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":"27 1","pages":""},"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":"98 1","pages":""},"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":"33 1","pages":""},"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}
Objective: Helicobacter pylori, as a carcinogen, has been related to the development of gastric cancer, particularly in developing countries. The main challenge with therapy is the recurrence of antibiotic-resistant bacteria, and vaccination is still a problem. Therefore, the objective of the current study was to rationally design a multi-epitope vaccine using two immunogenic proteins found in H. pylori. Methods: Promising epitopes for the Leb-binding adhesin A (BabA) and vacuolating cytotoxin (VacA) proteins were characterized through an immunoinformatics approach. Epitope-rich fragments were selected based on high-binding affinities with HLA classes I and II to be specifically presented to B and T lymphocytes and to selectively elicit both humoral and cellular immune responses. Results: Six constructs were planned by fusing these fragments in different arrangements with the help of GPGPG linkers. The most stable three-dimensional structure was found in Construct 6 during molecular dynamics. To improve immunogenicity and stability, an adjuvant called human β- defensin 2 (hBD-2) was joined to the N-terminus of Construct 6. Following molecular docking, the final vaccine reacted appropriately with each toll-like receptor 2 (TLR-2), TLR3, and TLR-4. The final DNA sequence was optimized for expression in E. coli K12 and in silico cloned into a pET-28a(+) plasmid. As a result of the vaccination in silico, substantial responses were developed against H. pylori. Conclusion: According to the immune response simulation, activated B and T lymphocytes and memory cell production increased. Macrophages and dendritic cells proliferated continuously, and IFN-γ and Cytokines, such as IL-2 were raised.
目的：幽门螺杆菌是一种致癌物质，与胃癌的发病有关，尤其是在发展中国家。治疗的主要挑战是耐抗生素细菌的复发，而疫苗接种仍是一个问题。因此，本研究的目的是利用幽门螺杆菌中的两种免疫原蛋白合理设计一种多表位疫苗。方法通过免疫信息学方法确定了Leb结合粘附素A（BabA）和空泡细胞毒素（VacA）蛋白的有望表位。根据与 HLA I 类和 II 类的高结合亲和力筛选出表位丰富的片段，以便特异性地呈现给 B 淋巴细胞和 T 淋巴细胞，并选择性地引起体液免疫和细胞免疫反应。结果：在 GPGPG 连接器的帮助下，将这些片段以不同的排列方式融合在一起，规划出了六种构建体。在分子动力学中，构建体 6 的三维结构最为稳定。为了提高免疫原性和稳定性，在构建体 6 的 N 端加入了一种名为人 β 防御素 2（hBD-2）的佐剂。经过分子对接，最终的疫苗与收费样受体 2（TLR-2）、TLR3 和 TLR-4 均有适当的反应。最终的 DNA 序列经过优化，可在大肠杆菌 K12 中表达，并被克隆到 pET-28a(+)质粒中。由于在硅学中进行了疫苗接种，对幽门螺杆菌产生了实质性的反应。结论根据免疫反应模拟，活化的 B 淋巴细胞和 T 淋巴细胞以及记忆细胞的生成都有所增加。巨噬细胞和树突状细胞不断增殖，IFN-γ 和细胞因子（如 IL-2）升高。
{"title":"An Immunoinformatic Approach to Designing a Multi-epitope Vaccine against Helicobacter pylori with the VacA Toxin and BabA Adhesion","authors":"Viana Dayhimi, Fatemeh Ziadlou, Simin Nafian, Fatemeh Nafian","doi":"10.2174/0115701646302487240524103934","DOIUrl":"https://doi.org/10.2174/0115701646302487240524103934","url":null,"abstract":"Objective: Helicobacter pylori, as a carcinogen, has been related to the development of gastric cancer, particularly in developing countries. The main challenge with therapy is the recurrence of antibiotic-resistant bacteria, and vaccination is still a problem. Therefore, the objective of the current study was to rationally design a multi-epitope vaccine using two immunogenic proteins found in H. pylori. Methods: Promising epitopes for the Leb-binding adhesin A (BabA) and vacuolating cytotoxin (VacA) proteins were characterized through an immunoinformatics approach. Epitope-rich fragments were selected based on high-binding affinities with HLA classes I and II to be specifically presented to B and T lymphocytes and to selectively elicit both humoral and cellular immune responses. Results: Six constructs were planned by fusing these fragments in different arrangements with the help of GPGPG linkers. The most stable three-dimensional structure was found in Construct 6 during molecular dynamics. To improve immunogenicity and stability, an adjuvant called human β- defensin 2 (hBD-2) was joined to the N-terminus of Construct 6. Following molecular docking, the final vaccine reacted appropriately with each toll-like receptor 2 (TLR-2), TLR3, and TLR-4. The final DNA sequence was optimized for expression in E. coli K12 and in silico cloned into a pET-28a(+) plasmid. As a result of the vaccination in silico, substantial responses were developed against H. pylori. Conclusion: According to the immune response simulation, activated B and T lymphocytes and memory cell production increased. Macrophages and dendritic cells proliferated continuously, and IFN-γ and Cytokines, such as IL-2 were raised.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"23 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217981","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}
aims: Investigating the binding of phosphatidylinositol 3 phosphate (PI3P) with Plasmodium falciparum heat shock protein 70 homologs background: The 70 kDa Plasmodium falciparum (Pf) heat shock proteins (PfHSP70s) are an important class of molecules that are critically involved in parasite survival through periods of stress. Interaction between a crucial lipid modulatorPI3P and the C terminal lid domain of cytosolic PfHSP70-1, stabilizes the parasite digestive vacuole (DV) to facilitate hemoglobin trafficking and breakdown in turn impacting parasite survival. PfHSP70 homologs and PI3P are amply expressed together in various subcellular compartments of the parasite providing these with an opportunity to interact and affect biological processes. objective: The objectives of this study included identification of the PI3P binding pockets on PfHSP70s, understanding the binding affinity of each homolog for PI3P and identifying residues involved in different types of interactions. method: We have analyzed PI3P binding of all four PfHSP70s by using bioinformatics tools like sequence analysis, molecular docking and LigPlot+ analysis. result: Our results show that differently localized PfHSP70 homologs bind PI3P with variable affinity. The mitochondrial and ER localized PfHSP70s bind more strongly with PI3P than their cytosolic counterpart PfHSP70-1. The PI3P binding region on all PfHSP70 homologs lies at the interface of helices 1 and 3 of their substrate binding domain . Analysis of these results has also helped to pinpoint specific residues on PfHSP70s that may be engaged in these interactions. conclusion: PI3P preferentially binds to a particular pocket on PfHSP70 homologs. Different PfHSP70s bind to PI3P with variable binding affinity. Specific residues of PfHSP70 homologs involved in these interactions have been identified. other: The present study may therefore form the basis for designing interventions that hinder PfHSP70-PI3P interaction and influence parasite survival.
{"title":"Investigating PI3P Binding with Plasmodium Falciparum HSP70 Proteins","authors":"Vipul Upadhyay, Satinder Kaur, Rachna Hora, Prakash Chandra Mishra","doi":"10.2174/0115701646297476240408042556","DOIUrl":"https://doi.org/10.2174/0115701646297476240408042556","url":null,"abstract":"aims: Investigating the binding of phosphatidylinositol 3 phosphate (PI3P) with Plasmodium falciparum heat shock protein 70 homologs background: The 70 kDa Plasmodium falciparum (Pf) heat shock proteins (PfHSP70s) are an important class of molecules that are critically involved in parasite survival through periods of stress. Interaction between a crucial lipid modulatorPI3P and the C terminal lid domain of cytosolic PfHSP70-1, stabilizes the parasite digestive vacuole (DV) to facilitate hemoglobin trafficking and breakdown in turn impacting parasite survival. PfHSP70 homologs and PI3P are amply expressed together in various subcellular compartments of the parasite providing these with an opportunity to interact and affect biological processes. objective: The objectives of this study included identification of the PI3P binding pockets on PfHSP70s, understanding the binding affinity of each homolog for PI3P and identifying residues involved in different types of interactions. method: We have analyzed PI3P binding of all four PfHSP70s by using bioinformatics tools like sequence analysis, molecular docking and LigPlot+ analysis. result: Our results show that differently localized PfHSP70 homologs bind PI3P with variable affinity. The mitochondrial and ER localized PfHSP70s bind more strongly with PI3P than their cytosolic counterpart PfHSP70-1. The PI3P binding region on all PfHSP70 homologs lies at the interface of helices 1 and 3 of their substrate binding domain . Analysis of these results has also helped to pinpoint specific residues on PfHSP70s that may be engaged in these interactions. conclusion: PI3P preferentially binds to a particular pocket on PfHSP70 homologs. Different PfHSP70s bind to PI3P with variable binding affinity. Specific residues of PfHSP70 homologs involved in these interactions have been identified. other: The present study may therefore form the basis for designing interventions that hinder PfHSP70-PI3P interaction and influence parasite survival.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"303 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140612995","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 : 2024-04-02DOI: 10.2174/0115701646297689240325062145
Maryam Rezaee, Mohsen Mohammadi, Amir Savardashtaki, Mohammad Reza Rahbar, Navid Nezafat
Background: Acinetobacter baumannii is an opportunistic pathogen that causes many infections, including nosocomial infections; this bacterium has a high mortality rate among other bacteria. A. baumannii has an elastic genome that changes rapidly when exposed to harsh environmental conditions, leading to widespread bacterial resistance to various disinfectants and antibiotics. The high ability of bacteria to bind to all surfaces and survive in different conditions has caused the spread of bacteria in various environments. Rapid detection is very important in preventing the spread and even treatment of the infection. Methods: Currently, the Polymerase Chain Reaction (PCR) method is the only effective method used for diagnosis, which has some pros and cons. Results and Conclusion: This study aimed to design a new recombinant multi-epitope protein from Acinetobacter baumannii that can be used in ELISA for rapid diagnosis. The unique feature of this study from others is the use of patient serum for antibody monitoring.
{"title":"Designing a Novel Multi-Epitope Peptide as a Potential Serodiagnosis Marker for the Diagnosis of Acinetobacter baumannii: An In silico Approach","authors":"Maryam Rezaee, Mohsen Mohammadi, Amir Savardashtaki, Mohammad Reza Rahbar, Navid Nezafat","doi":"10.2174/0115701646297689240325062145","DOIUrl":"https://doi.org/10.2174/0115701646297689240325062145","url":null,"abstract":"Background: Acinetobacter baumannii is an opportunistic pathogen that causes many infections, including nosocomial infections; this bacterium has a high mortality rate among other bacteria. A. baumannii has an elastic genome that changes rapidly when exposed to harsh environmental conditions, leading to widespread bacterial resistance to various disinfectants and antibiotics. The high ability of bacteria to bind to all surfaces and survive in different conditions has caused the spread of bacteria in various environments. Rapid detection is very important in preventing the spread and even treatment of the infection. Methods: Currently, the Polymerase Chain Reaction (PCR) method is the only effective method used for diagnosis, which has some pros and cons. Results and Conclusion: This study aimed to design a new recombinant multi-epitope protein from Acinetobacter baumannii that can be used in ELISA for rapid diagnosis. The unique feature of this study from others is the use of patient serum for antibody monitoring.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"50 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140585015","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: Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck region known for its high metastatic and invasive potential. Chlorpromazine (CPZ) has been shown to inhibit the growth of oral cancer cells. However, the effects of CPZ on OSCC migration and its underlying molecular mechanisms remain unclear. Objective: We aimed to identify global protein changes and potential core proteins involved in CPZ-mediated inhibition of migration in SCC-15 cells using proteomics. Methods: We assessed the effect of CPZ on SCC-15 using CCK-8 assays and wound healing experiments. Next, we performed LC-MS-based proteomic analysis to identify protein alterations in SCC-15 cells treated with CPZ at different times. Differential expression proteins (DEPs) were identified and subjected to bioinformatics analysis using GO, KEGG, and PPI tools. Key candidate proteins were selected and validated using the TCGA-HNSCC database and molecular docking. Results: It was found that 20μm of CPZ had no effect on cell proliferation, but inhibited cell migration. A total of 4748 proteins were identified by Proteomics, among which 56 DEPs were identified, including 34 upregulated proteins and 22 downregulated proteins. Three proteins (RPF2, ACTB, and TGFBI) were identified as key candidate proteins associated with cell adhesion and migration in oral cancer cells. Conclusion: CPZ may affect the expression of RPF2, ACTB, and TGFBI proteins and change the extracellular matrix and cell adhesion function, thus inhibiting the migration of SCC-15 cells. The results of this study provide a robust basis for further research on the molecular mechanism of CPZ to inhibit the migration of OSCC.
{"title":"Proteomic Analysis of the Molecular Mechanisms of Chlorpromazine Inhibiting Migration of Oral Squamous Cell Carcinoma","authors":"Nannan Zhang, Junzhi Liu, Qiuping Dong, Chen Liu, Xinyu Liang, Peiyuan Tang, Zheng Liang","doi":"10.2174/0115701646291510240212091951","DOIUrl":"https://doi.org/10.2174/0115701646291510240212091951","url":null,"abstract":"Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck region known for its high metastatic and invasive potential. Chlorpromazine (CPZ) has been shown to inhibit the growth of oral cancer cells. However, the effects of CPZ on OSCC migration and its underlying molecular mechanisms remain unclear. Objective: We aimed to identify global protein changes and potential core proteins involved in CPZ-mediated inhibition of migration in SCC-15 cells using proteomics. Methods: We assessed the effect of CPZ on SCC-15 using CCK-8 assays and wound healing experiments. Next, we performed LC-MS-based proteomic analysis to identify protein alterations in SCC-15 cells treated with CPZ at different times. Differential expression proteins (DEPs) were identified and subjected to bioinformatics analysis using GO, KEGG, and PPI tools. Key candidate proteins were selected and validated using the TCGA-HNSCC database and molecular docking. Results: It was found that 20μm of CPZ had no effect on cell proliferation, but inhibited cell migration. A total of 4748 proteins were identified by Proteomics, among which 56 DEPs were identified, including 34 upregulated proteins and 22 downregulated proteins. Three proteins (RPF2, ACTB, and TGFBI) were identified as key candidate proteins associated with cell adhesion and migration in oral cancer cells. Conclusion: CPZ may affect the expression of RPF2, ACTB, and TGFBI proteins and change the extracellular matrix and cell adhesion function, thus inhibiting the migration of SCC-15 cells. The results of this study provide a robust basis for further research on the molecular mechanism of CPZ to inhibit the migration of OSCC.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"43 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140008576","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 : 2024-02-23DOI: 10.2174/0115701646284439240218063821
Xiaoling Zhang, Sihuan Chen, Shuji Gao, Weiping Yang, Yuxin Wang, Yang Wang, Li Yi
Background: Streptococcus equi ssp. zooepidemicus(SEZ) is one important pathogen. There are still sporadic outbreaks in China, northern United States and the Netherlands. Adenylosuccinate synthetase PurA, a newly discovered protein in prior research, requires further assessment of its protective effectiveness. Methods: In this study, we focused on the expression of recombinant PurA from SEZ ATCC 35246. We evaluated the immunoreactivity of this recombinant protein using convalescent minipig sera. Additionally, we conducted experiments in mice to assess its immunogenic properties. Results: Our findings revealed that the recombinant PurA triggered a substantial antibody response in mice, resulting in an 80% protection rate against SEZ infection. Notably, mice immunized with PurA exhibited significantly reduced bacterial colonization in all organs compared to the PBS control group. Furthermore, the levels of IL-6, IL-8, IL-1β, and TNF-α in mouse serum were significantly elevated in the PurA-immunized group compared to the control group. Hyperimmune sera targeting PurA effectively eliminated SEZ in bactericidal tests. Remarkably, antibodies against PurA demonstrated a significant inhibitory effect on developing SEZ biofilm. Conclusion: Immunization with PurA elicited robust humoral and cellular immune responses in mice. These promising results suggest the potential utility of PurA in developing SEZ vaccine immunogens, providing a valuable avenue for further research into SEZ infection prevention and control.
{"title":"Immunoprotective Potential of Adenylosuccinate Synthetase Protein (PurA) in Streptococcus equi ssp. zooepidemicus Infections","authors":"Xiaoling Zhang, Sihuan Chen, Shuji Gao, Weiping Yang, Yuxin Wang, Yang Wang, Li Yi","doi":"10.2174/0115701646284439240218063821","DOIUrl":"https://doi.org/10.2174/0115701646284439240218063821","url":null,"abstract":" Background: Streptococcus equi ssp. zooepidemicus(SEZ) is one important pathogen. There are still sporadic outbreaks in China, northern United States and the Netherlands. Adenylosuccinate synthetase PurA, a newly discovered protein in prior research, requires further assessment of its protective effectiveness. Methods: In this study, we focused on the expression of recombinant PurA from SEZ ATCC 35246. We evaluated the immunoreactivity of this recombinant protein using convalescent minipig sera. Additionally, we conducted experiments in mice to assess its immunogenic properties. Results: Our findings revealed that the recombinant PurA triggered a substantial antibody response in mice, resulting in an 80% protection rate against SEZ infection. Notably, mice immunized with PurA exhibited significantly reduced bacterial colonization in all organs compared to the PBS control group. Furthermore, the levels of IL-6, IL-8, IL-1β, and TNF-α in mouse serum were significantly elevated in the PurA-immunized group compared to the control group. Hyperimmune sera targeting PurA effectively eliminated SEZ in bactericidal tests. Remarkably, antibodies against PurA demonstrated a significant inhibitory effect on developing SEZ biofilm. Conclusion: Immunization with PurA elicited robust humoral and cellular immune responses in mice. These promising results suggest the potential utility of PurA in developing SEZ vaccine immunogens, providing a valuable avenue for further research into SEZ infection prevention and control.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"20 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141165687","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 : 2023-12-11DOI: 10.2174/0115701646258315231102070151
Wang Zhenchang, Zhang Wenf, Wu Shanshan, Yang Lei
Introduction: Excessive oxidative stress is always associated with hepatic disease, including hepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). Despite this, the intricate molecular processes driving hepatocyte apoptosis due to oxidative stress remain incompletely comprehended. Aim: Consequently, we aimed to explore the role of miR-135a-5p in hepatoma cells (HepG2/3B). Methods: The assessment of protein expression was conducted through western blotting. Furthermore, miR-135a-5p expression was evaluated through RT-qPCR, and apoptosis detection was performed using a flow cytometry assay. Result: The findings suggest a connection between miR-135a-5p and mitochondrial-driven apoptosis through caspase signaling pathways. Furthermore, miR-135a-5p suppression inhibited the apoptotic response triggered by H2O2, reactive oxygen species (ROS) generation, as well as the decrease in mitochondrial membrane potential. Conclusion: Additionally, miR-135a-5p knockdown promoted mitophagy by regulating FoxO1/PINK1/Parkin signaling via targeting FoxO1. To conclude, our study implied that miR135a-5p might function as a probable regulator that protects cells against oxidative stress.
{"title":"Knockdown of miR-135a-5p Promotes Mitophagy by Regulating FoxO1/PINK1/Parkin Signaling in Hepatoma Cells Exposed to Oxidative Stress","authors":"Wang Zhenchang, Zhang Wenf, Wu Shanshan, Yang Lei","doi":"10.2174/0115701646258315231102070151","DOIUrl":"https://doi.org/10.2174/0115701646258315231102070151","url":null,"abstract":"Introduction: Excessive oxidative stress is always associated with hepatic disease, including hepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). Despite this, the intricate molecular processes driving hepatocyte apoptosis due to oxidative stress remain incompletely comprehended. Aim: Consequently, we aimed to explore the role of miR-135a-5p in hepatoma cells (HepG2/3B). Methods: The assessment of protein expression was conducted through western blotting. Furthermore, miR-135a-5p expression was evaluated through RT-qPCR, and apoptosis detection was performed using a flow cytometry assay. Result: The findings suggest a connection between miR-135a-5p and mitochondrial-driven apoptosis through caspase signaling pathways. Furthermore, miR-135a-5p suppression inhibited the apoptotic response triggered by H2O2, reactive oxygen species (ROS) generation, as well as the decrease in mitochondrial membrane potential. Conclusion: Additionally, miR-135a-5p knockdown promoted mitophagy by regulating FoxO1/PINK1/Parkin signaling via targeting FoxO1. To conclude, our study implied that miR135a-5p might function as a probable regulator that protects cells against oxidative stress.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"23 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138572423","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: Recent studies have validated the role of Pericentriolar Material 1 (PCM1) in several malignant tumour cell lines, but its specific biological function in lung adenocarcinoma (LUAD) remains unclear. Objective: To address this gap, this study analyzed 411 LUAD and control samples to evaluate the prognostic value of PCM1 using Cox regression analysis. objective: To address this gap, this study analyzed 411 LUAD and control samples to evaluate the prognostic value of PCM1 using Cox regression analysis. Methods: Multiple genes co-expressed with PCM1 were also analyzed to investigate the biological processes and roles involved in PCM1. An endogenous competitive network with PCM1 as the key gene was constructed to uncover its regulatory and competitive relationships in LUAD. The study further explored the immunological characteristics of PCM1 in different expression groups based on immune infiltration analysis. Results: These findings indicated that higher PCM1 expression levels were associated with better survival prognoses, possibly due to its antagonistic effects on RHOC. Immunological infiltration analysis revealed a significant correlation between PCM1 and various immune cell infiltration levels, including CD4+ T cells, naïve B cells, M2 macrophages, and mast cells. However, there was no significant relationship between PCM1 and MSI, TMB, or stemness, although it was positively correlated with m6A genes. Patients with lower PCM1 expression responded better to CTLA-4 therapy. The study also estimated that some chemotherapeutic and targeted agents might be effective in treating patients with high PCM1 levels. PCM1 was mainly expressed in the cytoplasmic and membranous structures. Conclusion: PCM1 shows potential as a prognostic biomarker for LUAD due to its strong correlation with immune cell infiltration and its ability to enhance anticancer treatment sensitivity. other: No.
{"title":"PCM1: A Potential Prognostic Biomarker Correlated with Immune Infiltration in Lung Adenocarcinoma","authors":"Zhihua Guo, Jinghao Liang, Xin Zhang, Qing Ai, Zixian Xie, Haonan Zhao, Fayuan Wu, Zhaofeng Tan, Weiqiang Yin, Linghua Ji","doi":"10.2174/0115701646270898231123065507","DOIUrl":"https://doi.org/10.2174/0115701646270898231123065507","url":null,"abstract":"Background: Recent studies have validated the role of Pericentriolar Material 1 (PCM1) in several malignant tumour cell lines, but its specific biological function in lung adenocarcinoma (LUAD) remains unclear. Objective: To address this gap, this study analyzed 411 LUAD and control samples to evaluate the prognostic value of PCM1 using Cox regression analysis. objective: To address this gap, this study analyzed 411 LUAD and control samples to evaluate the prognostic value of PCM1 using Cox regression analysis. Methods: Multiple genes co-expressed with PCM1 were also analyzed to investigate the biological processes and roles involved in PCM1. An endogenous competitive network with PCM1 as the key gene was constructed to uncover its regulatory and competitive relationships in LUAD. The study further explored the immunological characteristics of PCM1 in different expression groups based on immune infiltration analysis. Results: These findings indicated that higher PCM1 expression levels were associated with better survival prognoses, possibly due to its antagonistic effects on RHOC. Immunological infiltration analysis revealed a significant correlation between PCM1 and various immune cell infiltration levels, including CD4+ T cells, naïve B cells, M2 macrophages, and mast cells. However, there was no significant relationship between PCM1 and MSI, TMB, or stemness, although it was positively correlated with m6A genes. Patients with lower PCM1 expression responded better to CTLA-4 therapy. The study also estimated that some chemotherapeutic and targeted agents might be effective in treating patients with high PCM1 levels. PCM1 was mainly expressed in the cytoplasmic and membranous structures. Conclusion: PCM1 shows potential as a prognostic biomarker for LUAD due to its strong correlation with immune cell infiltration and its ability to enhance anticancer treatment sensitivity. other: No.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"159 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138572021","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}
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