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Living Bacteriophage Engineering for Functional Material Synthesis, Bioanalytical Sensing and Disease Theranostics 噬菌体活体工程用于功能材料合成、生物分析传感和疾病疗法
Pub Date : 2024-07-08 DOI: 10.3390/targets2030010
Jing Zhang, Xuewen He
Facing the increasingly global crisis of antibiotic resistance, it is urgent to develop new antibacterial agents and methods. Simultaneously, as research progresses, the occurrence, development, and treatment of diseases, especially some malignant cancers, are found to be closely associated with the bacterial microenvironment, prompting us to reconsider the efficiency of existing antibacterial strategies for disease treatments. Bacteriophages have been employed as antibacterial agents for an extended period owing to their high biocompatibility and particular targetability toward the host bacterial strains. Nonetheless, they are almost neglected due to their slow and limited efficacy in antibacterial practice, especially in acute and severe infectious cases. In recent years, fantastic advancements in various biochemical technologies, such as bacteriophage display technology, genetic engineering, and chemical molecular engineering, have enabled scientists to conduct a broader range of modifications and transformations on the existing bacteriophages with inherited unique characteristics of themselves. As a result, a series of novel bacteriophage platforms are designed and fabricated with significantly enhanced properties and multiplied functionalities. These offer new avenues for combating infections caused by drug-resistant bacteria and treatment of malignancies that are associated with bacterial infections, holding great significance and potential in the innovative theranostic applications.
面对全球日益严重的抗生素耐药性危机,开发新的抗菌药物和方法迫在眉睫。与此同时,随着研究的深入,人们发现疾病尤其是一些恶性癌症的发生、发展和治疗与细菌微环境密切相关,这促使我们重新考虑现有抗菌策略在疾病治疗中的有效性。由于噬菌体具有很高的生物相容性和对宿主细菌菌株的特殊靶向性,它们长期以来一直被用作抗菌剂。然而,由于噬菌体在抗菌实践中,尤其是在急性和严重感染病例中的疗效缓慢而有限,它们几乎被忽视。近年来,噬菌体展示技术、基因工程和化学分子工程等各种生化技术取得了突飞猛进的发展,使科学家们能够对现有的噬菌体进行更广泛的改造和转化,使其继承自身的独特特性。因此,一系列新型噬菌体平台被设计和制造出来,其特性和功能显著增强。这为抗击耐药细菌引起的感染和治疗与细菌感染相关的恶性肿瘤提供了新途径,在创新治疗学应用方面具有重大意义和潜力。
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引用次数: 0
Unveiling the Role of Concanavalin A in a Rodent Model of Chemical-Induced Hepatocellular Carcinoma: A Promising Guide in Understanding Liver Cancer Development 揭示康卡那瓦林 A 在化学物质诱发肝细胞癌啮齿动物模型中的作用:了解肝癌发展的有效指南
Pub Date : 2024-02-16 DOI: 10.3390/targets2010003
Romelia Pop, Dragoș Hodor, C. Catoi, T. Mocan, L. Mocan, A. Tabaran
Hepatocellular carcinoma is a pressing global health issue, ranking as the third leading cause of cancer-related mortality in humans. Chronic liver diseases, such as hepatitis B and C infections and cirrhosis, are often associated with hepatocellular carcinoma, necessitating ongoing research for improved diagnostic and therapeutic strategies. Animal models, including both spontaneous and chemically induced models like diethylnitrosamine, play a pivotal role in understanding hepatocellular carcinoma mechanisms. Metabolic alterations in tumoral hepatocytes contribute significantly to cancer initiation and progression, impacting energy metabolism and cell survival. Lectins, specifically Concanavalin A, provide valuable insights into altered glycosylation patterns in cancer cells. This study employs lectin histochemistry to assess hepatic alterations in Concanavalin A expression in a murine model of diethylnitrosamine-induced hepatocellular carcinoma. Utilizing confocal laser scanning microscopy, our study unveils notable changes in Concanavalin A subcellular localization and intensity distribution in hepatocellular carcinoma compared with healthy liver tissue. A significant increase in the Concanavalin A labeling within the tumoral cells and a shifting of the expression within the perinuclear space is observed. These findings offer valuable insights into molecular changes in hepatocellular carcinoma, providing potential avenues for diagnostic and therapeutic advancements.
肝细胞癌是一个紧迫的全球健康问题,是人类癌症相关死亡的第三大主要原因。慢性肝病,如乙型肝炎和丙型肝炎感染以及肝硬化,往往与肝细胞癌有关,因此需要不断研究改进诊断和治疗策略。动物模型,包括自发模型和化学诱导模型(如二乙基亚硝胺),在了解肝细胞癌机制方面发挥着关键作用。肿瘤肝细胞的代谢改变对癌症的发生和发展有重要作用,影响能量代谢和细胞存活。凝集素,特别是Concanavalin A,为了解癌细胞中糖基化模式的改变提供了宝贵的信息。本研究采用凝集素组织化学方法,评估二乙亚硝胺诱导的肝细胞癌鼠模型中肝脏中康卡那林 A 表达的改变。利用激光共聚焦扫描显微镜,我们的研究揭示了与健康肝组织相比,肝细胞癌中康奈伐林 A 亚细胞定位和强度分布的显著变化。我们观察到肿瘤细胞内的Concanavalin A标记明显增加,核周空间内的表达也发生了转移。这些发现为了解肝细胞癌的分子变化提供了宝贵的信息,为诊断和治疗的进步提供了潜在的途径。
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引用次数: 0
The Radiant World of Cyanobacterial Phycobiliproteins: Examining Their Structure, Functions, and Biomedical Potentials 蓝藻藻体蛋白的璀璨世界:研究它们的结构、功能和生物医学潜力
Pub Date : 2024-01-10 DOI: 10.3390/targets2010002
Sapana Jha, Varsha K. Singh, Ashish P. Singh, Amit Gupta, Palak Rana, R. Sinha
Phycobiliproteins (PBPs) are accessory light-harvesting pigment complexes found in cyanobacteria, red algae, and certain types of cryptophytes. The unique spectral features (strong absorbance and fluorescence), proteinaceous nature, and some imperative properties such as the anti-oxidative, hepato-protective, anti-inflammatory, and anti-aging activity of PBPs allow their use in biomedical industries. However, basic research and technological innovations are required to explore their potential in biomedical applications. The techniques responsible for therapeutic effects need to be standardized for medical application purposes. This review focuses on the current status of PBPs, their structure, functions, methods of preparation, and applications. Additionally, the stability, bioavailability, and safety issues of PBPs, along with their use in therapeutics, are discussed.
藻胆蛋白(PBPs)是蓝藻、红藻和某些隐藻中的辅助采光色素复合物。PBPs 具有独特的光谱特征(强吸光度和荧光)、蛋白质性质以及一些必要的特性,如抗氧化、保护肝脏、抗炎和抗衰老活性,因此可用于生物医学行业。然而,要挖掘其在生物医学应用中的潜力,还需要进行基础研究和技术创新。为达到医疗应用目的,需要对产生治疗效果的技术进行标准化。本综述重点介绍 PBPs 的现状、结构、功能、制备方法和应用。此外,还讨论了 PBPs 的稳定性、生物利用度和安全性问题,以及它们在治疗中的应用。
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引用次数: 0
Attomole Electrochemical Detection of MicroRNAs Based on Surface-Initiated Enzymatic Polymerization Coupled with Copper Enhancement 基于表面引发酶聚合耦合铜增强的微rna原子孔电化学检测
Pub Date : 2023-10-30 DOI: 10.3390/targets1020007
Wenyuan Zhu, Yuzhi Xu, Yanfei Zhang, Si-Yang Liu, Zong Dai, Xiaoyong Zou
The sensitive and effective detection of microRNAs (miRNAs) is of great significance since miRNAs have been proven to have undeniable importance in participating in many biological processes. Herein, we present a novel, sensitive, label-free electrochemical miRNA detection method. Three signal amplification techniques are incorporated in this method, including the efficient conjugate of primer-modified polystyrene spheres (PS) with magnetic beads (MBs) triggered by target miRNA, template-free surface-initiated enzymatic polymerization (SIEP) on the primers, and the use of copper ions in square wave voltammetry (SWV) for detecting acidically depurinated primers. Cooperating with the electrochemical approach, this method was able to achieve a detection limit of 120 aM. With an attomole level of sensitivity and easiness of manipulation, this novel method is suitable for miRNA routine detection in both research and clinical aspects.
由于miRNAs已被证明在参与许多生物过程中具有不可否认的重要性,因此对其进行灵敏有效的检测具有重要意义。在此,我们提出了一种新的、灵敏的、无标记的电化学miRNA检测方法。该方法采用了三种信号放大技术,包括引物修饰的聚苯乙烯球(PS)与靶miRNA触发的磁珠(mb)的有效共轭,引物上的无模板表面引发酶促聚合(SIEP),以及在方波伏安法(SWV)中使用铜离子检测酸去纯化的引物。与电化学方法相配合,该方法的检出限为120 aM。该方法具有原子级的灵敏度和操作简便,适用于研究和临床的miRNA常规检测。
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引用次数: 0
Photo-Cleavable Polycations-Wrapped Upconversion Nanoparticles for Efficient siRNA Delivery and Cancer Therapy 光可切割的聚阳离子包裹上转换纳米粒子用于高效siRNA递送和癌症治疗
Pub Date : 2023-09-12 DOI: 10.3390/targets1010006
Yuling He, Shuwen Guo, Huangxian Ju, Ying Liu
RNA interference (RNAi) therapy is a promising approach for cancer therapy. However, due to the weak binding affinity between a carrier and small interference RNA (siRNA) and complicated tumor environment, efficient loading and release of siRNA still remain challenging. Here, we design photo-cleavable polycations-wrapped upconversion nanoparticles (PC-UCNPs) for spatially and temporally controllable siRNA delivery. The PC-UCNPs are synthesized by in situ reversible addition−fragmentation chain transfer (RAFT) polymerization of photo-cleaved 5-(2-(dimethylamino)ethoxy)-2-nitrobenzyl acrylat (MENA) monomer and poly(oligo(ethylene oxide) methyl ether acrylate (OEMA) mononer through a chain transfer agent that anchored on the surface of silica-coated upconversion nanoparticles (UCNPs@SiO2). After reacting with CH3I, siRNA and hyaluronic acid (HA) are adsorbed on the particle surface to prepare PC-UCNPs/siRNA/HA. The reaction with cell-secreted hyaluronidase (HAase) achieves the intracellular delivery of PC-UCNPs/siRNA/HA, and 980 nm laser irradiation causes siRNA release, which effectively improves the gene silencing efficiency in vitro and suppresses tumor growth in vivo; therefore, these processes have a promising potential application in precision medicine.
RNA干扰(RNAi)治疗是一种很有前途的癌症治疗方法。然而,由于载体与小干扰RNA (small interference RNA, siRNA)的结合亲和力较弱,加之肿瘤环境复杂,siRNA的高效装载和释放仍然是一个挑战。在这里,我们设计了光可切割的聚合包覆转换纳米粒子(PC-UCNPs),用于空间和时间可控的siRNA递送。PC-UCNPs是由光裂解的5-(2-(二甲氨基)乙氧基)-2-硝基苯基丙烯酸酯(MENA)单体和聚低聚(环氧乙烷)丙烯酸甲酯(OEMA)单体通过链转移剂锚定在二氧化硅包覆的上转化纳米颗粒表面(UCNPs@SiO2),通过原位可逆加成-破碎链转移(RAFT)聚合合成的。与CH3I反应后,siRNA和透明质酸(HA)吸附在颗粒表面,制备PC-UCNPs/siRNA/HA。与细胞分泌透明质酸酶(HAase)反应,实现PC-UCNPs/siRNA/HA的细胞内递送,980 nm激光照射引起siRNA释放,在体外有效提高基因沉默效率,在体内抑制肿瘤生长;因此,这些工艺在精准医疗中具有广阔的应用前景。
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引用次数: 0
Patent perspective 专利的角度来看
Pub Date : 2003-12-01 DOI: 10.1016/S1477-3627(03)02384-5
Douglas Drysdale, Stella Fletcher

Patent Update is a regular column dedicated to the complex issues that affect patents in the genomics and proteomics field. In each issue, there are two sections compiled by patent attorneys. The first section, Patents – a Practical Perspective, is a commentary on current issues, landmark patents, useful patent resources and how to search them, and legislative changes that impact the pharma and biotech industries. The second section, Patent News, provides brief synopses of recently issued patents and other patent events, and their significance to drug discovery R&D.

专利更新是一个定期专栏,致力于影响基因组学和蛋白质组学领域专利的复杂问题。在每期中,有两个部分由专利律师汇编。第一部分,专利-一个实用的视角,是对当前问题的评论,具有里程碑意义的专利,有用的专利资源和如何搜索它们,以及影响制药和生物技术行业的立法变化。第二部分是专利新闻,简要介绍了最近发布的专利和其他专利事件,以及它们对药物发现研发的意义。
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引用次数: 0
Where do all the proteins go? 所有的蛋白质都去了哪里?
Pub Date : 2003-12-01 DOI: 10.1016/S1477-3627(03)02371-7
Anuj Kumar

The subcellular localization of a protein can be very informative in identifying its function and in understanding the regulatory mechanisms by which it is controlled. Past efforts to define protein localization have typically entailed methods of immunological and fluorescence-based detection applied to a limited number of gene products. Several current studies are shifting this paradigm – utilizing traditional and novel approaches in molecular biology, proteomics, histochemistry and bioinformatics to define protein localization on a proteome-wide scale. Selected studies highlighting each of these approaches are presented here as an overview of the diverse avenues by which protein localization may be investigated for the identification of new drug targets.

蛋白质的亚细胞定位在识别其功能和理解其控制的调节机制方面可以提供非常有用的信息。过去确定蛋白质定位的努力通常涉及应用于有限数量的基因产物的免疫学和荧光检测方法。目前的一些研究正在改变这一范式——利用分子生物学、蛋白质组学、组织化学和生物信息学的传统和新方法在蛋白质组范围内定义蛋白质定位。本文将重点介绍这些方法中的每一种,作为对多种途径的概述,通过这些途径可以研究蛋白质定位以识别新的药物靶点。
{"title":"Where do all the proteins go?","authors":"Anuj Kumar","doi":"10.1016/S1477-3627(03)02371-7","DOIUrl":"10.1016/S1477-3627(03)02371-7","url":null,"abstract":"<div><p>The subcellular localization of a protein can be very informative in identifying its function and in understanding the regulatory mechanisms by which it is controlled. Past efforts to define protein localization have typically entailed methods of immunological and fluorescence-based detection applied to a limited number of gene products. Several current studies are shifting this paradigm – utilizing traditional and novel approaches in molecular biology, proteomics, histochemistry and bioinformatics to define protein localization on a proteome-wide scale. Selected studies highlighting each of these approaches are presented here as an overview of the diverse avenues by which protein localization may be investigated for the identification of new drug targets.</p></div>","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"2 6","pages":"Pages 237-244"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1477-3627(03)02371-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75278048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Robert Strausberg on the future of genomics and his new role at TIGR Robert Strausberg谈基因组学的未来以及他在TIGR的新角色
Pub Date : 2003-12-01 DOI: 10.1016/S1477-3627(03)02391-2
Interview by Joanna Owens
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引用次数: 0
New antibiotic targets: should we still hope? 新的抗生素靶点:我们还应该抱有希望吗?
Pub Date : 2003-12-01 DOI: 10.1016/S1477-3627(03)02389-4
Paul F. Miller , C. Kenneth Stover
{"title":"New antibiotic targets: should we still hope?","authors":"Paul F. Miller ,&nbsp;C. Kenneth Stover","doi":"10.1016/S1477-3627(03)02389-4","DOIUrl":"10.1016/S1477-3627(03)02389-4","url":null,"abstract":"","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"2 6","pages":"Pages 227-228"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1477-3627(03)02389-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89348488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Hypothesis-driven gene identification goes high-throughput 假设驱动的基因鉴定是高通量的
Pub Date : 2003-12-01 DOI: 10.1016/S1477-3627(03)02386-9
Rabiya S. Tuma, BMN News
{"title":"Hypothesis-driven gene identification goes high-throughput","authors":"Rabiya S. Tuma,&nbsp;BMN News","doi":"10.1016/S1477-3627(03)02386-9","DOIUrl":"https://doi.org/10.1016/S1477-3627(03)02386-9","url":null,"abstract":"","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"2 6","pages":"Page 230"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1477-3627(03)02386-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92061664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
TARGETS
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