Hypothyroidism impairs endothelium-dependent dilatations, while hyperthyroidism augments the production of endothelial nitric oxide. Thus, experiments were designed to determine if thyroid hormone causes endothelium-dependent responses, or alleviates diabetic endothelial dysfunction. Isometric tension was measured in rings with or without endothelium of arteries from normal and diabetic Sprague-Dawley rats. Release of 6-keto prostaglandin F1α and thromboxane B2 were measured by enzyme linked immunosorbent assay and protein levels [endothelial nitric oxide synthase (eNOS), cyclooxygenases (COX)] by immunoblotting. Triiodothyronine (T3) caused concentration-dependent (3×10(-6)-3×10(-5)M) relaxations in mesenteric (pEC50, 4.96±0.19) and femoral (pEC50, 4.57±0.35) arteries without endothelium. In femoral arteries of rats with diabetes, 5-methylamino-2-[[(2S,3R,5R,8S,9S)-3,5,9-trimethyl-2-(1-oxo-(1H-pyrrol-2- -yl)propan-2-yl)-1,7-dioxaspiro-(5,5)undecan-8-yl]methyl]benzooxazole-4-carboxylic acid (A23187, 3×10(-7) to 10(-6)M) caused partly endothelium-dependent contractions. After chronic T3-treatment with (10μg/kg/day; four weeks), the contractions to A23187 of preparations with and without endothelium were comparable, the thromboxane B2-release was reduced (by 38.1±9.2%). The pEC50 of 9, 11-dideoxy-11α, 9α-epoxymethanoprostaglandin F2α (U46619, TP-receptor agonist) was increased in T3-treated diabetic rats compared with controls (8.53±0.06 vs 7.94±0.09). The protein expression of eNOS increased (by 228%) but that of COX-1 decreased (by 35%) after chronic T3 treatment. In human umbilical vein endothelial cells incubated for one week with T3 (10(-10)-10(-7)M) in the presence but not in the absence of interleukin-1β (1ng/ml), the expression of eNOS was increased compared to control. In conclusion, thyroid hormone acutely relaxes mesenteric and femoral vascular smooth muscle, but given chronically reduces the release of endothelium-derived vasoconstrictor prostanoids while enhancing the responsiveness of TP receptors of vascular smooth muscle.

BackgroundMesenchymal stromal cells (MSCs) are proven to have immunosuppressive functions via various mechanisms. These mechanisms were demonstrated by administering bone marrow derived human MSCs (hMSCs) to graft versus host disease (GVHD) murine models.MethodsBALB/c host mice were irradiated prior to receiving C57BL/6 donor T cell depleted bone marrow (TCDBM) cells (negative control) and donor CD4+ T lymphocyte with (treatment group) or without hMSCs (positive control). The presence of hMSCs in target tissues and lymphoid organs was documented by using in vivo imaging and measuring the expression of EphB2 and ephrin-B2 by RTqPCR. Survival rate and GVHD score were also monitored. Tissue sections were obtained for histopathologic analysis. Flow cytometry was used to document donor T cell alloreactivity and expression of CCR5, CXCR3 and CCR7. ELISA was utilized to determine levels of proinflammatory cytokines, RANTES (CCL5) and phosphorylated STAT 5A/B. RTqPCR was performed to quantify expression of CCL3 and CXCL9. Western blotting was performed to qualitatively measure iNOS expression.ResultsSurvival rate and GVHD score improved with hMSC treatment. Pathologic changes of GVHD were abrogated. Documentation of suppression of RANTES, CCL3, CXCL9, CCR5 and CXCR3 with simultaneous decrease of donor T cell alloreactivity was demonstrated 6 days after transplantation, along with reduction of levels of inflammatory cytokines, suppression of STAT 5A/B phosphorylation, increased expression of CCR7 and increased production of nitrous oxide by hMSCs. Documentation of homing of hMSCs to lymphoid organs and target tissues was also performed.ConclusionsThese mechanisms contribute to the current understanding of MSC mechanisms of immunosuppression and forms a comprehensive picture of how they exert immunosuppression in an in vivo model of immune dysregulation.Electronic supplementary materialThe online version of this article (doi:10.1186/s40164-015-0007-0) contains supplementary material, which is available to authorized users.

Objective Sexual and reproductive health (SRH) and service utilization among female migrant domestic workers are under-studied. No studies to date have investigated the unique health vulnerabilities that affect female foreign domestic workers. The objective of this study was to investigate how stay-in and stay-out living conditions in domestic work may differentially affect SRH status, service utilization, and sexual risk behavior among female migrant domestic workers in Macao (SAR), China. Methods Data were analyzed from a cross-sectional survey conducted between November 2016 and August 2017 among 1368 female Filipina migrant domestic workers living and working in Macao. Participants were recruited through respondent-driven sampling. Bivariable and multivariable logistic regression analyses were used to assess relationships between living context and outcomes of interest. Results Domestic workers’ living context (i.e. stay-in versus stay-out) was significantly related to sexual risk behavior patterns and SRH status and service utilization. Compared to stay-out workers, stay-in workers had reduced odds of sexual risk behaviors but were also more likely to report that their sexual partners were likely to have concurrent sexual partners. In addition, stay-in workers had significantly decreased odds of having visited an OBGYN in Macao in the past year. Conclusions This research is the first to evaluate the impact of stay-in and stay-out conditions within a foreign domestic worker population. This study further provides novel evidence of contextual factors (e.g. financial, employment, living conditions) that contribute to inequalities in SRH status and service utilization among Filipina migrant domestic workers. Results indicate that living context is significantly correlated with sexual risk behaviors, SRH status, and service utilization among domestic workers in Macao, highlighting the need to more effectively tailor specific interventions to meet female domestic workers’ needs.