Pre-Exposure to Radiofrequency Electromagnetic Fields and Induction of Radioadaptive Response in Rats Irradiated with High Doses of X-Rays.

Background: Some evidence shows that a pre-exposure to RF can mitigate the effects of subsequent exposures to high doses of ionizing radiation. Objective: We aimed to assess the effect of a pre-exposure to non-ionizing RF radiation on survival, weight changes, food consumption, and water intake of lethally irradiated rats. Material and Methods: In this case-control study, we used a commercial mobile phone (GSM, 900/1800 MHz) as well as a 2.4 GHz Wi-Fi router as the sources of pre-exposure to RF radiation. Forty-eight rats were randomly divided into six groups of control, "8 Gy X-rays", mobile phone, "mobile phone+8 Gy", Wi-Fi, and "Wi-Fi+8 Gy". Then, the survival fraction, weight loss, water, and food consumption changes were compared in different groups. Results: The survival analysis indicated that the survival rates in all of the exposed animals ("8 Gy X-rays", "mobile phone+8 Gy", "Wi-Fi+8 Gy") were significantly lower than the control, "Wi-Fi", and "mobile phone" groups. The changes in survival rates of "mobile+8 Gy", "Wi-Fi+8 Gy", and 8 Gy alone were not statistically significant. However, food and water intake were significantly affected by exposure to both RF pre-exposures and exposure to high dose ionizing radiation. Conclusion: To the best of our knowledge, the existence of a dose window for the induction of AR can be the cause of the lack of AR in our experiment. Our findings confirm that in a similar pattern with the adaptive responses induced by pre-exposure to ionizing radiation, the induction of adaptive response by RF-pre-exposures requires a minimum level of damage to trigger adaptive phenomena.

The hepatoprotective effects of Pyrus biossieriana buhse leaf extract on tert-butyl hydroperoxide toxicity in HepG2 cell line.

OBJECTIVE: In present study, the effects of the leaf extract of Pyrus biossieriana Buhse on tert-Butyl hydroperoxide (t-BHP) induced toxicity in the HepG2 cell line were investigated. RESULTS: HepG2 cells were exposed to different concentrations of both extract (1.5, 2.0, and 2.5 mg/mL) and t-BHP (100, 150, and 200 µM). The total flavonoid and phenolic contents, the cell viability, lipid peroxidation, NO generation, and the total antioxidant capacity in cell media were assessed. The amount of arbutin was estimated 12.6% of the dry weight of leaves (equivalent to 126 mg/g). Additionally, the amounts of flavonoids and phenols in extract were estimated 119 mg/g and 418 mg/g, respectively. The cells incubated with t-BHP showed a significant decrease in survival (p < 0.001). Preincubation with extract (1.5 mg/mL and 2.0 mg/mL) attenuated the t-BHP toxicity and increased the cell viability in cells exposed even to the highest concentration of t-BHP (200 µM) (p value < 0.001, and p value = 0.035) respectively. Additionally, treatment with extract reduced the cell growth suppression caused by t-BHP. The P. biossieriana Buhse leaf extract at concentrations of 1.5 and 2.0 mg/mL is capable of attenuating t-BHP-induced cytotoxicity in HepG2 cells.

Isolation and characterization of human amniotic fluid and SH-SY5Y/ BE(2)-M17 cell derived exosomes.

The application of stem cells as a therapy for degenerative disease holds great promise. Substantial evidence suggests that stem cell derived exosomes are a novel cell-free therapy for the corresponding cells. Exosomes are less complex as compared to their parental cells, due to the fewer number of membrane proteins. In addition, the smaller size and lower risk of immunogenicity makes exosomes potentially safe therapeutic nano-carriers. A large number of ongoing research studies are focused on characterizing exosomes that were derived from different sources, for their potential use in various therapeutic applications. In the present study, we focused on characterizing human amniotic fluid stem cell derived exosomes for future therapeutic applications, such as paracrine therapy/nano carrier. In addition, we characterized exosomes derived from SH-SY5Y and BE(2)-M17 cells, which are a known neuronal model, for further characteristic analyses of neuronal differentiation and neurobiology. Finally, we compared various exosome isolation techniques and procedures and evaluated exosome yield.

The effect of date palm seed extract as a new potential radioprotector in gamma-irradiated mice.

OBJECTIVE: Date palm seed extract (DPSE) has various compounds revealing antioxidant features. This study aimed to evaluate the radioprotective effect of DPSE in total body gamma irradiation. MATERIALS AND METHODS: At first, chemical characteristics of DPSE were analyzed by ultraviolet, visible and Fourier transform infrared spectroscopy. Then, the toxicity of DPSE was assessed. For this purpose, 60 mice were divided into five groups, and each of the groups were injected by the doses of 100, 200, 300, 400, and 500 mg/kg, respectively. At the termination of the experiment, mortality rate and weight loss of all mice were evaluated over a period of 30 days. Finally, the radioprotective effect of DPSE was evaluated by dividing 36 mice into three groups: control, test, and placebo and then were irradiated by Cobalt-60. RESULTS: According to the findings, there was no mortality due to DPSE. Furthermore, for the maximum dose of 500 mg/kg, the number of mice surviving at the termination of the experiment with and without injection of DPSE was reported as 83% and 41%, respectively. In addition, a significant difference was obtained between radiated mice with and without DPSE injection (P = 0.035). CONCLUSION: The findings showed that DPSE injected into mice before irradiation has no toxicity and could protect mice from lethal effects of total body irradiation. The use of DPSE as a new radioprotector agent in the human needs further studies, particularly clinical trials.

Current Status of Used Protocols for Mesenchymal Stem Cell Differentiation: A Focus on Insulin Producing, Osteoblast-Like and Neural Cells.

Mesenchymal stem cells (MSCs) have attracted a great deal of interest in the field of regenerative medicine because of their ability to differentiate into mesodermal derivatives and even other germ layers. The main requirement for better differentiation of MSCs into desired cell lineage is relied on pure population of these cells. During the past years, significant progresses have been developed for the identification of MSCs by introducing new markers or different combination of markers. Currently, direct in vitro differentiation protocols using standard media supplemented with specific growth factors generating osteoblast, insulin producing and neuron cells from MSCs show some key characteristic in in vivo counterparts. However, these efforts should be continued to achieve high amount of fully differentiated cells which have high capacity to be used in cell based therapies and drug screening. This review focuses on common culture based differentiation strategies used for osteoblast, insulin producing cells and neural cells generation from MSCs highlighting important findings and trends in this exciting area.

Targeting cholesterol metabolism in glioblastoma: a new therapeutic approach in cancer therapy.

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor known with a poor survival rate despite current advances in the field of cancer. Additional research into the pathophysiology of GBM is urgently needed given the devastating nature of this disease. Recent studies have revealed the unique cellular physiology of GBM cells as compared with healthy astrocytes. Intriguingly, GBM cells are incapable of de novo cholesterol synthesis via the mevalonate pathway. Thus, the survival of GBM cells depends on cholesterol uptake via low-density lipoprotein receptors (LDLRs) in the form of apolipoprotein-E-containing lipoproteins and ATP-binding cassette transporter A1 (ABCA1) that efflux surplus cholesterol out of cells. Liver X receptors regulate intracellular cholesterol levels in neurons and healthy astrocytes through changes in the expression of LDLR and ABCA1 in response to cholesterol and its derivatives. In GBM cells, due to the dysregulation of this surveillance pathway, there is an accumulation of intracellular cholesterol. Furthermore, intracellular cholesterol regulates temozolomide-induced cell death in glioblastoma cells via accumulation and activation of death receptor 5 in plasma membrane lipid rafts. The mevalonate pathway and autophagy flux are also fundamentally related with implications for cell health and death. Thus, via cholesterol metabolism, the mevalonate pathway may be a crucial player in the pathogenesis and treatment of GBM where our current understanding is still lacking. Targeting cholesterol metabolism in GBM may hold promise as a novel adjunctive clinical therapy for this devastating cancer.

ABO Blood Group and Prevalence of Osteoporosis and Osteopenia in the Elderly Population: An Amirkola Health and Ageing Project (AHAP)-Based Study.

Osteoporosis is known as a degenerative disease of the skeletal system and its main complication is fracture, which influences quality of life in the elderly. There are 4 major blood groups in humans based on the presence of A and B antigens. According to the investigations, there are reported relations between blood types and some diseases. In this study, the association between the ABO blood group and the prevalence of osteoporosis and osteopenia in an elderly population was investigated. Medical records of 990 elderly people were investigated in a cross-sectional study and the association between their blood group and the incidence of osteoporosis and osteopenia was analyzed using SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). The results showed that ABO blood groups had no association with the prevalence of osteoporosis in both elderly men and women. The association between age and osteoporosis was significant and the association between this disorder and gender was significant too. The results also indicate that there is no association between RH+ and RH- blood types and osteoporosis and osteopenia in both men and women. Based on this finding, it would be reasonable to conduct extensive studies.

Migration of dendritic cells to the lymph nodes and its enhancement to drive anti-tumor responses.

Better prognoses associated with increased T cell infiltration of tumors, as seen with chimeric antigen receptor (CAR) T cell therapies and immune checkpoint inhibitors, portray the importance and potential of the immune system in controlling tumors. This has rejuvenated the field of cancer immunotherapy leading to an increasing number of immunotherapies developed for cancer patients. Dendritic Cells (DCs) vaccines represent an appealing option for cancer immunotherapy since DCs have the ability to circumvent tolerance to tumors by its adjuvant properties and to induce memory T cells that can become persistent after initial tumor clearance to engage potential metastatic tumors. In the past, DC-based cancer vaccines have elicited only poor clinical response in cancer patients, which can be attributed to complex and a multitude of issues associated with generation, implementing, delivery of DC vaccine and their potential interaction with effector cells. The current review mainly focuses on migration/trafficking of DCs, as one of the key issues that affect the success of DC-based cancer vaccines, and discusses strategies to enhance it for cancer immunotherapy. Additionally, impact of maturation, route of DC delivery and negative effects of tumor microenvironment (TME) on DC homing to LN are reviewed. Moreover, strategies to increase the expression of genes involved in Lymph node homing, preconditioning of the vaccination site, enhancing lymph node ability to attract and receive DCs, while limiting negative impact of TME on DC migration are discussed.

A molecular perspective on rituximab: A monoclonal antibody for B cell non Hodgkin lymphoma and other affections.

Rituximab (a chimeric anti-CD20 monoclonal antibody) is the first Food and Drug Administration approved anti-tumor antibody. Immunotherapy by rituximab, especially in combination-therapy, is a mainstay for a vast variety of B-cell malignancies therapy. Its therapeutic value is unquestionable, yet the mechanisms of action responsible for anti-tumor activity of rituximab and rituximab resistance mechanisms are not completely understood. Investigation of the mechanisms of action that contribute to the rituximab activity have eventually directed to a suite of novel combinations and novel treatment schedules, and also have resulted new generations of antibodies with more desired effects. Although, further investigations are needed to define the mechanisms of rituximab resistance and prominent effector activity of the altered next generation anti-CD20 to improve their efficacies and develop new anti-CD20 monoclonal antibodies in NHL treatment. This article focuses on the properties of CD20 which led scientists to select it as an effective therapeutic target and the molecular details of mechanisms of rituximab action and resistance. We also discuss about the impact of rituximab in monotherapy and in combination with chemotherapy regimens. Finally, we comparatively summarize the next generations of anti CD20 monoclonal antibodies to highlight their advantages relative to their ancestor: Rituximab.

Interleukin-13 as an important cytokine: A review on its roles in some human diseases.

Interleukin-13 (IL-13) as a pleiotropic cytokine acts through the IL-13Ra1/IL-4Ra complex to induce activation responses which contribute to the inflammatory diseases. Genetic polymorphisms in IL-13 and its receptor components have been proved to be associated with higher disease prevalence rates. Animal models such as in IL-13 deficient mice and transgenic animals also have been confirmed the critical role of this cytokine in the immune responses, mostly by IL-13 neutralization and IL-13/IL-4 dual neutralization strategies. This review highlights IL-13 structure as well as its pivotal roles in the normal physiologic and pathologic states. It is followed by a section on the recent findings on IL-13 receptors and signalling mechanisms to briefly summarize its functions in the immune systems. IL-13 roles in the human diseases such as asthma, systematic sclerosis, and some inflammatory diseases are described concisely. Finally some of the ongoing therapeutic applications are presented to comprehensively review IL-13 mediator roles.

Is there association between ABO blood group and the risk factors of unfavorable outcomes of pregnancy?

There are four major blood groups in human based on the presence of A and B antigens. ABO gene encodes A and B antigens on the surface of red blood cells and there are reported relations between this blood phenotype and pregnancy outcomes in the women. In this study, medical records of 792 healthy pregnant women were investigated and their age and blood test results including blood group with fasting blood sugar, hemoglobin, hematocrit, urea, creatinine and red blood cell counts were analyzed in statistical package for the social sciences. The RBC count in AB blood type was significantly higher than A and O blood group, also FBS level in the people with AB blood group was meaningfully higher than A group. But the mean of HGB and HCT were not significantly different between groups. The serum urea in the AB group was higher than the three other groups and also it was significantly higher in B compared to O and A blood groups. The serum creatinine in the AB group was higher than the three other groups too. Also it was significantly higher in the B group compared to A blood groups. These results indicate that the ABO blood group may have association with some of the risk factors of the unfavorable outcomes of pregnancy and it may be one of the prognostic tools, also it addresses more extensive studies.

Is Radiosensitivity Associated to Different Types of Blood Groups? (A cytogenetic study).

Many biological factors affect radiosensitivity. In this study, radiosensitivity among the different blood groups was investigated. Peripheral blood sample of 95 healthy people were divided into two parts. One part was irradiated with 2 Gy Co-60 gamma rays and the second one was considered as control. Then all the samples were studied by cytokinesis-blocked micronucleus assay (CBMN assay). Our study showed that the radiosensitivity index of A+ and O+ groups was significantly higher and lower than other blood groups, respectively. It seems that blood type can be used as a radiosensitivity index for determining the given dose to radiotherapy, although extensive studies are necessary.

The study of radiosensitivity in left handed compared to right handed healthy women.

BACKGROUND: Radiosensitivity is an inheriting trait that mainly depends on genetic factors. it is well known in similar dose of ionizing radiation and identical biological characteristics 9-10 percent of normal population have higher radiation response. Some reports indicate that distribution of breast cancer, immune diseases including autoimmune diseases as example lupus, Myasthenia Gravies and even the rate of allergy are more frequent in left handed individuals compared to right handed individuals. The main goal of the present study is determination of radiosensitivity in left handed compared to right handed in healthy women by cytokinesis blocked micronuclei [CBMN] assay.5 ml peripheral fresh blood sample was taken from 100 healthy women including 60 right handed and 40 left handed. The age of participants was between 20-25 old years and they had been matched by sex. After blood sampling, blood samples were divided to 2 groups including irradiated and non-irradiated lymphocytes that irradiated lymphocytes were exposed to 2 Gy CO-60 Gama rays source then chromosomal aberrations was analyzed by CBMN [Cytokinesis Blocked Micronuclei Assay]. RESULTS: Our results have shown radiosensitivity index [RI] in left-handers compared to right-handers is higher. Furthermore, the mean MN frequency is elevated in irradiated lymphocytes of left-handers in comparison with right-handers. CONCLUSION: Our results from CBMN assay have shown radiosensitivity in the left handed is higher than right handed women but more attempts need to prove this hypothesis.

Is there association between handedness and radiosensitivity in breast cancer women?

Radiosensitivity is a biological response to radiation. This response depends on many factors such as radiation factors as well as biological system factors. It is shown that identical doses of radiation for the treatment of Cancer patients produce different biological responses that are assumed to be depend on different specifications of the biological systems. However, by elimination of these factors, people may still show different biological responses such as acute and low responses to radiotherapy in similar doses of radiation. Some reports indicate that breast cancer, immune diseases including autoimmune diseases such as lupus, Myasthenia Gravies and even the rate of allergy are more frequent in left-handed compared to right-handed individuals. The main goal of the present study is determination of radiosensitivity in left-handed compared to right-handed in breast cancer women by cytogenetic assay. Peripheral venous blood samples (10 ml) of 30 breast cancer women (10 left- and 20 right-handed) were divided into two identical parts. One part is exposed to 2 Gy Co-60 gamma rays, and the second part is considered as non-exposed controls. Lymphocytes were cultured in standard media, and cytokinesis blocked to score micronuclei in bi-nucleated cells. The frequency of micronuclei in 1,000 cells in each sample is considered as the rate of radiosensitivity and was compared in left- and right-handed breast cancer women by appropriate statistical analysis. Results showed that radiosensitivity index in left-handers is higher than right-handers also mean frequency of MN in exposed group of left-handers compare to right-handers is elevated. It seems that left-handed breast cancer women are more radiosensitive than right-handed. More investigations on right- and left-handed healthy people are ongoing in our laboratory.

Effects of Teucrium Polium Aerial Parts extract on oral glucose tolerance tests and pancreas histopathology in Streptozocin-induced diabetic rats.

Teucrium polium can reduce serum glucose. There are few reports in the literature related to this subject and the resolution of this mechanism requires further experiments. The aim of the present study was to evaluate the effects of Teucrium polium aerial parts extracts on oral glucose tolerance tests and pancreas histology in streptozocin-induced diabetic rats. In order to prepare the aqueous concentrate, aerial parts extract was dissolved in distilled water and was boiled for 30 minutes. For the preparation of ethanolic solution, powder was dissolved in ethanol and mixed by a shaker. Diabetic rats were induced with single IP injection of streptozotocin (STZ) at a dose of 50 mg/kg body weight dissolved in normal saline just before use to the 16 hr fast rats. Both groups, diabetic and normal were sacrificed by ether anesthesia. The tissue samples were formalin fixed and paraffin embedded for microscopic examination in accordance with routine laboratory procedures. Blood was collected from the tail vein of the rats. Serum glucose levels were then measured by commercial kits by using a glucose oxidized method. There were no biochemical abnormalities or histological changes in the pancreas of control rats. Post treatment of Teucrium polium aerial parts extract reduced the severity of streptozotocin diabetic pancreases. Our histopathological investigation along with the biochemical evaluations showed a significant effect on histological changes in the pancreas of induced diabetic rats upon Teucrium polium aerial parts extract treatment (P<0.05).