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Multifunctional peptide conjugated amphiphilic cationic copolymer for enhancing ECs targeting, penetrating and nuclear accumulation

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Frontiers of Chemical Science and Engineering 2020年第5期14卷 889-901页

作者： Xinghong Duo Lingchuang Bai Jun Wang Jintang Guo xiangkui Ren shihai xia Wencheng Zhang Abraham Domb Yakai Feng School of Chemical Engineering and Technology Tianjin UniversityTianjin 300350China School of Chemistry and Chemical Engineering Qinghai University for NationalitiesXining 810007China Collaborative Innovation Center of Chemical Science and Chemical Engineering(Tianjin) Tianjin 300350China Key Laboratory of Systems Bioengineering(Ministry of Education) Tianjin UniversityTianjin 300072China Department of Hepatopancreatobiliary and Splenic Medicine Afiliated HospitalLogistics University of People's Amed Police ForceTianjin 300162China Department of Physiology and Pathophysiology Logistics University of People's Armed Police ForceTianjin 300162China Institute of Drug Research(IDR) School of Pharmacy Faculty of MedicineThe Hebrew University of JerusalemJerusalem 91905Israel

Gene therapy has drawn great attention in the treatments of many diseases,especially for cardiovascular ***,the development of gene carriers with low cytotoxicity and multitargeting function is still a ***,the multitargeting REDV-G-TATG-NLS peptide was conjugated to amphiphilic cationic copolymer poly(e-caprolactone-co-3(S)-methyl-morpho-line-2,5-dione)-g-polyethyleneimine(PCLMD-g-PEI)via a heterobifunctional orthopyridyl disulfde-poly(ethylene glycol)-N-hydroxysuccinimide(OPSS-PEG-NHS)linker to prepare PCLMD-g-PEI-PEG-REDV-G-TAT-G-NLS copolymers with the aim to develop the gene carriers with low cytotoxicity and high transfection *** multitargeting micelles were prepared from PCLMD-g-PEI-PEG-REDV-G-TAT-G-NLS copolymers by self-assembly method and used to load pEGFP-ZNF580 plasmids(pDNA)to form gene complexes for enhancing the proliferation and migration of endothelial cells(ECs).The loading pDNA capacity was proved by agarose gel electrophoresis *** multitargeting gene com-plexes exhibited low cytotoxicity by 3-(4,-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide *** high internalization efficiency of these gene complexes was confirmed by flow *** results of in vitro transfection demonstrated that these multitargeting gene complexes possessed relatively high transfection *** rapid migration of ECs transfected by these gene complexes was verified by wound healing *** to ECs-targeting ability,cell-penetrating ability and nuclear targeting capacity of REDV-G-TAT-G-NLS pep-tide,the multitargeting polycationic gene carrier with low cytotoxicity and high transfection efficiency has great potential in gene therapy.

关键词： gene carriers multitargeting function ECs transfection efficiency

Zinc(Ⅱ)metal-organic framework eluting titanium implant as propulsive agent to boost the endothelium regeneration

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Frontiers of Chemical Science and Engineering 2024年第6期18卷 123-131页

作者： Wen Liu xiaoyu Wang Ying Li shihai xia Wencheng Zhang Yakai Feng School of Chemical Engineering and Technology Tianjin UniversityTianjin 300350China College of Materials Science and Engineering Qingdao UniversityQingdao 266071China Department of Hepatopancreatobiliary and Splenic Medicine Affiliated HospitalLogistics University of People’s Armed Police ForceTianjin 300162China Department of Physiology and Pathophysiology Logistics University of Chinese People’s Armed Police ForceTianjin 300309China Frontiers Science Center for Synthetic Biology Tianjin UniversityTianjin 300072China Key Laboratory of Systems Bioengineering(Ministry of Education) Tianjin UniversityTianjin 300072China

The advent of antiproliferative drug-eluting vascular stents can dramatically reduce in-stent restenosis via inhibiting the hyperproliferation of vascular smooth muscle ***,the antiproliferative drugs also restrain the repair of the injured endothelial layer,which in turn leads to the very later in-stent *** points that competent endothelium plays a critical role in guaranteeing the long-term patency via maintaining vascular *** the regeneration of endothelium on the implanted vascular stents could be rendered as a promising strategy to reduce stent implantation *** this regard,bioactive zinc(II)metal-organic framework modified with endothelial cell-targeting Arg-Glu-Asp-Val peptide was embedded in poly(lactide-co-caprolactone)to serve as a functional coating on the surface of titanium substrate,which can promote the proliferation and migration of endothelial *** in vitro cell experiments revealed that the zinc(II)metal-organic framework embedded in the polymer coating was able to modulate the behaviors of endothelial cells owing to the bioactive effects of zinc ion and *** results confirmed that zinc(II)metal-organic framework eluting coating represented a new possibility for promoting the repair of the damaged endothelium with potential clinical implications in vascular-related biomaterials and tissue engineering applications.

关键词： Zinc(II)metal-organic framework vascular stent REDV peptide endothelium regeneration coating

Exploring the links between gut microbiome changes and irritable bowel syndrome in Han populations in the Tibetan Plateau

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第9期24卷 823-838页

作者： Xingguang ZHANG Wei XU Weilong ZHONG Wencheng ZHANG Cheng YANG Lisa DUAN Haiyan NIU Yanmei DONG Taotao LIU shihai xia Bangmao WANG Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Institute of Digestive DiseasesTianjin Key Laboratory of Digestive DiseasesTianjin300052China Department of Gastroenterology Characteristic Medical Center of Chinese People’s Armed Police ForceTianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis&TreatmentTianjin300162China

The gut microbiome shows changes under a plateau environment,while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome(IBS);however,the relationship between the two remains *** this work,we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA(rRNA)sequencing analysis of their fecal *** evaluating the participants’clinical symptoms,combined with an IBS questionnaire,we screened the IBS sub-population in our *** sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut *** addition,we found that the longer the time volunteers spent in the plateau environment,the more similar their gut microbiota composition and abundance became compared to those before entering the plateau,and IBS symptoms were significantly ***,we speculated that the plateau may be a special environment that induces *** taxonomic units g_Alistipes,g_Oscillospira,and s_Ruminococcus_torques,which had been proved to play important roles in IBS pathogenesis,were also abundant in the IBS cohort at high ***,the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with *** results prompt further research to elucidate the relevant mechanism.

关键词： Gut microbiome Plateau environment Irritable bowel syndrome

胰腺星状细胞与胰腺癌前病变的关系及干预设想

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中华胰腺病杂志 2022年第2期22卷 81-86页

作者：夏时海武警特色医学中心消化内科(消化疾病研究所) 天津市肝脏胰腺纤维化与分子诊疗重点实验室天津300162

胰腺星状细胞(PSC)激活在正常胰腺-胰腺炎症-胰腺癌前病变-胰腺癌的进展过程中发挥重要作用,这是由PSC的生物学特性和功能异质性决定的。PSC通过分泌、自噬、能量代谢和微环境失衡等机制影响胰腺炎症和胰腺癌前病变,而抑制PSC激活、促... 详细信息

胰腺星状细胞(PSC)激活在正常胰腺-胰腺炎症-胰腺癌前病变-胰腺癌的进展过程中发挥重要作用,这是由PSC的生物学特性和功能异质性决定的。PSC通过分泌、自噬、能量代谢和微环境失衡等机制影响胰腺炎症和胰腺癌前病变,而抑制PSC激活、促进活化PSC状态改变及诱导PSC凋亡等可能是阻止胰腺炎症向胰腺癌前病变演化和进展的重要干预措施。

关键词：胰腺星状细胞胰腺纤维化胰腺癌前病变胰腺癌

《2018年欧洲胃肠道内窥镜学会多学科循证指南:急性坏死性胰腺炎的内镜管理》摘译

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临床肝胆病杂志 2018年第8期34卷 1654-1658页

作者：李嫚华许威夏时海武警后勤学院附属医院消化内科天津300162

该指南为欧洲胃肠道内窥镜学会（ESGE）关于急性坏死性胰腺炎（acute necrotizing pancreatitis,ANP）内镜管理的正式声明。指南采用GRADE系统对推荐程度、证据质量进行等级划分。1背景急性胰腺炎是最常见的需要急性入院治疗的消化道疾... 详细信息

该指南为欧洲胃肠道内窥镜学会（ESGE）关于急性坏死性胰腺炎（acute necrotizing pancreatitis,ANP）内镜管理的正式声明。指南采用GRADE系统对推荐程度、证据质量进行等级划分。1背景急性胰腺炎是最常见的需要急性入院治疗的消化道疾病。大部分患者（80%）可得到快速有效的治疗。然而,ANP治疗的有效率为20%,其发生早期器官衰竭（38%）.

关键词：内窥镜胰腺炎,急性坏死性欧洲诊疗准则

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慢性胰腺炎发生的分子机制

武警医学 2019年第4期30卷 277-282页

作者：夏时海李嫚华武警特色医学中心消化内科/武警部队肝胆胰脾专科中心/天津市肝脏胰腺纤维化与分子诊疗重点实验室 300162

慢性胰腺炎(chronic pancreatitis,CP)是饮酒、自身免疫、遗传因素等多种原因所致的胰腺实质内腺泡和小管的反复或持续性损伤,引起腺泡和胰岛细胞萎缩或消失,最终被纤维化组织替代,引起不同程度的胰腺内/外分泌功能障碍,是胰腺的一种进... 详细信息

慢性胰腺炎(chronic pancreatitis,CP)是饮酒、自身免疫、遗传因素等多种原因所致的胰腺实质内腺泡和小管的反复或持续性损伤,引起腺泡和胰岛细胞萎缩或消失,最终被纤维化组织替代,引起不同程度的胰腺内/外分泌功能障碍,是胰腺的一种进行性炎性疾病[1];临床上患者表现为持续性或反复发作性腹痛、食欲减退和脂肪泻等,严重影响患者生活,且可导致糖尿病的发生[2].

关键词：慢性胰腺炎分子机制

氧化苦参碱对脂多糖诱导的胰腺星状细胞NOD样受体蛋白3活化的影响

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药物评价研究 2019年第11期42卷 2159-2164页

作者：陈伟许威向晓辉陈凯张青夏时海武警后勤学院天津300309 武警后勤学院附属医院消化二科/肝胆胰脾中心天津300162 天津市西青医院消化内科天津300380

目的研究氧化苦参碱(OM)对脂多糖(LPS)诱导的大鼠胰腺星状细胞株(PSCs) NOD样受体蛋白3 (NLRP3)活化的影响。方法通过设置不同剂量(0、2.5、5、10、20、40μg/mL)的LPS并设置相同剂量(10μg/mL)的LPS刺激LTC14细胞不同时间(0、1、3、6、... 详细信息

目的研究氧化苦参碱(OM)对脂多糖(LPS)诱导的大鼠胰腺星状细胞株(PSCs) NOD样受体蛋白3 (NLRP3)活化的影响。方法通过设置不同剂量(0、2.5、5、10、20、40μg/mL)的LPS并设置相同剂量(10μg/mL)的LPS刺激LTC14细胞不同时间(0、1、3、6、9、12 h),利用Western blotting检测技术,考察LPS引起炎性小体活化的量效关系;使用OM、Janus蛋白酪氨酸激酶2 (JAK2)抑制剂AG490干预LPS诱导的LTC14细胞株后,通过Western blotting技术检测Janus蛋白酪氨酸激酶2/信号转导子和转录激活子3 (JAK2/STAT3)信号通路中相关分子以及NLRP3炎性小体相关蛋白表达的变化。结果与对照组比较,LTC14细胞接受不同浓度的LPS刺激后JAK2、STAT3、NLRP3、caspase1、白细胞介素-1β(IL-1β)蛋白表达呈显著增高趋势;与对照组比较,LTC14细胞接受相同浓度LPS刺激不同时间后JAK2、STAT3、NLRP3、caspase1、IL-1β蛋白表达呈显著增高趋势;与LPS组对比,OM和LPS共同处理组、AG490和LPS共同处理组JAK2、STAT3、NLRP3、caspase1及IL-1β的蛋白表达显著降低。结论LPS呈一定的时间-剂量关系激活LTC14细胞JAK2/STAT3信号通路及NLRP3炎性小体;OM可能通过抑制JAK2/STAT3信号通路起到抑制NLRP3炎性小体活化的作用。

关键词：氧化苦参碱脂多糖 LTC14细胞 JAK2/STAT3信号通路 NLRP3炎性小体

Smad蛋白在转化生长因子-β信号转导通路中的作用与机制

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医学分子生物学杂志 2008年第4期5卷 352-355,360页

作者：苏丽婷夏时海武警河南总队医院普通内科郑州市450000 武警医学院附属医院消化内科天津市300162

Smad蛋白是转化生长因子-β(transforming growth factor-β,TGF-β)信号转导通路中关键的介质,TGF-β通过结合细胞表面特异性受体而启动下游的Smad蛋白传导通路。Smad蛋白有着独特的结构及性质,根据其结构和功能的不同分为3类,在TGF-... 详细信息

Smad蛋白是转化生长因子-β(transforming growth factor-β,TGF-β)信号转导通路中关键的介质,TGF-β通过结合细胞表面特异性受体而启动下游的Smad蛋白传导通路。Smad蛋白有着独特的结构及性质,根据其结构和功能的不同分为3类,在TGF-β信号转导过程中发挥重要作用。同时众多的细胞因子对Smad蛋白起着抑制或激活等作用,形成细胞信号转导通路的交叉对话。

关键词： Smad蛋白转化生长因子-β 信号转导

sPLA_2在重症急性胰腺炎的变化及银杏苦内酯B对其影响

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天津医药 2007年第2期35卷 108-110页

作者：杨银治夏时海胡春秀邸瑶夏国栋武警医学院附属医院 300162 武警医学院附属医院消化内科胰腺中心 300162

目的:探讨分泌型磷脂酶A2(sPLA_2)在重症急性胰腺炎(SAP)的动态变化及银杏苦内酯B(BN52021)对sPLA2的影响。方法:180只Wistar大鼠随机分为阴性对照组(NC组,60只)、SAP模型组(SAP组,60只)、BN52021治疗组(BN组,60只)。每组按不同时相点(1... 详细信息

目的:探讨分泌型磷脂酶A2(sPLA_2)在重症急性胰腺炎(SAP)的动态变化及银杏苦内酯B(BN52021)对sPLA2的影响。方法:180只Wistar大鼠随机分为阴性对照组(NC组,60只)、SAP模型组(SAP组,60只)、BN52021治疗组(BN组,60只)。每组按不同时相点(1、2、3、6、12和24h)分组每小组各10只,分别测定血淀粉酶和sPLA2活性水平,同时对胰腺组织进行病理学观察。结果:淀粉酶和病理学结果显示SAP制模成功,BN52021能降低SAP的血淀粉酶并改善其病理变化;sPLA2结果显示,SAP组在3、6、12和24h较NC组升高,差异有统计学意义(P0.05)。结论:sPLA2在SAP中后期显著升高,对SAP的病情发展有重要意义,BN52021可降低SAP血淀粉酶并改善其病理变化,但对sPLA2无显著影响。

关键词：磷脂酶A 胰腺炎急性病银杏苦内酯大鼠 wistar