The Role of Genistein and its Derivatives in Ovarian Cancer: New Perspectives for Molecular Mechanisms and Clinical Applications.

Genistein (GEN) is a member of the polyphenol family, known chiefly for its effects on metabolic diseases and gynecological disorders. GEN has anti-cancer properties by inhibiting tumor proliferation, tumor metastasis, invasion, migration, and inducing apoptosis. Ovarian cancer (OC) is ranked 7th among the most common gynecological cancers. Despite its low incidence compared to other cancers, it is the first cause of death among gynecologic malignancies. Surgery and chemotherapy are the main options for treating this fatal cancer. Therefore, further investigations into GEN may aid in the discovery of novel therapeutics for preventing and/or treating OC. In this review, we aim to investigate the role of GEN in ovarian cancer. We investigate the anti-tumor effects of GEN on OC cell lines, including inducing apoptosis, suppressing tumor growth, and inhibiting metastasis. Also, we review the studies investigating GEN's roles as an adjuvant in therapeutic regimens with other chemotherapeutic agents (e.g., cisplatin, quercetin, and gemcitabine).

Pharmacokinetics and repeated dose 28-day oral toxicity studies of acetaminophen nanosuspension.

Wide availability and easy accessibility of acetaminophen oral dosage forms increase the risk of intentional poisoning or unintentional organ toxicity, leading to a wide range of liver failure, nephrotoxicity, and neurotoxicity. In this study, an attempt was made to improve oral bioavailability and reduce the toxicity of acetaminophen using nanosuspension technology. The acetaminophen nanosuspensions (APAP-NSs) were prepared by a nano-precipitation method using polyvinyl alcohol and hydroxypropylmethylcellulose as stabilizers. The mean diameter of APAP-NSs was 124 ± 3.8 nm. The dissolution profile of APAP-NSs was significantly point-to-point higher than the coarse drug in simulated gastrointestinal fluids. The in vivo study revealed 1.6- and 2.8-fold increases in the AUC0-inf and Cmax of the drug, respectively, in APAP-NSs-receiving animals compared to the control group. Moreover, no deaths and no abnormalities in clinical signs, body weights, and necropsy findings were detected in the dose groups up to 100 mg/kg of the 28-day repeated oral dose toxicity study in mice.

Is it possible to reduce the rate of vertical transmission and improve perinatal outcomes by inclusion of remdesivir in treatment regimen of pregnant women with COVID-19?

BACKGROUND: Coronavirus disease 2019 (COVID-19) is currently one of the world's most critical health issues so far. Given the importance of appropriate treatment in pregnancy and the controversies about Remdesivir effectiveness and complications, the present study aimed to evaluate the impact of Remdesivir on maternal, fetal, and perinatal outcomes in pregnant women with COVID-19 diseases. METHODS: A total of 189 pregnant women with positive polymerase chain reaction (PCR) results for SARS-COV-2, and oxygen saturation [SpO2] of < 95%) were admitted to 12 hospitals affiliated with the Iran University of Medical Sciences from March 1st, 2020 to June 7th, 2021, namely the first four COVID-19 Picks in Iran. They were enrolled in this retrospective cohort study by census method and categorized into case and control groups, based on the inclusion of Remdesivir in their treatment protocol. Demographics, clinical outcomes, and pregnancy-related complications of the mothers and the neonates were compared between the two study groups. RESULTS: A comparison of 54 mothers in the case and 135 in the control group showed no demographic and clinical characteristics difference. Neonates whose mothers did not receive Remdesivir had a higher rate of positive PCR (10.2%), compared to the Remdesivir group (1.9%) with a relative risk of 0.91 reported for Remdesivir (95% CI: 0.85-0.98, P = 0.04); besides, Remdesivir resulted in fewer neonatal intensive care unit admission rates in mild/moderate COVID-19 group (RR = 0.32, 95% CI: 0.105-1.02, P = 0.03). Although neonatal death between the two groups was not statistically significant, from the clinical point seems important; 1(1.9%) in the case vs. 9(7.2%) in the control group. Interestingly LOS (Length of Stay) in the hospital was longer in the case group (median of 7 vs. 3 days; P < 0.0001). CONCLUSION: The inclusion of Remdesivir in the treatment protocol of pregnant women with COVID-19 may reduce vertical transmission and improve perinatal outcomes, thus being suggested to be considered.

Increased risk of primary ovarian insufficiency by high-fructose diet consumption: a 90-day study in female rats.

There is ambiguous evidence that high-fructose diet can induce toxicity in different organ systems but its endocrine disrupting effects by abnormal changes in female reproductive organs is poorly evidenced. This study aimed to address the reproductive safety of high fructose diet through clinical, biochemical, hormonal, histopathological, and immunohistochemical analysis. For this purpose, 5-6 weeks mature female Wistar rats were divided in three groups and each five animals/group exposed to standard chow + water + HFCS-55, standard chow + water + sucrose 75%w/v and standard chow + water for 90 days. Remarkable increase in most lipid profile factors and total body weights of HFCS-55 fed rats and sucrose fed rats were detected in similar pattern compared to control. At the same time, a battery of differential signs and symptoms in HFCS-fed groups including squamous metaplasia in the uterine tissue and ovarian congestion, significant increase in FSH and LH levels, meaningful decreased serum testosterone and 17ß-estradiol levels, and strong androgen receptor expression in ovaries and uterine of HFCS group of animals were recorded compared to other two study groups. These thought-provoking signs and signals of fructose induced reproductive toxicity in this model emphasis the contribution of HFCS-55 to deteriorated ovarian and endometrial health and increased risk primary ovarian insufficiency (POI) in women.

LncRNAs and MiRNAs: New Targets for Resveratrol in Ovarian Cancer Research.

Ovarian cancer (OC) is the 3rd common gynecologic cancer. Numerous procedures are involved in the growth of OC, like migration, angiogenesis, proliferation, apoptosis, invasion, and metastasis. Therefore, a better knowledge of the molecular processes complicated in ovarian tumorigenesis can lead to better measures for the prevention and treatment of the disease and its diagnosis. Long non-coding RNAs (LncRNAs), a subclass of non-coding RNAs, are much more diverse than previously thought. It is suggested that these RNAs may play a role in controlling complex cellular signaling mechanisms via binding to proteins and influencing their function. Nevertheless, our acquaintance with the participation of LncRNAs in the pathogenesis of OC is still restricted. Especially, we do not yet recognize how to pharmacologically correct the epi-mutations. Resveratrol, a natural polyphenol mostly derived from grapes, has been evaluated in many studies to find its cancer therapeutic potential. In the current paper, we aimed to review the role of resveratrol as a potential natural product on lncRNAs as novel diagnostic and therapeutic targets in OC and represent new insights for further investigations.

Ovarian toxicity of plant-derived edible oils: a 28 days hormonal and histopathological study in Wistar rat.

Initial evidence on the endocrine-disrupting effects of genetically modified (GM) food motivated us to evaluate the reproductive toxicity of GM and non-GM plant-derived edible oils in female Wistar rats. Sunflower (non-GM), maize (GM), and canola (GM) oils as popular resource dietary oils were purchased from the local market. After tracking the target sequence of CaMV 35S and Nos terminator in all selected batch numbers of edible oils by real-time PCR, oil samples were daily gavaged to 10 weeks Wistar rats for 28 days. Clinical factors, serum lipid levels, sex hormones, and gonadotropins as well as the histopathological changes were compared among groups by statistical analysis. Besides normal lipid profile, gonadotropin levels, and LH/FSH ratio at day 28, serum estradiol levels were raised in both GM (canola oil (p=0.04)) and non-GM (sunflower oil (p=0.008)) groups. In necropsy studies, ovarian atrophies were detected in canola (p<0.001) and sunflower groups (p<0.043) although uterine remained unchanged in all groups. In histopathological evaluations, all sections showed severe congestion and multiple follicular cysts in the sunflower oil group. Simple and secondary cysts in the maize group were the other type of ovarian toxicity in this short period of time. Remarkable estrogenic properties of GM and non-GM plant-derived edible oils with signs of ovarian atrophy, congestion, and cysts may contribute to phthalate or other xenoestrogenic contaminations; therefore, analytical studies of samples and further human populations studies are highly recommended.

Ovarian cysts disappear after 14-day oral regimen of Korean red ginseng extract in letrozole-induced polycystic ovarian syndrome.

OBJECTIVE: Hormonal and inflammatory mechanisms are involved in the pathogenesis of polycystic ovarian syndrome (PCOS), which is a prevalent metabolic disorder among women of reproductive age. We aimed to evaluate the comparative efficiency of short-term oral administration of Korean red ginseng extract (KRGE) and the standard treatment on PCOS by focusing on the histopathological parameters and serum levels of luteinizing hormone (LH), folliclestimulating hormone (FSH), testosterone, and nuclear factor kappa B (NF-κB). METHODS: A PCOS rat model was established by oral gavage of letrozole (1 mg/kg) for 21 days. The serum levels of LH, FSH, testosterone, and NF-κB were measured, and the morphological features and differences of the ovaries were examined in each group using a light microscope before and after 14 days of treatment with oral regimens-KRGE, oral contraceptives (OCPs), KRGE+OCPs, and carboxymethyl cellulose (CMC). RESULTS: OCPs alone could not normalize the mean ovarian weights of PCOS rats despite the 14-day oral regimen, but they were more effective in reducing the number and size of cysts compared to others. KRGE alone and in combination with OCPs was effective in normalizing abnormal ovarian weights, decreasing LH serum levels, and dissipating the ovarian cysts in PCOS rats. However, when combined with the standard regimen, KRGE showed additional therapeutic effects by efficiently reducing serum testosterone and NF-κB levels. CONCLUSION: Our necropsy and histopathological evidence suggests the efficacy of KRGE as a novel integrative medicine against abnormal multiple follicular cysts. However, antiandrogenic and anti-inflammatory effects were only seen in animals that were administered a combination of KRGE and the standard regimen.

The Level of Testosterone, Vitamin D, and Irregular Menstruation More Important than Omega-3 in Non-Symptomatic Women Will Define the Fate of Multiple Scleroses in Future.

Multiple sclerosis is one of the most salient degenerative disorders of CNS with dysregulated immune process that resulted in axonal damage and demyelination. In the present investigation, the serum level of testosterone was assessed in women who were struggling with multiple sclerosis (MS). Also, the level of omega-3, vitamin D, and the irregular menstruation in women 5 years before the onset MS symptoms were surveyed. Although the levels of omega-3 and vitamin D in women MS patients were non-significant and significantly less than the healthy ones, they were significantly less in the whole population of MS patients. However, the MS patients more experienced more irregular menstruation some years before the onset of MS with the low level of testosterone. Based on the presented findings, it might be said that the vitamin D intake has significant protective role in women and men MS patients unlike the omega-3 that had significant protective role just in men. However, vitamin D metabolism encoding genes of CYP27B1 and CYP24A1 and predicting MS risk gene of HLA-DRB1*15:01 define its fate as well. Besides, vitamin D intake, through the proliferation decrement of pro-inflammatory cells, decreases of pro-inflammatory markers (IL-6, TNF-α, INF-γ) and auto-immune pathways have potential role in recovery of irregular menstruation in women with the low level of testosterone as a red warning factor of MS development. The low level of testosterone and vitamin D consumption increase the neural damage and pro-inflammatory pathways in MS patients, and the difference among the investigations is related to the long-standing history of MS that influences severity of damage to the neural cells and biomolecules and complicate its recovery.

Roles of Kermanshahi Oil, Animal Fat, Dietary and Non- Dietary Vitamin D and other Nutrients in Increased Risk of Premenopausal Breast Cancer: A Case Control Study in Kermanshah, Iran.

BACKGROUND: Kermanshahi oil is one the most favorable oils in Iran especially in Kermanshah province. We aimed to evaluate the role of usual intake of Kermanshahi oil and other kinds of dietary fats as well as different meats, vegetables and fruits, carbohydrates, cereals, grains, sweets, candy and lifestyle habits in risk of breast cancer. MATERIALS AND METHODS: A case-control study with 47 consecutive, newly diagnosed premenopausal breast- cancer patients and 105 age and socioeconomic matched healthy women was conducted from 2013-2014 in Imam Reza hospital of Kermanshah using a standardized, validated questionnaire assessing various anthropometric, socio-demographic, lifestyle and dietary characteristics. RESULTS: Kermanshahi oil intake was associated with a 2.1-fold (OR= 2.123, 95% CI 1.332- 3.38) (p= 0.002) higher likelihood of having breast cancer, while daily intake of other solid animal fats also increased the likelihood by 2.8-fold (OR = 2.754, 95% CI 1.43- 5.273) (p < 0.001), after various adjustments made. Lack of fish oil, white meat, vegetables, soy products, nuts and dairy products (especially during adolescence) in daily regimens and lack of sun exposure were significantly associated with premenopausal breast cancer risk in this region. CONCLUSIONS: This study suggested that animal fat increases the risk of premenopausal breast cancer but many other dietary and non-dietary factors including calcium and vitamin D deficiency are consistently associated with increased odds of breast cancer in this region.

Mutagenicity Assessment of Drinking Water in Combination with Flavored Black Tea Bags: a Cross Sectional Study in Tehran.

Diseases related to water impurities may present as major public health burdens. The present study aimed to assess the mutagenicity of drinking water from different zones of Tehran, and evaluate possible health risks through making tea with tea bags, by Ames mutagenicity test using TA 100, TA 98 and YG1029 strains. For this purpose, 450 water samples were collected over the period of July to December 2014 from 5 different zones of Tehran. Except for one sample, no mutagenic potential was detected during these two seasons and the MI scores were almost normal (≤ 1-1.6) in TA 100, TA 98 and YG1029 strains. Although no mutagenic effects were considered in TA 98 and TA 100 in the test samples of our three evaluated tea bag brands, one sample from a local company showed mutagenic effects in the YG1029 strain (MI=1.7-1.9 and 2) after prolonged (10-15 min.) steeping. Despite the mild mutagenic effect discovered for one of the brand, this cross sectional study showed relative safety of water samples and black tea bags in Tehran. According to the sensitivity of YG1029 to the mutagenic potential of water and black tea, even without metabolic activation by s9 fraction, this metabolizer strain could be considered as sensitive and applicable to food samples for quantitative analysis of mutagens.

Optimization of Self-Assembled Chitosan/Streptokinase Nanoparticles and Evaluation of Their Cytotoxicity and Thrombolytic Activity.

In this study, the enzyme streptokinase (thrombolysis agent) and chitosan (Cs) nanoparticles were prepared by self-assembly. Using experimental design, chitosan concentration, solution pH and stirring time were studied as independent variables to identify their effects on size, polydispersity index (PDI) and loading efficiency of nanoparticles. Results showed that pH and concentration have a direct effect on size. Additionally, minimum PDI was observed at lowest values of concentration and highest values of stirring time. pH-5.6 was also necessary to obtain the smallest PDI and highest loading efficiency values. The model predicted that to obtain maximum loading efficiency and minimum size along with low PDI, optimum values are 0.5 mg/mL, 5.18 and 30 min for the Cs concentration, solution pH and stirring time, respectively. The corresponding mean ± SD values for experimentally prepared nanoparticles were 43 ± 10%, 526 ± 121 nm, 0.3 ± 0.2, respectively. MTT and euglobulin clot lysis assays on the optimized nanoparticles showed that chitosan/streptokinase nanoparticles have slightly toxic effect on human fetal lung fibroblast cells (Mrc-5), compared with chitosan and streptokinase alone as a control. Also, thrombolytic activity of encapsulated streptokinase in nanoparticles is decreased slightly in comparison with free streptokinase. However, the preparation keeps a good potency for use as a thrombolytic agent in vivo.

Increased risk of childhood acute lymphoblastic leukemia (ALL) by prenatal and postnatal exposure to high voltage power lines: a case control study in Isfahan, Iran.

Childhood acute lymphoblastic leukemia (ALL) is one of the most common hematologic malignancies, accounting for one fourth of all childhood cancer cases. Exposure to environmental factors around the time of conception or pregnancy can increase the risk of ALL in the offspring.This study aimed to evaluted the role of prenatal and postnatal exposure to high voltage power lines on the incidence of childhood ALL.This cross-sectional case control study was carried out on 22 cases and 100 controls who were born and lived in low socioeconomic families in Isfahan and hospitalized for therapeutic purposes in different hospitals from 2013-2014.With regard to the underlying risk factors, familial history and parental factors were noted but in this age, socioeonomic and zonal matched case control study, prenatal and childhood exposure to high voltage power lines was considered as the most important environmental risk factors of ALL (p=0.006, OR=3.651, CI 95%, 1.692-7.878). As the population was of low socioeconomic background, use of mobiles, computers and microwave was negligible. Moreover prenatal and postnatal exposure to indoor electrically charged objects was not determined to be a significant environmental factor. Thus, pre and post natal exposure to high voltage power lines and living in pollutant regions as well as familial influence could be described as risk factors of ALL for the first time in a low socioeconomic status Iranian population.

Prostate-specific antigen levels in relation to background factors: are there links to endocrine disrupting chemicals and AhR expression?

BACKGROUND: Prostate-specific antigen (PSA) is a potential biomarker for early detection of prostate cancer (PCa) but its level is known to be affected by many background factors and roles of ubiquitous toxicants have not been determined. Endocrine disrupting chemicals (EDCs) are ubiquitous reproductive toxicants used in consumer products, which promote tumor formation in some reproductive model systems by binding to AhR, but human data on its expression in prostate cancer as well as its association with PSA levels are not clear. This study aimed to evaluate the expression levels of AhR and its association with serological levels of PSA and to detect possible effects of background factors and EDC exposure history on PSA levels in PCa cases. MATERIALS AND METHODS: A cross-sectional study was conducted on the tissue levels of AhR and serum levels of PSA in 53 PCa cases from 2008-2011 and associations between each and background and lifestyle related factors were determined. RESULTS: Although the AhR was overexpressed in PCa and correlated with the age of patients, it did not correlate with PSA levels.Of nutritional factors, increased intake of polysaturated fats and fish in the routine regimen of PCa cases increased the PSA levels significantly. CONCLUSIONS: AhR overexpression in PCa pontws to roles of EDCs in PCa but without any direct association with PSA levels. However, PSA levels are affected by exposure to possible toxicants in foods whichneed to be assessed as possible risk factors of PCa in future studies.

Role of vitamin D deficiency and lack of sun exposure in the incidence of premenopausal breast cancer: a case control study in Sabzevar, Iran.

BACKGROUND: Vitamin D has been suggested as one of the critical factors for female reproductive health with protective activities against different cancers but there are conflicting facts regarding its role on breast cancer without any clear data on premenopausal cases. This study aimed to evaluate the role of vitamin D from dietary sources and sunlight exposure on the incidence of premenopausal breast cancer. MATERIALS AND METHODS: We conducted a case control study on 60 newly diagnosed premenopausal breast cancer patients and 116 normal women who lived in Sabzevar and surrounding villages in Razavi, Khorasan, a rural and conservative area of Iran. RESULTS: The mean concentrations of 25-OH vitamin D in cases and controls were 15.2 ± 8.15 vs 15.5 ± 7/45 ng/ml, both well below normal values elsewhere. In fact 50% of analyzed individuals showed very severe or severe vitamin D deficiency and the rest (25%) were detected in suboptimal levels. Although the lack of vitamin D and calcium supplementation increased slightly the risk of premenopausal breast cancer (p=0.009, OR=1.115, CI 95%=1.049-1.187), higher prevalence of weekly egg consumption (86.66% vs 96.55%, p=0.023, OR=0.232, CI 95% 0.065-0.806) showed a slight protective role. The last but the most important risk factor was lack of sunlight exposure because the breast cancer patients had total body coverage from sun (p=0.007, OR=10.131, CI 98% 0.314-78.102). CONCLUSION: This study pointed out the role of vitamin D and other possible risk factors on the development and growth of breast tumors in this special geographical region. Although this study has revealed the interactions between hormonal and environmental factors in this province of Iran, understanding the deficiency pattern and its contribution to other lifestyle factors elsewhere is also necessary.

Retinoids and their biological effects against cancer.

There are more than 4000 natural and synthetic molecules structurally and/or functionally related to vitamin A. Retinoids are a class of these compounds that are structurally associated to vitamin A. The retinoids have a wide spectrum of functions. Retinoic acid, which is the active metabolite of retinol, regulates a wide range of biological processes including development, differentiation, proliferation and apoptosis. It suppresses carcinogenesis in tumorigenic animal models for the skin, oral, lung, breast, bladder, ovarian and prostate. It is important how major retinoids may act in cancer treatment or prevention. The reports have indicated that lower levels of vitamin A in humans may be associated with relative type 1 cytokine dominance and a higher proportion of NK cells. In addition, very low vitamin A levels would be undesirable explaining the essential role of vitamin A in epithelial and general cell maturation and function. However, the cytokine shifts associated with moderately low levels of vitamin A may be in some ways beneficial in an environment where HIV infection, M. tuberculosis infection, or other type 1 infections are highly prevalent and/or when acquired immunity is cooperated. In this review, we intend to describe the biochemical and immunological functions of retinoids against cancer.

Toxicity assessment of nanosilver wound dressing in Wistar rat.

Antibiotic resistance to microorganisms is one of the major problems faced in the field of wound care in burns patients. Silver nanoparticles have come up as potent antimicrobial agent and are being evaluated in diverse medical applications ranging from silver based dressings to silver coated medical devices. We aimed in present study to test the release of nanosilver from nanosilver wound dressing and compare the dermal and systemic toxicity of nanosilver dressings in a repeated dose (21 days) model. Under general anesthesia, a limited standard 2nd degree burns were provided on the back of each rat in all treatment, negative control (simple dressing) and 5% silver nitrate groups, each contained 5 male wistar rats. According to the analysis made by atomic absorption spectrometry, the wound dressings released 0.599 ± 0.083 ppm of nanosilver during first 24 hrs of study. Daily observations were recoded and wounds were covered with new dressings each 24 hrs. Burn healing was observed in nanosilver wound dressing group in shorter time periods than the control groups. In toxicity assessment, this dressing didn't cause any hematological and histopathological abnormalities in treatment group but biochemical studies showed significant rise of plasma transaminase (ALT) at the endpoint (21 days) of the study (P=0.027). Portal mononuclear lymphoid and polymorphonuclear leukocyte infiltrations in three to four adjacent foci were recognized around the central hepatic vein in treatment group. Mild hepatotoxic effects of nanosilver wound dressing in wistar rat emphasize the necessity of more studies on toxicity potentials of low dose nanosilver by dermal applications.

Role of endocrine disrupting chemicals in the occurrence of benign uterine leiomyomata: special emphasis on AhR tissue levels.

Although benign uterine leiomyomata (LMA) is the most common reproductive tumor in premenopausal women, its etiology is largely unknown. We aimed in the present study to demonstrate the potential role of environmental factors with estrogenic activity in tumor etiology by focusing on the role of aryl hydrocarbon receptor (AhR) which mediates the effects of many environmental endocrine disruptors and contributes to the loss of normal ovarian function in polluted environments. This case-control study aimed to compare the interactions between AhR and lifestyle factors in a clinical setting for the first time among 138 newly diagnosed LMA patients and 138 normal controls who lived in Tehran and Mashhad, respectively, during the last 10 years. To conduct immunohistochemical studies using appropriate monoclonal antibodies, 30 cases were selected retrospectively from 2009-2011 from the pathology departments of two university hospitals in Tehran. Although the levels of sex steroid receptors were similar in adjacent myometrium and uterine leiomyomas of all cases, AhR was significantly overexpressed (p=0.034, OR=1.667) in uterine LMA and this overexpression was correlated with living in Tehran [(p=0.04, OR=16 (1.216-210.58)], smoking[P=0.04, OR=2.085 (1.29-3.371)], living near polycyclic aromative hydrocarbon producing companies [p=0.007, OR=2.22 (1.256-3.926)] and eating grilled meat [p=0.042, OR=1.28 (1.92-3.842)]. Our study contributes to the understanding of the effects of EDCs on AhR levels as well as women's health and points out possible risk factors for the development and growth of uterine LMA. It seems that the development of LMA could be the result of interactions between hormonal and environmental factors.

Change in nicotine-induced VEGF, PGE2 AND COX-2 expression following COX inhibition in human oral squamous cancer.

Cigarette smoke has been documented to be related to the development of cancer. However, the exact mechanism for the carcinogenic action of cigarette smoke is still unknown. Nicotine is recognized to be the major compound in cigarette smoke and has been suggested to play a role in oral cancer via a cyclooxygenase (COX)/ prostaglandin-dependent pathway. This study was designed to evaluate the action of nicotine in the oral cancer cell and to further examine whether COX-2 is responsible for expression of tumor-associated angiogenic vascular endothelial growth factor (VEGF) in vitro. Viability of human oral squamous cancer cells (BHY) was measured using MTT assay. Protein expression was determined by Western blot and immunoassay kits. We found that exposure of BHY cells to nicotine (200 µg/mL for 6 hours) resulted in 2.9-fold induction of COX-2 expression as well as a 4-fold increase in VEGF levels compared with a control group. Pretreatment with celecoxib inhibited nicotine-induced change in the expression of VEGF and COX-2. The results suggest that stimulation of COX-2 and VEGF expression can contribute as important factors in the tumorigenic action of nicotine in oral cancer progression. This effect can be blocked by celecoxib, suggesting an interaction of nicotine and COX-2 pathways.

Role of exogenous and endogenous sources of estrogen on the incidence of breast fibroadenoma: case-control study in Iran.

Breast fibroadenoma (FAD) is the most common benign mammary condition among women but the environmental risk factors have not identified yet. As the role of long term estrogen exposure in the incidence of FAD has been remained controversial; we have decided to investigate the possible role of endogenous and exogenous sources of estrogens in present study. Women less than 45 years old who underwent surgery from June 2009 to June 2010 were matched with controls by age and hospital. From reproductive factors, lack of breast feeding (p< 0.001, 8.76 CI95% 3.79-20.24), Nulliparity (p=0.001, OR=8.09, CI95% 3.505-18.67), Lack of parity (p=0.001, OR=6.64, CI 95% 2.56-16.31) and Hormonal dysfunction (p=0.016, OR=4.66, CI 95% 1.26- 17.28) were considered as the most important ones. Adiposity and abnormal weight gain after 18 years were considered as major background factor which induce FAD and may be contributed to the level of endogenous estrogen. Out of evaluated exogenous sources of estrogen, lower age at first OCP consumption (20.76_+3.87 vs. 22.85_+3.88, p=0.046) and living near Polycyclic aromatic hydrocarbons (PAHs) producing factories (p< 0.001, OR=3.7, CI95%1.61-7.94), were considered as the main sources of exposure to xenestrogens in FAD patients but FAD showed inverse association with cigarette smoking because of antiestrogenic activities of cigarette smoking . This study concludes that the incidence and development of FAD could be associated with the reproductive history of women, activity of ovarian hormones as well as environmental factors.

Association between testicular Aryl hydrocarbon Receptor levels and idiopathic male infertility: a case-control study in Iran.

Increased urinary concentrations of Polycyclic Aromatic Hydrocarbons (PAHs) and their metabolites are associated with increased risk of unexplained infertility in males. The toxicity of PAHs and dioxins are exclusively mediated through Aryl hydrocarbon Receptor (AhR). AhR overexpression contributes to the loss of normal ovarian function in polluted environments but its expression level in unexplained male infertility has remained unclear. This study aimed to compare the differential testicular levels of AhR and its interactions with other fundamental genes (ER, AR, PgR and MMP9) in a case control study. To conduct the immunohistochemical studies, 29 unexplained infertile and 10 fertile males were selected retrospectively from Jahad pathology center of Tehran from 2007 to 2009. Differential expression of AhR in Leydig, Sertoli, spermatogonia, spermatocyte, spermatid, and spermatozoa cells was determined and AhR association with other genes was compared between cases and controls. Higher levels of AhR in Leydig cells (p=0.024), Sertoli cells (p=0.041) and spermatid cells (p=0.028) of infertile men have emphasized the susceptibility of these cells to environmental-induced impaired testicular functions. Moreover 85% of infertile cases showed coexpression of AhR and MMP9 in their Leydig cells (p=0.02). Inactivation of ER, PgR and AR in AhR positive testicular cells suggests the antagonistic interactions between AhR ligands and sex steroid hormones receptors. It seems that unexplained male infertility could be originated from environmental AhR ligands which overexpress the AhR in Leydig cells, downregulate the expression of sex steroid receptors and upregulate the MMP9 in Leydig cells as the main testicular target cell of AhR ligands.