Pub Date : 2024-07-30DOI: 10.2174/0115701646313765240610062419
Sonakshi Garg, Gurisha Garg, Preeti Patel, Ghanshyam Das Gupta, Balak Das Kurmi
: Monoclonal antibodies (mAbs) are magic bullets proved to be a wonder in the pharmaceutical as well as medical fields. These are produced by various methods like hybridoma technology, phage display technology, YAC technology, and transgenic animals and plants. Based on the percentage of animal origin, mAbs are divided into chimeric, murine, humanized, and fully human. This review covers the history and methods of mAb production, immunotoxicity (Immunosuppression, immunostimulant, autoimmunity, hypersensitivity) associated with mAbs, and targets of mAbs. It also compiles mAb production using AI, new modifications, and novel mAbs, with its various clinical trial information ensuring the use of mAbs in rare diseases and disorders.
:单克隆抗体(mAbs)是制药和医疗领域的神奇子弹。它们是通过杂交瘤技术、噬菌体展示技术、YAC 技术以及转基因动物和植物等各种方法生产出来的。根据动物来源的比例,mAbs 可分为嵌合型、鼠型、人源化和全人型。本综述涵盖 mAb 生产的历史和方法、与 mAb 相关的免疫毒性(免疫抑制、免疫刺激、自身免疫、超敏反应)以及 mAb 的靶点。它还汇编了使用人工智能生产的 mAb、新的修饰和新型 mAb,以及确保 mAb 用于罕见疾病和失调症的各种临床试验信息。
{"title":"A Complete Sojourn of Monoclonal Antibodies: AI, Rare Diseases / Disorders And Immunotoxic Effects","authors":"Sonakshi Garg, Gurisha Garg, Preeti Patel, Ghanshyam Das Gupta, Balak Das Kurmi","doi":"10.2174/0115701646313765240610062419","DOIUrl":"https://doi.org/10.2174/0115701646313765240610062419","url":null,"abstract":": Monoclonal antibodies (mAbs) are magic bullets proved to be a wonder in the pharmaceutical as well as medical fields. These are produced by various methods like hybridoma technology, phage display technology, YAC technology, and transgenic animals and plants. Based on the percentage of animal origin, mAbs are divided into chimeric, murine, humanized, and fully human. This review covers the history and methods of mAb production, immunotoxicity (Immunosuppression, immunostimulant, autoimmunity, hypersensitivity) associated with mAbs, and targets of mAbs. It also compiles mAb production using AI, new modifications, and novel mAbs, with its various clinical trial information ensuring the use of mAbs in rare diseases and disorders.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141872320","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 : 2024-07-22DOI: 10.2174/0115701646317215240712103448
Yang Zhang, Yu-Chen Ma, Jue Song, Yong Jin, Yan-Ni Bao
Objectives: Drug resistance reduces the antitumor efficacy of chemotherapy. Therefore, it is important to know how to reverse drug resistance. In this work, we investigated drug resistance reversal by StemRegenin-1(SR-1) in MCF-7/ADR cells and the mechanism by which it exerts its drug resistance effect. Methods: MTT test and protein blot were employed as the two main in vitro cell tests. The cells were treated with SR-1 and ADM to detect the changes in their proteomics, and then the effects of AhR downstream proteins, glucuronidase, and drug-resistant proteins were verified. The accumulation of ADM in the combined cells and its effect on the cell cycle were detected by flow cytometry. In vivo, a BALB/C mice xenograft test was conducted to observe the anti-tumor effect and side effects of the drug combination. Results: SR-1 combined with ADM inhibited cell proliferation and significantly decreased the expression of CYP1A1, UGT1A6, P-gP (ABCB1), and MRP1 (ABCC1). Furthermore, SR-1 caused apoptosis and cell cycle arrest. In vivo experiments showed that SR-1 significantly enhanced the antitumor effects of ADM and reduced the toxic effects of ADM. Conclusion: SR-1 inhibited AhR activity, decreased its downstream protein CYP1A1 and the expression of UGT1A6, P-gP, and MRP1 in MCF-7/ADR cells, and reversed drug resistance in MCF-7/ADR cells through AhR/ABC transports and AhR/UGTs pathways.
{"title":"StemRegenin-1 Reverses Drug Resistance of MCF-7/ADR Cells via AhR/ABC Transports and AhR/UGTs Pathways","authors":"Yang Zhang, Yu-Chen Ma, Jue Song, Yong Jin, Yan-Ni Bao","doi":"10.2174/0115701646317215240712103448","DOIUrl":"https://doi.org/10.2174/0115701646317215240712103448","url":null,"abstract":"Objectives: Drug resistance reduces the antitumor efficacy of chemotherapy. Therefore, it is important to know how to reverse drug resistance. In this work, we investigated drug resistance reversal by StemRegenin-1(SR-1) in MCF-7/ADR cells and the mechanism by which it exerts its drug resistance effect. Methods: MTT test and protein blot were employed as the two main in vitro cell tests. The cells were treated with SR-1 and ADM to detect the changes in their proteomics, and then the effects of AhR downstream proteins, glucuronidase, and drug-resistant proteins were verified. The accumulation of ADM in the combined cells and its effect on the cell cycle were detected by flow cytometry. In vivo, a BALB/C mice xenograft test was conducted to observe the anti-tumor effect and side effects of the drug combination. Results: SR-1 combined with ADM inhibited cell proliferation and significantly decreased the expression of CYP1A1, UGT1A6, P-gP (ABCB1), and MRP1 (ABCC1). Furthermore, SR-1 caused apoptosis and cell cycle arrest. In vivo experiments showed that SR-1 significantly enhanced the antitumor effects of ADM and reduced the toxic effects of ADM. Conclusion: SR-1 inhibited AhR activity, decreased its downstream protein CYP1A1 and the expression of UGT1A6, P-gP, and MRP1 in MCF-7/ADR cells, and reversed drug resistance in MCF-7/ADR cells through AhR/ABC transports and AhR/UGTs pathways.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754007","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: Parkinson's disease (PD) and its associated symptoms are closely associated with the self-assembly of α-Synuclein (α-Syn). Squalamine is a naturally occurring chemical substance with established antiviral and anticancer properties, and its profound impact on the α- Syn aggregation both in vivo and in vitro is well studied. Examining its interaction with lipid vesicles, which are known to encourage nucleation, can signify the mechanism of action of squalamine. The squalamine molecule is believed to displace α-Syn from the surfaces of the lipid vesicles, therefore preventing the initial steps in the process of aggregation. Additionally, the squalamine molecule reduces the harmful effects of α-Syn oligomers in human neuroblastoma cells by preventing them from interacting with lipid membranes. Objective: The aim of this study was to perform computational investigation of the conformational changes of membrane-bound α-Syn in the presence of squalamine inhibitor molecule objective: Computational investigation of the conformational changes of membrane-bound α-Synuclein in the presence of squalamine inhibitor molecule Method: Molecular Dynamics (MD) trajectory analysis was carried out to study the structural change of the α-Syn-squalamine conformers as a function of simulation time. The percentage of the secondary structural components of the α-Syn-squalamine complex was determined. Optimization of small molecule inhibitors was carried out using Density Functional Theory (DFT) analysis. Additionally, the values of electrophilicity (ω), nucleophilicity (N), Electron affinity (EA), and ionization potential (IP) were calculated. Results: The docking of the α-Syn-squalamine complex revealed the binding site and the best structure was selected based on the highest docking vina score (-5.8), and the contact residues were listed. From the conformational snapshots of the α-Syn-squalamine complex, it was evident that the α-Syn remained stable, maintaining its integrity throughout the simulation. The α-helical content was found to be retained from the secondary structural content analysis. The ω and N of the squalamine molecule were calculated to be -0.84 and 3.25, respectively. Conclusion: Our findings suggest that in the presence of a squalamine inhibitor molecule, α-Syn adopts a helical conformation that ensures stability and may indicate that the squalamine molecule causes gradual displacement of α-Syn across different regions within the lipid membrane.
{"title":"In silico Investigation on the Structural Insights into the Binding of Squalamine Inhibitor with Membrane-Bound Α-Synuclein","authors":"Dorothy Das, Priyam Bharadwaz, Venkata Satish Kumar Mattaparthi","doi":"10.2174/0115701646301714240703100842","DOIUrl":"https://doi.org/10.2174/0115701646301714240703100842","url":null,"abstract":"Background: Parkinson's disease (PD) and its associated symptoms are closely associated with the self-assembly of α-Synuclein (α-Syn). Squalamine is a naturally occurring chemical substance with established antiviral and anticancer properties, and its profound impact on the α- Syn aggregation both in vivo and in vitro is well studied. Examining its interaction with lipid vesicles, which are known to encourage nucleation, can signify the mechanism of action of squalamine. The squalamine molecule is believed to displace α-Syn from the surfaces of the lipid vesicles, therefore preventing the initial steps in the process of aggregation. Additionally, the squalamine molecule reduces the harmful effects of α-Syn oligomers in human neuroblastoma cells by preventing them from interacting with lipid membranes. Objective: The aim of this study was to perform computational investigation of the conformational changes of membrane-bound α-Syn in the presence of squalamine inhibitor molecule objective: Computational investigation of the conformational changes of membrane-bound α-Synuclein in the presence of squalamine inhibitor molecule Method: Molecular Dynamics (MD) trajectory analysis was carried out to study the structural change of the α-Syn-squalamine conformers as a function of simulation time. The percentage of the secondary structural components of the α-Syn-squalamine complex was determined. Optimization of small molecule inhibitors was carried out using Density Functional Theory (DFT) analysis. Additionally, the values of electrophilicity (ω), nucleophilicity (N), Electron affinity (EA), and ionization potential (IP) were calculated. Results: The docking of the α-Syn-squalamine complex revealed the binding site and the best structure was selected based on the highest docking vina score (-5.8), and the contact residues were listed. From the conformational snapshots of the α-Syn-squalamine complex, it was evident that the α-Syn remained stable, maintaining its integrity throughout the simulation. The α-helical content was found to be retained from the secondary structural content analysis. The ω and N of the squalamine molecule were calculated to be -0.84 and 3.25, respectively. Conclusion: Our findings suggest that in the presence of a squalamine inhibitor molecule, α-Syn adopts a helical conformation that ensures stability and may indicate that the squalamine molecule causes gradual displacement of α-Syn across different regions within the lipid membrane.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588403","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 : 2024-06-13DOI: 10.2174/0115701646300960240606093535
Ming-Chung Lin, Ming-Wei Lin, Erna Sulistyowati, Ching-Chieh Kao, Chung-Jung Liu, Shu-Ping Huang, S. C. Hsu, Bin Huang
Shear flow is a mechanical signal regulating the function of Endothelial Cells (ECs). The present study aimed to investigate the effects of different matrices on cell binding, Nitric Oxide (NO) production, protein S-nitrosylation, expression of adhesion proteins, ROS generation, and cell viability in ECs under shear flow. The ECs growing on glass slides separately coated with poly-L-lysine (p-Lys), collagen (Colla), fibronectin (Fibro), and a combined matrix (Colla+Fibro) were exposed to shear flow (25 dyne/cm2) for 0, 1, 4, 8 h. The number of ECs remaining attached on the glass slide was calculated. The expressions of endothelial Nitric Oxide Synthase (eNOS), peNOSS1177, VE-cadherin, FAK, and S-nitrosylated proteins were investigated by western blotting. The production of Nitric Oxide (NO) was measured by a specific reagent. Finally, the levels of ROS and cell viability were monitored. Under a constant shear flow for 1 h, the physiological responses of ECs were similar between these four matrices. When shear flow was extended to 4 and 8 h, higher cell binding, elevated NO production, increased S-nitrosylated proteins, enhanced expressions of FAK and VE-cadherin, mildly accumulated ROS, and cell death were observed in the matrix of Fibro and Colla+Fibro. We have concluded fibronectin to be the optimal matrix facilitating NO-mediated Snitrosylation that might be essential for superior binding efficiency, thereby preventing the stripping of ECs under shear flow. The results can be broadly applied to diverse biomechanical studies.
{"title":"Comparison of the Effects of Different Coating Matrices on Cell Binding and Nitric Oxide-Mediated Protein S-Nitrosylation in Endothelial Cells\u0000under Shear Flow","authors":"Ming-Chung Lin, Ming-Wei Lin, Erna Sulistyowati, Ching-Chieh Kao, Chung-Jung Liu, Shu-Ping Huang, S. C. Hsu, Bin Huang","doi":"10.2174/0115701646300960240606093535","DOIUrl":"https://doi.org/10.2174/0115701646300960240606093535","url":null,"abstract":"\u0000\u0000Shear flow is a mechanical signal regulating the function of Endothelial\u0000Cells (ECs). The present study aimed to investigate the effects of different matrices on cell binding,\u0000Nitric Oxide (NO) production, protein S-nitrosylation, expression of adhesion proteins, ROS\u0000generation, and cell viability in ECs under shear flow.\u0000\u0000\u0000\u0000The ECs growing on glass slides separately coated with poly-L-lysine (p-Lys), collagen\u0000(Colla), fibronectin (Fibro), and a combined matrix (Colla+Fibro) were exposed to shear flow (25\u0000dyne/cm2) for 0, 1, 4, 8 h. The number of ECs remaining attached on the glass slide was calculated.\u0000The expressions of endothelial Nitric Oxide Synthase (eNOS), peNOSS1177, VE-cadherin, FAK,\u0000and S-nitrosylated proteins were investigated by western blotting. The production of Nitric Oxide\u0000(NO) was measured by a specific reagent. Finally, the levels of ROS and cell viability were monitored.\u0000\u0000\u0000\u0000Under a constant shear flow for 1 h, the physiological responses of ECs were similar between\u0000these four matrices. When shear flow was extended to 4 and 8 h, higher cell binding, elevated\u0000NO production, increased S-nitrosylated proteins, enhanced expressions of FAK and VE-cadherin,\u0000mildly accumulated ROS, and cell death were observed in the matrix of Fibro and Colla+Fibro.\u0000\u0000\u0000\u0000We have concluded fibronectin to be the optimal matrix facilitating NO-mediated Snitrosylation\u0000that might be essential for superior binding efficiency, thereby preventing the stripping\u0000of ECs under shear flow. The results can be broadly applied to diverse biomechanical\u0000studies.\u0000","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141345850","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}