br RESULTS br DISCUSSION In this study we

RESULTS
DISCUSSION In this study, we found impaired apoptosis in the peripheral blood of RA patients when compared with peripheral blood from normal controls. Our previous studies have shown that the number of CD4 + T Bacitracin sale increased while regulatory T (Treg) cells diminished in the peripheral blood of patients with RA. This increase in the number of CD4+ T cells may be correlated with decreased apoptosis. The increased expression of CD4+ T cells and the decreased expression of annexin V might be associated with the decreased apoptotic rate, which may be involved in excessive activation of CD4+ T cells, and linked to disease activity. Thus, dysfunctional intracellular signaling induced by pro-inflammatory cytokines was shown to be responsible for aberrant immune cell survival, apoptosis, and/or “apoptosis-resistance” of CD4+ T cells in RA. The impaired mechanisms of apoptosis and the increased Fas gene expression may result in a number of genetic disorders. The genetic variations occurring in the Fas/FasL promoter region may be significantly involved in the pathogenesis of RA by affecting apoptosis. Caspases (cysteine-aspartic proteases or cysteine-dependent aspartate-directed proteases) are a family of cysteine proteases. Caspases are synthesized as inactive procaspases and acquire catalytic activity after cleavage of their prodomain. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. As an executioner caspase, the caspase 3 zymogen has virtually no activity until it is cleaved by an initiator caspase after apoptotic signaling events have occurred. The activation of caspase 3 is a sign that cell apoptosis enters an irreversible stage. In the Fas/FasL pathway, there is aggregation of the death receptors (DRs) and their death domains (DDs). This aggregation allows the recruitment and association, via DD, of the adaptor molecule FADD (Fas-associated death domain) directly or indirectly via the TNFR-associated death domain (TRADD). FADD molecules have a caspase-binding domain (death effector domain, DED), where initiator caspases 8 and 10 bind and form a complex called DISC (death-inducing signaling complex). The formation of DISC leads to cleavage and activation of caspase 8 by autoproteolysis. Active caspase 8 is released into the cytoplasm where it activates downstream effector caspases 3, 6, and 7, which then induce apoptosis. B-cell lymphoma-2 (Bcl-2) is specifically considered an important anti-apoptotic protein. When it is functional, it can cause immune unresponsiveness to self-antigens via both central and peripheral tolerance. In the case of defective apoptosis, it may contribute to etiological aspects of autoimmune diseases. Mice overexpressing Bcl-2 in all hematopoietic cells provide a useful tool to study the effects of Bcl-2 on innate and adaptive immunity. Bcl-2 overexpression-driven perturbation of effector or regulatory CD4 + T cells explains the reduced arthritis in a number of disease models XFC, one of the Chinese patented medicines produced by our hospital, has been widely used in the clinical treatment of RA. XFC was approved as a hospital preparation by the Anhui Province Food and Drug Administration in 1997, then renamed the Fufangqiyi capsule in 2005 (drug approval number: Anhui medicine system Z20050062). The drug is produced in compliance with strict QC control. The high-performance thin-layer chromatography fingerprint chromatographic for the evaluation of XFC was shown in a previous study. XFC consists of Huangqi (Radix Astragali Mongolici), Yiyiren (Semen Coicis), Wugong (Scolopendra), and Leigongteng (Radix et Rhizoma Tripterygii), which are components based on the theory of the monarch, which means basic principles of compatibility of prescriptions. Regarding pharmacological aspects, Huangqi (Radix Astragali Mongolici) can enhance the function of the adrenal cortex through excitation of the pituitary-adrenal cortex system. It might enhance the ability to scavenge immune complexes and regulate immune function. Yiyiren (Semen Coicis) contains substances effective for neuropathic pain that has significant analgesic and anti-inflammatory effects. Scolopendra is effective in the treatment of RA, and this beneficial effect may be accomplished through normalization of T lymphocyte subsets and the balance of Th1/Th2 cytokines. Leigongteng (Radix et Rhizoma Tripterygii) has immunosuppressive activity in vitro. Its inhibitory effect was found on lymphocyte transformation in the compounds test. Its xylem extract has been used in the clinical treatment of RA, skin disorders, male-fertility control, and other inflammatory and autoimmune diseases.