The mechanism by which oestrogens suppress experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is only partially understood. We here demonstrate that treatment with 17beta-oestradiol (E(2)) in C57BL/6 mice boosted the expression of programmed death 1 (PD-1), a negative regulator of immune responses, in the CD4(+) FoxP3(+) regulatory T (Treg) cell compartment in a dose-dependent manner that correlated with the efficiency of EAE protection. Administration of E(2) at pregnancy levels but not lower concentrations also enhanced the frequency of Treg cells. Additionally, E(2) treatment drastically reduced the production of interleukin-17 (IL-17) in the periphery of immunized mice. However, E(2) treatment did not protect against EAE or suppress IL-17 production in PD-1 gene-deficient mice. Finally, E(2) failed to prevent Treg-deficient mice from developing spontaneous EAE. Taken together, our results suggest that E(2)-induced protection against EAE is mediated by upregulation of PD-1 expression within the Treg-cell compartment.
The current research under the title of teaching Persian alphabets (identity of children of Islamic Iran) with an emphasis on the art of painting for preschoolers in the corona and post-corona periods was based on a descriptive research method. In this method, first, a general definition of art and how it affects Persian letters, and then an outline of it was presented. The design of educational letters in this research was done by the authors of this research and some elementary education students at Islamic Azad University, Bandar Abbas branch. In this research, an attempt was made to present a new way of working on correct, fluent, principled education and away from any stress and haste in Sama Bandar Abbas elementary schools. In this method, Persian letters were first designed in the form of a game, and through that, shapes were created that the child was excited to see and wanted to color. The form generated by random method among 30 preschoolers and sample method of 30 students of short-term academic Jihad courses in pre-primary teacher training and teacher training in first and secondgrade elementary schools, as well as 60 undergraduate students. The field of elementary education and 3 preschool and elementary teachers were also implemented. The students of the sample group had not benefited from any alphabetic teaching method until this experiment was conducted, and the children of the random method were new students who enter the first grade at the beginning of the school year. The results of this experiment are: 1- Newbies and teachers are interested in illustrated letters 2- Active participation of newbies in school and students in the educational environment of the university due to the similarity of the subject with the game.
The mechanisms by which prolonged estrogen exposures, such as estrogen therapy and pregnancy, reduce thymus weight, cellularity, and CD4 and CD8 phenotype expression, have not been well defined. In this study, the roles played by the membrane estrogen receptor, G protein-coupled receptor 30 (GPR30), and the intracellular estrogen receptors, estrogen receptor alpha (ERalpha) and beta (ERbeta), in 17beta-estradiol (E2)-induced thymic atrophy were distinguished by construction and the side-by-side comparison of GPR30-deficient mice with ERalpha and ERbeta gene-deficient mice. Our study shows that whereas ERalpha mediated exclusively the early developmental blockage of thymocytes, GPR30 was indispensable for thymocyte apoptosis that preferentially occurs in T cell receptor beta chain(-/low) double-positive thymocytes. Additionally, G1, a specific GPR30 agonist, induces thymic atrophy and thymocyte apoptosis, but not developmental blockage. Finally, E2 treatment attenuates the activation of nuclear factor-kappa B in CD25(-)CD4(-)CD8(-) double-negative thymocytes through an ERalpha-dependent yet ERbeta- and GPR30-independent pathway. Differential inhibition of nuclear factor-kappaB by ERalpha and GPR30 might underlie their disparate physiological effects on thymocytes. Our study distinguishes, for the first time, the respective contributions of nuclear and membrane E2 receptors in negative regulation of thymic development.
Many cultural phenomena to express and display art, an expression of the concept of pay. Cultural, metaphysical nature posters through to enact the implicit message that nations have helped to understand the cultural foundations, Perhaps the comparative posters metaphysical approach in different countries to fill the gaps in the field of comparative cultural posters, This study and implementation posters metaphysical approach in three countries, Japan, France and Italy in the field of poster art is culture trying to prove through scientific and theoretical arguments, bills can be very influential in the field of cultural transmission. Qualitative research is interpretive model approach, gathering materials for a documentary style and with first and second sources have been taking notes.The results show that non-conventional and lack of communication with the audience is the most important factor in this type of work. Its posters instrumental artists have understood, this lack of communication with the audience and the silence that exists in the type of messaging indirectly, is connected. The major issue, move the message to the audience but also strengthen and extend it, which is important in cultural posters. The perspective of the artist's imagination is born into the artistic beauty that pushes the aim of art in terms of aesthetics of art.
Although estrogens exert a pronounced protective effect on multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), their therapeutic application has been limited by undesirable side effects thought to be mediated primarily through estradiol binding to intracellular estrogen receptor alpha. In this study, we found that signaling through the putative membrane estrogen receptor, G protein-coupled receptor 30 (GPR30), was sufficient to mediate protection against EAE, which was significantly impaired in GPR30 gene-deficient mice. Treatment with G-1, an agonist that selectively activates GPR30 without engagement of the intracellular estrogen receptors, retained the ability of estradiol to protect against clinical and histological EAE without estradiol-associated side effects, deviated cytokine profiles, and enhanced suppressive activity of CD4(+)Foxp3(+) T regulatory cells through a GPR30- and programmed death 1-dependent mechanism. This study is the first to evaluate the protective effect of GPR30 activation on EAE, and provides a strong foundation for the clinical application of GPR30 agonists such as G-1 in multiple sclerosis.
