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Abstract: Cancer has remained to be one of the major challenges in medicine and regarded as the second leading cause of death worldwide. Different types of cancer may resist anti-cancer drugs following certain mutations such as those in tumor suppressor genes, exhaustion of the immune system, and overexpression of drug resistance mediators, which increase the required concentration of anticancer drugs so as to overcome drug resistance. Moreover, treatment with a high dose of such drugs is highly associated with severe normal tissue toxicity. Administration of low-toxic agents has long been an intriguing idea to enhance tumor suppression. Naturally occurring agents e.g., herb-derived molecules have shown a dual effect on normal and malignant cells. On the one hand, these agents may induce cell death in malignant cells, while on the other hand reduce normal cell toxicity. Nobiletin, one of the well-known polymethoxyflavones (PMFs), has reportedly shown various beneficial effects on the suppression of cancer and the protection of normal cells against different toxic agents. Our review aims to explain the main mechanisms underlying nobiletin as an inhibitor of cancer. We have reviewed the mechanisms of cancer cell death caused by nobiletin, such as stimulation of reactive oxygen species (ROS), modulation of immune evasion mechanisms, targeting tumor suppressor genes, and modulation of epigenetic modulators, among others; the inhibitory mechanisms of nobiletin affecting tumor resistance properties such as modulation of hypoxia, multidrug resistance, angiogenesis, epithelial-mesenchymal transition (EMT) have been fully investigated. Also, the inhibition of anti-apoptotic and invasive mechanisms induced by nobiletin will later be discussed. In the end, protective mechanisms of nobiletin on normal cells/tissue, clinical trial results, and future perspectives are reviewed.

Abstract: Induction of cell death and inhibition of cell proliferation in cancer have been set as some of the main goals in anti-tumor therapy. Cancer cell resistance leads to less efficient cancer therapy, and consequently, to higher doses of anticancer drugs, which may eventually increase the risk of serious side effects in normal tissues. Apigenin, a nature-derived and herbal agent, which has shown anticancer properties in several types of cancer, can induce cell death directly and/or amplify the induction of cell death through other anti-tumor modalities. Although the main mechanism of apigenin in order to induce cell death is apoptosis, other cell death pathways, such as autophagic cell death, senescence, anoikis, necroptosis, and ferroptosis, have been reported to be induced by apigenin. It seems that apigenin enhances apoptosis by inducing anticancer immunity and tumor suppressor genes, like p53 and PTEN, and also by inhibiting STAT3 and NF-κB signaling pathways. Furthermore, it may induce autophagic cell death and ferroptosis by inducing endogenous ROS generation. Stimulation of ROS production and tumor suppressor genes, as well as downregulation of drug-resistance mediators, may induce other mechanisms of cell death, such as senescence, anoikis, and necroptosis. It seems that the induction of each type of cell death is highly dependent on the type of cancer. These modulatory actions of apigenin have been shown to enhance anticancer effects by other agents, such as ionizing radiation and chemotherapy drugs. This review explains how cancer cell death may be induced by apigenin at the cellular and molecular levels.

Abstract: Cancer therapy through anticancer drugs and radiotherapy is associated with several side effects as well as tumor resistance to therapy. The genotoxic effects of chemotherapy and radiotherapy may lead to genomic instability and increased risk of second cancers. Furthermore, some responses in the tumor may induce the exhaustion of antitumor immunity and increase the resistance of cancer cells to therapy. Administration of low-toxicity adjuvants to protect normal tissues and improve therapy efficacy is an intriguing strategy. Several studies have focused on natural-derived agents for improving the antitumor efficiency of radiotherapy, chemotherapy, and novel anticancer drugs such as immunotherapy and targeted cancer therapy. Resveratrol is a naturally occurring substance with intriguing antioxidant, cardioprotective, anti-diabetes, and antitumor properties. Resveratrol has been demonstrated to modulate tumor resistance and mitigate normal tissue toxicity following exposure to various drugs and ionizing radiation. Compelling data suggest that resveratrol may be an appealing adjuvant in combination with various anticancer modalities. Although the natural form of resveratrol has some limitations, such as low absorption in the intestine and low bioavailability, several experiments have demonstrated that using certain carriers, such as nanoparticles, can increase the therapeutic efficacy of resveratrol in preclinical studies. This review highlights various effects of resveratrol that may be useful for cancer therapy. Consequently, we describe how resveratrol can protect normal tissue from genomic instability. In addition, the various mechanisms by which resveratrol exerts its antitumor effects are addressed. Moreover, the outcomes of combination therapy with resveratrol and other anticancer agents are reviewed.

Introduction: The results of studies on the biological effects of ionizing radiation can play an important role in reducing the risk of occupational hazards of personnel working at the radiological departments of the hospital. This study aimed to investigate the concentration of aluminum, manganese, and selenium in the blood serum of operating room staff and their association with occupational radiation exposure. Materials & Methods: In total, 100 healthy operating room staff was selected using systematic random sampling. They were then divided into three groups of radiation workers, non-radiation worker, and test (those who were exposed to X-rays but did not wear film badges). Subsequently, two milliliters of peripheral blood were taken intravenously from volunteers and centrifuged to separate serum. The concentration of three elements was read by the graphite furnace atomic absorption spectroscopy. The analysis of variance was used to analyze the concentration of aluminum, manganese, and selenium in all groups. Moreover, the fitting curve of the occupational exposure was described using the R software. Ethics code: ir.kums.rec.1397.467 Findings: The normality of the data was assessed and confirmed by the Kolmogorov-Smirnov test. Moreover, the concentration values (ng/ml) of aluminum, manganese, and selenium were 8.62, 9.08, and 76.15, as well as 13.53, 12.14, and 140.97 in the non- and radiation worker groups, respectively. The difference between the two groups was significant for all three elements (P

Abstract: The idea of cancer immunotherapy has spread, and it has made tremendous progress with the advancement of new technology. Immunotherapy, which serves to assist the natural defenses of the body in eradicating cancerous cells, is a remarkable achievement that has revolutionized both cancer research and cancer treatments. Currently, the use of stem cells in immunotherapy is widespread and shares a special characteristic, including cancer cell migration, bioactive component release, and immunosuppressive activity. In the context of cancer, mesenchymal stem cells (MSCs) are rapidly being identified as vital stromal regulators of tumor progression. MSCs therapy has been implicated in treating a wide range of diseases, including bone damage, autoimmune diseases, and particularly hematopoietic abnormalities, providing stem cell-based therapy with an extra dimension. Moreover, the implication of MSCs does not have ethical concerns, and the complications known in pluripotent and totipotent stem cells are less common in MSCs. MSCs have a lot of distinctive characteristics that, when coupled, make them excellent for cellular-based immunotherapy and as vehicles for gene and drug delivery in a variety of inflammations and malignancies. MSCs can migrate to the inflammatory site and exert immunomodulatory responses via cell-to-cell contacts with lymphocytes by generating soluble substances. In the current review, we discuss the most recent research on the immunological characteristics of MSCs, their use as immunomodulatory carriers, techniques for approving MSCs to adjust their immunological contour, and their usages as vehicles for delivering therapeutic as well as drugs and genes engineered to destroy tumor cells.

Immune system interactions within the tumour have a key role in the resistance or sensitization of cancer cells to anti-cancer agents. On the other hand, activation of the immune system in normal tissues following chemotherapy or radiotherapy is associated with acute and late effects such as inflammation and fibrosis. Some immune responses can reduce the efficiency of anti-cancer therapy and also promote normal tissue toxicity. Modulation of immune responses can boost the efficiency of anti-tumour therapy and alleviate normal tissue toxicity. Melatonin is a natural body agent that has shown promising results for modulating tumour response to therapy and also alleviating normal tissue toxicity. This review tries to focus on the immunomodulatory actions of melatonin in both tumour and normal tissues. We will explain how anti-cancer drugs may cause toxicity for normal tissues and how tumours can adapt themselves to ionizing radiation and anti-cancer drugs. Then, cellular and molecular mechanisms of immunoregulatory effects of melatonin alone or combined with other anti-cancer agents will be discussed.

Background: Lung is one of the radiosensitive and late responding organs, and is an important target for ionizing radiation. Radiation-induced pneumonitis and fibrosis are major consequences of lung exposure to a high dose of radiation and pose threats to the lives of exposed people. Mitigation of lung injury following an accidental radiation event or for patients with lung cancer is one of the most interesting issues in radiobiology. In the current study, we aimed to determine whether celecoxib, the most common cyclooxygenase-2 (COX-2) inhibitor, is able to mitigate pneumonitis and fibrosis following lung irradiation or not. Materials and methods: 20 male mice were assigned to 4 groups: control, celecoxib treatment, radiation, and radiation plus celecoxib. Irradiation was performed with a dose of 18 Gy cobalt-60 (60Co) gamma rays. Celecoxib treatment (50 mg/kg) started 24 h after irradiation and continued four times per week for 4 weeks. Results: Irradiation of lung led to remarkable infiltration of macrophages, lymphocytes, mast cells and neutrophils. Also, a mild increase in fibrosis markers including accumulation of collagen, and alveolar and vascular thickening, was observed. Post-exposure treatment with celecoxib was able to mitigate fibrosis as well as alveolar and vascular changes, however, it was unable to mitigate pneumonitis markers. Conclusion: Celecoxib showed that it may have an anti-fibrosis effect following exposure of mice lung to radiation, although it was unable to prevent pneumonitis.

Aim: In this study, we aimed to determine possible mitigation of radiationinduced toxicities in the duodenum, jejunum and colon using post-exposure treatment with resveratrol and alpha-lipoic acid. Background: After the bone marrow, gastrointestinal system toxicity is the second critical cause of death following whole-body exposure to radiation. Its side effects reduce the quality of life of patients who have undergone radiotherapy. Resveratrol has an antioxidant effect and stimulates DNA damage responses (DDRs). Alpha-lipoic acid neutralizes free radicals via the recycling of ascorbic acid and alpha-tocopherol. Objective: This study is a pilot investigation of the mitigation of enteritis using resveratrol and alpha-lipoic acid following histopathological study. Methods: 60 male mice were randomly assigned to six groups; control, resveratrol treatment, alpha-lipoic acid treatment, whole-body irradiation, irradiation plus resveratrol, and irradiation plus alpha-lipoic acid. The mice were irradiated with a single dose of 7 Gy from a cobalt-60 gamma-ray source. Treatment with resveratrol or alpha-lipoic acid started 24 h after irradiation and continued for 4 weeks. All mice were sacrificed after 30 days for histopathological evaluation of radiation-induced toxicities in the duodenum, jejunum and colon. Results and Conclusion: Exposure to radiation caused mild to severe damages to vessels, goblet cells and villous. It also led to significant infiltration of macrophages and leukocytes, especially in the colon. Both resveratrol and alpha-lipoic acid were able to mitigate morphological changes. However, they could not mitigate vascular injury. Conclusion: Resveratrol and alpha-lipoic acid could mitigate radiation-induced injuries in the small and large intestine. A comparison between these agents showed that resveratrol may be a more effective mitigator compared to alpha-lipoic acid.

Background: Lung is a radiosensitive organ. Studies have shown that exposure of the lung to acute and high doses of radiation following inhalation of radioactive agents or an accidental radiological event may lead to pneumonitis and fibrosis, which are associated with a risk of death. So far, some agents have been studied for mitigation of pneumonitis and fibrosis following exposure of murine lung tissues to ionizing radiation. In this study, we aimed to detect the possible mitigatory effect of alpha-lipoic acid, resveratrol and their combination on mice pneumonitis and fibrosis markers following irradiation. Methods: 25 mice were divided into 5 groups: control, radiation; radiation plus alpha-lipoic acid; radiation plus resveratrol; and radiation plus both resveratrol and alpha-lipoic acid. Mice chest regions were irradiated with 18 Gy using a cobalt-60 gamma rays source. Treatments started 24 h after irradiation and continued for two weeks. After 100 days, all mice were sacrificed and their lung tissues removed for histopathological evaluation. Results: Pathological study showed that exposure to radiation led to severe pneumonitis and moderate fibrosis after 100 days. Both resveratrol and alpha-lipoic acid, as well as their combination could mitigate pneumonitis and fibrosis markers. Although, resveratrol could not mitigate infiltration of most inflammatory cells as well as inflammation and vascular damage, alpha-lipoic acid and its combination were able to mitigate most damaged markers. Conclusion: Alpha-lipoic acid and its combination with resveratrol were able to mitigate fibrosis and pneumonitis markers in mice lung tissues following lung irradiation. Although resveratrol has a protective effect on some markers, it has a weaker effect on lung injury. In conclusion, our results suggest that the combination of resveratrol and alpha-lipoic acid has a potent mitigatory effect compared to the single forms of these agents.

Purpose: Efforts to produce radioprotective agents of high potential are appropriate strategies for overcoming possible IR toxicity in organisms. The present research aims to evaluate the signaling pathways and mechanisms through which arbutin exerts radioprotective effects on organisms. Methods: The databases of PubMed, Web of Sciences, Google Scholar, and Scopus were searched to find studies that reported radioprotective effects for arbutin. Besides, the data were searched within the time period from 2010 to 2020. Result: Five research articles met our criteria, which were included in the analysis based on their relevance to the topic. The present systematic review provides conclusions about various mechanisms and pathways through which arbutin induces radioprotection. Conclusions: Based on the relevant studies, various mechanisms can be proposed for inducing radioprotective effects by arbutin, including inhibition of oxidative stress, apoptosis, and inflammation.

Objective: Pentoxifylline enhances neurite elongation in PC12 cells. This study investigated the effects of pentoxifylline on staurosporine-induced neurite elongation in PC12 cells. Materials and Methods: There were five treatment groups, including treatment group I (1 nM), treatment group II (10 nM), treatment group III (100 nM), treatment group IV (1uM), and treatment group V (10 mM of pentoxifylline), together with 214 nM staurosporine for a range of time (6, 12 and 24 hours). Cells only treated with staurosporine at a concentration of 214 nM were used as the control group. Cell proliferation, cell death, immunocytochemistry assay, and Total Neurite Length were assessed. Results: The results showed that pentoxifylline increased cell viability (p

Background: Quantitative Magnetization Transfer Imaging (QMTI) is often used to quantify the myelin content in multiple sclerosis (MS) lesions and normal appearing brain tissues. Also, automated classifiers such as artificial neural networks (ANNs) can significantly improve the identification and classification processes of MS clinical datasets.Objective: We classified patients with relapsing-remitting multiple sclerosis (RRMS) from healthy subjects using QMTI and T1 longitudinal relaxation time data of brain white matter and the performance of three ANN-based classifiers have been investigated. Materials and Methods: Conventional magnetic resonance imaging (MRI) and quantitative magnetization transfer scans were obtained from RRMS patients (n=30) and age-matched healthy subjects (n=30). After image pre-processing and brain tissue segmentation, QMTI parameters including magnetization transfer ratio (MTR), magnetization transfer rate (Ksat), T1 relaxation time under MT saturation pulse (T1sat) and T1 longitudinal relaxation time were calculated as parametric maps. Three ANN algorithms, including multilayer perceptron (MLP), radial basis function (RBF) and ensemble neural network based on Akaike information criterion (ENN-AIC) input features were extracted in the form of QMTI and T1 mean values. The ANNs quantitative performance is measured by the standard evaluation of confusion matrix criteria.Results: The results indicate that ENN-AIC-based classification method has achieved 90% accuracy, 92% sensitivity and 86% precision compared to other ANN classification models such as RBF and MLP. NPV, FPR and FDR values of the proposed ENN-AIC model were found to be 0.933, 0.125 and 0.133, respectively. A graphical representation of how to track actual data by the predictive values derived from each of the three algorithms, was also presented. It has been demonstrated that ENN-AIC as an effective neural network improves the quality of classification results compared to MLP and RBF.Conclusion: The efficiency and robustness of ENN classifier will greatly enhance with the use of AIC-based combination weights assignment. In addition, this research provides a new direction to classify a large amount of quantitative MRI data that can help the physician in a correct MS diagnosis.

The main focus of the current study is the fabrication of a multifunctional nanohybrid based on graphene oxide (GO)/iron oxide/gold nanoparticles (NPs) as the combinatorial cancer treatment agent. Gold and iron oxide NPs formed on the GONPs via the in situ synthesis approach. The characterisations showed that gold and iron oxide NPs formed onto the GO. Cell toxicity assessment revealed that the fabricated nanohybrid exhibited negligible toxicity against MCF-7 cells in low doses (

Background: Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods: We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings: The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1-65·8), 17·4% (7·7-28·4), and 59·5% (34·2-86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation: By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health. This work was primarily supported by a grant from the Bill & Melinda Gates Foundation (OPP1132415). S Aljunid reports additional funding from the International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia and Department of Health Policy and Management, Faculty of Public Health, Kuwait University for the approval and support to participate in this research project outside of the study. A Awasthi is supported by the Department of Science and Technology, Government of India, New Delhi, through the INSPIRE Faculty Program outside of the study. A Badawi reports additional funding from the Public Health Agency of Canada outside of the study. A Barac reports additional funding from the Project of Ministry of Education, Science and Technology of the Republic of Serbia (no III45005) outside of the study. T Bärnighausen reports additional funding by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research outside of the study. F Carvalho and E Fernandez report additional funding from the Portuguese national funds (UID/MULTI/04378/2019 and UID/QUI/50006/2019) outside of the study. V M Costa reports additional funding from Fundação da Ciência e Tecnologia (FCT) for her grant (SFRH/BPD/110001/2015), which was funded by national funds through FCT – Fundação para a Ciência e a Tecnologia, IP, under the Norma Transitória – DL57/2016/CP1334/CT0006 outside of the study. J De Neve reports additional funding from the Alexander von Humboldt Foundation outside of the study. K Deribe reports additional funding from the Wellcome Trust (grant number 201900) as part of his International Intermediate Fellowship outside of the study. D Endalew and M Moradi report additional funding from Wolkite University. M Ausloos, C Herteliu, and A Pana report additional funding from the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI (project number PN-III-P4-ID-PCCF-2016-0084) outside of the study. C Herteliu reports additional funding from the European Fund for Regional Development through Operational Program for Competitiveness (Project ID P_40_382) and the European Fund for Regional Development, through InterReg Romania-Hungary (project code EMS ROHU 217) outside of the study. P Hoogar reports additional funding from the Centre for Holistic Development and Research (CHDR), Kalaghatagi and The Department of Studies in Anthropology, Karnatak University, D S Islam reports additional funding from the National Heart Foundation of Australia and the Institute for Physical Activity and Nutrition, Deakin University outside of the study. A Khatony reports additional funding from the Clinical Research Development Center of Imam Reza Hospital in Kermanshah outside of the study. J Khubchandani reports additional funding from Merck Research Laboratories outside of the study. K Krishan reports additional funding from the UGC Center of Advanced Study (CAS II) awarded to the Department of Anthropology, Panjab University, Chandigarh, India outside of the study. M Kumar reports additional funding from the Fogarty Foundation/NIH through a K43 award (TW010716-01A1) outside of the study. B Lacey reports additional funding from the National Institute for Health Research Oxford Biomedical Research Centre and the British Heart Foundation Centre of Research Excellence (Oxford, UK) outside of the study. A M Samy reports additional funding from the Egyptian Fulbright Mission Program (EFMP) outside of the study. S Seyedmousavi reports additional funding from the Intramural Program of National Institute of Health Clinical Center, Bethesda, MD, USA outside of the study. M Shey reports additional funding from the Wellcome Trust Kenji Shibuya reports additional funding from Japan's Ministry of Health, Labour and Welfare and Japan's Ministry of Education, Culture, Sport, Science and Technology outside of the study. M Sobhiyeh reports additional funding from the Clinical Research Development Center of Imam Reza Hospital, Kermanshah University of Medical Sciences outside of the study. J Soriano reports additional funding from Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain outside of the study. N Taveira reports additional funding from the LIFE study (RIA2016MC-1615) of the European and Developing Countries Clinical Trials Partnership (EDCTP) program supported by the European Union outside of the study. B Unnikrishnan reports additional funding from the Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India outside of the study. T Wijeratne reports additional funding from the Department of Medicine, Faculty of Medicine, University of Rajarata, Saliyapura, Sri Lanka outside of the study. C S Wiysonge reports additional funding from the South African Medical Research Council and the National Research Foundation of South Africa outside of the study.

Nuclear medicine patients are isolated in a room after the injection of a radiopharmaceutical. They may be active Wi-Fi option of its smartphone mobile or other environmental radiofrequency waves. The hypothesis of this study was the evaluation of increased biological effects of the simultaneous exposure to gamma-ray and the Wi-Fi waves by measuring the level of the increased double strand-breaks DNA in peripheral blood lymphocyte in the rat.Fifty male Wistar rats were exposed for 2, 24, and 72 h only by Wi-Fi,The manner of gamma-H2AX expression was not the same for three groups in time. The number of gamma-H2AX foci between the three groups was a significant difference after 72 h.Simultaneous Wi-Fi and gamma-ray exposures can increase the number of double-strand break DNA in peripheral blood lymphocytes to exposure of gamma-ray to 72 h after technetium injection in the rat.

INTRODUCTION: Professionalism and medical ethics are a vital quality for doctors, which has been taken into account seriously in recent years. Perception of the factors affecting professionalism may help develop more efficient approaches to promote this quality in medical education. This study was aimed to explain the role of hidden curriculum in the formation of professional ethics in Iranian medical students. MATERIALS AND METHODS: This qualitative study was performed on 15 medical interns of Kermanshah University of Medical Sciences in 2019, using grounded theory. Sampling was started by purposive sampling and continued through theoretical sampling until complete data saturation. Data collection and analysis were done simultaneously. Data were interpreted by a constant comparative method according to Strauss and Corbin's approach. RESULTS: The analysis of the participants' interviews and reduction of findings using common themes yielded one class and four categories as well as a number of concepts as the role of hidden curriculum in the formation of professional ethics in medical students. The categories included the role of modeling in the formation of professional ethics, role of education in the formation of professional ethics, role of environmental factors in the formation of professional ethics, and role of personal and inherent attributes in the formation of professional ethics. CONCLUSION: Curriculum developers and medical education authorities need to proceed in line with the findings of the present study to provide a proper learning environment, in which the modeling, learning, and teaching conditions and supportive environmental atmosphere are taken into account in accordance with the inherent and individual characteristics of the learners in order to guarantee the formation of professional ethics in medical students.

Accidental exposure to ionizing radiation is a serious concern to human life. Studies on the mitigation of side effects following exposure to accidental radiation events are ongoing. Recent studies have shown that radiation can activate several signaling pathways, leading to changes in the metabolism of free radicals including reactive oxygen species (ROS) and nitric oxide (NO). Cellular and molecular mechanisms show that radiation can cause disruption of normal reduction/oxidation (redox) system. Mitochondria malfunction following exposure to radiation and mutations in mitochondria DNA (mtDNA) have a key role in chronic oxidative stress. Furthermore, exposure to radiation leads to infiltration of inflammatory cells such as macrophages, lymphocytes and mast cells, which are important sources of ROS and NO. These cells generate free radicals via upregulation of some pro-oxidant enzymes such as NADPH oxidases, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Epigenetic changes also have a key role in a similar way. Other mediators such as mammalian target of rapamycin (mTOR) and peroxisome proliferator-activated receptor (PPAR), which are involved in the normal metabolism of cells have also been shown to regulate cell death following exposure to radiation. These mechanisms are tissue specific. Inhibition or activation of each of these targets can be suggested for mitigation of radiation injury in a specific tissue. In the current paper, we review the cellular and molecular changes in the metabolism of cells and ROS/NO following exposure to radiation. Furthermore, the possible strategies for mitigation of radiation injury through modulation of cellular metabolism in irradiated organs will be discussed.

Background: Professionalism and medical ethics are a vital quality for doctors, which has been taken into account seriously in recent years. Perception of the factors affecting professionalism may help to develop more efficient approaches to promote this quality in medical education. Objective: This study was aimed to explain the role of hidden curriculum in the formation of professional ethics in the Iranian medical students. Methods: This qualitative study was performed on 15 medical interns using grounded theory. Sampling was started by purposive sampling and continued through theoretical sampling until complete data saturation. Data collection and analysis were done simultaneously. Results: The analysis of the participants’ interviews and reduction of findings using common themes yielded one class and four categories as well as a number of concepts as the role of hidden curriculum in the formation of professional ethics in medical students. The categories included the role of modeling in the formation of professional ethics, role of education in formation of professional ethics, role of environmental factors in the formation of professional ethics, and role of personal and inherent attributes in the formation of professional ethics. Conclusion: The curriculum developers and medical education authorities need to proceed in line with the findings of the present study to provide a proper learning environment in which the modeling, learning, and teaching conditions and supportive environmental atmosphere are taken into account in accordance with the inherent and individual characteristics of the learners in order to guarantee the formation of professional ethics in the medical students.

Purpose: Lung tissue is one of the most sensitive organs to ionizing radiation (IR). Early and late side effects of exposure to IR can limit the radiation doses delivered to tumors that are within or adjacent to this organ. Pneumonitis and fibrosis are the main side effects of radiotherapy for this organ. IL-4 and IL-13 have a key role in the development of pneumonitis and fibrosis. Metformin is a potent anti-fibrosis and redox modulatory agent that has shown radioprotective effects. In this study, we aimed to evaluate possible upregulation of these cytokines and subsequent cascades such as IL4-R1, IL-13R1, Dual oxidase 1 (DUOX1) and DUOX2. In addition, we examined the potential protective effect of metformin in these cytokines and genes, as well as histopathological changes in rat’s lung tissues. Methods: 20 rats were divided into 4 groups: control; metformin treated; radiation + metformin; and radiation. Irradiation was performed with a 60Co source delivering 15 Gray (Gy) to the chest area. After 10 weeks, rats were sacrificed and their lung tissues were removed for histopathological, real-time PCR and ELISA assays. Results: Irradiation of lung was associated with an increase in IL-4 cytokine level, as well as the expression of IL-4 receptor-a1 (IL4ra1) and DUOX2 genes. However, there was no change in the level of IL-13 and its downstream gene including IL-13 receptor-a2 (IL13ra2). Moreover, histopathological evaluations showed significant infiltration of lymphocytes and macrophages, fibrosis, as well as vascular and alveolar damages. Treatment with metformin caused suppression of upregulated genes and IL-4 cytokine level, associated with amelioration of pathological changes. Conclusion: Results of this study showed remarkable pathological damages, an increase in the levels of IL-4, IL4Ra1 and Duox2, while that of IL-13 decreased. Treatment with metformin showed ability to attenuate upregulation of IL-4–DUOX2 pathway and other pathological damages to the lung after exposure to a high dose of IR.

Protection of normal tissues against toxic effects of ionizing radiation is a critical issue in clinical and environmental radiobiology. Investigations in recent decades have suggested potential targets that are involved in the protection against radiation-induced damages to normal tissues and can be proposed for mitigation of radiation injury. Emerging evidences have been shown to be in contrast to an old dogma in radiation biology; a major amount of reactive oxygen species (ROS) production and cell toxicity occur during some hours to years after exposure to ionizing radiation. This can be attributed to upregulation of inflammatory and fibrosis mediators, epigenetic changes and disruption of the normal metabolism of oxygen. In the current review, we explain the cellular and molecular changes following exposure of normal tissues to ionizing radiation. Furthermore, we review potential targets that can be proposed for protection and mitigation of radiation toxicity.

Background : Accurate dose assessment and correct identification of irradiated from non-irradiated people are goals of biological dosimetry in radiation accidents. Objectives: Changes in the FDXR and the RAD51 gene expression (GE) levels were here analyzed in response to total body exposure (TBE) to a 6 MV x-ray beam in rats. We determined the accuracy for absolute quantification of GE to predict the dose at 24 hours. Materials and Methods : For this in vivo experimental study, using simple randomized sampling, peripheral blood samples were collected from a total of 20 Wistar rats at 24 hours following exposure of total body to 6 MV X-ray beam energy with doses (0.2, 0.5, 2 and 4 Gy) for TBE in Linac Varian 2100C/D (Varian, USA) in Golestan Hospital, in Ahvaz, Iran. Also, 9 rats was irradiated with a 6MV X-ray beam at doses of 1, 2, 3 Gy in 6MV energy as a validation group. A sham group was also included. After RNA extraction and DNA synthesis, GE changes were measured by the QRT-PCR technique and an absolute quantification strategy by taqman methodology in peripheral blood from rats. ROC analysis was used to distinguish irradiated from non-irradiated samples (qualitative dose assessment) at a dose of 2 Gy. Results: The best fits for mean of responses were polynomial equations with a R2 of 0.98 and 0.90 (for FDXR and RAD51 dose response curves, respectively). Dose response of the FDXR gene produced a better mean dose estimation of irradiated “validation” samples compared to the RAD51 gene at doses of 1, 2 and 3 Gy. FDXR gene expression separated the irradiated rats from controls with a sensitivity, specificity and accuracy of 87.5%, 83.5% and 81.3%, respectively, 24 hours after dose of 2 Gy. These values were significantly (p

Emerging evidences show that changes in tumor stroma can adapt cancer cells to radiotherapy, thereby leading to a reduction in tumor response to treatment. On the other hand, radiotherapy is associated with severe reactions in normal tissues which limit the amount radiation dose received by tumor. These challenges open a window in radiobiology and radiation oncology to explore mechanisms for improving tumor response and also alleviate side effects of radiotherapy. Transforming growth factor beta (TGF-β) is a well-known and multitasking cytokine that regulates a wide range of reactions and interactions within tumor and normal tissues. Within tumor microenvironment (TME), TGF-β is the most potent suppressor of immune system activity against cancer cells. This effect is mediated through stimulation of CD4+ which differentiates to T regulatory cells (Tregs), infiltration of fibroblasts and differentiation into cancer associated fibroblasts (CAFs), and also polarization of macrophages to M2 cells. These changes lead to suppression of cytotoxic CD8 + T lymphocytes (CTLs) and natural killer (NK) cells to kill cancer cells. TGF-β also plays a key role in the angiogenesis, invasion and DNA damage responses (DDR) in cancer cells. In normal tissues, TGF-β triggers the expression of a wide range of pro-oxidant and pro-fibrosis genes, leading to fibrosis, genomic instability and some other side effects. These properties of TGF-β make it a potential target to preserve normal tissues and sensitize tumor via its inhibition. In the current review, we aim to explain the mechanisms of upregulation of TGF-β and its consequences in both tumor and normal tissues.

Small variations in trace element levels may cause important physiological changes in the human body. This study aims to evaluate five important trace elements in radiation workers.In this study, 44 radiation workers and an equal number of non-radiation workers were selected as the case and control group, respectively. The concentrations of iron, magnesium, zinc, copper, and selenium in the serum of the participants were measured using an Atomic Absorption Spectrometry (AAS).The mean concentrations of iron, magnesium, zinc, copper, and selenium for the case group were 107.3 µg/dl, 2.3 mg/dl, 80.9 µg/dl, 112.6 µg/dl and 216.7 ng/ml, respectively. The results for the control group were 121.9 µg/dl, 2.3 mg/dl, 82.3 µg/dl, 112.8 µg/dl and 225.2 ng/ml, respectively.The mean concentration of iron in the case group was significantly lower than the control group (p-value = 0.012), while the concentrations of other elements in both of the groups were not significantly different. In the case group, except magnesium (p-value = 0.021), no significant relationship was found between age and the elemental concentrations. According to Spearman's test, there was a meaningful statistical correlation between the sex and concentration of iron, Mg, Zn, and Se. Also, the correlation between the concentration of magnesium and the weights of radiation workers was significant (p-value =0.044).

Background: Rapid dose assessment using biological dosimetry methods is essential to increase the chance of survival of exposed individuals in radiation accidents. Objectives: We compared the expression levels of the FDXR and RAD51 genes at 6 and 18 MV beam energies in human peripheral blood lymphocytes. The results of our study can be used to analyze radiation energy in biological dosimetry. Methods: For this in vitro experimental study, from 36 students in the medical physics and virology departments, seven voluntary, healthy, non-smoking male blood donors of Khuzestan ethnicity with no history of exposure to ionization radiation were selected using simple randomized sampling. Sixty-three peripheral blood samples were collected from the seven healthy donors. Human peripheral blood was then exposed to doses of 0, 0.2, 0.5, 2, and 4 Gy with 6 and 18 MV beam energies in a Linac Varian 2100C/D (Varian, USA) at Golestan hospital in Ahvaz, Iran. After RNA extraction and cDNA synthesis, the expression levels of FDXR and RAD51 were determined 24 hours post-irradiation using the gel-purified reverse transcription polymerase chain reaction (RT-PCR) technique and TaqMan strategy (by real-time PCR). Results: The expression level of FDXR gene was significantly increased at doses of 2 Gy and 4 Gy in the 6 - 18 MV energy range (P < 0.001 and P < 0.008, respectively). The medians with interquartile ranges (IQRs) of the copy numbers of the FDXR gene at 2 Gy and 4 Gy doses under 6 and 18 MV beam energies were 2393.59 (1798.21, 2575.37) and 2983.00 (2199.48, 3643.82) and 3779.12 (3051.40, 5120.74) and 5051.26 (4704.83, 5859.17), respectively. However, RAD51 gene expression levels only showed a significant difference between samples at a dose of 2 Gy with 6 and 18 MV beam energies, respectively (P < 0.040). The medians with IQRs of the copy numbers of the RAD51 gene were 2092.77 (1535.78, 2705.61) and 3412.57 (2979.72, 4530.61) at beam energies of 6 and 18 MV, respectively. Conclusions: The data suggest that the expression analysis of the FDXR gene, contrary to that of the RAD51 gene, may be suitable for assessment of high-energy X-ray. In addition, RAD51 is not a suitable gene for dose assessment in biological dosimetry.

Reiner RC Jr, Hay SI. Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17: analysis for the Global Burden of Disease Study 2017. Lancet 2020; 395: 1779–801—In this Article, the author byline has been amended to Local Burden of Disease Diarrhoea Collaborators. This correction has been made to the online version as of June 4, 2020, and the printed version is correct. © 2020 Elsevier Ltd