简介：Regulatingserotoninexpressioncanbeusedtotreatpsychoticdepression.Mifepristone,aglucocorticoidreceptorantagonist,isaneffectivecandidateforpsychoticdepressiontreatment.However,theunderlyingmechanismrelatedtoserotonintransporterexpressionispoorlyunderstood.Inthisstudy,weclonedthehumanbrainserotonintransporterintoXenopusoocytes,toestablishaninvitroexpressionsystem.Two-electrodevoltageclamprecordingswereusedtodetectserotonintransporteractivity.Ourresultsshowthatmifepristoneattenuatesserotonintransporteractivitybydirectlyinhibitingtheserotonintransporter,andsuggeststhattheserotonintransporterisapharmacologicaltargetofmifepristoneforthetreatmentofpsychoticdepression.

简介：AbstractObjective:To study the 12-month effects and possible mechanisms of low-dose mifepristone in the treatment of adenomyosis.Methods:Patients included in this retrospective study had painful adenomyosis and previously received 5 mg mifepristone daily (group A, n = 45) or 5 mg mifepristone daily with a poor-effect levonorgestrel-releasing intrauterine device (group B, n = 13) for 12 months. Uterine size, serum CA125 levels, estradiol levels, Visual Analogue Scale (VAS) score, endometrial thickness, and hemoglobin levels were compared before and after treatment and investigated again at 3 to 6 months after drug withdrawal. Another 8 patients with adenomyosis (group C, n = 8) who underwent surgery for severe dysmenorrhea during the same period were only used as a control group for immunohistochemical research. Endometrial biopsy results and expression of nerve growth factor (NGF), cyclooxygenase-2 (COX-2), and nuclear-associated antigen Ki-67 (Ki-67) in endometrial tissues and adenomyotic lesions were also analyzed.Results:The VAS scores in both experimental groups at all time points during treatment and follow-up were significantly lower (P <0.001) than those before treatment. The uterine size was significantly reduced, and endometrial thickness was distinctly thicker after 12 months of treatment than that before treatment in group A receiving 5 mg/d mifepristone. The immunohistochemical expression of NGF and COX-2 decreased in both eutopic and ectopic endometrium after treatment, whereas that of Ki-67 slightly increased in eutopic endometrium after treatment and rapidly recovered to the baseline value after stopping mifepristone. There were no signs of hyperplasia, atypical hyperplasia, or malignancy in the endometrial biopsies.Conclusions:The results suggested that a daily dose of 5 mg mifepristone for 12 months down-regulated the expression of NGF and COX-2 and was effective in treating painful adenomyosis with few side effects.

简介：AbstractObjective:Mifepristone (RU486), one of the most common medications for artificial abortion, attenuates the immunoregulatory effects of progesterone. However, the specific immune regulatory mechanism of RU486 in abortion remains unknown. We intended to investigate the immunomodulatory effects of RU486 on abortion.Methods:Sixty female mice were divided into the control group (0 mg RU486) and RU486 group (2 mg/kg RU486). The uterus, peripheral blood, and spleen were obtained for isolation of specific cell types. The population and phenotype of immune cells in the decidua, peripheral blood, and spleen were analyzed using flow cytometry. Statistical differences between groups were determined using two-tailed t-test. For all statistical tests, P < 0.05 was considered statistically significant.Results:RU486 effectively induced abortion in pregnant mice, with a significantly higher number of decidual macrophages (dMφ) (control group = 25.55% ± 2.467%, RU486 group = 19.41% ± 1.423%; P < 0.05), especially the major histocompatibility complex IIhigh subset. No difference in Mφ number was observed in the spleen or peripheral blood. Moreover, the dMφ from mice with RU486-induced abortion displayed a remarkable activated phenotype, with increased expressions of inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin (IL)-12 but decreased expressions of arginase-1 and IL-10. We also found elevated levels of decidual CD4+ T-cells in the RU486 group that exhibited a higher level of the proinflammatory cytokine interferon-γ and a lower level of the anti-inflammatory cytokines, IL-4 and IL-10.Conclusions:We report a new mechanism of RU486-induced abortion via the regulation of innate cell Mφ activation and the adaptive response of CD4+ T-cells present in the decidua but not the periphery.

简介：Objective:Toexplorethereversaleffectofmifepristoneonmultidrugresistance(MDR)indrug-resistanthumanbreastcancercelllineMCF7/ADRanditsmechanisms.Methods:ExpressionofMDR1andMDR-associatedprotein(MRP)mRNAinMCF7/ADRcellswasdetectedusingreversetranscription-polymerasechainreaction(RT-PCR).WesternblottingwasusedtoassaytheproteinlevelsofP-glycoprotein(P-gp)andMRP.Intracellularrhodamine123retentionand[3H]vincristine(VCR)accumulationweremeasuredbyflowcytometryandliquidscintillationcounter,respectively.MTTreductionassaywasusedtodeterminethesensitivityofcellstotheanticanceragent,adriamycin(ADR).Additionally,aMCF7/ADRcellxenograftmodelwasestablishedtoassessthereversaleffectofmifeprisoneonMDRinMCF7/ADRcellsinvivo.Results:Miferpristonedose-dependentlydown-regulatedtheexpressionofMDR1andMRPmRNAinMCF7/ADRcells,accompaniedbyasignificantdecreaseintheproteinlevelsofP-gpandMRP.Afterexposureto5,10,and20μmol/Lmifepristone,MCF7/ADRcellsshoweda3.87-,5.81-,and7.40-foldincreaseintheaccumulationofintracellularVCR(aknownsubstrateofMRP),anda2.14-,4.39-,and5.53-foldincreaseintheretentionofintracellularrhodamine123(anindicatorofP-gpfunction),respectively.MTTanalysisshowedthatthesensitivityofMCF7/ADRcellstoADRwasenhancedby7.23-,13.62-,and20.96-foldafterincubationwithmifepristoneasabove-mentioneddosesfor96h.Invivo,mifepristoneeffectivelyrestoredthechemosensitivityofMCF7/ADRcellstoADR.After8weeksofadministrationwithADR(2mg·kg-1·d-1)aloneorincombinationwithmifepristone(50mg·kg-1·d-1),thegrowthinhibitoryrateofxenograftedtumorsinnudemicewas8.08%and37.25%,respectively.Conclusion:MifepristoneexertspotentreversaleffectsonMDRinMCF7/ADRcellsinvitroandinvivothroughdown-regulationofMDR1/P-gpandMRPexpressionandinhibitionofP-gp-andMRP-dependentdrugefflux,thusincreasing