Pub Date : 2024-01-01DOI: 10.2174/0113892037275751231221053730
Yasmim A Grangeiro, Ana L E Santos, Flávia E V Barbosa, Renato R Roma, Racquel O S Souza, Cláudio G L Silva, Claudener S Teixeira
Lectins are proteins widely distributed among plants, animals and microorganisms that have the ability to recognize and interact with specific carbohydrates. They have varied biological activities, such as the inhibition of the progression of infections caused by fungi, bacteria, viruses and protozoa, which is related to the interaction of these proteins with the carbohydrates present in the cell walls of these microorganisms. Leishmaniasis are a group of endemic infectious diseases caused by protozoa of the genus Leishmania. In vitro and in vivo tests with promastigotes and amastigotes of Leishmania demonstrated that lectins have the ability to interact with glycoconjugates present on the cell surface of the parasite, it prevents their development through various mechanisms of action, such as the production of ROS and alteration of membrane integrity, and can also interact with defense cells present in the human body, thus showing that these molecules can be considered alternative pharmacological targets for the treatment of leishmaniasis. The objective of the present work is to carry out a bibliographic review on lectins with leishmanicidal activity, emphasizing the advances and perspectives of research in this theme. Through the analysis of the selected studies, we were able to conclude that lectins have great potential for inhibiting the development of leishmaniasis. However, there are still few studies on this subject.
{"title":"A Review of the Leishmanicidal Properties of Lectins.","authors":"Yasmim A Grangeiro, Ana L E Santos, Flávia E V Barbosa, Renato R Roma, Racquel O S Souza, Cláudio G L Silva, Claudener S Teixeira","doi":"10.2174/0113892037275751231221053730","DOIUrl":"10.2174/0113892037275751231221053730","url":null,"abstract":"<p><p>Lectins are proteins widely distributed among plants, animals and microorganisms that have the ability to recognize and interact with specific carbohydrates. They have varied biological activities, such as the inhibition of the progression of infections caused by fungi, bacteria, viruses and protozoa, which is related to the interaction of these proteins with the carbohydrates present in the cell walls of these microorganisms. Leishmaniasis are a group of endemic infectious diseases caused by protozoa of the genus <i>Leishmania. In vitro</i> and <i>in vivo</i> tests with promastigotes and amastigotes of <i>Leishmania</i> demonstrated that lectins have the ability to interact with glycoconjugates present on the cell surface of the parasite, it prevents their development through various mechanisms of action, such as the production of ROS and alteration of membrane integrity, and can also interact with defense cells present in the human body, thus showing that these molecules can be considered alternative pharmacological targets for the treatment of leishmaniasis. The objective of the present work is to carry out a bibliographic review on lectins with leishmanicidal activity, emphasizing the advances and perspectives of research in this theme. Through the analysis of the selected studies, we were able to conclude that lectins have great potential for inhibiting the development of leishmaniasis. However, there are still few studies on this subject.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570046","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: 10.2174/0113892037278814231226104509
Sarah Oluwatobi Otun, Richard Graca, Ikechukwu Achilonu
A comprehensive knowledge of aminoglycoside-modifying enzymes (AMEs) and their role in bacterial resistance mechanisms is urgently required due to the rising incidence of antibiotic resistance, particularly in Klebsiella pneumoniae infections. This study explores the essential features of AMEs, including their structural and functional properties, the processes by which they contribute to antibiotic resistance, and the therapeutic importance of aminoglycosides. The study primarily examines the Recombinant Klebsiella pneumoniae Aminoglycoside Adenylyl Transferase (RKAAT), particularly emphasizing its biophysical characteristics and the sorts of resistance it imparts. Furthermore, this study examines the challenges presented by RKAAT-mediated resistance, an evaluation of treatment methods and constraints, and options for controlling infection. The analysis provides a prospective outlook on strategies to address and reduce antibiotic resistance. This extensive investigation seeks to provide vital insights into the continuing fight against bacterial resistance, directing future research efforts and medicinal approaches.
{"title":"Combating Aminoglycoside Resistance: From Structural and Functional Characterisation to Therapeutic Challenges with RKAAT.","authors":"Sarah Oluwatobi Otun, Richard Graca, Ikechukwu Achilonu","doi":"10.2174/0113892037278814231226104509","DOIUrl":"10.2174/0113892037278814231226104509","url":null,"abstract":"<p><p>A comprehensive knowledge of aminoglycoside-modifying enzymes (AMEs) and their role in bacterial resistance mechanisms is urgently required due to the rising incidence of antibiotic resistance, particularly in <i>Klebsiella pneumoniae</i> infections. This study explores the essential features of AMEs, including their structural and functional properties, the processes by which they contribute to antibiotic resistance, and the therapeutic importance of aminoglycosides. The study primarily examines the Recombinant <i>Klebsiella pneumoniae</i> Aminoglycoside Adenylyl Transferase (RKAAT), particularly emphasizing its biophysical characteristics and the sorts of resistance it imparts. Furthermore, this study examines the challenges presented by RKAAT-mediated resistance, an evaluation of treatment methods and constraints, and options for controlling infection. The analysis provides a prospective outlook on strategies to address and reduce antibiotic resistance. This extensive investigation seeks to provide vital insights into the continuing fight against bacterial resistance, directing future research efforts and medicinal approaches.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680767","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: 10.2174/0113892037282522240130090156
Jasweer Kaur, Prakash Chandra Mishra, Rachna Hora
The apicomplexan pathogenic parasite 'Plasmodium falciparum' (Pf) is responsible for most of the malaria related mortality. It resides in and refurbishes the infected red blood cells (iRBCs) for its own survival and to suffice its metabolic needs. Remodeling of host erythrocytes involves alteration of physical and biochemical properties of the membrane and genesis of new parasite induced structures within the iRBCs. The generated structures include knobs and solute ion channels on the erythrocyte surface and specialized organelles i.e. Maurer's clefts (MCs) in the iRBC cytosol. The above processes are mediated by exporting a large repertoire of proteins to the host cell, most of which are transported via MCs, the sorting stations in parasitized erythrocytes. Information about MC biogenesis and the molecules involved in maintaining MC architecture remains incompletely elucidated. Here, we have compiled a list of experimentally known MC resident proteins, several of which have roles in maintaining its architecture and function. Our short review covers available data on the domain organization, orthologues, topology and specific roles of these proteins. We highlight the current knowledge gaps in our understanding of MCs as crucial organelles involved in parasite biology and disease pathogenesis.
恶性疟原虫(Plasmodium falciparum,Pf)是造成大多数疟疾相关死亡的致病寄生虫。它寄生在受感染的红细胞(iRBCs)中并对其进行改造,以满足自身生存和新陈代谢的需要。宿主红细胞的重塑包括改变膜的物理和生化特性,以及在 iRBC 内生成新的寄生虫诱导结构。生成的结构包括红细胞表面的旋钮和溶质离子通道,以及 iRBC 细胞质中的特化细胞器,即毛雷尔裂隙(MC)。上述过程是通过向宿主细胞输出大量蛋白质来完成的,其中大部分蛋白质是通过 MCs(寄生红细胞中的分拣站)运输的。有关 MC 生物发生和参与维持 MC 结构的分子的信息仍未完全阐明。在此,我们汇编了一份实验已知的 MC 驻留蛋白清单,其中一些蛋白在维持 MC 结构和功能方面发挥着作用。我们的简短综述涵盖了关于这些蛋白质的结构域组织、同源物、拓扑结构和特定作用的现有数据。我们强调了目前在了解 MCs 作为参与寄生虫生物学和疾病发病机制的关键细胞器方面存在的知识空白。
{"title":"Molecular Players at the Sorting Stations of Malaria Parasite <i>'Plasmodium falciparum'</i>.","authors":"Jasweer Kaur, Prakash Chandra Mishra, Rachna Hora","doi":"10.2174/0113892037282522240130090156","DOIUrl":"10.2174/0113892037282522240130090156","url":null,"abstract":"<p><p>The apicomplexan pathogenic parasite <i>'Plasmodium falciparum</i>' (Pf) is responsible for most of the malaria related mortality. It resides in and refurbishes the infected red blood cells (iRBCs) for its own survival and to suffice its metabolic needs. Remodeling of host erythrocytes involves alteration of physical and biochemical properties of the membrane and genesis of new parasite induced structures within the iRBCs. The generated structures include knobs and solute ion channels on the erythrocyte surface and specialized organelles i.e. Maurer's clefts (MCs) in the iRBC cytosol. The above processes are mediated by exporting a large repertoire of proteins to the host cell, most of which are transported <i>via</i> MCs, the sorting stations in parasitized erythrocytes. Information about MC biogenesis and the molecules involved in maintaining MC architecture remains incompletely elucidated. Here, we have compiled a list of experimentally known MC resident proteins, several of which have roles in maintaining its architecture and function. Our short review covers available data on the domain organization, orthologues, topology and specific roles of these proteins. We highlight the current knowledge gaps in our understanding of MCs as crucial organelles involved in parasite biology and disease pathogenesis.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971294","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: 10.2174/0113892037284277240126094716
Anna Ploch-Jankowska
Background: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are one of the most commonly used groups of medicinal compounds in the world. The wide access to NSAIDs and the various ways of storing them due to their easy accessibility often entail the problem with the stability and durability resulting from the exposure of drugs to external factors. The aim of the research was to evaluate in vitro the mechanism of competition between ibuprofen (IBU) and its degradation products, i.e., 4'-isobutylacetophenone (IBAP) and (2RS)-2-(4- formylphenyl)propionic acid (FPPA) during transport in a complex with fatted (HSA) and defatted (dHSA) human serum albumin.
Methods: The research was carried out using spectroscopic techniques, such as spectrophotometry, infrared spectroscopy and nuclear magnetic resonance spectroscopy.
Results: The comprehensive application of spectroscopic techniques allowed, among others, for the determination of the binding constant, the number of classes of binding sites and the cooperativeness constant of the analyzed systems IBU-(d)HSA, IBU-(d)HSA-FPPA, IBU-(d)HSA-IBAP; the determination of the effect of ibuprofen and its degradation products on the secondary structure of albumin; identification and assessment of interactions between ligand and albumin; assessment of the impact of the presence of fatty acids in the structure of albumin and the measurement temperature on the binding of IBU, IBAP and FPPA to (d)HSA.
Conclusion: The conducted research allowed us to conclude that the presence of ibuprofen degradation products and the increase in their concentration significantly affect the formation of the IBU-albumin complex and thus, the value of the association constant of the drug, changing the concentration of its free fraction in the blood plasma. It was also found that the presence of an ibuprofen degradation product in a complex with albumin affects its secondary structure.
{"title":"Spectroscopic Analysis of the Effect of Ibuprofen Degradation Products on the Interaction between Ibuprofen and Human Serum Albumin.","authors":"Anna Ploch-Jankowska","doi":"10.2174/0113892037284277240126094716","DOIUrl":"10.2174/0113892037284277240126094716","url":null,"abstract":"<p><strong>Background: </strong>Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are one of the most commonly used groups of medicinal compounds in the world. The wide access to NSAIDs and the various ways of storing them due to their easy accessibility often entail the problem with the stability and durability resulting from the exposure of drugs to external factors. The aim of the research was to evaluate <i>in vitro</i> the mechanism of competition between ibuprofen (IBU) and its degradation products, i.e., 4'-isobutylacetophenone (IBAP) and (2RS)-2-(4- formylphenyl)propionic acid (FPPA) during transport in a complex with fatted (HSA) and defatted (dHSA) human serum albumin.</p><p><strong>Methods: </strong>The research was carried out using spectroscopic techniques, such as spectrophotometry, infrared spectroscopy and nuclear magnetic resonance spectroscopy.</p><p><strong>Results: </strong>The comprehensive application of spectroscopic techniques allowed, among others, for the determination of the binding constant, the number of classes of binding sites and the cooperativeness constant of the analyzed systems IBU-(d)HSA, IBU-(d)HSA-FPPA, IBU-(d)HSA-IBAP; the determination of the effect of ibuprofen and its degradation products on the secondary structure of albumin; identification and assessment of interactions between ligand and albumin; assessment of the impact of the presence of fatty acids in the structure of albumin and the measurement temperature on the binding of IBU, IBAP and FPPA to (d)HSA.</p><p><strong>Conclusion: </strong>The conducted research allowed us to conclude that the presence of ibuprofen degradation products and the increase in their concentration significantly affect the formation of the IBU-albumin complex and thus, the value of the association constant of the drug, changing the concentration of its free fraction in the blood plasma. It was also found that the presence of an ibuprofen degradation product in a complex with albumin affects its secondary structure.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729190","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: Interaction of PD-1 protein (present on immune T-cell) with its ligand PD-L1 (over-expressed on cancerous cell) makes the cancerous cell survive and thrive. The association of PD-1/PD-L1 represents a classical protein-protein interaction (PPI), where receptor and ligand binding through a large flat surface. Blocking the PD-1/PDL-1 complex formation can restore the normal immune mechanism, thereby destroying cancerous cells. However, the PD-1/PDL1 interactions are only partially characterized.
Objective: We aim to comprehend the time-dependent behavior of PD-1 upon its binding with PD-L1.
Methods: The current work focuses on a molecular dynamics simulation (MDs) simulation study of apo and ligand bound PD-1.
Results: Our simulation reveals the flexible nature of the PD-1, both in apo and bound form. Moreover, the current study also differentiates the type of strong and weak interactions which could be targeted to overcome the complex formation.
Conclusion: The current article could provide a valuable structural insight about the target protein (PD-1) and its ligand (PD-L1) which could open new opportunities in developing small molecule inhibitors (SMIs) targeting either PD-1 or PD-L1.
{"title":"Structural Insights of PD-1/PD-L1 Axis: An <i>In silico</i> Approach.","authors":"Shishir Rohit, Mehul Patel, Yogesh Jagtap, Umang Shah, Ashish Patel, Swayamprakash Patel, Nilay Solanki","doi":"10.2174/0113892037297012240408063250","DOIUrl":"10.2174/0113892037297012240408063250","url":null,"abstract":"<p><strong>Background: </strong>Interaction of PD-1 protein (present on immune T-cell) with its ligand PD-L1 (over-expressed on cancerous cell) makes the cancerous cell survive and thrive. The association of PD-1/PD-L1 represents a classical protein-protein interaction (PPI), where receptor and ligand binding through a large flat surface. Blocking the PD-1/PDL-1 complex formation can restore the normal immune mechanism, thereby destroying cancerous cells. However, the PD-1/PDL1 interactions are only partially characterized.</p><p><strong>Objective: </strong>We aim to comprehend the time-dependent behavior of PD-1 upon its binding with PD-L1.</p><p><strong>Methods: </strong>The current work focuses on a molecular dynamics simulation (MDs) simulation study of <i>apo</i> and ligand bound PD-1.</p><p><strong>Results: </strong>Our simulation reveals the flexible nature of the PD-1, both in <i>apo</i> and bound form. Moreover, the current study also differentiates the type of strong and weak interactions which could be targeted to overcome the complex formation.</p><p><strong>Conclusion: </strong>The current article could provide a valuable structural insight about the target protein (PD-1) and its ligand (PD-L1) which could open new opportunities in developing small molecule inhibitors (SMIs) targeting either PD-1 or PD-L1.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855956","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: 10.2174/0113892037291318240130103348
Felipe Pantoja Mesquita, Luina Benevides Lima, Emerson Lucena da Silva, Pedro Filho Noronha Souza, Maria Elisabete Amaral de Moraes, Rommel Mario Rodrigues Burbano, Raquel Carvalho Montenegro
Gastric adenocarcinoma is a complex disease with diverse genetic modifications, including Anaplastic Lymphoma Kinase (ALK) gene changes. The ALK gene is located on chromosome 2p23 and encodes a receptor tyrosine kinase that plays a crucial role in embryonic development and cellular differentiation. ALK alterations can result from gene fusion, mutation, amplification, or overexpression in gastric adenocarcinoma. Fusion occurs when the ALK gene fuses with another gene, resulting in a chimeric protein with constitutive kinase activity and promoting oncogenesis. ALK mutations are less common but can also result in the activation of ALK signaling pathways. Targeted therapies for ALK variations in gastric adenocarcinoma have been developed, including ALK inhibitors that have shown promising results in pre-clinical studies. Future studies are needed to elucidate the ALK role in gastric cancer and to identify predictive biomarkers to improve patient selection for targeted therapy. Overall, ALK alterations are a relevant biomarker for gastric adenocarcinoma treatment and targeted therapies for ALK may improve patients' overall survival.
{"title":"A Review on Anaplastic Lymphoma Kinase (ALK) Rearrangements and Mutations: Implications for Gastric Carcinogenesis and Target Therapy.","authors":"Felipe Pantoja Mesquita, Luina Benevides Lima, Emerson Lucena da Silva, Pedro Filho Noronha Souza, Maria Elisabete Amaral de Moraes, Rommel Mario Rodrigues Burbano, Raquel Carvalho Montenegro","doi":"10.2174/0113892037291318240130103348","DOIUrl":"10.2174/0113892037291318240130103348","url":null,"abstract":"<p><p>Gastric adenocarcinoma is a complex disease with diverse genetic modifications, including Anaplastic Lymphoma Kinase (ALK) gene changes. The ALK gene is located on chromosome 2p23 and encodes a receptor tyrosine kinase that plays a crucial role in embryonic development and cellular differentiation. ALK alterations can result from gene fusion, mutation, amplification, or overexpression in gastric adenocarcinoma. Fusion occurs when the ALK gene fuses with another gene, resulting in a chimeric protein with constitutive kinase activity and promoting oncogenesis. ALK mutations are less common but can also result in the activation of ALK signaling pathways. Targeted therapies for ALK variations in gastric adenocarcinoma have been developed, including ALK inhibitors that have shown promising results in pre-clinical studies. Future studies are needed to elucidate the ALK role in gastric cancer and to identify predictive biomarkers to improve patient selection for targeted therapy. Overall, ALK alterations are a relevant biomarker for gastric adenocarcinoma treatment and targeted therapies for ALK may improve patients' overall survival.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995878","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: 10.2174/0113892037291597240429094515
A Miraclin Prasanna, Priyankar Sen
Amyloid fibrils are formed from various pathological proteins. Monitoring their aggregation process is necessary for early detection and treatment. Among the available detection techniques, fluorescence is simple, intuitive, and convenient due to its sensitive and selective mode of detection. It has certain disadvantages like poor photothermal stability and detection state limitation. Research has focused on minimising the limitation by developing hybrid fluorescence techniques. This review focuses on the two ways fluorescence (intrinsic and extrinsic) has been used to monitor amyloid fibrils. In intrinsic/label free fluorescence: i) The fluorescence emission through aromatic amino acid residues like phenylalanine (F), tyrosine (Y) and tryptophan (W) is present in amyloidogenic peptides/protein sequence. And ii) The structural changes from alpha helix to cross-β-sheet structures during amyloid formation contribute to the fluorescence emission. The second method focuses on the use of extrinsic fluorophores to monitor amyloid fibrils i) organic dyes/small molecules, ii) fluorescent tagged proteins, iii) nanoparticles, iv) metal complexes and v) conjugated polymers. All these fluorophores have their own limitations. Developing them into hybrid fluorescence techniques and converting it into biosensors can contribute to early detection of disease.
{"title":"Recent Developments of Hybrid Fluorescence Techniques: Advances in Amyloid Detection Methods.","authors":"A Miraclin Prasanna, Priyankar Sen","doi":"10.2174/0113892037291597240429094515","DOIUrl":"10.2174/0113892037291597240429094515","url":null,"abstract":"<p><p>Amyloid fibrils are formed from various pathological proteins. Monitoring their aggregation process is necessary for early detection and treatment. Among the available detection techniques, fluorescence is simple, intuitive, and convenient due to its sensitive and selective mode of detection. It has certain disadvantages like poor photothermal stability and detection state limitation. Research has focused on minimising the limitation by developing hybrid fluorescence techniques. This review focuses on the two ways fluorescence (intrinsic and extrinsic) has been used to monitor amyloid fibrils. In intrinsic/label free fluorescence: i) The fluorescence emission through aromatic amino acid residues like phenylalanine (F), tyrosine (Y) and tryptophan (W) is present in amyloidogenic peptides/protein sequence. And ii) The structural changes from alpha helix to cross-β-sheet structures during amyloid formation contribute to the fluorescence emission. The second method focuses on the use of extrinsic fluorophores to monitor amyloid fibrils i) organic dyes/small molecules, ii) fluorescent tagged proteins, iii) nanoparticles, iv) metal complexes and v) conjugated polymers. All these fluorophores have their own limitations. Developing them into hybrid fluorescence techniques and converting it into biosensors can contribute to early detection of disease.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876117","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: Lung cancer (LC) is primarily responsible for cancer-related deaths worldwide. Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features and is associated with the development of tumors. CBX8, a member of the PcG protein family, plays a critical role in various cancers, containing LC. However, specific regulatory mechanisms of CBX8 in LC progression are not fully understood. This study aimed to investigate the regulatory role of CBX8 in LC progression.
Methods: Bioinformatics was used to analyze the relationship between CBX8 level and tumor and the enrichment pathway of CBX8 enrichment. qRT-PCR was used to detect the differential expression of CBX8 in LC cells and normal lung epithelial cells. The effects of knockdown or overexpression of CBX8 on the proliferation, migration and invasion of LC cells were evaluated by CCK- -8 assay and Transwell assay, and the levels of proteins associated with the EMT pathway and Wnt/ β-catenin signaling pathway were detected by western blot.
Results: Bioinformatics analysis revealed that CBX8 was highly expressed in LC and enriched on the Wnt/β-catenin signaling pathway. The expression level of CBX8 was significantly elevated in LC cells. Knockdown of CBX8 significantly inhibited cell proliferation, migration and invasion, and decreased the expression levels of EMT-related proteins and Wnt/β-catenin pathway-related proteins. Conversely, overexpression of CBX8 promoted cell proliferation, migration and invasion, and increased the expression levels of EMT-related proteins and Wnt/β-catenin pathway-related proteins. The Wnt inhibitor IWP-4 alleviated the effects produced by overexpression of CBX8.
Conclusion: Collectively, these data demonstrated that CBX8 induced EMT through Wnt/β-- catenin signaling, driving migration and invasion of LC cells.
{"title":"CBX8 Promotes Epithelial-mesenchymal Transition, Migration, and Invasion of Lung Cancer through Wnt/β-catenin Signaling Pathway.","authors":"Xiaoping Cai, Yuankai Lv, Jiongwei Pan, Zhuo Cao, Junzhi Zhang, Yuling Li, Hao Zheng","doi":"10.2174/0113892037273375231204080906","DOIUrl":"10.2174/0113892037273375231204080906","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer (LC) is primarily responsible for cancer-related deaths worldwide. Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features and is associated with the development of tumors. CBX8, a member of the PcG protein family, plays a critical role in various cancers, containing LC. However, specific regulatory mechanisms of CBX8 in LC progression are not fully understood. This study aimed to investigate the regulatory role of CBX8 in LC progression.</p><p><strong>Methods: </strong>Bioinformatics was used to analyze the relationship between CBX8 level and tumor and the enrichment pathway of CBX8 enrichment. qRT-PCR was used to detect the differential expression of CBX8 in LC cells and normal lung epithelial cells. The effects of knockdown or overexpression of CBX8 on the proliferation, migration and invasion of LC cells were evaluated by CCK- -8 assay and Transwell assay, and the levels of proteins associated with the EMT pathway and Wnt/ β-catenin signaling pathway were detected by western blot.</p><p><strong>Results: </strong>Bioinformatics analysis revealed that CBX8 was highly expressed in LC and enriched on the Wnt/β-catenin signaling pathway. The expression level of CBX8 was significantly elevated in LC cells. Knockdown of CBX8 significantly inhibited cell proliferation, migration and invasion, and decreased the expression levels of EMT-related proteins and Wnt/β-catenin pathway-related proteins. Conversely, overexpression of CBX8 promoted cell proliferation, migration and invasion, and increased the expression levels of EMT-related proteins and Wnt/β-catenin pathway-related proteins. The Wnt inhibitor IWP-4 alleviated the effects produced by overexpression of CBX8.</p><p><strong>Conclusion: </strong>Collectively, these data demonstrated that CBX8 induced EMT through Wnt/β-- catenin signaling, driving migration and invasion of LC cells.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542055","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: 10.2174/1389203724666230818111515
Haixing Lin, Runhong Zhou, Minna Zhang, Ruifeng Huang, Cuiqiong Fan, Shaofen Zhou, Jingnan Qiu, Jian He
Background: Dental caries is an oral disease associated with infection by microbial biofilm. The metabolic activity of cariogenic bacteria results in a pH decrease in the plaque biofilm, causing tooth demineralization. This acidic environment favors the growth of cariogenic bacteria that are highly resistant to strong acids, which, in turn, produce more acid resulting in a further decrease in the pH of the plaque biofilm. Therefore, the strategy of utilizing the acidic dental plaque microenvironment to prevent and treat dental caries has become a hot research topic in recent years, such as the development of pH-sensitive drug delivery systems.
Aims: Design of a new acid-activated antibacterial peptide.
Objectives: To design and synthesis an acid targeted antimicrobial peptide with the GWHHFFHFFHFF sequence.
Methods: Minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) testing confirmed its antibacterial activity. Propidium iodide (PI) staining was used to detect nucleic acid leakage. Determination of anti-biofilm activity by biofilm inhibition assay. A phototoxicity study confirmed the phototoxicity of PPIX-P12.
Results: MIC and MBC testing confirmed that P12 possessed acid-activated anti-Streptococcus mutans activity. Bactericidal kinetic experiments and propidium iodide (PI) staining experiments showed that P12 killed planktonic S. mutans UA159 cells leading to the leakage of nucleic acids in the acidic medium. Moreover, P12 showed acid-activated anti-biofilms at the early and mature biofilm stages. P12 was conjugated with the phototherapeutic agent protoporphyrin IX (PpIX) to construct the protoporphyrin derivative PpIX-P12. In vitro experiments revealed that PpIX-P12 displayed better antibacterial activity in pH 5.5 medium than in pH 7.2 medium.
Conclusion: In conclusion, we designed an acid-activated AMP, which had no antimicrobial activity at neutral pH, but had antimicrobial activity at an acidic pH.
{"title":"<i>In Vitro</i> Antibacterial Activity of a Novel Acid-Activated Antimicrobial Peptide against <i>Streptococcus mutans</i>.","authors":"Haixing Lin, Runhong Zhou, Minna Zhang, Ruifeng Huang, Cuiqiong Fan, Shaofen Zhou, Jingnan Qiu, Jian He","doi":"10.2174/1389203724666230818111515","DOIUrl":"10.2174/1389203724666230818111515","url":null,"abstract":"<p><strong>Background: </strong>Dental caries is an oral disease associated with infection by microbial biofilm. The metabolic activity of cariogenic bacteria results in a pH decrease in the plaque biofilm, causing tooth demineralization. This acidic environment favors the growth of cariogenic bacteria that are highly resistant to strong acids, which, in turn, produce more acid resulting in a further decrease in the pH of the plaque biofilm. Therefore, the strategy of utilizing the acidic dental plaque microenvironment to prevent and treat dental caries has become a hot research topic in recent years, such as the development of pH-sensitive drug delivery systems.</p><p><strong>Aims: </strong>Design of a new acid-activated antibacterial peptide.</p><p><strong>Objectives: </strong>To design and synthesis an acid targeted antimicrobial peptide with the GWHHFFHFFHFF sequence.</p><p><strong>Methods: </strong>Minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) testing confirmed its antibacterial activity. Propidium iodide (PI) staining was used to detect nucleic acid leakage. Determination of anti-biofilm activity by biofilm inhibition assay. A phototoxicity study confirmed the phototoxicity of PPIX-P12.</p><p><strong>Results: </strong>MIC and MBC testing confirmed that P12 possessed acid-activated anti-<i>Streptococcus mutans</i> activity. Bactericidal kinetic experiments and propidium iodide (PI) staining experiments showed that P12 killed planktonic <i>S. mutans</i> UA159 cells leading to the leakage of nucleic acids in the acidic medium. Moreover, P12 showed acid-activated anti-biofilms at the early and mature biofilm stages. P12 was conjugated with the phototherapeutic agent protoporphyrin IX (PpIX) to construct the protoporphyrin derivative PpIX-P12. <i>In vitro</i> experiments revealed that PpIX-P12 displayed better antibacterial activity in pH 5.5 medium than in pH 7.2 medium.</p><p><strong>Conclusion: </strong>In conclusion, we designed an acid-activated AMP, which had no antimicrobial activity at neutral pH, but had antimicrobial activity at an acidic pH.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10019205","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: 10.2174/1389203724666230830125423
Hugo Fernandes Oliveira Pires, Pablo Rayff da Silva, Arthur Lins Dias, Cleyton de Sousa Gomes, Natália Ferreira de Sousa, Aline Matilde Ferreira Dos Santos, Lívia Roberta Pimenta Souza, Jaislânia Lucena de Figueiredo Lima, Mayara Cecile Nascimento Oliveira, Cícero Francisco Bezerra Felipe, Reinaldo Nóbrega de Almeida, Ricardo Dias de Castro, Mirian Graciela da Silva Stiebbe Salvadori, Marcus Tullius Scotti, Luciana Scotti
Introduction: Brain tumors have high morbidity and mortality rates, accounting for 1.4% of all cancers. Gliomas are the most common primary brain tumors in adults. Currently, several therapeutic approaches are used; however, they are associated with side effects that affect patients'quality of life. Therefore, further studies are needed to develop novel therapeutic protocols with a more favorable side effect profile. In this context, cannabinoid compounds may serve as potential alternatives.
Objective: This study aimed to review the key enzymatic targets involved in glioma pathophysiology and evaluate the potential interaction of these targets with four cannabinoid derivatives through molecular docking simulations.
Methods: Molecular docking simulations were performed using four cannabinoid compounds and six molecular targets associated with glioma pathophysiology.
Results: Encouraging interactions between the selected enzymes and glioma-related targets were observed, suggesting their potential activity through these pathways. In particular, cannabigerol showed promising interactions with epidermal growth factor receptors and phosphatidylinositol 3- kinase, while Δ-9-tetrahydrocannabinol showed remarkable interactions with telomerase reverse transcriptase.
Conclusion: The evaluated compounds exhibited favorable interactions with the analyzed enzymatic targets, thus representing potential candidates for further in vitro and in vivo studies.
{"title":"Mechanisms Involved in the Therapeutic Effect of Cannabinoid Compounds on Gliomas: A Review with Experimental Approach.","authors":"Hugo Fernandes Oliveira Pires, Pablo Rayff da Silva, Arthur Lins Dias, Cleyton de Sousa Gomes, Natália Ferreira de Sousa, Aline Matilde Ferreira Dos Santos, Lívia Roberta Pimenta Souza, Jaislânia Lucena de Figueiredo Lima, Mayara Cecile Nascimento Oliveira, Cícero Francisco Bezerra Felipe, Reinaldo Nóbrega de Almeida, Ricardo Dias de Castro, Mirian Graciela da Silva Stiebbe Salvadori, Marcus Tullius Scotti, Luciana Scotti","doi":"10.2174/1389203724666230830125423","DOIUrl":"10.2174/1389203724666230830125423","url":null,"abstract":"<p><strong>Introduction: </strong>Brain tumors have high morbidity and mortality rates, accounting for 1.4% of all cancers. Gliomas are the most common primary brain tumors in adults. Currently, several therapeutic approaches are used; however, they are associated with side effects that affect patients'quality of life. Therefore, further studies are needed to develop novel therapeutic protocols with a more favorable side effect profile. In this context, cannabinoid compounds may serve as potential alternatives.</p><p><strong>Objective: </strong>This study aimed to review the key enzymatic targets involved in glioma pathophysiology and evaluate the potential interaction of these targets with four cannabinoid derivatives through molecular docking simulations.</p><p><strong>Methods: </strong>Molecular docking simulations were performed using four cannabinoid compounds and six molecular targets associated with glioma pathophysiology.</p><p><strong>Results: </strong>Encouraging interactions between the selected enzymes and glioma-related targets were observed, suggesting their potential activity through these pathways. In particular, cannabigerol showed promising interactions with epidermal growth factor receptors and phosphatidylinositol 3- kinase, while Δ-9-tetrahydrocannabinol showed remarkable interactions with telomerase reverse transcriptase.</p><p><strong>Conclusion: </strong>The evaluated compounds exhibited favorable interactions with the analyzed enzymatic targets, thus representing potential candidates for further <i>in vitro</i> and <i>in vivo</i> studies.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10112575","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}