Pub Date : 2024-07-12DOI: 10.3390/biologics4030016
Samantha J. Pralle, Stephanie K. Gatrell, Cassidy C. Keating, Susan M. Moore
The measurement of rabies-neutralizing antibody is important for monitoring the response to rabies vaccination. For all the purposes of measurement, such as routine monitoring of vaccine response in humans and animals, serosurveys, and biologics qualification, accurate and precise results are necessary. The risks associated with sample handling variation, which may impact the test results, can be overlooked within a laboratory. To determine the robustness of rabies-neutralizing antibodies in human and animal serum, samples were treated to mimic various possible deviations in the sample handling protocols. Potential deviations were designed to investigate common client inquiries and possible sample conditions experienced during shipping, storage, and laboratory processes. The treatments included the duration that sera were kept at a temperature greater than that of a refrigerator (room temperature, zero hours to two weeks), the number and duration of heat inactivation treatments (i.e., heat inactivation directly from freezer storage, etc.), the number of freeze–thaw cycles (zero, four, or six cycles), and the storage duration of sample dilutions in chamber slides before the addition of virus (zero hours to overnight). The results provided evidence for the robustness of rabies antibodies and the antibodies’ neutralizing function in uncontaminated, clear human and animal serum. In addition, prolonged heat exposure was identified as exerting the greatest impact on the measurement of rabies antibodies.
{"title":"The Effect of Sample Handling on Rabies-Neutralizing Antibody Stability","authors":"Samantha J. Pralle, Stephanie K. Gatrell, Cassidy C. Keating, Susan M. Moore","doi":"10.3390/biologics4030016","DOIUrl":"https://doi.org/10.3390/biologics4030016","url":null,"abstract":"The measurement of rabies-neutralizing antibody is important for monitoring the response to rabies vaccination. For all the purposes of measurement, such as routine monitoring of vaccine response in humans and animals, serosurveys, and biologics qualification, accurate and precise results are necessary. The risks associated with sample handling variation, which may impact the test results, can be overlooked within a laboratory. To determine the robustness of rabies-neutralizing antibodies in human and animal serum, samples were treated to mimic various possible deviations in the sample handling protocols. Potential deviations were designed to investigate common client inquiries and possible sample conditions experienced during shipping, storage, and laboratory processes. The treatments included the duration that sera were kept at a temperature greater than that of a refrigerator (room temperature, zero hours to two weeks), the number and duration of heat inactivation treatments (i.e., heat inactivation directly from freezer storage, etc.), the number of freeze–thaw cycles (zero, four, or six cycles), and the storage duration of sample dilutions in chamber slides before the addition of virus (zero hours to overnight). The results provided evidence for the robustness of rabies antibodies and the antibodies’ neutralizing function in uncontaminated, clear human and animal serum. In addition, prolonged heat exposure was identified as exerting the greatest impact on the measurement of rabies antibodies.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"30 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141653802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-05DOI: 10.3390/biologics4020014
S. Goenka
Hyperpigmentation skin disorders are marked by an abnormal accumulation or export of melanin pigment synthesized within melanocytes and pose a significant aesthetic concern. The search for novel natural compounds that exhibit pharmacological potential for treating pigmentation disorders is growing. In this study, kahweol (KW) and cafestol (CFS), two structural analogs of coffee diterpenes, were evaluated and compared for their effects on melanogenesis using B16F10 mouse melanoma cells and primary human melanocytes derived from Asian and African American skin. To the best of our knowledge, there are no reports of the effects of KW and CFS on melanogenesis yet. We first screened nontoxic concentrations of both compounds using an MTS assay after 72 h incubations and subsequently tested their effects on melanin synthesis and export. Cellular tyrosinase activity and cell-free mushroom tyrosinase activity were assayed to study the mechanisms of melanogenesis suppression. Human melanocytes from a moderately pigmented donor (HEMn-MP cells) and from a darkly pigmented donor (HEMn-DP cells) were next examined, and effects on cellular viability, melanin content, cellular tyrosinase activity, and melanin export (quantitated via dendricity) were similarly examined for both compounds. Our results show that KW and CFS did not significantly affect intracellular melanin content but suppressed extracellular melanin in B16F10 cells and dendritic parameters in human melanocytes, indicating their unique capacity to target extracellular melanogenesis and melanin export. Although KW showed a greater extracellular melanogenesis inhibitory capacity in B16F10 cells, in both primary melanocyte cells, CFS emerged as a potent inhibitor of melanin export compared to KW. Together, these results reveal novel modes of action of both compounds and indicate a promise to use CFS as a novel candidate for treating hyperpigmentation disorders of the human skin for clinical and cosmetic use. Additional research is necessary to shed light on the molecular pathways and the efficacy of melanogenesis inhibition by CFS in 3D human skin equivalents and in vivo studies.
{"title":"Two Coffee Diterpenes, Kahweol and Cafestol, Inhibit Extracellular Melanogenesis: An In Vitro Pilot Study","authors":"S. Goenka","doi":"10.3390/biologics4020014","DOIUrl":"https://doi.org/10.3390/biologics4020014","url":null,"abstract":"Hyperpigmentation skin disorders are marked by an abnormal accumulation or export of melanin pigment synthesized within melanocytes and pose a significant aesthetic concern. The search for novel natural compounds that exhibit pharmacological potential for treating pigmentation disorders is growing. In this study, kahweol (KW) and cafestol (CFS), two structural analogs of coffee diterpenes, were evaluated and compared for their effects on melanogenesis using B16F10 mouse melanoma cells and primary human melanocytes derived from Asian and African American skin. To the best of our knowledge, there are no reports of the effects of KW and CFS on melanogenesis yet. We first screened nontoxic concentrations of both compounds using an MTS assay after 72 h incubations and subsequently tested their effects on melanin synthesis and export. Cellular tyrosinase activity and cell-free mushroom tyrosinase activity were assayed to study the mechanisms of melanogenesis suppression. Human melanocytes from a moderately pigmented donor (HEMn-MP cells) and from a darkly pigmented donor (HEMn-DP cells) were next examined, and effects on cellular viability, melanin content, cellular tyrosinase activity, and melanin export (quantitated via dendricity) were similarly examined for both compounds. Our results show that KW and CFS did not significantly affect intracellular melanin content but suppressed extracellular melanin in B16F10 cells and dendritic parameters in human melanocytes, indicating their unique capacity to target extracellular melanogenesis and melanin export. Although KW showed a greater extracellular melanogenesis inhibitory capacity in B16F10 cells, in both primary melanocyte cells, CFS emerged as a potent inhibitor of melanin export compared to KW. Together, these results reveal novel modes of action of both compounds and indicate a promise to use CFS as a novel candidate for treating hyperpigmentation disorders of the human skin for clinical and cosmetic use. Additional research is necessary to shed light on the molecular pathways and the efficacy of melanogenesis inhibition by CFS in 3D human skin equivalents and in vivo studies.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"18 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141385205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-14DOI: 10.3390/biologics4020012
Shahed Kamal, S. W. Lo, Samantha McCall, Beverly Rodrigues, Andrew H. Tsoi, Jonathan P. Segal
Background: Janus kinase (JAK) inhibitors represent a novel class of oral therapies showing efficacy in treating ulcerative colitis (UC) and Crohn’s disease (CD), challenging conventional treatment paradigms. Summary: This review provides an overview of the potential novel uses of JAK inhibitors, focusing on their current approved indications and exploring possibilities beyond these indications. Tofacitinib and filgotinib are approved for UC, while upadacitinib is approved for both UC and CD. Additionally, their potential in acute severe UC, as steroid alternatives, and in managing fistulizing CD or extraintestinal manifestations are discussed. Key Message: JAK inhibitors play an important role in IBD (inflammatory bowel disease) treatment; however, clinicians must balance their promising efficacy with safety concerns. Individualized care and vigilance are essential for optimizing therapeutic benefits while mitigating potential adverse effects. Further research is necessary to clarify their efficacy, safety, and potential applications.
背景：Janus激酶（JAK）抑制剂是一类新型口服疗法，在治疗溃疡性结肠炎（UC）和克罗恩病（CD）方面疗效显著，对传统治疗模式提出了挑战。摘要：本综述概述了JAK抑制剂的潜在新用途，重点关注其目前已获批准的适应症，并探讨了这些适应症之外的可能性。托法替尼（Tofacitinib）和非尔戈替尼（filgotinib）已获批用于UC，而乌达替尼（upadacitinib）已获批用于UC和CD。此外，还讨论了这些药物在急性重症 UC 中的潜力、作为类固醇替代药物的潜力以及在治疗瘘性 CD 或肠道外表现方面的潜力。关键信息：JAK 抑制剂在 IBD（炎症性肠病）治疗中发挥着重要作用；然而，临床医生必须在其良好疗效与安全性之间取得平衡。在减轻潜在不良反应的同时，个体化护理和警惕对于优化治疗效果至关重要。有必要开展进一步研究，以明确其疗效、安全性和潜在应用。
{"title":"Unveiling the Potential of JAK Inhibitors in Inflammatory Bowel Disease","authors":"Shahed Kamal, S. W. Lo, Samantha McCall, Beverly Rodrigues, Andrew H. Tsoi, Jonathan P. Segal","doi":"10.3390/biologics4020012","DOIUrl":"https://doi.org/10.3390/biologics4020012","url":null,"abstract":"Background: Janus kinase (JAK) inhibitors represent a novel class of oral therapies showing efficacy in treating ulcerative colitis (UC) and Crohn’s disease (CD), challenging conventional treatment paradigms. Summary: This review provides an overview of the potential novel uses of JAK inhibitors, focusing on their current approved indications and exploring possibilities beyond these indications. Tofacitinib and filgotinib are approved for UC, while upadacitinib is approved for both UC and CD. Additionally, their potential in acute severe UC, as steroid alternatives, and in managing fistulizing CD or extraintestinal manifestations are discussed. Key Message: JAK inhibitors play an important role in IBD (inflammatory bowel disease) treatment; however, clinicians must balance their promising efficacy with safety concerns. Individualized care and vigilance are essential for optimizing therapeutic benefits while mitigating potential adverse effects. Further research is necessary to clarify their efficacy, safety, and potential applications.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"26 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140980485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-11DOI: 10.3390/biologics4020011
K. Habashy, Saad Omais, Benedikt Haupt, A. Sonabend, Christopher S. Ahuja
Traumatic Brain Injury (TBI) is a debilitating condition that poses a significant public health concern. Historically linked to motor vehicle accidents, the epidemiology of TBI has evolved. Falls now emerge as the predominant cause, particularly among older adults. Sport-related TBIs have also garnered increased attention due to concerns regarding long-term neurological sequelae. To date, therapeutic interventions remain limited and have yet to yield substantial clinical benefits. Cell-based therapies offer promising avenues for neural repair and regeneration: endogenous stem cell therapies capitalize on endogenous pools that can be triggered by the injury and further enhanced by therapeutic approaches. In contrast, exogenous cell therapies provide an exogenous source of cells. However, challenges such as age-related decline in neurogenesis, age-related inflammation, and the heterogeneity of TBI present significant hurdles to overcome. Moreover, translating stem cell research from the laboratory to clinical applications necessitates the adherence to good manufacturing practice standards, which presents distinct obstacles. Addressing these challenges requires a multifaceted approach, including careful patient selection in clinical trials, appropriate experimental models, and the optimization of therapeutic techniques. Ultimately, a combination of strategies is likely to yield the most promising outcomes in the pursuit of effective TBI therapies.
{"title":"Cell-Based Therapies for the Treatment of Traumatic Brain Injury: Promises and Trajectories","authors":"K. Habashy, Saad Omais, Benedikt Haupt, A. Sonabend, Christopher S. Ahuja","doi":"10.3390/biologics4020011","DOIUrl":"https://doi.org/10.3390/biologics4020011","url":null,"abstract":"Traumatic Brain Injury (TBI) is a debilitating condition that poses a significant public health concern. Historically linked to motor vehicle accidents, the epidemiology of TBI has evolved. Falls now emerge as the predominant cause, particularly among older adults. Sport-related TBIs have also garnered increased attention due to concerns regarding long-term neurological sequelae. To date, therapeutic interventions remain limited and have yet to yield substantial clinical benefits. Cell-based therapies offer promising avenues for neural repair and regeneration: endogenous stem cell therapies capitalize on endogenous pools that can be triggered by the injury and further enhanced by therapeutic approaches. In contrast, exogenous cell therapies provide an exogenous source of cells. However, challenges such as age-related decline in neurogenesis, age-related inflammation, and the heterogeneity of TBI present significant hurdles to overcome. Moreover, translating stem cell research from the laboratory to clinical applications necessitates the adherence to good manufacturing practice standards, which presents distinct obstacles. Addressing these challenges requires a multifaceted approach, including careful patient selection in clinical trials, appropriate experimental models, and the optimization of therapeutic techniques. Ultimately, a combination of strategies is likely to yield the most promising outcomes in the pursuit of effective TBI therapies.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":" 370","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140989738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-19DOI: 10.3390/biologics4020010
Nikolaos Evangelidis, P. Evangelidis
Cardiovascular disease remains the main cause of mortality in the 21st century. Hypertension, vessel atherosclerosis, and familial hypercholesterolemia (FH) are responsible for increased mortality and morbidity in patients. Therapies for cardiovascular disease are based on drug treatment options, but in the era of precision medicine, personalized treatments are being developed. Studies have shown that these conditions have a strong genetic background, creating an opportunity for the implementation of gene therapy for these diseases. Currently, gene therapy is not widely used in clinical practice. Recent advances in this research field are making gene therapy a very promising preventive and therapeutic tool for cardiovascular disease. Essential hypertension’s (EH) pathophysiology is mostly based on the activation of both the sympathetic nervous system and the renin angiotensin aldosterone system (RAAS), natriuretic peptide production, and endothelial dysfunction. Plasmid DNA and viral vectors can be used, targeting the main mechanisms in the pathogenesis of EH. Many preclinical studies have been developed across the years, presenting a significant decrease in blood pressure. Nevertheless, no clinical studies have been developed studying the implementation of gene therapy in EH. Atherosclerotic damage is caused by monogenic diseases or is deteriorated by the activation of inflammation in the vessel wall. Gene therapy studies have been developed in the pre- and clinical phases targeting the lipoprotein and cholesterol metabolism and the inflammation of the vessels. FH is a common inherited metabolic disease associated with high levels of cholesterol in the blood. Clinical trials of gene therapy have been developed and presented optimistic results. In this review, the challenges of gene therapy for cardiovascular disease are outlined. Nevertheless, more clinical trials are needed to be performed for the development of convenient and safe drug schemes for our patients.
在 21 世纪，心血管疾病仍然是导致死亡的主要原因。高血压、血管粥样硬化和家族性高胆固醇血症（FH）是导致患者死亡率和发病率上升的原因。心血管疾病的治疗方法以药物治疗为主，但在精准医疗时代，个性化治疗方法正在被开发出来。研究表明，这些疾病有很强的遗传背景，这为针对这些疾病实施基因疗法创造了机会。目前，基因疗法尚未广泛应用于临床实践。这一研究领域的最新进展使基因疗法成为一种非常有前景的心血管疾病预防和治疗工具。本质性高血压（EH）的病理生理学主要基于交感神经系统和肾素血管紧张素醛固酮系统（RAAS）的激活、钠利肽的产生以及内皮功能障碍。质粒 DNA 和病毒载体可用于针对 EH 发病的主要机制。多年来已开展了许多临床前研究，结果显示血压显著下降。然而，目前还没有关于在 EH 中使用基因疗法的临床研究。动脉粥样硬化损伤是由单基因疾病引起的，或因血管壁的炎症激活而恶化。针对脂蛋白和胆固醇代谢以及血管炎症的基因治疗研究已进入前期和临床阶段。高胆固醇血症是一种常见的遗传代谢疾病，与血液中的高胆固醇水平有关。基因疗法的临床试验已经开展，并取得了令人乐观的结果。本综述概述了基因疗法治疗心血管疾病所面临的挑战。尽管如此，还需要进行更多的临床试验，以便为我们的患者开发出方便、安全的药物方案。
{"title":"Gene Therapy for Hypertension, Atherosclerosis, and Familial Hypercholesterolemia: The Old Concepts and the New Era","authors":"Nikolaos Evangelidis, P. Evangelidis","doi":"10.3390/biologics4020010","DOIUrl":"https://doi.org/10.3390/biologics4020010","url":null,"abstract":"Cardiovascular disease remains the main cause of mortality in the 21st century. Hypertension, vessel atherosclerosis, and familial hypercholesterolemia (FH) are responsible for increased mortality and morbidity in patients. Therapies for cardiovascular disease are based on drug treatment options, but in the era of precision medicine, personalized treatments are being developed. Studies have shown that these conditions have a strong genetic background, creating an opportunity for the implementation of gene therapy for these diseases. Currently, gene therapy is not widely used in clinical practice. Recent advances in this research field are making gene therapy a very promising preventive and therapeutic tool for cardiovascular disease. Essential hypertension’s (EH) pathophysiology is mostly based on the activation of both the sympathetic nervous system and the renin angiotensin aldosterone system (RAAS), natriuretic peptide production, and endothelial dysfunction. Plasmid DNA and viral vectors can be used, targeting the main mechanisms in the pathogenesis of EH. Many preclinical studies have been developed across the years, presenting a significant decrease in blood pressure. Nevertheless, no clinical studies have been developed studying the implementation of gene therapy in EH. Atherosclerotic damage is caused by monogenic diseases or is deteriorated by the activation of inflammation in the vessel wall. Gene therapy studies have been developed in the pre- and clinical phases targeting the lipoprotein and cholesterol metabolism and the inflammation of the vessels. FH is a common inherited metabolic disease associated with high levels of cholesterol in the blood. Clinical trials of gene therapy have been developed and presented optimistic results. In this review, the challenges of gene therapy for cardiovascular disease are outlined. Nevertheless, more clinical trials are needed to be performed for the development of convenient and safe drug schemes for our patients.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":" 404","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140682363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-15DOI: 10.3390/biologics4020009
Radina Andonova, Dzhaner Bashchobanov, Veronika Gadzhovska, Georgi Popov
Tick-borne diseases account for a large proportion of vector-borne illnesses. They include, for example, a variety of infections caused by bacteria, spirochetes, viruses, rickettsiae, and protozoa. We aim to present a review that demonstrates the connection between the diagnosis, treatment, prevention, and the significance of certain emergency tick-borne diseases in humans and their clinical–epidemiological features. This review covers three diseases: anaplasmosis, ehrlichiosis, and babesiosis. The emergence of ehrlichiosis and anaplasmosis is become more frequently diagnosed as the cause of human infections, as animal reservoirs and tick vectors have increased in numbers and humans have inhabited areas where reservoir and tick populations are high. They belong to the order Rickettsiales and the family Anaplasmataceae, and the clinical manifestations typically coexist. Furthermore, prompt diagnosis and appropriate treatment are critical to the patient’s recovery. Similar to malaria, babesiosis causes hemolysis. It is spread by intraerythrocytic protozoa, and the parasitemia dictates how severe it can get. Left untreated, some patients might have a fatal outcome. The correct diagnosis can be difficult sometimes; that is why an in-depth knowledge of the diseases is required. Prevention, prompt diagnosis, and treatment of these tick-borne diseases depend on the understanding of their clinical, epidemiological, and laboratory features.
{"title":"Tick-Borne Diseases—Still a Challenge: A Review","authors":"Radina Andonova, Dzhaner Bashchobanov, Veronika Gadzhovska, Georgi Popov","doi":"10.3390/biologics4020009","DOIUrl":"https://doi.org/10.3390/biologics4020009","url":null,"abstract":"Tick-borne diseases account for a large proportion of vector-borne illnesses. They include, for example, a variety of infections caused by bacteria, spirochetes, viruses, rickettsiae, and protozoa. We aim to present a review that demonstrates the connection between the diagnosis, treatment, prevention, and the significance of certain emergency tick-borne diseases in humans and their clinical–epidemiological features. This review covers three diseases: anaplasmosis, ehrlichiosis, and babesiosis. The emergence of ehrlichiosis and anaplasmosis is become more frequently diagnosed as the cause of human infections, as animal reservoirs and tick vectors have increased in numbers and humans have inhabited areas where reservoir and tick populations are high. They belong to the order Rickettsiales and the family Anaplasmataceae, and the clinical manifestations typically coexist. Furthermore, prompt diagnosis and appropriate treatment are critical to the patient’s recovery. Similar to malaria, babesiosis causes hemolysis. It is spread by intraerythrocytic protozoa, and the parasitemia dictates how severe it can get. Left untreated, some patients might have a fatal outcome. The correct diagnosis can be difficult sometimes; that is why an in-depth knowledge of the diseases is required. Prevention, prompt diagnosis, and treatment of these tick-borne diseases depend on the understanding of their clinical, epidemiological, and laboratory features.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"58 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140702654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-28DOI: 10.3390/biologics4020008
Y. Matsuzaka, R. Yashiro
Heparan sulfate proteoglycans are highly glycosylated proteins in which heparan sulfate, a glycosaminoglycan sugar chain, is an acidic sugar chain consisting of a repeating disaccharide structure of glucuronic acid and N-acetylglucosamine is locally sulfated. Syndecan, one of the transmembrane HSPGs, functions as a receptor that transmits signals from the extracellular microenvironment to the inside of the cell. In the vascular system, heparan sulfate proteoglycans, a major component of the glycocalyx, enable the binding of various plasma-derived molecules due to their diversity, epimerization of glycosaminoglycans chains, long chains, and sulfation. Heparan sulfate proteoglycans present in the extracellular matrix serve as a reservoir for bioactive molecules such as chemokines, cytokines, and growth factors. Aberrant expression of heparan sulfate proteoglycans, heparanase, and sulfatase is observed in many pathological conditions. Therefore, it can be applied to therapeutic strategies for a wide range of fields including Alzheimer’s disease, heart failure, cancer, organ transplants, diabetes, chronic inflammation, aging, and autoimmune diseases.
{"title":"Classification and Molecular Functions of Heparan Sulfate Proteoglycans and Their Molecular Mechanisms with the Receptor","authors":"Y. Matsuzaka, R. Yashiro","doi":"10.3390/biologics4020008","DOIUrl":"https://doi.org/10.3390/biologics4020008","url":null,"abstract":"Heparan sulfate proteoglycans are highly glycosylated proteins in which heparan sulfate, a glycosaminoglycan sugar chain, is an acidic sugar chain consisting of a repeating disaccharide structure of glucuronic acid and N-acetylglucosamine is locally sulfated. Syndecan, one of the transmembrane HSPGs, functions as a receptor that transmits signals from the extracellular microenvironment to the inside of the cell. In the vascular system, heparan sulfate proteoglycans, a major component of the glycocalyx, enable the binding of various plasma-derived molecules due to their diversity, epimerization of glycosaminoglycans chains, long chains, and sulfation. Heparan sulfate proteoglycans present in the extracellular matrix serve as a reservoir for bioactive molecules such as chemokines, cytokines, and growth factors. Aberrant expression of heparan sulfate proteoglycans, heparanase, and sulfatase is observed in many pathological conditions. Therefore, it can be applied to therapeutic strategies for a wide range of fields including Alzheimer’s disease, heart failure, cancer, organ transplants, diabetes, chronic inflammation, aging, and autoimmune diseases.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"115 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140370722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-04DOI: 10.3390/biologics4010006
Wim Buijs
There is a continuous interest in cannabinoids like Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Previous experimental research has described the conversion of CBD to either Δ8-THC or Δ9-THC, depending on the acid catalyst applied. The use of para-toluene sulfonic acid (pTSA) has led to the formation of Δ8-THC, while boron trifluoride etherate (BF3·Et2O) has mainly yielded Δ9-THC. The enormous difference in product selectivity between these two catalysts was investigated with Molecular Modeling, applying quantum chemical density functional theory. It was found that pTSA leads to fast isomerization of Δ9-CBD to Δ8-CBD and subsequent ring closure to Δ8-THC. BF3·Et2O catalysis leads to the formation of tertiary carbenium ions in the transition states, which yield Δ9-THC and some iso THC. Under dry conditions in refluxing toluene, it was found that pTSA is predominantly present as a dimer, and only a small fraction is available as monomeric catalyst. Applying the computationally derived activation barriers in transition state theory yielded reaction rates that predicted the amounts of cannabinoids that are in close agreement with the experimental findings from the previous literature.
{"title":"A Molecular Modeling Study into Brønsted and Lewis Acid Catalyzed Conversion of CBD into Other Cannabinoids","authors":"Wim Buijs","doi":"10.3390/biologics4010006","DOIUrl":"https://doi.org/10.3390/biologics4010006","url":null,"abstract":"There is a continuous interest in cannabinoids like Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Previous experimental research has described the conversion of CBD to either Δ8-THC or Δ9-THC, depending on the acid catalyst applied. The use of para-toluene sulfonic acid (pTSA) has led to the formation of Δ8-THC, while boron trifluoride etherate (BF3·Et2O) has mainly yielded Δ9-THC. The enormous difference in product selectivity between these two catalysts was investigated with Molecular Modeling, applying quantum chemical density functional theory. It was found that pTSA leads to fast isomerization of Δ9-CBD to Δ8-CBD and subsequent ring closure to Δ8-THC. BF3·Et2O catalysis leads to the formation of tertiary carbenium ions in the transition states, which yield Δ9-THC and some iso THC. Under dry conditions in refluxing toluene, it was found that pTSA is predominantly present as a dimer, and only a small fraction is available as monomeric catalyst. Applying the computationally derived activation barriers in transition state theory yielded reaction rates that predicted the amounts of cannabinoids that are in close agreement with the experimental findings from the previous literature.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"89 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140079995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-23DOI: 10.3390/biologics4010005
Tiantian Zhang, Zhe Wang
Thirty-four years ago, the groundbreaking work of John McCafferty and Sir Gregory Winter in developing phage display technology revolutionized the discovery of human antibodies, paving the way for diverse applications. Since then, numerous phage-derived antibodies have been successfully developed and advanced into clinical studies, resulting in the approval of more than a dozen therapeutic antibodies. These antibodies have demonstrated efficacy across a spectrum of medical conditions, ranging from autoimmune diseases to various cancers. In this article, we provide an in-depth review of the development of phage display libraries as powerful platforms for therapeutic antibody discovery, elucidating the intricate procedures involved in antibody development. Additionally, we conduct a review of the current ntibody drugs for cancer treatment that have been developed using the phage display platform. Furthermore, we discuss the challenges inherent in this technology, offering insights into potential solutions to enhance crucial steps and facilitate more efficient drug discovery in the field of phage display technology.
{"title":"Monoclonal Antibody Development for Cancer Treatment Using the Phage Display Library Platform","authors":"Tiantian Zhang, Zhe Wang","doi":"10.3390/biologics4010005","DOIUrl":"https://doi.org/10.3390/biologics4010005","url":null,"abstract":"Thirty-four years ago, the groundbreaking work of John McCafferty and Sir Gregory Winter in developing phage display technology revolutionized the discovery of human antibodies, paving the way for diverse applications. Since then, numerous phage-derived antibodies have been successfully developed and advanced into clinical studies, resulting in the approval of more than a dozen therapeutic antibodies. These antibodies have demonstrated efficacy across a spectrum of medical conditions, ranging from autoimmune diseases to various cancers. In this article, we provide an in-depth review of the development of phage display libraries as powerful platforms for therapeutic antibody discovery, elucidating the intricate procedures involved in antibody development. Additionally, we conduct a review of the current ntibody drugs for cancer treatment that have been developed using the phage display platform. Furthermore, we discuss the challenges inherent in this technology, offering insights into potential solutions to enhance crucial steps and facilitate more efficient drug discovery in the field of phage display technology.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"64 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140436893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.3390/biologics4010004
L. Nosetti, Claudio Tirelli, F. Marino, M. Gaiazzi, Lucia Sacchi, Mara De Amici, F. Barocci, R. Maio, M. Cosentino, Luigi Nespoli
Introduction: Obstructive Sleep Apnea (OSA) in children is characterized by repeated episodes of partial or complete obstruction of the upper airways that impair normal ventilation and cause hypoxia and sleep disruption. These episodes activate innate and adaptive immunity resulting in the production of proinflammatory cytokines: IL-1β, IL-6, TNF-α, and reactive oxygen species. The hypothalamic–pituitary–adrenal (HPT) axis is also activated with alteration of the circadian rhythm of cortisol synthesis. OSA in children, and even more in adults, induces a systemic inflammatory condition that contributes to the genesis of clinical complications: poor growth, learning disabilities, cardiovascular changes, insulin resistance, and metabolic syndrome. Methods: A total of 42 non-obese children (age 1–15 years) were enrolled among those sent to our sleep center to perform full polysomnography (PSG). After PSG, 6 children did not show OSA (controls), 20 had mild OSA (m OSA), and 16 had medium-severe OSA (MS OSA). In vitro IL-1β, TNF-α, and serum cortisol levels were measured at 2 and 8 am in the analyzed groups. Results: Cortisol levels did not differ between controls and OSA children. At 2 am, there were no differences between controls and OSA in TNF-α production, whereas at 8 am, TNF-α was reduced in MS-OSA. IL-1β production showed no differences between OSA and controls. Conclusions: In our population, only TNF-α production is suppressed in MS-OSA: this might indicate a role of OSA severity in inducing inflammation. In adults, the phenomenon is more pronounced due to the habitual greater severity/duration of OSA, presence of comorbidities (cardiovascular and metabolic), and different immune system function.
导言：儿童阻塞性睡眠呼吸暂停（OSA）的特点是反复发作的上呼吸道部分或完全阻塞，影响正常通气，导致缺氧和睡眠障碍。这些发作会激活先天性和适应性免疫，导致促炎细胞因子的产生：IL-1β、IL-6、TNF-α 和活性氧。下丘脑-垂体-肾上腺（HPT）轴也会随着皮质醇合成昼夜节律的改变而被激活。儿童的 OSA 会诱发全身性炎症，成人的情况更为严重，从而导致临床并发症：发育不良、学习障碍、心血管变化、胰岛素抵抗和代谢综合征。研究方法在被送往睡眠中心进行全面多导睡眠图检查的儿童中，共选取了 42 名非肥胖儿童（1-15 岁）。PSG检查后，6名儿童未发现OSA（对照组），20名儿童患有轻度OSA（m OSA），16名儿童患有中重度OSA（MS OSA）。分析组分别在凌晨 2 点和 8 点测量了体外 IL-1β、TNF-α 和血清皮质醇水平。结果显示对照组和 OSA 儿童的皮质醇水平没有差异。凌晨2点，TNF-α的产生在对照组和OSA之间没有差异，而在早晨8点，TNF-α在MS-OSA中有所减少。IL-1β的产生在OSA和对照组之间没有差异。结论在我们的人群中，只有 TNF-α 的产生在 MS-OSA 中受到抑制：这可能表明 OSA 的严重程度在诱发炎症方面起了作用。在成人中，这种现象更为明显，原因是OSA的习惯性严重程度/持续时间更长、存在合并症（心血管和代谢）以及免疫系统功能不同。
{"title":"Cytokines and Obstructive Sleep Apnea in Childhood: Study of a Group of Children","authors":"L. Nosetti, Claudio Tirelli, F. Marino, M. Gaiazzi, Lucia Sacchi, Mara De Amici, F. Barocci, R. Maio, M. Cosentino, Luigi Nespoli","doi":"10.3390/biologics4010004","DOIUrl":"https://doi.org/10.3390/biologics4010004","url":null,"abstract":"Introduction: Obstructive Sleep Apnea (OSA) in children is characterized by repeated episodes of partial or complete obstruction of the upper airways that impair normal ventilation and cause hypoxia and sleep disruption. These episodes activate innate and adaptive immunity resulting in the production of proinflammatory cytokines: IL-1β, IL-6, TNF-α, and reactive oxygen species. The hypothalamic–pituitary–adrenal (HPT) axis is also activated with alteration of the circadian rhythm of cortisol synthesis. OSA in children, and even more in adults, induces a systemic inflammatory condition that contributes to the genesis of clinical complications: poor growth, learning disabilities, cardiovascular changes, insulin resistance, and metabolic syndrome. Methods: A total of 42 non-obese children (age 1–15 years) were enrolled among those sent to our sleep center to perform full polysomnography (PSG). After PSG, 6 children did not show OSA (controls), 20 had mild OSA (m OSA), and 16 had medium-severe OSA (MS OSA). In vitro IL-1β, TNF-α, and serum cortisol levels were measured at 2 and 8 am in the analyzed groups. Results: Cortisol levels did not differ between controls and OSA children. At 2 am, there were no differences between controls and OSA in TNF-α production, whereas at 8 am, TNF-α was reduced in MS-OSA. IL-1β production showed no differences between OSA and controls. Conclusions: In our population, only TNF-α production is suppressed in MS-OSA: this might indicate a role of OSA severity in inducing inflammation. In adults, the phenomenon is more pronounced due to the habitual greater severity/duration of OSA, presence of comorbidities (cardiovascular and metabolic), and different immune system function.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"39 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139824893","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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