Journal of pharmaceutical analysis最新文献_第4页

Inhibiting neddylation: A new strategy for tumor therapy. 抑制类化修饰：肿瘤治疗的新策略。

Journal of pharmaceutical analysis Pub Date : 2025-05-01 Epub Date: 2024-11-08 DOI: 10.1016/j.jpha.2024.101140

Jian Sun, Cui Liu, Changhui Lang, Jing Wang, Qingxiang Li, Chang Peng, Zuochen Du, Yan Chen, Pei Huang

引用次数: 0

The final stretch of the animal-free approach in new drug research. 新药研究中无动物实验的最后一步。

Journal of pharmaceutical analysis Pub Date : 2025-05-01 Epub Date: 2025-05-15 DOI: 10.1016/j.jpha.2025.101344

Li Liu

引用次数: 0

Impact of FASN-enriched EVs on endothelial cell function in obstructive sleep apnea hypopnea syndrome. fasn富集的ev对阻塞性睡眠呼吸暂停低通气综合征内皮细胞功能的影响。

Journal of pharmaceutical analysis Pub Date : 2025-05-01 Epub Date: 2025-03-01 DOI: 10.1016/j.jpha.2025.101251

Yuan Tian, Dan Zhang, Huaian Yang, Xiaoli Zhang, Shengqun Xu

引用次数: 0

Screen of FDA-approved drug library identifies vitamin K as anti-ferroptotic drug for osteoarthritis therapy through Gas6. fda批准的药物文库筛选发现维生素K是通过Gas6治疗骨关节炎的抗铁张力药物。

Journal of pharmaceutical analysis Pub Date : 2025-05-01 Epub Date: 2024-08-29 DOI: 10.1016/j.jpha.2024.101092

Yifeng Shi, Sunlong Li, Shuhao Zhang, Caiyu Yu, Jiansen Miao, Shu Yang, Yan Chen, Yuxuan Zhu, Xiaoxiao Huang, Chencheng Zhou, Hongwei Ouyang, Xiaolei Zhang, Xiangyang Wang

{"title":"Screen of FDA-approved drug library identifies vitamin K as anti-ferroptotic drug for osteoarthritis therapy through Gas6.","authors":"Yifeng Shi, Sunlong Li, Shuhao Zhang, Caiyu Yu, Jiansen Miao, Shu Yang, Yan Chen, Yuxuan Zhu, Xiaoxiao Huang, Chencheng Zhou, Hongwei Ouyang, Xiaolei Zhang, Xiangyang Wang","doi":"10.1016/j.jpha.2024.101092","DOIUrl":"10.1016/j.jpha.2024.101092","url":null,"abstract":"Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 5","pages":"101092"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the impact of the liver-intestine-brain axis on brain function in non-alcoholic fatty liver disease. 探讨肝-肠-脑轴对非酒精性脂肪性肝病脑功能的影响。

Journal of pharmaceutical analysis Pub Date : 2025-05-01 Epub Date: 2024-08-19 DOI: 10.1016/j.jpha.2024.101077

Jingting Zhang, Keyan Chen, Fu Chen

{"title":"Exploring the impact of the liver-intestine-brain axis on brain function in non-alcoholic fatty liver disease.","authors":"Jingting Zhang, Keyan Chen, Fu Chen","doi":"10.1016/j.jpha.2024.101077","DOIUrl":"10.1016/j.jpha.2024.101077","url":null,"abstract":"This study investigates the molecular complexities of non-alcoholic fatty liver disease (NAFLD)-induced brain dysfunction, with a focus on the liver-intestine-brain axis and potential therapeutic interventions. The main objectives include understanding critical microbiota shifts in NAFLD, exploring altered metabolites, and identifying key regulatory molecules influencing brain function. The methods employed encompassed 16S ribosomal RNA (rRNA) sequencing to scrutinize stool microbiota in NAFLD patients and healthy individuals, non-targeted metabolomics using LC-MS to uncover elevated levels of deoxycholic acid (DCA) in NAFLD mice, and single-cell RNA sequencing (scRNA-seq) to pinpoint the pivotal gene Hpgd in microglial cells and its downstream Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Behavioral changes and brain function were assessed in NAFLD mice with and without Fecal microbiota transplantation (FMT) treatment, utilizing various assays and analyses. The results revealed significant differences in microbiota composition, with increased levels of Bacteroides in NAFLD patients. Additionally, elevated DCA levels were observed in NAFLD mice, and FMT treatment demonstrated efficacy in ameliorating liver function and brain dysfunction. Hpgd inhibition by DCA activated the JAK2/STAT3 pathway in microglial cells, leading to inflammatory activation, inhibition of mitochondrial autophagy, induction of neuronal apoptosis, and reduction in neuronal action potentials. This study elucidates the intricate molecular mechanisms underlying the liver-gut-brain axis in NAFLD, and the identification of increased DCA and the impact of JAK2/STAT3 signaling on microglial cells highlight potential therapeutic targets for addressing NAFLD-induced brain dysfunction.","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 5","pages":"101077"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Natural products for the treatment of age-related macular degeneration: New insights focusing on mitochondrial quality control and cGAS/STING pathway. 治疗老年性黄斑变性的天然产物：线粒体质量控制和cGAS/STING通路的新见解

Journal of pharmaceutical analysis Pub Date : 2025-05-01 Epub Date: 2024-11-16 DOI: 10.1016/j.jpha.2024.101145

Xuelu Xie, Shan Lian, Wenyong Yang, Sheng He, Jingqiu He, Yuke Wang, Yan Zeng, Fang Lu, Jingwen Jiang

{"title":"Natural products for the treatment of age-related macular degeneration: New insights focusing on mitochondrial quality control and cGAS/STING pathway.","authors":"Xuelu Xie, Shan Lian, Wenyong Yang, Sheng He, Jingqiu He, Yuke Wang, Yan Zeng, Fang Lu, Jingwen Jiang","doi":"10.1016/j.jpha.2024.101145","DOIUrl":"10.1016/j.jpha.2024.101145","url":null,"abstract":"Age-related macular degeneration (AMD) is a disease that affects the vision of elderly individuals worldwide. Although current therapeutics have shown effectiveness against AMD, some patients may remain unresponsive and continue to experience disease progression. Therefore, in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment. Recently, studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species (ROS) and activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathways, ultimately resulting in sterile inflammation and cell death in various cells, such as cardiomyocytes and macrophages. Therefore, combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management. Notably, emerging evidence indicates that natural products targeting mitochondrial quality control (MQC) and the cGAS/STING innate immunity pathways exhibit promise in treating AMD. Here, we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways, as well as their interconnected mediators, which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses, thereby hoping to offer new insights into therapeutic interventions for AMD treatment.","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 5","pages":"101145"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting tumor metabolism to augment CD8⁺ T cell anti-tumor immunity. 靶向肿瘤代谢增强CD8+ T细胞抗肿瘤免疫。

Journal of pharmaceutical analysis Pub Date : 2025-05-01 Epub Date: 2024-11-20 DOI: 10.1016/j.jpha.2024.101150

Huan Liu, Wenyong Yang, Jingwen Jiang

{"title":"Targeting tumor metabolism to augment CD8+ T cell anti-tumor immunity.","authors":"Huan Liu, Wenyong Yang, Jingwen Jiang","doi":"10.1016/j.jpha.2024.101150","DOIUrl":"10.1016/j.jpha.2024.101150","url":null,"abstract":"CD8+ T cell-based immune-therapeutics, including immune checkpoint inhibitors and adoptive cell therapies (tumor-infiltrating lymphocytes (TILs), T cell receptor-engineered T cells (TCR-T), chimeric antigen receptor T cells (CAR-T)), have achieved significant successes and prolonged patient survival to varying extents and even achieved cure in some cases. However, immunotherapy resistance and tumor insusceptibility frequently occur, leading to treatment failure. Recent evidences have highlighted the ponderance of tumor cells metabolic reprogramming in establishing an immunosuppressive milieu through the secretion of harmful metabolites, immune-inhibitory cytokines, and alteration of gene expression, which suppress the activity of immune cells, particularly CD8+ T cells to evade immune surveillance. Therefore, targeting tumor cell metabolic adaptations to reshape the immune microenvironment holds promise as an immunomodulatory strategy to facilitate immunotherapy. Here, we summarize recent advances in the crosstalk between immunotherapy and tumor reprogramming, focusing on the regulatory mechanisms underlying tumor cell glucose metabolism, amino acid metabolism, and lipid metabolism in influencing CD8+ T cells to provide promising metabolic targets or combinational strategies for immunotherapy.","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 5","pages":"101150"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergistic approach to combating triple-negative breast cancer: DDR1-targeted antibody-drug conjugate combined with pembrolizumab. 对抗三阴性乳腺癌的协同方法：ddr1靶向抗体-药物偶联药物联合派姆单抗

Journal of pharmaceutical analysis Pub Date : 2025-05-01 Epub Date: 2024-09-13 DOI: 10.1016/j.jpha.2024.101100

Shoubing Zhou, Wenyu Li, Dan Zhao, Qiujun Zhang, Hu Liu, Tengchuan Jin, Yueyin Pan

{"title":"Synergistic approach to combating triple-negative breast cancer: DDR1-targeted antibody-drug conjugate combined with pembrolizumab.","authors":"Shoubing Zhou, Wenyu Li, Dan Zhao, Qiujun Zhang, Hu Liu, Tengchuan Jin, Yueyin Pan","doi":"10.1016/j.jpha.2024.101100","DOIUrl":"10.1016/j.jpha.2024.101100","url":null,"abstract":"Discoidin domain receptor 1 (DDR1) is overexpressed in various tumors, such as triple-negative breast cancer (TNBC), and is rarely expressed in normal tissues. These characteristics make DDR1 a preferable target candidate for the construction of an antibody-drug conjugate (ADC) for targeted therapy. Here, we investigated the preparation and preclinical efficacy of DDR1-DX8951, an ADC that includes an anti-DDR1 monoclonal antibody conjugated to DX8951 by a cleavable Gly-Gly-Phe-Gly (GGFG) linker. The anti-DDR1 monoclonal antibody was coupled to DX8951 (i.e., DDR1-DX8951), producing the targeted therapy ADC. The antitumor activities of DDR1-DX8951 monotherapy or DDR1-DX8951 plus pembrolizumab were assessed in TNBC mouse models. DDR1-DX8951 can specifically target DDR1, be quickly internalized by TNBC cells, and reduce the viability of TNBC cells in vitro. The potent antitumor activity of DDR1-DX8951 was revealed in TNBC xenograft models. Importantly, our investigation demonstrated that DDR1-DX8951 plus pembrolizumab not only revealed the inhibitory efficacy on tumor growth and metastasis but also played an important role in improving the immunosuppressive tumor microenvironment (TME) of TNBC. Taken together, this investigation provides justification for large-sample studies to further assess the safety and efficacy of DDR1-DX8951 plus pembrolizumab for TNBC clinical trials.","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 5","pages":"101100"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The biological roles of exosome-encapsulated traditional Chinese medicine monomers in neuronal disorders. 外泌体包封中药单体在神经疾病中的生物学作用。

Journal of pharmaceutical analysis Pub Date : 2025-05-01 Epub Date: 2024-10-28 DOI: 10.1016/j.jpha.2024.101131

Chen Pang, Jie Zhang, Yujin Gu, Qili Zhang, Yanfang Zhao

{"title":"The biological roles of exosome-encapsulated traditional Chinese medicine monomers in neuronal disorders.","authors":"Chen Pang, Jie Zhang, Yujin Gu, Qili Zhang, Yanfang Zhao","doi":"10.1016/j.jpha.2024.101131","DOIUrl":"10.1016/j.jpha.2024.101131","url":null,"abstract":"A traditional Chinese medicine (TCM) monomer is a bioactive compound extracted from Chinese herbal medicines possessing determined biological activity and pharmacological effects, and has gained much attention for treating neuronal diseases. However, the application of TCM monomers is limited by their low solubility and poor ability to cross the blood-brain barrier (BBB). Exosomes are small extracellular vesicles (EVs) ranging in size from 30 to 150 nm in diameter and can be used as drug delivery carriers that directly target cells or tissues with unique advantages, including low toxicity, low immunogenicity, high stability in blood, and the ability to cross the BBB. This review discusses the biogenesis, components, stability, surface modification, isolation technology, advantages, and disadvantages of exosomes as drug carriers and compares exosomes and other similar drug delivery systems. Furthermore, exosome-encapsulated TCM monomers exert neuroprotective roles, such as anti-inflammation, anti-apoptosis, anti-mitophagy, and anti-oxidation, in various neuronal diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and cerebral ischemia and reperfusion (CI/R) injury, as well as anti-drug resistance, anti-tumorigenesis, anti-angiogenesis, and promotion of apoptosis in brain tumors, providing more inspiration to promote the development of an exosome-based delivery tool in targeted therapy for neuronal diseases.","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 5","pages":"101131"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liquiritin improves macrophage degradation of engulfed tumour cells by promoting the formation of phagolysosomes via NOX2/gp91phox. Liquiritin通过NOX2/gp91phox促进吞噬溶酶体的形成，从而改善吞噬肿瘤细胞的巨噬细胞降解。

Journal of pharmaceutical analysis Pub Date : 2025-05-01 Epub Date: 2024-08-28 DOI: 10.1016/j.jpha.2024.101093

Caiyi Yang, Kehan Chen, Yunliang Chen, Xuting Xie, Pengcheng Li, Meng Zhao, Junjie Liang, Xueqian Xie, Xiaoyun Chen, Yanping Cai, Bo Xu, Qing Wang, Lian Zhou, Xia Luo

{"title":"Liquiritin improves macrophage degradation of engulfed tumour cells by promoting the formation of phagolysosomes via NOX2/gp91phox.","authors":"Caiyi Yang, Kehan Chen, Yunliang Chen, Xuting Xie, Pengcheng Li, Meng Zhao, Junjie Liang, Xueqian Xie, Xiaoyun Chen, Yanping Cai, Bo Xu, Qing Wang, Lian Zhou, Xia Luo","doi":"10.1016/j.jpha.2024.101093","DOIUrl":"10.1016/j.jpha.2024.101093","url":null,"abstract":"The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 5","pages":"101093"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0