Protein arginine methylation stands as a prevalent post-translational modification process, exerting vital roles in cellular signal transduction, gene expression, and cell cycle regulation. Amidst the protein arginine methyltransferase (PRMT) family, PRMT2 stands as a less explored constituent. Nonetheless, its regulatory roles in transcriptional regulation, post-transcriptional modification, methylation activity regulation, immunoregulation, and developmental regulation have garnered attention. These capabilities enable PRMT2 to exert pivotal regulatory functions in certain malignancies, metabolic disorders, inflammatory diseases, and atherosclerosis. In this review, we highlight the structure and functions of PRMT2, emphasizing its association with diseases. We also discuss PRMT2 inhibitors and explore the potential for therapeutic targeting.
{"title":"Advances in Research on Protein Arginine Methyltransferase 2: Functions and Diseases.","authors":"Zhen-Qi Min, Ming-Jun Jiang, Xi-Lian Liu, Su-Peng Yuan, Ping-An Chen, Chu-Hao Wang, Ya-Jun Chen, Xian-Peng Dai","doi":"10.2174/0109298665281395231211060535","DOIUrl":"10.2174/0109298665281395231211060535","url":null,"abstract":"<p><p>Protein arginine methylation stands as a prevalent post-translational modification process, exerting vital roles in cellular signal transduction, gene expression, and cell cycle regulation. Amidst the protein arginine methyltransferase (PRMT) family, PRMT2 stands as a less explored constituent. Nonetheless, its regulatory roles in transcriptional regulation, post-transcriptional modification, methylation activity regulation, immunoregulation, and developmental regulation have garnered attention. These capabilities enable PRMT2 to exert pivotal regulatory functions in certain malignancies, metabolic disorders, inflammatory diseases, and atherosclerosis. In this review, we highlight the structure and functions of PRMT2, emphasizing its association with diseases. We also discuss PRMT2 inhibitors and explore the potential for therapeutic targeting.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0109298665272845231121064717
Vladislav Victorovich Khrustalev, Aleksander Nicolaevich Stojarov, Anastasia Aleksandrovna Akunevich, Oleg Evgenyevich Baranov, Anna Vladimirovna Popinako, Elena Olegovna Samoilovich, Marina Anatolyevna Yermalovich, Galina Valeryevna Semeiko, Egor Gennadyevich Sapon, Victoria Igorevna Cheprasova, Nikolai Vladimirovich Shalygo, Victor Vitoldovich Poboinev, Tatyana Aleksandrovna Khrustaleva, Olga Victorovna Khrustaleva
Background: Binding appropriate cellular receptors is a crucial step of a lifecycle for any virus. Structure of receptor-binding domain for a viral surface protein has to be determined before the start of future drug design projects.
Objectives: Investigation of pH-induced changes in the secondary structure for a capsid peptide with loss of function mutation can shed some light on the mechanism of entrance.
Methods: Spectroscopic methods were accompanied by electrophoresis, ultrafiltration, and computational biochemistry.
Results: In this study, we showed that a peptide from the receptor-binding domain of Parvovirus B19 VP1 capsid (residues 13-31) is beta-structural at pH=7.4 in 0.01 M phosphate buffer, but alpha- helical at pH=5.0, according to the circular dichroism (CD) spectroscopy results. Results of infra- red (IR) spectroscopy showed that the same peptide exists in both alpha-helical and beta-structural conformations in partial dehydration conditions both at pH=7.4 and pH=5.0. In contrast, the peptide with Y20W mutation, which is known to block the internalization of the virus, forms mostly alpha-helical conformation in partial dehydration conditions at pH=7.4. According to our hypothesis, an intermolecular antiparallel beta structure formed by the wild-type peptide in its tetramers at pH=7.4 is the prototype of the similar intermolecular antiparallel beta structure formed by the corresponding part of Parvovirus B19 receptor-binding domain with its cellular receptor (AXL).
Conclusion: Loss of function Y20W substitution in VP1 capsid protein prevents the shift into the beta-structural state by the way of alpha helix stabilization and the decrease of its ability to turn into the disordered state.
{"title":"Structural Shifts of the Parvovirus B19 Capsid Receptor-binding Domain: A Peptide Study.","authors":"Vladislav Victorovich Khrustalev, Aleksander Nicolaevich Stojarov, Anastasia Aleksandrovna Akunevich, Oleg Evgenyevich Baranov, Anna Vladimirovna Popinako, Elena Olegovna Samoilovich, Marina Anatolyevna Yermalovich, Galina Valeryevna Semeiko, Egor Gennadyevich Sapon, Victoria Igorevna Cheprasova, Nikolai Vladimirovich Shalygo, Victor Vitoldovich Poboinev, Tatyana Aleksandrovna Khrustaleva, Olga Victorovna Khrustaleva","doi":"10.2174/0109298665272845231121064717","DOIUrl":"10.2174/0109298665272845231121064717","url":null,"abstract":"<p><strong>Background: </strong>Binding appropriate cellular receptors is a crucial step of a lifecycle for any virus. Structure of receptor-binding domain for a viral surface protein has to be determined before the start of future drug design projects.</p><p><strong>Objectives: </strong>Investigation of pH-induced changes in the secondary structure for a capsid peptide with loss of function mutation can shed some light on the mechanism of entrance.</p><p><strong>Methods: </strong>Spectroscopic methods were accompanied by electrophoresis, ultrafiltration, and computational biochemistry.</p><p><strong>Results: </strong>In this study, we showed that a peptide from the receptor-binding domain of Parvovirus B19 VP1 capsid (residues 13-31) is beta-structural at pH=7.4 in 0.01 M phosphate buffer, but alpha- helical at pH=5.0, according to the circular dichroism (CD) spectroscopy results. Results of infra- red (IR) spectroscopy showed that the same peptide exists in both alpha-helical and beta-structural conformations in partial dehydration conditions both at pH=7.4 and pH=5.0. In contrast, the peptide with Y20W mutation, which is known to block the internalization of the virus, forms mostly alpha-helical conformation in partial dehydration conditions at pH=7.4. According to our hypothesis, an intermolecular antiparallel beta structure formed by the wild-type peptide in its tetramers at pH=7.4 is the prototype of the similar intermolecular antiparallel beta structure formed by the corresponding part of Parvovirus B19 receptor-binding domain with its cellular receptor (AXL).</p><p><strong>Conclusion: </strong>Loss of function Y20W substitution in VP1 capsid protein prevents the shift into the beta-structural state by the way of alpha helix stabilization and the decrease of its ability to turn into the disordered state.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0109298665301698240404061300
Mohammadjavad Sotoudeheian
Metabolic dysfunction-associated Fatty Liver Disease (MAFLD) is a chronic liver disease characterized by the accumulation of fat in the liver and hepatic steatosis, which can progress to critical conditions, including Metabolic dysfunction-associated Steatohepatitis (MASH), liver fibrosis, hepatic cirrhosis, and hepatocellular carcinoma. Galectin-3, a member of the galectin family of proteins, has been involved in cascades that are responsible for the pathogenesis and progression of liver fibrosis in MAFLD. This review summarizes the present understanding of the role of galectin-3 in the severity of MAFLD and its associated liver fibrosis. The article assesses the underlying role of galectin-3-mediated fibrogenesis, including the triggering of hepatic stellate cells, the regulation of extracellular degradation, and the modulation of immune reactions and responses. It also highlights the assessments of the potential diagnostic and therapeutic implications of galectin-3 in liver fibrosis during MAFLD. Overall, this review provides insights into the multifaceted interaction between galectin-3 and liver fibrosis in MAFLD, which could lead to the development of novel strategies for diagnosis and treatment of this prevalent liver disease.
{"title":"Galectin-3 and Severity of Liver Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease.","authors":"Mohammadjavad Sotoudeheian","doi":"10.2174/0109298665301698240404061300","DOIUrl":"10.2174/0109298665301698240404061300","url":null,"abstract":"<p><p>Metabolic dysfunction-associated Fatty Liver Disease (MAFLD) is a chronic liver disease characterized by the accumulation of fat in the liver and hepatic steatosis, which can progress to critical conditions, including Metabolic dysfunction-associated Steatohepatitis (MASH), liver fibrosis, hepatic cirrhosis, and hepatocellular carcinoma. Galectin-3, a member of the galectin family of proteins, has been involved in cascades that are responsible for the pathogenesis and progression of liver fibrosis in MAFLD. This review summarizes the present understanding of the role of galectin-3 in the severity of MAFLD and its associated liver fibrosis. The article assesses the underlying role of galectin-3-mediated fibrogenesis, including the triggering of hepatic stellate cells, the regulation of extracellular degradation, and the modulation of immune reactions and responses. It also highlights the assessments of the potential diagnostic and therapeutic implications of galectin-3 in liver fibrosis during MAFLD. Overall, this review provides insights into the multifaceted interaction between galectin-3 and liver fibrosis in MAFLD, which could lead to the development of novel strategies for diagnosis and treatment of this prevalent liver disease.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0109298665308572240513113105
Fan Yang, Hongxun Gong, Shiyan Chen, Jianzhong Li, Ning Huang, Maoxin Wang
Background: Radiotherapy is the primary treatment choice for Nasopharyngeal Carcinoma (NPC). However, its efficacy is compromised due to radioresistance. Ferroptosis, a novel iron-dependent regulated cell death induced by Ionizing Radiation (IR), plays a role in promoting cancer cell death. Yet, the relationship between enhanced ferroptosis and increased sensitivity of NPC cells to IR remains poorly understood.
Objective: This study aimed to explore the association between IR and ferroptosis in NPC, as well as the role of the ferroptosis repressor SLC7A11 in IR-treated NPC cells.
Methods: CNE1 and HNE-2 NPC cells were subjected to IR treatment. We performed qPCR and western blotting to evaluate the expression of ferroptosis-related genes in both control and IR-treated NPC cells. Additionally, we used the MTT assay to measure the viability of these NPC cells. JC-1 and DCFH-DA staining were employed to assess mitochondrial membrane potential and Reactive Oxygen Species (ROS) levels in both control and IR-treated NPC cells. Furthermore, we examined the levels of Fe2+, Malondialdehyde (MDA), reduced Glutathione (GSH), and oxidized glutathione (GSSG) in these cells. Moreover, we depleted SLC7A11 in IR-treated NPC cells to investigate its impact on the ferroptosis of these cells.
Results: IR upregulated the expression of ferroptosis-related genes, including SLC7A11, ACSL4, COX2, FTH1, and GPX4, in CNE1 and HNE-2 cells. IR treatment also resulted in decreased cell viability, disrupted mitochondrial membrane potential, increased ROS levels, altered glutathione levels, and elevated Fe2+ levels. Knockdown of SLC7A11 enhanced the sensitivity of NPC cells to IR.
Conclusion: IR may induce ferroptosis in NPC cells, and stimulating ferroptosis could potentially serve as a therapeutic strategy to enhance the efficacy of IR in treating NPC patients.
背景:放疗是鼻咽癌(NPC)的主要治疗方法。然而,由于放射抗药性的存在,放疗的疗效大打折扣。铁突变是电离辐射(IR)诱导的一种新型铁依赖性细胞死亡调节机制,在促进癌细胞死亡方面发挥着作用。然而,人们对铁突变的增强与鼻咽癌细胞对 IR 敏感性增加之间的关系仍知之甚少:本研究旨在探讨红外辐射与鼻咽癌铁突变之间的关系,以及铁突变抑制因子 SLC7A11 在红外辐射处理的鼻咽癌细胞中的作用:方法:对 CNE1 和 HNE-2 NPC 细胞进行 IR 处理。方法:CNE1和HNE-2鼻咽癌细胞均接受了IR处理,我们采用qPCR和Western印迹法评估了对照组和IR处理组鼻咽癌细胞中铁突变相关基因的表达。此外,我们还使用 MTT 法检测了这些 NPC 细胞的存活率。我们采用 JC-1 和 DCFH-DA 染色法评估对照组和经 IR 处理的鼻咽癌细胞的线粒体膜电位和活性氧(ROS)水平。此外,我们还检测了这些细胞中Fe2+、丙二醛(MDA)、还原型谷胱甘肽(GSH)和氧化型谷胱甘肽(GSSG)的水平。此外,我们还删除了经 IR 处理的鼻咽癌细胞中的 SLC7A11,以研究其对这些细胞铁变态反应的影响:结果:在 CNE1 和 HNE-2 细胞中,IR 上调了铁氧化相关基因的表达,包括 SLC7A11、ACSL4、COX2、FTH1 和 GPX4。红外处理还导致细胞活力下降、线粒体膜电位紊乱、ROS 水平升高、谷胱甘肽水平改变和 Fe2+ 水平升高。敲除 SLC7A11 可增强鼻咽癌细胞对 IR 的敏感性:结论:红外线可诱导鼻咽癌细胞的铁变态反应,刺激铁变态反应有可能成为一种治疗策略,以提高红外线治疗鼻咽癌患者的疗效。
{"title":"Depletion of SLC7A11 Sensitizes Nasopharyngeal Carcinoma Cells to Ionizing Radiation.","authors":"Fan Yang, Hongxun Gong, Shiyan Chen, Jianzhong Li, Ning Huang, Maoxin Wang","doi":"10.2174/0109298665308572240513113105","DOIUrl":"10.2174/0109298665308572240513113105","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy is the primary treatment choice for Nasopharyngeal Carcinoma (NPC). However, its efficacy is compromised due to radioresistance. Ferroptosis, a novel iron-dependent regulated cell death induced by Ionizing Radiation (IR), plays a role in promoting cancer cell death. Yet, the relationship between enhanced ferroptosis and increased sensitivity of NPC cells to IR remains poorly understood.</p><p><strong>Objective: </strong>This study aimed to explore the association between IR and ferroptosis in NPC, as well as the role of the ferroptosis repressor SLC7A11 in IR-treated NPC cells.</p><p><strong>Methods: </strong>CNE1 and HNE-2 NPC cells were subjected to IR treatment. We performed qPCR and western blotting to evaluate the expression of ferroptosis-related genes in both control and IR-treated NPC cells. Additionally, we used the MTT assay to measure the viability of these NPC cells. JC-1 and DCFH-DA staining were employed to assess mitochondrial membrane potential and Reactive Oxygen Species (ROS) levels in both control and IR-treated NPC cells. Furthermore, we examined the levels of Fe<sup>2+</sup>, Malondialdehyde (MDA), reduced Glutathione (GSH), and oxidized glutathione (GSSG) in these cells. Moreover, we depleted SLC7A11 in IR-treated NPC cells to investigate its impact on the ferroptosis of these cells.</p><p><strong>Results: </strong>IR upregulated the expression of ferroptosis-related genes, including SLC7A11, ACSL4, COX2, FTH1, and GPX4, in CNE1 and HNE-2 cells. IR treatment also resulted in decreased cell viability, disrupted mitochondrial membrane potential, increased ROS levels, altered glutathione levels, and elevated Fe<sup>2+</sup> levels. Knockdown of SLC7A11 enhanced the sensitivity of NPC cells to IR.</p><p><strong>Conclusion: </strong>IR may induce ferroptosis in NPC cells, and stimulating ferroptosis could potentially serve as a therapeutic strategy to enhance the efficacy of IR in treating NPC patients.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Heat-labile uracil-DNA glycosylase (HL-UDG) is commonly employed to eliminate carry-over contamination in DNA amplifications. However, the prevailing HL-UDG is markedly inactivated at 50°C, rendering it unsuitable for specific one-step RT-qPCR protocols utilizing reverse transcriptase at an optimal temperature of 42°C.
Objective: This study aimed to explore novel HL-UDG with lower inactivation temperature and for recombinant expression.
Methods: The gene encoding an HL-UDG was cloned from the cold-water fish rainbow trout (Oncorhynchus mykiss) and expressed in Escherichia coli with high yield. The thermostability of this enzyme and other enzymatic characteristics were thoroughly examined. The novel HL-UDG was then applied for controlling carry-over contamination in one-step RT-qPCR.
Results: This recombinantly expressed truncated HL-UDG of rainbow trout (OmUDG) exhibited high amino acids similarity (84.1% identity) to recombinant Atlantic cod UDG (rcUDG) and was easily denatured at 40°C. The optimal pH of OmUDG was 8.0, and the optimal concentrations of both Na+ and K+ were 10 mM. Since its inactivation temperature was lower than that of rcUDG, the OmUDG could be used to eliminate carry-over contamination in one-step RT-qPCR with moderate reverse transcription temperature.
Conclusion: We successfully identified and recombinantly expressed a novel HL-UDG with an inactivation temperature of 40°C. It is suitable for eliminating carry-over contamination in one-step RT-qPCR.
{"title":"Characterization of Heat-labile Uracil-DNA Glycosylase from <i>Oncorhynchus mykiss</i> and its Application for Carry-over Contamination Control in RT-qPCR.","authors":"Qingyuan Huang, Yaqi Zhang, Wenhao Hu, Keqi Chen, Jian Zhang, Zhidan Luo, Chen Lu","doi":"10.2174/0109298665283737240122105923","DOIUrl":"10.2174/0109298665283737240122105923","url":null,"abstract":"<p><strong>Background: </strong>Heat-labile uracil-DNA glycosylase (HL-UDG) is commonly employed to eliminate carry-over contamination in DNA amplifications. However, the prevailing HL-UDG is markedly inactivated at 50°C, rendering it unsuitable for specific one-step RT-qPCR protocols utilizing reverse transcriptase at an optimal temperature of 42°C.</p><p><strong>Objective: </strong>This study aimed to explore novel HL-UDG with lower inactivation temperature and for recombinant expression.</p><p><strong>Methods: </strong>The gene encoding an HL-UDG was cloned from the cold-water fish rainbow trout <i>(Oncorhynchus mykiss)</i> and expressed in <i>Escherichia coli</i> with high yield. The thermostability of this enzyme and other enzymatic characteristics were thoroughly examined. The novel HL-UDG was then applied for controlling carry-over contamination in one-step RT-qPCR.</p><p><strong>Results: </strong>This recombinantly expressed truncated HL-UDG of rainbow trout (OmUDG) exhibited high amino acids similarity (84.1% identity) to recombinant Atlantic cod UDG (rcUDG) and was easily denatured at 40°C. The optimal pH of OmUDG was 8.0, and the optimal concentrations of both Na<sup>+ </sup> and K<sup>+</sup> were 10 mM. Since its inactivation temperature was lower than that of rcUDG, the OmUDG could be used to eliminate carry-over contamination in one-step RT-qPCR with moderate reverse transcription temperature.</p><p><strong>Conclusion: </strong>We successfully identified and recombinantly expressed a novel HL-UDG with an inactivation temperature of 40°C. It is suitable for eliminating carry-over contamination in one-step RT-qPCR.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: TNF-α is a proinflammatory cytokine and plays a role in cell proliferation, differentiation, survival, and death pathways. When administered at high doses, it may cause damage to the tumor vasculature, thereby increasing the permeability of the blood vessels. Therefore, monitoring the dose and the response of the TNF-α molecule is essential for patients' health.
Objectives: This study aimed to clone, express, and purify the active form of the TNF-α protein, which can interact with various anti-TNF-α inhibitors with high efficiency.
Methods: Recombinant DNA technology was used to clone three different versions of codon-optimized human TNF-α sequences to E. coli. Colony PCR protocol was used for verification and produced proteins were analyzed through SDS-PAGE and western blot. Size exclusion chromatography was used to purify sTNF-α. ELISA techniques were used to analyze and compare binding efficiency of sTNF-α against three different standards.
Results: Under native condition (25°C), interaction between sTNF-α and anti-TNF-α antibody was 3,970, compared to positive control. The interaction was 0,587, whereas it was 0,535 for TNF- α and anti-TNF-α antibodies under denaturing conditions (37°C). F7 of sTNF-α (920 μg/mL) had the same/higher binding efficiency to adalimumab, etanercept, and infliximab, compared to commercial TNF-α.
Conclusion: This study was the first to analyze binding efficiency of homemade sTNF-α protein against three major TNF-α inhibitors (adalimumab, etanercept, and infliximab) in a single study. The high binding efficiency of sTNF-α with adalimumab, etanercept, and infliximab, evidenced in this study supports the feasibility of its use in therapeutic applications, contributing to more sustainable, cost-effective, and independent healthcare system.
{"title":"Study on Cloning and Expression of TNF-α Variants in <i>E. coli</i>: Production, Purification, and Interaction with Anti-TNF-α Inhibitors.","authors":"Gülşah Akçadağ, Demet Cansaran-Duman, Emine Sümer Aras, Haluk Ataoğlu","doi":"10.2174/0109298665312592240516111404","DOIUrl":"10.2174/0109298665312592240516111404","url":null,"abstract":"<p><strong>Background: </strong>TNF-α is a proinflammatory cytokine and plays a role in cell proliferation, differentiation, survival, and death pathways. When administered at high doses, it may cause damage to the tumor vasculature, thereby increasing the permeability of the blood vessels. Therefore, monitoring the dose and the response of the TNF-α molecule is essential for patients' health.</p><p><strong>Objectives: </strong>This study aimed to clone, express, and purify the active form of the TNF-α protein, which can interact with various anti-TNF-α inhibitors with high efficiency.</p><p><strong>Methods: </strong>Recombinant DNA technology was used to clone three different versions of codon-optimized human TNF-α sequences to <i>E. coli.</i> Colony PCR protocol was used for verification and produced proteins were analyzed through SDS-PAGE and western blot. Size exclusion chromatography was used to purify sTNF-α. ELISA techniques were used to analyze and compare binding efficiency of sTNF-α against three different standards.</p><p><strong>Results: </strong>Under native condition (25°C), interaction between sTNF-α and anti-TNF-α antibody was 3,970, compared to positive control. The interaction was 0,587, whereas it was 0,535 for TNF- α and anti-TNF-α antibodies under denaturing conditions (37°C). F7 of sTNF-α (920 μg/mL) had the same/higher binding efficiency to adalimumab, etanercept, and infliximab, compared to commercial TNF-α.</p><p><strong>Conclusion: </strong>This study was the first to analyze binding efficiency of homemade sTNF-α protein against three major TNF-α inhibitors (adalimumab, etanercept, and infliximab) in a single study. The high binding efficiency of sTNF-α with adalimumab, etanercept, and infliximab, evidenced in this study supports the feasibility of its use in therapeutic applications, contributing to more sustainable, cost-effective, and independent healthcare system.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0109298665266730240118054023
Shahzad Khan
Background: Inhibitors of interleukin 6 [IL-6] have been utilized to treat severe COVID-19 disease. Their immunosuppressive or immunomodulating impact may be beneficial in COVID-19.
Objectives: To discuss the role of IL-6 inhibitors and assess various trials conducted to evaluate the efficacy of IL-6 inhibitors in COVID-19 disease.
Summary: Two of the most common causes of mortality in COVID-19-infected critically ill individuals are acute respiratory distress syndrome (ARDS) and multiorgan failure. Increased levels of inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), is involved in the etiology of COVID-19. Most tissue damage, sepsis, and pulmonary and cardiovascular problems are caused mainly by the host defense system. Therefore, regulating this inflammatory cascade using immunomodulators is a prudent strategy. Although corticosteroids, as immunomodulators, are routinely used in COVID-19 management, interleukin (IL) inhibitors, especially IL-6 inhibitors, are also tested in many trials. Many studies have demonstrated that IL-6 inhibitors improve disease outcomes and decrease mortality, whereas others have shown that they are ineffective. In this paper, we briefly examined the role of IL-6 in COVID-19 pathogenesis and trials that support or refute the use of IL-6 inhibitors in treating COVID-19 disease.
Results: Though mixed results are coming from trials regarding the adjuvant use of IL-6 inhibitors and standard anti-viral therapy with dexamethasone, a consensus favors using IL-6 inhibitors in severely ill COVID-19 patients regardless of the outcome.
{"title":"Interleukin 6 Antagonists in Severe COVID-19 Disease: Cardiovascular and Respiratory Outcomes.","authors":"Shahzad Khan","doi":"10.2174/0109298665266730240118054023","DOIUrl":"10.2174/0109298665266730240118054023","url":null,"abstract":"<p><strong>Background: </strong>Inhibitors of interleukin 6 [IL-6] have been utilized to treat severe COVID-19 disease. Their immunosuppressive or immunomodulating impact may be beneficial in COVID-19.</p><p><strong>Objectives: </strong>To discuss the role of IL-6 inhibitors and assess various trials conducted to evaluate the efficacy of IL-6 inhibitors in COVID-19 disease.</p><p><strong>Summary: </strong>Two of the most common causes of mortality in COVID-19-infected critically ill individuals are acute respiratory distress syndrome (ARDS) and multiorgan failure. Increased levels of inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), is involved in the etiology of COVID-19. Most tissue damage, sepsis, and pulmonary and cardiovascular problems are caused mainly by the host defense system. Therefore, regulating this inflammatory cascade using immunomodulators is a prudent strategy. Although corticosteroids, as immunomodulators, are routinely used in COVID-19 management, interleukin (IL) inhibitors, especially IL-6 inhibitors, are also tested in many trials. Many studies have demonstrated that IL-6 inhibitors improve disease outcomes and decrease mortality, whereas others have shown that they are ineffective. In this paper, we briefly examined the role of IL-6 in COVID-19 pathogenesis and trials that support or refute the use of IL-6 inhibitors in treating COVID-19 disease.</p><p><strong>Results: </strong>Though mixed results are coming from trials regarding the adjuvant use of IL-6 inhibitors and standard anti-viral therapy with dexamethasone, a consensus favors using IL-6 inhibitors in severely ill COVID-19 patients regardless of the outcome.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0109298665292469240228064739
Md Moidul Islam, Sarjana Raikwar
Oral drug delivery is a prevalent and cost-effective method due to its advantages, such as increased drug absorption surface area and improved patient compliance. However, delivering proteins and peptides orally remains a challenge due to their vulnerability to degradation by digestive enzymes, stomach acids, and limited intestinal membrane permeability, resulting in poor bioavailability. The use of nanotechnology has emerged as a promising solution to enhance the bioavailability of these vital therapeutic agents. Polymeric NPs, made from natural or synthetic polymers, are commonly used. Natural polysaccharides, such as alginate, chitosan, dextran, starch, pectin, etc., have gained preference due to their biodegradability, biocompatibility, and versatility in encapsulating various drug types. Their hydrophobic-hydrophilic properties can be tailored to suit different drug molecules.
{"title":"Enhancement of Oral Bioavailability of Protein and Peptide by Polysaccharide-based Nanoparticles.","authors":"Md Moidul Islam, Sarjana Raikwar","doi":"10.2174/0109298665292469240228064739","DOIUrl":"10.2174/0109298665292469240228064739","url":null,"abstract":"<p><p>Oral drug delivery is a prevalent and cost-effective method due to its advantages, such as increased drug absorption surface area and improved patient compliance. However, delivering proteins and peptides orally remains a challenge due to their vulnerability to degradation by digestive enzymes, stomach acids, and limited intestinal membrane permeability, resulting in poor bioavailability. The use of nanotechnology has emerged as a promising solution to enhance the bioavailability of these vital therapeutic agents. Polymeric NPs, made from natural or synthetic polymers, are commonly used. Natural polysaccharides, such as alginate, chitosan, dextran, starch, pectin, etc., have gained preference due to their biodegradability, biocompatibility, and versatility in encapsulating various drug types. Their hydrophobic-hydrophilic properties can be tailored to suit different drug molecules.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/092986653101240120233748
{"title":"Tribute to Prof. Ben M. Dunn: A Remarkable Biochemist and Editor-in-Chief of Protein & Peptide Letters and Current Protein & Peptide Science.","authors":"","doi":"10.2174/092986653101240120233748","DOIUrl":"10.2174/092986653101240120233748","url":null,"abstract":"","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0109298665284293240409045359
A R Satvik Iyengar, Prakash Y Khandave, Janek Bzdrenga, Florian Nachon, Xavier Brazzolotto, Abhay H Pande
Nerve agents are a class of lethal neurotoxic chemicals used in chemical warfare. In this review, we have discussed a brief history of chemical warfare, followed by an exploration of the historical context surrounding nerve agents. The article explores the classification of these agents, their contemporary uses, their toxicity mechanisms, and the disadvantages of the current treatment options for nerve agent poisoning. It then discusses the possible application of enzymes as prophylactics against nerve agent poisoning, outlining the benefits and drawbacks of paraoxonase- 1. Finally, the current studies on paraoxonase-1 are reviewed, highlighting that several challenges need to be addressed in the use of paraoxonase-1 in the actual field and that its potential as a prophylactic antidote against nerve agent poisoning needs to be evaluated. The literature used in this manuscript was searched using various electronic databases, such as PubMed, Google Scholar, Web of Science, Elsevier, Springer, ACS, Google Patent, and books using the keywords chemical warfare agent, butyrylcholinesterase, enzyme, nerve agent, prophylactic, and paraoxonase-1, with the time scale for the analysis of articles between 1960 to 2023. The study has suggested that concerted efforts by researchers and agencies must be made to develop effective countermeasures against NA poisoning and that paraoxonase-1 has suitable properties for the development of efficient prophylaxis against NA poisoning.
神经毒剂是化学战中使用的一类致命的神经毒性化学品。在这篇综述中,我们简要讨论了化学战的简史,随后探讨了神经毒剂的历史背景。文章探讨了这些制剂的分类、当代用途、毒性机制以及神经毒剂中毒现有治疗方案的缺点。然后,文章讨论了酶作为神经毒剂中毒预防剂的可能应用,概述了副氧合酶-1 的优点和缺点。最后,回顾了目前有关副氧杂蒽酮酶-1 的研究,强调了在实际领域使用副氧杂蒽酮酶-1 时需要应对的几个挑战,并需要评估其作为神经毒剂中毒预防性解毒剂的潜力。本手稿中使用的文献是通过PubMed、Google Scholar、Web of Science、Elsevier、Springer、ACS、Google Patent和书籍等多个电子数据库进行检索的,使用的关键词分别为化学战剂、丁酰胆碱酯酶、酶、神经毒剂、预防性、副氧自由基酶-1,分析文章的时间范围分别为1960年至2023年。研究表明,研究人员和机构必须齐心协力,开发针对NA中毒的有效对策,而PON1具有适合开发针对NA中毒的高效预防药物的特性。
{"title":"Warfare Nerve Agents and Paraoxonase-1 as a Potential Prophylactic Therapy against Intoxication.","authors":"A R Satvik Iyengar, Prakash Y Khandave, Janek Bzdrenga, Florian Nachon, Xavier Brazzolotto, Abhay H Pande","doi":"10.2174/0109298665284293240409045359","DOIUrl":"10.2174/0109298665284293240409045359","url":null,"abstract":"<p><p>Nerve agents are a class of lethal neurotoxic chemicals used in chemical warfare. In this review, we have discussed a brief history of chemical warfare, followed by an exploration of the historical context surrounding nerve agents. The article explores the classification of these agents, their contemporary uses, their toxicity mechanisms, and the disadvantages of the current treatment options for nerve agent poisoning. It then discusses the possible application of enzymes as prophylactics against nerve agent poisoning, outlining the benefits and drawbacks of paraoxonase- 1. Finally, the current studies on paraoxonase-1 are reviewed, highlighting that several challenges need to be addressed in the use of paraoxonase-1 in the actual field and that its potential as a prophylactic antidote against nerve agent poisoning needs to be evaluated. The literature used in this manuscript was searched using various electronic databases, such as PubMed, Google Scholar, Web of Science, Elsevier, Springer, ACS, Google Patent, and books using the keywords chemical warfare agent, butyrylcholinesterase, enzyme, nerve agent, prophylactic, and paraoxonase-1, with the time scale for the analysis of articles between 1960 to 2023. The study has suggested that concerted efforts by researchers and agencies must be made to develop effective countermeasures against NA poisoning and that paraoxonase-1 has suitable properties for the development of efficient prophylaxis against NA poisoning.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}