1.Podocyte apoptosis is suppressed by 1,25(OH)2D3 in puromycin aminonudeoside nephropathy rats
Houqin XIAO ; Wei SHI ; Shuangxin LIU ; Wenjian WANG ; Xinling LIANG ; Yongzheng LIANG ; Qiuxiong LIN
Chinese Journal of Nephrology 2008;24(12):890-896
ObjectiveTo evaluate the effects of 1,25(OH)zD3 on podocyte apoptosis in kidney of puremyein aminonueleoside nephropathy (PAN) rats. Methods Seventy-two male Sprague-Dawley rats were randomly divided into three groups: PAN model group(PAN), 1,25 (OH)2D3 treated group (T, 0.2 μg·kg-1d-1 by garages) and normal control group (NC). PAN rat model was constructed by a single intravenous injection of 100 mg/kg body weight. Renal function and 24hour urinary protein were measured at day 3, 7, 14, 21 after PAN injection. The renal tissue morphology was observed by light and electron microscope. Podocyte apeptosis was evaluated by TUNEL. Protein expressions of nephrin, TGF-β1 and p-Smad2/3 were examined by immunofluoreacence, immunohistochemistry and Western blot, respectively. Results(1)The levels of serum creafinine, BUN and 24-h urinary protein [(20.26±4.87) mg vs (1.01±0.41) mg at day 7, P <0.01] were significantly higher and the number of glomerular pedocyte was significantly lower [(10.9±4.2)/glomerular volume vs (31.9±6.2)/glomerular volume at day 14, P<0.01] in PAN group compared with NC group. T group rats had less urinary protein excretion [(9.95±3.82) mg/24 h, P<0.01] and more glomerular podocytes compared with PAN group. (2) Distribution of nephrin expression was changed from linear to granular pattern in PAN rats on day 7, nephrin mRNA and protein expressions were markedly decreased(P<0.01), while the number of apoptotic podocyte was increased in PAN group(P<0.01). However, higher nephrin expression and less apoptotic podocytes were found in T group (P<0.01). (3) Compared with NC group, the mRNA and protein expression of TGF-β1 and p-Smad2/3 were higher in PAN group (P<0.01), while 1,25 (OH)2D3 treatment abrogated PAN-induced changes in the expression of TGF-β1 and p-Smad2/3 (P<0.01). Conclusions 1,25 (OH)2D3 can significantly suppress PAN-induced podocyte apoptosis and ameliorate proteinnuria. The beneficial effect of 1,25(OH)2D3 on podocyte may contribute to direct suppression of TGF-β signaling.
2.Cure ofpancreaticoduodenal anastomotic leakage after simultaneous pancreas-kidney transplantation with enteric drainage:a case report and literature review
Desheng LI ; Shanbin ZHANG ; Fanjun ZENG ; Yi WANG ; Jinzhu XIAO ; Jian XU ; Houqin LIU ; Liang XU ; Peng CAO ; Huajun ZHANG
Chinese Journal of Organ Transplantation 2019;40(5):280-283
Objective To summarize the experience of one case of anastomotic leakage after simultaneous pancreas-kidney transplantation (SPK ) with enteric drainage .Methods One case of type 2 diabetes mellitus complicated with end-stage nephropathy undergoing SPK was retrospectively analyzed .Iliac venous systemic circulation was employed for pancreatic venous reflux ,transplanted pancreas exocrine via enteric drainage and side-to-side anastomosis between donor pancreaticoduodenum and recipient jejunum . Pancreatoduodenal anastomotic leakage occurred at 12 days post-operation .During re-operation ,Roux-en-Y anastomosis was established between donor pancreaticoduodenum and recipient jejunum .And the relevant domestic and foreign literatures were searched .Results The follow-up time was 3 month after a second operation .Recipient pancreas and kidney transplantation survived well . There was no onset of enteric leakage .The incidence of anastomotic leakage varies greatly between different transplantation centers both at home and abroad .The incidence ranged from 3 .6% to 11 .3% .And the risk of pancreatic loss was as high as 54 .6% .Conclusions As a severe postoperative complication ,anastomotic fistula after SPK may cuase abdominal infection . Even after reparing enteric fistula , the risk of leakage remains high . Roux-en-Y anastomosis is other therapeutic option .
3.Renal expression of RANK-RANKL in a rat model of puromycin aminonucleoside nephropathy.
Zhonglin FENG ; Shuangxin LIU ; Wei SHI ; Houqin XIAO ; Xinling LIANG ; Xiaoying LIU ; Zhiming YE ; Suxia WANG ; Yongzheng LIANG ; Bin ZHANG ; Wenjian WANG ; Yanhui LIU ; Ping MEI ; Lixia XU ; Jianchao MA ; Yunfeng XIA
Journal of Southern Medical University 2014;34(1):65-69
OBJECTIVETo investigate RANK-RANKL expression in the kidneys of a rat model of puromycin aminonucleoside nephropathy (PAN).
METHODSThirty-six SD rats were randomly divided into PAN model group and normal control group. PAN was induced by a single intravenous injection of 100 mg/kg puromycin aminonucleoside. Serum creatinine and 24-hour urinary protein were measured on days 3, 7, and 14 after the injection, and renal pathologies were assessed with optical and immune transmission electron microscopy. The expression of RANK and RANKL in the kidneys was examined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.
RESULTSThe PAN model rats showed massive proteinuria and elevated serum creatinine on day 3, which peaked on day 7. RANK-RANKL protein and mRNA expressions in PAN model group was higher than those in the control group. In the PAN rats, RANK was expressed mainly on the top cell membrane and in the cytoplasm of renal podocytes with a significantly increased expression level compared with that in the control group.
CONCLUSIONThe PAN rat model shows aberrant RANK and RANKL expressions in the podocytes, indicating their contribution to podocyte injury in PAN.
Animals ; Creatinine ; blood ; Female ; Kidney ; drug effects ; metabolism ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Male ; Podocytes ; drug effects ; metabolism ; Proteinuria ; pathology ; Puromycin Aminonucleoside ; adverse effects ; RANK Ligand ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor Activator of Nuclear Factor-kappa B ; metabolism
4.Preliminary results of multicenter studies on ABO-incompatible kidney transplantation
Hongtao JIANG ; Tao LI ; Kun REN ; Xiaohua YU ; Yi WANG ; Shanbin ZHANG ; Desheng LI ; Huiling GAN ; Houqin LIU ; Liang XU ; Zhigang LUO ; Peigen GUI ; Xiangfang TAN ; Bingyi SHI ; Ming CAI ; Xiang LI ; Junnan XU ; Liang XU ; Tao LIN ; Xianding WANG ; Hongtao LIU ; Lexi ZHANG ; Jianyong WU ; Wenhua LEI ; Jiang QIU ; Guodong CHEN ; Jun LI ; Gang HUANG ; Chenglin WU ; Changxi WANG ; Lizhong CHEN ; Zheng CHEN ; Jiali FANG ; Xiaoming ZHANG ; Tongyi MEN ; Xianduo LI ; Chunbo MO ; Zhen WANG ; Xiaofeng SHI ; Guanghui PEI ; Jinpeng TU ; Xiaopeng HU ; Xiaodong ZHANG ; Ning LI ; Shaohua SHI ; Hua CHEN ; Zhenxing WANG ; Weiguo SUI ; Ying LI ; Qiang YAN ; Huaizhou CHEN ; Liusheng LAI ; Jinfeng LI ; Wenjun SHANG ; Guiwen FENG ; Gang CHEN ; Fanjun ZENG ; Lan ZHU ; Jun FANG ; Ruiming RONG ; Xuanchuan WANG ; Guisheng QI ; Qiang WANG ; Puxun TIAN ; Yang LI ; Xiaohui TIAN ; Heli XIANG ; Xiaoming PAN ; Xiaoming DING ; Wujun XUE ; Jiqiu WEN ; Xiaosong XU
Chinese Journal of Organ Transplantation 2020;41(5):259-264
Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.
5.Fucoidan-functionalized activated platelet-hitchhiking micelles simultaneously track tumor cells and remodel the immunosuppressive microenvironment for efficient metastatic cancer treatment.
Rong GUO ; Miao DENG ; Xuan HE ; Mengmeng LI ; Jiaxin LI ; Penghui HE ; Houqin LIU ; Man LI ; Zhirong ZHANG ; Qin HE
Acta Pharmaceutica Sinica B 2022;12(1):467-482
Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. Platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells (CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β (TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle (FD/DOX) was constructed, which could efficiently adhere to activated platelets through P-selectin. Compared with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOX treatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.