Current pharmaceutical design最新文献

{"title":"Unveiling Targeted Approaches to Combat Drug Resistance in Cancer Chemotherapy.","authors":"Siddharth, Siddhant, Salahuddin, Avijit Mazumder, Rajnish Kumar, Abhijit Debnath","doi":"10.2174/0113816128380235250627143945","DOIUrl":"https://doi.org/10.2174/0113816128380235250627143945","url":null,"abstract":"<p><p>Despite significant advancements in medical science, cancer continues to be a major cause of morbidity and mortality worldwide. A key factor contributing to this persistent burden is the emergence of resistance to conventional therapeutic modalities, including chemotherapy, radiation therapy, and surgery. This phenomenon of drug resistance significantly hampers the efficacy of these treatments, leading to therapeutic failure and poor clinical outcomes. A detailed understanding of the molecular and cellular mechanisms underlying drug resistance is crucial for devising targeted strategies to overcome these barriers. In this review, we aim to critically assess and highlight various approaches that can effectively reduce chemotherapy resistance, with the goal of improving the therapeutic efficacy of chemotherapy and enhancing overall patient survival.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636462","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":"Recent Developments in Vesicular Nanocarriers for Targeted Drug Delivery in Breast Cancer.","authors":"Shreastha Gautam, Priya Jindal, Sachin Joshi, Rashmi Maurya, Preeti Patel, Ghanshyam Das Gupta, Balak Das Kurmi","doi":"10.2174/0113816128385024250625212516","DOIUrl":"https://doi.org/10.2174/0113816128385024250625212516","url":null,"abstract":"<p><p>Breast cancer remains one of the most challenging malignancies worldwide due to its heterogeneity, which affects tumor behavior, progression, and treatment response. The complexity of breast cancer necessitates innovative therapeutic strategies to improve treatment outcomes. This review explores the potential of vesicular nanocarriers, including liposomes, niosomes, ethosomes, polymerosomes, phytosomes, and transferosomes, in enhancing breast cancer treatment efficacy through targeted drug delivery. A detailed analysis of recent progress in the functionalization and application of vesicular nanocarriers is discussed, highlighting their contribution to enhancing pharmacokinetics, drug solubility, and targeted delivery. Both passive and active targeting strategies were assessed for their ability to enhance tumor-specific drug accumulation. Vesicular nanocarriers offer significant advantages, including reduced systemic toxicity, improved drug bioavailability, and precise delivery to cancer cells. Passive targeting utilizes the enhanced permeation and retention effect for tumor accumulation, while active targeting employs surface modifications with antibodies, aptamers, or peptides to enhance specificity. The integration of vesicular nanocarriers in breast cancer therapy presents a promising strategy for more effective and personalized treatment approaches. Their ability to optimize drug delivery and minimize off-target effects highlights their potential to revolutionize breast cancer treatment.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636461","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":"miRNA in Diagnosis and Therapeutics of Tuberculosis: Importance in Latent and Brain Associated Pathologies.","authors":"Parul Gupta, Ravindra Kumar, Rituraj Niranjan","doi":"10.2174/0113816128362931250619113617","DOIUrl":"https://doi.org/10.2174/0113816128362931250619113617","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are the regulators of gene expression and several cellular processes related to the immune system. miRNAs during tuberculosis (TB) infection are considered regulatory factors for the host immune system. Mycobacterium tuberculosis has a great ability to survive and multiply in phagocytic cells, which makes it difficult to treat. It can replicate through various cellular pathways. To establish the infection in the host cell, m. tuberculosis changes in the miRNA expression and increases survival capacity with high infectivity. miRNAs are widely used as biomarkers and therapeutic agents for tuberculosis. During m. tuberculosis infection, altered miRNA expressions can cause the progression of the disease and discriminate between latent and active TB infection. Due to their active involvement in disease progression, miRNAs may be utilized as potential biomarkers. Furthermore, the involvement of miRNA in autophagy and apoptosis modulation against m. highlights its potential for host-directed therapy. In this review article, we attempt to summarize the expression and role of various miRNAs in TB as immune modulators, differential activators between different phases of TB, including neuronal dysfunction in the brain, and as therapeutic targets and diagnostic tools against TB.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636460","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":"Integrated Network Pharmacology and Molecular Modeling Approach for Potential PTGS2 Inhibitors against Rheumatoid Arthritis.","authors":"Huda Abbasi, Maria Sharif, Peter John, Attya Bhatti","doi":"10.2174/0113816128370525250407164738","DOIUrl":"https://doi.org/10.2174/0113816128370525250407164738","url":null,"abstract":"<p><strong>Introduction: </strong>Rheumatoid arthritis (RA) is a chronic inflammatory condition of the joints and a leading cause of global disability. However, the use of current anti-inflammatory treatments is often limited by serious side effects and multi-organ toxicity, necessitating the exploration of safer alternatives.</p><p><strong>Objective: </strong>This study aims to investigate the anti-rheumatic potential of natural compounds of Cassia angustifolia as small-molecule inhibitors of PTGS2.</p><p><strong>Methods: </strong>The therapeutic potential of C. angustifolia was evaluated through antioxidant and antiinflammatory assays. Gas chromatography-mass spectrometry (GC-MS) was used to identify its constituents. ADMET profiling (absorption, distribution, metabolism, excretion, and toxicity), network pharmacology, and molecular dynamics simulation were employed to uncover the active compounds against PTGS2 for RA treatment.</p><p><strong>Results: </strong>C. angustifolia extract contained significant phenolic (18.2 ± 0.008 mg GAE/g DW) and flavonoid (27.57 ± 0.03 mg RE/g DW) content. GC-MS yielded 288 compounds of which four passed the toxicity parameters. Protein-protein interaction analysis revealed 10 RA-related targets, with PTGS2 emerging as the most prominent one. Molecular docking and simulations revealed that compound-2 [2-Benzo [1,3] dioxol-5- yl-8-methoxy-3-nitro-2H-chromene] and compound-4 [alpha-hydroxy-N-[2-methoxyphenyl]-benzene propanamide] binds strongly with PTGS2 (-7.7 kcal/mol and -7.9 kcal/mol, respectively) predicting its stable interaction.</p><p><strong>Conclusion: </strong>C. angustifolia compounds present a significant potential as PTGS2 inhibitors, warranting further in vitro and in vivo investigations to confirm their therapeutic efficacy against RA.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607750","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":"Incretin-based Agents and Metabolic Dysfunction-associated Steatotic Liver Disease.","authors":"Emir Muzurović, Martin Haluzik, Ludek Horváth, Bogdan Vlacho, Didac Mauricio","doi":"10.2174/0113816128378484250619080753","DOIUrl":"https://doi.org/10.2174/0113816128378484250619080753","url":null,"abstract":"<p><p>Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease worldwide, primarily driven by the rising prevalence of both obesity and type 2 diabetes mellitus (T2DM). Historically, treatment options for patients with more advanced stages of hepatic dysfunction (steatohepatitis, fibrosis, cirrhosis) have been limited, with only resmetirom, a thyroid hormone receptor-β agonist, recently being approved for use as a metabolic dysfunction-associated steatohepatitis (MASH)-specific treatment option. Incretin-based receptor agonists are emerging as promising treatments for MASLD, and multiple liver-biopsy powered trials are underway. This group of drugs has gained attention as possible treatment options for MASLD/MASH, due to their significant weight-loss and body fat reduction effects, and there is also a growing body of evidence that incretin-based agents lead to a significant reduction in liver fat content. However, the evidence concerning improvement of steatohepatitis and/or fibrosis is limited. Most authorities consider incretin mimetics to be only one contributing factor to the treatment paradigm of the MASLD/MASH/ fibrosis/cirrhosis continuum. Specifically, according to the data to date, incretin-based treatments may improve metabolic abnormalities in MASLD/MASH patients, especially in patients with obesity and/or T2DM, and may mitigate its progression at the early stages. However, no incretin-based treatment is officially approved in this indication yet. This review discusses the rationale for the use of incretin-based treatment options in patients with MASLD/MASH, explaining the pathophysiological background of this disorder and describing the possible mechanism of action of these drugs.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607749","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":"Neuroprotective Effects of Eugenol in Alzheimer's Disease: Mitigating Oxidative Stress, Inflammation and Amyloid Plaques.","authors":"Aniket Kakkar, Harpreet Singh, Amit Anand, Hitesh Chopra, Arun Kumar Mishra","doi":"10.2174/0113816128373290250620054118","DOIUrl":"https://doi.org/10.2174/0113816128373290250620054118","url":null,"abstract":"<p><p>Eugenol, a phenolic phytochemical found in many medicinal plants, exhibits various pharmacological properties, including analgesic, antipyretic, antioxidant, anti-inflammatory, antimicrobial, anticancer, neuroprotective, and anaesthetic effects. It has shown potential in addressing neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease, and motor neuron disease, which are primarily caused by mechanisms such as apoptosis, protein accumulation, aging, and oxidative stress within the central nervous system (CNS). This review explores the mechanisms through which eugenol may influence AD. Eugenol appears to counter oxidative stress, reduce inflammation, and prevent amyloid beta (Aβ) plaque accumulation, suggesting it could delay the onset or progression of AD. However, more research is required to establish its safety and effectiveness in treating or preventing this disease.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599652","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":"Stem Cell Nanotechnology Applications as Drug Delivery Systems for Cancer Therapy: A New Era in Targeted Treatment.","authors":"Gyas Khan","doi":"10.2174/0113816128379044250620122425","DOIUrl":"https://doi.org/10.2174/0113816128379044250620122425","url":null,"abstract":"<p><p>Cancer is still one of the most serious and life-threatening diseases in humans, and the conventional chemotherapies, radiation treatments, and surgical methods have yet to provide an effective resolution due to some drawbacks concerning drug resistance, general toxicity, and poor targeting to tumor sites. To surmount these challenges, some innovative approaches are under exploration; hence, the emergence of more promising solutions in the format of nanotechnology that combine with stem cell (SC)-based drug delivery systems (DDS). Its advantages include autonomous proliferative potential and the ability to clonally generate various cell types, leading to malignant transformation. Additionally, they possess an innate ability to migrate toward tumor sites, making them highly effective vectors for targeted DDS. The integration of nanotechnology with SCs offers several benefits, such as controlled release of therapeutic molecules, improved bioavailability, and reduced systemic toxicity. These advantages may provide the opportunity to improve cancer therapy with fewer side effects than those resulting from conventional treatments. This review has focused on the emerging role of SC-nanotechnology-based DDS as a new era in targeted cancer treatment and has emphasized enhancing therapeutic outcomes with a more precise approach to cancer therapy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599681","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 Cannabis as a Sustainable Antimicrobial Approach: What to Foreknow?","authors":"Natália Cruz-Martins, Latifa Bouissane","doi":"10.2174/0113816128406019250702060456","DOIUrl":"https://doi.org/10.2174/0113816128406019250702060456","url":null,"abstract":"","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599682","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":"Sorafenib Resistance in Hepatocellular Carcinoma: Emerging Molecular Insights from Long Non-Coding RNAs.","authors":"Dengke Jia, Yaping He, Qianle Chen, Hao Wu, Yawu Zhang","doi":"10.2174/0113816128371240250619102820","DOIUrl":"https://doi.org/10.2174/0113816128371240250619102820","url":null,"abstract":"<p><strong>Background: </strong>Sorafenib is a first-line treatment for patients with advanced hepatocellular carcinoma (HCC), but its clinical efficacy is often compromised by the acquisition of drug resistance. Various cancers, including HCC, are affected by long non-coding RNA (lncRNA), but the mechanisms underlying HCC sorafenib resistance have not been extensively studied. This article aims to summarize the recently reported pathways associated with sorafenib resistance and discusses potential applications for the treatment of HCC.</p><p><strong>Methods: </strong>Relevant studies on the resistance of HCC to anti-tumor drugs were retrieved from PubMed. Given the compelling evidence that sorafenib is an effective treatment for advanced HCC, we analyzed the research papers on lncRNA and sorafenib resistance in HCC in the PubMed system in the past decade and found that lncRNA may be involved in sorafenib resistance in HCC through multiple pathways.</p><p><strong>Results: </strong>lncRNA is widely involved in the resistance mechanism of HCC to sorafenib. Recent studies have revealed that numerous lncRNAs, such as NEAT1, affect the sensitivity of HCC to sorafenib through various mechanisms, including autophagy and AKT signaling pathways.</p><p><strong>Conclusion: </strong>lncRNAs play a pivotal role in modulating HCC resistance to sorafenib. And lncRNA is expected to become a new solution to the resistance of sorafenib and other targeted drugs.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599653","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":"Mebendazole as an Adjunct Therapy with Mesalamine to Increase Efficacy and Maintenance Therapy for Ulcerative Colitis Patients: A Pilot Study.","authors":"Moein Eskandari, Ayat Heydar-Abdolamir Alkhafaji, Abdulridha Mohammed Al-Asady, Hamideh Naimi, Amir Mahmoud Ahmadzadeh, Amir Avan, Hassan Vossoughinia, Ali Mehri, Mikhail Ryzhikov, Majid Khazaei, Mitra Ahadi, Seyed Mahdi Hassanian","doi":"10.2174/0113816128372513250616182826","DOIUrl":"https://doi.org/10.2174/0113816128372513250616182826","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is an inflammatory disorder of the large intestine characterized by inflammation in the mucosal tissue of the colon and rectal area. In the present pilot study, we assessed the efficacy of combining mebendazole with mesalamine in moderate UC patients.</p><p><strong>Methods: </strong>In the present exploratory pilot trial, designed to assess both the safety and preliminary efficacy of mebendazole, a total number of 10 moderate UC patients with Mayo scores ranging from 6 to 9 were enrolled. The participants were divided into two groups at random and were treated with 3 gr mesalamine per day plus 300 mg/day mebendazole or matching placebo for 3 months. The efficacy of treatment was assessed in 8 and 12-week timelines with Mayo score. Moreover, the safety of the given dose of mebendazole in UC patients was also assessed by laboratory tests.</p><p><strong>Results: </strong>The addition of mebendazole to the mesalamine in the treatment regimen of patients suffering from UC caused a greater decrease in the Mayo score of the patients compared to the mesalamine monotherapy at 8 and 12-week timelines. Despite this trend, statistical significance was not reached, likely due to the limited sample size. Moreover, all the patients in the mebendazole group experienced clinical remission at the 12-week timeline, but 4 of 5 patients in the placebo group experienced a clinical remission state, indicating that mebendazole caused a 20% increase in the clinical remission rate. As indicated by the results of the laboratory tests, the given dose of mebendazole showed no toxicity in the patients.</p><p><strong>Conclusion: </strong>The addition of mebendazole to mesalamine for UC treatment appears to be a safe and potentially beneficial approach to enhance mesalamine's efficacy and reduce clinical symptoms. However, given the small sample size and the short study duration, further large-scale, long-term trials are necessary to validate these preliminary findings.</p><p><strong>Clinical trial registration number: </strong>IRCT20220115053713N2.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583325","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}