1.Clinical analysis of effect of Dexmedetomidine on postoperative cognitive function and preoperative inflammation in the elderly patients undergoing general anesthesia
Haibing MENG ; Wei LAI ; Jun SHUAI ; Guoyou DING
The Journal of Practical Medicine 2014;(14):2300-2301
Objective To study the effect of dexmedetomidine (DEX) on postoperative cognitive function and preoperative inflammation in the elderly patients undergoing general anesthesia. Methods 70 elderly patients undergoing general anesthesia operation were chosen and divided into observation group and control group randomly. DEX and physiological saline were applied in observation group on the basis of routine general anesthesia. The cognitive function of patients in both groups were tested by mini-mental state examination (MMSE) and the incidence rate of cognitive dysfunction (POCD) were measured at 1 day before surgery, 1 day, 3 days, 5 days, and 7 days after surgery. The level of interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) were tested before anesthesia, during skin incision, rightly after operation and 1h after operation. Results MMSE scores were significantly higher and the incident rates of POCD were lower in observation group than those in control group at 1 day and 3 days after surgery (P<0.05). The levels of IL-6 and TNF-αincreased obviously during skin incision and postoperative period, and they were significantly lower in observation group (P<0.05). The levels of IL-6 and TNF-αdecreased to the levels before anesthesia in observation group, and were still much higher in control group than that of preanesthesia (P < 0.05). Conclusions DEX infusion intraoperatively may effectively decrease the incidence of early POCD, whose mechanism could be reducing inflammation response.
2.Anti-rejection effects of CTLA-4 Ig fusion protein on cardiac allografts in mice and its mechanism in vivo
Guoshan DING ; Quanxing WANG ; Ming ZHANG ; Wenji SUN ; Yushan LIU ; Guoyou CHEN ; Zhiren FU ; Xuetao CAO ;
Academic Journal of Second Military Medical University 1985;0(06):-
Objective: To determine the anti rejection effects of CTLA 4 Ig fusion protein on cardiac allografts in mice and to discuss its mechanism in vivo . Methods: BALB/c recipients were performed cervical heterotopic heart transplantation to receive C57BL/6 donor hearts with a cuff technique. BALB/c recipients were intraperitoneally injected with CTLA 4 Ig [100 ?g/d?15 times], control immunoglobins and PBS to observe the survival time of allografts with ECG. The hyporesponsiveness of splenic T cell, the polarization of the T subsets were analyzed after the recipients treated with CTLA 4 Ig. Results: After treated with CTLA 4 Ig, the survival of cardiac grafts was significantly prolonged compared with the control groups, and more than 40% cardiac grafts survived over 2 months. The splenic T cells isolated from recipients did not respond to restimulation of donor splenocytes in MLR, but did exhibit the capacity to proliferate in response to C3H splenocytes(third party).The levels of IL 2 and IFN ? decreased and the level of IL 10 increased in CTLA 4 Ig treated mice. Conclusion: Administration of CTLA 4 Ig can induce donor specific tolerance, which induce T subsets to polarize toward Th2 subset and hyporesponsiveness to alloantigen, and prolong the survival time of the cardiac grafts effectively. [
3.Chaperone-mediated Autophagy Regulates Cell Growth by Targeting SMAD3 in Glioma.
Hanqun LIU ; Yuxuan YONG ; Xingjian LI ; Panghai YE ; Kai TAO ; Guoyou PENG ; Mingshu MO ; Wenyuan GUO ; Xiang CHEN ; Yangfu LUO ; Yuwan LIN ; Jiewen QIU ; Zhiling ZHANG ; Liuyan DING ; Miaomiao ZHOU ; Xinling YANG ; Lin LU ; Qian YANG ; Pingyi XU
Neuroscience Bulletin 2022;38(6):637-651
Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.