检索范围：
排序： 展示方式：
Optimized human factor IX expression cassettes for hepatic-directed gene therapy of hemophilia B
null
《医学前沿（英文）》 2015年 第9卷 第1期 页码 90-99 doi: 10.1007/s11684-015-0390-2
Gene therapy provides a potential cure for hemophilia B, and significant progress has been achieved in liver-directed gene transfer mediated by adeno-associated viral vectors. Recent clinical trials involving the use of a self-complementary adeno-associated virus serotype 8-human codon-optimized factor IX (AAV8-hFIXco) vector demonstrated encouraging efficacy with hFIX expression stabilized at 1% to 6% of normal level in patients, but safety concerns related to high vector doses are still present. Thus, further improvement of AAV vectors and hFIX expression cassette may positively contribute to the ultimate success of hemophilia B gene therapy. In this study, to obtain a higher expression level of hFIX that potentiates the coagulant capacity of recipients, human FIX expression vector was optimized by upgrading the codon adaption index and adjusting the GC content, inserting a Kozak sequence (GCCACC), and introducing a gain-of-function mutation, R338L (FIX Padua). The efficiency of the published and the presently constructed cassettes was compared through in vivo screening. In addition, the regulatory elements that control the FIX gene expression in these cassettes were screened for liver-specific effectiveness. Among all the constructed cassettes, scAAV-Pre-hFIXco-SIH-R338L, which was the construct under the control of the prothrombin enhancer and prealbumin promoter, resulted in the highest level of coagulant activity, and the expression levels of two constructed cassettes (scAAV-Chi-hFIXco-SIH-R338L and scAAV-Pre-hFIXco-SIH-R338L) were also higher than that of the published cassette (scAAV-LP1-hFIXco-SJ). In summary, our strategies led to a substantial increase in hFIX expression at the protein level or a remarkably elevated coagulant activity. Thus, these reconstructs of hFIX with AAV vector may potentially contribute to the creation of an efficacious gene therapy of hemophilia B.
关键词： factor IX hemophilia B liver-specific regulatory elements hydrodynamic gene transfer
Liver cell therapies: cellular sources and grafting strategies
《医学前沿（英文）》 2023年 第17卷 第3期 页码 432-457 doi: 10.1007/s11684-023-1002-1
关键词： liver regeneration hepatocytes cholangiocytes stem cells organoids regulatory mechanisms transplantation/grafting strategies
利用CES1和DPP-IV的组织残余活性准确评估和追踪特异性肝损伤过程 Article
潘秋莎, 宋培放, 倪振华, 钱星凯, 王安琪, 邹立伟, 刘勇, 王平, 张卫东, 马红, 杨凌
《工程（英文）》 2022年 第19卷 第12期 页码 153-165 doi: 10.1016/j.eng.2021.09.014
准确评估和追踪特异性肝损伤及其进程仍然是当前生物标志物研究中的一大挑战。本研究建立了一种回顾追溯验证方法，用以表征α-萘异硫氰酸酯（ANIT）诱导的特异性肝脏胆管损伤后血清标志物与组织标志物之间的互动关系。研究发现羧酸酯酶1（CES1）作为肝内标志物和二肽基肽酶4（DPP-IV）作为肝外标志物可反映肝脏损伤的不同病理生理状态。CES1 和DPP-IV 水平可甄别肝损伤本身和炎症损伤之间的差异。相比之下，常规血清学标志物碱性磷酸酶（ALP）、丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）在ANIT诱导损伤后血清和组织水平同时升高，胆汁中胆汁酸水平下降，血清中胆汁酸水平升高，肝内组织中胆汁酸水平升高。尽管血清与组织中γ-谷氨酰基转肽酶（γ-GT）升降水平的变化方向相反，但其持续时间远短于CES1，并迅速恢复到正常水平。在上述生物标志物中，只有CES1 能够明确排除炎症干扰下的肝细胞损伤。CES1 还能准确评估熊去氧胆酸（UDCA；单成分药物）和清肺排毒汤（QFPDD；多组分药物）的抗胆汁淤积作用。研究发现QFPDD和UDCA均能减轻ANIT 诱导的肝损伤。UDCA在促进胆汁排泄方面的效果更强，但其抗损伤和抗炎作用相对较弱，而QFPDD在阻断肝脏炎症和修复肝损伤方面更有效。本文数据强调了联合使用CES1（作为肝内肝损伤标志物）和DPP-IV（作为肝外炎症作用标志物）可准确评估和追踪特异性肝损伤，并可区分肝损伤和炎症性肝损伤的差异。
The regulatory sciences for stem cell-based medicinal products
null
《医学前沿（英文）》 2014年 第8卷 第2期 页码 190-200 doi: 10.1007/s11684-014-0323-5
Over the past few years, several new achievements have been made from stem cell studies, many of which have moved up from preclinical stages to early, or from early to middle or late, stages thanks to relatively safe profile and preliminary evidence of effectiveness. Moreover, some stem cell-based products have been approved for marketing by different national regulatory authorities. However, many critical issues associated mainly with incomplete understanding of stem cell biology and the relevant risk factors, and lack of effective regulations still exist and need to be urgently addressed, especially in countries where establishment of appropriate regulatory system just commenced. More relevantly, the stem cell regulatory sciences need to be established or improved to more effectively evaluate quality, safety and efficacy of stem cell products, and for building up the appropriate regulatory framework. In this review, we summarize some new achievements in stem cell studies, especially the preclinical and clinical studies, the existing regulations, and the associated challenges, and we then propose some considerations for improving stem cell regulatory sciences with a goal of promoting the steadfast growth of the well-regulated stem cell therapies abreast of evolvement of stem cell sciences and technologies.
关键词： stem cell-based medicinal products (SCMPs) stem cell therapy (SCT) safety effectiveness standards guidelines regulatory science
Mohsen Jalali, Ziba Hurseresht
《环境科学与工程前沿（英文）》 2020年 第14卷 第1期 doi: 10.1007/s11783-019-1186-4
关键词： Mobility Calcareous soils Extracting agents Trace elements
null
《医学前沿（英文）》 2011年 第5卷 第1期 页码 1-7 doi: 10.1007/s11684-010-0105-7
Partial liver transplantation, including reduced-size liver transplantation, split liver transplantation, and living donor liver transplantation, has been developed with several innovative techniques because of donor shortage. Reduced-size liver transplantation is based on Couinaud’s anatomical classification, benefiting children and small adult recipients but failing to relieve the overall donor shortage. Split liver transplantation provides chances to two or even more recipients when only one liver graft is available. The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situto ensure long-term quality. The first and most important issue involving living donor liver transplantation is donor safety. Before surgery, a series of donor evaluations—including anatomical, liver volume, and liver function evaluations—is indispensable, followed by ethnic agreement. At different recipient conditions, auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation, which employ piggyback techniques, are good alternatives. Partial liver transplantation enriches the practice and knowledge of the transplant society.
关键词： partial liver transplantation reduced-size liver transplantation split liver transplantation living donor liver transplantation
null
《医学前沿（英文）》 2018年 第12卷 第3期 页码 262-268 doi: 10.1007/s11684-017-0584-x
γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues. γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and liver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.
关键词： γδT cells liver infection non-alcoholic fatty liver disease autoimmune hepatitis liver fibrosis and cirrhosis liver cancer liver regeneration
Zero E-waste: Regulatory impediments and blockchain imperatives
Mengjun Chen, Oladele A. Ogunseitan
《环境科学与工程前沿（英文）》 2021年 第15卷 第6期 doi: 10.1007/s11783-021-1402-x
关键词： Blockchain E-waste Regulatory Policy Copyright Laws Repair-Reuse-Remanufacture Toxicity
Disinfection byproducts in drinking water and regulatory compliance: A critical review
Xiaomao WANG,Yuqin MAO,Shun TANG,Hongwei YANG,Yuefeng F. XIE
《环境科学与工程前沿（英文）》 2015年 第9卷 第1期 页码 3-15 doi: 10.1007/s11783-014-0734-1
关键词： Disinfection byproducts (DBPs) drinking water standards regulatory compliance alternative disinfection information collection rule (ICR) emerging DBPs
null
《医学前沿（英文）》 2018年 第12卷 第3期 页码 249-261 doi: 10.1007/s11684-018-0622-3
Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.
关键词： natural killer T cells hepatitis B virus and hepatitis C virus infection autoimmune liver diseases alcoholic liver disease nonalcoholic fatty liver disease hepatocellular carcinoma
《工程管理前沿（英文）》 2022年 第9卷 第2期 页码 221-238 doi: 10.1007/s42524-022-0195-3
关键词： knowledge transfer knowledge management project management project environment literature review
Natural killer cells in liver diseases
null
《医学前沿（英文）》 2018年 第12卷 第3期 页码 269-279 doi: 10.1007/s11684-018-0621-4
The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct “killer” functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.
关键词： natural killer cell phenotype immune activation immune tolerance liver diseases
Ling Dai, Xiang Gao, Zhihua Ye, Hanmin Li, Xin Yao, Dingbo Lu, Na Wu
《医学前沿（英文）》 2021年 第15卷 第3期 页码 495-505 doi: 10.1007/s11684-020-0790-9
关键词： hepatitis B virus-related liver failure traditional Chinese medicine liver regeneration liver regeneration microenvironment cytokines
Assessment of liver volume variation to evaluate liver function
null
《医学前沿（英文）》 2012年 第6卷 第4期 页码 421-427 doi: 10.1007/s11684-012-0223-5
In order to assess the value of liver volumetry in cirrhosis and acute liver failure (ALF) patients, we explored the correlation between hepatic volume and severity of the hepatic diseases. The clinical data of 48 cirrhosis patients with 60 normal controls and 39 ALF patients were collected. Computed tomography-derived liver volume (CTLV) and body surface area (BSA) of normal controls were calculated to get a regression formula for standard liver volume (SLV) and BSA. Then CTLV and SLV of all patients were calculated and grouped by Child-Turcotte-Pugh classification for cirrhosis patients and assigned according to prognosis of ALF patients for further comparison. It turned out that the mean liver volume of the control group was 1 058±337 cm3. SLV was correlated with BSA according to the regression formula. The hepatic volume of cirrhosis patients in Child A, B level was not reduced, but in Child C level it was significantly reduced with the lowest liver volume index (CTLV/SLV). Likewise, in the death group of ALF patients, the volume index was significantly lower than that of the survival group. Based on volumetric study, we proposed an ROC (receiver operating characteristic) analysis to predict the prognosis of ALF patients that CTLV/SLV<83.9% indicates a poor prognosis. In conclusion, the CTLV/SLV ratio, which reflects liver volume variations, correlates well with the liver function and progression of cirrhosis and ALF. It is also a very useful marker for predicting the prognosis of ALF.
关键词： liver volume variation cirrhosis acute liver failure (ALF)
嵌合抗原受体和调节性T细胞——移植中人类白细胞抗原特异性免疫抑制的潜力 Review
Sabrina Wright, Conor Hennessy, Joanna Hester, Fadi Issa
《工程（英文）》 2022年 第10卷 第3期 页码 30-43 doi: 10.1016/j.eng.2021.10.018
嵌合抗原受体（CAR）是基因工程领域的一项突破，它彻底改变了过继细胞疗法（ACT）领域。表达这些受体的细胞通过在合成的CAR构建体中包含抗原特异性结合区域而被重新定向到预定的靶点。程序化特异性细胞在肿瘤学领域的优势已被临床证明，与同类未修饰的细胞相比，这种细胞具有更高的准确性、效力与更少的脱靶效应。与常规T细胞（Tconvs）不同，调节性T细胞（Treg）在抑制免疫激活和调节宿主免疫反应方面发挥着重要作用。Treg 中CAR的表达被认为是治疗自身免疫和炎症性疾病、移植物抗宿主病（GVHD）和器官移植排斥反应的一种方法。在后者中，它们作为同种异体移植受者免疫耐受的介质具有巨大的潜力。然而，目前对CAR-Treg 工程的研究非常有限，并且关于治疗用途的最佳设计存在不确定性。本文综述了CAR-Treg 发展的理论基础、其对人类移植的意义、潜在的设计、安全性考虑因素，以及迄今为止CAR-Treg在移植模型中的对比。
关键词： 嵌合抗原受体（CAR） 调节性T细胞 异性免疫 CAR设计 基因编辑
标题 作者 时间 类型 操作
Optimized human factor IX expression cassettes for hepatic-directed gene therapy of hemophilia B
null
期刊论文
Assessment of mobile and potential mobile trace elements extractability in calcareous soils using different
Mohsen Jalali, Ziba Hurseresht
期刊论文
Zero E-waste: Regulatory impediments and blockchain imperatives
Mengjun Chen, Oladele A. Ogunseitan
期刊论文
Disinfection byproducts in drinking water and regulatory compliance: A critical review
Xiaomao WANG,Yuqin MAO,Shun TANG,Hongwei YANG,Yuefeng F. XIE
期刊论文
Linking elements to outcomes of knowledge transfer in the project environment: Current review and future
期刊论文
The “Traditional Chinese medicine regulating liver regeneration” treatment plan for reducing mortalityof patients with hepatitis B-related liver failure based on real-world clinical data
Ling Dai, Xiang Gao, Zhihua Ye, Hanmin Li, Xin Yao, Dingbo Lu, Na Wu
期刊论文
京公网安备 11010502051620号
