Current medicinal chemistry最新文献

{"title":"Dermal Melanocytes Detectability for Distinguishing In Situ and Early Invasive Melanoma: A Narrative Review.","authors":"Łukasz Kuźbicki","doi":"10.2174/0109298673339877250210105022","DOIUrl":"https://doi.org/10.2174/0109298673339877250210105022","url":null,"abstract":"<p><p>The melanoma incidence has been increasing over the past three decades, with a disproportionately high fraction of in situ tumors. The diagnosis of melanoma at its earliest stages can be challenging. The detectability of tumor melanocytes in the dermis is of key importance for distinguishing in situ from invasive melanomas. In this review, a total of 475 melanomas diagnosed as in situ tumors by hematoxylin and eosin staining were analyzed. This diagnosis was confirmed for 68% of cases, but 15% of in situ melanomas were reassessed as invasive lesions using immunohistochemistry. The cases were upstaged by Melan-A/Mart-1, S-100, and SOX-10 with frequencies of 14.6%, 11.7%, and 10.8%, respectively. Whereas, the diagnosis of in situ melanoma was confirmed by SOX-10, Melan-A/Mart-1, and S-100 in 81.4%, 63.8%, and 59.1% of cases, respectively. Moreover, the analysis of immunohistochemical detectability of melanocyte markers in different types of dermal cells was carried out for 574 various skin lesions. The stainings of S-100, SOX-10, MITF, and PRAME in fibroblasts and histiocytes, as well as Melan-A/Mart-1, HMB-45, and MITF in melanophages, were noted. The diagnosis of in situ melanoma based on hematoxylin and eosin staining is confirmed by immunohistochemistry in most cases. However, some in situ tumors become reassessed as invasive malignancies. Although none of the currently used melanocyte markers is absolutely specific, simultaneous analysis of nuclear SOX-10 and cytoplasmic Melan-A/Mart-1 stainings can support the diagnosis. However, immunohistochemistry remains an auxiliary tool, and the results should be analyzed in association with the cytomorphological features.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457132","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":"Evaluation of Antiseptic Drug Candidate Pyridosept in Preclinical in Vitro Studies.","authors":"Renata Kazakova, Alfiya Iksanova, Mariya Agafonova, Anna Lubina, Elena Bulatova, Elena Nikitina, Svetlana Lisovskaya, Airat Kayumov, Oxana Bondar, Albina Malanyeva, Olga Vasileva, Marina Zeldi, Alina Gatina, Sergei Koshkin, Natalia Komcharova, Yulia Konyakhina, Kseniia Titova, Aleksandr Sergeev, Sergey Sapozhnikov, Nikita Shtyrlin, Yurii Shtyrlin","doi":"10.2174/0109298673356654250122063321","DOIUrl":"10.2174/0109298673356654250122063321","url":null,"abstract":"<p><strong>Introduction: </strong>This work provides preclinical in vitro studies of an innovative antimicrobial agent named pyridosept, belonging to the quaternary bis-ammonium salts and synthesized on the base of pyridoxine. Since the wide spread of pathogens with tolerance to both antibiotics and antiseptics challenges the development of new antimicrobials providing high efficiency against fungi and microorganisms with multiple resistance.</p><p><strong>Method: </strong>This work presents in vitro studies of pyridosept, such as antibacterial and anti-fungal activities (determination of minimal inhibitory concentration and quantitative suspension test method), as well as antibacterial activity of metal surface test, sporicidal and spermicidal activities, formation of resistance (to bacteria and fungi), Skin-PAMPA\u0000(study of membrane transdermal permeability), mutagenicity assays (in Ames test and OS-chromotest), cytotoxicity (MTT-assay) and comet assay in human skin fibroblasts.</p><p><strong>Results: </strong>Pyridosept demonstrates advantageous antibacterial and antifungal activity in both suspension and metal surface tests; it has anti-SARS-CoV-2, spermicidal and sporicidal activities (comparable to chlorhexidine digluconate). On the other hand, it demonstrates a low frequency of bacterial resistance development (no more than 2-4-fold in-\u0000crease of the MIC in 30 passages, with MIC values fluctuating within 1-8 μg/ml for Gram-positive bacteria and 4-32 μg/ml for Gram-negative bacteria) and membrane transdermal permeability (Skin-PAMPA, 500-fold less compared to progesterone). While cytotoxicity (in MTT- and comet assay) of pyridosept is comparable with those for bezalkonium chloride and chlorhexidine, our results suggest that pyridosept represents an advantageous structure for the design of new antiseptics.</p><p><strong>Conclusion: </strong>The information obtained during the studies demonstrated that pyridosept has a good efficacy and safety profile, which allows us to consider it as a potential anti-septic and disinfectant, for which it is necessary to conduct additional in vivo studies.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457135","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":"DDX59-AS1: A Novel Prognostic Biomarker and Immunotherapy Predictor in Lung Adenocarcinoma.","authors":"Yanli Wang, Wei Li, Su Wei, Lixi Zhang, Dongbing Li, Xu Qi","doi":"10.2174/0109298673359149250212073143","DOIUrl":"https://doi.org/10.2174/0109298673359149250212073143","url":null,"abstract":"<p><strong>Background: </strong>The precise function of DDX59 Antisense RNA 1 (DDX59- AS1) in lung adenocarcinoma (LUAD) has yet to be fully elucidated.</p><p><strong>Objective: </strong>This study uses bioinformatics analysis and experimental validation to investigate the association between DDX59-AS1 and LUAD.</p><p><strong>Methods: </strong>This study uses statistical analysis and database interrogation to investigate the potential association between DDX59-AS1 expression and various clinical characteristics, prognostic factors, regulatory networks, and immune infiltration in LUAD. The quantification of DDX59-AS1 expression in LUAD cell lines is conducted through the use of quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong>DDX59-AS1 showed significantly elevated levels of expression in patients with LUAD. High levels of DDX59-AS1 expression were found to be significantly associated with poorer overall survival (OS) in patients with LUAD (p = 0.024). Furthermore, an independent correlation was observed between high DDX59-AS1 expression (p = 0.037) and OS in LUAD patients. DDX59-AS1 was found to be involved in various pathways, including glutathione metabolism, proteasome function, and the cytosolic DNA sensing pathway, among others. A significant correlation was observed between the expression levels of DDX59-AS1 and immune cell infiltration in the context of LUAD. Notably, elevated expression of DDX59-AS1 was observed in LUAD cell lines compared to the non-cancerous Beas-2B cell line.</p><p><strong>Conclusion: </strong>A significant correlation was observed between elevated DDX59-AS1 expression in patients with LUAD and adverse prognosis, alongside increased immune infiltration. These results indicate that DDX59-AS1 may function as a prognostic marker for LUAD and a potential predictor of immunotherapy response.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457129","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":"Protective Effect of Curcumin on Metabolic Syndrome Components through the Microbiota.","authors":"Farzane Vafaeie, Tahereh Farkhondeh, Saeed Samarghandian, Ebrahim Miri-Moghaddam","doi":"10.2174/0109298673371503250210092741","DOIUrl":"https://doi.org/10.2174/0109298673371503250210092741","url":null,"abstract":"<p><p>Curcumin, a natural polyphenolic compound found in turmeric, has garnered increasing research interest due to its potential health benefits, particularly in the context of the rising global prevalence of metabolic syndrome (MetS). With MetS affecting a significant portion of the global population and serving as a precursor to chronic diseases, such as type 2 diabetes and cardiovascular diseases, identifying effective, accessible, and safe interventions has become a critical public health priority. This review explores curcumin's role in regulating gut microbiota composition, enhancing intestinal barrier function, and reducing inflammation, which can collectively improve key components of MetS, such as hyperglycemia, dyslipidemia, obesity, and hypertension. Supplementation with curcumin has shown promising results in improving metabolic health by promoting the production of short-chain fatty acids (SCFAs), such as butyric and propionic acids. These effects may protect against dyslipidemia and reduce the risk of chronic conditions. Furthermore, curcumin has demonstrated potential in reducing hypertension through various mechanisms, including inflammation reduction, modulation of lipopolysaccharide (LPS) production, activation of G-protein-coupled receptor 43 (GPR43), and increased levels of SCFAs. Given the significant public health implications of MetS, understanding curcumin's impact on gut microbiota presents an opportunity for developing novel therapeutic strategies that address this urgent health challenge. Despite its promise, further research is necessary to fully comprehend the underlying mechanisms involved. Additionally, determining the optimal dosage and duration of curcumin supplementation for achieving its effects on metabolic syndrome is crucial for future therapeutic applications. This review highlights curcumin's potential as a natural compound with multifaceted health benefits, particularly in the context of metabolic syndrome and its associated complications, emphasizing the pressing need for clinical studies to validate findings and inform evidence-based therapeutic applications.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457141","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":"Bibliometric Analysis of Research on Traditional Chinese Medicine Treatment of Myocardial Infarction from 2007 to 2024 Based on the Web of Science Database.","authors":"Qi Lan, Hao Wu, Ming-Tai Chen, Jin-Yi Xue, Maryam Mazhar, Zi-Wen Deng, Yuan Zou, Ping Liu, Gang Luo, Li Dong, Meng-Nan Liu","doi":"10.2174/0109298673362741250128065027","DOIUrl":"https://doi.org/10.2174/0109298673362741250128065027","url":null,"abstract":"<p><strong>Background: </strong>Myocardial infarction (MI) is a common critical syndrome in the late development of cardiovascular diseases (CVDs), and traditional Chinese Medicine (TCM) treatment has become an essential branch in this field.</p><p><strong>Objective: </strong>This study aimed to use bibliometric methods to examine the research trajectory of TCM treatment of MI from 2007 to 2024 from a multidimensional perspective and analyse its characteristics, hotspots, and frontiers.</p><p><strong>Methods: </strong>This study used the search formula TS OR TI OR AB OR A (\"traditional Chinese medicine\" or \"Chinese medicine\" or \"TCM\" or \"traditional medicine, Chinese\" or \" Chinese traditional medicine\" or \"Chinese medicine, traditional\") AND TS OR TI OR AB OR AK (\"myocardial infarction\" or \"myocardial infarctions\" or \" infarction, myocardial\" or \"infarctions, myocardial\" or \"myocardial infarct\" or \"MI\") to find the Web of Science Core Collection (WOSCC) of relevant studies from 01/01/2007 to 04/29/2024. Target literature records were analysed and graphed using CiteSpace, VOSviewer, and Scimago Graphica.</p><p><strong>Results: </strong>A total of 754 records were obtained and 399 records were finally retained after screening. Countries, institutions, authors, and journals were visually analyzed. The current research hotspots and frontiers included Salvia miltiorrhiza, ischemia-reperfusion injury, pathway, molecular docking, and network pharmacology.</p><p><strong>Conclusion: </strong>This research study would enrich the researchers' understanding of the existing research methodology and future development trends and provide a more efficient research methodology for the research on the mechanism of action of TCM for the treatment of MI and its clinical trials.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457127","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":"Identification of Ferroptosis-Related Prognostic Models and FDFT1 as a Potential Ferroptosis Driver in Colorectal Cancer.","authors":"Lili Duan, Lu Cao, Jinqiang Liu, Zixiang Wang, Jie Liang, Fan Feng, Jian Zhang, Liu Hong, Jianyong Zheng","doi":"10.2174/0109298673377428250131112647","DOIUrl":"https://doi.org/10.2174/0109298673377428250131112647","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to develop Ferroptosis-Related Gene (FRG) signatures to predict overall survival (OS) along with disease-free survival (DFS) in individuals with colorectal cancer (CRC).</p><p><strong>Background: </strong>Prediction of CRC prognosis is challenging. Ferroptosis constitutes a newly reported kind of cell death, and its association with CRC prognosis remains unexplored.</p><p><strong>Objective: </strong>This research endeavored to establish a prognostic risk signature for colorectal cancer by leveraging ferroptosis-related genes (FRGs), with the objective of refining prognostic precision in clinical settings.</p><p><strong>Methods: </strong>The clinical data and mRNA expression profiles were obtained from The Cancer Genome Atlas (TCGA) colorectal cancer cohorts. The Lasso algorithm was employed to develop the overall survival (OS) and disease-free survival (DFS) prediction models. These models were subsequently validated using independent data from GSE38832.</p><p><strong>Results: </strong>Our research unveiled a significant difference in the expression levels of 85% of ferroptosis-related genes (FRGs) between CRC tissues and paracancer tissues. Out of these, 11 prognostic genes were pinpointed through univariate Cox analysis. By employing two models, patients were stratified into low- and high-risk groups based on predicted risk scores, which were subsequently validated as independent prognostic factors via multivariate Cox analysis. The robustness of these models was further confirmed through Receiver Operating Characteristic (ROC) curve analysis. Functional enrichment analysis indicated a predominance of cancer-associated pathways in the high-risk group, including WNT signaling, along with variations in immune status between the two risk categories. Leveraging the Connectivity Map (CMap) database, a total of sixteen potential therapeutic drugs were identified. Additionally, in vitro experiments corroborated that Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1) was underexpressed in CRC and exhibited tumor suppressive properties. More specifically, FDFT1 may augment ferroptosis in CRC by modulating the expression of the Iron-Sulfur Cluster Assembly Enzyme (ISCU).</p><p><strong>Conclusion: </strong>Our study highlighted the significance of ferroptosis-related genes in the pathogenesis of CRC and underscored the potential of ferroptosis-related gene-based risk signatures as valuable tools for improving prognostic accuracy and tailoring therapeutic strategies. However, the validity of these predictive models required further validation through real- world studies to ensure their reliability and applicability.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413663","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 Pathophysiological Role of Mitochondria-associated Membranes in Coronary Artery Disease and Atherosclerosis.","authors":"Junyan Zhang, Zhongxiu Chen, Li Rao, Yong He","doi":"10.2174/0109298673343245250128093845","DOIUrl":"https://doi.org/10.2174/0109298673343245250128093845","url":null,"abstract":"<p><p>Mitochondria-associated membranes (MAMs) are pivotal in cellular homeostasis, mediating communication between the endoplasmic reticulum and mitochondria. They are increasingly recognized for their role in atherosclerosis and coronary artery disease (CAD). This review delves into the cellular perspective of MAMs' impact on atherosclerosis and CAD, highlighting their influence on disease progression and the potential for therapeutic intervention. MAMs are implicated in key pathophysiological processes such as the generation of reactive oxygen species, calcium homeostasis, myocardial ischemia-reperfusion injury, autophagy, lipid synthesis and transport, and energy metabolism-fundamental to the development and progression of atherosclerosis and CAD. The complex interplay of MAMs with these pathological processes underscores their potential as therapeutic targets. This review synthesizes current understanding and emphasizes the need for further research to elucidate the multifaceted roles of MAMs in atherosclerosis and CAD, offering avenues for developing novel strategies aimed at improving mitochondrial health and mitigating the impact of these conditions.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406226","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":"Analyzing and Validating the Role of Genes Related to Glucagon-like Peptide-1 Signaling in the Prognosis of Pancreatic Cancer.","authors":"Anbin Wang, Hong Yang, Yuming Zhu","doi":"10.2174/0109298673367232250102015441","DOIUrl":"https://doi.org/10.2174/0109298673367232250102015441","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to develop a reliable prognostic tool related to glucagon-like peptide-1 (GLP-1) for guiding treatment of pancreatic cancer (PC).</p><p><strong>Background: </strong>The treatment strategies for PC being greatly advanced the prognosis of cancer still remains unfavorable.</p><p><strong>Objective: </strong>To develop a RiskScore model for evaluating PC prognosis.</p><p><strong>Method: </strong>The bulk RNA-seq data of PC patients were obtained from the UCSCXena and GEO database, and the GSE156405 cohort was used for single-cell RNA-seq (scRNA- seq) analysis in the \"Seurat\" package. Firstly, the gene expression and mutation in the PC samples were analyzed to perform differentially expressed genes (DEGs) analysis using the \"limma\" package. The \"survival\" package was employed to conduct un/- multivariate Cox regression and Kaplan-Meier (KM) survival analysis. Secondly, a RiskScore model was developed and assessed using the \"glmnet\" and \"timeROC\" packages. Next, the CIBERSORT algorithm and the ssGSEA method were applied for immune infiltration analysis and calculation of the immune cell scores, respectively. Finally, pathway enrichment analysis was conducted using gene set enrichment analysis (GSEA).</p><p><strong>Results: </strong>Most GLP-1 signaling genes were overexpressed in the PC samples with multiple mutation types. LASSO analysis selected 3 GLP-1 genes for the development of a RiskScore model with a high classification accuracy (AUC >0.6). Notably, high-risk patients showed a significantly shorter survival time in both training and validation sets. In addition, as an independent factor, the RiskScore was further used to establish a nomogram model for the survival prediction of PC in clinical practice. The tumor microenvironment (TME) analysis revealed that low-risk patients with more abundant immune and stroma components had higher levels of anti-tumor immune cell infiltration (such as activated B and T cells), while the proliferation pathways (E2F targets, G2M checkpoint) were significantly activated in the high-risk groups. The genes in the RiskScore model may affect the survival of PC patients through modulating the activities of NK cells and macrophages.</p><p><strong>Conclusion: </strong>We demonstrated that the GLP-1 signaling affected PC development and developed a reliable RiskSocre model for the prognosis assessment in PC. Our findings are expected to improve PC diagnosis and treatment in clinical practice.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406202","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 Nutraceuticals in Chemoprevention and their Therapeutic Effects when Used in Combination with Synthetic Drugs.","authors":"Carla Di Chio, Fabiola De Luca, Josè Starvaggi, Santo Previti, Maria Zappalà, Roberta Ettari","doi":"10.2174/0109298673348105250102040623","DOIUrl":"https://doi.org/10.2174/0109298673348105250102040623","url":null,"abstract":"<p><p>Recently, increasing attention has been directed toward nutraceuticals, natural substances extracted from plants, fruits, or cereals. These compounds are well-known for their antibacterial, anti-inflammatory, antioxidant, and antitumor properties, with the latter being the primary focus of this review. The use of nutraceuticals, both as standalone treatments and in combination with standard chemotherapy, has been extensively studied through in vitro, in vivo experiments, and clinical trials for the prevention and treatment of various types of cancer, including breast, colon, pancreatic, prostate cancers, and leukemia. Findings from these studies emphasize the benefits of nutraceuticals in improving patient compliance and mitigating the adverse effects of conventional drugs. Specifically, the combination of nutraceuticals with chemotherapy allows for reduced dosages of synthetic drugs, thereby lessening their often-severe side effects. In this review, we explore the diverse mechanisms of action underlying the antitumor activity of key nutraceuticals-including curcumin, resveratrol, tocotrienols, ursolic acid, fisetin, gambogic acid, catechins, silibinin, berberine, emodin, piperine, deguelin, garcinol, plumbagin, zerumbone, and ginger. Furthermore, we summarize the most significant outcomes from clinical trials investigating these compounds. The clinical studies addressed various aspects of treatment, such as efficacy, safety, maximum tolerated doses, potential adverse effects, and patient compliance. The majority of the findings highlight the positive impact of combining nutraceuticals with chemotherapy, demonstrating enhanced therapeutic outcomes in anticancer treatments.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406292","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":"Improving Non-alcoholic Fatty Liver Disease Treatment in High-fat Diet Fed Mice with Fisetin and Hydroxychloroquine: The Cooperative Pathways for Improved Metabolic Health.","authors":"Mahboobe Sattari, Ghodratollah Panahi, Mohammad Esmaeil Shahaboddin, Mohadese Sattari, Siavash Amiri, Maryam Akhavan Taheri, Amin Karimpour, Jamal Amri","doi":"10.2174/0109298673342421241126060049","DOIUrl":"https://doi.org/10.2174/0109298673342421241126060049","url":null,"abstract":"<p><strong>Background: </strong>The high incidence of Non-Alcoholic Fatty Liver Disease (NAFLD) as a hepatic component of metabolic syndrome is attributed to the ongoing rise in obesity rates. Given the beneficial effects of hydroxychloroquine (HCQ) on metabolism, there is growing interest in combining it with fisetin (FSN), a natural product, to treat NAFLD more effectively.</p><p><strong>Objective: </strong>The efficacy and safety of the combined therapy of FSN and HCQ in animal models of NAFLD were assessed, focusing on liver function, insulin sensitivity, oxidative stress, and inflammation.</p><p><strong>Materials: </strong>and Methods: C57BL/6J mice were fed either a standard chow diet or a high- -fat diet to induce NAFLD. FSN and HCQ were administered to the mice, and biochemical parameters related to glucose and lipid metabolism, as well as oxidative stress markers, were measured in serum and liver tissue. Analyses included Oil Red O staining, mRNA levels of key lipid metabolism molecules, and immunohistochemical assessments of macrophage infiltration. Statistical analyses were performed using GraphPad Prism 9.</p><p><strong>Results: </strong>While the HCQ group exhibited some improvements in certain markers, it also displayed adverse effects. The FSN group, particularly the FSN + HCQ group, effectively reversed insulin sensitivity, glucose homeostasis, and NAFLD markers by modulating lipid metabolism and inflammation pathways. HCQ exacerbated oxidative stress, which was mitigated by the effects of FSN.</p><p><strong>Conclusion: </strong>Despite concerns regarding the long-term side effects of HCQ, its combination with FSN presents a promising approach for improving the management of NAFLD by reducing risks and enhancing outcomes.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390456","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}