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Diseases (Basel, Switzerland) Mar 2020Evidence of altered cholesterol and steroid hormones in autism is increasing. However, as boys are more often affected, evidence mainly relates to autistic males,...
Evidence of altered cholesterol and steroid hormones in autism is increasing. However, as boys are more often affected, evidence mainly relates to autistic males, whereas evidence for affected autistic girls is sparse. Therefore, a comprehensive gas chromatography mass spectrometry-based steroid hormone metabolite analysis was conducted from autistic girls. Results show increased levels of several steroid hormones, especially in the class of androgens in autistic girls such as testosterone or androstenediol. The increase of the majority of steroid hormones in autistic girls is probably best explained multifactorially by a higher substrate provision in line with the previously developed cholesterol hypothesis of autism.
PubMed: 32183287
DOI: 10.3390/diseases8010006 -
Molecules (Basel, Switzerland) Jan 2020Steroidal glycosides are important sources of innovative drugs. The increased diversification of steroidal glycosides will expand the probability of discovering active...
Steroidal glycosides are important sources of innovative drugs. The increased diversification of steroidal glycosides will expand the probability of discovering active molecules. It is an efficient approach to diversify steroidal glycosides by using steroidal glycosyltransferases. OcUGT1, a uridine diphosphate-d-glucose (UDP-Glc)-dependent glycosyltransferase from , is a multifunctional enzyme, and its glycodiversification potential towards steroids has never been fully explored. Herein, the glycodiversification capability of OcUGT1 towards 25 steroids through glucosylation and transglucosylation reactions were explored. Firstly, each of 25 compounds was glucosylated with UDP-Glc. Under the action of OcUGT1, five steroids (testosterone, deoxycorticosterone, hydrocortisone, estradiol, and 4-androstenediol) were glucosylated to form corresponding mono-glucosides and biosides. Next, OcUGT1-mediated transglucosylation activity of these compounds with another sugar donor -nitrophenyl-β-d-glucopyranoside (NPGlc) was investigated. Results revealed that the same five steroids could be glucosylated to generate mono-glucosides and biosides by OcUGT1 through transglucosylation reactions. These data indicated that OcUGT1-assisted glycodiversification of steroids could be achieved through glucosylation and transglucosylation reactions. These results provide a way to diversify steroidal glycosides, which lays the foundation for the increase of the probability of obtaining active lead compounds.
Topics: Glucosides; Glycosides; Glycosylation; Glycosyltransferases; Ornithogalum; Steroids
PubMed: 31979165
DOI: 10.3390/molecules25030475 -
Scientific Reports Dec 2019Genetic research of elite athletic performance has been hindered by the complex phenotype and the relatively small effect size of the identified genetic variants. The... (Clinical Trial)
Clinical Trial
Genetic research of elite athletic performance has been hindered by the complex phenotype and the relatively small effect size of the identified genetic variants. The aims of this study were to identify genetic predisposition to elite athletic performance by investigating genetically-influenced metabolites that discriminate elite athletes from non-elite athletes and to identify those associated with endurance sports. By conducting a genome wide association study with high-resolution metabolomics profiling in 490 elite athletes, common variant metabolic quantitative trait loci (mQTLs) were identified and compared with previously identified mQTLs in non-elite athletes. Among the identified mQTLs, those associated with endurance metabolites were determined. Two novel genetic loci in FOLH1 and VNN1 are reported in association with N-acetyl-aspartyl-glutamate and Linoleoyl ethanolamide, respectively. When focusing on endurance metabolites, one novel mQTL linking androstenediol (3alpha, 17alpha) monosulfate and SULT2A1 was identified. Potential interactions between the novel identified mQTLs and exercise are highlighted. This is the first report of common variant mQTLs linked to elite athletic performance and endurance sports with potential applications in biomarker discovery in elite athletic candidates, non-conventional anti-doping analytical approaches and therapeutic strategies.
Topics: Athletes; Female; Genome-Wide Association Study; Genotype; Humans; Male; Physical Endurance; Polymorphism, Single Nucleotide; Quantitative Trait Loci
PubMed: 31882771
DOI: 10.1038/s41598-019-56496-7 -
Cancer Causes & Control : CCC Feb 2020Alcohol consumption is an established breast cancer risk factor, though further research is needed to advance our understanding of the mechanism underlying the...
PURPOSE
Alcohol consumption is an established breast cancer risk factor, though further research is needed to advance our understanding of the mechanism underlying the association. We used global metabolomics profiling to identify serum metabolites and metabolic pathways that could potentially mediate the alcohol-breast cancer association.
METHODS
A cross-sectional analysis of reported alcohol consumption and serum metabolite concentrations was conducted among 211 healthy women 25-29 years old who participated in the Dietary Intervention Study in Children 2006 Follow-Up Study (DISC06). Alcohol-metabolite associations were evaluated using multivariable linear mixed-effects regression.
RESULTS
Alcohol was significantly (FDR p < 0.05) associated with several serum metabolites after adjustment for diet composition and other potential confounders. The amino acid sarcosine, the omega-3 fatty acid eicosapentaenoate, and the steroid 4-androsten-3beta,17beta-diol monosulfate were positively associated with alcohol intake, while the gamma-tocopherol metabolite gamma-carboxyethyl hydroxychroman (CEHC) was inversely associated. Positive associations of alcohol with 2-methylcitrate and 4-androsten-3beta,17beta-diol disulfate were borderline significant (FDR p < 0.10). Metabolite set enrichment analysis identified steroids and the glycine pathway as having more members associated with alcohol consumption than expected by chance.
CONCLUSIONS
Most of the metabolites associated with alcohol in the current analysis participate in pathways hypothesized to mediate the alcohol-breast cancer association including hormonal, one-carbon metabolism, and oxidative stress pathways, but they could also affect risk via alternative pathways. Independent replication of alcohol-metabolite associations and prospective evaluation of confirmed associations with breast cancer risk are needed.
Topics: Adult; Alcohol Drinking; Androstenediol; Breast Neoplasms; Child; Chromans; Citrates; Cross-Sectional Studies; Diet; Eicosapentaenoic Acid; Female; Follow-Up Studies; Humans; Metabolomics
PubMed: 31828464
DOI: 10.1007/s10552-019-01256-1 -
Biomedicine & Pharmacotherapy =... Jan 2020In the present study, the therapeutic effects of 5-androstenediol on radiation-induced myeloid suppression and tissue damage in mice and the possible mechanism were...
In the present study, the therapeutic effects of 5-androstenediol on radiation-induced myeloid suppression and tissue damage in mice and the possible mechanism were explored. The mice were subjected to whole-body irradiation, and 5-androstenediol was administered subcutaneously at different times and doses. The evaluation of the survival rate showed that the administration of 5-androstenediol every three days post-irradiation was the most effective in decreasing the death of the mice. Additionally, 5-androstenediol dose-dependently reduced the death caused by 9 Gy radiation. The pharmacological mechanism was investigated by blood analysis, western blot analysis, immunofluorescence and immunohistochemistry. 5-Androstenediol significantly ameliorated myeloid suppression, as demonstrated by elevated levels of total white blood cells, including neutrophils and platelets, in the peripheral blood. By H&E staining, we found that radiation-induced myeloid suppression in the bone marrow and spleen, as well as tissue damage in the lung and colon, was significantly ameliorated by treatment with 5-androstenediol. Immunohistochemistry showed elevated phosphorylation of p65 in the bone marrow and spleen, indicating the activation of NF-κB signaling. Moreover, 5-androstenediol markedly hampered the radiation-induced activation of caspase-1 and GSDMD in the colon by decreasing the interaction between AIM2 and ASC. Taken together, our results suggest that, by promoting NF-κB signaling and inhibiting inflammasome-mediated pyroptosis, 5-androstenediol can be used as a radioprotective drug.
Topics: Anabolic Agents; Androstenediol; Animals; DNA-Binding Proteins; Dose-Response Relationship, Drug; Female; Inflammasomes; Mice; Mice, Inbred C57BL; NF-kappa B; Radiation Injuries; Radiation-Protective Agents; Signal Transduction
PubMed: 31726369
DOI: 10.1016/j.biopha.2019.109597