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Light-triggered NO-releasing nanoparticles for treating mice with liver fibrosis

Nano Research 2020年第8期13卷 2197-2202页

作者： Hongxia Liang Zhenhua Li Zhigang Ren Qiaodi Jia Linna Guo Shasha Li Hongyu Zhang Shiqi Hu Dashuai Zhu Deliang Shen zujiang yu Ke Cheng Department of Infectious Disease and Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Department of Molecular Biomedical Sciences and Comparative Medicine Institute North Carolina State UniversityRaleighNC27607USA Joint Department of Biomedical Engineering University of North Carolina at Chapel Hill and North Carolina State UniversityRaleighNC27695USA Department of Cardiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China The Key Lab of Chemical Biology and Organic Chemistry of Henan Province Zhengzhou UniversityZhengzhou450001China

Liver fibrosis, resulting from chronic liver damage and characterized by the accumulation of extracellular matrix (ECM) proteins, is a characteristic of most types of chronic liver diseases. The activation of hepatic stellate cells (HSC) is considered an essential pathological hallmark in liver fibrosis. Although nitric oxide (NO) can effectively induce HSC apoptosis, the systemic administration of NO is ineffective and may cause severe complications such as hypotension. To overcome this limitation, nanoparticles were designed to target HSCs and release NO locally under the exposure of near infrared light (NIR). To achieve this, upconversion nanoparticle (UCNP) cores were enveloped in mesoporous silica shells (UCNP@mSiO2), which were modified with hyaluronic acid (HA-UCNP@mSiO2) and Roussin’s black salt (RBS). HA molecules recognize and bind to CD44 proteins, which are overexpressed on activated HSCs. Under exposure to a 980-nm NIR laser, the UCNP cores convert the 980-nm wavelength into ultraviolet (UV) light, which then energizes the RBS (NO donors), resulting in an efficient release of NO inside of the HSCs. Once released, NO triggers HSC apoptosis and reverses the liver fibrosis. This targeted and controlled release method provides the theoretical and experimental basis for novel therapeutic approaches to treat hepatic fibrosis.

关键词： liver fibrosis nitric oxide(NO) hepatic stellate cells(HSC) nanoparticles near infrared light(NIR)-controlled release

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The successful treatment for cardiac tamponade during radiofrequency ablation of hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2019年第1期18卷 90-92页

作者： Chen Xue Zhigang Ren Xiaobo Hu yuting He Ranran Sun Juan Li Guangying Cui zujiang yu Department of Infectious Disease The First Affiliated Hospital of Zhengzhou University Precision Medicine Center The First Affiliated Hospital of Zhengzhou University

To the Editor:Hepatocellular carcinoma(HCC)is the second most common cause of cancer-related death worldwide[1].Repeated liver resection remains a valid and safe curative therapy option for recurrent HCC in a minority of patients,because of multifocal intrahepatic or extra-hepatic recurrence and tumors in unresectable locations[2].HCC nodules less than 3 cm located in the hepatic dome beneath the diaphragm may represent one of the most difficult sites for resection[3].Therefore,some local invasive therapies,such as radiofrequency ablation(RFA),microwave ablation,transarterial chemoembolization(TACE)and laser hyperthermia,have been developed and applied in clinical HCC treatment[4].RFA has high frequency energy which heats the surrounding tissues and causes severe complications such as acute massive hemorrhage,thermal injury to viscera,pneumothorax and cardiac tamponade[5].

关键词： hepatocellular HCC

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Alterations of the oral and gut mycobiome and cytokines during long-term follow-up of COVID-19 convalescents

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2061-2063页

作者： Zhigang Ren Shanshuo Liu Qiong Wang Benchen Rao Zhaohai Zeng Yakun Xu Haiyu Wang Hong Luo Jianjun Gou zujiang yu Department of Infectious Diseases the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Health Management Center the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Department of Infectious Diseases Guangshan County People’s HospitalGuangshan CountyXinyang465450HenanChina

Dear Editor,A large number of COVID-19 patients experience body-specific conditions such as fatigue,sleep disturbances,anxiety,depression,and dyspnea after the disease has subsided,which is called“long COVID-19”.1 Studies have confirmed reduced microbial diversity,enrichment of opportunistic pathogens and depletion of beneficial symbiotic bacteria in patients with COVID-19.2,3 Long-term dysregulation of the microbiota has also been observed in recovered patients.4 Nevertheless,long-term fungal microbiota follow-up was still blank.

关键词： patients cytokines sided

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Heparin inhibits burn-induced spleen cell apoptosis by suppressing interleukin-1 expression

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Chinese Medical Journal 2014年第13期127卷 2463-2469页

作者： Zhao Songfeng Zhang Xiao Zhang Xiaojian Shi Xiuqin yu zujiang Kan Quancheng Department of Pharmacology the Provincial Key Lab of ClinicalMedicine the First Affiliated Hospital Zhengzhou UniversityZhengzhou Henan 450052 China

Background Epidermal burn injury may trigger significant apoptosis of the spleen cells,which might be caused by a burninduced systemic inflammatory *** has been shown to possess anti-inflammatory *** 1 （IL-1） is centrally important among pro-inflammatory *** hypothesized that heparin might inhibit burn-induced apoptosis in the spleen via suppression of the IL-1 *** Burn injury was performed on IL-1 R＋/＋（IL-1 receptor wild-type mouse） and IL-1 R-/-（IL-1 receptor knockout mouse） mice,and they were then treated with heparin,saline or IL-1 receptor antagonist ***,IL-1α and IL-1β expression were assessed in the spleens and *** curve analysis was further applied to elucidate the mechanism of heparin＇s protective *** Burn induced significant apoptosis （sham：3.6％±2.1％ ***：28.8％±5.9％; P ＜0.001）and remarkable expression o IL-1α and IL-1β in the mouse spleens and *** reduced the burn-induced apoptosis in the spleens （heparin treated：8.6％±3.4％,P ＜0.005）,which could be blocked by *** markedly decreased both IL-1α and IL-1β expression in the spleens and serum of burned ***-1 R-/-mice demonstrated considerably less apoptosis in the spleens and had a higher survival rate after *** did not significantly decrease apoptosis in the spleen and the mortality rate in IL-1 R-/-mice after *** Heparin inhibits burn-induced apoptosis of the spleen cells by suppressing IL-1 expression in mice.

关键词： burn spleen apoptosis heparin interleukin-1

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Hyperammonemia Influences Nonsense-mediated mRNA Decay(NMD) By Change The Quantity Of UPF1,UPF2 and SMG1

Hyperammonemia Influences Nonsense-mediated mRNA Decay(NMD) ...

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中华医学会第十三次全国感染病学术会议

作者： Fulei Li Jingjing Li Qiongye Wang Shasha Li Yanling Chen Lu Bai zujiang yu The First Affiliated Hospital of Zhengzhou University

Backround Chronic severe hepatitis is a critical disease with high ***,effective drugs and therapy still *** observed many patients with severe hepatitis always had hyperammonemia and with using medicine or therapy by Lowering blood ammonia the mortality was also ***’s more,a lot of patients got liver cancer after suffering severe *** nonsense-mediated RNA decay(NMD)was viewed as an important constitutive mechanism to rapidly eliminate mutated *** recently,it has been apprecia-

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靶向B7-H3的CAR-T细胞在实体瘤免疫治疗的研究进展

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中国免疫学杂志 2022年第21期38卷 2650-2655页

作者：张贵珍余祖江韩双印郑州大学第一附属医院感染科郑州450052 郑州大学人民医院消化内科郑州450003

近年,以嵌合抗原受体修饰T细胞(CAR-T)为代表的过继细胞免疫疗法在血液系统肿瘤中的治疗取得了突破性进展。然而对于实体瘤的治疗,CAR-T疗法仍面临着一系列挑战。肿瘤异质性、T细胞归巢效率低下、肿瘤免疫抑制性微环境和特异性抗原的缺... 详细信息

近年,以嵌合抗原受体修饰T细胞(CAR-T)为代表的过继细胞免疫疗法在血液系统肿瘤中的治疗取得了突破性进展。然而对于实体瘤的治疗,CAR-T疗法仍面临着一系列挑战。肿瘤异质性、T细胞归巢效率低下、肿瘤免疫抑制性微环境和特异性抗原的缺乏是限制CAR-T在实体瘤中发挥作用的重要因素。B7-H3是B7免疫球蛋白超家族成员,在多种实体瘤中高表达,作为肿瘤免疫治疗的分子靶点受到广泛关注。本文总结了B7-H3的分子特点及其在肿瘤中的功能,并对以B7-H3为靶点的CAR-T疗法在实体瘤中的研究进展做一综述。

关键词： B7-H3 嵌合抗原受体实体瘤免疫治疗

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氟苯达唑对肝癌Huh7细胞活力、迁移、侵袭、凋亡及自噬的影响

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郑州大学学报（医学版） 2022年第1期57卷 27-31页

作者：罗霞董子慧余祖江郑州大学第一附属医院感染科郑州450052

目的:探讨氟苯达唑对肝癌Huh7细胞活力、迁移、侵袭、凋亡和自噬的影响。方法:Huh7细胞分为空白对照组和氟苯达唑低、中、高浓度组,分别给予0、2、4、8μmol/L的氟苯达唑处理。采用CCK-8法观察处理24、48、72 h后的细胞活力,采用划痕实... 详细信息

目的:探讨氟苯达唑对肝癌Huh7细胞活力、迁移、侵袭、凋亡和自噬的影响。方法:Huh7细胞分为空白对照组和氟苯达唑低、中、高浓度组,分别给予0、2、4、8μmol/L的氟苯达唑处理。采用CCK-8法观察处理24、48、72 h后的细胞活力,采用划痕实验观察处理24 h后的细胞迁移能力,采用Transwell小室检测处理48 h后的侵袭能力,同时用Annexin V-FITC/PI双染法检测细胞凋亡,并采用Western blot法检测自噬和凋亡标志蛋白的表达情况。结果:氟苯达唑可显著抑制Huh7细胞活力,且呈浓度和时间依赖性(P<0.05)。随氟苯达唑给药浓度的增加,细胞迁移率降低,侵袭细胞数减少,而细胞凋亡率升高,LC3-Ⅱ/LC3-Ⅰ比值升高,P62蛋白表达水平下降,Bax/Bcl-2比值升高(P均<0.05)。结论:氟苯达唑可抑制肝癌Huh7细胞的活力、迁移和侵袭,促进其凋亡和自噬。

关键词：氟苯达唑肝癌细胞活力迁移侵袭凋亡自噬

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Ammonia-induced energy disorders interfere with bilirubin metabolism in hepatocytes

Ammonia-induced energy disorders interfere with bilirubin me...

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中华医学会第十三次全国感染病学术会议

作者： qiongye Wang yanfang Wang zujiang yu duolu Li bin Jia jingjing Li kelei Guan fulei Li yanling Chen quancheng Kan Departments of Infectious Diseases the First Affiliated Hospital of Zhengzhou University Department of Pharmacology the First Affiliated Hospital of Zhengzhou University

Hyperammonemia and jaundice are the most common clinical symptoms of hepatic *** clinical practice,a reduction in blood ammonia is often accompanied by a reduction in bilirubin in patients with hepatic *** studies have shown that hyperammonemia can cause bilirubin metabolism ***,exactly how hyperammonemia interferes with bilirubin metabolism in hepatocytes remains *** purpose of the current study was to determine the mechanism by which hyperammonemia interferes with bilirubin metabolism

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白细胞介素-28B的基因多态性与干扰素抗丙型肝炎病毒治疗应答的关系

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第三军医大学学报 2012年第9期34卷 832-835页

作者：高晓娟余祖江刘翠萍郑州大学第一附属医院感染科郑州450052 菏泽市立医院肿瘤科山东菏泽274000

目的探讨IL-28B基因多态性与慢性丙型肝炎患者对干扰素治疗应答的关系。方法采用分子生物学方法提取基因组DNA,PCR扩增后直接测序,对我院感染科门诊和住院的63例应答组(SVR)和34例无应答组(NVR)的HCV 1型患者的SNPs rs8099917和rs12980... 详细信息

目的探讨IL-28B基因多态性与慢性丙型肝炎患者对干扰素治疗应答的关系。方法采用分子生物学方法提取基因组DNA,PCR扩增后直接测序,对我院感染科门诊和住院的63例应答组(SVR)和34例无应答组(NVR)的HCV 1型患者的SNPs rs8099917和rs12980275位点进行检测分析。结果 (1)rs12980275只检测到AA、AG,rs8099917只检测到TT、TG,二者均未发现GG型。(2)rs12980275、rs8099917基因型分布在SVR组和NVR组之间差异均具有统计学意义(OR=3.288,95%CI=[1.171～9.234],χ2=5.416,P=0.020;OR=2.865,95%CI=[1.006～8.154],χ2=4.081,P=0.043)。(3)rs12980275等位基因频率在SVR组和NVR组之间差异具有统计学意义(OR=2.846,95%CI=[1.086～7.464],χ2=4.828,P=0.028);rs8099917等位基因频率在SVR组和NVR组之间差异无统计学意义(OR=2.543,95%CI=[0.953～6.785],χ2=3.664,P=0.056)。(4)rs12980275、rs8099917的基因型及等位基因频率在SVR、NVR组中的相关性分析r均大于0(r=0.236,r=0.205,r=0.158,r=0.137),均呈正相关。结论 rs12980275和rs8099917多态性对干扰素抗丙型肝炎病毒治疗应答有重要影响,可以预测抗病毒疗效,为实现个体化治疗提供依据。

关键词：丙型肝炎病毒单核苷酸多态性 IL-28B基因多态性干扰素持续性病毒应答

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反义乙型肝炎病毒S基因T载体克隆的构建

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郑州大学学报（医学版） 2009年第5期44卷 963-965页

作者：李朵璐余祖江阚全程郑州大学第一附属医院药剂科郑州450052 郑州大学第一附属医院感染科郑州450052

目的:构建含部分乙型肝炎病毒(HBV)S基因反义序列的基因克隆。方法:根据GenBank中HBVS基因序列和计算机软件mCLONE分析的结果,设计S基因2侧引物,直接扩增出适合长度的反义HBVS基因,与PMD18T载体连接后转化DH5α,筛选阳性克隆,抽提重组... 详细信息

目的:构建含部分乙型肝炎病毒(HBV)S基因反义序列的基因克隆。方法:根据GenBank中HBVS基因序列和计算机软件mCLONE分析的结果,设计S基因2侧引物,直接扩增出适合长度的反义HBVS基因,与PMD18T载体连接后转化DH5α,筛选阳性克隆,抽提重组质粒并进行PCR及酶切鉴定,再行序列分析。结果:获得226bp含限制性内切酶位点的阳性产物,T载体克隆经PCR及酶切鉴定和序列分析后证实,克隆片段的反向序列与GenBank中该基因的序列同源性为97%。结论:成功构建了含反义HBVS基因部分序列的T载体克隆。

关键词：肝炎病毒乙型 S基因反义 T载体

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