The effect of hormonal levels and oxidative stress on bisphenol A and soy isoflavone reproductive toxicity in murine offspring.

Previous studies have suggested that human exposure to bisphenol A (BPA) and soy isoflavones (SIFs) can occur during pregnancy. The combination of these chemicals is hypothesized to have a toxic impact on the fetus. While BPA is an industrial chemical used widely in the manufacture of polycarbonate plastics and epoxy resins, SIFs are naturally occurring estrogen­like phytoestrogens. To determine the impact of the combination of BPA and SIFs on fetal development, the body weight, organ weight, anogenital distance and histopathological changes in the testes of F1 offspring were assessed in mice. Hormonal effects were determined by measuring serum levels of estrogen receptor (ESR), follicle­stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T). Additionally, mitochondrial DNA copy numbers, and the serum levels of malondialdehyde and superoxide dismutase, were determined to evaluate alterations in oxidative stress and potential toxicity. Exposure to BPA increased the body weight of the pups and reduced the ratio of anogenital distance to body weight, as well as testes weight. Moreover, BPA exposure also induced testicular lesions. The seminiferous tubules of testis were denatured in varying degrees and the lumen wall structure was disordered. The levels of ESR in all offspring and the T levels in male offspring significantly increased, compared with controls. Co­exposure to BPA and SIFs exacerbated these changes in body weight, testicular lesions and hormonal levels, relative to BPA exposure alone. Additionally, oxidative damage was only induced by high­dose BPA. Collectively, these findings suggested that BPA and SIFs could have synergistic effect on the reproductive system, which could be mediated by the regulation of ESR expression and testosterone release.

Mongolian Medicine echinops prevented postmenopausal osteoporosis and induced ER/AKT/ERK pathway in BMSCs.

Hormone replacement medicine such as traditional Chinese medicine has proven to be effective in decreasing the risk of osteoporosis. Mongolian medicine echinops prevents osteoporosis, but its mechanism remains unclear. In this study, we explored the mechanism underlying echinops prevents and treats postmenopausal osteoporosis. Osteoporosis model was established by ovariectomy in rats. Rats were treated to Echinops (16.26, 32.5, or 65 mg/kg/day) by oral gavage for 3 months. Bone mineral density (BMD) was detected by micro-CT detection of left proximal medial metaphyseal tibia. Hematoxylin and eosin (H&E) and toluidine blue O staining were also performed. Serum levels of E2, ALP and testosterone were examined. Bone marrow-derived bone marrow stem cells (BMSCs) were isolated and treated with echinops-containing serum. Estrogen receptors (ER) including ERα and ERß in bone specimens and BMSCs were detected by qRT-PCR. Cell viability and colon formation of BMSCs were detected. Expressions of ERα, ERß, AKT, p-AKT, ERK, and p-ERK in BMSCs were detected by western blot. Results showed that echinops significantly increased trabecular interconnectivity, thickness of trabeculae, and connection of trabecula. Echinops significantly increased BMD and E2, but significantly reduced ALP and testosterone in dose-dependent manners. Echinops induced ERα and ERß in both bone specimens and BMSCs. Echinops enhanced cell viability and ability of colony formation of BMSCs, and increased ERα, ERß, p-AKT, and p-ERK. Thus, Mongolian echinops reduced bone loss and delayed the occurrence and development of osteoporosis, and increased ERα, ERß, p-AKT, and P-ERK in BMSCs. These results provide experimental basis for clinical prevention and treatment of postmenopausal osteoporosis by echniops.

Results of 1-year Diet and Exercise Interventions for ER+/PR±/HER2- Breast Cancer Patients Correlated with Treatment Type.

PURPOSE: Many breast cancer patients gain weight during chemotherapy and antiestrogenic treatment increasing recurrence, oncologic specific and all-cause mortality risks. Patients and Methods: 165 ER+/PR±/HER2- breast cancer patients under antiestrogenic treatment were randomly assigned to follow an at-home diet based on food naturally high in proteins, calcium, probiotics and prebiotics (D), or this diet and 4' isometric exercises (D+Ex) for 1 year. We measured weight (W), body (BF) and visceral fat (VF) using a multi-frequency bioelectrical impedance scale on the 6th and 12th month and we correlated results with chemotherapy, surgery and antiestrogenic medication type. Results were analysed using the Friedman Test, then with Wilcoxon signed-rank tests if Friedman Test was significant. Results: Overall, the patients 1-year results show that both D+Ex and D patients obtained statistically significant weight loss and fat loss. D patients lost 3.3 kg, 3.2% BF and 1% visceral fat. D+Ex patients lost 6.5 kg, 3.3% BF and 2% visceral fat. D+Ex patients obtained statistically significance for W, BF and VF regardless of chemotherapy, surgery or antiestrogenic treatment type. D patients with mastectomy or with aromatase inhibitors lost W, BF and VF. D patients with conservatory surgery, adjuvant or both neoadjuvant and adjuvant chemotherapy and those on Tamoxifen only lost W. D patients with neoadjuvant chemotherapy also lost VF. CONCLUSION: This diet is effective for ER+/PR±/HER2- breast cancer patients on antiestrogenic medication. Adding at least a minimal exercise protocol improves patients chances of counteracting sarcopenic obesity.

The effect of fermented red ginseng on depression is mediated by lipids.

OBJECTIVES: The cortico-limbic hypothalamic-pituitary-adrenal axis has emerged as an important area for the cause and treatment of depression. The primary aim of this study was to test the hypothesis that hormones, energy sources, and minerals have a causal relationship with depression. The secondary aim was to test whether consumption of fermented red ginseng (FRG) would influence that causal relationship. METHODS: For this study, 93 postmenopausal women were randomly divided into two groups. One group (49 women) was supplied with FRG capsules, and the other group (44 women) with placebo capsules, for 2 weeks. Both before and after the study, the participants filled out the Beck depression inventory questionnaire, and then blood samples were collected. The structural regression model was established. The causative latent variables were hormone (adrenocorticotropic hormone and cortisol), energy (low-density lipoprotein (LDL) cholesterol, total cholesterol, and blood glucose), mineral 1 (potassium, sodium, chloride, and iron), and mineral 2 (magnesium, calcium), and the resultant latent variables were cognitive depression (CD) and somatic depression. The goodness-of-fit statistics of the final model were good (root mean square error of approximation =0.033, comparative fit index =0.877, and Tucker-Lewis index =0.870). RESULTS: The structural regression path of the energy factor on CD showed a significant difference between the FRG group (0.259) and the placebo group (-0.201). The factor loadings of total cholesterol (1.236) and LDL cholesterol (1.000) on the energy factor were much higher than that of glucose (0.166). CONCLUSION: Based on the analysis used in this model, the effect of FRG consumption on CD occurred via the energy factor, which is mainly attributable to cholesterol.

Association of serum level of 25 hydroxy-vitamin D with prognostic factors for breast cancer.

BACKGROUND AND AIM: In recent years, there has been considerable interest in whether vitamin D inhibits breast cancer development. Experimental studies have shown that vitamin D promotes cell differentiation and retards or terminates proliferation of breast cancer cells. However, there is little evidence supporting the association of vitamin D and prognosis of breast cancer. METHODS AND MATERIALS: In this analytic-descriptive study, 119 female patients with histological proven breast cancer were recruited in Tabriz oncology clinics in a 15-month period of time. History of chemotherapy, radiotherapy or receiving vitamin D/Ca supplements and presence of other malignancies were exclusion criteria. Serum level of 25 hydroxy vitamin D (25(OH)D) was measured in all patients. RESULTS: One hundred and nineteen patients with a mean age of 50.4∓12.6 (26-76) years were enrolled in the study. Metastasis was present in 21.8% of the cases. Stage of tumor was I, II, III and IV in 11, 56, 26 and 26 patients, respectively. The Tumor grade was low in 37 cases, intermediate in 46 cases, and high in 36 cases. The P53, Ki-67, HER2, ER and PR were positive in 30.3%, 49.6%, 17.6%, 61.2% and 55.5% of the patients, respectively. The mean serum level of 25(OH)D was 15.7∓17.8 (4-122) ng/ml, deficient in 66 cases, insufficient in 36 cases and normal level in 17 cases. The median level of 25(OH)D was lower in the P53+ group in a borderline trend (17.3 vs. 13.6 ng/ml; p=0.07). The median level of 25(OH)D was significantly higher in the patients with metastasis, as well (27.7 vs. 12.0 ng/ml; p=0.03). There was no significant association between the serum level of 25(OH)D and other studied parameters. CONCLUSION: Based on our findings, there may be an association between the serum level of 25(OH)D and prognosis of breast cancer.

Modulators of vascular sex hormone receptors and their effects in estrogen-deficiency states associated with menopause.

Cardiovascular disease (CVD) is more prevalent in postmenopausal than premenopausal women, suggesting vascular protective effects of estrogen. Also, experimental studies have demonstrated beneficial effects of estrogen in improving vascular function and reducing vascular injury. However, clinical trials including HERS I, HERS II, WHI and WISDOM have demonstrated minimal beneficial vascular effects of menopausal hormone therapy (MHT) in postmenopausal women with CVD. The discrepancies between the experimental findings and clinical data may be related to the vascular estrogen receptors (ER), the type, route of administration, or dosage of MHT, and subject's age. Vascular ERs mediate both genomic and non-genomic effects of estrogen on the endothelium, vascular smooth muscle (VSM), and extracellular matrix (ECM). Postmenopausal changes in vascular ER structure, polymorphisms, amount, subcellular location, affinity or signaling could modify their responsiveness to estrogen and thereby the outcome of MHT. Recent investigations and patents have been centered on developing new ER modulators and alternatives for the traditional natural and synthetic forms of MHT which carry the risk of invasive breast cancer and venous thromoboembolism. Phytoestrogens may have similar effects as traditional MHT and have not demonstrated harmful side effects. Specific estrogen receptor modulators (SERMs) such as raloxifene and tamoxifen have also been tested. ER agonists that selectively target ERalpha, ERbeta and perhaps GPR30 may modify specific vascular signaling pathways. Also, the dose, route of administration, and timing of MHT are integral to optimizing the beneficial effects and minimizing the side effects of MHT. Progesterone, testosterone and modulators of their specific receptors may also affect the overall vascular effects of MHT in estrogen-deficiency states associated with menopause.

[Improvement effects of Jincao tablet on immune function of model of hysteromyoma in rats].

OBJECTIVE: To investigate the improvement effects of Jincao tablet on immune function of the model of hysteromyoma in rat and the relationship between the model and pathogenesis. METHOD: Rats were randomly divided into 6 groups: normal group, model group, treatment groups including low,middle and high dosage groups of Jincao tablet and Guizhi Fuling pill. Rats were injected respectively with diethyl stilbestrol and progesterone. The immune apparatus of rats were measured. The levels of CD3, CD4 and CD4/ CD8 in serum were determined by flow cytometer. The estrogen and receptor were measured by radioligand binding assay and pathologic changes of womb tissue were observed microscopically. RESULT: Compared with normal group, the weight of thymus, the levels of CD3, CD4 and CD4/CD8 of model group were significantly decreased, and the levels of estrogen, estrogen receptor and CD8 were obviously increased. Jincao tablet groups were significant difference compared with model group and could alleviate the pathological changes of womb tissue. CONCLUSION: Jincao tablet could improve the levels of immune function of the model of hysteromyoma in rat, and it might play a role in the pathogenesis of leiomyoma.