Weihua Song, Wu Sun, Zilong Wang, K. Teo, C. Cheung, Xiaomeng Wang
Review Targeting Inflammation to Control Tissue Fibrosis Weihua Song 1, Wu Sun 2, Zilong Wang 3, Kelvin Yi Chong Teo 2,4,5, Chui Ming Gemmy Cheung 2,4,5, and Xiaomeng Wang 4,5,6,* 1 Innoland Biosciences, 6 West Beijing Road, Taicang 215400, Jiangsu, China. 2 Singapore National Eye Center, 11 Third Hospital Ave 168751, Singapore. 3 Ocean University of China, 5 Yushan Rd, Shinan District, Qingdao 266005, Shandong, China. 4 Singapore Eye Research Institute, 20 College Road 169856, Singapore. 5 Duke-NUS Graduate Medical School, 20 College Road 169856, Singapore. 6 Insitute of Molecular and Cell Biology, 61 Biopolis Dr, Proteos 138673, Singapore. * Correspondence: xiaomeng.wang@duke-nus.edu.sg Received: 17 November 2022 Accepted: 19 November 2022 Published: 21 December 2022 Abstract: Remodeling of the extracellular matrix (ECM) is an essential process in host defense against pathogens and tissue repair following injury. However, aberrant inflammatory responses could disturb ECM homeostasis leading to progressive disruption in tissue architecture and organ function. Fibrosis is the common outcome of a wide range of diseases, especially chronic inflammatory disorders, and represents the leading cause of morbidity and mortality globally. This review provides the current understanding of the pathogenesis of fibrosis, with particular emphasis on the role of inflammation in this process and the translational potential of targeting inflammation as a strategy to control fibrotic progression.
{"title":"Targeting Inflammation to Control Tissue Fibrosis","authors":"Weihua Song, Wu Sun, Zilong Wang, K. Teo, C. Cheung, Xiaomeng Wang","doi":"10.53941/ijddp.v1i1.206","DOIUrl":"https://doi.org/10.53941/ijddp.v1i1.206","url":null,"abstract":"Review\u0000Targeting Inflammation to Control Tissue Fibrosis\u0000\u0000Weihua Song 1, Wu Sun 2, Zilong Wang 3, Kelvin Yi Chong Teo 2,4,5, Chui Ming Gemmy Cheung 2,4,5, and Xiaomeng Wang 4,5,6,*\u0000\u0000\u00001 Innoland Biosciences, 6 West Beijing Road, Taicang 215400, Jiangsu, China.\u00002 Singapore National Eye Center, 11 Third Hospital Ave 168751, Singapore.\u00003 Ocean University of China, 5 Yushan Rd, Shinan District, Qingdao 266005, Shandong, China.\u00004 Singapore Eye Research Institute, 20 College Road 169856, Singapore.\u00005 Duke-NUS Graduate Medical School, 20 College Road 169856, Singapore.\u00006 Insitute of Molecular and Cell Biology, 61 Biopolis Dr, Proteos 138673, Singapore.\u0000* Correspondence: xiaomeng.wang@duke-nus.edu.sg\u0000 \u0000 \u0000Received: 17 November 2022\u0000Accepted: 19 November 2022\u0000Published: 21 December 2022\u0000 \u0000\u0000Abstract: Remodeling of the extracellular matrix (ECM) is an essential process in host defense against pathogens and tissue repair following injury. However, aberrant inflammatory responses could disturb ECM homeostasis leading to progressive disruption in tissue architecture and organ function. Fibrosis is the common outcome of a wide range of diseases, especially chronic inflammatory disorders, and represents the leading cause of morbidity and mortality globally. This review provides the current understanding of the pathogenesis of fibrosis, with particular emphasis on the role of inflammation in this process and the translational potential of targeting inflammation as a strategy to control fibrotic progression.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73290653","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}
Group I p21-activated kinases (Paks) are members of the serine/threonine protein kinase family. Paks are encoded by three genes (Pak 1 - 3) and are involved in the regulation of various biological processes. Pak1 and Pak2 are key members, sharing 91% sequence identity in their kinase domains. Recent studies have shown that Pak1/2 protect the heart from various types of stresses. Activated Pak1/2 participate in the maintenance of cellular homeostasis and metabolism, thus enhancing the adaptation and resilience of cardiomyocytes to stress. The structure, activation and function of Pak1/2 as well as their protective roles against the occurrence of cardiovascular disease are described in this review. The values of Pak1/2 as therapeutic targets are also discussed.
{"title":"The P21-Activated Kinase 1 and 2 As Potential Therapeutic Targets for the Management of Cardiovascular Disease.","authors":"Honglin Xu, Dingwei Wang, Chiara Ramponi, Xin Wang, Hongyuan Zhang","doi":"10.53941/ijddp.v1i1.179","DOIUrl":"10.53941/ijddp.v1i1.179","url":null,"abstract":"<p><p>Group I p21-activated kinases (Paks) are members of the serine/threonine protein kinase family. Paks are encoded by three genes (Pak 1 - 3) and are involved in the regulation of various biological processes. Pak1 and Pak2 are key members, sharing 91% sequence identity in their kinase domains. Recent studies have shown that Pak1/2 protect the heart from various types of stresses. Activated Pak1/2 participate in the maintenance of cellular homeostasis and metabolism, thus enhancing the adaptation and resilience of cardiomyocytes to stress. The structure, activation and function of Pak1/2 as well as their protective roles against the occurrence of cardiovascular disease are described in this review. The values of Pak1/2 as therapeutic targets are also discussed.</p>","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"24 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83307226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mini Review Injectable Multifunctional Natural Polymer-Based Hydrogels for the Local Delivery of Therapeutic Agents Xue Bai 1，Annalisa Tirella1,2,* 1 Division of Pharmacy and Optometry, School of Health Science, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK. 2 BIOtech-Center for Biomedical Technologies, Department of Industrial Engineering, University of Trento, Via delle Regole 101, Trento 38123, Italy. * Correspondence: annalisa.tirella@unitn.it , annalisa.tirella@manchester.ac.uk (Annalisa Tirella). Received: 13 November 2022 Accepted: 15 November 2022 Published: 21 December 2022 Abstract: Hydrogels are water-based polymeric three-dimensional network with advantageous properties for the delivery of bioactive components, ranging from small therapeutic agents to therapeutic cells. Natural-based hydrogels have great potential as delivery vehicles for the local controlled release of therapeutic agents at the target site. Injectable hydrogels are designed to load therapeutic agents by simple mixing within the polymer solutions, as well as use nanoparticles able to respond to specific external conditions, such as temperature and pH. Herein, we present an overview of the properties of natural injectable hydrogels and recent developments for their use to control the local release of therapeutic agents; as well as strategies to crosslink in-situ multifunctional injectable hydrogels that act as therapeutical depot system. The mini review focuses on alginate-based injectable hydrogels as controlled drug delivery systems, presenting advantages and challenges of their application in cancer therapy
{"title":"Injectable Multifunctional Natural Polymer-Based Hydrogels for the Local Delivery of Therapeutic Agents","authors":"Xue Bai, A. Tirella","doi":"10.53941/ijddp.v1i1.203","DOIUrl":"https://doi.org/10.53941/ijddp.v1i1.203","url":null,"abstract":"Mini Review\u0000Injectable Multifunctional Natural Polymer-Based Hydrogels for the Local Delivery of Therapeutic Agents\u0000\u0000Xue Bai 1，Annalisa Tirella1,2,*\u0000\u0000\u00001 Division of Pharmacy and Optometry, School of Health Science, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK.\u00002 BIOtech-Center for Biomedical Technologies, Department of Industrial Engineering, University of Trento, Via delle Regole 101, Trento 38123, Italy.\u0000* Correspondence: annalisa.tirella@unitn.it , annalisa.tirella@manchester.ac.uk (Annalisa Tirella).\u0000 \u0000 \u0000Received: 13 November 2022\u0000Accepted: 15 November 2022\u0000Published: 21 December 2022\u0000 \u0000\u0000Abstract: Hydrogels are water-based polymeric three-dimensional network with advantageous properties for the delivery of bioactive components, ranging from small therapeutic agents to therapeutic cells. Natural-based hydrogels have great potential as delivery vehicles for the local controlled release of therapeutic agents at the target site. Injectable hydrogels are designed to load therapeutic agents by simple mixing within the polymer solutions, as well as use nanoparticles able to respond to specific external conditions, such as temperature and pH. Herein, we present an overview of the properties of natural injectable hydrogels and recent developments for their use to control the local release of therapeutic agents; as well as strategies to crosslink in-situ multifunctional injectable hydrogels that act as therapeutical depot system. The mini review focuses on alginate-based injectable hydrogels as controlled drug delivery systems, presenting advantages and challenges of their application in cancer therapy","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77475607","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}
Review Cardiac β-Adrenoceptor Signaling: The New Insight on An Old Target in the Therapy of Cardiovascular Disease Ying Song 1, Anthony Yiu-Ho Woo 2,*, Yan Zhang 3,4,*, and Ruiping Xiao 5,6,7,8 1 Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China. 2 School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China. 3 Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, School of Basic Medical Sciences, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China. 4 Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, 100191, China. 5 State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, 100871, China. 6 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China. 7 Beijing City Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing, 100871, China. 8 PKU-Nanjing Joint Institute of Translational Medicine, Nanjing, 210000, China. * Correspondence: yiuhowoo@syphu.edu.cn (Anthony Yiu-Ho Woo), Tel.: +86-24-23986375; zhangyan9876@pku.edu.cn (Yan Zhang), Tel.: +86-10-82805945. Received: 19 October 2022 Accepted: 28 October 2022 Published: 21 December 2022 Abstract: A variety of G protein-coupled receptors (GPCRs) are involved in the regulation of cardiovascular function. The β-adrenoceptors (β-ARs), with three subtypes, are the dominant receptor species in the heart, in which the β1-AR and the β2-AR are considered functional. Stimulation of the β-ARs produces myocardial inotropy via activation of the Gs-cAMP-PKA signaling cascade. Prolonged stimulation of the β1-AR is cardiac harmful because the stimulated β1-AR couples only to Gs proteins and it mediates a cardiotoxic signal. On the other hand, the β2-AR couples dually to both Gs and Gi proteins and the β2-AR-Gi pathway is antiapoptotic. The activated Gi signal also counteracts the β-AR-Gs-promoted positive inotropic effect. Other key players in cardiac β-AR signaling include Ca2+/calmodulin-dependent protein kinases (CaMKs), GPCR kinases (GRKs), β-arrestins and phosphodiesterases. During heart failure, excessive sympathetic stimulation results in the activation of the cardiotoxic β1-AR-CaMKIIδ pathway and the upregulation of GRK2 and Gi in the heart. GRK2 promotes the desensitization of β-ARs and enhances a β2-AR-mediated Gi signaling. These signal transduction processes accompanying the downregulation of the β1-AR are involved in cardiac dysfunction, maladaptive cardiac remodeling, and the progression of chronic heart failure. β-Blockers are widely used in the treatment of cardiovascular disease. They have established their position as one of the “four pillars of heart failure” thirty years ago. In the present review, we provide an overview of the
{"title":"Cardiac β-Adrenoceptor Signaling: The New Insight on An Old Target in the Therapy of Cardiovascular Disease","authors":"Ying Song, A. Woo, Yan Zhang, Ruiping Xiao","doi":"10.53941/ijddp.v1i1.177","DOIUrl":"https://doi.org/10.53941/ijddp.v1i1.177","url":null,"abstract":"Review\u0000Cardiac β-Adrenoceptor Signaling: The New Insight on An Old Target in the Therapy of Cardiovascular Disease\u0000\u0000Ying Song 1, Anthony Yiu-Ho Woo 2,*, Yan Zhang 3,4,*, and Ruiping Xiao 5,6,7,8\u0000\u0000\u00001 Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China.\u00002 School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.\u00003 Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, School of Basic Medical Sciences, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China.\u00004 Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, 100191, China.\u00005 State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, 100871, China.\u00006 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.\u00007 Beijing City Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing, 100871, China.\u00008 PKU-Nanjing Joint Institute of Translational Medicine, Nanjing, 210000, China.\u0000* Correspondence: yiuhowoo@syphu.edu.cn (Anthony Yiu-Ho Woo), Tel.: +86-24-23986375; zhangyan9876@pku.edu.cn (Yan Zhang), Tel.: +86-10-82805945.\u0000 \u0000 \u0000Received: 19 October 2022\u0000Accepted: 28 October 2022\u0000Published: 21 December 2022\u0000 \u0000\u0000Abstract: A variety of G protein-coupled receptors (GPCRs) are involved in the regulation of cardiovascular function. The β-adrenoceptors (β-ARs), with three subtypes, are the dominant receptor species in the heart, in which the β1-AR and the β2-AR are considered functional. Stimulation of the β-ARs produces myocardial inotropy via activation of the Gs-cAMP-PKA signaling cascade. Prolonged stimulation of the β1-AR is cardiac harmful because the stimulated β1-AR couples only to Gs proteins and it mediates a cardiotoxic signal. On the other hand, the β2-AR couples dually to both Gs and Gi proteins and the β2-AR-Gi pathway is antiapoptotic. The activated Gi signal also counteracts the β-AR-Gs-promoted positive inotropic effect. Other key players in cardiac β-AR signaling include Ca2+/calmodulin-dependent protein kinases (CaMKs), GPCR kinases (GRKs), β-arrestins and phosphodiesterases. During heart failure, excessive sympathetic stimulation results in the activation of the cardiotoxic β1-AR-CaMKIIδ pathway and the upregulation of GRK2 and Gi in the heart. GRK2 promotes the desensitization of β-ARs and enhances a β2-AR-mediated Gi signaling. These signal transduction processes accompanying the downregulation of the β1-AR are involved in cardiac dysfunction, maladaptive cardiac remodeling, and the progression of chronic heart failure. β-Blockers are widely used in the treatment of cardiovascular disease. They have established their position as one of the “four pillars of heart failure” thirty years ago. In the present review, we provide an overview of the ","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90613163","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}
Editorial Current Progress in Drug Target Identification and Drug Delivery Xin Wang Faculty of Biology, Medicine, and Health, University of Manchester, Oxford Road, M13 9PT Manchester, UK. * Correspondence: xin.wang@manchester.ac.uk
{"title":"Current Progress in Drug Target Identification and Drug Delivery","authors":"X. Wang","doi":"10.53941/ijddp.v1i1.214","DOIUrl":"https://doi.org/10.53941/ijddp.v1i1.214","url":null,"abstract":"Editorial\u0000Current Progress in Drug Target Identification and Drug Delivery\u0000\u0000Xin Wang\u0000\u0000\u0000Faculty of Biology, Medicine, and Health, University of Manchester, Oxford Road, M13 9PT Manchester, UK.\u0000* Correspondence: xin.wang@manchester.ac.uk\u0000","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74107210","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}
Yingjuan Liu, Honglin Xu, S. Abraham, X. Wang, B. Keavney
Review Progress of 3D Organoid Technology for Preclinical Investigations: Towards Human In Vitro Models Yingjuan Liu *, Honglin Xu, Sabu Abraham, Xin Wang, and Bernard D. Keavney* Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, M13 9PT, UK. * Correspondence: yingjuan.liu@manchester.ac.uk (Yingjuan Liu); bernard.keavney@manchester.ac.uk (Bernard D. Keavney) Received: 1 November 2022 Accepted: 24 November 2022 Published: 21 December 2022 Abstract: Currently, with an increased requirement for new therapeutic strategies, preclinical drug testing or screening platforms have rapidly evolved in recent years. In comparison to traditional 2D cell cultures, 3D organoids or spheroids with or without scaffolds improve the microenvironment of in vitro cultures, advancing the in vitro biological observation and enabling mechanistic studies of drug reactions in the human tissue-like environment. 3D organoids and spheroids are straightforward to produce, and relatively uniform in size and shape. This helps to facilitate high throughput screening requirements. Spheroids and organoids have been applied in anti-cancer drug testing, toxicity evaluations, as well as mechanism studies for variable organ systems, including the intestine, liver, pancreas, brain, and heart. Among 3D cultures of spheroids and organoids, ‘tumour spheroids’ formed by dissociated tumour tissues or cancer cell lines are relatively simple in composition and commonly applied to anticancer drug screening. The ‘healthy organoids’ differentiated from hiPSCs/hESCs are more complex in cell composition, distribution, structure and function with higher similarity to in vivo organs, and have found applications in toxicity tests, personalised medicine, and therapeutic and mechanistic studies. In most cases, the multicellular 3D organoids are more resistant and stable in reaction to stimulations or chemicals in vitro , suggesting more accurate modelling of in vivo responses. Here, we review recent progress in human-origin organoid/spheroid systems and their applications in preclinical studies.
刘颖娟*，徐宏林，Sabu Abraham，王鑫，Bernard D. Keavney*英国曼彻斯特大学生物医学与健康学院心血管科学部，M13 9PT，英国。*通讯:yingjuan.liu@manchester.ac.uk (Yingjuan Liu);bernard.keavney@manchester.ac.uk (Bernard D. Keavney)收稿日期:2022年11月1日接收日期:2022年11月24日发布日期:2022年12月21日摘要:目前，随着对新的治疗策略的需求增加，临床前药物测试或筛选平台近年来迅速发展。与传统的二维细胞培养相比，有或无支架的三维类器官或球体改善了体外培养的微环境，推进了体外生物学观察，使药物在人体类组织环境中的反应机理研究成为可能。3D类器官和球体的制作很简单，尺寸和形状也相对统一。这有助于促进高通量筛选要求。球体和类器官已被应用于抗癌药物测试、毒性评估以及各种器官系统的机制研究，包括肠、肝、胰腺、脑和心脏。在球体和类器官的三维培养中，由游离的肿瘤组织或癌细胞系形成的“肿瘤球体”成分相对简单，通常用于抗癌药物筛选。从hiPSCs/hESCs分化出来的“健康类器官”在细胞组成、分布、结构和功能上更复杂，与体内器官具有更高的相似性，并已在毒性测试、个性化药物以及治疗和机制研究中得到应用。在大多数情况下，多细胞3D类器官在体外对刺激或化学物质的反应更有抵抗力和稳定性，这表明更准确的体内反应建模。在此，我们综述了人类来源的类器官/球体系统及其在临床前研究中的应用的最新进展。
{"title":"Progress of 3D Organoid Technology for Preclinical Investigations: Towards Human In Vitro Models","authors":"Yingjuan Liu, Honglin Xu, S. Abraham, X. Wang, B. Keavney","doi":"10.53941/ijddp.v1i1.188","DOIUrl":"https://doi.org/10.53941/ijddp.v1i1.188","url":null,"abstract":"Review\u0000Progress of 3D Organoid Technology for Preclinical Investigations: Towards Human In Vitro Models\u0000\u0000Yingjuan Liu *, Honglin Xu, Sabu Abraham, Xin Wang, and Bernard D. Keavney*\u0000\u0000\u0000Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, M13 9PT, UK.\u0000* Correspondence: yingjuan.liu@manchester.ac.uk (Yingjuan Liu);\u0000bernard.keavney@manchester.ac.uk (Bernard D. Keavney)\u0000 \u0000 \u0000Received: 1 November 2022\u0000Accepted: 24 November 2022\u0000Published: 21 December 2022\u0000 \u0000\u0000Abstract: Currently, with an increased requirement for new therapeutic strategies, preclinical drug testing or screening platforms have rapidly evolved in recent years. In comparison to traditional 2D cell cultures, 3D organoids or spheroids with or without scaffolds improve the microenvironment of in vitro cultures, advancing the in vitro biological observation and enabling mechanistic studies of drug reactions in the human tissue-like environment. 3D organoids and spheroids are straightforward to produce, and relatively uniform in size and shape. This helps to facilitate high throughput screening requirements. Spheroids and organoids have been applied in anti-cancer drug testing, toxicity evaluations, as well as mechanism studies for variable organ systems, including the intestine, liver, pancreas, brain, and heart. Among 3D cultures of spheroids and organoids, ‘tumour spheroids’ formed by dissociated tumour tissues or cancer cell lines are relatively simple in composition and commonly applied to anticancer drug screening. The ‘healthy organoids’ differentiated from hiPSCs/hESCs are more complex in cell composition, distribution, structure and function with higher similarity to in vivo organs, and have found applications in toxicity tests, personalised medicine, and therapeutic and mechanistic studies. In most cases, the multicellular 3D organoids are more resistant and stable in reaction to stimulations or chemicals in vitro , suggesting more accurate modelling of in vivo responses. Here, we review recent progress in human-origin organoid/spheroid systems and their applications in preclinical studies.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"132 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83743757","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}
Review From Bench to Bedside: Current Developments in RNA-Based Therapies for Treatment of Hyperlipidemia Yufei Zhou and Chen Chen * Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. * Correspondence: chenchen@tjh.tjmu.edu.cn; Tel. & Fax: 86-27-6937-8422. Received: 7 October 2022 Accepted: 1 November 2022 Published: 21 December 2022 Abstract: Hyperlipidemia is one of the conditions that constitute metabolic disorder and it is a common public health problem. The condition is characterized by increased levels of cholesterol, triglycerides and/or lipoproteins; it is a recognized as a risk factor for the onset of many diseases such as type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. Up to now, the primary drugs for treating hyperlipidemia are statins and monoclonal antibody drugs against proprotein convertase subtilisin/kexin type 9 (PCSK9). The main limitation of statins for long-term use is intolerable side effects. Evolocumab and Alirocumab, two monoclonal antibodies against PCSK9, can effectively decrease the level of low-density lipoprotein cholesterol (LDL-C) in patients with statin intolerance and familial hypercholesterolemia, while causing fewer side effects. However, due to its short half-life and high costs, these monoclonal antibody treatments might result in patients’ non-compliance with medication and considerable economic burden on patients. Given that RNA plays a key role in gene regulation, RNA-based therapeutics have become powerful blueprints for designing new anti-hyperlipidemia drugs. Here, we summarized RNA-based therapeutic strategies and the current clinical trials for RNA drugs in hyperlipidemia treatment.
{"title":"From Bench to Bedside: Current Developments in RNA-Based Therapies for Treatment of Hyperlipidemia","authors":"Yufei Zhou, Chen Chen","doi":"10.53941/ijddp.v1i1.141","DOIUrl":"https://doi.org/10.53941/ijddp.v1i1.141","url":null,"abstract":"Review\u0000From Bench to Bedside: Current Developments in RNA-Based Therapies for Treatment of Hyperlipidemia\u0000\u0000Yufei Zhou and Chen Chen *\u0000\u0000\u0000Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.\u0000* Correspondence: chenchen@tjh.tjmu.edu.cn; Tel. & Fax: 86-27-6937-8422.\u0000 \u0000 \u0000Received: 7 October 2022\u0000Accepted: 1 November 2022\u0000Published: 21 December 2022\u0000 \u0000\u0000Abstract: Hyperlipidemia is one of the conditions that constitute metabolic disorder and it is a common public health problem. The condition is characterized by increased levels of cholesterol, triglycerides and/or lipoproteins; it is a recognized as a risk factor for the onset of many diseases such as type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. Up to now, the primary drugs for treating hyperlipidemia are statins and monoclonal antibody drugs against proprotein convertase subtilisin/kexin type 9 (PCSK9). The main limitation of statins for long-term use is intolerable side effects. Evolocumab and Alirocumab, two monoclonal antibodies against PCSK9, can effectively decrease the level of low-density lipoprotein cholesterol (LDL-C) in patients with statin intolerance and familial hypercholesterolemia, while causing fewer side effects. However, due to its short half-life and high costs, these monoclonal antibody treatments might result in patients’ non-compliance with medication and considerable economic burden on patients. Given that RNA plays a key role in gene regulation, RNA-based therapeutics have become powerful blueprints for designing new anti-hyperlipidemia drugs. Here, we summarized RNA-based therapeutic strategies and the current clinical trials for RNA drugs in hyperlipidemia treatment.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81076074","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}
Shou-bao Wang, Zihan Wang, Lianhua Fang, Yang Lv, G. Du
Review Advances of the Target-Based and Phenotypic Screenings and Strategies in Drug Discovery Shoubao Wang 1,*, Zihan Wang1, Lianhua Fang1, Yang Lv2, and Guanhua Du1,* 1 Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. 2 Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. * Correspondence: shoubaowang@imm.ac.cn (Shoubao Wang); dugh@imm.ac.cn (Guanhua Du). Received: 8 November 2022 Accepted: 15 November 2022 Published: 21 December 2022 Abstract: Drug discovery and development is a complex and expensive process. There are two approaches, phenotypic and target-based approaches, each holding different advantages for screening novel drug candidates when pursuing successful marketing authorization. However, the attrition rates of drug candidates continue to increase. In this review, we discuss recent successes and ongoing advances in phenotypic screening and target-based screening for drug discovery. We also explore how strategic and technological innovations may fuel new approaches in drug discovery. There are two approaches in drug discovery.
{"title":"Advances of the Target-Based and Phenotypic Screenings and Strategies in Drug Discovery","authors":"Shou-bao Wang, Zihan Wang, Lianhua Fang, Yang Lv, G. Du","doi":"10.53941/ijddp.v1i1.199","DOIUrl":"https://doi.org/10.53941/ijddp.v1i1.199","url":null,"abstract":"Review\u0000Advances of the Target-Based and Phenotypic Screenings and Strategies in Drug Discovery\u0000\u0000Shoubao Wang 1,*, Zihan Wang1, Lianhua Fang1, Yang Lv2, and Guanhua Du1,*\u0000\u0000\u00001 Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.\u00002 Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.\u0000* Correspondence: shoubaowang@imm.ac.cn (Shoubao Wang); dugh@imm.ac.cn (Guanhua Du).\u0000 \u0000 \u0000Received: 8 November 2022\u0000Accepted: 15 November 2022\u0000Published: 21 December 2022\u0000 \u0000\u0000Abstract: Drug discovery and development is a complex and expensive process. There are two approaches, phenotypic and target-based approaches, each holding different advantages for screening novel drug candidates when pursuing successful marketing authorization. However, the attrition rates of drug candidates continue to increase. In this review, we discuss recent successes and ongoing advances in phenotypic screening and target-based screening for drug discovery. We also explore how strategic and technological innovations may fuel new approaches in drug discovery. There are two approaches in drug discovery.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82225834","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}
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