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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

摘要:

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    

药品监管科学推动中国新冠病毒疫苗研发概述 Review

黄志明, 付志浩, 王军志

《工程(英文)》 2022年 第10卷 第3期   页码 127-132 doi: 10.1016/j.eng.2022.01.001

摘要:

监管科学是一门综合应用自然科学、社会科学和人文科学,开发新工具、新标准和新方法,以评估受监管产品的安全性、有效性、质量和性能的学科。监管科学研究的根本目的是为行政决策提供技术支撑。在甲型H1N1流感、严重急性呼吸综合征(SARS)和中东呼吸综合征(MERS)等传染病大流行期间,监管科学研究有力支持了抗病毒药物和疫苗的研发。特别在新型冠状病毒(简称新冠病毒)肺炎(COVID-19)疫情大流行期间,药品监管科学支持下的疫苗研发在疫情防控中发挥了重要作用。本文总结了中国疫苗产业、新冠病毒疫苗研发以及疫苗监管科学发展的总体概况。此外,本文重点从国家规划、法律法规、技术指南、质量控制和疫苗上市后监管等方面,回顾和分析了监管科学研究为推动中国新冠病毒疫苗研发所发挥的重要作用。本文为当前大流行阶段以及后疫情时代的疫苗研发策略制定提供参考,并为将来如何更好地应对新发和再发传染病提供借鉴和指导。

关键词: 监管科学     新冠病毒疫苗     疫苗产业    

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

摘要: Abstract • Copyrights on electronic products are impediments in promoting circular economy. • Manufacturers antagonize refurbishment and remanufacturing to maximize profit. • International harmonization of copyright laws will aid repair and remanufacture. • Blockchain–digital immutable ledgers–can promote trust among stakeholders. The concept of zero waste is an ideal situation that will require different solutions for different categories of waste. Electronic waste (E-waste), the fastest growing category of solid hazardous waste presents various unique challenges. Electronic product repair, reuse and remanufacture (3re) are crucial for effective source reduction of E-waste and the integration of the electronics industry into a circular or zero-waste economy framework. Increasingly, 3re implementation is restricted by regulatory difficulties, particularly the invocation of copyright laws. Here, we use the examples of electronic printer cartridges and restored compact discs (CDs) to identify the challenges and to explore solutions for managing the risks associated with E-waste through circular economy and the opportunities presented by innovative Blockchain solutions. A set of international consensuses on judicial definitions, such as 3re, refurbish fake/counterfeit product and copyright exhaustion, are proposed to accelerate source reduction in E-waste management toward the goal of zero waste.

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

摘要: Disinfection by-products (DBPs) are regulated in drinking water in a number of countries. This critical review focuses on the issues associated with DBP regulatory compliance, including methods for DBP analysis, occurrence levels, the regulation comparison among various countries, DBP compliance strategies, and emerging DBPs. The regulation comparison between China and the United States (US) indicated that the DBP regulations in China are more stringent based on the number of regulated compounds and maximum levels. The comparison assessment using the Information Collection Rule (ICR) database indicated that the compliance rate of 500 large US water plants under the China regulations is much lower than that under the US regulations (e.g. 62.2% versus 89.6% for total trihalomethanes). Precursor removal and alternative disinfectants are common practices for DBP regulatory compliance. DBP removal after formation, including air stripping for trihalomethane removal and biodegradation for haloacetic acid removal, have gained more acceptance in DBP control. Formation of emerging DBPs, including iodinated DBPs and nitrogenous DBPs, is one of unintended consequences of precursor removal and alternative disinfection. At much lower levels than carbonaceous DBPs, however, emerging DBPs have posed higher health risks.

关键词: Disinfection byproducts (DBPs)     drinking water standards     regulatory compliance     alternative disinfection     information collection rule (ICR)     emerging DBPs    

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

摘要: The liver has a complex cellular composition and a remarkable regenerative capacity. The primary cell types in the liver are two parenchymal cell populations, hepatocytes and cholangiocytes, that perform most of the functions of the liver and that are helped through interactions with non-parenchymal cell types comprising stellate cells, endothelia and various hemopoietic cell populations. The regulation of the cells in the liver is mediated by an insoluble complex of proteins and carbohydrates, the extracellular matrix, working synergistically with soluble paracrine and systemic signals. In recent years, with the rapid development of genetic sequencing technologies, research on the liver’s cellular composition and its regulatory mechanisms during various conditions has been extensively explored. Meanwhile breakthroughs in strategies for cell transplantation are enabling a future in which there can be a rescue of patients with end-stage liver diseases, offering potential solutions to the chronic shortage of livers and alternatives to liver transplantation. This review will focus on the cellular mechanisms of liver homeostasis and how to select ideal sources of cells to be transplanted to achieve liver regeneration and repair. Recent advances are summarized for promoting the treatment of end-stage liver diseases by forms of cell transplantation that now include grafting strategies.

关键词: liver regeneration     hepatocytes     cholangiocytes     stem cells     organoids     regulatory mechanisms     transplantation/grafting strategies    

METABOLIC AND TRANSCRIPTOME ANALYSIS REVEALS METABOLITE VARIATION AND FLAVONOID REGULATORY NETWORKS IN

《农业科学与工程前沿(英文)》 2021年 第8卷 第2期

摘要:

Metabolites, especially secondary metabolites, are very important in the adaption of tea plants and the quality of tea products. Here, we focus on the seasonal variation in metabolites of fresh tea shoots and their regulatory mechanism at the transcriptional level. The metabolic profiles of fresh tea shoots of 10 tea accessions collected in spring, summer, and autumn were analyzed using ultra-performance liquid chromatography coupled with quadrupole-obitrap mass spectrometry. We focused on the metabolites and key genes in the phenylpropanoid/flavonoid pathway integrated with transcriptome analysis. Multivariate statistical analysis indicates that metabolites were distinctly different with seasonal alternation. Flavonoids, amino acids, organic acids and alkaloids were the predominant metabolites. Levels of most key genes and downstream compounds in the flavonoid pathway were lowest in spring but the catechin quality index was highest in spring. The regulatory pathway was explored by constructing a metabolite correlation network and a weighted gene co-expression network.

 

调节性T细胞及其在抗肿瘤免疫疗法中的临床应用 Review

解丰, 梁瑞, 李丹, 李斌

《工程(英文)》 2019年 第5卷 第1期   页码 132-139 doi: 10.1016/j.eng.2018.12.002

摘要:

癌症是可能危及生命的疾病,特点在于肿瘤细胞在宿主身上无限增殖。最近,因其具有预防肿瘤进展和转移的巨大潜力,免疫疗法受到越来越多研究者的关注。调节性T 细胞(Treg)是对维持宿主免疫稳态起重要作用的抑制性CD4+ T 细胞的一个亚群。调节性T 细胞缺陷可引起严重的自身免疫、过敏和自身炎症等疾病。调节性T 细胞通常富集在肿瘤微环境中,而大量免疫抑制调节性T细胞往往表明预后较差。因此,人们对调节性T 细胞的功能及其在抗肿瘤免疫疗法中的临床应用再次产生了兴趣。越来越多的策略关注调节性T 细胞的消耗,这在抗肿瘤免疫方面似乎有效。预计调节性T 细胞靶向策略与其他疗法(如嵌合抗原受体T 细胞疗法或免疫检查点阻断)联用将为提高抗肿瘤疗效带来重大机遇。

关键词: 调节性T细胞     癌症     免疫疗法    

METABOLIC AND TRANSCRIPTOME ANALYSIS REVEALS METABOLITE VARIATION AND FLAVONOID REGULATORY NETWORKS IN

Chen-Kai JIANG, De-Jiang NI, Ming-Zhe YAO, Jian-Qiang MA, Liang CHEN

《农业科学与工程前沿(英文)》   页码 215-230 doi: 10.15302/J-FASE-2021382

摘要: Metabolites, especially secondary metabolites, are very important in the adaption of tea plants and the quality of tea products. Here, we focus on the seasonal variation in metabolites of fresh tea shoots and their regulatory mechanism at the transcriptional level. The metabolic profiles of fresh tea shoots of 10 tea accessions collected in spring, summer, and autumn were analyzed using ultra-performance liquid chromatography coupled with quadrupole-obitrap mass spectrometry. We focused on the metabolites and key genes in the phenylpropanoid/flavonoid pathway integrated with transcriptome analysis. Multivariate statistical analysis indicates that metabolites were distinctly different with seasonal alternation. Flavonoids, amino acids, organic acids and alkaloids were the predominant metabolites. Levels of most key genes and downstream compounds in the flavonoid pathway were lowest in spring but the catechin quality index was highest in spring. The regulatory pathway was explored by constructing a metabolite correlation network and a weighted gene co-expression network.

关键词: harvest season     metabolites     tea shoots     transcriptomics     untargeted metabolomics    

Regulatory issues for genetically modified animals

Perry Bradbury HACKETT

《农业科学与工程前沿(英文)》 2020年 第7卷 第2期   页码 188-203 doi: 10.15302/J-FASE-2019307

摘要:

Precision genetics and breeding have the potential to meet the agricultural needs and goals of the world in the 21st century. These needs include increasing the efficiency of production of animals and improving their products with minimal impact on the environment. The USA is the major innovator in genomic science and the acknowledged leader in formulating policies to regulate genetic applications in medicine and agriculture. However, governments worldwide have been exceedingly reluctant to support the introduction of genetically modified (GM) animals into agriculture. Regulatory policies have stagnated due to legal guidelines that could not anticipate the needs and solutions that are evident today. This must change if we are to maintain planetary integrity. I propose a new, market-based regulatory model for GM livestock that has both a strong scientific foundation and has worked for 10000 years. The model is similar to that for information technology in which specific algorithms drive computer and cell phone applications. Genome engineers write genetic algorithms that drive the traits in biological organisms. Accordingly, GM products should be viewed in terms of their use and public benefit rather than by limitations to the genetic programing coming from a few highly vocal groups. Genetic algorithms (Genapps) of the 21st century will include not only introduction of synthetic genes, but also complete natural and synthetic biochemical pathways to produce agricultural products that are maximally efficient, healthy to humans and animals, and sustainable in an era of changing climates while avoiding environmental degradation.

关键词: algorithms     editing     FDA     GMO     recombinant DNA     USDA    

巨噬细胞在器官移植急性排斥反应中的双重作用 Review

谭亮, 郭易难, 冯畅, 侯仰潇, 谢续标, 赵勇

《工程(英文)》 2022年 第10卷 第3期   页码 21-29 doi: 10.1016/j.eng.2021.10.015

摘要:

天然免疫细胞在移植免疫反应中发挥着重要作用。巨噬细胞是重要的天然免疫细胞;在发生排斥反应的同种异基因移植器官中,巨噬细胞也是浸润的众多免疫细胞之一。巨噬细胞的浸润与器官移植的短期和长期效果呈负相关。在功能方面,巨噬细胞具有异质性和可塑性。在器官移植排斥反应中,巨噬细胞可以为适应性免疫提呈同种异基因抗原以及提供共刺激信号和细胞因子,也可以直接损伤移植器官。此外,一些具有免疫调节功能的巨噬细胞亚群,可以通过抑制排斥反应和促进免疫耐受来保护移植器官。尽管目前研究人员已认识到巨噬细胞在移植器官损伤过程中的潜在作用,但他们对巨噬细胞在移植排斥反应中的不同作用关注不够。为此,本文就巨噬细胞在急性移植免疫反应中的独特作用以及免疫抑制剂对巨噬细胞的影响进行了综述和讨论。通过分析发现,对于巨噬细胞在移植免疫中的作用的相关研究中,应更多地关注其复杂性和关键功能,并应更多地致力于开发针对巨噬细胞的免疫抑制药物,并使之有利于提高移植器官的长期存活率和移植免疫耐受的建立。

关键词: 巨噬细胞     移植     耐受     排斥反应     调节性巨噬细胞    

The biopharmaceutical industry in China: history and future perspectives

null

《医学前沿(英文)》 2012年 第6卷 第2期   页码 101-111 doi: 10.1007/s11684-012-0191-9

摘要:

Biopharmaceuticals reflect the rapid progress achieved in modern biomedical research. This area has also become one of the main criteria for assessing the development level of biotechnology for a particular country. Although it has been only three decades since the first biopharmaceutical, recombinant human insulin, was licensed by the US Food and Drug Administration, the biopharmaceutical industry has become the fastest growing, most dynamic and technology-intensive sector in the biomedical field. Since the licensing of recombinant human interferon α1b in 1989, the biopharmaceutical industry in China has gone through initial developments and gradually entered a period of rapid growth. This paper provides an overview of the status and development trends of biopharmaceuticals in China, and compares them with those observed in developed countries.

关键词: biopharmaceuticals     antibodies     market trends     diseases     China     national regulatory agency    

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

摘要:

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    

免疫调节细胞生物学及其在急性移植物抗宿主病预防或治疗中的临床应用 Review

Bruce R. Blazar

《工程(英文)》 2019年 第5卷 第1期   页码 98-105 doi: 10.1016/j.eng.2018.11.016

摘要:

预防和治疗移植物抗宿主病(GVHD)最常见的方法是尝试耗竭或抑制能介导或支持同种异体反应的T细胞;但这会导致T细胞受体功能缺陷,并因此对感染和肿瘤复发高度敏感。通常通过广泛使用反应性抗体来实现耗竭,而功能损坏通常在使用需长期给药(一般为6个月或更长时间)且具有明显副作用的药物后发生,这种药物可能不会导致供体T细胞对耐调节方案且携带宿主同种抗原的细胞产生耐受性(即无反应性)。随着对免疫系统稳态认识的深化,我们已能鉴定和表征具有免疫调节功能的细胞群。虽然这种细胞群通常比较少见,但可通过分离和扩增此类细胞的方法在移植后晚期增补供体移植物或进行输注,来抑制GVHD。本文将探讨GVHD模型中的生物学和临床前概念验证,以及现已发展至临床测试阶段的免疫调节细胞疗法对GVHD的疗效。

关键词: 移植物抗宿主病(GVHD)     免疫调节细胞     细胞疗法    

钱学森论地理科学

马蔼乃

《中国工程科学》 2002年 第4卷 第1期   页码 1-8

摘要:

钱学森在现代人类知识体系11个门类中,将地理科学归结为自然科学与社会科学之间的桥梁科学;在五大开放的复杂巨系统中,把地理系统排在星系系统与社会系统之间;在社会总体设计部下设四大建设中,将地理建设与政治文明、物质文明、精神文明建设并列。钱学森把地理科学看做是举足轻重的科学体系。钱学森从哲学高度,从人类知识体系的高度,从复杂性系统科学的理论框架中,从社会总体设计工程的实践出发,把地理学提升到为国民经济服务的科学,因此,地理科学具有重要的理论与实践意义,必须重新认识地理。

关键词: 地理科学     理论地理科学     地理信息科学     地理系统工程    

Mechanisms of “kidney governing bones” theory in traditional Chinese medicine

null

《医学前沿(英文)》 2014年 第8卷 第3期   页码 389-393 doi: 10.1007/s11684-014-0362-y

摘要:

Studies conducted by our group on the mechanism of “kidney governing bones” theory in traditional Chinese medicine (TCM) are reviewed in this paper. Conclusions can be summarized as follows. (1) Neuroendocrine-immune network (NIN)-osteoclast regulatory pathway OPG-RANKL-RANK is one of the mechanisms of “kidney governing bones.” Although kidney-reinforcing therapy is regarded as one of the holistic regulatory mechanisms of the body, characteristic holistic regulation in TCM can be reflected through nonselective regulation of the NIN during kidney reinforcement therapy, which can be used to treat osteoporosis through microadjustments in the microenvironment of the bone marrow. (2) Marrow exhaustion in TCM, which is the state wherein lipocytes in the bone marrow increase whereas other cells decrease, serves as the pathogenesis of osteoporosis brought about by failure of the “kidney governing bones.” (3) The kidney in TCM can be regarded as a complex system comprising multiple functional units in the body, including the unit “governing bones.” Kidney deficiency refers to a deficiency in only one or more units of the kidney system and not the whole system itself, which explains the kidney-reinforcing effect of many herbs; some herbs can treat osteoporosis, but some cannot. Although both classified as kidney-reinforcing agents, the former can resolve failure of the “kidney governing bones” unit while the latter regulates the failure of other units in the kidney system. Despite the current understanding on “kidney governing bones” theory, the mechanism of “kidney governing bones” remains complicated and unresolved. Thus, further studies in this area are warranted.

关键词: kidney governing bones     kidney deficiency     marrow     osteoporosis     neuroendocrine-immune network     osteoclast regulatory pathway    

标题 作者 时间 类型 操作

The regulatory sciences for stem cell-based medicinal products

null

期刊论文

药品监管科学推动中国新冠病毒疫苗研发概述

黄志明, 付志浩, 王军志

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

Liver cell therapies: cellular sources and grafting strategies

期刊论文

METABOLIC AND TRANSCRIPTOME ANALYSIS REVEALS METABOLITE VARIATION AND FLAVONOID REGULATORY NETWORKS IN

期刊论文

调节性T细胞及其在抗肿瘤免疫疗法中的临床应用

解丰, 梁瑞, 李丹, 李斌

期刊论文

METABOLIC AND TRANSCRIPTOME ANALYSIS REVEALS METABOLITE VARIATION AND FLAVONOID REGULATORY NETWORKS IN

Chen-Kai JIANG, De-Jiang NI, Ming-Zhe YAO, Jian-Qiang MA, Liang CHEN

期刊论文

Regulatory issues for genetically modified animals

Perry Bradbury HACKETT

期刊论文

巨噬细胞在器官移植急性排斥反应中的双重作用

谭亮, 郭易难, 冯畅, 侯仰潇, 谢续标, 赵勇

期刊论文

The biopharmaceutical industry in China: history and future perspectives

null

期刊论文

Optimized human factor IX expression cassettes for hepatic-directed gene therapy of hemophilia B

null

期刊论文

免疫调节细胞生物学及其在急性移植物抗宿主病预防或治疗中的临床应用

Bruce R. Blazar

期刊论文

钱学森论地理科学

马蔼乃

期刊论文

Mechanisms of “kidney governing bones” theory in traditional Chinese medicine

null

期刊论文