The global pandemic caused by COVID-19 posed a significant challenge to public health, necessitating rapid scientific interventions to tackle the spread of infection. The review discusses the key areas of research on COVID-19 including viral genomics, epidemiology, pathogenesis, diagnostics, and therapeutics. The genome sequencing of the virus facilitated the tracking of its evolution, transmission dynamics, and identification of variants. Epidemiological studies have provided insights into disease spread, risk factors, and the impact of public health infrastructure and social distancing measures. Investigations of the viral pathogenesis have elucidated the mechanisms underlying immune responses and severe manifestations including the long-term effects of COVID-19. Overall, the article provides an updated overview of the diagnostic methods developed for SARS-CoV-2 and discusses their strengths, limitations, and appropriate utilization in different clinical and public health settings. Furthermore, therapeutic approaches including antiviral drugs, immunomodulatory therapies, and repurposed medications have been investigated to alleviate disease severity and improve patient outcomes. Through a comprehensive analysis of these scientific efforts, the review provides an overview of the advancements made in understanding and tackling SARS-CoV-2, while underscoring the need for continued research to address the evolving challenges posed by this global health crisis.
{"title":"Global Emergence of SARS-CoV2 Infection and Scientific Interventions to Contain its Spread.","authors":"Himanshu Ajmera, Sudarshan Singh Lakhawat, Naveen Malik, Akhilesh Kumar, Jasvinder Singh Bhatti, Vikram Kumar, Himanshu Gogoi, Sunil Kumar Jaswal, Sanjeev Chandel, Pushpender Kumar Sharma","doi":"10.2174/0113892037274719231212044235","DOIUrl":"10.2174/0113892037274719231212044235","url":null,"abstract":"<p><p>The global pandemic caused by COVID-19 posed a significant challenge to public health, necessitating rapid scientific interventions to tackle the spread of infection. The review discusses the key areas of research on COVID-19 including viral genomics, epidemiology, pathogenesis, diagnostics, and therapeutics. The genome sequencing of the virus facilitated the tracking of its evolution, transmission dynamics, and identification of variants. Epidemiological studies have provided insights into disease spread, risk factors, and the impact of public health infrastructure and social distancing measures. Investigations of the viral pathogenesis have elucidated the mechanisms underlying immune responses and severe manifestations including the long-term effects of COVID-19. Overall, the article provides an updated overview of the diagnostic methods developed for SARS-CoV-2 and discusses their strengths, limitations, and appropriate utilization in different clinical and public health settings. Furthermore, therapeutic approaches including antiviral drugs, immunomodulatory therapies, and repurposed medications have been investigated to alleviate disease severity and improve patient outcomes. Through a comprehensive analysis of these scientific efforts, the review provides an overview of the advancements made in understanding and tackling SARS-CoV-2, while underscoring the need for continued research to address the evolving challenges posed by this global health crisis.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"307-325"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542014","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: DHFR is an indispensable enzyme required for the survival of almost all prokaryotic and eukaryotic cells, making it an attractive molecular target for drug design.
Objective: In this study, a combined in silico and in vitro approach was utilized to screen out potential anticancer and antimicrobial agents by using DHFR PDB ID 2W9S (for antimicrobial) and 1U72 (for anticancer).
Methods: Computational work was performed using Maestro Schrodinger Glide software. The DHFR inhibitory activity of the selected compounds was assessed using the DHFR test kit (CS0340-Sigma- Aldrich).
Results: Exhaustive analysis of in silico results revealed that some natural phenolic acids have a good docking score when compared to standards, i.e., trimethoprim and methotrexate, and have astonishing interactions with crucial amino acid residues available in the binding pocket of DHFR, such as Phe 92, Asp 27, Ser 49, Asn 18, and Tyr 98. In particular, digallic acid and chlorogenic acid have amazing interactions with docking scores of -9.9 kcal/mol and -9.6 kcal/mol, respectively, for the targeted protein 2W9S. Docking scores of -10.3 kcal/mol and -10.2 kcal/mol, respectively, for targeted protein 1U72. The best hits were then tested in vitro to evaluate the DHFR inhibitory activity of the compounds. DHFR inhibition activity results are in correlation with molecular docking results.
Conclusion: In silico and in vitro results confirmed the good binding and inhibitory activity of some phenolic acids to the modeled target proteins. Among all the studied natural phenolic acids, chlorogenic acid, digallic acid, and rosmarinic acid appeared to be the most potential leads for future chemical alteration. This study can provide significant speculative guidance for the design and development of potent DHFR inhibitors in the future by using these compounds as leads.
{"title":"<i>In Silico</i> and <i>In vitro</i> Analysis of Phenolic Acids for Identification of Potential DHFR Inhibitors as Antimicrobial and Anticancer Agents.","authors":"Renu Sehrawat, Priyanka Rathee, Pooja Rathee, Sarita Khatkar, Esra Küpeli Akkol, Anurag Khatkar","doi":"10.2174/1389203724666230825142558","DOIUrl":"10.2174/1389203724666230825142558","url":null,"abstract":"<p><strong>Background: </strong>DHFR is an indispensable enzyme required for the survival of almost all prokaryotic and eukaryotic cells, making it an attractive molecular target for drug design.</p><p><strong>Objective: </strong>In this study, a combined <i>in silico</i> and <i>in vitro</i> approach was utilized to screen out potential anticancer and antimicrobial agents by using DHFR PDB ID 2W9S (for antimicrobial) and 1U72 (for anticancer).</p><p><strong>Methods: </strong>Computational work was performed using Maestro Schrodinger Glide software. The DHFR inhibitory activity of the selected compounds was assessed using the DHFR test kit (CS0340-Sigma- Aldrich).</p><p><strong>Results: </strong>Exhaustive analysis of <i>in silico</i> results revealed that some natural phenolic acids have a good docking score when compared to standards, i.e., trimethoprim and methotrexate, and have astonishing interactions with crucial amino acid residues available in the binding pocket of DHFR, such as Phe 92, Asp 27, Ser 49, Asn 18, and Tyr 98. In particular, digallic acid and chlorogenic acid have amazing interactions with docking scores of -9.9 kcal/mol and -9.6 kcal/mol, respectively, for the targeted protein 2W9S. Docking scores of -10.3 kcal/mol and -10.2 kcal/mol, respectively, for targeted protein 1U72. The best hits were then tested <i>in vitro</i> to evaluate the DHFR inhibitory activity of the compounds. DHFR inhibition activity results are in correlation with molecular docking results.</p><p><strong>Conclusion: </strong><i>In silico</i> and <i>in vitro</i> results confirmed the good binding and inhibitory activity of some phenolic acids to the modeled target proteins. Among all the studied natural phenolic acids, chlorogenic acid, digallic acid, and rosmarinic acid appeared to be the most potential leads for future chemical alteration. This study can provide significant speculative guidance for the design and development of potent DHFR inhibitors in the future by using these compounds as leads.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"44-58"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10111446","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: 10.2174/1389203724666230908114115
Renato R Roma, Lucas P Dias, Ana L E Santos, Romério R S Silva, Maria H C Santos, Bruno A M Rocha, Rômulo F Carneiro, Celso S Nagano, Alexandre H Sampaio, Maria L V Oliva, Cláudio G L Silva, Racquel O S Souza, Claudener S Teixeira
Introduction: Trypsin inhibitors (TIs) have the ability to competitively or non-competitively bind to trypsin and inhibit its action. These inhibitors are commonly found in plants and are used in protease inhibition studies involved in biochemical pathways of pharmacological interest.
Objectives: This work aimed to purify a trypsin inhibitor from Bauhinia pulchella seeds (BpuTI), describing its kinetic mechanism and anticoagulant effect.
Methods: Affinity chromatography, protein assay, and SDS-PAGE were used to purify the inhibitor. Mass spectrometry, inhibition assays, and enzyme kinetics were used to characterize the inhibitor. In vitro assays were performed to verify its ability to prolong blood clotting time.
Results: Affinity chromatography on a Trypsin-Sepharose 4B column gave a yield of 43.1. BpuTI has an apparent molecular mass of 20 kDa with glycosylation (1.15%). Protein identification was determined by MS/MS, and BpuTI showed similarity to several Kunitz-type trypsin inhibitors. BpuTI inhibited bovine trypsin as an uncompetitive inhibitor with IC50 (3 x 10-6 M) and Ki (1.05 x 10-6 M). Additionally, BpuTI showed high stability to temperature and pH variations, maintaining its activity up to 100ºC and in extreme pH ranges. However, the inhibitor was susceptible to reducing agents, such as DTT, which completely abolished its activity. BpuTI showed an anticoagulant effect in vitro at a concentration of 33 μM, prolonging clotting time by 2.6 times.
Conclusion: Our results suggest that BpuTI can be a biological tool to be used in blood clotting studies.
{"title":"Purification, Characterization and Evaluation of the Anticoagulant Effect of an Uncompetitive Trypsin Inhibitor obtained from <i>Bauhinia pulchella</i> (Benth) Seeds.","authors":"Renato R Roma, Lucas P Dias, Ana L E Santos, Romério R S Silva, Maria H C Santos, Bruno A M Rocha, Rômulo F Carneiro, Celso S Nagano, Alexandre H Sampaio, Maria L V Oliva, Cláudio G L Silva, Racquel O S Souza, Claudener S Teixeira","doi":"10.2174/1389203724666230908114115","DOIUrl":"10.2174/1389203724666230908114115","url":null,"abstract":"<p><strong>Introduction: </strong>Trypsin inhibitors (TIs) have the ability to competitively or non-competitively bind to trypsin and inhibit its action. These inhibitors are commonly found in plants and are used in protease inhibition studies involved in biochemical pathways of pharmacological interest.</p><p><strong>Objectives: </strong>This work aimed to purify a trypsin inhibitor from <i>Bauhinia pulchella</i> seeds (<i>Bpu</i>TI), describing its kinetic mechanism and anticoagulant effect.</p><p><strong>Methods: </strong>Affinity chromatography, protein assay, and SDS-PAGE were used to purify the inhibitor. Mass spectrometry, inhibition assays, and enzyme kinetics were used to characterize the inhibitor. <i>In vitro</i> assays were performed to verify its ability to prolong blood clotting time.</p><p><strong>Results: </strong>Affinity chromatography on a Trypsin-Sepharose 4B column gave a yield of 43.1. <i>Bpu</i>TI has an apparent molecular mass of 20 kDa with glycosylation (1.15%). Protein identification was determined by MS/MS, and <i>Bpu</i>TI showed similarity to several Kunitz-type trypsin inhibitors. <i>Bpu</i>TI inhibited bovine trypsin as an uncompetitive inhibitor with IC50 (3 x 10<sup>-6</sup> M) and Ki (1.05 x 10<sup>-6</sup> M). Additionally, <i>Bpu</i>TI showed high stability to temperature and pH variations, maintaining its activity up to 100ºC and in extreme pH ranges. However, the inhibitor was susceptible to reducing agents, such as DTT, which completely abolished its activity. <i>Bpu</i>TI showed an anticoagulant effect <i>in vitro</i> at a concentration of 33 μM, prolonging clotting time by 2.6 times.</p><p><strong>Conclusion: </strong>Our results suggest that <i> Bpu</i>TI can be a biological tool to be used in blood clotting studies.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"172-182"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10554809","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}
The human genetic structure undergoes continuous wear and tear process due to the mere presence of extrinsic as well as intrinsic factors. In normal physiological cells, DNA damage initiates various checkpoints that may activate the repair system or induce apoptosis that helps maintain cellular integrity. While in cancerous cells, due to alterations in signaling pathways and defective checkpoints, there exists a marked deviation of error-free DNA repairing/synthesis. Currently, cancer therapy targeting the DNA damage response shows significant therapeutic potential by tailoring the therapy from non-specific to tumor-specific activity. Recently, numerous drugs that target the DNA replicating enzymes have been approved or some are under clinical trial. Drugs like PARP and PARG inhibitors showed sweeping effects against cancer cells. This review highlights the mechanistic study of different drug categories that target DNA replication and thus depicts the futuristic approach of targeted therapy.
仅仅由于外在和内在因素的存在,人类基因结构就经历了持续的磨损过程。在正常的生理细胞中,DNA 损伤会启动各种检查点,从而激活修复系统或诱导细胞凋亡,帮助维持细胞的完整性。而在癌细胞中,由于信号通路的改变和检查点的缺陷,存在着明显的无差错 DNA 修复/合成偏差。目前,以 DNA 损伤反应为靶点的癌症疗法具有显著的治疗潜力,可将非特异性疗法调整为肿瘤特异性疗法。最近,许多针对 DNA 复制酶的药物已经获得批准,或正在进行临床试验。PARP和PARG抑制剂等药物对癌细胞产生了巨大的作用。这篇综述重点介绍了针对 DNA 复制的不同药物类别的机理研究,从而描绘了靶向治疗的未来发展方向。
{"title":"Mechanism-based Suppression of Cancer by Targeting DNA-Replicating Enzymes.","authors":"Preeti Arya, Hitesh Malhotra, Benu Chaudhary, Amrit Sarwara, Rajat Goyal, Chunpeng Wan, Dinesh Kumar Mishra, Rupesh Kumar Gautam","doi":"10.2174/1389203724666230512144011","DOIUrl":"10.2174/1389203724666230512144011","url":null,"abstract":"<p><p>The human genetic structure undergoes continuous wear and tear process due to the mere presence of extrinsic as well as intrinsic factors. In normal physiological cells, DNA damage initiates various checkpoints that may activate the repair system or induce apoptosis that helps maintain cellular integrity. While in cancerous cells, due to alterations in signaling pathways and defective checkpoints, there exists a marked deviation of error-free DNA repairing/synthesis. Currently, cancer therapy targeting the DNA damage response shows significant therapeutic potential by tailoring the therapy from non-specific to tumor-specific activity. Recently, numerous drugs that target the DNA replicating enzymes have been approved or some are under clinical trial. Drugs like PARP and PARG inhibitors showed sweeping effects against cancer cells. This review highlights the mechanistic study of different drug categories that target DNA replication and thus depicts the futuristic approach of targeted therapy.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"4-11"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9462864","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: 10.2174/0113892037238265231006051215
Zhuoyu Li, Ziming Han
In recent years, the CRISPR/Cas9 system has become a rapidly advancing gene editing technology with significant advantages in various fields, particularly biomedicine. Liver cancer is a severe malignancy that threatens human health and is primarily treated with surgery, radiotherapy, and chemotherapy. However, surgery may not be suitable for advanced cases of liver cancer with distant metastases. Moreover, radiotherapy and chemotherapy have low specificity and numerous side effects that limit their effectiveness; therefore, more effective and safer treatments are required. With the advancement of the biomolecular mechanism of cancer, CRISPR/Cas9 gene editing technology has been widely used in the study of liver cancer to gain insights into gene functions, establish tumor models, screen tumor phenotype-related genes, and perform gene therapy. This review outlines the research progress of CRISPR/Cas9 gene editing technology in the treatment of liver cancer and provides a relevant theoretical basis for its research and application in the treatment of liver cancer.
{"title":"Advancements of the CRISPR/Cas9 System in the Treatment of Liver Cancer.","authors":"Zhuoyu Li, Ziming Han","doi":"10.2174/0113892037238265231006051215","DOIUrl":"10.2174/0113892037238265231006051215","url":null,"abstract":"<p><p>In recent years, the CRISPR/Cas9 system has become a rapidly advancing gene editing technology with significant advantages in various fields, particularly biomedicine. Liver cancer is a severe malignancy that threatens human health and is primarily treated with surgery, radiotherapy, and chemotherapy. However, surgery may not be suitable for advanced cases of liver cancer with distant metastases. Moreover, radiotherapy and chemotherapy have low specificity and numerous side effects that limit their effectiveness; therefore, more effective and safer treatments are required. With the advancement of the biomolecular mechanism of cancer, CRISPR/Cas9 gene editing technology has been widely used in the study of liver cancer to gain insights into gene functions, establish tumor models, screen tumor phenotype-related genes, and perform gene therapy. This review outlines the research progress of CRISPR/Cas9 gene editing technology in the treatment of liver cancer and provides a relevant theoretical basis for its research and application in the treatment of liver cancer.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"154-162"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233097","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}
Diabetic wound healing is expected to affect 25% of all diabetics, resulting in less severe external factors, economic costs, and less trauma. Topical formulations have been continually improved to achieve a range of amazing properties and have had a significant impact on the management of diabetic wounds. Topical insulin has become one of the most attractive and convenient wound healing techniques due to its excellent biocompatibility, water retention, and therapeutic properties. Multiple versatile topical insulins have been identified and have shown promise over the past few years as they greatly facilitate the management of diabetic wounds as we understand their etiology. The physiological wound healing process repairs damaged tissue and restores skin integrity. For about a century, insulin, a powerful healing agent, and it has been utilized in several clinical and experimental researches research studies to accelerate the healing of various injuries.
{"title":"Diabetic Wound: Pathophysiology, Complications and Treatment Strategies.","authors":"Sunita Chauhan, Monika Gulia, Rahul Pratap Singh, Vikas Jhawat","doi":"10.2174/0113892037276171231016103320","DOIUrl":"10.2174/0113892037276171231016103320","url":null,"abstract":"<p><p>Diabetic wound healing is expected to affect 25% of all diabetics, resulting in less severe external factors, economic costs, and less trauma. Topical formulations have been continually improved to achieve a range of amazing properties and have had a significant impact on the management of diabetic wounds. Topical insulin has become one of the most attractive and convenient wound healing techniques due to its excellent biocompatibility, water retention, and therapeutic properties. Multiple versatile topical insulins have been identified and have shown promise over the past few years as they greatly facilitate the management of diabetic wounds as we understand their etiology. The physiological wound healing process repairs damaged tissue and restores skin integrity. For about a century, insulin, a powerful healing agent, and it has been utilized in several clinical and experimental researches research studies to accelerate the healing of various injuries.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"200-205"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421455","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: 10.2174/0113892037264538231128072614
Muhammad Haris Ramzan, Mohsin Shah, Faiqah Ramzan
Background: Neurokinin B; an endogenous decapeptide, mediates its reproductive physiological actions through gonadotropin releasing hormone. Despite the potential role of Neurokinin B on seminal vesicles, its effects on seminal vesicles in adult male mammals remain elusive. We aimed to investigate the potentials of variable doses of Neurokinin B, its agonist and antagonist on histomorphology and expression of NK3R on seminal vesicles, and secretory activity of seminal vesicles in adult male rats.
Methods: Adult male Sprague Dawley rats (n=10 in each group) were administered intraperitoneally with Neurokinin B in three variable doses: 1 μg, 1 ηg and 10 ρg while, Senktide (Neurokinin B agonist) and SB222200 (Neurokinin B antagonist) in 1 μg doses consecutively for 12 days. After 12 days of peptide treatment, half of the animals (n=05) in each group were sacrificed while remaining half (n=05) were kept for another 12 days without any treatment to investigate treatment reversal. Seminal vesicles were dissected and excised tissue was processed for light microscopy, immunohistochemistry and estimation of seminal fructose levels.
Results: Treatment with Neurokinin B and Senktide significantly increased while SB222200 slightly decrease the seminal vesicles weight, epithelial height and seminal fructose levels as compared to control. Light microscopy revealed increased epithelial height and epithelial folding as compared to control in all Neurokinin B and Senktide treated groups while decreased in SB222200. Effects of various doses of Neurokinin B, Senktide and SB222200 on seminal vesicles weight, epithelial height, seminal fructose levels and histomorphology were reversed when rats were maintained without treatments. Immuno-expression of Neurokinin B shows no change in treatment and reversal groups.
Conclusion: Continuous administration of Neurokinin B and Senktide effect positively while SB222200 have detrimental effects on cellular morphology, epithelial height and seminal fructose levels in seminal vesicles. Effects of peptide treatments depicted a reversal towards control group when rats were kept without any treatment.
背景:神经激肽 B 是一种内源性十肽,通过促性腺激素释放激素介导其生殖生理作用。尽管神经激肽B对精囊具有潜在作用,但其对成年雄性哺乳动物精囊的影响仍然难以捉摸。我们旨在研究不同剂量的神经激肽B、其激动剂和拮抗剂对成年雄性大鼠精囊组织形态学、精囊上NK3R的表达以及精囊分泌活性的潜在影响:成年雄性 Sprague Dawley 大鼠(每组 10 只)腹腔注射三种不同剂量的神经激肽 B:1 μg、1 ηg和10 μg,同时连续注射1 μg剂量的Senktide(神经激肽B激动剂)和SB222200(神经激肽B拮抗剂)12天。多肽治疗 12 天后,每组一半动物(n=05)被处死,另一半动物(n=05)在没有任何治疗的情况下再保留 12 天,以研究治疗逆转。解剖精囊并对切除的组织进行光镜观察、免疫组化和精液果糖水平评估:结果:与对照组相比,神经激肽B和Senktide能明显增加精囊重量、上皮高度和精液果糖水平,而SB222200能略微降低精囊重量、上皮高度和精液果糖水平。光镜观察显示,与对照组相比,所有神经激肽 B 和参肽处理组的上皮高度和上皮褶皱均有所增加,而 SB222200 处理组则有所减少。不同剂量的神经激肽 B、Senktide 和 SB222200 对精囊重量、上皮高度、精液果糖水平和组织形态学的影响在大鼠未接受治疗的情况下被逆转。神经激肽 B 的免疫表达在治疗组和逆转组均无变化:连续给药神经激肽 B 和 SB222200 会对精囊细胞形态、上皮高度和精液果糖水平产生积极影响,而 SB222200 则会产生有害影响。当大鼠未接受任何治疗时,肽治疗的效果会向对照组逆转。
{"title":"Neurokinin B Administration Induces Dose Dependent Proliferation of Seminal Vesicles in Adult Rats.","authors":"Muhammad Haris Ramzan, Mohsin Shah, Faiqah Ramzan","doi":"10.2174/0113892037264538231128072614","DOIUrl":"10.2174/0113892037264538231128072614","url":null,"abstract":"<p><strong>Background: </strong>Neurokinin B; an endogenous decapeptide, mediates its reproductive physiological actions through gonadotropin releasing hormone. Despite the potential role of Neurokinin B on seminal vesicles, its effects on seminal vesicles in adult male mammals remain elusive. We aimed to investigate the potentials of variable doses of Neurokinin B, its agonist and antagonist on histomorphology and expression of NK3R on seminal vesicles, and secretory activity of seminal vesicles in adult male rats.</p><p><strong>Methods: </strong>Adult male Sprague Dawley rats (n=10 in each group) were administered intraperitoneally with Neurokinin B in three variable doses: 1 μg, 1 ηg and 10 ρg while, Senktide (Neurokinin B agonist) and SB222200 (Neurokinin B antagonist) in 1 μg doses consecutively for 12 days. After 12 days of peptide treatment, half of the animals (n=05) in each group were sacrificed while remaining half (n=05) were kept for another 12 days without any treatment to investigate treatment reversal. Seminal vesicles were dissected and excised tissue was processed for light microscopy, immunohistochemistry and estimation of seminal fructose levels.</p><p><strong>Results: </strong>Treatment with Neurokinin B and Senktide significantly increased while SB222200 slightly decrease the seminal vesicles weight, epithelial height and seminal fructose levels as compared to control. Light microscopy revealed increased epithelial height and epithelial folding as compared to control in all Neurokinin B and Senktide treated groups while decreased in SB222200. Effects of various doses of Neurokinin B, Senktide and SB222200 on seminal vesicles weight, epithelial height, seminal fructose levels and histomorphology were reversed when rats were maintained without treatments. Immuno-expression of Neurokinin B shows no change in treatment and reversal groups.</p><p><strong>Conclusion: </strong>Continuous administration of Neurokinin B and Senktide effect positively while SB222200 have detrimental effects on cellular morphology, epithelial height and seminal fructose levels in seminal vesicles. Effects of peptide treatments depicted a reversal towards control group when rats were kept without any treatment.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"339-352"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511251","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}
Bioconjugation techniques have emerged as powerful tools for enhancing the stability and targeting efficiency of protein and peptide therapeutics. This review provides a comprehensive analysis of the various bioconjugation strategies employed in the field. The introduction highlights the significance of bioconjugation techniques in addressing stability and targeting challenges associated with protein and peptide-based drugs. Chemical and enzymatic bioconjugation methods are discussed, along with crosslinking strategies for covalent attachment and site-specific conjugation approaches. The role of bioconjugation in improving stability profiles is explored, showcasing case studies that demonstrate successful stability enhancement. Furthermore, bioconjugation techniques for ligand attachment and targeting are presented, accompanied by examples of targeted protein and peptide therapeutics. The review also covers bioconjugation approaches for prolonging circulation and controlled release, focusing on strategies to extend half-life, reduce clearance, and design-controlled release systems. Analytical characterization techniques for bioconjugates, including the evaluation of conjugation efficiency, stability, and assessment of biological activity and targeting efficiency, are thoroughly examined. In vivo considerations and clinical applications of bioconjugated protein and peptide therapeutics, including pharmacokinetic and pharmacodynamic considerations, as well as preclinical and clinical developments, are discussed. Finally, the review concludes with an overview of future perspectives, emphasizing the potential for novel conjugation methods and advanced targeting strategies to further enhance the stability and targeting efficiency of protein and peptide therapeutics.
{"title":"Bioconjugation Techniques for Enhancing Stability and Targeting Efficiency of Protein and Peptide Therapeutics.","authors":"Tanuja Bisht, Anupriya Adhikari, Shivanand Patil, Shivang Dhoundiyal","doi":"10.2174/0113892037268777231013154850","DOIUrl":"10.2174/0113892037268777231013154850","url":null,"abstract":"<p><p>Bioconjugation techniques have emerged as powerful tools for enhancing the stability and targeting efficiency of protein and peptide therapeutics. This review provides a comprehensive analysis of the various bioconjugation strategies employed in the field. The introduction highlights the significance of bioconjugation techniques in addressing stability and targeting challenges associated with protein and peptide-based drugs. Chemical and enzymatic bioconjugation methods are discussed, along with crosslinking strategies for covalent attachment and site-specific conjugation approaches. The role of bioconjugation in improving stability profiles is explored, showcasing case studies that demonstrate successful stability enhancement. Furthermore, bioconjugation techniques for ligand attachment and targeting are presented, accompanied by examples of targeted protein and peptide therapeutics. The review also covers bioconjugation approaches for prolonging circulation and controlled release, focusing on strategies to extend half-life, reduce clearance, and design-controlled release systems. Analytical characterization techniques for bioconjugates, including the evaluation of conjugation efficiency, stability, and assessment of biological activity and targeting efficiency, are thoroughly examined. <i>In vivo</i> considerations and clinical applications of bioconjugated protein and peptide therapeutics, including pharmacokinetic and pharmacodynamic considerations, as well as preclinical and clinical developments, are discussed. Finally, the review concludes with an overview of future perspectives, emphasizing the potential for novel conjugation methods and advanced targeting strategies to further enhance the stability and targeting efficiency of protein and peptide therapeutics.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"226-243"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421552","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}
ARL15 is a member of the RAS superfamily of small GTPases and is associated with several metabolic traits, including increased risk of diabetes, rheumatoid arthritis and lipid metabolism disorders. The ARL15 gene encodes for an uncharacterized small GTP binding protein. Its precise role in human physiology remains unknown, but several genetic association studies have recognized different variants in this gene to be statistically associated with numerous traits and complex diseases. Here, we provided the unique features of ARL15 small G protein, its association with varied metabolic and lifestyle diseases, its function in vesicular and lipid trafficking, and its binding partners. We outlined this protein as a promising and emerging therapeutic target to combat metabolic disorders like cardiovascular diseases, diabetes and rheumatoid arthritis. The review provides a comprehensive description of the current advancements in ARL15 research with a perspective that focused research will position this small GTPase as a viable target for the treatment of rheumatoid arthritis.
{"title":"ARL15 and its Multiple Disease Association: Emerging Functions and Potential Therapeutic Application.","authors":"Manisha Saini, Varnita Anand, Aditya Sharma, Anuj Pandey, Bittianda Kuttapa Thelma, Suman Kundu","doi":"10.2174/1389203724666230915123217","DOIUrl":"10.2174/1389203724666230915123217","url":null,"abstract":"<p><p>ARL15 is a member of the RAS superfamily of small GTPases and is associated with several metabolic traits, including increased risk of diabetes, rheumatoid arthritis and lipid metabolism disorders. The ARL15 gene encodes for an uncharacterized small GTP binding protein. Its precise role in human physiology remains unknown, but several genetic association studies have recognized different variants in this gene to be statistically associated with numerous traits and complex diseases. Here, we provided the unique features of ARL15 small G protein, its association with varied metabolic and lifestyle diseases, its function in vesicular and lipid trafficking, and its binding partners. We outlined this protein as a promising and emerging therapeutic target to combat metabolic disorders like cardiovascular diseases, diabetes and rheumatoid arthritis. The review provides a comprehensive description of the current advancements in ARL15 research with a perspective that focused research will position this small GTPase as a viable target for the treatment of rheumatoid arthritis.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"137-153"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286952","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}
Skeletal muscle tissue has the critical function of mechanical support protecting the body. In addition, its functions are strongly influenced by the balanced synthesis and degradation processes of structural and regulatory proteins. The inhibition of protein synthesis and/or the activation of catabolism generally determines a pathological state or condition called muscle atrophy, a reduction in muscle mass that results in partial or total loss of function. It has been established that many pathophysiological conditions can cause a decrease in muscle mass. Skeletal muscle innervation involves stable and functional neural interactions with muscles via neuromuscular junctions and is essential for maintaining normal muscle structure and function. Loss of motor innervation induces rapid skeletal muscle fiber degeneration with activation of atrophy-related signaling and subsequent disassembly of sarcomeres, altering normal muscle function. After denervation, an inflammation stage is characterized by the increased expression of pro-inflammatory cytokines that determine muscle atrophy. In this review, we highlighted the impact of some soluble factors on the development of muscle atrophy by denervation.
{"title":"Soluble Factors Associated with Denervation-induced Skeletal Muscle Atrophy.","authors":"Marianny Portal Rodríguez, Claudio Cabello-Verrugio","doi":"10.2174/0113892037189827231018092036","DOIUrl":"10.2174/0113892037189827231018092036","url":null,"abstract":"<p><p>Skeletal muscle tissue has the critical function of mechanical support protecting the body. In addition, its functions are strongly influenced by the balanced synthesis and degradation processes of structural and regulatory proteins. The inhibition of protein synthesis and/or the activation of catabolism generally determines a pathological state or condition called muscle atrophy, a reduction in muscle mass that results in partial or total loss of function. It has been established that many pathophysiological conditions can cause a decrease in muscle mass. Skeletal muscle innervation involves stable and functional neural interactions with muscles <i>via</i> neuromuscular junctions and is essential for maintaining normal muscle structure and function. Loss of motor innervation induces rapid skeletal muscle fiber degeneration with activation of atrophy-related signaling and subsequent disassembly of sarcomeres, altering normal muscle function. After denervation, an inflammation stage is characterized by the increased expression of pro-inflammatory cytokines that determine muscle atrophy. In this review, we highlighted the impact of some soluble factors on the development of muscle atrophy by denervation.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"189-199"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451166","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}