instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: Sigma-1 receptors are involved in the pathophysiological process of several neuropsychiatric diseases such as epilepsy, depression. Allosteric modulation represents an important mechanism for receptor functional regulation. In this study, we examined antidepressant activity of the latest identified novel and selective allosteric modulator of sigma-1 receptor 3-methyl-phenyl-2, 3, 4, 5-tetrahydro-1H-benzo[d]azepin-7-ol (SOMCL-668).', 'A single administration of SOMCL-668 decreased the immobility time in the forced swimming test (FST) and tailing suspended test in mice, which were abolished by pretreatment of sigma-1 receptor antagonist BD1047. In the chronic unpredicted mild stress (CUMS) model, chronic application of SOMCL-668 rapidly ameliorated anhedonia-like behavior (within a week), accompanying with the enhanced expression of brain-derived neurotrophic factor (BDNF) and phosphorylation of glycogen synthase kinase 3β (GSK3β) (Ser-9) in the hippocampus. SOMCL-668 also rapidly promoted the phosphorylation of GSK3β (Ser-9) in an allosteric manner in vitro. In the cultured primary neurons, SOMCL-668 enhanced the sigma-1 receptor agonist-induced neurite outgrowth and the secretion of BDNF.\Question: Does allosteric Modulation of Sigma-1 Receptors elicit Rapid Antidepressant Activity?
answer:
SOMCL-668, a novel allosteric modulator of sigma-1 receptors, elicits a potent and rapid acting antidepressant effect. The present data provide the first evidence that allosteric modulation of sigma-1 receptors may represent a new approach for antidepressant drug discovery.


question:
Context: To examine whether trichostatin A (TSA), a histone deacetylase inhibitor (HDACI), can induce up-regulation of peroxisome proliferator-activating receptor gamma (PPAR gamma) and to see whether LG100268, a retinoid X receptor (RXR) ligand, can inhibit proliferation of endometriotic cells alone or in synergy with ciglitazone, a PPAR gamma agonist.', 'One endometrial stromal cell line and two endometriotic cell lines used as a model system: Western blot analysis to determine whether TSA can up-regulate PPAR gamma expression, and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) proliferation assay to see whether ciglitazone and LG100268 have any antiproliferative effects individually or jointly.', 'Academic.', 'None.', 'Culture of immortalized endometrial and endometriotic cell lines with TSA, or ciglitazone or LG100268.', 'PPAR gamma protein expression levels in cells treated with or without TSA, and number of viable cells treated with or without ciglitazone, LG100268, or both.', 'The TSA treatment resulted in up-regulation of PPAR gamma expression in all cell lines in a dose-dependent fashion. Both ciglitazone and LG100268 inhibited proliferation in a dose-dependent manner, and the antiproliferative effects appeared to be synergistic. In addition, endometriotic cells were more sensitive than endometrial stromal cells to LG100268 treatment.\Question: Do peroxisome proliferator-activated receptor-gamma and retinoid X receptor agonists synergistically suppress proliferation of immortalized endometrial stromal cells?
answer:
The up-regulation of PPAR gamma induced by TSA indicates that the action of HDACIs also includes the PPAR gamma signaling pathway, suggesting that the activation of PPAR gamma is a desirable way to contain endometriosis phenotypes. The higher sensitivity of endometriotic cells than their endometrial counterpart to LG100268 treatment suggests that the sensitivity differential could be exploited effectively to eradicate unwanted ectopic endometrial tissues while minimizing the collateral damage to the normal endometrial tissues.


question:
Context: Growing evidence documents elevated behavioral risk among sexual-minorities, including gay, lesbian, and bisexual individuals; however, tests of biological or psychological indicators of stress as explanations for these disparities have not been conducted.', 'Data were from the 2005-2010 National Health and Nutrition Examination Survey, and included 9662 participants; 9254 heterosexuals, 153 gays/lesbians and 255 bisexuals. Associations between sexual orientation and tobacco, alcohol, substance, and marijuana use, and body mass index, were tested using the chi-square test. Stress, operationalized as depressive symptoms and elevated C-reactive protein, was tested as mediating the association between sexual orientation and behavioral health risks. Multiple logistic regression was used to test for mediation effects, and the Sobel test was used to evaluate the statistical significance of the meditating effect.', 'Gays/lesbians and bisexuals were more likely to report current smoking (p\u2009<\u2009.001), a lifetime history of substance use (p\u2009<\u2009.001), a lifetime history of marijuana use (p\u2009<\u2009.001), and a lifetime period of risky drinking (p\u2009=\u2009.0061). The largest disparities were observed among bisexuals. Depressive symptoms partially mediated the association between sexual orientation and current smoking (aOR 2.04, 95% CI 1.59, 2.63), lifetime history of substance use (aOR 3.30 95% CI 2.20, 4.96), and lifetime history of marijuana use (aOR 2.90, 95% CI 2.02, 4.16), among bisexuals only. C-reactive protein did not mediate the sexual orientation/behavior relationship.\Question: Does stress mediate the relationship between sexual orientation and behavioral risk disparities?
answer:

Higher prevalence of current smoking and lifetime history of substance use was observed among sexual minorities compared to heterosexuals. Among bisexuals, depressive symptoms accounted for only 0.9-3% of the reduction in the association between sexual orientation and marijuana use and tobacco use, respectively. More comprehensive assessments of stress are needed to inform explanations of the disparities in behavioral risk observed among sexual minorities.