Pub Date : 2024-01-01Epub Date: 2024-03-12DOI: 10.1016/bs.apcsb.2024.02.001
Meenakshi Kandpal, Nidhi Varshney, Kunal Sameer Rawal, Hem Chandra Jha
The human gut microbiota is a complex and dynamic community of microorganisms, that influence metabolic, neurodevelopmental, and immune pathways. Microbial dysbiosis, characterized by changes in microbial diversity and relative abundances, is implicated in the development of various chronic neurological and neurodegenerative disorders. These disorders are marked by the accumulation of pathological protein aggregates, leading to the progressive loss of neurons and behavioural functions. Dysregulations in protein-protein interaction networks and signalling complexes, critical for normal brain function, are common in neurological disorders but challenging to unravel, particularly at the neuron and synapse-specific levels. To advance therapeutic strategies, a deeper understanding of neuropathogenesis, especially during the progressive disease phase, is needed. Biomarkers play a crucial role in identifying disease pathophysiology and monitoring disease progression. Proteomics, a powerful technology, shows promise in accelerating biomarker discovery and aiding in the development of novel treatments. In this chapter, we provide an in-depth overview of how proteomic techniques, utilizing various biofluid samples from patients with neurological conditions and diverse animal models, have contributed valuable insights into the pathogenesis of numerous neurological disorders. We also discuss the current state of research, potential challenges, and future directions in proteomic approaches to unravel neuro-pathological conditions.
{"title":"Gut dysbiosis and neurological modalities: An engineering approach via proteomic analysis of gut-brain axis.","authors":"Meenakshi Kandpal, Nidhi Varshney, Kunal Sameer Rawal, Hem Chandra Jha","doi":"10.1016/bs.apcsb.2024.02.001","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.02.001","url":null,"abstract":"<p><p>The human gut microbiota is a complex and dynamic community of microorganisms, that influence metabolic, neurodevelopmental, and immune pathways. Microbial dysbiosis, characterized by changes in microbial diversity and relative abundances, is implicated in the development of various chronic neurological and neurodegenerative disorders. These disorders are marked by the accumulation of pathological protein aggregates, leading to the progressive loss of neurons and behavioural functions. Dysregulations in protein-protein interaction networks and signalling complexes, critical for normal brain function, are common in neurological disorders but challenging to unravel, particularly at the neuron and synapse-specific levels. To advance therapeutic strategies, a deeper understanding of neuropathogenesis, especially during the progressive disease phase, is needed. Biomarkers play a crucial role in identifying disease pathophysiology and monitoring disease progression. Proteomics, a powerful technology, shows promise in accelerating biomarker discovery and aiding in the development of novel treatments. In this chapter, we provide an in-depth overview of how proteomic techniques, utilizing various biofluid samples from patients with neurological conditions and diverse animal models, have contributed valuable insights into the pathogenesis of numerous neurological disorders. We also discuss the current state of research, potential challenges, and future directions in proteomic approaches to unravel neuro-pathological conditions.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-02-24DOI: 10.1016/bs.apcsb.2023.11.009
Shivangi Mathur, Deeksha Singh, Rajiv Ranjan
The growing population, climate change, and limited agricultural resources put enormous pressure on agricultural systems. A plateau in crop yields is occurring and extreme weather events and urbanization threaten the livelihood of farmers. It is imperative that immediate attention is paid to addressing the increasing food demand, ensuring resilience against emerging threats, and meeting the demand for more nutritious, safer food. Under uncertain conditions, it is essential to expand genetic diversity and discover novel crop varieties or variations to develop higher and more stable yields. Genomics plays a significant role in developing abundant and nutrient-dense food crops. An alternative to traditional breeding approach, translational genomics is able to improve breeding programs in a more efficient and precise manner by translating genomic concepts into practical tools. Crop breeding based on genomics offers potential solutions to overcome the limitations of conventional breeding methods, including improved crop varieties that provide more nutritional value and are protected from biotic and abiotic stresses. Genetic markers, such as SNPs and ESTs, contribute to the discovery of QTLs controlling agronomic traits and stress tolerance. In order to meet the growing demand for food, there is a need to incorporate QTLs into breeding programs using marker-assisted selection/breeding and transgenic technologies. This chapter primarily focuses on the recent advances that are made in translational genomics for crop improvement and various omics techniques including transcriptomics, metagenomics, pangenomics, single cell omics etc. Numerous genome editing techniques including CRISPR Cas technology and their applications in crop improvement had been discussed.
不断增长的人口、气候变化和有限的农业资源给农业系统带来了巨大压力。作物产量出现高原现象,极端天气事件和城市化威胁着农民的生计。当务之急是立即关注如何应对日益增长的粮食需求,确保抵御新出现的威胁,满足人们对更有营养、更安全的粮食的需求。在不确定的条件下,必须扩大遗传多样性,发现新的作物品种或变种,以提高产量和稳定性。基因组学在开发营养丰富的粮食作物方面发挥着重要作用。作为传统育种方法的替代方案,转化基因组学通过将基因组概念转化为实用工具,能够更高效、更精确地改进育种计划。基于基因组学的作物育种为克服传统育种方法的局限性提供了潜在的解决方案,包括改良作物品种,使其具有更高的营养价值,并免受生物和非生物胁迫。SNP 和 EST 等遗传标记有助于发现控制农艺性状和抗逆性的 QTL。为了满足日益增长的粮食需求,有必要利用标记辅助选择/育种和转基因技术将 QTLs 纳入育种计划。本章主要介绍用于作物改良的转化基因组学的最新进展,以及包括转录组学、元基因组学、泛基因组学、单细胞组学等在内的各种组学技术。还讨论了包括 CRISPR Cas 技术在内的大量基因组编辑技术及其在作物改良中的应用。
{"title":"Recent advances in plant translational genomics for crop improvement.","authors":"Shivangi Mathur, Deeksha Singh, Rajiv Ranjan","doi":"10.1016/bs.apcsb.2023.11.009","DOIUrl":"10.1016/bs.apcsb.2023.11.009","url":null,"abstract":"<p><p>The growing population, climate change, and limited agricultural resources put enormous pressure on agricultural systems. A plateau in crop yields is occurring and extreme weather events and urbanization threaten the livelihood of farmers. It is imperative that immediate attention is paid to addressing the increasing food demand, ensuring resilience against emerging threats, and meeting the demand for more nutritious, safer food. Under uncertain conditions, it is essential to expand genetic diversity and discover novel crop varieties or variations to develop higher and more stable yields. Genomics plays a significant role in developing abundant and nutrient-dense food crops. An alternative to traditional breeding approach, translational genomics is able to improve breeding programs in a more efficient and precise manner by translating genomic concepts into practical tools. Crop breeding based on genomics offers potential solutions to overcome the limitations of conventional breeding methods, including improved crop varieties that provide more nutritional value and are protected from biotic and abiotic stresses. Genetic markers, such as SNPs and ESTs, contribute to the discovery of QTLs controlling agronomic traits and stress tolerance. In order to meet the growing demand for food, there is a need to incorporate QTLs into breeding programs using marker-assisted selection/breeding and transgenic technologies. This chapter primarily focuses on the recent advances that are made in translational genomics for crop improvement and various omics techniques including transcriptomics, metagenomics, pangenomics, single cell omics etc. Numerous genome editing techniques including CRISPR Cas technology and their applications in crop improvement had been discussed.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2023-11-22DOI: 10.1016/bs.apcsb.2023.11.001
Vladimir N Uversky
Intrinsically disordered proteins (IDPs), which are functional proteins without stable tertiary structure, and hybrid proteins containing ordered domains and intrinsically disordered regions (IDRs) constitute prominent parts of all proteomes collectively known as unfoldomes. IDPs/IDRs exist as highly dynamic structural ensembles of rapidly interconverting conformations and are characterized by the exceptional structural heterogeneity, where their different parts are (dis)ordered to different degree, and their overall structure represents a complex mosaic of foldons, inducible foldons, inducible morphing foldons, non-foldons, semifoldons, and even unfoldons. Despite their lack of unique 3D structures, IDPs/IDRs play crucial roles in the control of various biological processes and the regulation of different cellular pathways and are commonly involved in recognition and signaling, indicating that the disorder-based functional repertoire is complementary to the functions of ordered proteins. Furthermore, IDPs/IDRs are frequently multifunctional, and this multifunctionality is defined by their structural flexibility and heterogeneity. Intrinsic disorder phenomenon is at the roots of the structure-function continuum model, where the structure continuum is defined by the presence of differently (dis)ordered regions, and the function continuum arises from the ability of all these differently (dis)ordered parts to have different functions. In their everyday life, IDPs/IDRs utilize a broad spectrum of interaction mechanisms thereby acting as interaction specialists. They are crucial for the biogenesis of numerous proteinaceous membrane-less organelles driven by the liquid-liquid phase separation. This review introduces functional unfoldomics by representing some aspects of the intrinsic disorder-based functionality.
{"title":"Functional unfoldomics: Roles of intrinsic disorder in protein (multi)functionality.","authors":"Vladimir N Uversky","doi":"10.1016/bs.apcsb.2023.11.001","DOIUrl":"10.1016/bs.apcsb.2023.11.001","url":null,"abstract":"<p><p>Intrinsically disordered proteins (IDPs), which are functional proteins without stable tertiary structure, and hybrid proteins containing ordered domains and intrinsically disordered regions (IDRs) constitute prominent parts of all proteomes collectively known as unfoldomes. IDPs/IDRs exist as highly dynamic structural ensembles of rapidly interconverting conformations and are characterized by the exceptional structural heterogeneity, where their different parts are (dis)ordered to different degree, and their overall structure represents a complex mosaic of foldons, inducible foldons, inducible morphing foldons, non-foldons, semifoldons, and even unfoldons. Despite their lack of unique 3D structures, IDPs/IDRs play crucial roles in the control of various biological processes and the regulation of different cellular pathways and are commonly involved in recognition and signaling, indicating that the disorder-based functional repertoire is complementary to the functions of ordered proteins. Furthermore, IDPs/IDRs are frequently multifunctional, and this multifunctionality is defined by their structural flexibility and heterogeneity. Intrinsic disorder phenomenon is at the roots of the structure-function continuum model, where the structure continuum is defined by the presence of differently (dis)ordered regions, and the function continuum arises from the ability of all these differently (dis)ordered parts to have different functions. In their everyday life, IDPs/IDRs utilize a broad spectrum of interaction mechanisms thereby acting as interaction specialists. They are crucial for the biogenesis of numerous proteinaceous membrane-less organelles driven by the liquid-liquid phase separation. This review introduces functional unfoldomics by representing some aspects of the intrinsic disorder-based functionality.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139465950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Translational bioinformatics (TBI) has transformed healthcare by providing personalized medicine and tailored treatment options by integrating genomic data and clinical information. In recent years, TBI has bridged the gap between genome and clinical data because of significant advances in informatics like quantum computing and utilizing state-of-the-art technologies. This chapter discusses the power of translational bioinformatics in improving human health, from uncovering disease-causing genes and variations to establishing new therapeutic techniques. We discuss key application areas of bioinformatics in clinical genomics, such as data sources and methods used in translational bioinformatics, the impact of translational bioinformatics on human health, and how machine learning and artificial intelligence are being used to mine vast amounts of data for drug development and precision medicine. We also look at the problems, constraints, and ethical concerns connected with exploiting genomic data and the future of translational bioinformatics and its potential impact on medicine and human health. Ultimately, this chapter emphasizes the great potential of translational bioinformatics to alter healthcare and enhance patient outcomes.
{"title":"From genome to clinic: The power of translational bioinformatics in improving human health.","authors":"Satyendra Singh, Anurag Kumar Pandey, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2023.11.010","DOIUrl":"10.1016/bs.apcsb.2023.11.010","url":null,"abstract":"<p><p>Translational bioinformatics (TBI) has transformed healthcare by providing personalized medicine and tailored treatment options by integrating genomic data and clinical information. In recent years, TBI has bridged the gap between genome and clinical data because of significant advances in informatics like quantum computing and utilizing state-of-the-art technologies. This chapter discusses the power of translational bioinformatics in improving human health, from uncovering disease-causing genes and variations to establishing new therapeutic techniques. We discuss key application areas of bioinformatics in clinical genomics, such as data sources and methods used in translational bioinformatics, the impact of translational bioinformatics on human health, and how machine learning and artificial intelligence are being used to mine vast amounts of data for drug development and precision medicine. We also look at the problems, constraints, and ethical concerns connected with exploiting genomic data and the future of translational bioinformatics and its potential impact on medicine and human health. Ultimately, this chapter emphasizes the great potential of translational bioinformatics to alter healthcare and enhance patient outcomes.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-02-15DOI: 10.1016/bs.apcsb.2023.11.005
Vinay Kumar, Kunal Roy
This study presents a strategy for extracting significant gene complexes and then provides prospective therapeutics for AD. In this research, a total of 7905 reports published from 1981 to 2022 were retrieved. Following a review of all those articles, only the genetic association studies on AD were considered. Finally, there is a list of 453 Alzheimer-related genes in our dataset for network analysis. To this end, an experimentally derived protein-protein interaction (PPI) network from the String database was utilized to extract four meaningful gene complexes functionally interconnected using Cytoscape v3.9.1 software. The acquired gene complexes were subjected to an enrichment analysis using the ClueGO v2.5.9 tool to emphasize the most significant biological processes and pathways. Afterward, extracted gene complexes were used to extract the drugs related to AD from DGI v3.0 database and introduce some new drugs which may be helpful for this disease. Finally, a comprehensive network that included every gene connected to each gene complex group as well as the drug targets for each gene has been shown. Moreover, molecular docking studies have been performed with the selected compounds to identify the interaction pattern with the respective targets. Finally, we proposed a list of 62 compounds as multi-targeted directed drug-like compounds with a degree value between 2 and 5 and 30 compounds as target-specific drug-like compounds, which have not been proclaimed as AD-related drugs in prior scientific and medical investigations. Then, new drugs were suggested that can be experimentally examined for future work. In addition to this, four bipartite networks representing each group's genes and target miRNAs were established to introduce target miRNAs by using the miRWalk v3 server.
{"title":"Protein-protein interaction network analysis for the identification of novel multi-target inhibitors and target miRNAs against Alzheimer's disease.","authors":"Vinay Kumar, Kunal Roy","doi":"10.1016/bs.apcsb.2023.11.005","DOIUrl":"10.1016/bs.apcsb.2023.11.005","url":null,"abstract":"<p><p>This study presents a strategy for extracting significant gene complexes and then provides prospective therapeutics for AD. In this research, a total of 7905 reports published from 1981 to 2022 were retrieved. Following a review of all those articles, only the genetic association studies on AD were considered. Finally, there is a list of 453 Alzheimer-related genes in our dataset for network analysis. To this end, an experimentally derived protein-protein interaction (PPI) network from the String database was utilized to extract four meaningful gene complexes functionally interconnected using Cytoscape v3.9.1 software. The acquired gene complexes were subjected to an enrichment analysis using the ClueGO v2.5.9 tool to emphasize the most significant biological processes and pathways. Afterward, extracted gene complexes were used to extract the drugs related to AD from DGI v3.0 database and introduce some new drugs which may be helpful for this disease. Finally, a comprehensive network that included every gene connected to each gene complex group as well as the drug targets for each gene has been shown. Moreover, molecular docking studies have been performed with the selected compounds to identify the interaction pattern with the respective targets. Finally, we proposed a list of 62 compounds as multi-targeted directed drug-like compounds with a degree value between 2 and 5 and 30 compounds as target-specific drug-like compounds, which have not been proclaimed as AD-related drugs in prior scientific and medical investigations. Then, new drugs were suggested that can be experimentally examined for future work. In addition to this, four bipartite networks representing each group's genes and target miRNAs were established to introduce target miRNAs by using the miRWalk v3 server.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-02-15DOI: 10.1016/bs.apcsb.2023.11.006
Shahjahan, Joy Kumar Dey, Sanjay Kumar Dey
Bioinformatics is an interconnected subject of science dealing with diverse fields including biology, chemistry, physics, statistics, mathematics, and computer science as the key fields to answer complicated physiological problems. Key intention of bioinformatics is to store, analyze, organize, and retrieve essential information about genome, proteome, transcriptome, metabolome, as well as organisms to investigate the biological system along with its dynamics, if any. The outcome of bioinformatics depends on the type, quantity, and quality of the raw data provided and the algorithm employed to analyze the same. Despite several approved medicines available, cardiovascular disorders (CVDs) and cancers comprises of the two leading causes of human deaths. Understanding the unknown facts of both these non-communicable disorders is inevitable to discover new pathways, find new drug targets, and eventually newer drugs to combat them successfully. Since, all these goals involve complex investigation and handling of various types of macro- and small- molecules of the human body, bioinformatics plays a key role in such processes. Results from such investigation has direct human application and thus we call this filed as translational bioinformatics. Current book chapter thus deals with diverse scope and applications of this translational bioinformatics to find cure, diagnosis, and understanding the mechanisms of CVDs and cancers. Developing complex yet small or long algorithms to address such problems is very common in translational bioinformatics. Structure-based drug discovery or AI-guided invention of novel antibodies that too with super-high accuracy, speed, and involvement of considerably low amount of investment are some of the astonishing features of the translational bioinformatics and its applications in the fields of CVDs and cancers.
{"title":"Translational bioinformatics approach to combat cardiovascular disease and cancers.","authors":"Shahjahan, Joy Kumar Dey, Sanjay Kumar Dey","doi":"10.1016/bs.apcsb.2023.11.006","DOIUrl":"10.1016/bs.apcsb.2023.11.006","url":null,"abstract":"<p><p>Bioinformatics is an interconnected subject of science dealing with diverse fields including biology, chemistry, physics, statistics, mathematics, and computer science as the key fields to answer complicated physiological problems. Key intention of bioinformatics is to store, analyze, organize, and retrieve essential information about genome, proteome, transcriptome, metabolome, as well as organisms to investigate the biological system along with its dynamics, if any. The outcome of bioinformatics depends on the type, quantity, and quality of the raw data provided and the algorithm employed to analyze the same. Despite several approved medicines available, cardiovascular disorders (CVDs) and cancers comprises of the two leading causes of human deaths. Understanding the unknown facts of both these non-communicable disorders is inevitable to discover new pathways, find new drug targets, and eventually newer drugs to combat them successfully. Since, all these goals involve complex investigation and handling of various types of macro- and small- molecules of the human body, bioinformatics plays a key role in such processes. Results from such investigation has direct human application and thus we call this filed as translational bioinformatics. Current book chapter thus deals with diverse scope and applications of this translational bioinformatics to find cure, diagnosis, and understanding the mechanisms of CVDs and cancers. Developing complex yet small or long algorithms to address such problems is very common in translational bioinformatics. Structure-based drug discovery or AI-guided invention of novel antibodies that too with super-high accuracy, speed, and involvement of considerably low amount of investment are some of the astonishing features of the translational bioinformatics and its applications in the fields of CVDs and cancers.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-06-10DOI: 10.1016/bs.apcsb.2024.03.001
Yoshifumi Itoh
Multicellular organisms consist of cells and extracellular matrix (ECM). ECM creates a cellular microenvironment, and cells locally degrade the ECM according to their cellular activity. A major group of enzymes that modify ECM belongs to matrix metalloproteinases (MMPs) and play major roles in various pathophysiological events. ECM degradation by MMPs does not occur in all cellular surroundings but only where it is necessary, and cells achieve this by directionally secreting these proteolytic enzymes. Recent studies have indicated that such enzyme secretion is achieved by targeted vesicle transport along the microtubules, and several kinesin superfamily proteins (KIFs) have been identified as responsible motor proteins involved in the processes. This chapter discusses recent findings of the vesicle transport of MMPs and their roles.
{"title":"Vesicle transport of matrix metalloproteinases.","authors":"Yoshifumi Itoh","doi":"10.1016/bs.apcsb.2024.03.001","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.03.001","url":null,"abstract":"<p><p>Multicellular organisms consist of cells and extracellular matrix (ECM). ECM creates a cellular microenvironment, and cells locally degrade the ECM according to their cellular activity. A major group of enzymes that modify ECM belongs to matrix metalloproteinases (MMPs) and play major roles in various pathophysiological events. ECM degradation by MMPs does not occur in all cellular surroundings but only where it is necessary, and cells achieve this by directionally secreting these proteolytic enzymes. Recent studies have indicated that such enzyme secretion is achieved by targeted vesicle transport along the microtubules, and several kinesin superfamily proteins (KIFs) have been identified as responsible motor proteins involved in the processes. This chapter discusses recent findings of the vesicle transport of MMPs and their roles.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cardiovascular disease (CVD) and cancer are major contributors to global morbidity and mortality. This book chapter delves into the intricate relationship between the immune system and the pathogenesis of both cardiovascular and cancer diseases, exploring the roles of innate and adaptive immunities, immune regulation, and immunotherapy in these complex conditions. The innate immune system acts as the first line of defense against tissue damage and infection, with a significant impact on the initiation and progression of CVD and cancer. Endothelial dysfunction, a hallmark in CVD, shares commonalities with the tumor microenvironment in cancer, emphasizing the parallel involvement of the immune system in both conditions. The adaptive immune system, particularly T cells, contributes to prolonged inflammation in both CVD and cancer. Regulatory T cells and the intricate balance between different T cell subtypes influence disease progression, wound healing, and the outcomes of ischemic injury and cancer immunosurveillance. Dysregulation of immune homeostasis can lead to chronic inflammation, contributing to the development and progression of both CVD and cancer. Thus, immunotherapy emerged as a promising avenue for preventing and managing these diseases, with strategies targeting immune cell modulation, cytokine manipulation, immune checkpoint blockade, and tolerance induction. The impact of gut microbiota on CVD and cancer too is explored in this chapter, highlighting the role of gut leakiness, microbial metabolites, and the potential for microbiome-based interventions in cardiovascular and cancer immunotherapies. In conclusion, immunomodulatory strategies and immunotherapy hold promise in reshaping the landscape of cardiovascular and cancer health. Additionally, harnessing the gut microbiota for immune modulation presents a novel approach to prevent and manage these complex diseases, emphasizing the importance of personalized and precision medicine in healthcare. Ongoing research and clinical trials are expected to further elucidate the complex immunological underpinnings of CVD and cancer thereby refining these innovative approaches.
心血管疾病(CVD)和癌症是导致全球发病率和死亡率的主要因素。本书的这一章深入探讨了免疫系统与心血管疾病和癌症发病机制之间错综复杂的关系,探讨了先天性免疫和适应性免疫、免疫调节和免疫疗法在这些复杂疾病中的作用。先天性免疫系统是抵御组织损伤和感染的第一道防线,对心血管疾病和癌症的发生和发展具有重要影响。内皮功能障碍是心血管疾病的标志之一,与癌症的肿瘤微环境有共同之处,强调了免疫系统在这两种疾病中的平行参与。适应性免疫系统,尤其是 T 细胞,对心血管疾病和癌症的长期炎症都有影响。调节性 T 细胞和不同 T 细胞亚型之间错综复杂的平衡影响着疾病的进展、伤口愈合以及缺血性损伤和癌症免疫监视的结果。免疫平衡失调会导致慢性炎症,导致心血管疾病和癌症的发生和发展。因此,免疫疗法成为预防和控制这些疾病的一个很有前景的途径,其策略以免疫细胞调节、细胞因子操纵、免疫检查点阻断和耐受诱导为目标。本章还探讨了肠道微生物群对心血管疾病和癌症的影响,强调了肠道渗漏、微生物代谢物的作用,以及基于微生物群的干预措施在心血管和癌症免疫疗法中的潜力。总之,免疫调节策略和免疫疗法有望重塑心血管和癌症健康的格局。此外,利用肠道微生物群进行免疫调节是预防和控制这些复杂疾病的一种新方法,强调了个性化和精准医疗在医疗保健中的重要性。正在进行的研究和临床试验有望进一步阐明心血管疾病和癌症的复杂免疫学基础,从而完善这些创新方法。
{"title":"Engineering immune response to regulate cardiovascular disease and cancer.","authors":"Diksha Rani, Smaranjot Kaur, Shahjahan, Joy Kumar Dey, Sanjay Kumar Dey","doi":"10.1016/bs.apcsb.2023.12.004","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.12.004","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) and cancer are major contributors to global morbidity and mortality. This book chapter delves into the intricate relationship between the immune system and the pathogenesis of both cardiovascular and cancer diseases, exploring the roles of innate and adaptive immunities, immune regulation, and immunotherapy in these complex conditions. The innate immune system acts as the first line of defense against tissue damage and infection, with a significant impact on the initiation and progression of CVD and cancer. Endothelial dysfunction, a hallmark in CVD, shares commonalities with the tumor microenvironment in cancer, emphasizing the parallel involvement of the immune system in both conditions. The adaptive immune system, particularly T cells, contributes to prolonged inflammation in both CVD and cancer. Regulatory T cells and the intricate balance between different T cell subtypes influence disease progression, wound healing, and the outcomes of ischemic injury and cancer immunosurveillance. Dysregulation of immune homeostasis can lead to chronic inflammation, contributing to the development and progression of both CVD and cancer. Thus, immunotherapy emerged as a promising avenue for preventing and managing these diseases, with strategies targeting immune cell modulation, cytokine manipulation, immune checkpoint blockade, and tolerance induction. The impact of gut microbiota on CVD and cancer too is explored in this chapter, highlighting the role of gut leakiness, microbial metabolites, and the potential for microbiome-based interventions in cardiovascular and cancer immunotherapies. In conclusion, immunomodulatory strategies and immunotherapy hold promise in reshaping the landscape of cardiovascular and cancer health. Additionally, harnessing the gut microbiota for immune modulation presents a novel approach to prevent and manage these complex diseases, emphasizing the importance of personalized and precision medicine in healthcare. Ongoing research and clinical trials are expected to further elucidate the complex immunological underpinnings of CVD and cancer thereby refining these innovative approaches.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer is no longer recognized as a single disease but a collection of diseases each with its defining characteristics and behavior. Even within the same cancer type, there can be substantial heterogeneity at the molecular level. Cancer cells often accumulate various genetic mutations and epigenetic alterations over time, leading to a coexistence of distinct subpopulations of cells within the tumor. This tumor heterogeneity arises not only due to clonal outgrowth of cells with genetic mutations, but also due to interactions of tumor cells with the tumor microenvironment (TME). The latter is a dynamic ecosystem that includes cancer cells, immune cells, fibroblasts, endothelial cells, stromal cells, blood vessels, and extracellular matrix components, tumor-associated macrophages and secreted molecules. The complex interplay between tumor heterogeneity and the TME makes it difficult to develop one-size-fits-all treatments and is often the cause of therapeutic failure and resistance in solid cancers. Technological advances in the post-genomic era have given us cues regarding spatial and temporal tumor heterogeneity. Armed with this knowledge, oncologists are trying to target the unique genomic, epigenetic, and molecular landscape in the tumor cell that causes its oncogenic transformation in a particular patient. This has ushered in the era of personalized precision medicine (PPM). Immunotherapy, on the other hand, involves leveraging the body's immune system to recognize and attack cancer cells and spare healthy cells from the damage induced by radiation and chemotherapy. Combining PPM and immunotherapy represents a paradigm shift in cancer treatment and has emerged as a promising treatment modality for several solid cancers. In this chapter, we summarise major types of cancer immunotherapy and discuss how they are being used for precision medicine in different solid tumors.
{"title":"Immunotherapy guided precision medicine in solid tumors.","authors":"Sanjana Mehrotra, Manu Kupani, Jaismeen Kaur, Jashandeep Kaur, Rajeev Kumar Pandey","doi":"10.1016/bs.apcsb.2024.02.004","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.02.004","url":null,"abstract":"<p><p>Cancer is no longer recognized as a single disease but a collection of diseases each with its defining characteristics and behavior. Even within the same cancer type, there can be substantial heterogeneity at the molecular level. Cancer cells often accumulate various genetic mutations and epigenetic alterations over time, leading to a coexistence of distinct subpopulations of cells within the tumor. This tumor heterogeneity arises not only due to clonal outgrowth of cells with genetic mutations, but also due to interactions of tumor cells with the tumor microenvironment (TME). The latter is a dynamic ecosystem that includes cancer cells, immune cells, fibroblasts, endothelial cells, stromal cells, blood vessels, and extracellular matrix components, tumor-associated macrophages and secreted molecules. The complex interplay between tumor heterogeneity and the TME makes it difficult to develop one-size-fits-all treatments and is often the cause of therapeutic failure and resistance in solid cancers. Technological advances in the post-genomic era have given us cues regarding spatial and temporal tumor heterogeneity. Armed with this knowledge, oncologists are trying to target the unique genomic, epigenetic, and molecular landscape in the tumor cell that causes its oncogenic transformation in a particular patient. This has ushered in the era of personalized precision medicine (PPM). Immunotherapy, on the other hand, involves leveraging the body's immune system to recognize and attack cancer cells and spare healthy cells from the damage induced by radiation and chemotherapy. Combining PPM and immunotherapy represents a paradigm shift in cancer treatment and has emerged as a promising treatment modality for several solid cancers. In this chapter, we summarise major types of cancer immunotherapy and discuss how they are being used for precision medicine in different solid tumors.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It is critical to emphasize the importance of vaccination as it protects us against harmful pathogens. Despite significant progress in vaccine development, there is an ongoing need to develop vaccines that are not only safe but also highly effective in protecting against severe infections. Subunit vaccines are generally safe, but they frequently fail to elicit strong immune responses. As a result, there is a need to improve vaccine effectiveness by combining them with adjuvants, which have the potential to boost the immune system many folds. The process of developing these adjuvants requires searching for molecules capable of activating the immune system, combining these promising compounds with an antigen, and then testing this combination using animal models before approving it for clinical use. Liposomal adjuvants work as delivery adjuvants and its activity depends on certain parameters such as surface charge, vesicle size, surface modification and route of administration. Self-assembly property of peptide adjuvants and discovery of hybrid peptides have widened the scope of peptides in vaccine formulations. Since most pathogenic molecules are not peptide based, phage display technique allows for screening peptide mimics for such pathogens that have potential as adjuvants. This chapter discusses about peptide and liposome-based adjuvants focusing on their properties imparting adjuvanticity along with the methods of formulating them. Methods of adjuvant characterization important for an adjuvant to be approved for clinical trials are also discussed. These include assays for cytotoxicity, T-lymphocyte proliferation, dendritic cell maturation, cytokine and antibody production, toll-like receptor dependent signaling and adjuvant half-life.
{"title":"Exploring structural engineering approach to formulate and characterize next-generation adjuvants.","authors":"Aditi Rattan, Takhellambam Malemnganba, Sagar, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2023.12.020","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.12.020","url":null,"abstract":"<p><p>It is critical to emphasize the importance of vaccination as it protects us against harmful pathogens. Despite significant progress in vaccine development, there is an ongoing need to develop vaccines that are not only safe but also highly effective in protecting against severe infections. Subunit vaccines are generally safe, but they frequently fail to elicit strong immune responses. As a result, there is a need to improve vaccine effectiveness by combining them with adjuvants, which have the potential to boost the immune system many folds. The process of developing these adjuvants requires searching for molecules capable of activating the immune system, combining these promising compounds with an antigen, and then testing this combination using animal models before approving it for clinical use. Liposomal adjuvants work as delivery adjuvants and its activity depends on certain parameters such as surface charge, vesicle size, surface modification and route of administration. Self-assembly property of peptide adjuvants and discovery of hybrid peptides have widened the scope of peptides in vaccine formulations. Since most pathogenic molecules are not peptide based, phage display technique allows for screening peptide mimics for such pathogens that have potential as adjuvants. This chapter discusses about peptide and liposome-based adjuvants focusing on their properties imparting adjuvanticity along with the methods of formulating them. Methods of adjuvant characterization important for an adjuvant to be approved for clinical trials are also discussed. These include assays for cytotoxicity, T-lymphocyte proliferation, dendritic cell maturation, cytokine and antibody production, toll-like receptor dependent signaling and adjuvant half-life.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}