The immunomodulatory drug leflunomide (LEF) is frequently used for treating human cytomegalovirus (HCMV), but its antiviral mechanism is still unclear.
Objectives
In this study,we therefore investigated the effects of the active LEF metabolite A771726 on the HCMV lifecycle in human embryonic lung fibroblasts. We clarified the mechanism of LEF antiviral infection, and provide a new way to treat immune dysfunction patients with HCMV infection.
Methods
The experiment was divided into four groups:the control group, the HCMV group, the ganciclovir + HCMV group as well as the LEF + HCMV group. MTT was usedfor assessmentof the cell inhibitory rate. Apoptosis was measured by staining with fluoresceinisothiocyanate Annexin V and propidium iodide. Statistical significance was determined by paired t-test using SPSS software.
Results
The results of the study showed that cell proliferation was significantly inhibited by HCMV at 24 hours and 48 hours. With increasing HCMV concentration, the value-added inhibition of the cells was significantly decreased compared with the control group, and was statistically significant (P<0.01). Ganciclovir can increase proliferation of cellsinfected with HCMV;compared with the control group it was statistically significant (P<0.05). Meanwhile,with LEF treatment cell proliferation was significantly improved at 24 hours and 48 hours, with statistical significance (P<0.05). The apoptosis rate of human embryonic lung fibroblasts infected with HCMV increased significantly at 24 hours, 48 hours and 72 hours,and as time goes on the apoptosis rate increases statistically significantly (P<0.01) compared with the control group The apoptosis rate of theHCMV infection group decreased by adding LEF,and was statistically significant (P<0.05).
Conclusions
In this studywe show that LEF is an exciting new drug for cytomegalovirus infection. LEF significantly inhibited HCMV infection-induced apoptosis and proliferation, playing an important role in the treatment of patients infected by HCMV. In this study we explored the potential usefulness of LEF for cytomegalovirus infection and found it to be a cost-effective new treatment for cytomegalovirus infection that deserves further study.
A phytochemical study on the methanol extracts from the seeds of Peganum harmala L. led to a new quizonaline alkaloid (S)-vasicinone-1-O-β-d-glucopyranoside (1) and four known ones, (R)-vasicinone-1-O-β-d-glucopyranoside (2), (S)-vasicinone (3), vasicine (4), and deoxyvasicinone (5). Their structures were elucidated by spectroscopic analysis including IR, HR-ESI-MS, 1D and 2D NMR, and specific rotation as well as by comparison of the data with those in the literature. All of the alkaloids were screened for antiproliferative activity against human gastric cancer cells MCG-803 with MTT method. Compounds 1 and 3 exhibited moderate inhibitory activity.
The oxidation behavior of a novel Ni-based single-crystal 4774DD1 superalloy for industrial gas turbine applications was investigated by the isothermal oxidation at 980 °C and discontinuous oxidation weight gain methods. The phase constitution and morphology of surface oxides and the characteristics of the cross-section oxide film were analyzed by XRD, SEM and EDS. Results show that the oxidation kinetics of the 4774DD1 superalloy follows the cubic law, indicating its weak oxidation resistance at this temperature. As the oxidation time increases, the composition of the oxide film evolves as following: One layer consisting of a bottom Al2O3 sublayer and an upper (Al2O3+NiO) mixture sublayer after oxidized for 25 h. Then, two layers composed of an outermost small NiO discontinuous grain layer and an internal layer for 75 h. This internal layer is consisted of the bottom Al2O3 sublayer, an intermediate narrow CrTaO4 sublayer, and an upper (Al2O3+NiO) mixture sublayer. Also two layers comprising an outermost relative continuous NiO layer with large grain size and an internal layer as the oxidation time increases to 125 h. This internal layer is composed of the upper (Al2O3+NiO) mixture sublayer, an intermediate continuous (CrTaO4+NiWO4) mixture sublayer, and a bottom Al2O3 sublayer. Finally, three layers consisting of an outermost (NiAl2O4+NiCr2O4) mixture layer, an intermediate (CrTaO4+NiWO4) mixture layer, and a bottom Al2O3 layer for 200 h.
Abstract Background Whether MTHFR C677T genotype affects pregnancy outcomes following assisted reproductive technology is conflicting. And the role of MTHFR C677T genotype on cumulative live birth has not been reported. This study aims to investigate the effect of MTHFR C677T genotype on cumulative live birth following in-vitro fertilization and embryo transfer (IVF-ET). Methods This is a retrospective cohort study that includes 1173 women undergoing their first IVF-ET. We retrospectively compared the reproductive outcomes among the groups stratified by MTHFR C677T genotypes (677CC, 677CT, 677TT). We performed interaction analysis to detect the factor that interacts with the MTHFR C677T genotype. Poisson regression analyses were used to evaluate the associations between MTHFR C677T genotypes with the number of transferable embryos and the number of good-quality embryos. Cox regression analysis was used to evaluate the association between MTHFR C677T genotypes with cumulative live birth. All regression analyses were adjusted with the confounding factors which may independently impact reproductive outcomes. Results There is a significant interactive effect of MTHFR 677TT genotype with GnRHa protocol on reproductive outcomes (P for interaction<0.05). MTHFR 677TT homozygous mutation was found to impact reproductive outcomes under GnRHa short protocol but not GnRHa long protocol. MTHFR 677TT is significantly associated with decreased number of transferable embryos ( p -value=0.028), decreased number of good-quality embryos ( p -value=0.005), and decreased cumulative live birth rate ( p -value=0.024) in patients undergoing GnRHa short protocol. However, the clinical pregnancy rate, miscarriage rate and live birth rate at the first embryo transfer cycle were not significantly different between the groups under both protocols ( p -values>0.05). Conclusions MTHFR 677TT genotype is associated with decreased number of transferable embryos, decreased number of good-quality embryos, and decreased cumulative live birth rate in the first complete cycle in patients undergoing GnRHa short protocol.
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