Introducing BDNF and SNAI1 as the Crucial Targeted Genes by UV Radiation.

Introduction: Due to widespread penetration of UV radiation in human life, the biological effect of UV radiation is studied through many investigations in the field of medicine. There are many assessments about UV radiation which are concerned with protein-protein interaction (PPI) network analysis. In the present study, a network analysis associated with the complementary evaluation of UV radiation on human primary melanocytes is presented. Methods: The gene expression profiles of the irradiated human primary melanocytes and the control cells were extracted from Gene Expression Omnibus (GEO) and were evaluated via PPI network analysis and action map assessment. Results: 69 significant differentially expressed genes (DEGs) were included in the main component of the PPI network. Brain-derived neurotrophic factor (BDNF), SNAI1, and SOCS1 were highlighted as the top dysregulated and hub genes. Results indicate that BDNF and SNAI1 participate in the regulatory unit including the total hubs and top dysregulated genes. Conclusion: Considerable down-regulation of BDNF and up-regulation of SNAI1 as the two critical targeted genes by UV radiation are accompanied by gross alteration in cell functions.

Investigation into Chronic Low-Dose Ionizing Radiation Effect on Gene Expression Profile of Human HUVECs Cells.

Introduction: Understanding the molecular mechanism of chronic low-dose ionizing radiation (LDIR) effects on the human body is the subject of many research studies. Several aspects of cell function such as cell proliferation, apoptosis, inflammation, and tumorigenesis are affected by LDIR. Detection of the main biological process that is targeted by LIDR via network analysis is the main aim of this study. Methods: GSE66720 consisting of gene expression profiles of human umbilical vein endothelial cells (HUVECs) (a suitable cell line to be investigated), including irradiated and control cells, was downloaded from Gene Expression Omnibus (GEO). The significant differentially expressed genes (DEGs) were determined and analyzed via protein-protein interaction (PPI) network analysis to find the central individuals. The main cell function which was related to the central nodes was introduced. Results: Among 64 queried DEGs, 48 genes were recognized by the STRING database. C-X-C motif chemokine ligand 8 (CXCL8), intercellular adhesion molecule 1 (ICAM1), Melanoma growth-stimulatory activity/growth-regulated protein α (CXCL1), vascular cell adhesion molecule 1 (VCAM-1), and nerve growth factor (NGF) were introduced as hub nodes. Conclusion: Findings indicate that inflammation is the main initial target of LDIR at the cellular level which is associated with alteration in the other essential functions of the irradiated cells.

Hypofractionated Radiation Versus Conventional Fractionated Radiation: A Network Analysis.

Introduction: Conventional fractionation (CF) and hypofractionation (HF) are two radiotherapy methods against cancer, which are applied in medicine. Understanding the efficacy and molecular mechanism of the two methods implies more investigations. In the present study, proteomic findings about the mentioned methods relative to the controls were analyzed via network analysis. Methods: The significant differentially expressed proteins (DEPs) of prostate cancer (PCa) cell line DU145 in response to CF and HF radiation therapy versus controls were extracted from the literature. The protein-protein interaction (PPI) networks were constructed via the STRING database via Cytoscape software. The networks were analyzed by "NetworkAnalyzer" to determine hub DEPs. Results: 126 and 63 significant DEPs were identified for treated DU145 with CF and HF radiation respectively. The PPI networks were constructed by the queried DEPs plus 100 first neighbors. ALB, CD44, THBS1, EPCAM, F2, KRT19, and MCAM were highlighted as common hubs. VTM, OCLN, HSPB1, FLNA, AHSG, and SERPINC1 appeared as the discriminator hub between the studied cells. Conclusion: 70% of the hubs were common between CF and HF conditions, and they induced radio-resistance activity in the survived cells. Six central proteins which discriminate the function of the two groups of the irradiated cells were introduced. On the basis of these findings, it seems that DU145-CF cells, relative to the DU145-UF cells, are more radio-resistant.

The impact of HIV on the risk of COVID-19 death among hospitalized patients.

BACKGROUND: Little is known about the association between Human Immunodeficiency Virus (HIV) infection and risk of death among hospitalized COVID-19 patients. We aimed to investigate this association using a multicenter study. MATERIAL AND METHODS: This multicenter study was conducted using the registry database of Coronavirus Control Operations Headquarter from March 21, 2021 to January 18, 2020 in the province of Tehran, Iran. The interest outcome was COVID-19 death among hospitalized patients living with and without HIV. The Cox regression models with robust standard error were used to estimate the association between HIV infection and risk of COVID-19 death. The subgroup and interaction analysis were also performed in this study. RESULTS: 326052 patients with COVID-19 were included in the study, of whom 127 (0.04%) were living with HIV. COVID-19 patients with HIV were more likely to be female, older, and to have symptoms such as fever, muscular pain, dyspnea and cough. The death proportion due to COVID-19 was 18 (14.17%) and 21595 (6.63%) among HIV and non-HIV patients, respectively. Patients living with HIV had lower mean survival time compared to those without HIV (26.49 vs. 15.31 days, P-value = 0.047). Crude risk of COVID-19 death was higher among HIV patients than in non-HIV group (hazard ratio[HR]: 1.60, 1.08-2.37). Compared to those without HIV, higher risk of COVID-19 death was observed among patients with HIV after adjusting for sex (1.60, 1.08-2.36), comorbidities (1.49, 1.01-2.19), cancer (1.59, 1.08-2.33), and PO2 (1.68, 1.12-2.50). However, the risk of COVID-19 death was similar in patients with and without HIV after adjusting for age (1.46, 0.98-2.16) and ward (1.30, 0.89-1.89). CONCLUSION: We found no strong evidence of association between HIV infection and higher risk of COVID-19 death among hospitalized patients. To determine the true impact of HIV on the risk of COVID-19 death, factors such as age, comorbidities, hospital ward, viral load, CD4 count, and antiretroviral treatment should be considered.

Assessment of colon cancer molecular mechanism: a system biology approach.

AIM: The current study aimed to assess and compare colon cancer dysregulated genes from the GEO and STRING databases. BACKGROUND: Colorectal cancer is known as the third most common kind of cancer and the second most important reason for global cancer-related mortality rates. There have been many studies on the molecular mechanism of colon cancer. METHODS: From the STRING database, 100 differentially expressed proteins related to colon cancers were retrieved and analyzed by network analysis. The central nodes of the network were assessed by gene ontology. The findings were compared with a GSE from GEO. RESULTS: Based on data from the STRING database, TP53, EGFR, HRAS, MYC, AKT1, GAPDH, KRAS, ERBB2, PTEN, and VEGFA were identified as central genes. The central nodes were not included in the significant DEGs of the analyzed GSE. CONCLUSION: A combination of different database sources in system biology investigations provides useful information about the studied diseases.

The Principal Role of Several Members of HLA and IRF Genes in Prevention of Oral Mucositis After Chemoradiotherapy.

Introduction: One of the chemoradiotherapy (CRT) side effects is oral mucositis (OM). Since photobiomodulation therapy (PBMT) is a public method for the repair process, in the present study the mechanism of PBMT in the prevention of OM is investigated via the bioinformatics approach. Methods: Six validated and significant differentially expressed genes (DEGs) associated with the prevention of OM in head and neck cancer (HNC) patients who had experienced CRT were extracted from the literature. After adding 50 neighbors from STRING, the network was constructed and analyzed. The results of the action map and network analysis were compared and discussed. Results: HLA gene family were identified as central nodes of the analyzed network. Based on action map finding, activation is prominent action and IRF9 was the potent activator. The role of the IRF gene family was highlighted by action map analysis. Conclusion: Regulation of the immune system by HLA and IRF genes family is a crucial factor in the prevention of OM in the studied patients.

Baseline Characteristics and Associated Factors of Mortality in COVID-19 Patients; an Analysis of 16000 Cases in Tehran, Iran.

Introduction. INTRODUCTION: Given the importance of evidence-based decision-making, this study aimed to evaluate epidemiological and clinical characteristics as well as associate factors of mortality among admitted COVID-19 cases. METHODS: This multicenter, cross-sectional study was conducted on confirmed and suspected COVID-19 cases who were hospitalized in 19 public hospitals affiliated to Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran, between February 19 and May 12, 2020. Epidemiological and clinical characteristics of the infected cases were compared between the deceased and survivors after discharge. Case fatality rates (CFRs) were calculated across all study variables. Single and multiple logistic regressions were used to explore the risk factors associated with COIVD-19 mortality. RESULTS: Out of the 16035 cases that referred to the hospitals affiliated to SBMU, 16016 patients (99.93% of Confirmed and 99.83% of suspected cases) were hospitalized. 1612 patients died with median hospitalization days of 5 (interquartile range (IQR): 2-9) and 3 (1-7) for confirmed and suspected COVID-19 cases, respectively. The highest death rate was observed among ages>65 (63.4% of confirmed cases, 62.3% of suspected cases) and intensive care unit (ICU)/critical care unit (CCU) patients (62.7% of confirmed cases, 52.2% of suspected cases). Total case fatality rate (CFR) was 10.05% (13.52% and 6.37% among confirmed and suspected cases, respectively). The highest total CFR was observed in patients with age>65 years (25.32%), underlying comorbidities (25.55%), and ICU/CCU patients (41.7%). The highest CFR was reported for patients who had diabetes and cardiovascular diseases (38.46%) as underlying non-communicable diseases (NCDs), and patients with cancer (35.79%). CONCLUSION: This study showed a high CFR among suspected and confirmed COVID-19 cases, and highlighted the main associated risk factors including age, sex, underlying NCDs, and ICU/CCU admission affecting survival of COVID-19 patients.

Monoclonal Antibody Against ROR1 Induces Apoptosis in Human Bladder Carcinoma Cells.

BACKGROUND: Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) is one of the promising cell surface antigens for targeting cancer cells. The aim of this study was to evaluate ROR1 cell surface expression in bladder cancer cells using a murine anti-ROR1 monoclonal antibody (mAb) called 5F1-B10 as well as investigate its potential in apoptosis induction. METHODS: Expression of ROR1 in two human bladder cell lines, 5637 and EJ138, as well as a non-cancerous human cell line, Human Fetal Foreskin Fibroblast (HFFF), was examined by flow cytometry and immunocytochemistry. Immunohistochemical staining of cancer and normal bladder tissues was also performed. RESULTS: The flow cytometry results showed that 5F1-B10 mAb could recognize ROR1 molecules in 86.1% and 45.6% of 5637 and EJ138 cells, respectively. The expression level of ROR1 was 5.49% in HFFF cells. The immunocytochemistry and immunohistochemistry staining results also confirmed the presence of ROR1 on the surface of both bladder cancer cells and tissues, respectively. The obtained data from apoptosis assay demonstrated that 5F1-B10 mAb could induce apoptosis in both 5637 and EJ138 cell lines. CONCLUSION: Taken together, our finding indicates the role of ROR1 in bladder cancer cell survival and suggests this receptor might be a promising target for developing novel therapeutic agents against bladder carcinoma.

Efficacy of Momiai in Tibia Fracture Repair: A Randomized Double-Blinded Placebo-Controlled Clinical Trial.

Objectives: Momiai ( shilajit, mummy, mumie, or mineral pitch) has been used traditionally in different medical systems for the treatment of a variety of ailments since hundreds of years ago. It is a natural substance found in different rocky parts of the world, formed by plants, mineral, and animal remains gradually. There is also worthwhile evidence supporting its oral use for bone repair in Persian medicine. The aim of this study was to evaluate the efficacy and safety of momiai in tibia fracture healing. Design: This study is a randomized double-blinded controlled trial. Settings/Location: Three different hospitals in Tehran, Iran. Subjects: Patients with age range of 18-60 years admitted due to new tibia fracture were enrolled after meeting the inclusion criteria. Interventions: The patients were divided into two groups randomly and received two 500 mg capsules of momiai or placebo for 28 days. Outcome measures: The process of bone healing was assessed by frequent X-ray radiographies and adverse effects were recorded. Results: Totally, 160 patients participated in the study either in two equal intervention or placebo groups. There was no significant difference between groups in terms of demographic and descriptive data. At the end of the study, the mean time of tibial bone union was 129 days in the experimental group, while it was 153 days in the placebo group (p < 0.049). There was no significant difference in the reported adverse effects between the two groups (p = 0.839). Conclusions: The current study showed that oral consumption of momiai after tibial shaft fracture surgery could be a promising option to reduce the healing time.

The efficacy of topical sesame oil in patients with knee osteoarthritis: A randomized double-blinded active-controlled non-inferiority clinical trial.

OBJECTIVE: Sesame oil is an herbal product that has been used to treat the joints pain in several traditional medicines. In this study, we evaluated the efficacy of topical sesame oil versus diclofenac gel in patients with knee osteoarthritis (OA). METHODS: One hundred and four patients were randomly enrolled in two arms of the trial. Patients were treated by topical sesame oil or diclofenac (three times a day) for 4 weeks. Outcome measures were knee pain via visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, knee joint's flexion angle, 8-meter walk test and number of used analgesics. Patients were evaluated at baseline, 2 and then 4 weeks after the intervention. RESULTS: At the follow-up visits, sesame oil was not inferior to diclofenac regarding scores of WOMAC pain, 8-meter walk test, and knee flexion angle. Although, its non-inferiority was not proved regarding scores of VAS, WOMAC stiffness, and WOMAC total at the 4th week. Moreover, sesame oil was not inferior to diclofenac regarding consumed analgesics. CONCLUSION: It seems that the topical sesame oil was non-inferior to diclofenac gel on the reduction of the knee OA pain and improvement of some indicators of its function.

The Study of Anti-Inflammatory Activity of Oil-Based Dill (Anethum graveolens L.) Extract Used Topically in Formalin-Induced Inflammation Male Rat Paw.

Inflammation is one of the symptoms of many common and harmful diseases. As it is incurable through chemical drugs, the study on this ailment using new methods and drugs seems necessary. In addition, the adverse effects of the present anti-inflammatory drugs like NSAIDS and Glucocorticoid appeared in the long time use make such study more demanded. Accordingly, in this study we examined the effects of aerial organs' extract and seed of a plant commonly used in Iranian traditional medicine named Dill on the inflammation caused by plantar injection of formalin in rats and compared them with Diclofenac-gel. One of the methods used for the inflammation assessment is injecting formalin in the rat paw and then measuring the paw volume by the new plethysmometer (weighing method). The assessment is done at a specific time on day for 8 days and then recorded. This study includes 3 groups of 6 male rats: Formalin, Dill-Oil and Diclofenac-gel groups. The Dill-Oil group received 2 g of Dill-Oil, containing 100 mg Dill-extract and the Diclofenac group received 2 g gel containing, 20 mg Diclofenac Na. Data were analyzed with SPSS 17 using ANOVA, Kruskal-Wallis, and Repeated-Measures. The average paw volumes changes in these groups after Formalin-induced inflammation on 1st day, were 0.31 (standard error (SEM) = 0.02), 0.30 (SEM = 0.01) and 0.32 (SEM = 0.05) respectively, with no significant difference. Regarding the peak of inflammation on the 2nd day, it was indicated that the average inflammations in Formalin, Dill-Oil and Diclofenac-gel groups were 0.44 (SEM = 0.03), 0.15 (SEM = 0.04) and 0.36 (SEM = 0.08), respectively. The paw volume changes in groups receiving Dill-oil and Diclofenac-gel, after the daily formalin injection in 8 days compared to the blank group, had a significant decrease (p < 0.001). The Dill group showed even more decrease in the paw volume compared to the Diclofenac one. The results of paw volume measurement analyzed by the Plethysmometer manifest that the Dill-Oil is able to decrease the paw volume significantly.