Current drug targets最新文献

{"title":"Cytokeratin 8 as a Novel Therapeutic Target in Type 2 Diabetes Mellitus: Suppression of Hepatic Glycogen Synthesis via IRS1/PI3K/Akt/GSK3β Signaling.","authors":"Mingzhu Sun, Xiuli Li, Jin Sun, Zhidong Wang","doi":"10.2174/0113894501394500250903095958","DOIUrl":"https://doi.org/10.2174/0113894501394500250903095958","url":null,"abstract":"<p><strong>Introduction: </strong>Recent studies have established that cytokeratin 8 (CK8) is closely linked to glycogen synthesis; however, its mechanistic role in hepatic glycogen synthesis in type 2 diabetes mellitus (T2DM) remains unclear. This study aimed to elucidate the effects and underlying molecular mechanisms of CK8.</p><p><strong>Methods: </strong>We analyzed CK8 expression and the IRS1 (Insulin Receptor Substrate 1)/PI3K (Phosphoinositide 3-Kinase)/Akt (Protein Kinase B)/GSK3β (Glycogen Synthase Kinase 3 beta) pathway in liver samples from T2DM patients, diabetic C57BL/6J mouse models, and high glucose- treated NCTC 1469 cells using Western blotting, immunohistochemistry, and PAS staining.</p><p><strong>Results: </strong>CK8 was significantly upregulated in all T2DM models, correlating with suppressed IRS1/PI3K/Akt/GSK3β signaling and reduced glycogen synthesis. Our functional studies demonstrated that CK8 overexpression exacerbated these effects, while CK8 knockdown restored glycogen levels to near-normal.</p><p><strong>Discussion: </strong>In our study, CK8 was identified as a negative regulator of hepatic glycogen synthesis by modulating the IRS1/PI3K/Akt/GSK3β pathway.</p><p><strong>Conclusion: </strong>These findings position CK8 as a promising therapeutic target for T2DM, with CK8 inhibition offering a novel strategy to improve hepatic insulin resistance and glycogen storage without requiring β-cell stimulation.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Situation on Diabetes Management: New Weapons Fighting the Disease in 2025.","authors":"Mehmet Evren Okur, Androulla N Miliotou, Vasiliki Nitsola, Ioannis D Karantas, Neslihan Üstündağ Okur, Panoraia I Siafaka","doi":"10.2174/0113894501399175250916110738","DOIUrl":"https://doi.org/10.2174/0113894501399175250916110738","url":null,"abstract":"<p><strong>Introduction: </strong>The global prevalence of Diabetes Mellitus is rising; this complex metabolic disorder marked with hyperglycemia comes with increased morbidity and more associated health risks. Type 1 Diabetes Mellitus, an autoimmune disorder primarily affecting young individuals, lacks innovative pharmacological therapies. While current treatments for Type 2 Diabetes Mellitus-including lifestyle interventions and medications-can be effective, many patients still struggle with glycemic control. This review aims to highlight recent advances in diabetes mellitus management, emphasizing novel therapeutics and drug delivery systems that aim to decrease dosage frequency, target the manifestation of side effects, and enhance anti-diabetic effectiveness.</p><p><strong>Methods: </strong>We conducted a comprehensive review of over 300 articles published between 2017 and 2025, utilizing databases such as PubMed and ScienceDirect.</p><p><strong>Results: </strong>Recent therapeutic innovations include nanocarrier-mediated drug delivery, microneedle patches, and mRNA- and gene-based systems.</p><p><strong>Discussions: </strong>These technologies aim to improve glycemic control, reduce dosing frequency, and minimize side effects. The 2024 American Diabetes Association Standards of Care introduced updated diagnostic criteria and management recommendations, which are summarized herein.</p><p><strong>Conclusion: </strong>This review outlines key developments in pharmacological and delivery strategies of the past 5 years, targeting all types of diabetes. Special focus is placed on emerging therapies such as mRNA, nanotechnology, and innovative delivery systems, which may transform future diabetes management. The content is designed to support clinicians, researchers, and healthcare professionals in developing future therapeutic strategies.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteasome Fine-Tunes the Generation of Antimicrobial Peptides.","authors":"Anita Kovalaske, Ian McLauchlan, Megan Murphy, Hope Omoniyi, Grace Hohman, Mohamed Eldeeb","doi":"10.2174/0113894501421031250919055232","DOIUrl":"https://doi.org/10.2174/0113894501421031250919055232","url":null,"abstract":"<p><p>Antimicrobial peptides (AMPs), part of the body's innate immune response, are natural compounds that inhibit bacteria during bacterial infections. Despite their important role in counteracting cellular pathogens, the precise mechanism of generating AMPs in response to bacterial infection remains elusive. However, recent findings demonstrate that the proteasome, a cellular complex involved in the degradation of intracellular proteins, plays a key role in generating AMPs during bacterial infection. Intriguingly, bacterial infections have been shown to mediate the remodeling of the proteasome, resulting in altered cleavage activity that increases the generation of antimicrobial peptides and helps reduce intracellular bacterial load. Additionally, the 11S proteasome subunit PSME3 has been identified as the key regulatory particle responsible for triggering proteasome remodeling in response to bacterial stress. Remarkably, given the burgeoning research on antimicrobial agents, the recent findings uncover an important anti-bacterial functional role of the proteasome and open avenues for investigating strategies to modulate or enhance the cell's natural defense against pathogens to develop new antimicrobial therapeutics.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Scorpion Venom Proteins: Innovations in Cancer Treatment and Future Directions.","authors":"Nooshin Ghadiri, Vida Homayouni, Zahra Akbari Jonoush, Roya Mahdavi, Nastaran Mohammadi, Amir Mohamad Amiri, Mahdieh Sadat Badiee, Mazdak Ganjalikhani Hakemi","doi":"10.2174/0113894501396738250904071722","DOIUrl":"https://doi.org/10.2174/0113894501396738250904071722","url":null,"abstract":"<p><p>Cancer is a significant human health concern due to its increasing mortality rate and profound impact on public health and healthcare systems. The cytotoxic, antiproliferative, immunosuppressive, and apoptogenic properties of scorpion venom proteins and peptides have been observed in various cancer cell lines. Therefore, the purpose of this study was to investigate the potential use of proteins derived from scorpion venom in cancer treatment. In this study, the effects of different scorpion venoms on transmembrane channels, the inhibition of angiogenesis, the inhibition of invasion and metastasis, the inhibition of proliferation, and the induction of apoptosis were investigated, as were their clinical applications in the treatment of hepatocellular carcinoma and breast, cervical, prostate, colorectal, and melanoma cancers. The results showed that various scorpion venoms can suppress cell growth, stimulate apoptosis, reduce tumor size, and enhance the immune response, thereby serving as alternative drugs for treating various types of cancers and their metastasis. This review suggests a positive association between scorpion venom (SV) proteins and the treatment of these cancers. Future research should focus on understanding the underlying mechanisms, identifying biomarkers to predict response, and exploring potential combination therapies to increase the efficacy of scorpion venom proteins in cancer treatment.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Therapeutic Potential of Plant-Based Natural Products in Combating Aging.","authors":"Adarsh Sharma, Arya Ojha, Sunny Rathee, Sanjay K Jain, Umesh K Patil","doi":"10.2174/0113894501384653250903110249","DOIUrl":"https://doi.org/10.2174/0113894501384653250903110249","url":null,"abstract":"<p><p>Aging is a complex biological process marked by progressive cellular and tissue decline, leading to an increased risk of age-related diseases. Plant-based natural compounds, including polyphenols, flavonoids, carotenoids, alkaloids, and terpenoids, have gained attention for their potential in mitigating aging-related damage through antioxidant, anti-inflammatory, and cellular repair mechanisms. The review identified that plant-derived bioactive compounds target key pathways involved in aging, including Sirtuins (SIRT1), AMP-activated protein kinase (AMPK), and Nuclear Factor-kappa B (NF-κB). These compounds address key hallmarks of aging, such as oxidative stress, mitochondrial dysfunction, cellular senescence, and chronic inflammation. Evidence suggests their potential in preventing or delaying age-related disorders, including neurodegenerative diseases, cardiovascular conditions, and skin aging. Plant-derived compounds offer a promising alternative to synthetic anti-aging interventions due to their efficacy, safety, and sustainability. However, challenges such as low bioavailability and limited clinical validation must be addressed. Advances in drug delivery systems and comprehensive clinical trials are critical to realizing their full therapeutic potential. Plant-based bioactive compounds represent a significant opportunity for developing safer and more sustainable anti-aging therapies. Continued research is essential to overcome existing limitations and facilitate the integration of these approaches into mainstream healthcare practices.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Mechanism of Astragalus mongholicus-Mediated Treatment of Silicosis in Mice from the Perspective of Alternative Splicing.","authors":"Yu Zhang, Zhiyan Jiang, Yuanyuan Zhai, Yongqiang Xing","doi":"10.2174/0113894501408966250903070801","DOIUrl":"https://doi.org/10.2174/0113894501408966250903070801","url":null,"abstract":"<p><strong>Introduction: </strong>Astragalus mongholicus is distributed in Inner Mongolia, China, and has a certain therapeutic effect on silicosis. However, the regulatory mechanisms of Astragalus mongholicus mediated by alternative splicing (AS) in silicosis pathology and treatment remain unclear.</p><p><strong>Methods: </strong>The pathological examination was performed on the lung tissue of a constructed mouse model of silicosis. Then, rMATS-based AS detection, target prediction, PPI analysis, and molecular docking were conducted to investigate the mechanism of Astragalus mongholicus-mediated treatment of silicosis in mice from the perspective of AS.</p><p><strong>Results: </strong>A total of 404 differentially alternatively spliced genes (DASGs) were identified between the Astragalus mongholicus treatment and the silicosis model group. Moreover, 194 potential targets were predicted from 33 active components of Astragalus mongholicus, of which the targets, Rps6ka2 and Clk4, underwent differential AS. Network pharmacology analysis indicated that the Isomucronulatol, 7-o-methylisomucronulatol, and Medicarpin in Astragalus mongholicus might participate in the treatment of silicosis through differential spliced of Rps6ka2 or Clk4. Molecular docking confirmed a strong binding affinity between the protein Rps6ka2 and Medicarpin.</p><p><strong>Discussion: </strong>This study suggests that Isomucronulatol, 7-o-methylisomucronulatol, and Medicarpin, being active components in Astragalus mongholicus, may intervene in silicosis pathogenesis through differential splicing of Rps6ka2 or Clk4, involving biological processes such as protein serine/threonine kinase activity. However, further experimental validation is required to confirm these findings.</p><p><strong>Conclusion: </strong>A large number of DASEs exist in the development and treatment of silicosis. Astragalus mongholicus may alleviate silicosis through AS-regulated mechanisms involving Rps6ka2 and Clk4. This finding provides novel strategies and potential molecular targets for silicosis treatment.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Emerging Landscape of LINC01123 in Cancer: Roles, Mechanisms, and Clinical Significance.","authors":"Jingjie Yang, Fan Peng, Haodong He, Haoran Liu, Kexing Liu, Zhouya Xu, Yaqi Hu, Guihua Liao, Yan Cai, Chengfu Yuan","doi":"10.2174/0113894501398484250903074131","DOIUrl":"https://doi.org/10.2174/0113894501398484250903074131","url":null,"abstract":"<p><strong>Introduction: </strong>Long intergenic non-coding RNA 01123 (LINC01123) is a lncRNA located on the human chromosome 2q13. It is upregulated in various cancers and has been identified as an oncogene. Its expression is associated with the risk and poor prognosis of multiple cancers.</p><p><strong>Methods: </strong>A systematic literature search was conducted in PubMed, Web of Science, and Google Scholar databases using \"LINC01123\" as the search term. The retrieved studies were reviewed to analyze the expression patterns, oncogenic mechanisms, and clinical significance of LINC01123 in cancers.</p><p><strong>Results: </strong>LINC01123 is activated by transcription factors such as c-Myc, ZEB1, and FOXC1. It promotes cancer progression, metastasis, and drug resistance by acting as a \"molecular sponge\" for miRNAs, activating signaling pathways, or interacting with proteins. Its upregulation correlates with adverse clinicopathological features and poor prognosis in multiple cancers.</p><p><strong>Discussion: </strong>The findings suggest that LINC01123 plays a multifaceted role in cancer biology. Its ability to regulate gene expression through various mechanisms highlights its potential as both a prognostic biomarker and a therapeutic target. However, further research is needed to elucidate its mechanisms fully and to explore its clinical applications across different cancer types.</p><p><strong>Conclusion: </strong>LINC01123 has potential as a novel prognostic biomarker and therapeutic target for cancer. Further research is needed to elucidate its mechanisms and clinical applications fully.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalised Transdermal Therapy for Chronic Pain with Digital Twin Technology.","authors":"Sejal Porwal, Rishabha Malviya, Sathvik Belagodu Sridhar, Javedh Shareef, Musarrat Husain Warsi, Tarun Wadhwa","doi":"10.2174/0113894501395522250903070018","DOIUrl":"https://doi.org/10.2174/0113894501395522250903070018","url":null,"abstract":"<p><p>Digital twin technology has emerged as a breakthrough development in healthcare, providing personalised transdermal drug delivery systems for chronic pain treatment. Digital twins provide accurate, customised therapy to enhance therapeutic outcomes and reduce risks by combining patient-specific computational models. This article aims to explore the applicability of digital twin technology in improving the transdermal delivery of drugs for successful chronic pain management. It is enabling personalised treatment through patient-specific simulations. By integrating physiological data with computational models, digital twins optimise drug absorption, patch application, and dosage adjustments in real-time, enhancing therapeutic outcomes while minimising side effects. Recent advancements highlight improvements in fentanyl patch optimisation, site-specific drug delivery, and thermally controlled systems. However, challenges such as ethical concerns, data security, and standardisation need to be addressed. Future research should focus on integrating AI and IoT to refine digital twin applications in precision medicine. It can be concluded from the findings of various studies that digital twin technology offers a promising future for precise and individualised transdermal drug delivery in chronic pain, paving the way for safer and more effective therapeutic interventions.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticle-Based Drug Delivery Systems: Current Advances and Future Directions.","authors":"Mannat Mittal, Shreya Juneja, Neelesh Pandey, Rahul Mittal","doi":"10.2174/0113894501393535250903071153","DOIUrl":"https://doi.org/10.2174/0113894501393535250903071153","url":null,"abstract":"<p><p>Nanotechnology in drug delivery has revolutionized modern therapeutics by addressing the limitations of conventional drug delivery methods. This review article explores the significant advancements in nanoparticle-based drug delivery systems, highlighting their role in enhancing therapeutic efficacy and overcoming drug resistance. Nanoparticles, including lipid-based, polymer- based, inorganic, and biological types, offer improved solubility, stability, targeted delivery, and controlled release of therapeutic agents. By enabling precise delivery to specific tissues or cells, these advancements minimize off-target effects and toxicity, particularly in cancer therapy. Additionally, nanomedicine facilitates the delivery of drugs across biological barriers such as the blood-brain barrier, which opens new avenues for treating neurological disorders. The ability to co-encapsulate multiple therapeutic agents in nanoparticles also supports combination therapies that target multiple pathways simultaneously, thereby reducing the development of resistance. As research progresses, the integration of nanotechnology in drug delivery promises to transform healthcare by providing more effective, safer, and personalized treatments. This article advocates for continued exploration and innovation in the field by emphasizing the need for interdisciplinary collaboration to fully realize the potential of nanomedicine in improving patient outcomes and addressing unmet clinical needs.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Pivotal Role of LncRNA DUXAP9 in Cancer: Current Progress and Future Perspectives.","authors":"Jingjie Yang, Siqi Yang, Wenjin Peng, Haodong He, Haoran Liu, Jiahe Zhang, Guihua Liao, Chengfu Yuan","doi":"10.2174/0113894501400842250903112123","DOIUrl":"https://doi.org/10.2174/0113894501400842250903112123","url":null,"abstract":"<p><p>Double homeobox A pseudogene 9 (DUXAP9), also known as long intergenic non-coding RNA 1296 (LINC01296) and lymph node metastasis-associated transcript 1 (LNMAT1), is an emerging lncRNA encoded by a pseudogene. It has been reported to be upregulated in various tumor types and functions as an oncogenic factor. The high expression of DUXAP9 is closely related to clinical pathological features and poor prognosis in 16 types of malignant tumors. DUXAP9 is transcriptionally activated by YY-1 and Twist1 and functions as a guide or scaffold for biomolecular complexes and chromatin modifiers, or as a 'decoy' for miRNAs, mRNAs, and proteins, thereby regulating gene expression. Moreover, the PI3K/AKT, NF-κB, MAPK/ERK, and Wnt/β- catenin signaling pathways are variously activated or inhibited by DUXAP9, subsequently influencing the biological behaviors of tumor cells, including proliferation, apoptosis, cell cycle arrest, migration, invasion, epithelial-mesenchymal transition (EMT), and drug resistance. This review summarizes recent research on DUXAP9 in oncology, offering insights into its expression characteristics, biological functions, molecular mechanisms, and clinical significance for cancer diagnosis, treatment, and prognosis.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}