Pub Date : 2023-11-01Epub Date: 2023-10-15DOI: 10.1177/02611929231206692
Judith C Madden
{"title":"Editorial.","authors":"Judith C Madden","doi":"10.1177/02611929231206692","DOIUrl":"10.1177/02611929231206692","url":null,"abstract":"","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1177/02611929231193416
Shayana Saravanakumar, Jhinuk Chatterjee
The constant evolution of pathogenic viral variants and the emergence of new viruses have reinforced the need for broad-spectrum vaccines to combat such threats. The spread of new viral variants leading to epidemic and pandemic infection can be effectively contained, if broad-spectrum vaccines effective against the newer viral variants are readily available. The development of broad-spectrum, pan-neutralising antibodies against viruses which, in general terms, are very antigenically different - such as HIV, influenza virus and paramyxoviruses - has been reported in the literature. The amino acid sequences used to generate a range of approved recombinant anti-viral vaccines were analysed by using in silico methods, with the aim of identifying highly antigenic peptide regions that may be suitable for the development of broad-spectrum peptide-based anti-viral vaccines. This was achieved through the use of open-source data, an algorithm-driven probability matrix, and published in silico prediction tools (SVMTriP, IEDB-AR, VaxiJen 2.0, AllergenFP v. 1.0, AllerTOP v. 2.0, ToxinPred and ProtParam) to evaluate antigenicity, MHC-I and MHC-II binding potential, immunogenicity, allergenicity, toxicity and physicochemical properties. We report a pan-antigenic peptide region with strong affinity for MHC-I and MHC-II, and good immunogenic potential. According to the output from the relevant in silico tools, the peptide was predicted to be non-toxic, non-allergic and to possess the desired physicochemical properties for potentially successful vaccine production. With further investigation and optimisation, this peptide could be considered for use in the development of a broad-spectrum anti-viral vaccine that may protect against emerging new viruses. Our approach of using in silico methods to identify candidate antigenic peptides with the desired physicochemical properties could potentially circumvent the use of some animal studies for peptide vaccine candidate evaluation.
致病性病毒变体的不断演变和新病毒的出现,加强了对广谱疫苗的需求,以应对这类威胁。如果能够随时获得对较新的病毒变体有效的广谱疫苗,就可以有效地控制导致流行病和大流行感染的新病毒变体的传播。一般来说,针对HIV、流感病毒和副粘病毒等在抗原性上非常不同的病毒的广谱、泛中和抗体的开发已经在文献中有所报道。利用计算机方法分析了用于生产一系列已获批准的重组抗病毒疫苗的氨基酸序列,目的是确定可能适合开发广谱肽基抗病毒疫苗的高抗原肽区。这是通过使用开源数据,算法驱动的概率矩阵,并在计算机预测工具(SVMTriP, IEDB-AR, VaxiJen 2.0, AllergenFP v. 1.0, AllerTOP v. 2.0, ToxinPred和ProtParam)中发布来评估抗原,MHC-I和MHC-II结合潜力,免疫原性,过敏原性,毒性和物理化学性质来实现的。我们报道了一个对MHC-I和MHC-II具有强亲和力的泛抗原肽区,具有良好的免疫原性潜力。根据相关硅工具的输出,预测该肽无毒、不过敏,并具有潜在成功生产疫苗所需的物理化学性质。随着进一步的研究和优化,这种肽可以考虑用于开发广谱抗病毒疫苗,以防止新出现的病毒。我们使用计算机方法鉴定具有所需物理化学性质的候选抗原肽的方法可能会避免使用一些动物研究来评估肽疫苗候选物。
{"title":"The Use of <i>In Silico</i> Methods to Identify and Assess Antigenic Regions Suitable for the Development of Peptide-based Pan-viral Vaccines.","authors":"Shayana Saravanakumar, Jhinuk Chatterjee","doi":"10.1177/02611929231193416","DOIUrl":"https://doi.org/10.1177/02611929231193416","url":null,"abstract":"<p><p>The constant evolution of pathogenic viral variants and the emergence of new viruses have reinforced the need for broad-spectrum vaccines to combat such threats. The spread of new viral variants leading to epidemic and pandemic infection can be effectively contained, if broad-spectrum vaccines effective against the newer viral variants are readily available. The development of broad-spectrum, pan-neutralising antibodies against viruses which, in general terms, are very antigenically different - such as HIV, influenza virus and paramyxoviruses - has been reported in the literature. The amino acid sequences used to generate a range of approved recombinant anti-viral vaccines were analysed by using <i>in silico</i> methods, with the aim of identifying highly antigenic peptide regions that may be suitable for the development of broad-spectrum peptide-based anti-viral vaccines. This was achieved through the use of open-source data, an algorithm-driven probability matrix, and published <i>in silico</i> prediction tools (SVMTriP, IEDB-AR, VaxiJen 2.0, AllergenFP v. 1.0, AllerTOP v. 2.0, ToxinPred and ProtParam) to evaluate antigenicity, MHC-I and MHC-II binding potential, immunogenicity, allergenicity, toxicity and physicochemical properties. We report a pan-antigenic peptide region with strong affinity for MHC-I and MHC-II, and good immunogenic potential. According to the output from the relevant <i>in silico</i> tools, the peptide was predicted to be non-toxic, non-allergic and to possess the desired physicochemical properties for potentially successful vaccine production. With further investigation and optimisation, this peptide could be considered for use in the development of a broad-spectrum anti-viral vaccine that may protect against emerging new viruses. Our approach of using <i>in silico</i> methods to identify candidate antigenic peptides with the desired physicochemical properties could potentially circumvent the use of some animal studies for peptide vaccine candidate evaluation.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10285056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1177/02611929231194309
Gwi Hyang Lee, Heui-Jin Kim, Young-Shin Joo, Seung Yeon Kim, Barney Reed, Lynette A Hart, Byung In Choe
In Korea, Institutional Animal Care and Use Committees (IACUCs) have been legally required to apply the Three Rs principles (i.e. replacement, reduction and refinement) and undertake the ethical review of animal study protocols, since 2008. According to Korean law, each IACUC is required to appoint at least one lay member recommended by a non-governmental animal protection organisation, who participates in the ethical review process as part of this role. Despite the importance of the Three Rs and the ethical review process, limited information and practical resources are available for IACUC members in the Korean language, particularly for lay members who are inexperienced in animal experimentation. In January 2020, the Animal and Plant Quarantine Agency announced the funding for a six-month research project to develop guidance to assist IACUC members in carrying out effective and efficient protocol reviews in line with Korean legislative requirements. This funding was awarded for the production of two IACUC guidance documents - 'Guide for Animal Study Protocols' and 'Guide for the IACUC Lay Member' - which were published in December 2020. These guidance documents aim to foster the implementation of the Three Rs and provide practical resources for IACUC members, researchers and other relevant personnel. This paper describes the framework for animal use in Korea and the overall production of these two IACUC Guidance Documents.
{"title":"Development of Two Korean IACUC Guidance Documents to Foster Implementation of the Three Rs.","authors":"Gwi Hyang Lee, Heui-Jin Kim, Young-Shin Joo, Seung Yeon Kim, Barney Reed, Lynette A Hart, Byung In Choe","doi":"10.1177/02611929231194309","DOIUrl":"https://doi.org/10.1177/02611929231194309","url":null,"abstract":"<p><p>In Korea, Institutional Animal Care and Use Committees (IACUCs) have been legally required to apply the Three Rs principles (i.e. <i>replacement</i>, <i>reduction</i> and <i>refinement</i>) and undertake the ethical review of animal study protocols, since 2008. According to Korean law, each IACUC is required to appoint at least one lay member recommended by a non-governmental animal protection organisation, who participates in the ethical review process as part of this role. Despite the importance of the Three Rs and the ethical review process, limited information and practical resources are available for IACUC members in the Korean language, particularly for lay members who are inexperienced in animal experimentation. In January 2020, the Animal and Plant Quarantine Agency announced the funding for a six-month research project to develop guidance to assist IACUC members in carrying out effective and efficient protocol reviews in line with Korean legislative requirements. This funding was awarded for the production of two IACUC guidance documents - 'Guide for Animal Study Protocols' and 'Guide for the IACUC Lay Member' - which were published in December 2020. These guidance documents aim to foster the implementation of the Three Rs and provide practical resources for IACUC members, researchers and other relevant personnel. This paper describes the framework for animal use in Korea and the overall production of these two IACUC Guidance Documents.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10302642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1177/02611929231190863
Ernest S Fung, Jillian A Parker, Andrew D Monnot
Human hair follicles traverse the epidermis and dermis, and are comprised of specialised cells including dermal papilla cells (DPCs). DPCs play a critical role in the development and growth of both hair and follicle structure. While exposure of DPCs to undiluted exogenous compounds is unlikely, exposure to diluted compounds is possible should dermal penetration occur. The goal of this study was to evaluate the impact on hair and scalp health following application of a hair care product. Due to the lack of standardised and validated test systems for evaluating hair follicle health, the HairSkin® model, which uses intact human scalp samples, was adapted to evaluate hair follicle and scalp health. Similarly, the Franz diffusion cell assay and matrix-assisted laser desorption ionisation-Fourier transform ion cyclotron resonance (MALDI-FTICR) were adapted to evaluate dermal penetration. The results of this study demonstrate that application of the hair care product does not result in appreciable dermal penetration, suggesting that DPCs are unlikely to be exposed to undiluted product. Additionally, hair follicle health was not impacted following product application. While this study is exploratory, these results suggest that the combination of test systems utilised herein provides valuable insight and warrants further development and validation.
{"title":"Evaluating the Impact of Hair Care Product Exposure on Hair Follicle and Scalp Health.","authors":"Ernest S Fung, Jillian A Parker, Andrew D Monnot","doi":"10.1177/02611929231190863","DOIUrl":"https://doi.org/10.1177/02611929231190863","url":null,"abstract":"<p><p>Human hair follicles traverse the epidermis and dermis, and are comprised of specialised cells including dermal papilla cells (DPCs). DPCs play a critical role in the development and growth of both hair and follicle structure. While exposure of DPCs to undiluted exogenous compounds is unlikely, exposure to diluted compounds is possible should dermal penetration occur. The goal of this study was to evaluate the impact on hair and scalp health following application of a hair care product. Due to the lack of standardised and validated test systems for evaluating hair follicle health, the HairSkin<sup>®</sup> model, which uses intact human scalp samples, was adapted to evaluate hair follicle and scalp health. Similarly, the Franz diffusion cell assay and matrix-assisted laser desorption ionisation-Fourier transform ion cyclotron resonance (MALDI-FTICR) were adapted to evaluate dermal penetration. The results of this study demonstrate that application of the hair care product does not result in appreciable dermal penetration, suggesting that DPCs are unlikely to be exposed to undiluted product. Additionally, hair follicle health was not impacted following product application. While this study is exploratory, these results suggest that the combination of test systems utilised herein provides valuable insight and warrants further development and validation.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10284072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1177/02611929231200532
Judith C Madden
{"title":"Editorial.","authors":"Judith C Madden","doi":"10.1177/02611929231200532","DOIUrl":"https://doi.org/10.1177/02611929231200532","url":null,"abstract":"","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10296892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1177/02611929231193421
Ece Sariyar, Zeynep Firtina Karagonlar
Liver cancer is the third leading cause of cancer-related mortality, and hepatocellular carcinoma (HCC) is the most common form of liver cancer, and it usually occurs in the setting of chronic liver disease and cirrhosis. For patients with advanced HCC, systemic treatment is the first choice - however, resistance occurs frequently. Sorafenib was the first tyrosine kinase inhibitor approved for advanced HCC, and resistance to the therapy is a serious concern. When sorafenib therapy fails in a patient, it can be challenging to decide whether they can undergo a second-line therapy, and to determine which therapy they will be able to tolerate. Thus, physiologically relevant in vitro preclinical models are crucial for screening potential therapies, and 3-D tumour spheroids permit studies of tumour pathobiology. In this study, a drug-resistant 3-D tumour spheroid model was developed, based on sorafenib-resistant hepatocellular carcinoma cells, LX2 stellate cells and THP-1 monocytes. Model tumour spheroids that were formed with the sorafenib-resistant cells demonstrated lower diffusion of doxorubicin and exhibited increased resistance to regorafenib. Moreover, in the sorafenib-resistant spheroids, there was increased presence of CD68-positive cells and a reduction in inflammatory marker secretion. The sorafenib-resistant cell line-derived spheroids also showed a higher expression of FGF-19, PDGF-AA and GDF-15, which are known to be involved in malignancies. This multi-cell type spheroid model represents a potentially useful system to test drug candidates in a microenvironment that mimics the drug-resistant tumour microenvironment in HCC.
{"title":"Modelling the Sorafenib-resistant Liver Cancer Microenvironment by Using 3-D Spheroids.","authors":"Ece Sariyar, Zeynep Firtina Karagonlar","doi":"10.1177/02611929231193421","DOIUrl":"https://doi.org/10.1177/02611929231193421","url":null,"abstract":"<p><p>Liver cancer is the third leading cause of cancer-related mortality, and hepatocellular carcinoma (HCC) is the most common form of liver cancer, and it usually occurs in the setting of chronic liver disease and cirrhosis. For patients with advanced HCC, systemic treatment is the first choice - however, resistance occurs frequently. Sorafenib was the first tyrosine kinase inhibitor approved for advanced HCC, and resistance to the therapy is a serious concern. When sorafenib therapy fails in a patient, it can be challenging to decide whether they can undergo a second-line therapy, and to determine which therapy they will be able to tolerate. Thus, physiologically relevant <i>in vitro</i> preclinical models are crucial for screening potential therapies, and 3-D tumour spheroids permit studies of tumour pathobiology. In this study, a drug-resistant 3-D tumour spheroid model was developed, based on sorafenib-resistant hepatocellular carcinoma cells, LX2 stellate cells and THP-1 monocytes. Model tumour spheroids that were formed with the sorafenib-resistant cells demonstrated lower diffusion of doxorubicin and exhibited increased resistance to regorafenib. Moreover, in the sorafenib-resistant spheroids, there was increased presence of CD68-positive cells and a reduction in inflammatory marker secretion. The sorafenib-resistant cell line-derived spheroids also showed a higher expression of FGF-19, PDGF-AA and GDF-15, which are known to be involved in malignancies. This multi-cell type spheroid model represents a potentially useful system to test drug candidates in a microenvironment that mimics the drug-resistant tumour microenvironment in HCC.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10334317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}