Current protein & peptide science最新文献

{"title":"Revolutionizing Infertility Management through Novel Peptide-based Targets.","authors":"Vijay Kumar, Gaurav Doshi","doi":"10.2174/0113892037304433240430144106","DOIUrl":"10.2174/0113892037304433240430144106","url":null,"abstract":"<p><p>Around 48 million couples and 186 million people worldwide have infertility; of these, approximately 85% have an identifiable cause, the most common being ovulatory dysfunctions, male infertility, polycystic ovary syndrome, and tubule disease. The remaining 15% have infertility for unknown reasons, including lifestyle and environmental factors. The regulation of the hypothalamic- pituitary-adrenal axis (HPA) is crucial for the secretion of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), which are essential for female reproductive functions. GnRH is the primary reproductive axis regulator. The pattern of GnRH, FSH, and LH release is determined by its pulsatile secretion, which in turn controls endocrine function and gamete maturation in the gonads. Peptides called Kisspeptin (KP), Neurokinin-B (NKB), and Orexin influence both positive and negative feedback modulation of GnRH, FSH, and LH secretion in reproduction. This review article mainly focuses on the historical perspective, isoform, and signaling pathways of KP, NKB, and Orexin novel peptide-based targets including clinical and preclinical studies and having a promising effect in the management of infertility.</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":"141080728","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}

{"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":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":"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}

{"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":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":"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}

{"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^-6 M) and Ki (1.05 x 10^-6 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":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":"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}

{"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":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":"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}

{"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":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":"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}

{"title":"Hypoxia A Typical Target in Human Lung Cancer Therapy.","authors":"Asmat Ullah, Somia Shehzadi, Najeeb Ullah, Touseef Nawaz, Haroon Iqbal, Tariq Aziz","doi":"10.2174/0113892037252820231114045234","DOIUrl":"10.2174/0113892037252820231114045234","url":null,"abstract":"<p><p>Lung cancer (LC) is the leading cause of cancer-related death globally. Comprehensive knowledge of the cellular and molecular etiology of LC is perilous for the development of active treatment approaches. Hypoxia in cancer is linked with malignancy, and its phenotype is implicated in the hypoxic reaction, which is being studied as a prospective cancer treatment target. The hypervascularization of the tumor is the main feature of human LC, and hypoxia is a major stimulator of neo-angiogenesis. It was seen that low oxygen levels in human LC are a critical aspect of this lethal illness. However, as there is a considerable body of literature espousing the presumed functional relevance of hypoxia in LC, the direct measurement of oxygen concentration in Human LC is yet to be determined. This narrative review aims to show the importance and as a future target for novel research studies that can lead to the perception of LC therapy in hypoxic malignancies.</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":"138458461","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}

{"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":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":"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}

{"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":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":"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}

{"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":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":"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}