease event : a cohort study

There are no consistent results between previous studies for an independent association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) events. To determine if there is an independent association between NAFLD and CVD events. In the present study, valid outcome data of 4808 subjects were available for phase 2 of our cohort study. These subjects had been followed up for seven years from phase 1, beginning in 2009-2010 to phase 2 during 2016-2017. Simple and multiple Cox proportional models were used to determine the association between NAFLD in the primary phase of the cohort and subsequent fatal and non-fatal CVD events during follow-up. The incidence of non-fatal CVD events in males with NAFLD was significantly higher ( = 0.004) than in males without NAFLD. A positive association was demonstrated between NAFLD and non-fatal CVD events in males (Hazard ratio = 1.606; 95%CI: 1.166-2.212; = 0.004) by the simple Cox proportional hazard model, but no independent association was detected between these in the multiple Cox models. No independent association was detected between NAFLD and CVD. It is likely that diabetes mellitus and age may be the principle mediators in this regard. [Abstract copyright: ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

Signal transduction pathway mutations in gastrointestinal (GI) cancers : a systematic review and meta-analysis

The present study was conducted to evaluate the prevalence of the signaling pathways mutation rate in the Gastrointestinal (GI) tract cancers in a systematic review and meta-analysis study. The study was performed based on the PRISMA criteria. Random models by confidence interval (CI: 95%) were used to calculate the pooled estimate of prevalence via Metaprop command. The pooled prevalence indices of signal transduction pathway mutations in gastric cancer, liver cancer, colorectal cancer, and pancreatic cancer were 5% (95% CI: 3–8%), 12% (95% CI: 8–18%), 17% (95% CI: 14–20%), and 20% (95% CI: 5–41%), respectively. Also, the mutation rates for Wnt pathway and MAPK pathway were calculated to be 23% (95% CI, 14–33%) and 20% (95% CI, 17–24%), respectively. Moreover, the most popular genes were APC (in Wnt pathway), KRAS (in MAPK pathway) and PIK3CA (in PI3K pathway) in the colorectal cancer, pancreatic cancer, and gastric cancer while they were beta-catenin and CTNNB1 in liver cancer. The most altered pathway was Wnt pathway followed by the MAPK pathway. In addition, pancreatic cancer was found to be higher under the pressure of mutation compared with others based on pooled prevalence analysis. Finally, APC mutations in colorectal cancer, KRAS in gastric cancer, and pancreatic cancer were mostly associated gene alterations

A population-based prospective study on obesity-related non-communicable diseases in northern Iran: rationale, study design, and baseline analysis

BackgroundIran is facing an epidemiological transition with the increasing burden of non-communicable diseases, such as obesity-related disorders and cardiovascular diseases (CVDs). We conducted a population-based prospective study to assess the prevalence and incidence rates of CVDs and obesity-related metabolic disorders and to evaluate the predictive ability of various CVD risk assessment tools in an Iranian population.MethodWe enrolled 5,799 participants in Amol, a city in northern Iran, in 2009–2010 and carried out the first repeated measurement (RM) after seven years (2016–2017). For all participants, demographic, anthropometric, laboratory, hepatobiliary imaging, and electrocardiography data have been collected in the enrollment and the RM. After enrollment, all participants have been and will be followed up annually for 20 years, both actively and passively.ResultsWe adopted a multidisciplinary approach to overcome barriers to participation and achieved a 7-year follow-up success rate of 93.0% with an active follow-up of 5,394 participants aged 18–90 years. In the RM, about 64.0% of men and 81.2% of women were obese or overweight. In 2017, about 16.2% and 5.2% of men had moderate or severe non-alcoholic fatty liver disease, while women had a significantly higher prevalence of metabolic syndrome (35.9%), and type 2 diabetes mellitus (20.9%) than men. Of 160 deceased participants, 69 cases (43.1%) died due to CVDs over seven years.ConclusionThe most prevalent obesity-related chronic disease in the study was metabolic syndrome. Across the enrollment and RM phases, women exhibited a higher prevalence of obesity-related metabolic disorders. Focusing on obesity-related metabolic disorders in a population not represented previously and a multidisciplinary approach for enrolling and following up were the strengths of this study. The study outcomes offer an evidence base for future research and inform policies regarding non-communicable diseases in northern Iran

Roles of Integrin and Its Application for Anti-viral Drug Development

Integrins are a large family of adhesion molecules under cellular control that could act bilabially in different situations; on the other hand, they play a significant role in adsorption and entry of immune system cells or other helper cells. Furthermore, they could be good targets for entry, localization and replication of infectious viruses into cells. As viruses apply various strategies for entry and infiltration to cells, comparison of these ways (especially integrin mediated), elucidates effective mechanisms in the inception of viral infection and the host cells interactions. At this point, the present study reviewed the relationships between common viruses such as Adenovirus, Papillomavirus, Herpesvirus, Hantavirus, Rotavirus, Echovirus, foot-and-mouth disease virus, Coxsackievirus type 9, Parechovirus type 1 and Human immunodeficiency virus type 1 with integrins and their viable interactions for therapeutical issues and better recognition of the commencement process of the infection by these viruses

Molecular survey on Merkel cell polyomavirus in patients with colorectal cancer

Background: Merkel cell polyomavirus (MCV) has been associated with Merkel cell carcinoma (MCC) in humans, and its role in other human cancers is under investigation. The aim of this study was to investigate MCV genome infection in patients with colorectal cancer (CRC). Methods: This retrospective, case-control study used archived formalin-fixed, paraffin-embedded (FFPE) tissue samples from colorectal cancer patients (cases) and matched healthy subjects (controls) diagnosed by an expert pathologist from hospitals affiliated with Iran University of Medical Sciences, Tehran, Iran from 2011 to 2016. After DNA extraction with a QIAamp® DNA FFPE Tissue Kit, real-time polymerase chain reaction (PCR) was used for diagnosis. A positive control was produced by cloning with the Generay Biotechnology system. SPSS v.22 was used for analysis of demographic variables. Results: There were 157 participants included in the study: 66 were cases and 91 were controls. Their mean ages (±SD) were 59.35±14.48 and 57.21±14.66, respectively. The proportion of males was 57.6% in the case group and 57.1% in the control group. None of the samples were positive for MCV expression by real-time PCR assay. Association was detected between males with CRC and tumor location in the rectum and between males with CRC and the mucinous tumor type. Conclusion: None of the tissues from the CRC or non-cancerous control groups were positive for MCV genome infection, although a low viral load, the sample type, or the method of use should not be neglected. Further studies are recommended to obtain more comprehensive results

A survey on human T-cell lymphotropic virus type 1 (HTLV-1) and xenotropic murine leukemia virus-related virus (XMRV) coinfection in Tehran, Iran

Background: Xenotropic murine leukemia virus-related virus (XMRV) is a gamma retrovirus, which has been detected in patients with prostate cancer, chronic fatigue syndrome, and general population with a number of acquired infections such as infection with human T-cell lymphotropic virus (HTLV) and human immunodeficiency virus (HIV). The aim of this study was to determine the HTLV-1 and XMRV coinfection for the first time in Iranian patients who were admitted to the Tehran hospitals. Materials and Methods: Two hundred and ninety one patients suspected with HTLV-1 were referred to the hospitals affiliated to the Iran University of Medical Sciences, Tehran, Iran from April 2012 to October 2016. Genomic deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) from peripheral blood mononuclear cells/cerebrospinal fluids was extracted by High Pure Viral Nucleic Acid Kit (Roche, Germany). After complementary DNA synthesis, conventional reverse transcriptase polymerase chain reaction was used for the detection of HTLV-1 or XMRV-infected patients. Statistical Package for Social Sciences (SPSS) software, version 16 (SPSS, Chicago, IL, USA) was used for statistical analyses. Results: Of the 291 patients suspected of HTLV infection, 123 (42.3%) were male with a mean age of 38±15 years. HTLV-1 RNA was found in 93 (31.9%) specimens comprising 40 men (41.3%) and 53 women (56.9%). Of the 93 patients who were HTLV-1 positive, one sample (1%) was positive for XMRV env gene. Conclusion: These findings suggest that the lack of significant detection of XMRV in patients who were HTLV-1 positive could not be associated with complications of HTLV-1. Although this is a preliminary report from Iranian patients with HTLV-1, further studies are needed to show the actual prevalence of XMRV infection by geographical distribution and various populations

The association between CD3+ and CD8+tumor-infiltrating lymphocytes (TILs) and prognosis in patients with pancreatic adenocarcinoma

Background: : Pancreatic adenocarcinoma (PDAC), with more than 250,000 deaths each year, is the eighth leading cause of death worldwide, with a five-year survival of less than 5% and a median recurrence time between 5 and 23 months. The association between PDAC and CD3+/CD8+ tumor-infiltrating lymphocytes (TILs) and the extent of tumor spread and clinical outcomes has been recently shown. This study aimed to determine and compare the density of TILs and their association with disease prognosis in patients with PDAC. Materials and Methods: : In this study, we collected PDAC tissues and corresponding adjacent normal tissues from 64 patients with TIL-positive PDAC. The immunohistochemistry method was used for the detection of the expression levels of CD3+ and CD8+ TILs in PDAC tissues. Also, the completed follow-up history was evaluated for at least five years. Results: : The frequency of intratumoral and peritumoral TILs was 20 (31.2%) and 44 (68.8%), respectively. The mean density of CD3+ TILs and CD8+ TILs was 67.73%±20.17% and 69.45%±17.82%, respectively. The density of CD3+ TILs and CD8+ TILs was not associated with overall survival nor metastasis-free survival of the patients and tumor grade. However, the density of TILs was significantly lower in those patients who experienced tumor recurrence than those without this recurrence. Conclusion: : TILs density was high in patients with PDAC. The density of both CD3+ and CD8+ TILs was significantly lower in patients who experienced tumor recurrence. Thus, this study suggests that tracking and determining the density of CD3+ and CD8+ TILs might be effective in predicting PDAC recurrence

Human Papillomavirus Type 16 Integration Analysis by Real-time PCR Assay in Associated Cancers

Human papillomavirus (HPV) is a common viral infection worldwide associated with a variety of cancers. The integration of the HPV genome in these patients causes chromosomal instability and triggers carcinogenesis. The aim of this study was to investigate the HPV-16 genome physical status in four major cancers related to HPV infection. Formalin-fixed paraffin-embedded blocks from our previous projects on head and neck, colorectal, penile, and cervical cancers were collected, and HPV-16–positive specimens were used for further analysis. The DNA extraction copy number of E2 and E7 genes was calculated by qualitative real-time PCR method. Serially diluted standards that were cloned in PUC57 plasmid were used. Standard curve and melting curve analysis was used for quantification. Of the 672 specimens studied, 76 (11.3%) were HPV-16 positive. We found that 35.6% (16/45) were integrated. Statistical analysis showed that there were significant correlations between integration of HPV-16 and cervical cancer end-stage carcinogenesis (P < .0001), episomal form, and ASCUS lesions (P = .045). Significant correlation in penile cancer patients was seen between the episomal form and high-grade cancer stage (P = .037). Integration is a major factor in the carcinogenesis mechanism of HPV and has different prevalence in various cancers with a higher rate in progression except in penile cancer

The ability of the Framingham Steatosis Index (FSI) to predict Non-alcoholic Fatty Liver Disease (NAFLD) : a cohort study

Background: The utilization of indexes for the diagnosis of non-alcoholic fatty liver disease (NAFLD) can be valuable. This study was conducted to determine the ability of the Framingham steatosis index (FSI) to distinguish between people with NAFLD and those without and to predict people at risk of NAFLD to establish the need for lifestyle modifications in such individuals. Methods: Our study was conducted in two phases from 2009-2010 (phase I) to 2016-2017 (phase II). A total of 4670 people in northern Iran were included. NAFLD was diagnosed by ultrasound. The FSI was calculated based on age, sex, hypertension, diabetes mellitus status, liver enzyme levels and triglyceride levels. Receiver operating characteristic (ROC) analysis was conducted to determine the discriminatory and predictive abilities of the FSI. To remove the confounding effects of potential mediators, logistic regression was performed in which NAFLD was considered the outcome and the FSI as the predictor. Results: The odds ratios of the FSI when the outcome was the prevalence of NAFLD in phase I and when the outcome was new cases of NAFLD from 2009�2010 to 2016-2017 were 4.909 (4.243�5.681) and 2.453 (2.024�2.972), respectively (P < 0.001). The areas under the curve (AUCs) for the discriminatory and predictive abilities of the FSI were 0.8421 (95 CI: 0.8314�0.8527) and 0.7093 (95 CI: 0.6863�0.7322), respectively. Conclusion: The FSI has a strong ability to diagnose NAFLD while it has an acceptable ability to predict the occurrence of new cases of NAFLD. © 202