Effects of cadmium on the reproductive axis of Japanese medaka (Oryzias latipes)

Cadmium (Cd) is a ubquitous element and a significant inorganic pollutant that has previously been found to bioaccumulate in reproductive organs of fish and disrupt important endocrine processes, especially those involved in synthesis, release and metabolism of hormones. Clearly, there is potential for reproductive effects in fish populations exposed to Cd, however, few studies have investigated the non-lethal consequences of Cd in fish. To this extent, adult male and female Japanese medaka were exposed to 0-10 ppb Cd for 7 weeks. Reproductive endpoints were monitored during weeks 6 and 7 of exposure and compared to physiological responses along the hypothalamus-pituitary-gonadal (HPG) axis, including plasma vitellogenin (VTG), hepatic estrogen receptor (ER), plasma steroids, gonadal-somatic indices (GSI), and gonadal steroid release. There were no observed effects on VTG and ER by long-term Cd exposure. However, gonadal steroid release was significantly decreased in males and females at all exposure concentrations and female plasma estradiol levels were significantly altered at concentrations higher than 5 ppb Cd. Overall, responses along the HPG axis were more sensitive to Cd exposure than the reproductive and developmental endpoints, which were not affected in this study, indicating that higher level impairment in fish might be relatively protected.     

Effects of exposure to 17alpha-ethinylestradiol during early development on sexual differentiation and induction of vitellogenin in zebrafish (Danio rerio)

The effect of acute stress on plasma beta-corticosterone (B), testosterone (T) and estradiol-17beta (E2) concentrations in juvenile alligators collected from sites with varying sediment contaminants was examined in this study. Dramatic increases in plasma B concentrations were observed in alligators from all of the sites after 2 h of capture although females from the intermediate contaminant site exhibited a significantly lower percentage increase in B than females from the other two sites. Males from the site with the highest contaminant levels exhibited elevated initial B concentrations relative to the other sites. This pattern was not observed after 2 h of restraint. Females from the highest contaminant site exhibited depressed initial T when compared to the other sites although this pattern was not observed after 2 h of restraint. Neither E2 nor T decreased after 2 h in females, whereas T concentrations decreased in all males over the same time period. The variance associated with these endpoints was also examined to determine whether it could serve as a more sensitive marker for perturbations of the endocrine system and stress response. Females from the higher and intermediate contaminant sites exhibited the lowest and highest standard errors (respectively) associated with 2 h plasma B concentrations with no differences among mean concentrations suggesting a perturbation of the stress response in these animals that was not detected by examining the means. We concluded that the environmental contaminants could be acting as stressors, leading to the observed differences.     

雌激素与丹栀逍遥丸对更年期女性生殖内分泌系统及免疫功能的调节作用

目的:探究雌激素联合丹栀逍遥胶囊对更年期综合征妇女生殖内分泌系统及免疫功能的调节作用。方法:选取2014年5月至2014年9月我院收治的女性更年期综合症患者60例并将其随机分为两组,其中对照组给予雌激素替代等临床常规疗法;实验组在雌激素替代治疗基础上加用丹栀逍遥胶囊联合治疗。观察并比较两组患者生殖内分泌激素(E2、FSH、LH)水平、T淋巴细胞亚群(CD3+、CD4+、CD8+、CD4+/CD8+)比例以及IL-2活性的变化。结果:治疗后,两组血清E2、CD3+、CD4+、CD4+/CD8+水平及IL-2活性均较治疗前显著升高,而FSH、LH水平均明显低于治疗前,且实验组治疗后E2、CD3+、CD4+、CD4+/CD8+水平及IL-2活性显著高于对照组,FSH、LH水平均明显低于对照组,差异均有统计学意义(P0.05)。结论:雌激素联合丹栀逍遥胶囊能更加有效调节女性更年期综合征患者生殖内分泌激素水平,提高免疫功能,值得临床推广。     

Proteomics profiling identify CAPS as a potential predictive marker of tamoxifen resistance in estrogen receptor positive breast cancer

Background

Despite the success of tamoxifen since its introduction, about one-third of patients with estrogen (ER) and/or progesterone receptor (PgR) - positive breast cancer (BC) do not benefit from therapy. Here, we aim to identify molecular mechanisms and protein biomarkers involved in tamoxifen resistance.

Results

Using iTRAQ and Immobilized pH gradient-isoelectric focusing (IPG-IEF) mass spectrometry based proteomics we compared tumors from 12 patients with early relapses (<2 years) and 12 responsive to therapy (relapse-free > 7 years). A panel of 13 proteins (TCEAL4, AZGP1, S100A10, ALDH6A1, AHNAK, FBP1, S100A4, HSP90AB1, PDXK, GFPT1, RAB21, MX1, CAPS) from the 3101 identified proteins, potentially separate relapse from non-relapse BC patients. The proteins in the panel are involved in processes such as calcium (Ca²⁺) signaling, metabolism, epithelial mesenchymal transition (EMT), metastasis and invasion. Validation of the highest expressed proteins in the relapse group identify high tumor levels of CAPS as predictive of tamoxifen response in a patient cohort receiving tamoxifen as only adjuvant therapy.

Conclusions

This data implicate CAPS in tamoxifen resistance and as a potential predictive marker.

Electronic supplementary material

The online version of this article (doi:10.1186/s12014-015-9080-y) contains supplementary material, which is available to authorized users.     

Between plant and diurnal variation in quantities and ratios of volatile compounds emitted by Vicia faba plants

Ratios of volatile phytochemicals potentially offer a means for insects to recognise their host-plant species. However, for this to occur ratios of volatiles would need to be sufficiently consistent between plants and over time to constitute a host-characteristic cue. In this context we collected headspace samples from Vicia faba plants to determine how consistent ratios of key volatile phytochemicals used in host location by one of its insect pests, the black bean aphid, Aphis fabae, were. These were (E)-2-hexenal, (Z)-3-hexen-1-ol, 1-hexanol, benzaldehyde, 6-methyl-5-hepten-2-one, octanal, (Z)-3-hexen-1-yl acetate, (R)-linalool, methyl salicylate, decanal, undecanal, (E)-caryophyllene, (E)-β-farnesene, (S)-germacrene D, and (E, E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene, which had previously been found to be electrophysiologically and behaviourally active to A. fabae. Although the quantities of volatiles produced by V. faba showed large between plant and diurnal variation, correlations between quantities of compounds indicated that the ratios of certain pairs of volatiles were very consistent. This suggests that there is a host-characteristic cue available to A. fabae in the form of ratios of volatiles.     

Fungicidal effect of pleurocidin by membrane-active mechanism and design of enantiomeric analogue for proteolytic resistance

Pleurocidin (Ple) is a 25-residue peptide which is derived from the skin mucous secretion of the winter flounder (Pleuronectes americanus). In this study, we investigated antifungal effects and its mode of action of Ple on human pathogenic fungi. Ple showed potent antifungal activity with low hemolytic activity. To investigate the antifungal mechanisms of Ple, the cellular localization and membrane interaction of Ple were examined. Protoplast regeneration and membrane-disrupting activity by DPH-labeled membrane support the idea, that Ple exerts fungicidal activity against the human pathogenic fungus Candida albicans with the disruption of a plasma membrane. To aim for which was the application of a therapeutic agent, we designed a synthetic enantiomeric peptide composed of all-d-amino acids to enhance proteolytic resistance. The synthetic all-d-Ple also displayed two-fold more potent antifungal activity than that of all-l-Ple, and its antifungal activity showed proteolytic resistance against various proteases. Therefore, these results suggest a therapeutic potential of all-d-Ple with regard to its proteolytic resistance against human fungal infections.     

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

Polychlorinated biphenyls (PCBs) are a family of toxicants that persist in measurable quantities in human and wildlife tissues, despite their ban in production in 1977. Some PCB mixtures can act as endocrine disrupting chemicals (EDCs) by mimicking or antagonizing the actions of hormones in the brain and periphery. When exposure to hormonally active substances such as PCBs occurs during vulnerable developmental periods, particularly prenatally or in early postnatal life, they can disrupt sex-specific patterning of the brain, inducing permanent changes that can later be manifested as improper sexual behaviors. Here, we investigated the effects of prenatal exposure to the PCB mixture Aroclor (A) 1221 on adult female reproductive behaviors in a dose-response model in the Sprague-Dawley rat. Using a paced mating paradigm that permits the female to set the timing of mating and control contact with the male during copulation, we were able to uncover significant differences in female-typical sexual activities in A1221-exposed females. Specifically, A1221 causes significant effects on mating trial pacing, vocalizations, ambulation and the female's likelihood to mate. The results further demonstrate that the intermediate treatment group has the greatest number of disrupted endpoints, suggestive of non-linear dose responses to A1221. These data demonstrate that the behavioral phenotype in adulthood is disrupted by low, ecologically relevant exposures to PCBs, and the results have implications for reproductive success and health in wildlife and women.     

Regulation of protogynous sex change by competition between corticosteroids and androgens: an experimental test using sandperch, Parapercis cylindrica

Cortisol, the dominant corticosteroid in fish, and 11-ketotestosterone (11KT), the most potent androgen in fish, are both synthesized and (or) deactivated by the same two enzymes, 11beta-hydroxylase and 11beta-hydroxysteroid dehydrogenase. Cortisol is synthesized in response to stress (such as that caused by interaction with a dominant conspecific), whereas 11KT is synthesized during protogynous sex change. It has been hypothesized that corticosteroids (such as cortisol) inhibit 11KT synthesis via substrate competition, thereby providing a mechanism for the regulation of socially mediated, protogynous sex change. We tested this hypothesis by administering cortisol (50 microg g(-1) body weight) to female sandperch (Parapercis cylindrica) under social conditions that were permissive to sex change (i.e. in the absence of suppressive male dominance). Twenty-one days later, mean physiological cortisol concentration in cortisol-treated fish was 4.2-fold greater than that in 'socially stressed' female fish maintained in a semi-natural system. Although the dosage of cortisol was therefore considered to be favorable for engendering competitive inhibition of 11KT synthesis, all cortisol-treated fish changed sex, as did all sham-treated and control fish (n=7 fish per treatment). In addition, there was no effect of cortisol treatment on the rate of sex change or on the pattern of steroidogenesis. Thus, our results refute the hypothesis that protogynous sex change is regulated by substrate competition between corticosteroids and androgens.     

Elevated rates of testosterone-related disorders in women with autism spectrum conditions

The androgen theory of autism proposes that autism spectrum conditions (ASC) are in part due to elevated fetal testosterone (FT) levels, which are positively correlated with a number of autistic traits and inversely correlated with social development and empathy. A medical questionnaire was completed by n=54 women with ASC, n=74 mothers of children with ASC, and n=183 mothers of typically developing children to test whether women with ASC have an increased rate of testosterone-related medical conditions, and to see whether mothers of children with ASC show similar abnormalities, as part of the 'broader autism phenotype'. Compared to controls, significantly more women with ASC reported (a) hirsutism, (b) bisexuality or asexuality, (c) irregular menstrual cycle, (d) dysmenorrhea, (e) polycystic ovary syndrome, (f) severe acne, (g) epilepsy, (h) tomboyism, and (i) family history of ovarian, uterine, and prostate cancers, tumors, or growths. Compared to controls, significantly more mothers of ASC children reported (a) severe acne, (b) breast and uterine cancers, tumors, or growths, and (c) family history of ovarian and uterine cancers, tumors, or growths. These results suggest current hormone abnormalities in women with ASC and their mothers. Direct investigations of serum testosterone levels and genetic susceptibility to high testosterone production or sensitivity in women with ASC would illuminate the origin of these conditions. The relationship between FT and current testosterone levels also needs to be clarified. The present results may be relevant to understanding the increased male risk to developing autism.     

Estimation of hydroxyl radical generation by salicylate hydroxylation method in kidney of mice exposed to ferric nitrilotriacetate and potassium bromate

Hydroxyl radical (·OH) generation in the kidney of mice treated with ferric nitrilotriacetate (Fe-NTA) or potassium bromate (KBrO₃) in vivo was estimated by the salicylate hydroxylation method, using the optimal experimental conditions we recently reported. Induction of DNA lesions and lipid peroxidation in the kidney by these nephrotoxic compounds was also examined. The salicylate hydroxylation method revealed significant increases in the ·OH generation after injection of Fe-NTA or KBrO₃ in the kidneys. A significant increase in 8-hydroxy-2'-deoxyguanosine in nuclei of the kidney was detected only in the KBrO₃ treated mice, while the comet assay showed that the Fe-NTA and KBrO₃ treatments both resulted in significant increases in DNA breakage in the kidney. With respect to lipid peroxidation, the Fe-NTA treatment enhanced lipid peroxidation and ESR signals of the alkylperoxy radical adduct. These DNA breaks and lipid peroxidation mediated by ·OH were diminished by pre-treatment with salicylate in vivo. These results clearly demonstrated the usefulness of the salicylate hydroxylation method as well as the comet assay in estimating the involvement of ·OH generation in cellular injury induced by chemicals in vivo.