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.
{"title":"Living Bacteriophage Engineering for Functional Material Synthesis, Bioanalytical Sensing and Disease Theranostics","authors":"Jing Zhang, Xuewen He","doi":"10.3390/targets2030010","DOIUrl":"https://doi.org/10.3390/targets2030010","url":null,"abstract":"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.","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":" 36","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141670418","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}
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。
{"title":"Unveiling the Role of Concanavalin A in a Rodent Model of Chemical-Induced Hepatocellular Carcinoma: A Promising Guide in Understanding Liver Cancer Development","authors":"Romelia Pop, Dragoș Hodor, C. Catoi, T. Mocan, L. Mocan, A. Tabaran","doi":"10.3390/targets2010003","DOIUrl":"https://doi.org/10.3390/targets2010003","url":null,"abstract":"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.","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"36 42","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139961718","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}
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.
{"title":"The Radiant World of Cyanobacterial Phycobiliproteins: Examining Their Structure, Functions, and Biomedical Potentials","authors":"Sapana Jha, Varsha K. Singh, Ashish P. Singh, Amit Gupta, Palak Rana, R. Sinha","doi":"10.3390/targets2010002","DOIUrl":"https://doi.org/10.3390/targets2010002","url":null,"abstract":"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.","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"7 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139439958","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}
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.
{"title":"Attomole Electrochemical Detection of MicroRNAs Based on Surface-Initiated Enzymatic Polymerization Coupled with Copper Enhancement","authors":"Wenyuan Zhu, Yuzhi Xu, Yanfei Zhang, Si-Yang Liu, Zong Dai, Xiaoyong Zou","doi":"10.3390/targets1020007","DOIUrl":"https://doi.org/10.3390/targets1020007","url":null,"abstract":"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.","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"461 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136022643","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}
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.
{"title":"Photo-Cleavable Polycations-Wrapped Upconversion Nanoparticles for Efficient siRNA Delivery and Cancer Therapy","authors":"Yuling He, Shuwen Guo, Huangxian Ju, Ying Liu","doi":"10.3390/targets1010006","DOIUrl":"https://doi.org/10.3390/targets1010006","url":null,"abstract":"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.","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135885417","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}
Pub Date : 2003-12-01DOI: 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.
{"title":"Patent perspective","authors":"Douglas Drysdale, Stella Fletcher","doi":"10.1016/S1477-3627(03)02384-5","DOIUrl":"https://doi.org/10.1016/S1477-3627(03)02384-5","url":null,"abstract":"<div><p><em>Patent Update</em> 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, <em>Patents – a Practical Perspective</em>, 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, <em>Patent News</em>, provides brief synopses of recently issued patents and other patent events, and their significance to drug discovery R&D.</p></div>","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"2 6","pages":"Pages 271-272"},"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)02384-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137344436","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}
Pub Date : 2003-12-01DOI: 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.
{"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}
Pub Date : 2003-12-01DOI: 10.1016/S1477-3627(03)02391-2
Interview by Joanna Owens
{"title":"Robert Strausberg on the future of genomics and his new role at TIGR","authors":"Interview by Joanna Owens","doi":"10.1016/S1477-3627(03)02391-2","DOIUrl":"https://doi.org/10.1016/S1477-3627(03)02391-2","url":null,"abstract":"","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"2 6","pages":"Pages 232-234"},"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)02391-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92061665","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}
Pub Date : 2003-12-01DOI: 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 , 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}