{"title":"Peptide Biomarkers - An Emerging Diagnostic Tool and Current Applicable Assay.","authors":"Jing Wu, Rui Yang","doi":"10.2174/0113892037315736240907131856","DOIUrl":"10.2174/0113892037315736240907131856","url":null,"abstract":"<p><p>In the past few decades, impressive progress achieved in technology development and improvement has accelerated the application of peptides as diagnostic biomarkers for various diseases. We outline the advantages of peptides as good diagnostic targets, since they serve as molecular surrogates of enzyme activities, much more specific biomarkers than proteins, and also play vital roles in many biological processes. On the basis of an extensive literature survey, peptide markers with high specificity and sensitivity that are currently applied in clinical tests, as well as recently identified, are summarized for the following four major categories of diseases: neurodegenerative disease, heart failure, infectious disease, and cancer. In addition, we summarize a few prevalent techniques used in peptide biomarker discovery and analysis, such as immunoassays, nanopore-based and nanoparticle-based peptide detection, and also MS-based peptide analysis techniques, and their pros and cons. Currently, there are plenty of analytical technologies available to achieve fast, sensitive and reliable peptide analyses, benefiting from the developments of hardware and instrumentation, as well as data analysis software and databases. Thus, with peptides emerging as sensitive, specific and reliable biomarkers for early detection of diseases, therapeutic monitoring, clinical treatment decisions and disease prognosis, the medical need for peptide biomarkers will increase strongly in the future.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"167-184"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343284","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":"An Anticancer Bioactive Peptide Combined with Oxaliplatin Inhibited Gastric Cancer Cells <i>In vitro</i> and <i>In vivo</i>.","authors":"Xian Li, Lihua Kang, Wenyan Han, Xiulan Su","doi":"10.2174/0113892037350632241205040150","DOIUrl":"10.2174/0113892037350632241205040150","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer has become one of the major diseases threatening human health. This study aimed to investigate the mechanism of an anticancer bioactive peptide (ACBP) combined with oxaliplatin (OXA) on MKN-45, SGC7901, and NCI-N87 differentiated human gastric cancer cells and GES-1 immortalized human gastric mucosal epithelial cells. The therapeutic effect and action mechanism of short-term intermittent ACBP combined with OXA on nude mice with human gastric cancer were also investigated.</p><p><strong>Methods: </strong>The half-maximal inhibitory concentrations of these agents in these cells were measured by an MTT assay, and cell morphological changes were observed by H&E staining. The expression of Lin28, miR-107, miR-609, and Let-7 in these four cell lines was determined by q-PCR after drug treatment. Lin28 protein expression in these four cell lines treated with these drugs was measured by western blotting. Furthermore, activity and quality of life were observed daily in all tumor-bearing nude mice, and the expression of Lin28 in tumor tissue was determined by immunohistochemistry and RT-PCR.</p><p><strong>Results: </strong>The results showed that ACBP inhibited the proliferation of MKN-45, SGC7901, and NCI-N87 gastric cancer cells in a dose-dependent manner and weakly suppressed the proliferation of GES-1 cells. Moreover, its inhibitory effect on proliferation was stronger in poorly differentiated gastric cancer cells. ACBP, OXA, and the combination upregulated Lin28 gene expression in MKN-45 cells and downregulated it in SGC7901 and GES-1 cells. ACBP and the combination therapy downregulated Let-7 expression in MKN-45 cells and upregulated Let-7 expression in SGC7901 cells. The combination of ACBP with OXA demonstrated significant anticancer sensitization. Moreover, it also significantly improved the quality of life of tumor-bearing nude mice and reduced the toxic side effects of chemotherapeutic drugs on nude mice.</p><p><strong>Conclusion: </strong>ACBP alone and in combination with oxaliplatin influenced the expression of tumor stem cell marker gene Lin28 and regulated the expression of microRNAs specifically regulated by Lin28. In addition, the anticancer effects and attenuated sensitization effects of ACBP may be related to the Lin28/miRNA-107 signaling pathway, acting by inhibiting the proliferation of cancerous stem cells. The findings of this study provide a scientific basis for exploring the antitumor mechanism of ACBP alone and combined with chemotherapeutic drugs.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"493-510"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946116","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":"Chitosan-Peptide Composites for Tissue Engineering Applications: Advances in Treatment Strategies.","authors":"Swati Gupta Sanjaykumar, Rishabha Malviya, Saurabh Srivastava, Irfan Ahmad, Prerna Uniyal, Bhupinder Singh, Nazima Nisar","doi":"10.2174/0113892037323136240910052119","DOIUrl":"10.2174/0113892037323136240910052119","url":null,"abstract":"<p><p>One of the most well-known instances of an interdisciplinary subject is tissue engineering, where experts from many backgrounds collaborate to address important health issues and improve people's quality of life. Many researchers are interested in using chitosan and its derivatives as an alternative to fabricating scaffold engineering and skin grafts in tissue because of its natural abundance, affordability, biodegradability, biocompatibility, and wound healing properties. Nanomaterials based on peptides can provide cells with the essential biological cues required to promote cellular adhesion and are easily fabricated. Due to such worthy properties of chitosan and peptide, they find their application in tissue engineering and regeneration processes. The implementation of hybrids of chitosan and peptide is increasing in the field of tissue engineering and scaffolding for improved cellular adherence and bioactivity. This review covers the individual applications of peptide and chitosan in tissue engineering and further discusses the role of their conjugates in the same. Here, the recent findings are also discussed, along with studies involving the use of these hybrids in tissue engineering applications.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"185-200"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343282","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":"Human Paraoxonase 1: From Bloodstream Enzyme to Disease Fighter & Therapeutic Intervention.","authors":"Prakash Yadnyakant Khandave, Khushi Goyal, Prakashkumar Dobariya, Abhay Hariram Pande","doi":"10.2174/0113892037335325241011162207","DOIUrl":"10.2174/0113892037335325241011162207","url":null,"abstract":"<p><p>Human paraoxonase 1 (hPON1) is a Ca2+-dependent metalloenzyme with multifunctional properties. Due to its diverse activities (arylesterase, phosphotriesterase, and lactonase), it plays a significant role in disease conditions. Researchers across the globe have demonstrated different properties of PON1, like anti-oxidant, anti-inflammatory, anti-atherogenic, anti-diabetic, and OPneutralization. Due to its pleotropic role in disease conditions like atherosclerosis, diabetes, cardiovascular diseases, neurodegenerative disorders, and OP-poisoning, it can be considered as a potential candidate for the development of therapeutic interventions. Attempts are being made in this direction to identify the exact role of PON1 in these disease conditions. Different approaches like directed evolution, genetic as well as chemical fusion, liposomal delivery of PON1, etc., are being developed and evaluated for their therapeutic effects in different pathological conditions. In this review, we outline the exact role and involvement of different properties of PON1 in the pathophysiology of different diseases and how it can be utilized and developed as a therapeutic intervention in PON1-associated disease conditions.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"282-295"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892819","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}
Cadena-Cadena Francisco, Ezquerra-Brauer Josafat Marina, Cinco-Moroyoqui Francisco Javier, López-Zavala Alonso Alexis, Santacruz-Ortega Hisila Del Carmen, Rivero-Espejel Ignacio Alfredo, Rouzaud-Sández Ofelia, Cardenas-Lopez Jose Luis
{"title":"The Impact of Thermal and pH Variations on the Structure of Cathepsin D in the Hepatopancreas of Japanese Clam (<i>Ruditapes philippinarum</i>).","authors":"Cadena-Cadena Francisco, Ezquerra-Brauer Josafat Marina, Cinco-Moroyoqui Francisco Javier, López-Zavala Alonso Alexis, Santacruz-Ortega Hisila Del Carmen, Rivero-Espejel Ignacio Alfredo, Rouzaud-Sández Ofelia, Cardenas-Lopez Jose Luis","doi":"10.2174/0113892037244173241206055736","DOIUrl":"10.2174/0113892037244173241206055736","url":null,"abstract":"<p><strong>Background: </strong>Cathepsin D is a lysosomal enzyme that plays a critical role in the process of protein catabolism. In marine organisms, research has primarily concentrated on the identification of the enzyme. However, in crustaceans and molluscs, it is known to have digestive functions, as it is the sole enzyme responsible for protein degradation at extremely acidic pH in the hepatopancreas. In the Japanese clam (<i>Ruditapes philippinarum</i>), cathepsin D was purified and partially characterised from the hepatopancreas.</p><p><strong>Methods: </strong>To evaluate changes in secondary structure, circular dichroism (CD) was employed under a range of 5-70°C and pH of 1-7.5. Following dissection, the enzyme was purified from the hepatopancreas by ultrafiltration and affinity chromatography. SDS-PAGE was used to verify the sample purity, and gel filtration was used to determine the molecular weight. CD spectra were obtained at a concentration of 0.125 mg/mL, expressed as mean ellipticity per residue.</p><p><strong>Results: </strong>The purified cathepsin D demonstrated a specific activity of 5,553 ± 220 U/mg and a molecular weight of 36.5 kDa. The enzyme demonstrated optimal activity within a temperature range of 45-50°C and a pH range of 3-3.5. CD analyses demonstrated alterations in the secondary structure at elevated temperatures and pH fluctuations, which were correlated with a reduction in enzyme activity.</p><p><strong>Conclusion: </strong>cathepsin D from <i>R. philippinarum</i> exhibited high thermostability up to 50°C and activity at pH 2-4. Its stability and characteristics are comparable to those of other species, which opens avenues in biotechnology for protein hydrolysis and peptide production.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"467-479"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122216","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":"The Expression Characteristics and Interrelationships of FNDC5 and Pyroptosis-Associated Molecules in the Peripheral Blood of Patients with Coronary Heart Disease.","authors":"Yujia Pan, Hangjun Ou, Danan Liu","doi":"10.2174/0113892037338952241113104224","DOIUrl":"10.2174/0113892037338952241113104224","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to investigate the expression characteristics and interrelationships of FNDC5 and pyroptosis-associated molecules in peripheral blood mononuclear cells of patients with coronary heart disease (CHD).</p><p><strong>Methods: </strong>Patients were divided into stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI) groups based on different clinical symptoms. According to the Gensini score, they were then divided into mild, moderate, and severe lesion groups. The control (NC) group was also set. ELISA assay was employed to detect the levels of Irisin, IL-1β, and IL-18, and the levels of pyroptosis-associated molecules, NF-κB p50, NF-κB p65, and FNDC5 were detected and compared by qRT-PCR and Western blot (WB). Logistic regression and Spearman's partial correlation analysis were used to analyze the pathogenic factors of CHD and explore the interrelationships between FNDC5 and the molecules.</p><p><strong>Results: </strong>IL-1β and IL-18 of CHD patients were increased, while the Irisin was decreased. With the aggravation of symptoms and severity of coronary artery stenosis, the former increased, and the Irisin gradually decreased (P<0.05). About qRT-PCR and WB: With the aggravation of symptoms, the levels of pyroptosis-associated molecules and other indicators were increased, and FNDC5 was decreased (Pπ0.05). NLRP3, Caspase-1, and NF-κB p50 protein were positively correlated with the incidence of CHD, and FNDC5 was also negatively correlated with that of CHD. Even when common risk factors for CHD were taken into account, FNDC5 and NLRP3 were still found to be negatively connected.</p><p><strong>Conclusion: </strong>The decreased expression level of FNDC5 and the increased level of pyroptosis-associated molecules may be related to CHD.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"480-492"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983087","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":"Chaperones as Potential Pharmacological Targets for Treating Protein Aggregation Illness.","authors":"Shikha Rani, Minkal Tuteja","doi":"10.2174/0113892037338028241230092414","DOIUrl":"10.2174/0113892037338028241230092414","url":null,"abstract":"<p><p>The three-dimensional structure of proteins, achieved through the folding of the nascent polypeptide chain <i>in vivo</i>, is largely facilitated by molecular chaperones, which are crucial for determining protein functionality. In addition to aiding in the folding process, chaperones target misfolded proteins for degradation, acting as a quality control system within the cell. Defective protein folding has been implicated in a wide range of clinical conditions, including neurodegenerative and metabolic disorders. It is now well understood that the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and Creutzfeldt-Jakob disease shares a common mechanism: the accumulation of misfolded proteins, which aggregate and become toxic to cells. Among the family of molecular chaperones, Heat Shock Proteins (HSPs) are highly expressed in response to cellular stress and play a pivotal role in preventing protein aggregation. Specific chaperones, particularly HSPs, are now recognized as critical in halting the accumulation and aggregation of misfolded proteins in these conditions. Consequently, these chaperones are increasingly considered promising pharmacological targets for the treatment of protein aggregation-related diseases. This review highlights research exploring the potential roles of specific molecular chaperones in disorders characterized by the accumulation of misfolded proteins.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"451-466"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051908","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":"TLR4 Targeting: A Promising Therapeutic Approach Across Multiple Human Diseases.","authors":"Sakshi Kumar, Vikram Sharma, Shikha Yadav","doi":"10.2174/0113892037324425241018061548","DOIUrl":"10.2174/0113892037324425241018061548","url":null,"abstract":"<p><p>TLR4 stands at the forefront of innate immune responses, recognizing various pathogen- associated molecular patterns and endogenous ligands, thus serving as a pivotal mediator in the immune system's defense against infections and tissue damage. Beyond its canonical role in infection, emerging evidence highlights TLR4's involvement in numerous non-infectious human diseases, ranging from metabolic disorders to neurodegenerative conditions and cancer. Targeting TLR4 signaling pathways presents a promising therapeutic approach with broad applicability across these diverse pathological states. In metabolic disorders such as obesity and diabetes, dysregulated TLR4 activation contributes to chronic low-grade inflammation and insulin resistance, driving disease progression. In cardiovascular diseases, TLR4 signaling promotes vascular inflammation and atherogenesis, implicating its potential as a therapeutic target to mitigate cardiovascular risk. Neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, exhibit aberrant TLR4 activation linked to neuroinflammation and neuronal damage, suggesting TLR4 modulation as a strategy to attenuate neurodegeneration. Additionally, in cancer, TLR4 signaling within the tumor microenvironment promotes tumor progression, metastasis, and immune evasion, underscoring its relevance as a target for anticancer therapy. Advances in understanding TLR4 signaling cascades and their contributions to disease pathogenesis have spurred the development of various pharmacological agents targeting TLR4. These agents range from small molecule inhibitors to monoclonal antibodies, with some undergoing preclinical and clinical evaluations. Furthermore, strategies involving TLR4 modulation through dietary interventions and microbiota manipulation offer additional avenues for therapeutic exploration. Hence, targeting TLR4 holds significant promise as a therapeutic strategy across a spectrum of human diseases, offering the potential to modulate inflammation, restore immune homeostasis, and impede disease progression.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"241-258"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892750","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":"Current Trends and Challenges in Targeting Tumor Mitochondrial Glycolysis and Oxidative Phosphorylation Pathways for Cancer Therapy.","authors":"Rahul Pratap Singh, Sonali","doi":"10.2174/0113892037307636240612112408","DOIUrl":"10.2174/0113892037307636240612112408","url":null,"abstract":"","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"2-5"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497345","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":"Comparative Study of Lactogenic Effect and Milk Nutritional Density of Oral Galactagogue in Female Rabbit.","authors":"Saurabh Maru, Sateesh Belemkar","doi":"10.2174/0113892037300581240830052536","DOIUrl":"10.2174/0113892037300581240830052536","url":null,"abstract":"<p><strong>Background: </strong>Hypogalactia and agalactia in lactating mothers are the major causes of child malnutrition, mortality, morbidity, and overall ill health. The development of such treatments requires a well-designed preclinical study with suitable laboratory animals, which needs to be improved. Thus, a suitably designed study with a laboratory animal to analyse galactagogue activity, along with an assessment of the quality and quantity of milk, is required.</p><p><strong>Objectives: </strong>This study aimed to evaluate the potential of rabbit as an animal model for studying lactogenic activity.</p><p><strong>Methods: </strong>The structural homology of prolactin, gene prolactin receptor, and prolactin hormone in humans, rabbit, and rat was studied using BLAST and PyMol to assess similarity in the lactogenic system. Daily and cumulative milk production and pre-treatment (control) and post-treatment (three drugs) in rabbits were recorded and evaluated by analysing protein, fat, lactose, solid non-- fat, and ash values. All parameters were recorded on the 0th day and at the end of weeks 1, 2, and 3. Mammary gland histopathology was performed to evaluate the effects on mammary glands.</p><p><strong>Results: </strong>Homology studies revealed that the sequences of the human and rabbit prolactin genes, receptors, and hormones had a high similarity index. Treatment with Domperidone, Metoclopramide, and Shatavari significantly enhanced milk production by enhancing prolactin secretion; only Shatavari increased milk nutrition. Enlargement of the tubuloalveolar ducts of the mammary glands was observed.</p><p><strong>Conclusion: </strong>Our findings suggest that rabbits are robust, reproducible, ethically superior, and preclinically relevant animals for assessing lactogenic activity.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"125-138"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125023","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}