Current pharmaceutical design最新文献

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A Nanophytomedicine Approach Including Tea Tree Essential Oil for Possible Dental Applications: In vitro and In silico Evaluations. 包括茶树精油在内的纳米植物医学方法可能用于牙科:体外和计算机评估。
IF 2.8 4区 医学
Current pharmaceutical design Pub Date : 2026-04-20 DOI: 10.2174/0113816128401462251128162600
Yasemin Budama-Kilinc, Nisanur Cakmakci, Serda Kecel-Gunduz, Şeyma Suyabatmaz, Sengul Alpay-Karaoglu, Pınar Yilmaz-Atali, Evren Algın Yapar, Murat Kartal
{"title":"A Nanophytomedicine Approach Including Tea Tree Essential Oil for Possible Dental Applications: In vitro and In silico Evaluations.","authors":"Yasemin Budama-Kilinc, Nisanur Cakmakci, Serda Kecel-Gunduz, Şeyma Suyabatmaz, Sengul Alpay-Karaoglu, Pınar Yilmaz-Atali, Evren Algın Yapar, Murat Kartal","doi":"10.2174/0113816128401462251128162600","DOIUrl":"https://doi.org/10.2174/0113816128401462251128162600","url":null,"abstract":"<p><strong>Introduction: </strong>Tea tree essential oil (TTO) incorporated polylactic-co-glycolic acid (PLGA) nanoparticulate powder form was aimed to desined that can be applied with water and is effective against oral pathogens to prevent caries, and that is able to provide a long-lasting oral antiseptic effect.</p><p><strong>Methods: </strong>TTO-PLGA nanoparticles (TTO-NPs) was synthesized by single emulsion technique; average particle size, PdI value and zeta potential was measured by Zetasizer; TTO-PLGA interactions were investigated by FTIR, and morphological analysis was performed by TEM analysis. Phytoactive release and performans tests were carried out with in vitro dissolution and DNA binding-cleavage tests while antimicrobial performance was investigated by Ames-Salmonella assay, susceptibility test, in silico Molecular Docking and Molecular Dynamics studies.</p><p><strong>Results: </strong>TTO-NPs had an average particle size of 221.6 nm, a PdI of 0.103, and a zeta potential of -5.22 mV, 59.25% encapsulation efficiency and 25.65%. loading capacity. At the end of 5 h and 72 h the TTO release was 33.34±2.17% and 97.61±3.91% respectively. TTO-NPs were not mutagenic and were effective on investigated four cariogenic bacteria. The binding interactions of terpinen-4-ol, the main component of TTO, with Streptococcus mutans and Lactobacillus casei were revealed with enzyme-active-site-key residues.</p><p><strong>Discussion: </strong>In vitro and in silico studies confirmed that TTO-NPs were non-mutagenic and exhibited strong antimicrobial activity against dental caries-causing bacteria like Streptococcus mutans and Lactobacillus casei.</p><p><strong>Conclusion: </strong>In conclusion, TTO-NPs, which can be used as a mouthwash or powder, represent a promising solution for reducing oral pathogens, meriting further in vivo and clinical evaluations.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765147","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}
引用次数: 0
Review on the Potential Anti-aging Effects of Gastrodia elata. 天麻潜在抗衰老作用研究进展。
IF 2.8 4区 医学
Current pharmaceutical design Pub Date : 2026-04-20 DOI: 10.2174/0113816128428972251204212438
Ruoying Wang, Chenran Xin, Wencong Liu, Zhiqiang Cheng, Hongyan Zhu, Jihong Han
{"title":"Review on the Potential Anti-aging Effects of Gastrodia elata.","authors":"Ruoying Wang, Chenran Xin, Wencong Liu, Zhiqiang Cheng, Hongyan Zhu, Jihong Han","doi":"10.2174/0113816128428972251204212438","DOIUrl":"https://doi.org/10.2174/0113816128428972251204212438","url":null,"abstract":"<p><p>Gastrodia elata Blume (G. elata) is a valuable traditional Chinese medicine (TCM) that has been widely used in China. We systematically reviewed tonic and life-extending records in ancient medical literature, as well as the life-prolonging and senescence-delaying effects identified in modern pharmacological research, to provide a theoretical basis for the clinical application and product development of G. elata in tonification and anti-aging. Scientific databases, including CNKI (Chinese literature) and PubMed, were searched to gather relevant literature on the anti-aging effects of G. elata. The targets of the main chemical components of G. elata were predicted and collected through a database, and the intersection of compound targets and disease targets was identified. Protein-protein interaction network analysis, Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the potential mechanisms underlying the anti-aging effects of G. elata. The record of G. elata demonstrates a definitive life-extending effect. Modern pharmacological studies have confirmed that it prolongs the lifespan of short-lived animals and slows the aging processes of the brain, skin, bone, and skeletal muscle in animals. Network pharmacology analysis identified 15 common targets shared between candidate target genes of G. elata and anti-aging target genes. TP53, ESR1, EP300, SIRT1, STAT3, CCND1, HDAC2, MDM2, PPARG, TNF, and HSP90AA1 were identified as core genes in the protein-protein interaction (PPI) network analysis. KEGG enrichment analysis indicated that the anti-aging mechanisms of G. elata may be associated with chemical receptor activation, insulin resistance, the citric acid cycle, the PPAR signaling pathway, the glucagon signaling pathway, and the thyroid hormone signaling pathway. This article summarizes previous studies and modern research on the anti-aging effects of G. elata, suggesting that it holds significant potential for clinical applications in anti-aging.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765074","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}
引用次数: 0
Advances in Cell Membrane Biomimetic Nano-Delivery Systems for Brain Tumor Therapy. 用于脑肿瘤治疗的细胞膜仿生纳米递送系统研究进展。
IF 2.8 4区 医学
Current pharmaceutical design Pub Date : 2026-04-16 DOI: 10.2174/0113816128417270251125062956
Wenbo Zhou, Ruiyao Liu, Wuting Dai, Lingyi Guo, Yuan Yu
{"title":"Advances in Cell Membrane Biomimetic Nano-Delivery Systems for Brain Tumor Therapy.","authors":"Wenbo Zhou, Ruiyao Liu, Wuting Dai, Lingyi Guo, Yuan Yu","doi":"10.2174/0113816128417270251125062956","DOIUrl":"https://doi.org/10.2174/0113816128417270251125062956","url":null,"abstract":"<p><p>Based on the concept of \"imitating nature,\" biomimetic nano-delivery systems (BNDS) for brain tumor therapy are designed to simulate or utilize endogenous biological materials as delivery carriers, such as hybrids of engineered cell membranes and exogenous nanocarriers. These systems not only retain the physical and chemical properties of nanomaterials-enabling responses to photothermal stimuli, enzymes, and pH- but also inherit the advantages of their source cells, including physiological barrier-transport capabilities, specific targeting of focal tissues, and immunomodulatory effects. This enables the delivery of small-molecule drugs, nucleic acids, or therapeutic proteins across the blood-brain barrier (BBB) or the blood-tumor barrier (BTB) to tumor tissue. This article provides a comprehensive review of the construction, targeting mechanisms, and research progress of cell membrane-based nano-delivery systems derived from erythrocytes, immune cells, tumor cells, stem cells, and platelet membranes, with particular emphasis on their potential applications in brain tumor therapy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722077","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}
引用次数: 0
Unleashing the Potential of 6-Mercaptopurine: Microemulsion Innovations for Enhanced Oral Bioavailability and Therapeutic Impact. 释放6-巯基嘌呤的潜力:提高口服生物利用度和治疗效果的微乳创新。
IF 2.8 4区 医学
Current pharmaceutical design Pub Date : 2026-04-16 DOI: 10.2174/0113816128427856251208064319
Priya Singh
{"title":"Unleashing the Potential of 6-Mercaptopurine: Microemulsion Innovations for Enhanced Oral Bioavailability and Therapeutic Impact.","authors":"Priya Singh","doi":"10.2174/0113816128427856251208064319","DOIUrl":"https://doi.org/10.2174/0113816128427856251208064319","url":null,"abstract":"<p><strong>Introduction: </strong>6-Mercaptopurine (6-MP) is an anticancer agent that disrupts cancer cell growth, ultimately causing cell death. It is classified as a BCS Class II drug, indicating poor aqueous solubility and limited oral bioavailability. To reduce these problems, nanocarriers have been prepared, which are non-toxic, biodegradable, and biocompatible.</p><p><strong>Methods: </strong>The 6-MP loaded microemulsion has been formulated and characterized for physicochemical characterization, morphology, drug content, and release study. The cell line studies were implemented on the MDA-MB-231 cell line for cell viability and cellular uptake analysis.</p><p><strong>Results: </strong>The optimized formulation (ME4) exhibited a droplet size of 115.47 ± 1.53 nm, entrapment efficiency of >90%, and a stable physicochemical profile. It demonstrated sustained drug release and significantly higher cellular uptake with an IC50 value of 2.17 ± 0.21 μM, compared to 3.87 ± 0.11 μM for free 6-MP. Ex-vivo permeation studies showed 80% drug permeation within 120 minutes versus 42% for pure 6-MP. Invivo pharmacokinetics revealed a 1.79-fold increase in oral bioavailability compared to the marketed tablet. XO inhibition studies confirmed ME4's role in reducing presystemic metabolism, with 59.60 ± 2.25% inhibition at 200 μg/mL, comparable to the standard inhibitor allopurinol (73.42 ± 2.34%).</p><p><strong>Discussion: </strong>The developed microemulsion successfully addresses the dual challenge of poor solubility and extensive first-pass metabolism of 6-MP, resulting in significantly enhanced bioavailability and anticancer activity. These findings highlight its potential for future clinical development as a novel oral delivery platform for cancer therapy.</p><p><strong>Conclusion: </strong>The results demonstrate the future potential of 6-MP as a successful nanotherapeutic agent for cancer treatment that is more effective and safer.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721841","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}
引用次数: 0
Chebulinic Acid Exerts Anti-rotavirus Effects through the p38MAPK/ERK1/2 Signaling Pathway. 车布林酸通过p38MAPK/ERK1/2信号通路发挥抗轮状病毒作用
IF 2.8 4区 医学
Current pharmaceutical design Pub Date : 2026-04-15 DOI: 10.2174/0113816128431943251206212256
Junxian Yu, Didong Zhang, Yupei Qian, Yongdui Ruan, Yunmei Zhou, Xiaoying Jiang, Fenglin Liu, Jie Zhou, Ziyi Rong, Ziyue He, Lijun Song, Wenchang Zhao
{"title":"Chebulinic Acid Exerts Anti-rotavirus Effects through the p38MAPK/ERK1/2 Signaling Pathway.","authors":"Junxian Yu, Didong Zhang, Yupei Qian, Yongdui Ruan, Yunmei Zhou, Xiaoying Jiang, Fenglin Liu, Jie Zhou, Ziyi Rong, Ziyue He, Lijun Song, Wenchang Zhao","doi":"10.2174/0113816128431943251206212256","DOIUrl":"https://doi.org/10.2174/0113816128431943251206212256","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Rotavirus (RV) is a leading cause of diarrhea in infants and young children. Drugs effective against RV infection are not yet available in clinical practice. To investigate the anti-RV activity of chebulinic acid (CA) and its potential mechanism against RV.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The anti-RV activity of CA in vitro was evaluated by CCK8 assay, and the effects of CA on VP6 expression for RV RNA synthesis and protein expression were assessed using qRT-PCR、western blotting, and immunofluorescence, respectively. Before mechanistic validation, an in silico network pharmacology screen was performed to build a CA-host target-interaction map; DAVID enrichment flagged the p38/ERK axis as a top hit. Additionally, immunofluorescence and DCFH-DA ROS fluorescent probe were used to assess CA's effects against RV-induced ROS production and its direct ROS-scavenging activity, respectively, and western blotting was employed to evaluate whether CA exerts anti-RV activity by inhibiting the p38MAPK/ERK1/2 signaling pathway. Furthermore, we also evaluated the anti-viral effect of CA in RVinfected 4 days post-fertilization (4dpf) zebrafish model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Our results indicated that 4-10 μmol/L of CA has the ability to hinder VP6 expression, and it also decreased mitochondrial ROS production. Network pharmacology screening had previously identified 38 CA- RV intersection targets and ranked the p38 MAPK axis as the top-enriched pathway. Further research confirmed that CA downregulated p38MAPK/ERK1/2 phosphorylation levels in response to viral infection. In the RV-infected zebrafish model, CA greatly improved the survival rate. In addition, RV infection resulted in abnormal behavior in zebrafish, and CA was found to substantially decrease the incidence of convulsive behavior. The intestinal tract of zebrafish treated with CA led to the restoration of intestinal morphology and exhibited fewer inflammatory cell infiltrates, with a significantly reduced degree of inflammation compared to the viral group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;This study comprehensively evaluated the anti-RV activity of CA using two RV strains, RV-WA and SA-11, an infected-cell model in vitro, as well as the RV-WA-infected zebrafish model in vivo. As we know, CA, belonging to polyphenolic compounds, possesses notable antioxidant and anti-inflammatory potential; therefore, we investigated how RV-induced oxidative stress affected the host cell apoptosis and mitochondrial membrane potential, and how it activated the p38MAPK/ERK1/2 kinase signaling pathway. Our findings demonstrate that CA can reverse these pathological alterations and thereby exert anti-RV effects, offering a new therapeutic strategy against RV infection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study first demonstrated that CA possessed anti-RV properties by inhibiting mitochondrial oxidation-induced apoptosis via the p38MAPK/ERK1/2 kinase signaling pathway. These fi","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721436","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}
引用次数: 0
Emerging Diagnostic Tools and Therapeutic Approaches for Liver Cirrhosis Management. 肝硬化管理的新兴诊断工具和治疗方法。
IF 2.8 4区 医学
Current pharmaceutical design Pub Date : 2026-04-14 DOI: 10.2174/0113816128444314260409071748
Subhrojyoti Mukherjee, Manish Kumar, Somnath Das, Sheeba Shafi, Shruti Srivastava, Manoj Kumar Mishra, Arun Kumar Singh, Ravi Raj Pal
{"title":"Emerging Diagnostic Tools and Therapeutic Approaches for Liver Cirrhosis Management.","authors":"Subhrojyoti Mukherjee, Manish Kumar, Somnath Das, Sheeba Shafi, Shruti Srivastava, Manoj Kumar Mishra, Arun Kumar Singh, Ravi Raj Pal","doi":"10.2174/0113816128444314260409071748","DOIUrl":"https://doi.org/10.2174/0113816128444314260409071748","url":null,"abstract":"<p><p>Liver cirrhosis, a chronic liver disease identified by the formation of regenerative nodules along with fibrous bands, poses significant challenges in diagnosis and treatment. In the world, the most common factors of cirrhosis are Hepatitis C Virus (HCV), alcoholic liver disease, and Non-Alcoholic Steatohepatitis (NASH). The disease develops from a presymptomatic phase to a symptomatic phase, which often results in hospitalization, poor quality of life, and high mortality. The treatment of liver cirrhosis is centred on the treatment of the causes and complications, and liver transplantation is required in some cases. This mini-review explores innovative strategies in liver cirrhosis detection and intervention, highlighting recent advancements and future directions. Current diagnostic methods include physical examination and serologic tests detecting secondary indicators of liver dysfunction and fibrosis. Diagnostic tools encompass established biomarkers such as serum albumin, prothrombin time, bile acid levels, and platelet count, as well as AI-assisted diagnostic tools that use digital imaging and pathology data. Novel therapeutic approaches like antifibrotic agents, targeted therapies for specific etiologies, endoscopic interventions, and innovative stem cell-based therapies, particularly mesenchymal stem cells, offer promising approaches for liver regeneration and fibrosis reduction through their multidirectional differentiation potential and secretion of cytokines, growth factors, and matrix metalloproteinases. However, additional studies are required to enhance the effectiveness of these interventions. Future directions emphasize primary prevention, early fibrosis screening using non-invasive testing, and active targeting of fibrogenesis pathways. More clinical studies are essential to treat cirrhosis and improve patient outcomes.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721766","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}
引用次数: 0
Cubosomes as Versatile Multifunctional Lipid-Based Nanocarriers for Drug Delivery: A Comprehensive Review. 立方体体作为多功能脂基纳米药物递送载体:综述。
IF 2.8 4区 医学
Current pharmaceutical design Pub Date : 2026-04-14 DOI: 10.2174/0113816128448670260318044416
Avinash Tekade, Ashutosh Shewale, H N Shivakumar, Rushikesh Shinde, Janhavi Nimbalkar
{"title":"Cubosomes as Versatile Multifunctional Lipid-Based Nanocarriers for Drug Delivery: A Comprehensive Review.","authors":"Avinash Tekade, Ashutosh Shewale, H N Shivakumar, Rushikesh Shinde, Janhavi Nimbalkar","doi":"10.2174/0113816128448670260318044416","DOIUrl":"https://doi.org/10.2174/0113816128448670260318044416","url":null,"abstract":"<p><p>Cubosomes (QBS) are self-assembled, nanostructured lipid carriers characterized by a bicontinuous cubic liquid crystalline architecture with a three-dimensional honeycomb-like morphology. Their unique internal structure allows simultaneous encapsulation of hydrophilic, lipophilic, and amphiphilic compounds, enabling sustained, site-specific, and targeted drug delivery through various routes, including oral, ocular, nasal, transdermal, and vaginal administration. Composed primarily of amphiphilic lipids such as Glyceryl Monooleate (GMO) and stabilized with surfactants like Pluronic F-127, QBS exhibits superior biocompatibility, structural integrity, and long-term colloidal stability. QBS are typically fabricated using either top-down or bottom-up strategies. Top-down approaches such as high-pressure homogenization, probe sonication, and spray drying fragment bulk cubic phases into nanosized dispersions, ensuring scalability and uniformity. Conversely, bottom-up methods, including the hydrotrope technique, vortex dispersion, and solvent evaporation, enable spontaneous QBS formation under mild conditions ideal for thermolabile actives. Physicochemical properties depend on lipid-to-stabilizer ratios, solvent composition, and processing parameters. Characterization techniques such as Dynamic Light Scattering (DLS), Small-Angle X-ray Scattering (SAXS), Transmission Electron Microscopy (TEM), and Confocal Laser Scanning Microscopy (CLSM) confirm particle size, morphology, and internal nanostructure. Zeta potential and MTT assays evaluate stability and cytocompatibility, while in vitro and ex vivo studies assess drug entrapment, release, and permeation behaviour. QBS represent an advanced class of lyotropic liquid-crystalline nanocarriers with high drug-loading potential, excellent biocompatibility, and controlled-release performance. Their multifunctional versatility underscores their promise as next-generation platforms for targeted and sustained drug delivery applications.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721430","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}
引用次数: 0
Interplay between ADP-Ribosylation and Androgen Receptor Function in Prostate Cancer. 前列腺癌中adp -核糖基化与雄激素受体功能的相互作用。
IF 2.8 4区 医学
Current pharmaceutical design Pub Date : 2026-04-14 DOI: 10.2174/0113816128442440260321120151
Gali Sri Venkata Sai Rishma Reddy, Krishna Samanta, Pulak Kar
{"title":"Interplay between ADP-Ribosylation and Androgen Receptor Function in Prostate Cancer.","authors":"Gali Sri Venkata Sai Rishma Reddy, Krishna Samanta, Pulak Kar","doi":"10.2174/0113816128442440260321120151","DOIUrl":"https://doi.org/10.2174/0113816128442440260321120151","url":null,"abstract":"<p><p>Androgen receptor (AR) signalling is central to both normal prostate physiology and prostate cancer (PCa) progression. Its activity is tightly regulated by localization, transcriptional control, and post-translational modifications. Among these, poly (ADP-ribose) polymerase (PARP) mediated ADP-ribosylation has emerged as a key regulator. Multisite cysteine mono-ADP-ribosylation of AR by PARP7 modulates its function. Molecular recognition of ADP-ribosyl-cysteine by PARP9/DTX3L influences AR-driven gene expression. Importantly, defects in homologous recombination repair (HRR) genes have made PARP inhibitors (PARPi) an effective treatment for BRCA (Breast cancer susceptibility genes 1 and 2)-mutated metastatic castration-resistant prostate cancer (mCRPC). Clinical trials such as TALAPRO-2 show that combining PARPi with AR signalling inhibitors can be effective; however, their benefit in tumours without HRR mutations remains unclear. PARP enzymes regulate AR via MARylation and PARylation, with inhibitors such as Olaparib, which disrupts AR-PARP crosstalk. In this review, we present current knowledge on the interplay between ADP-ribosylation and AR signalling in prostate cancer, emphasizing the roles of distinct PARP enzymes in shaping AR activity and therapeutic response. Herein, we focus on the combined contributions of MARylation and PARylation to prostate tumorigenesis. We also discuss how this complex regulatory network may contribute to the development of advanced prostate cancer therapies in the future. This could improve PARP inhibitor and AR signalling inhibitor combinations and allow more patients to benefit from them.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721856","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}
引用次数: 0
Bromocriptine Attenuated Ulcerative Colitis and Colonic Inflammation by Inhibiting IL-1β, Likely through NF-κB Down-regulation: Integrated Network Pharmacology and in vivo Experimental Validation. 溴隐亭通过抑制IL-1β减轻溃疡性结肠炎和结肠炎症,可能通过下调NF-κB:综合网络药理学和体内实验验证。
IF 2.8 4区 医学
Current pharmaceutical design Pub Date : 2026-04-10 DOI: 10.2174/0113816128418229260223013818
Sarthak Saha, Sourav Mondal, Oishani Chatterjee, Piyali Devroy, Debjeet Sur, Asis Bala
{"title":"Bromocriptine Attenuated Ulcerative Colitis and Colonic Inflammation by Inhibiting IL-1β, Likely through NF-κB Down-regulation: Integrated Network Pharmacology and in vivo Experimental Validation.","authors":"Sarthak Saha, Sourav Mondal, Oishani Chatterjee, Piyali Devroy, Debjeet Sur, Asis Bala","doi":"10.2174/0113816128418229260223013818","DOIUrl":"https://doi.org/10.2174/0113816128418229260223013818","url":null,"abstract":"<p><strong>Introduction: </strong>Gastrointestinal dopamine (DA) plays a crucial role in maintaining gut homeostasis. In patients with ulcerative colitis (UC), a decrease in DA levels due to changes in the gut microbiome can activate immune cells in the colon's mucosal layer, leading to the secretion of various inflammatory mediators and ultimately causing damage to the colonic mucosa. In the present study, we initially analysed integrated network pharmacology and investigated the protective effect of bromocriptine (BRO), a dopamine D2 receptor (D2R) agonist, on acetic acid (AA)-induced UC in rats.</p><p><strong>Methods: </strong>Wistar rats were randomly divided into six groups (N=6/group). The intrarectal administration of AA induced UC. Treatment groups (III-IV) received three doses (2, 5, and 10 mg/kg) of BRO once daily for seven days. Group VI animals were administered mesalamine. On the eighth day, the animals were sacrificed to evaluate the lesion scores, ulcer indices, histopathological findings, nitric oxide (NO) levels, and myeloperoxidase (MPO). Finally, tissue levels of interleukin (IL-1β) and nuclear factor kappa B (NF-κB) were measured using ELISA.</p><p><strong>Results: </strong>BRO treatment effectively improved the disease severity index (DAI), colonic lesion score, and ulcer index in rats with AA-induced UC. Histopathological studies revealed that treatment with BRO limited mucosal damage and neutrophil extravasation in colonic tissue. Moreover, biochemical assessments of MPO and NO showed a significant decrease in the levels of both inflammatory mediators following treatment with BRO. Additionally, the results indicated a reduction in the expression of IL-1β and NF-κB in colonic tissue, further supporting the amelioration of colonic inflammation caused by BRO.</p><p><strong>Discussion: </strong>The present research demonstrated that BRO exerts a protective effect by influencing the expression of IL-1β and NF-κB in rats with AA-induced UC, thus restricting the activity of immune cells in the colonic mucosa.</p><p><strong>Conclusion: </strong>Findings of this research suggest that BRO may be a promising therapeutic agent for the management of UC.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671055","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}
引用次数: 0
The Emerging Roles of lncRNA GAPLINC as a Promising Biomarker and Therapeutic Target in Oncology. lncRNA GAPLINC作为一种有前景的生物标志物和肿瘤治疗靶点的新作用。
IF 2.8 4区 医学
Current pharmaceutical design Pub Date : 2026-04-10 DOI: 10.2174/0113816128455595260309062416
Haoran Liu, Yining Pan, Haoyi Liu, Yuxiang Peng, Xinyan Zheng, Yuhan Zhang, Zhouya Xu, Zhaoying Tang, Enduo Yan, Yutong Wu, Haodong He, Gang Zhou, Chengfu Yuan
{"title":"The Emerging Roles of lncRNA GAPLINC as a Promising Biomarker and Therapeutic Target in Oncology.","authors":"Haoran Liu, Yining Pan, Haoyi Liu, Yuxiang Peng, Xinyan Zheng, Yuhan Zhang, Zhouya Xu, Zhaoying Tang, Enduo Yan, Yutong Wu, Haodong He, Gang Zhou, Chengfu Yuan","doi":"10.2174/0113816128455595260309062416","DOIUrl":"https://doi.org/10.2174/0113816128455595260309062416","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) have garnered significant attention recently since they are fundamental to many biological processes, including gene expression, chromatin remodeling, and cell cycle control. Among these, the gastric adenocarcinoma-associated positive CD44 regulator, long intergenic non-coding RNA (GAPLINC), plays a crucial role in tumor biology. GAPLINC interacts with microRNAs (miRNAs) and RNA-binding proteins to control important oncogenic pathways, including cancer cell proliferation, migration, invasion, and Epithelial-Mesenchymal Transition (EMT), as a competitive endogenous RNA (ceRNA). GAPLINC's potential as both a prognostic biomarker and a therapeutic target is highlighted by its dysregulated expression in cancer tissues, which is associated with poor prognosis and enhanced disease aggressiveness. This review focuses on the interactions of GAPLINC with miRNAs, RNA-binding proteins, and key signaling pathways, and it investigates the molecular routes through which it shapes tumor cell biology. Moreover, GAPLINC's participation in EMT and cancer stem cell control emphasizes its importance in carcinogenesis, disease development, and therapy resistance. GAPLINC has great promise for individualized cancer treatment, given its several functions in the disease. Future studies should seek to confirm GAPLINC's clinical relevance, look at its therapeutic potential, and create focused RNA-based inhibitory techniques. Such initiatives might open the path for better patient outcomes for a variety of cancer types and more efficient therapies.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670969","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}
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