Current pharmaceutical design最新文献

{"title":"Identification of Novel Selective Transient Receptor Potential Vanilloid 4 (TRPV4) Agonists.","authors":"Yuxin Jia, Meiying Liu, Heng Xu, Yixin Zhang","doi":"10.2174/0113816128381222250428094819","DOIUrl":"https://doi.org/10.2174/0113816128381222250428094819","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to synthesize small-molecule compounds by modifying the chemical structure of GSK101 and screening for novel TRPV4 agonists with high specificity and selective sensory response.</p><p><strong>Background: </strong>GSK1016790A (GSK101) effectively activates Transient Receptor Potential Vanilloid 4 (TRPV4) and simultaneously induces mechanical allodynia and acute itch. However, as a commonly used tool compound for studying sensory function, its dual effects of pain and itch can interfere with each other.</p><p><strong>Objective: </strong>To design and synthesize a series of small-molecule compounds targeting TRPV4, evaluate their properties to identify the most specific tool compounds targeting TRPV4, and determine the correlation between TRPV4 activation and sensory response.</p><p><strong>Methods: </strong>In this study, live-cell Ca2+ imaging in a heterogeneous expression system was employed to evaluate the activity of synthetic compounds, molecular docking was performed to predict binding interactions and behavioral tests for itch and pain were combined with pharmacological and genetic strategies to assess physiological responses.</p><p><strong>Results: </strong>We synthesized nine GSK101 analogues and identified six small-molecule agonists that exhibited TRPV4- targeting excitability, preserved TRPV4-mediated mechanical pain perception, and attenuated the acute itch response.</p><p><strong>Conclusion: </strong>Our study provides new insight into the role of TRPV4 in pain and itch sensation and introduces LM0038, the most potent agonist, as a novel alternative to GSK101. With enhanced biological activity, it may serve as a valuable tool for studying TRPV4 function.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980561","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":"Exploration of 4D Printing and its Applications in the Biomedical Sciences.","authors":"Anjali Rana, Arun Mittal, Chetan Vashist, Shivam Rajput, Sathvik Belagodu Sridhar, Rishabha Malviya","doi":"10.2174/0113816128358473250331175536","DOIUrl":"https://doi.org/10.2174/0113816128358473250331175536","url":null,"abstract":"<p><p>The potential for 3D printing to completely transform future advanced manufacturing systems has been widely acknowledged. Recent developments in 3D printing technology, particularly in the areas of materials, printers, and procedures, have the potential to revolutionize numerous industries and improve our quality of life on a worldwide scale. 4D printed structures evolve and display intelligent behavior based on specific stimulus-smart material interaction mechanisms and the right design of multi-material structures from mathematical modelling. Time, printer, and shape/property/functionality evolution are the goals of 4D printing, which differs from 3D printing in that it is predictable and not dependent on any one factor. These features enable the product to be self-assembled, multi-functional, and self-repairing. The idea behind fourdimensional printing is the creation of sophisticated three-dimensional structures that can change form in response to various external stimuli. The article provides a comprehensive overview of the smart materials, activation mechanisms, and shape-changing processes used in 4D printing. 4D printing items can be engineered for diverse biomedical purposes, including cell scaffolds, vascular stents, bone scaffolds, tracheal stents, and cardiac stents, through various 3D printing methodologies, influenced by diverse challenges. Additionally, the article explores the potential of shape-changing structures and their present uses in several scientific and biomedical areas.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972311","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":"Connection Between Mitochondria and Rheumatoid Arthritis and Osteoarthritis: Personalized Treatment Strategies.","authors":"Anastasia V Poznyak, Nikolay A Orekhov, Alexey V Churov, Irina Alexandrovna Starodubtseva, Tatiana Ivanovna Kovyanova, Tamara Borzalievna Pecherina, Vasily N Sukhorukov, Alexander N Orekhov","doi":"10.2174/0113816128354572250408165158","DOIUrl":"https://doi.org/10.2174/0113816128354572250408165158","url":null,"abstract":"<p><p>This review explores the critical role of mitochondria in the immunometabolic processes underlying rheumatoid arthritis (RA) and osteoarthritis (OA). It examines the interplay between immune cells, metabolic demands, and tissue environments, emphasizing the impact of bioenergetics on immune responses and disease progression. Mitochondrial dysfunction in chondrocytes and immune cells contributes to OA and RA through mechanisms such as oxidative stress, disrupted calcium homeostasis, and inflammasome activation. In OA, mitochondrial dysfunction in chondrocytes results in impaired energy production, elevated reactive oxygen species (ROS), and calcium imbalance, leading to cartilage degradation and inflammation. The review highlights how disturbances in the mitochondrial respiratory chain and apoptotic pathways drive joint tissue damage. In contrast, RA shows how mitochondrial dysfunction influences chronic inflammation and synovial hyperplasia. The role of mitochondrial DNA (mtDNA) as a damage-associated molecular pattern (DAMP) is emphasized, illustrating how oxidized mtDNA activates inflammatory pathways, triggers immune responses, and contributes to joint destruction. Additionally, mitochondrial genetic variations may exacerbate inflammation and oxidative stress in RA. The review also discusses the effects of various RA treatments-conventional synthetic anti-rheumatic drugs, biological agents, and targeted synthetic DMARDs-on mitochondrial function. Insights into how these therapies modulate mitochondrial pathways and oxidative stress in immune and joint cells highlight new potential treatment strategies. This review enhances our understanding of OA and RA pathophysiology by elucidating the connections between mitochondria, immune responses, and rheumatic diseases, paving the way for innovative therapies targeting mitochondrial dysfunction.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986823","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":"A Spotlight on PLGA-Based Nanoparticles: Pioneering a New Era in the Therapeutics of Cardiovascular Disorders.","authors":"Neelam Sharma, Vaishnavi Chauhan, Sukhbir Singh, Philips Kumar, Sakshi Verma, Sumeet Gupta, Ladli Kishore, Shahid Nazir Wani","doi":"10.2174/0113816128361869250409171305","DOIUrl":"https://doi.org/10.2174/0113816128361869250409171305","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disorders (CVDs) are the primary cause of mortality globally, and the community is significantly affected when young people suffer from CVDs. Coronary artery disease, myocardial infarction, fibrosis, atherosclerosis, pulmonary arterial hypertension, thrombosis, and ischemic diseases are different types of CVDs, which encompass a wide range of conditions that interfere with the functioning of the cardiovascular system. The relevance of nanotechnology in the treatment of CVDs has emerged progressively in previous decades.</p><p><strong>Objective: </strong>This review offers concise insights into the physiochemical characteristics of poly (lactic-coglycolic acid) (PLGA) imperative for drug delivery. This article highlights the application of PLGA-NPs in myocardial ischemia, atherosclerosis, myocardial infarction, pulmonary artery hypertension, valvular heart disease, tumour thrombus, cardiac myocyte, restenosis, cardiovascular theranostics, vascular disorders, and angiogenesis. Further, this review gives updates about published patents pertaining to the current state-of-art about PLGA-NPs in CVDs.</p><p><strong>Methods: </strong>An extensive review was undertaken employing the Google Scholar, PubMed, and ScienceDirect databases using scientific papers published in peer-reviewed journals from 2000 to 2024.</p><p><strong>Results: </strong>Owing to their minuscule size and increased surface area accessible for surface functionalization, the PLGA-NPs offer a cutting-edge technology to provide an efficient platform for controlled and targeted drug delivery, therefore, imparting tremendous relevance in reducing the occurrence of CVDs.</p><p><strong>Conclusion: </strong>This has been concluded that PLGA is the highly effective biodegradable copolymer, also known as \"Smart polymers,\" because of their biodegradability, biocompatibility, controlled drug release profile, and potential for surface modification with targeting molecules.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986829","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":"Harnessing PANoptosis for Innate Immune Response.","authors":"Ayesha Sultana, Gyas Khan, Md Sadique Hussain","doi":"10.2174/0113816128390458250423112018","DOIUrl":"https://doi.org/10.2174/0113816128390458250423112018","url":null,"abstract":"","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988889","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":"Advancing Melanoma Care: Microneedles for Diagnosis and Therapeutic Precision.","authors":"Shreyansh Chauhan, Jai Naik, Preksha Vinchhi, Mayur M Patel","doi":"10.2174/0113816128384441250422045753","DOIUrl":"https://doi.org/10.2174/0113816128384441250422045753","url":null,"abstract":"<p><p>Melanoma, an aggressive skin tumor derived from melanocytes, is associated with a high mortality rate attributed to its frequent metastasis, drug resistance, and high invasion rate. The current therapeutic interventions for melanoma, such as surgery, chemotherapy, immunotherapy, and radiation therapy, are not efficient enough to treat melanoma. The current melanoma care is associated with limitations, such as late diagnosis and staging, false positives, treatment resistance, immune-related side effects, lack of standardization, challenges in metastatic melanoma cure, high treatment costs, recurrence, etc. Conventional therapies have poor anti- cancer efficacy due to premature drug degradation, severe adverse effects owing to systemic drug exposure, and low drug concentration at the malignancy site. Moreover, the current diagnosis for melanoma is associated with painful sample collection techniques, limited imaging techniques, limited understanding of genetic markers, etc., leading to misdiagnosis or delayed diagnosis. An extensive literature review on Microneedles (MNs) for melanoma diagnosis and treatment was conducted using PubMed, ScienceDirect, and Google Scholar databases from 2012 to 2025. This mini-review presents the advantages of MNs over current therapy, their formulation aspects, and their advancements for the diagnosis and treatment of melanoma. MNs, an emerging drug delivery system, can efficiently penetrate the skin barriers and form reversible microchannels to deliver the drug at melanoma sites without drug leakage, mitigating the adverse effects and increasing drug accumulation. MNs also provide an excellent platform to integrate novel and conventional therapies by encompassing discrete therapeutic agents in a single matrix. Moreover, MNs can capture biomarkers by absorbing the skin Interstitial Fluid (ISF) and facilitate diagnosis by minimal biological samples.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983560","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":"Small Intestinal Bacterial Overgrowth (SIBO) - Prevention and Therapeutic Role of Nutrition, Prebiotics, Probiotics, and Prokinetics.","authors":"Faheem Mustafa, Remesah Noor, Asifa Murtaza, Wajeeha Kanwal, Fareeha Kanwal, Tayyaba Kaleem, Farwa Munir, Rabiatul Adawiyah Binti Umar, Wan Rohani Wan Taib, Shanthi Krishnasamy, Shivani Chopra, Hitesh Chopra","doi":"10.2174/0113816128373584250407134451","DOIUrl":"https://doi.org/10.2174/0113816128373584250407134451","url":null,"abstract":"<p><p>Small Intestinal Bacterial Overgrowth (SIBO) is a condition marked by an increased proliferation of bacteria in the small intestine. This leads to a range of GI symptoms and nutritional issues. This article examines the preventive and therapeutic roles of nutrition, prebiotics, probiotics, and prokinetics in managing SIBO. Finding the prevalence of SIBO in the general population is challenging due to challenges in diagnosis and different diagnostic methods. Nevertheless, SIBO has been linked to several clinical conditions, such as obesity, celiac disease, irritable bowel syndrome, inflammatory bowel disease, and hepatic cirrhosis. The connection between SIBO and obesity remains controversial and unclear, with contraindicating evidence regarding its prevalence and association with body mass index (BMI). Anatomical changes from surgeries may also contribute to the development of SIBO, and disruptions in the migrating motor complex (MMC) can facilitate intestinal permeability. SIBO can lead to significant malabsorption of nutrients, including carbohydrates, fats, proteins, and iron, resulting in deficiencies and malnourishment. Additionally, increased levels of immunoglobulins observed point toward a possible immune response to bacterial overgrowth. Hence, understanding the prevalence, clinical manifestations, and nutritional impacts of SIBO is crucial for effective prevention and management. This article underscores the potential benefits of nutrition, including prebiotics and probiotics, in modulating gut microbiota and managing SIBO. Furthermore, prokinetics that enhance gastrointestinal motility may offer possible therapeutic advantages in the future. Continued research is necessary to clarify the underlying mechanisms and refine treatment strategies for SIBO.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980777","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":"Naringenin Attenuates Ox-LDL-induced Injury in HUVECs by Regulating Lipophagy Partly through the SOCE Pathway.","authors":"Linhong Jiang, Dandan Bai, Yunjun Yang, Yingying Wu, Yanran Chen, Mengyuan Wang, Wenxin Wang, Haixia Wang, Yanzhe Xiong, Siqi Zhu, Xinyu He, Jun Long, Dongping Yuan, Jingwei Chen","doi":"10.2174/0113816128335261241216110529","DOIUrl":"https://doi.org/10.2174/0113816128335261241216110529","url":null,"abstract":"<p><strong>Objective: </strong>Naringenin (NAR) is a naturally occurring tiny molecule that has a significant role in lipid metabolism. However, the molecular mechanism by which NAR is involved in lipid metabolism to protect ECs is not clear. This study aims to investigate the effect of NAR on autophagy in oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs) and its potential molecular mechanisms.</p><p><strong>Methods: </strong>Oxidized LDL-induced HUVECs injury in vitro was treated with NAR. Chloroquine was used as an autophagy inhibitor. Ionomycin (Iono) and 2-aminoethoxydiphenylborate (2-APB) were used as an SOCE pathway agonist and an inhibitor, respectively. The autophagy levels in HUVECs were determined by quantitative real-time PCR, western blot, and immunofluorescence methods. The concentration of calcium ions in HUVECs was measured by flow cytometry.</p><p><strong>Results: </strong>The findings revealed that NAR increased the viability of ox-LDL-impaired HUVECs. NAR increased the level of autophagy and decreased lipid accumulation in ox-LDL-treated HUVECs, which could interfere with chloroquine. Moreover, NAR significantly downregulated the expression of STIM1 and ORAI1 proteins and Ca2+ levels in the SOCE, which could be interfered with Iono or 2-APB, respectively.</p><p><strong>Conclusion: </strong>In summary, NAR can increase autophagy levels and decrease lipid accumulation in HUVECs, eventually protecting against ox-LDL-induced injury in HUVECs, which is associated with inhibition of the SOCE pathway.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957852","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":"Anti-hypertensive Function of Plant-derived Bioactive Peptides: A Review.","authors":"Monalisa Gochhi, Priyanka Dash, Biswakanth Kar, Deepak Pradhan, Jitu Halder, Chandan Das, Vineet Kumar Rai, Saroj Kumar Rout, Goutam Ghosh, Goutam Rath","doi":"10.2174/0113816128386781250415105515","DOIUrl":"https://doi.org/10.2174/0113816128386781250415105515","url":null,"abstract":"<p><p>Hypertension is considered to be a crucial factor in the development of chronic diseases like obesity, diabetes, and Cardiovascular Disease (CVD). Several conventional medications are frequently used to manage hypertension. However, they have certain adverse effects that limit their use. Therefore, alternative medications, including bioactive peptides, could be valuable in managing CVD because they are safer, less expensive, and more effective. In light of this, this article aimed to explore the potential application of plantderived peptides for their efficient role in ameliorating hypertension. In particular, the authors summarise the current understanding of the anti-hypertensive function of plant-derived bioactive peptides, focusing on the source, isolation technique, purification process, and potential CVD applications. The potential antihypertensive peptides are highlighted in particular, and their molecular mechanisms, such as ACE inhibition, renin inhibition, and CCB blockers, are highlighted in terms of in vitro, in vivo, and in-silico models. Recent literature evidence revealed that plant peptides with low molecular weight show better potential for inhibiting ACE and renin. Moreover, the molecular structure, solubility, and types of amino acids play an important role in determining antihypertensive activity. This review will improve the understanding of plant-derived bioactive peptides and provide some constructive inspiration for further research and industrial application in cardiovascular disorders.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988888","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 Role of MicroRNAs, CircRNAs, and LncRNAs in Chronic Lymphocytic Leukemia.","authors":"Nan Chen, Yaping Zhang, Yongning Jiang, Guangcan Gao, Jianyong Li, Wenyu Shi","doi":"10.2174/0113816128361848250401200001","DOIUrl":"https://doi.org/10.2174/0113816128361848250401200001","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) constitutes a heterogeneous hematological malignancy, often correlated with disruptions in various signaling pathways, chromosomal deletions, and gene mutations. A comprehensive grasp of CLL pathogenesis and its associated risk factors remains vital for the development of more efficacious treatment strategies. Although non-coding RNAs (ncRNAs) do not encode proteins, they possess substantial regulatory influence over target genes. These ncRNAs govern a multitude of target genes implicated in the pathogenesis of CLL. Furthermore, some ncRNAs serve as prognostic markers in CLL and might contribute to overcoming chemotherapy resistance. This review determines the association between ncRNAs and the molecular mechanisms driving the onset and advancement of CLL, with particular emphasis on the roles of these ncRNAs in modulating signaling pathways, encompassing NF-κB/PI3K-AKT/TNF and P53 in CLL. It also underscores their relevance as significant biomarkers and their potential as therapeutic targets in clinical CLL settings.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972321","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}