Polymorphisms in Phase I (CYP450) Genes CYP1A1 (rs4646421), CYP1B1 (rs1056836), CYP19A1 (rs749292) and CYP2C8 (rs1058930) and Their Relation to Risk of Breast Cancer: A Case-Control Study in Mazandaran Province in North of Iran

BACKGROUND: The second leading cause of cancer-related death in women is breast cancer. Xenobiotic Metabolizing Enzymes (XMEs) contribute to the detoxification of numerous cancer therapy-induced products. In the metabolism of xenobiotic, cytochrome P450s or monooxygenases perform an important function by catalysing the hydroxylation reaction. In this study, the susceptibility and genetic polymorphisms of CYP450 isoenzymes was investigated that may have an etiological role in breast cancer. AIM: The main purpose of this study was to evaluate the association of CYP1A1 (rs4646421), CYP1B1 (rs1056836), CYP2C8 (rs1058930), and CYP19A1 (rs749292) polymorphisms with the risk of breast cancer in Mazandaran province. MATERIAL AND METHODS: This cross-sectional case-control study were recruited 72 patients and 51 healthy individuals and was performed between March 2018 to May 2018 in the Oncology Department at Imam Hospital in Sari city, Iran. Peripheral blood samples were collected in EDTA tube, and DNA extraction was performed using the salting-out method and WizPrep extraction kits. Breast cancer patients with known clinicopathological characters and healthy women as control group were genotyped for genes polymorphisms by PCR-RFLP technique, using restriction enzymes. Chi-square, Fisher exact test and Logistic regression model, were applied for statistical analysis. RESULTS: The results of the experiments showed that there was a significant relationship between two groups and the age of the patients is significantly higher than the control group (p = 0.044). According to the chi-square and Fisher exact test, education, pregnancy, menopause status and oppose were significant between the two groups. Based on using a logistic regression model in two normalized and age-adjusted models to finding relationship between the genotypes of each gene and breast cancer risk, it was determined that in the CYP2C8 genotype, those who have the CG allele have a 7.74 degree increased risk of breast cancer (CI = 95% 0.95-62.5) and in the CYP19A1 gene, individuals with GA genotype, increased risk of breast cancer (CI = %95 1.52-27.21), about the CYP1B1 gene, people with two genotypes of CG + GG had higher risk of breast cancer (CI = %95 1.19-5.71) and allele G has decreased risk of breast cancer in this gene (P = 0.0271), also allele G in CYP2C8 gene had the protective effect (P = 0.02). In the age-adjusted model, for the CYP2C8 gene, GG genotype increased risk of breast cancer (CI = %95 1.11-75.84) as well as, the CG + GG genotype in CYP1B1 gene (CI = %95 1.31-6.57). CONCLUSION: Our results confirm the association between CYP2C8 (rs1058930), CYP19A1 (rs749292) and CYP1B1 (rs1056836) gene polymorphisms and increased risk of breast cancer in women in Mazandaran province

The effect of dexamethasone on uterine receptivity, mediated by the ERK1/2-mTOR pathway, and the implantation window: An experimental study

Background: The role of glucocorticoids in implantation has been demonstrated. Objective: This study aimed to evaluate the effect of dexamethasone on endometrial receptivity. Materials and Methods: In this experimental study, 40 BALB/c female mice aged eight wk old weighing approximately 25.0 ± 1.4 gr were used. The mice were divided into four groups (n = 10/each) of control, dexamethasone (100 μg/kg, intraperitoneal injection), mammalian target of rapamycin (mTOR) inhibitor (PP242) (30 mg/kg, intraperitoneal injection), and dexamethasone and PP242. The endometrial epithelium of the mouse was separated to measure messenger RNA expression of heart and neural crest derivativesexpressed protein 2 (HAND2), Msh homeobox 1 (Msx-1), heparin binding epidermal growth factor (HB-EGF), microRNA (miRNA) Let-7a, miRNA-145 and miRNA-451, using real-time polymerase chain reaction. Also, protein expression of mammalian mTOR and eukaryotic translation initiation factor 4E-binding protein1 (4E-BP1) was measured using western blot. Results: The results revealed that the expression of Msx-1, HAND2, HB-EGF, miRNA-451, and miRNA-Let-7a was significantly decreased in the endometrium in the dexamethasone group compared to the control, while the expression of miRNA-145 in the endometrium was up-regulated. Additionally, the administration of PP242, known as an inhibitor of mTOR, was associated with significantly reduced expression of Msx-1, HAND2, HB-EGF, miRNA-451, and miRNA-Let-7a, while PP242 induced messenger RNA expression of miRNA-145. Conclusion: It appears that dexamethasone can diminish uterine receptivity during the implantation period, at least to some extent, through the alteration of particular genes that impact endometrial receptivity. Furthermore, the mTOR pathway seemingly showed an essential role in endometrial receptivity. Key words: Endometrial receptivity, Dexamethasone, HB-EGF, MSX-1, mTOR, Mouse

Prevention Effects of Hydroalcoholic Extracts Bottle Gourd (Lagenaria siceraria standl.) on Life Cells Faced with Anti-Cancer Drug Doxorubicin

Introduction: In most cases, drugs used for chemotherapy are ineffective and have unpleasant side-effects. This has made scientists to find more effective drugs with less toxicity. Lagenaria siceraria is an important medicinal plant in the world and anti-tumoral activity of Lagenaria species has been reported in some studies.In this study, the preventive effects of hydraualcoholic lagenaria siceraria on the toxicity resulting from doxorubicin in the cells of normal and cancer cells were investigated. Methods and Results: Hydroalcoholic extract of Lagenaria siceraria was prepared by percolation method. Then, the effects of solutions containing the sample with different concentrations (1, 50, 100, 250, 500, 1000 µg/ml) of each extract were provided and then were studied  by the evaluation method MTT on the renal fibroblast cell line (NIH3T3) and breast cancer cell line (MCF7). Doxorubicin was considered as positive control. The results were analyzed through ANOVA and T-test. P<0.05 is considered as the level of significance. The findings indicated that the IC50 dose of Doxorubicin on the normal fibroblast cell line (NIH3T3) and breast cancer cell line (MCF7) is 402± and 101± µg/ml, respectively. On the other hand, lagenaria siceraria has no significant cytotoxic effects. Conclusions: This extract lagenaria siceraria caused a significant decrease in proliferation of breast cancer cells. Therefore, it is recommended to diagnose the active materials in this extract and determine the mechanism of their effect

The hepatoprotective effect of Arnebia euchroma hydro-alcoholic extract against liver toxicity induced by CCl4 in mice

Arnebia euchroma is from Boraginaceae family. Various therapeutic effects have been reported for different species of this plant. The aim of this study was to investigate antioxidant activity of hydroalcoholic extract of the root of A. euchroma and its protective effect on hepatotoxicity induced by CCl4 in mice. In this experimental study, A. euchroma was extracted with ethanol solvent by maceration method. Antioxidant activity of the plant has been evaluated by the DPPH free radical scavenging method. Then, the hepatoprotective effect of A. euchroma was evaluated through determination the content of glutathione in liver tissue, ALP, AST, ALT serum levels and histopathology of liver in different groups. The total phenolic content determined as 0.56% per 100 g of plant was equivalent to gallic acid. The total flavonoid content was 0.079% per 100 g of plant that was equivalent to quercetin. The IC50 of the extract for free radical scavenging was obtained 139.2 µg/ml. The extract increased liver glutathione and serums ALP, AST, ALT that were decreased by CCl4 administration in animal. All protective effects were dose-dependent and the results of liver histopathology showed a significant improvement of inflammation and necrosis that were caused by CCl4 in mice. The results of this study revealed that the hydroalcoholic extract of A. euchroma root has an antioxidant effect and excellent hepatoprotection in mice

Investigation of cadmium content in Iranian rice (Oryza Sativa):

Cadmium is one of the dangerous heavy metals which its presence in nature and entrance to humans food chain, causes the serious damage in kidneys, lungs, bones, and also anemia and sometimes hypertension. The major source of cadmium intake is rice for rice eating countries such as Iran. Cadmium in rice comes from soil through plant roots. Thus, Rice may be the best indicator for the environment mentoring of cadmium especially in rice eating countries. The most important sources of soil pollution to cadmium are industrial sludge sewage discharge for increasing its fertility, applying superphosphate fertilizers and etc. At this investigation surveyed Cd content of tarrom rice. A total of 60 samples were collected from four areas of Qaemshahr region in north of Iran (Mazandaran province). The samples were collected in during harvesting of rice in filed. The first step, grains of rice were digested by acid digestion method then were analyzed for cadmium by atomic absorption spectrometer. The results showed that average concentration of Cd in rice was 0.41\ub10.17 mg/kg dry wt. Notably the Cd content in the rice samples was found to be upper the FAO/WHO Guidelines. We concluded that a substantial exists in Cd contents in the rice of four areas and hence health risk is maximum and this risk will increase to eating other foods such as vegetable, fish and etc and also the situation could worsen in the future. Treatment and remediation of polluted soils and environment, decreasing easing of fertilizer using could reduce Cd intake by plant and consequently health risk

Effect of organophosphorous pesticides on acetyl cholinesterase activity in agricultural workers

زمینه و هدف: استفاده از سموم ارگانوفسفره به عنوان حشره کش یا علف کش از دیر باز در استانهایی مانند مازندران بعلت وفور مزارع کشاورزی رواج داشته است. از آنجا که بسیاری از کارگران مزارع در تماس با این سموم قرار می گیرند بنابراین امکان جذب این سموم از طریق پوست وجود دارد. این کار تحقیقی به منظور بررسی میزان جذب سموم از طرق مختلف در این کارگران انجام شده است. روش مطالعه: بدین منظور از روش رنگ سنجی المن در سنجش فعالیت آنزیم استیل کولین استراز (AchE) استفاده شد. نمونه ها از 35 کارگر زمین کشاورزی برنج که 10 تا 15 روز پس از استفاده از سموم ارگانو فسفره، در داخل زمین کشاورزی بطور پا برهنه کار می کردند، گرفته شد و 35 نفر نمونه به عنوان شاهد از بین افراد سالم با شرایط یکسان انتخاب شدند با این تفاوت که در تماس یا مواجهه با این سموم نبوده و در زمین کشاورزی نیز کار نمی کردند. فعالیت آنزیم استیل کولین استراز به صورت واحد در میلی لیتر گلبول قرمز محاسبه شد. نتایج: تفاوت معنی داری بین میانگین فعالیت آنزیم در مردان و زنان شاهد بدست نیامد اما این تفاوت در مردان و زنان کارگر از نظر آماری معنی دار نشان داده شد (05/0

An epidemiological survey of drug poisoning and a comparison with other poisonings cases admitted to a university hospital in Gorgan, Iran, 2008-2015

Background and aims: Acute drug poisoning is a major public health problem in the world.The aim of this study was to investigate the trends and characteristics of acute drug poisoning and to compare that with other poisonings in Gorgan, Iran. Methods: This descriptive cross-sectional study was done from March 2008 to march 2015. Data were obtained from medical records. Stata software and Pearson's chi-squared test were used for data analysis. Results: A total of 800 poisoning cases, 573 cases were due to drug poisoning. The majority of the 573 patients (50.8 male) were in the age range of 20-29 years (47.8) and 78 of them were living in urban areas. The maximum number of poisoning occurred during summer season (27). The most common agents involved in acute drug poisoning were sedatives-hypnotics drugs, especially BZDs (37.2), followed by Tramadol (17.3) and Cardiac drugs (13.1). Poisoning most commonly occurred as ingestion of single drug (55). More than half (77.1) of the cases were intentional poisoning (suicide), followed by overdose (63.1), drug abuse (51.9) and accidental poisoning (17.3). Moreover, the most common drug involved in intentional poisoning was BZDs (44).9 patients (1.6) died, of which 3(33.3) were due to Narcotic drugs. Conclusion: Drugs were the most common cause of poisonings and the majority of acute drug poisoning in Gorgan was associated with suicide attempts. So, easy access to the most prominent methods of suicide i.e. consumption of drugs particularly BZDs should be restricted