Regulatory role of miRNAs on Wnt/ß-catenin signaling in tumorigenesis of glioblastoma.

Glioblastoma (GBM) is one of the most aggressive tumors in the brain with high mortality worldwide. Despite recent advances in therapeutic strategies, the survival rate remains low in patients with GBM. The pathogenesis of GBM is a very complicated process involving various genetic mutations affecting several oncogenic signaling pathways like Wnt/ß-catenin axis. Overactivation of the Wnt/ß-catenin signaling pathway is associated with decreased survival and poor prognosis in patients with GBM. MicroRNAs (miRNAs) were shown to play important roles in the regulation of cell proliferation, differentiation, apoptosis, and tumorigenesis by modulating the expression of their target genes. Aberrant expression of miRNAs were reported in various human malignancies including GBM, breast, colorectal, liver, and prostate cancers, but little is known about their cellular mechanisms. Therefore, recognition of the expression profile and regulatory effects of miRNAs on the Wnt/ß-catenin pathway may offer a novel approach for the classification, diagnosis, prognosis, and treatment of patients with GBM. This review summarizes previous data on the modulatory role of miRNAs on the Wnt/ß-catenin pathway implicated in tumorigenesis of GBM.

Secondary Infertility: A Neglected Aspect of Buerger's Disease.

Background: During the gathering of demographic data for the biobank on Buerger's Disease (BD), we found that, after the clinical manifestation of BD, the patients usually became infertile, and the age of their last child was compatible with the time of disease diagnosis. The aim of this study was to evaluate the underlying cause of secondary infertility in BD patients. Methods: Anti-sperm antibodies (ASA), testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in the sera of 39 male BD patients were measured and compared with 39 age-matched Caucasian male controls. Results: Six patients declared that they suffered from impotency. The ASA level was positive in 25.6% of the patients and 2.4% of the controls (p= 0.003, CC= 6.96). The mean levels of testosterone in the patients and controls were 393.12±32.9 ng/dl and 354.37±30.9 ng/dl, respectively. The mean levels of LH in the patients and controls were 0.88±0.12 mIU/r and 0.85±0.1 mIU/r, respectively. The mean levels of FSH in the patients and controls were 4.1± 0.35 mIU/r and 3.56±0.33 mIU/r, respectively. No significant difference in the serum levels of testosterone, LH, or FSH was found between the patients and controls (p> 0.05). The spermograms of three ASA-negative patients demonstrated impaired sperm motility. Discussion: Anti-sperm antibodies, disturbed genital circulation, autonomic dysfunction and sperm motility may be responsible for secondary infertility in Buerger's Disease.

A Mini Review on the Pathogenesis, Diagnosis and Treatment Options for COVID-19.

Coronavirus disease 2019 (COVID-19) is a serious viral disease caused by SARS-CoV-2, associated with high morbidity and mortality, and represents a significant public health crisis worldwide. Despite recent efforts for developing novel antiviral agents, no specific drugs are approved for the management and treatment of COVID-19. The immune responses to viral infection followed by cytokine storm and acute respiratory distress syndrome are serious issues that may cause death in patients with severe COVID-19. Therefore, developing a novel therapeutic strategy for the management of COVID-19 is urgently needed to control the virus spread and to improve the patient survival rate and clinical outcomes. In this mini-review, we summarize the symptoms, pathogenesis, and therapeutic approaches currently being used to manage the spread of SARS-CoV-2.

Inhibition of angiotensin II type 1 receptor by candesartan reduces tumor growth and ameliorates fibrosis in colorectal cancer.

Colorectal cancer (CRC) is an important cause of cancer-related mortality. Aberrant activation of the renin-angiotensin system (RAS) is reported to be associated with poor clinical outcomes in patients with CRC. This study was designed to explore the anti-tumor effects of the angiotensin receptor blocker Candesartan either alone or in combination with 5-FU in in vitro and in vivo models of CRC. The cytotoxic effects of Candesartan were assessed using the MTT assay in two colorectal cancer cell lines (CT-26 and SW-480). To investigate the potential regulatory role of Candesartan on tumor growth, apoptosis, and migration, the expression levels of Cyclin D1, Survivin, MMP3, MMP9, and E-cadherin mRNAs were evaluated. The oxidant/antioxidant balance was also examined by determining the levels of MDA, thiols, SOD, and CAT. We used a xenograft model of colon cancer to investigate the effects of Candesartan alone, or in combination with 5-FU, on tumor growth following histological staining (Hematoxylin & Eosin and Masson trichrome staining) and biochemical studies as well as gene expression analyses by RT-PCR and western blotting. Candesartan suppressed tumor cell proliferation and migration by modulating Cyclin D1, MMP3/9, and E-cadherin. Treatment with Candesartan either alone, or in combination with 5-FU decreased tumor size in the mouse model, and also increased the level of oxidative markers MDA and reduced CAT, SOD, and thiols. Histological evaluation showed that Candesartan increased tumor necrosis, reduced tumor density and attenuated collagen deposition reducing tumor fibrosis in tumor xenograft. Candesartan, an inhibitor of the RAS, when used in combination with 5-FU reduced tumor growth by inhibiting fibrosis and inducing ROS production, supporting further clinical studies on this therapeutic approach for treatment of CRC.

"Infection prevention and control idea challenge" contest: a fresh view on medical education and problem solving.

BACKGROUND: Healthcare-associated infections (HAIs) challenge modern medicine. Considering their high prevalence in Iran, we aimed to provide knowledge on the subject, and to teach about the importance of infection prevention and control (IPC) to a broad audience of pre-graduate healthcare professionals, focusing on education as the cornerstone of IPC. MAIN BODY: We invited Iranian medical students to present ideas on "how to reduce HAIs." Projects were eligible if being original and addressing the call. Accepted projects were quality assessed using a scoring system. Forty-nine projects were submitted, of which 37 met the inclusion criteria. They had a mean score of 69.4 ± 18.3 out of the maximum possible score of 115. Four reviewers assessed the 37 projects for clinical applicability, impact on patient safety, and innovation, and selected the best 12 to compete at the 2nd International Congress on Prevention Strategies for Healthcare-associated Infections, Mashhad, Iran, 2018. The competition took place in three rounds. The selected teams presented their projects in the first round and debated one by one in a knockout manner, while the jury reviewed their scientific content and presentation skills. In the second round, the top 5 projects competed for reaching the final stage, in which the teams presented their ideas in front of a panel of international IPC experts to determine the first three ranks. At the end of the contest, the participants gained valuable criticisms on how to improve their ideas. Moreover, by its motivating atmosphere, the contest created an excellent opportunity to promote IPC in medical schools. CONCLUSIONS: Using innovation contests in pre-graduates is an innovative education strategy. It sensitizes medical students to the challenges of IPC and antimicrobial resistance and drives them to think about solutions. By presenting and defending their innovations, they deepen their understanding on the topic and generate knowledge transfer in both ways, from students to teachers and vice versa.

Investigating the prevalence of risk factors of papillary thyroid carcinoma recurrence and disease-free survival after thyroidectomy and central neck dissection in Iranian patients.

Background: Papillary thyroid carcinoma (PTC) is considered the most frequent thyroid malignancy (85-90%) with a good prognosis. However, its frequent recurrence increases mortality and morbidity. In this inquiry we investigated the prevalence of risk factors of PTC recurrence and disease free survival after thyroidectomy and central neck dissection. Method: In this retrospective study, all patients with confirmed PTC who underwent total thyroidectomy and central neck dissection in Imam Reza and Omid hospitals of Mashhad University of Medical Sciences from 2004 to 2011 were included. Total locoregional and distant recurrence rate, 5-year disease free survival rate (DFS) and contributing factors of recurrence were investigated after at least 5 years. Results: In this study 289 patients were included with a mean follow-up of 72.90 ± 11.02 months. 70.6% were female and 29.4% were male. Recurrence occurred in 58 cases from which 10 were distant and 48 were loco-regional. 5-year DFS was 80% and total-survival-rate was 99%. Our analysis showed that primary tumor size, vascular-invasion, extra-thyroid extension, and lymph node ratio (LNR) were significantly related to DFS.

Role of regulatory miRNAs of the PI3K/AKT/mTOR signaling in the pathogenesis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the common malignant human tumors with high morbidity worldwide. Aberrant activation of the oncogenic phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling is related to clinicopathological features of HCC. Emerging data revealed that microRNAs (miRNAs) have prominent implications for regulating cellular proliferation, differentiation, apoptosis, and metabolism through targeting the PI3K/AKT/mTOR signaling axis. The recognition of the crucial role of miRNAs in hepatocarcinogenesis represents a promising area to identify novel anticancer therapeutics for HCC. The present study summarizes the major findings about the regulatory role of miRNAs in the PI3K/AKT/mTOR pathway in the pathogenesis of HCC.

Evaluation of Interleukin17and Interleukin 23 expression in patients with active and latent tuberculosis infection.

OBJECTIVES: Tuberculosis is one of the most important infectious diseases with high mortality rates worldwide, especially in developing countries. Interleukin17 (IL-17) is an important acquired immunity cytokine, which is mainly produced by CD4+TH17 cells. It can recruit neutrophils and macrophages to the infected site in the lungs. IL-23 is one of the most important inducers of IL-17. In the present study, the expressions of IL-23 and IL-17 were examined in the pathogenesis of tuberculosis. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from subjects with latent tuberculosis infection (LTB) and newly diagnosed active tuberculosis patients (ATB). PBMCs were activated with purified protein derivative (PPD) for 72 hr. Activated cells were harvested, RNA was extracted, and cDNA was synthesized. IL-17 and IL-23 mRNA expressions were evaluated by real-time PCR. The frequency of Th17 cells was examined by flowcytometry. RESULTS: The expressions of IL-17 and IL-23 mRNA were lower in patients than subjects with LTB (P<0.05). The frequency of IL-17 producing CD4+ T cells in patients with active TB was lower than LTB subjects (P<0.05). CONCLUSION: The results of the present study might suggest that IL-17 and IL-23 play critical roles in the immune response against TB.