ABSTRACT
Objective:To investigate any change in the effective connectivity between the bilateral anterior central gyruses after transcranial magnetic stimulation (TMS).Methods:Twenty-one healthy subjects were examined using resting state functional magnetic resonance imaging (rs-fMRI) before and after receiving continuous theta burst stimulation (cTBS). The brain atlas of the Institute of Automation of the Chinese Academy of Sciences was used for fine partitioning of the bilateral anterior central gyruses. Granger causality analysis was used to compare any changes in the effective connectivity between them.Results:After the cTBS inhibited the right M1 area, significant changes in effective connectivity among the sub-regions of the bilateral M1 area were observed. The effective connectivity of the right upper limb to the left upper limb and the left head to face were weakened, while that of the left upper limb to the right head, as well as of the face to the right upper limb was enhanced.Conclusion:For people whose right M1 area has been inhibited by cTBS, the effective connectivity changes in both upper limb functional areas of the M1 region reflect inter-hemispheric inhibition. Opposite changes were found in the trunk and upper limbs.
ABSTRACT
Obej ctive Abnormal proliferation of T cells plays an important role in the development of autoimmune diseases. The article aimed to study the inhibitory effect of small molecule compound BD691 on T cell proliferation and its mechanism. Methods Human peripheral blood T-lymphocytes were isolated and purified by the immunomagnetic microbeads,then T cells were ac-tivated with anti-CD3/CD28 mAbs or alloantigen.The inhibitory effect of BD691 on activated T cell proliferation, the cytotoxic effect BD891 on resting T cells and the expression of activated T cells marker CD25 were measured by flow cytometry.Furthermore, ELISA was used to detect the secretion of cytokines associated with T cell differentiation. Results BD691 significantly inhibited the prolif-eration of T cells being stimulated by anti-CD3/CD28 mAb or alloantigen in a dose-dependent manner, and IC50 values are (8.5 ± 1.5)μmol/L and (7.2 ±1.3)μmol/L, respectively.However, BD691 had no obvious cytotoxic effects on resting T cells and periph-eral blood mononuclear cells, even at a high concentration ( up to 100μmol/L) .In T cells which were not activated by anti-CD3/CD28 mAb, the percentage of CD25+T cells is only 1.6%of the total cells, while the number increased to 68% after activating treatment.Mean-while, in T cells which were activated by 0, 3.3, 10, 30μmol/L BD691, no obvious change of CD25 expression were observed, while immunosuppressant FK506 (0.1μmol/L) significantly decreased the expression of CD25 +T cells (14.9%).In unactivated T cells, 95.6%cells were at G0/G1 phase, while after activation, the percentage of cells at G0/G1 phase reduced to 57.7%.In addition, BD691 inhibited the secretion of IFN-γ, IL-6 and IL-17 in activated T cells, but had no effects on the secretion of IL-2, IL-4 and IL-10. Co nclusion BD691 exerts no effects on T cell activation, but it inhibits T cell proliferation by inducing T cell cycling arrest at G0/G1 phase.Moreover, BD691 inhibits the secretion of key cytokines (such as IFN-γ, IL-6, IL-17) closely related to the differ-entiation of Th1 and Th17 cells.The results suggest that BD 691 is a potential lead compound to develop a new immunosuppressant for the inhibition of abnormal proliferation and differentiation of T cells.
ABSTRACT
Obej ctive Knockout mice are widely used in the studies of joint diseases .This article investigated the effects of joint processing methods , collagenase types ,and collagenase digestion time on the number of primary fibroblast -like synoviocytes (FLSs) obtained from mice. Methods The hind legs of 6 of the 12 male mice were cut open from the hip joints , but not those of the other 6.FLSs were isolated using the type-Ⅳcollagenase digestion method and purified by differential digestion .Cell morphology was observed under the inverted microscope .The type, viability, and purity of the cells were determined by flow cytometry . Rse ults Significantly fewer FLSs were obtained from the mice with the hind legs cut open ( 19 133 ±115 ) than from those without (24 933 ± 503) (P<0.05).The numbers of FLSs collected from the cell suspension at 1, 2, 3, 4, 5,6 , and 7 hours after digestion were 700 ±300 , 600 ±100 , 15 200 ±900 , 5100 ±800 ,2700 ±300 , 900 ±200, and 300 ±100, respectively, the highest at 3 hours. There were statistically significant differences in the total number of FLSs obtained by type-Ⅳ and type-Ⅱ collagenase digestions (24900 ±500v s 18 100 ±400, P<0.05). Conclusion For in virt o culture of primary mouse FLSs, it is recommended that the hip joints be not cut open, and type-Ⅳcollagenase be used with cell sus-pension at 2-6hours after digestion .