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NQO1 dependent non-canonical necroptosis mediated by ROS and RIP1/RIP3 in parallel in glioma cancer cells

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中国药理学与毒理学杂志 2018年第4期32卷 326-327页

作者： Jie YU xia-xia WU chang-xi wang Hong-wei GAO Wen SUN Jin-Jian LU xiu-ping CHEN State Key Laboratory of Quafity Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macao Macao China

OBJECTIVE Glioblastomas(GBM) are the most malignant brain tumors in humans and have a very poor *** therapeutics are urgently ***,we reported 2-methoxy-6-acetyl-7-methyljuglone(MAM)-induced cell death in U87 and U251 glioma cancer *** Cells were cultured and treated with MAM,the cell viability was determined by MTT assay and LDH *** reactive oxygen species(ROS) generation was observed by DCF *** protein expression was determined by Western *** MAM induced glioma cancer cell death without caspase *** cell death induced by MAM was attenuated by the pharmacological or genetic blockage of necroptosis signaling,including RIP1 inhibitor necrostatin-1 s(Nec-1 s) and siRNA-mediated gene silencing of RIP1 and RIP3,but was unaffected by caspase inhibitor z-vad-fmk or necrosis inhibitor 2-(1 H-Indol-3-yl)-3-pentylamino-maleimide(IM54).MAM treated U87 and U251 glioma cancer cells induced RIP1/RIP3 complex formation,ROS level increased,ATP concentration decreased and loss of plasma membrane integrity,further confirmed this process was *** essential role of ROS was confirmed by the protective effect of ROS scavenger ***,MAM induced necroptosis both triggered by RIP1/RIP3 complex and ROS ***,MAM induced necroptosis through cytosolic calcium(Ca2 +) accumulation and sustained c-Jun N-terminal kinase(JNK) *** calcium chelator BAPTA-AM and JNK inhibitor SP600125 could attenuate cell ***,we found there exists a feedback loop between RIP1 and JNK ***,MAM induced necroptosis was inhibited by dicoumarol(a NQO1 inhibitor).Dicoumarol exposed glioma cancer cells were resistant to RIP1/RIP3 complex formation and ROS *** induced necroptosis was independent of *** MAM induced non-canonical necroptosis through the NQO1-dependent ROS and RIP1/RIP3 *** study also provided new insights into the molecular regul

关键词：脑肿瘤药物治疗治疗方法临床分析

Hemodynamics in Transplant Renal Artery Stenosis and its Alteration after Stent Implantation Based on a Patient-specific Computational Fluid Dynamics Model

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Chinese Medical Journal 2017年第1期130卷 23-31页

作者： Hong-Yang wang Long-Shan Liu Hai-Ming Cao Jun Li Rong-Hai Deng Qian Fu Huan-xi Zhang Ji-Guang Fei chang-xi wang Organ Transplant Center The First Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong 510080 China Guangdong Provincial Key Laboratory on Organ Donation and Transplant Immunology Guangzhou Guangdong 510080 China

Background： Accumulating studies on computational fluid dynamics （CFD） support the involvement of hemodynamic factors in artery stenosis. Based on a patient-specific CFD model, the present study aimed to investigate the hemodynamic characteristics of transplant renal artery stenosis （TRAS） and its alteration after stent treatment. Methods： Computed tomography angiography （CTA） data of kidney transplant recipients in a single transplant center from April 2013 to November 2014 were reviewed. The three-dimensional geometry of transplant renal artery （TRA） was reconstructed from the qualified CTA images and categorized into three groups： the normal, stenotic, and stented groups. Hemodynamic parameters including pressure distribution, velocity, wall shear stress （WSS）, and mass flow rate （MFR） were extracted. The data of hemodynamic parameters were expressed as median （interquartile range）, and Mann-Whitney U-test was used for analysis. Results： Totally, 6 normal, 12 stenotic, and 6 stented TRAs were included in the analysis. TRAS presented nonuniform pressure distribution, adverse pressure gradient across stenosis throat, flow vortex, and a separation zone at downstream stenosis. Stenotic arteries had higher maximal velocity and maximal WSS （2.94 [2.14, 3.30] vs. 1.06 /0.89, 1.15] m/s, 256.5 [149.8, 349.4] vs. 41.7 [37.8, 45.3] Pa at end diastole, P - 0.001 ; 3.25 [2.67, 3.56] vs. 1.65 [ 1.18, 1.72] m/s, 281.3 [ 184.3,364.7] vs. 65.8 [61.2, 71.9] Pa at peak systole, P - 0.001 ） and lower minimal WSS and MFRs （0.07 [0.03, 0.13] vs. 0.52 [0.45, 0.67] Pa, 1.5 [1.0, 3.0] vs. 11.0 [8.0, 11.3] g/s at end diastole, P = 0.001 ; 0.08 [0.03, 0.19] vs. 0.70 [0.60, 0.81] Pa, 2.0 [1.3, 3.3] vs. 16.5 [13.0, 20.3] g/s at peak systole, P 0.001） as compared to normal arteries. Stent implantation ameliorated all the alterations of the above hemodynamic factors except low WSS. Conclusions： Hemodynamic factors were significantly changed in severe TRAS. Stent implantation can restore or ame

关键词： Hemodynamics Kidney Transplantation Patient-specific Modeling Renal Artery Obstruction

Prognostic factors of young patients with colon cancer after surgery

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World Journal of Gastroenterology 2006年第9期12卷 1458-1462页

作者： Han Liang xiao-Na wang Bao-Gui wang Yuan Pan Ning Liu Dian-chang wang xi-Shan Hao Department of Gastrointestinal Ontological Surgery Tianjin Cancer Hospital Tianjin Medical University Tianjin 300060 China

AIM： To investigate the prognostic factors of 96 young patients with colon cancer within a cancer center by univariate and multivariate analysis. METHODS： A total of 723 patients with colon cancer were treated surgically during a period of 10 years. Ninty six of them were 40 years old or younger. R0, R1 and R2 operations were performed in 69 （71.9%）, 4 （4.1%） and 23 patients （24%）, respectively. Left hemicolectomy was performed in 43 patients, right hemicolectomy in 37 patients, transverse colon resection in 9 patients and low anterior resection in 7 patients. Cox multivariate regression analysis was performed to identify predictors of survival. RESULTS： The operation mortality was 0%, 54 patients died within 111 mo after operation due to occurrence or metastases of the tumor. Liver, lung and bone metastases occurred in 3, 1 and 5 patients, respectively. The mean survival time for all patients was 77.9 ± 5.01 mo and the overall 3-, 5- and 10- year survival rates were 66.68%, 58.14% and 46.54%, respectively. In the univariate survival analysis, patient age, type of operation, radical resection, blood transfusion, histological type, diameter of tumor, depth of tumor invasion, lymphatic invasion, distant metastases, liver metastases and TNM stage were found to be predictors of survival in young patients with colon cancer. In the Cox-regression analysis, blood transfusion and lymphatic invasion were determined as independent prognostic factors of survival. CONCLUSIONS： Age, type of operation, radical resection, blood transfusion, histological type, diameter of tumor, depth of tumor invasion, lymphatic invasion, distant metastasis and TNM stage are the predictors of survival in young patients with colon cancer after surgery.

关键词： Prognosis Colon cancer Young patient Surgery

Diltiazem augments the influence of MDR1 genotype status on cyclosporine concentration in Chinese patients with renal transplantation

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Diltiazem augments the influence of MDR1 genotype status on ...

Prognosis of BK polyomavirus nephropathy: 10-year analysis of 133 renal transplant recipients at a single center

2016年广东省药师周大会

作者： Yi-xi wang Jia-li Li Xue-ding wang Yu Zhang chang-xi wang Min Huang Institute of Clinical Pharmacology School of Pharmaceutical SciencesSun Yat-sen University Department of Pharmacy The Second Affiliated Hospital of Guangzhou Medical University Department of Organ Transplant The First Affiliated HospitalSun Yat-sen University

Objective:The aim of the present study was to assess the influence of diltiazem on the relationship between MDR1 genetic polymorphisms and cyclosporine concentration(Cs A) after renal transplantation in Chinese ***:MDR1 C1236 T,G2677 T/A and C3435 T polymorphisms were determined through PCR-RFLP.A total of 126 Chinese renal transplant patients were enrolled in this *** whole blood concentration was measured using the FPIA method,and the adjusted trough concentrations were compared among groups with different ***:The adjusted Cs A trough concentration was significantly higher in MDR1-3435 TT carriers than in CC and CT carriers,showing 58.83±13.95 versus 46.14±7.55 and 45.18±12.35 ng/m L per mg/kg,respectively,in patients using diltiazam(p=0.011),and these differences were not observed in patients who did not use *** adjusted Cs A trough concentration was significantly higher in MDR1-2677 TT carriers than in GG or GT carriers,showing 61.31±12.93 versus 52.25±7.83 and 39.70±7.26 ng/m L per mg/kg,respectively,in patients using diltiazam(p=0.004);however,these differences were also observed in patients who did not use diltiazam,showing 43.27±5.95 versus 35.22±7.55 and 29.54±5.35 ng/m L per mg/kg(p=0.001),*** adjusted Cs A trough blood concentration was significantly higher in haplotype T-T-T and haplotype T-T-C carriers than in non-carriers,regardless of co-treatment with diltiazem or ***:We concluded that the MDR1 variant was associated with adjusted Cs A trough concentration,and this effect was more obvious in renal transplant patients co-treated with diltiazem compared with the patients treated with Cs A alone.

关键词： cyclosporin diltiazem MDR1 genotype

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Chinese Medical Journal 2019年第4期132卷 388-394页

作者： Xu-Tao Chen Shi-Cong Yang Jun Li Rong-Hai Deng Wen-Fang Chen Jiang Qiu Li-Zhong Chen chang-xi wang Gang Huang Department of Organ Transplantation The First Affiliated Hospital of Sun Yat Sen UniversityGuangzhouGuangdong 510080China Department of Pathology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdong 510080China.

Background: BK virus-associated nephropathy (BKVN) is an important cause of chronic allograft dysfunction. The objective of our study was to evaluate the prognosis of BKVN. Methods: We retrospectively reviewed the data of 133 renal transplant recipients with BKVN treated at the First Affiliated Hospital of Sun Yat-Sen University between July 2007 and July 2017. BK viral loads, graft function, and pathologic indexes were compared between initial diagnosis and last follow-up. Results: After a mean follow-up period of 14.4 (range, 0.3–109.6) months after diagnosis of BKVN, BK viruria, and BK viremia become negative in 19.5% and 90.2% of patients, respectively. The mean estimated glomerular filtration rate (eGFR) at last follow- up was lower than at diagnosis of BKVN (18.3 ± 9.2 vs. 32.8 ± 20.6 mL·min^-1·1.73 m^-2, t= 7.426, P < 0.001). Eight (6.0%) patients developed acute rejection after reducing immunosuppression. At last follow-up, the eGFR was significantly lower in patients with subsequent rejection than those without (21.6 ± 9.8 vs. 33.5 ± 20.9 mL·min^-1·1.73 m^-2, t= 3.034, P= 0.011). In 65 repeat biopsies, SV40-T antigen staining remained positive in 40 patients and became negative in the other 20 patients. The eGFR (42.6 ± 14.3 vs. 26.5 ± 12.3 mL·min^-1·1.73 m^-2), urine viral loads (median, 1.3 × 105vs. 1.4 × 107 copies/mL), and plasma viral load (median, 0 vs. 0 copies/mL) were all significantly lower in patients with negative SV40-T antigen staining than those with persistent BK involvement (all, P < 0.05). Five (3.8%) recipients lost their graft at diagnosis of BKVN, and 13 (9.8%) lost their graft during the follow-up period. The 1-, 3-, and 5-year graft survival rates after diagnosis of BKVN were 99.2%, 90.7%, and 85.7%, respectively. Higher pathologic stage correlated with lower allograft survival rate (χ^2= 6.341, P= 0.042). Conclusion: Secondary rejection and persistent histologic infection in BKVN lead to poor prognosis.

关键词： Kidney transplantation BK virus Pathology Rejection Prognosis

Comprehensive external evaluation of published population pharmacokinetics models of mycophenolic mofetil in adult kidney transplant recipients co-administered with tacrolimus

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Comprehensive external evaluation of published population ph...

Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

2018年中国药理学会定量药理学专业委员会学术年会

作者： chang-Cheng Sheng Huan-xi Zhang Long-Shan Liu Bi Luo Qian Fu Qun Zhao Jun Li Yan-Feng Liu Rong-Hai Deng chang-xi wang Zheng Jiao Department of Pharmacy Huashan HospitalFudan University Department of Pharmacy Guizhou Provincial People's Hospital Organ Transplant Center the First Affiliated HospitalSun Yat-sen University Department of urology Shenzhen People's Hospital

Objective Various mycophenolate mofetil (MMF) population pharmacokinetic (popPK) models have been developed to describe its pharmacokinetic (PK) characteristics and facilitate its optimal dosing in adult kidney transplant recipients co-administered with ***,their applicability when extrapolated to other centres remains ***,this study aimed to comprehensively evaluate the

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu chang Lin xi Shi Wei Chen Shiming Yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

固体氧化物燃料电池Sr系钙钛矿电极B位元素成分优化规律

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无机材料学报 2017年第10期32卷 1055-1062页

作者：常希望陈宁王丽君李福燊卞刘振周国治北京科技大学钢铁冶金新技术国家重点实验室北京100083 北京科技大学无机非金属材料系北京100083 北京科技大学物理化学系北京100083

采用第一性原理,对元素周期表中3~6周期52种元素作为固体氧化物燃料电池(SOFC)Sr为A位系列钙钛矿结构电极材料B位替换元素的相关结构相的结合能进行了系统计算,据此分析了各元素对生成立方相和六方相结构稳定性影响的趋势。通过对相关... 详细信息

采用第一性原理,对元素周期表中3~6周期52种元素作为固体氧化物燃料电池(SOFC)Sr为A位系列钙钛矿结构电极材料B位替换元素的相关结构相的结合能进行了系统计算,据此分析了各元素对生成立方相和六方相结构稳定性影响的趋势。通过对相关体系的成分比例进行推算,讨论了这些实验体系在稳定性趋势图中的分布规律,进一步对上述体系的实验数据进行分析,得到了以Mo-Fe-Co连线为中心的成分优化区域。根据相关氧离子扩散模型的计算,结果显示该区域形成的原因与氧空位形成能、迁移能以及禁带宽度均较为适中有关。以上理论结合实验的研究为电极材料的成分优化提供了理论指导。

关键词： SOFC 钙钛矿型电极材料第一性原理计算数据分析

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固体氧化物燃料电池阳极材料成份的优化规律

无机材料学报 2015年第10期30卷 1043-1048页

作者：常希望陈宁王丽君卞刘振李福燊周国治北京科技大学钢铁冶金新技术国家重点实验室北京100083 北京科技大学无机非金属材料系北京100083

本研究借助第一性原理总能量计算法,针对可能用于固体氧化物燃料电池阳极材料的3～6周期金属元素及其氧化物,进行了稳定性、电学性能及力学性能等方面的研究。对工作条件下（高温、还原性气氛）阳极的结构形态、综合性能等的演化情况进... 详细信息

本研究借助第一性原理总能量计算法,针对可能用于固体氧化物燃料电池阳极材料的3～6周期金属元素及其氧化物,进行了稳定性、电学性能及力学性能等方面的研究。对工作条件下（高温、还原性气氛）阳极的结构形态、综合性能等的演化情况进行了研究分析,得到了金属/氧化物体系体模量、禁带宽度的变化趋势,及其与稳定性的关系。结果显示,位于生成趋势图中部区域的金属/氧化物稳定性适中,易于发生氧化/还原反应,可能是阳极工作条件下综合性能较优的原因,其中靠近金属区的元素更能为体系提供电子电导和催化活性,靠近氧化物区的元素更能为体系提供氧离子并增加稳定性,这些结果为不同条件下的阳极选择提供了理论指导。

关键词：固体氧化物燃料电池阳极材料第一性原理生成趋势图优化规律