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The famous Abraham Flexner's 1910 report to the Carnegie Foundation launched the modern medical educmion.The report'S focus on the medical education standards and the curricula frameworks was laudable and appropriate.At the centennial of this report.we were still able to get a lot of inspiration and the direction of development and reforms of medical education by reviewing Flexner'd Report.
ABSTRACT
Objective To investigate the effects of different doses of estradiol on apoptosis of T lymphocytes from spleens in ovariectomized mice and explore the possible mechanisms.Methods The mice splenic T lymphocytes were isolated and divided into ten groups: young group, sham- ovariectomized group, ovariectomized group, ovariectomized plus estradiol(10-11, 10-10, 10-8 and 106groups, ovariectomized plus estradiol (10-10mol/L) plus 1CI182 780 (10-7tool/L) group, ovariectomized plus estradiol(10-10mol/L) plus 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPP, 10-6mol/L) group, ovariectomized plus estradiol(10-10mol/L) plus pyrroline dithiocarbamate(PDTC, 10-6mol/L) group. The apoptosis rates were determined by flow eytometry using Annexin V-FITC/ PI and the protein levels of ERa, ERβ, Bax, Bcl-2 and P65 were detected by Western blot. Results The apoptosis rate of ovariectomized group was(19. 4±2.5)%, which was higher than that of young group [(14.6±2.4%) 3 and sham-ovariectomized group [p (14.5±2.3)%], and the levels of Bcl-2 and nuclear P65 were lower than the young group [(0. 25±0. 05, 0. 09±0. 01) vs. (0. 40± 0.07,0. 15±0. 02), P<0.01]. The ovariectomized plus estradiol (10-10tool/L) group had lower apoptosis rate and higher Bcl-2 and P65 levels compared to the ovariectornized group[(16.6±1.8)% vs.(19.4±2.5)%,P<0.05;0.36±0.03 vs. 0.25～0.05, 0.14±0.01 vs. 0.09±0.01, P< 0. 01)], while the ovariectomized plus estradiol(10-8mol/L, 10-6tool/L) groups had higher apoptosis rates than the ovariectomized group[(22. 55±2. 5)% vs. (19. 4±2. 5)% ,P<0. 05;(27.8±3.1)% vs. (19.4 4±2. 5)%,P<0. 01, respectively]. The 2protein levels of ERa and ERβ of ovariectomized group were 0. 23±k0.01 and 0. 22±0. 03, respectively, which were lower than those of young((0. 27±0. 02) and (0. 29±0.04)] and sham-ovariectomized group [(0. 28±0. 03) and (0. 29±0.02)]. The ovariectomized plus estradiol(10-1110-1010-8tool/L) groups had higher while ovariectomized plus estradiol(10-6mol/L) group had lower ERα and ERβ protein levels (0. 09±0. 01,0. 14±0.02) than the ovariectomized group(P<0. 01). There was no significant difference between ovariectomized plus estradiol(10-10mol/L) plus ICI182 780 group or ovariectomized plus estradiol(10-10tool/L) plus PDTC group and ovariectomized group [(19.4±1.6)% vs. (19.4±2. 5)%, (21.0±2. 9)% vs. (19.4d±2. 5)%, P>0. 05). There were also no significant difference between ovariectomized plus estradiol(10-10mol/L) plus MPP group and ovariectomized plus estradiol (10-10mol/L) grou p[(16.9±2.2)% vs. (16.6±1.8)%, P>0.05]. Conclusions The ovariectomy of mice leads to increased apoptosis rates of splenic T lymphocytes. The effects of estradiol on the apoptosis of T lymphocytes in ovariectomized mice are dependent on doses: physiological dose of estradiol inhibits while higher dose of estradiol exacerbats the apoptosis of T lymphocytes in ovariectomized mice.Physiological dose of estradiol may act on Rice T lymphocytes via ERβ and NFkB signaling.
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Objective To investigate the effects of D-limonene on the proliferation and ras P21 expression in human bladder carcinoma EJ cell.Methods The cell proliferation was measured by XTT assay.The expression of ras mRNA was detected by real-time PCR,and the expression of its protein product was analyzed by Western Blot.Results The proliferation of EJ cell was inhibited by exposure to 2 mmol/L and 4 mmol/L D-limonene for 48h.The optical density (A) was 0.801±0.016 and 0.148±0.008,respectively.There were significant differences between the experimental groups and the control group (1.2181±0.031,P<0.05).The expressions of ras P21 and its protein product of EJ cell were decreased obviously when exposure to 1 mmol/L of D-limonene for 48h.The expres-sions were significantly different compared with the control group(P<0.05).Conclusions D-limo-nene could inhibit human bladder carcinoma EJ cell proliferation,which is in a dose-dependant man-ner.In a lower dose (<1 mmol/L),D-limonene can decrease the expression of ras mRNA and its protein product.
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Purpose:To further investigate the role of the novel negative immuno-regulatory molecules in tumor evasion by testing B7-H4 e xpression on tumor tissues and spleen macrophages induced by tumor antigen of mi ce and BTLA expression on T cells of the tumor bearing mice. Methods:Via RT-PCR, we evaluated the differences in the expres sion of B7-H4 mRNA of the tumor cell lines (3LL and Renca) in vitro,tumor t issues and the expression of BTLA mRNA of the tumor bearing mice T cells;via flo w cytometry, we evaluated the differences in the expression of B7-H4 surface pr otein of the spleen macrophages from tumor bearing mice and the normal spleen ma crophages after stimulation with the tumor antigen. Moreover, via immunohistoche mistry , we also evaluated the differences in the expression of B7-H4 surface p rotein of tumor tissues. Results:Tumor cell lines (3LL and Renca) did not express the B 7-H4 mRNA in vitro.All tumor tissues or spleen macrophages in tumor bearing mice have a high expression of both B7-H4 mRNA and B7-H4 protein. Compared wi th those from normal mice, T cells from tumor bearing mice showed a higher expre ssion of BTLA. Stimulated by tumor antigen in vitro, normal mice spleen macr ophages B7-H4 expression increased significantly; while no apparent difference was found in the groups stimulated by the corresponding normal tissue antigen. Conclusions:The aberrant expression of the costimulatory molecu les, B7-H4 and its receptor BTLA, may have a regulative effect in tumor evasion immunity.