ABSTRACT
Objective:To investigate the effect and underlying mechanism of BRCC3 knockout on acute GVHD(aGVHD) of mice.Methods:A total of 12 recipient C57BL/6J mice were divided into two groups, including 6 wild type(WT) and BRCC3 -/-(KO). The recipients were exposed to 4.5 Gy + 4.5 Gy 60Co γ-rays in total body irradiation (TBI) at 30 min intervals. At 6 h post-irradiation, 1×10 7bone marrow cells and 8×10 6 splenocytes from BALB/c mice were infused into C57BL/6J mouse via tail vein to develop aGVHD mouse model. BRCC3 was specifically knocked out in aGVHD mouse model. The organ damage was examined through histopathology. The levels of serum cytokines were measured by enzyme-linked immuno sorbent assay (ELISA) and cytometric bead array (CBA), respectively. Spleen, liver and small intestine lymphocytes were isolated at 9 d post-transplantation, and the infiltration and activation of T cells in the target organs were assayed using flow cytometry. Results:The absence of BRCC3 in recipient mice significantly shortened survival ( P<0.05) with increased liver injury of aGVHD mice. In BRCC3 -/-recipient mice, the proportions of CD8+ T cells and CD8+ CD25+ T cells were significantly higher than those in the spleen( t=6.53, 5.52, P<0.05), and the proportions of CD8+ T cells and CD8+ CD25+ T cells were significantly increased in the liver ( t=3.74, 3.19, P<0.05). Similarly, the proportions of CD8+ T cells, CD8+ CD25+ T cells and CD8+ CD69+ T cells were significantly elevated in the small intestine ( t=3.52, 4.06, 3.29, P<0.05). Conclusions:BRCC3 deletion increased the proliferation and activation of donor CD8+ T cells and aggravated aGVHD, which might provide a new prevention and treatment target for aGVHD.
ABSTRACT
Glucose transporters protein (GLUTs) is the main carrier of glucose transport in mammalian cells, in which GLUT1 is the most widely distributed in glucose transporter in vivo. Studies have shown that GLUT1 has abnormally high expression in urinary tract tumors such as renal cell carcinoma,prostate cancer,bladder cancer and nephroblastoma,cleading to increased intracellu-lar glucose uptake,which is closely related to tumor occurrence,evolution,invasion,prognosis and drug resistance. As a new target of tumor therapy,GLUT1 has attracted extensive attention. This review summarizes the recent advances on the expression of GLUT1 in tumor and its mechanism,which can provide a new perspective for the treatment and prognosis evaluation of tumor.
ABSTRACT
After target blood glucose (HbA1C,fasting plasma glucose),serum lipid profiles (total cholesterol,triglyeeride) and control of blood pressure were achieved in 532 patients with type 2 diabetes mellitus, the level of serum uric acid was significantly decreased and the number of case of hyperuricacidemia also reduced (all P<0.01).
ABSTRACT
During the last forty years, although cytotoxic chemotherapy for gastric cancer patients has improved to some extent, its therapeutic effect is limited. Simultaneously, great progression of oncobiology to increase our understanding of the molecular basis of gastric cancer has been made. Currently the cancer cell has been characterized by several genetic changes that lead to altered cellular functions. In addition, multiple cancer-cell environment factors affect the tumor cell via various receptors and subsequent signaling pathways. The increasing knowledge of cellular signaling offers the opportunity to develop novel substances that target specific pathway molecules.