Shahid Beheshti University of Medical Sciences and Health Services

About: Shahid Beheshti University of Medical Sciences and Health Services is a education organization based out in Tehran, Iran. It is known for research contribution in the topics: Population & Medicine. The organization has 19456 authors who have published 33659 publications receiving 365676 citations.

OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer

Abstract: OCT-4 (also known as POU5F1) is a key regulator of self-renewal in embryonic stem cells. Regarding the new cancer stem cell concept, the expression of such genes is potentially correlated with tumorigenesis and can affect some aspects of tumor behavior, such as tumor recurrence or resistance to therapies. Although OCT-4 has been introduced as a molecular marker for germ cell tumors, little is known about its expression in somatic cancers. Here, we have investigated the potential expression of OCT-4 in bladder cancer. We used semiquantitative RT-PCR to examine the expression of OCT-4 in 32 tumors, 13 apparently nontumor tissues taken from the margin of tumors and 9 normal urothelial tissues. The expression of OCT-4 at protein level was further determined by Western blotting and immunohistochemical (IHC) analysis. OCT-4 expression was detected in almost all examined tumors (31/32), but at much lower level (p<0.001) in some nonneoplastic samples (6/22). A significantly strong correlation of 0.6 has been observed between OCT-4 expression and the presence of tumors (p<0.001). Western blot analysis further confirmed the expression of OCT-4 in tumor biopsies. According to IHC results, OCT-4 is primarily localized in the nuclei of tumor cells, with no or low immunoreactivity in nontumor cells. Our study demonstrated, for the first time, the expression of OCT-4 in bladder cancer and a further clue to the involvement of embryonic genes in carcinogenesis.

Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome

Abstract: Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17+ T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans.

Predicting COVID-19 Incidence Through Analysis of Google Trends Data in Iran: Data Mining and Deep Learning Pilot Study.

Abstract: Background: The recent global outbreak of coronavirus disease (COVID-19) is affecting many countries worldwide. Iran is one of the top 10 most affected countries. Search engines provide useful data from populations, and these data might be useful to analyze epidemics. Utilizing data mining methods on electronic resources’ data might provide a better insight into the COVID-19 outbreak to manage the health crisis in each country and worldwide. Objective: This study aimed to predict the incidence of COVID-19 in Iran. Methods: Data were obtained from the Google Trends website. Linear regression and long short-term memory (LSTM) models were used to estimate the number of positive COVID-19 cases. All models were evaluated using 10-fold cross-validation, and root mean square error (RMSE) was used as the performance metric. Results: The linear regression model predicted the incidence with an RMSE of 7.562 (SD 6.492). The most effective factors besides previous day incidence included the search frequency of handwashing, hand sanitizer, and antiseptic topics. The RMSE of the LSTM model was 27.187 (SD 20.705). Conclusions: Data mining algorithms can be employed to predict trends of outbreaks. This prediction might support policymakers and health care managers to plan and allocate health care resources accordingly.

Epigenetically Deregulated microRNA-375 Is Involved in a Positive Feedback Loop with Estrogen Receptor α in Breast Cancer Cells

Abstract: Estrogen receptor α (ERα) upregulation causes abnormal cell proliferation in about two thirds of breast cancers, yet understanding of the underlying mechanisms remains incomplete. Here, we show that high expression of the microRNA miR-375 in ERα-positive breast cell lines is a key driver of their proliferation. miR-375 overexpression was caused by loss of epigenetic marks including H3K9me2 and local DNA hypomethylation, dissociation of the transcriptional repressor CTCF from the miR-375 promoter, and interactions of ERα with regulatory regions of miR-375. Inhibiting miR-375 in ERα-positive MCF-7 cells resulted in reduced ERα activation and cell proliferation. A combination of expression profiling from tumor samples and miRNA target prediction identified RASD1 as a potential miR-375 target. Mechanistic investigations revealed that miR-375 regulates RASD1 by targeting the 3′ untranslated region in RASD1 mRNA. Additionally, we found that RASD1 negatively regulates ERα expression. Our findings define a forward feedback pathway in control of ERα expression, highlighting new strategies to treat ERα-positive invasive breast tumors. Cancer Res; 70(22); 9175–84. ©2010 AACR.