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Sorting nexin 3 exacerbates doxorubicin-induced cardiomyopathy via regulation of TFRC-dependent ferroptosis

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Acta Pharmaceutica Sinica B 2023年第12期13卷 4875-4892页

作者： Wenjing Yu Yuehuai Hu Zhiping Liu Kaiteng Guo Dinghu Ma Mingxia Peng Yuemei Wang Jing zhang Xiaolei zhang Panxia Wang Jiguo zhang peiqing Liu Jing Lu National and Local United Engineering Lab of Druggability and New Drugs Evaluation School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China Guangdong Provincial Key Laboratory of New Drug Design and Evaluation Guangdong Province Engineering Laboratory for Druggability and New Drug EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China School of Pharmacy Jinan UniversityGuangzhou 510632China School of Pharmaceutical Sciences Shandong First Medical University&Shangdong Academy of Medical SciencesTaian 271016China

The clinical utilization of doxorubicin(Dox)in various malignancies is restrained by its major adverse effect:irreversible *** studies have been done to explore the prevention of Dox ***,ferroptosis has been shown to participate in the incidence and development of Dox *** Nexin 3(SNX3),the retromer-associated cargo binding protein with important physiological functions,was identified as a potent therapeutic target for cardiac hypertrophy in our previous ***,few study has shown whether SNX3 plays a critical role in Dox-induced *** this study,a decreased level of SNX3 in Dox-induced cardiomyopathy was ***-specific Snx3 knockout(Snx3-cKO)significantly alleviated cardiomyopathy by downregulating Dox-induced ferroptosis ***3 was further demonstrated to exacerbate Dox-induced cardiomyopathy via induction of ferroptosis in vivo and in vitro,and cardiac-specific Snx3 transgenic(Snx3-cTg)mice were more susceptible to Dox-induced feroptosis and ***,SNX3 facilitated the recycling of transferrin 1 receptor(TFRC)via direct interaction,disrupting iron homeostasis,increasing the accumulation of iron,triggering ferroptosis,and eventually exacerbating Dox-induced ***,these findings established a direct SNX3-TFRC-ferroptosis positive regulatory axis in Dox-induced cardiomyopathy and suggested that targeting SNX3 provided a new effective therapeutic strategy for Dox-induced cardiomyopathy through TFRCdependentferroptosis.

关键词： SNX3 Ferroptosis TFRC Cardiomyopathy Doxorubicin Iron homeostasis Cell death Mitochondria

基于TLR4/BAFF/APRIL信号通路探讨肾炎止血丸对IgA肾病大鼠的作用机制

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中国中医药科技 2023年第6期30卷 1061-1066页

作者：陈明闫晓明王海艳尚国旗李莲花程楚楚陈瑶张佩青黑龙江省中医药科学院黑龙江哈尔滨150036

目的:观察肾炎止血丸对IgA肾病(IgAN)模型大鼠的治疗作用及其对TLR4/BAFF/APRIL通路的影响。方法:采用“牛血清白蛋白+四氯化碳+脂多糖”联用法构建IgAN大鼠模型,48只大鼠随机分为正常对照组、模型组、氯沙坦钾片组[20 mg/(kg·d)]、肾... 详细信息

目的:观察肾炎止血丸对IgA肾病(IgAN)模型大鼠的治疗作用及其对TLR4/BAFF/APRIL通路的影响。方法:采用“牛血清白蛋白+四氯化碳+脂多糖”联用法构建IgAN大鼠模型,48只大鼠随机分为正常对照组、模型组、氯沙坦钾片组[20 mg/(kg·d)]、肾炎止血丸高剂量组[3.6 g/(kg·d)]、中剂量组[1.8 g/(kg·d)]、低剂量组[0.9 g/(kg·d)],每组8只,均连续给药6周。留取尿液、血液、肾组织标本,分别进行尿红细胞计数、尿白蛋白检测;ELISA法检测大鼠血清Toll样受体4(TLR4)、核因子κB(NF-κB)、B细胞活化因子(BAFF)、增殖诱导配体(APRIL)、核心1β1,3半乳糖基转移酶伴侣蛋白(Cosmc)、半乳糖缺陷型IgA1(Gd-IgA1)、白介素6(IL-6)水平;光镜观察各组大鼠肾组织病理变化。结果:①尿红细胞、尿蛋白变化:与模型组比较,各给药组减少明显(均P<0.01);与阳性组组比较,肾炎止血丸中剂量组、高剂量组减少明显(均P<0.01);与低剂量组比较,肾炎止血丸中剂量组、高剂量组减少明显(均P<0.01)。②TLR4、NF-κB、BAFF、APRIL、Cosmc、Gd-IgA1、IL-6:与模型组比较,各给药组TLR4、NF-κB、BAFF、APRIL、Gd-IgA1、IL-6减少明显(均P<0.01),Cosmc升高明显(P<0.01);与阳性组比较,肾炎止血丸低剂量组NF-κB、BAFF减少明显(均P<0.01),中剂量组TLR4、Gd-IgA1减少(均P<0.05)及IL-6减少明显(P<0.01),高剂量组TLR4、NF-κB、BAFF、APRIL、Gd-IgA1、IL-6减少明显(均P<0.01),Cosmc升高明显(P<0.01);与低剂量组比较,中剂量及高剂组TLR4、NF-κB、Gd-IgA1、IL-6减少明显(均P<0.01),中剂量组BAFF减少明显(P<0.01),高剂量组BAFF减少(P<0.05),高剂量组APRIL减少明显(P<0.01)及Cosmc升高明显(P<0.01);与中剂量组比较,高剂量组治疗后NF-κB、BAFF、APRIL、Gd-IgA1、IL-6减少明显(均P<0.01),Cosmc升高明显(P<0.01)。③病理学变化:与模型组比较,各给药组IgA、C3的免疫荧光累积光密度值(IOD)减少明显(均P<0.01);与阳性组比较,高剂量组C3 IOD减少明显(P<0.01);与低剂量组比较,高剂量组C3 IOD减少明显(P<0.01);与中剂量组比较,高剂量组IgA IOD减少(P<0.05),高剂量组C3 IOD减少明显(P<0.01)。结论:肾炎止血丸能够改善IgAN大鼠蛋白尿,减轻血尿及肾组织病理损伤;其作用机制可能与调控TLR4/BAFF/APRIL通路有关。

关键词：肾炎止血丸 IgA肾病 TLR4 BAFF APRIL C1GALT1 Cosmc Gd-IgA1 IL-6 病理学大鼠

WIP1 promotes cancer stem cell properties by inhibiting p38 MAPK in NSCLC

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2055-2064页

作者： Kaiyuan Deng Liang Liu Xiaoming Tan Zhen zhang Jianjun Li Yang Ou Xin Wang Shuang Yang Rong Xiang peiqing Sun School of Medicine Nankai UniversityTianjin 30071China Departments of Immunology and Microbial Science The Scripps Research InstituteLa JollaCA 92037USA Department of Cancer Biology and Wake Forest Baptist Comprehensive Cancer Center Wake Forest School of MedicineWinston-SalemNC 27157USA Department of Respiratory Disease South CampusRenji HospitalSchool of Medicine Shanghai Jiaotong UniversityShanghaiChina

Cancer stem cells(CSCs)are a small population of stem cell-like cancer cells that can initiate tumors in vivo,and are the major source of cancer initiation,relapse,and drug *** previously reported that the p38 MAPK,through its downstream effectors MK2 and HSP27,suppressed CSC properties by downregulating the expression of transcription factors that mediate stemness in non-small-cell lung cancer(NSCLC)cells,and that despite unaltered total expression of total p38 proteins,the levels of activated p38 were reduced in NSCLC ***,the mechanism underlying the reduced levels of activated p38 in NSCLC is *** this study,we identified WIP1,a p38 phosphatase frequently overexpressed in cancer,as a suppressor of p38 in a pathway that regulates CSC properties in *** WIP1 expression correlated with reduced levels of activated p38,and with increased levels of a CSC marker in NSCLC *** investigation revealed that WIP1 promoted stemness-related protein expression and CSC properties by inhibiting p38 activity in NSCLC ***1 inhibitors are currently under development as anticancer drugs based on their ability to reactivate *** found that a WIP1 inhibitor suppressed stemness-related protein expression and CSC properties by activating p38 in NSCLC cells in vitro and in *** studies have identified the WIP1–p38–MK2–HSP27 cascade as a novel signaling pathway that,when altered,promotes CSC properties in NSCLC development,and have defined novel mechanisms underlying the oncogenic activity of WIP1 and the anticancer efficacy of WIP1 inhibitors.

关键词： HSP27 NSCLC drugs

CDK4/6 inhibition blocks cancer metastasis through a USP51-ZEB1-dependent deubiquitination mechanism

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2214-2226页

作者： Zhen zhang Jianjun Li Yang Ou Guang Yang Kaiyuan Deng Qiong Wang Zhaoyang Wang Wenhao Wang Quansheng zhang Hang Wang Wei Sun peiqing Sun Shuang Yang Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation Medical College of Nankai UniversityTianjin 300071China College of Pharmacy Nankai UniversityTianjin 300071China Tianjin Key Laboratory of Organ Transplantation Tianjin First Center HospitalTianjin 300192China Department of Cancer Biology Wake Forest University School of MedicineWinston-SalemNC 27157USA

Tumor metastasis is the most common cause of cancer-related deaths,yet it remains poorly *** transcription factor zinc-finger E-box binding homeobox 1(ZEB1)is involved in the epithelial-to-mesenchymal transition(EMT)and plays a pivotal role in tumor ***,the underlying mechanisms of the posttranslational modification of ZEB1 remain largely ***,we demonstrated that specific inhibition of CDK4/6 was able to block tumor metastasis of breast cancer by destabilizing the ZEB1 protein in vitro and in ***,we determined that the deubiquitinase USP51 is a bona fide target of CDK4/*** phosphorylation and activation of USP51 by CDK4/6 is necessary to deubiquitinate and stabilize ***,we found a strong positive correlation between the expression of p-RB(an indicator of CDK4/6 activity),p-USP51 and ZEB1 in metastatic human breast cancer ***,the high expression of p-RB,p-USP51,and ZEB1 was significantly correlated with a poor clinical *** together,our results provide evidence that the CDK4/6-USP51-ZEB1 axis plays a key role in breast cancer metastasis and could be a viable therapeutic target for the treatment of advanced human cancers.

关键词： metastasis CDK4 ubiquitin

Increased expression of human T-cell immunoglobulin-and mucin-domain-containing molecule-4 in peripheral blood mononuclear cells from patients with system lupus erythematosus

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Cellular & Molecular Immunology 2010年第2期7卷 152-156页

作者： peiqing Zhao Liyun Xu Piming Wang Xiaohong Liang Jianni Qi Peng Liu Chun Guo Lining zhang Chunhong Ma Lifen Gao Institute of Immunology Shandong University School of Medicine Jinan China Department of Clinical Laboratories Wujing Shandong Zongdui Hospital Jinan ChinaCorrespondence: Dr LF Gao Institute of Immunology Shandong University School of Medicine 44# Wenhua Xi Road Jinan 250012 China.

Systemic lupus erythematosus （SLE） is a prototypic autoimmune disease. Innate and adaptive immunity cooperatively contribute to the development of SLE. Antigen-presenting cells （APCs） have been suggested to link innate and adaptive immunity. T-cell immunoglobulin- and mucin-domain-containing molecule-4 （Tim-4; also known as Timd4）, expressed primarily on the surface of APCs, is a member of the TIM family, a recently described group of molecules that have received much attention as potential regulators of the immune system. In this study, we used quantitative real-time reverse transcription-polymerase chain reaction to examine the mRNA expression of Tim-4 in peripheral blood mononuclear cells （PBMCs） from SLE patients and further analyzed the correlation between the expression of Tim-4 and Tim- 1 （a potential l igand for Tim-4） in PB MCs and serum tumor necrosis factor （TNF）-a levels. The results showed that Tim-4 mRNA expression in PBMCs was significantly higher in SLE patients than in healthy controls, especially those patients in the active phase of disease. Moreover, Tim-4 mRNA levels were closely correlated with Tim- 1 mRNA levels in PBMCs and with serum TNF-a levels in SLE patients but not in the control group. Taken together, these results demonstrate that Tim-4 may be involved in the pathogenesis of SLE.

关键词： Real-time RT-PCR SLE Tim-1 Tim-4 TNF-a

Diagnostic value of ACR TI-RADS combined with three-dimensional shear wave elastography in ACR TI-RADS 4 and 5 thyroid nodules

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Chinese Medical Journal 2023年第10期136卷 1225-1230页

作者： Lijun Hao peiqing Liu Changwei Ding Jing Li Yingchun zhang Department of Ultrasound The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215004China

Background:Three-dimensional shear wave elastography(3D-SWE)is a promising method in distinguishing benign and malignant thyroid *** combining with conventional method,it may further improve the diagnostic *** study aimed to assess the diagnostic value of American College of Radiology(ACR)thyroid imaging reporting and data system(TI-RADS)combined with 3D-SWE in ACR TI-RADS 4 and 5 thyroid ***:All nodules were examined by conventional ultrasonography,ACR TI-RADS classification,and 3D-SWE *** ultrasonography was used to observe the location,size,shape,margin,echogenicity,taller-than-wide sign,microcalcification,and blood flow of thyroid nodules,and then ACR TI-RADS classification was *** Young’s modulus values(3D-C-Emax,3D-C-Emean,and elastography standard deviation[3D-C-Esd])were measured on the reconstructed coronal plane *** to the receiver operating characteristic(ROC)curve,the best diagnostic efficiency among 3D-C-Emax,3D-C-Emean,and 3D-C-Esd was selected and the cut-off threshold was *** to the surgical pathology,they were divided into benign group and malignant *** appropriate statistical methods such as t-test and Mann-Whitney U test were used to compare the difference between the two *** this basis,3D-SWE combined with conventional ACR TI-RADS was reclassified as combined ACR TI-RADS to determine benign or malignant thyroid ***:Of the 112 thyroid nodules,62 were malignant and 50 were *** optimal cut-off value of three-dimensional maximum Young’s modulus in coronal plane(3D-C-Emax)was 51.5 kPa and the area under the curve(AUC)was *** AUC,sensitivity,specificity,and accuracy of conventional ACR TI-RADS were 0.828,83.9%,66.0%,and 75.9%,*** AUC,sensitivity,specificity,and accuracy of combined ACR TI-RADS were 0.845,90.3%,66.0%,and 79.5%,*** difference between the two AUC values was statistically ***

关键词： Three-dimensional shear wave elastography Thyroid nodules American College of Radiology thyroid imaging reporting and data system ACR TI-RADS

推拿联合Bobath疗法在小儿运动发育迟缓康复治疗中的应用效果

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中国当代医药 2024年第9期31卷 75-78页

作者：谭丽婷陈志玮梁佩清陈丽华林少漫张敏婷广东省肇庆市第二人民医院儿童保健科广东肇庆526040

目的观察推拿联合Bobath疗法在小儿运动发育迟缓康复治疗中的应用效果。方法选取2022年1月至2023年7月肇庆市第二人民医院儿童保健科收治的30例运动发育迟缓小儿为研究组,采用推拿联合Bobath疗法,选取2019年1月至2021年12月的30例患儿... 详细信息

目的观察推拿联合Bobath疗法在小儿运动发育迟缓康复治疗中的应用效果。方法选取2022年1月至2023年7月肇庆市第二人民医院儿童保健科收治的30例运动发育迟缓小儿为研究组,采用推拿联合Bobath疗法,选取2019年1月至2021年12月的30例患儿为对照组,单纯采用Bobath疗法。比较两组患儿治疗前后的五大区发育商和治疗效果。结果两组治疗后的五大区发育商(大运动、精细运动、语言、适应能力及社交能力)高于治疗前,且研究组精细运动、语言、适应能力及社交能力评分高于对照组,差异有统计学意义(P0.05);但研究组的治疗效果整体优于对照组,差异有统计学意义(P<0.05)。结论推拿联合Bobath疗法在运动发育迟缓小儿的语言、适应能力及社交能力康复治疗中较单纯Bobath疗法更具有优势,值得临床应用和基层技术推广。

关键词： Bobath疗法推拿小儿运动发育迟缓脑损伤综合征

服用抗甲状腺药物Graves病患者血清抗中性粒细胞胞质抗体阳性与HLA-DRB1*09∶01基因多态性相关

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中华内分泌代谢杂志 2024年第4期40卷 305-311页

作者：王佩青裴剑浩陈重陈红梅蓝颖茹李忠文傅晓莹赖水清张舒婷黄萍余琴谭少珍南方医科大学附属广东省人民医院(广东省医学科学院)内分泌科广州510000 桂林市人民医院内分泌科 541000

目的调查血清抗中性粒细胞胞质抗体(antineutrophil cytoplasmic antibody,ANCA)阳性在服用抗甲状腺药物的Graves病人群中的流行情况及相关影响因素,并探讨CD18 rs235326、HLA-DRB1*09∶01、HLA-DQB1*03∶01基因多态性与血清ANCA阳性的相关性。方法收集2020年9月至2021年12月于广东省人民医院就诊的Graves病患者的临床及实验室检查数据进行横断面分析,并从中选取年龄、性别匹配的血清ANCA阳性及阴性患者对上述基因位点进行测序。结果共有173例患者纳入最终分析,其中ANCA阳性患者42例(24.28%),ANCA阴性患者131例(75.72%)。ANCA阳性患者诊断后病程及服药疗程均显著较ANCA阴性组患者长(P<0.001)。在ANCA阳性患者中,71.43%患者均服用过甲巯咪唑及丙硫氧嘧啶,而在ANCA阴性组,66.41%患者仅服用甲巯咪唑(P<0.001)。各有24例ANCA阳性和25例阴性患者进行基因检测,CD18 rs235326基因多态性在2组间无显著差异,HLA-DRB1*09∶01 rs17886918(P=0.005)、rs9269959(P=0.002)和HLA-DQB1*03∶01 rs1130399(P=0.016)、rs1140317(P=0.029)在2组间等位基因分布存在差异。多因素logistic回归分析显示仅HLA-DRB1*09∶01 rs17886918与血清ANCA阳性呈独立相关(P=0.005)。结论Graves病患者服用抗甲状腺药物期间出现ANCA阳性与更长的诊断后病程及服药疗程相关。位于HLA-DRB1*09∶01上的rs17886918基因多态性可能与ANCA阳性相关。

关键词：抗中性粒细胞胞质抗体 Graves病抗甲状腺药物基因多态性人类白细胞抗原基因

High-performance all-solution-processed inverted quantum dot light-emitting diodes enabled by water treatment

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Nano Research 2023年第7期16卷 10215-10221页

作者： Qianqing Hu Junjie Si Desui Chen Xiaoming Hao Rui Xu Yihang Du Zhuopeng Du Xinquan Gong Hong Zhao peiqing Cai Qi Ai Xin Yao Yu Yan Zenan zhang Muzhi Cai Wei Liu Yongyin Kang Zugang Liu College of Optical and Electronic Technology China Jiliang UniversityHangzhou 310018China Key Laboratory of Excited-State Materials of Zhejiang Province State Key Laboratory of Silicon MaterialsDepartment of ChemistryZhejiang UniversityHangzhou 310027China Institute of Flexible Electronics Technology of THU ZhejiangJiaxing Key Laboratory of Flexible Electronics based Intelligent Sensing and Advanced Manufacturing TechnologyJiaxing 314000China Zhejiang Najing Technology Co. Ltd.Quzhou 324004China Najing Technology Corporation Ltd. Hangzhou 310052China

All-solution-processed inverted quantum dot(QD)light-emitting diodes(QLEDs)with transparent bottom cathodes can be directly connected to the n-type thin-film transistors,offering a feasible solution for low-cost active matrix-driven QD ***,the subsequent solution-deposition of the hole-transporting layer destroys the underneath QD films,resulting in largely deteriorated device *** strategies have been implemented to prevent QD film from dissolution,but all at a heavy cost of device performance suffering from either reduced efficiency or increased driving ***,a facile and effective water-treatment approach for QD film to fabricate inverted QLEDs through all solution processing is *** water treatment substitutes the long-chain oleate ligands with hydroxyl groups,resulting in significantly improved non-polar solvent resistance of the QD ***,the QD films reserve their excellent photoluminescence efficiency after water *** the water-treated QD film as the emissive layer,all-solution-processed inverted red QLED with a peak external quantum efficiency of 19.6%,a turn-on voltage of 1.8 V,and a T50 operational lifetime of 150,000 h at 100 cd·m^(-2) was ***,efficient and low-voltage-driven green and blue QLEDs can also be prepared with this *** work provides a feasible strategy for the fabrication of high-performance all-solution-processed inverted QLEDs,paving the way toward achieving QLEDs by all ink-jet printing.

关键词： solvent-resistance quantum dots inverted electroluminescence all solution processing