Journal of pharmaceutical analysis最新文献

{"title":"Intelligence on the graph: Graph neural networks for mechanistic drug target discovery.","authors":"Jing Chen, Nini Fan, Yuqing Lu, Jianhua Yang, Wenchao Song, Haiyang Sheng, Yinfeng Yang, Shengxi Chen, Jinghui Wang","doi":"10.1016/j.jpha.2025.101508","DOIUrl":"10.1016/j.jpha.2025.101508","url":null,"abstract":"<p><p>Drug discovery is increasingly challenged by rising costs, long development cycles and high attrition rates, with accurate target identification remaining a critical bottleneck. Although artificial intelligence (AI) has demonstrated transformative potential, the systematic application of graph neural networks (GNNs) to drug target discovery remains underexplored. To address this gap, this paper provides a comprehensive and structured analysis of recent advances in GNN-based methods for drug-target interaction (DTI) and drug-target affinity (DTA) prediction. We dissect the methodological foundations of representative architectures including graph convolutional networks (GCNs), graph attention networks (GATs) and graph autoencoders (GAEs), and compare their mechanisms, advantages and applicable scenarios in modeling complex molecular and biological systems. Also, we synthesize frontier paradigms such as multimodal data fusion, high-order graph reasoning and dynamic GNNs, which enable the capture of atom-residue interactions, multi-target coordination mechanisms and cross-scale biological features. By systematically mapping methodological innovations to biological applications, this paper offers both theoretical guidance and translational insights. The key contributions of this paper include: (1) establishing a comparative framework that clarifies when and how different GNNs architectures can be applied in drug target discovery; (2) integrating cutting-edge paradigms rarely addressed in prior reviews, such as multimodal fusion and high-order graph modeling; and (3) highlighting representative case studies that bridge algorithmic innovation with practical drug discovery outcomes. Collectively, this work provides an authoritative and forward-looking reference, promoting the development of AI-driven, efficient and interpretable drug discovery pipelines.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 7","pages":"101508"},"PeriodicalIF":8.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581909","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}

{"title":"Multiple gastric cancer tissue proteomic identification predicts CLU as a biomarker for anti-PD-1 immunotherapy.","authors":"Yu Zhang, Hao-Yi Zhu, Cong-Cong Ma, Ning Wang, Yan Li, Guo-Liang Lu, Xing-Jie Dai, Bo Wang, Maa Mamun, Ying Li, Xiao-Ying Zhao, Jing-Ru Pang, Ning-Jie Guo, Feng-Yu Qi, Jian-Gang Sun, Hong-Min Liu, Feng-Wu Liu, Piet Herdewijn, Long-Fei Zhao, Yi-Chao Zheng","doi":"10.1016/j.jpha.2026.101615","DOIUrl":"10.1016/j.jpha.2026.101615","url":null,"abstract":"<p><p>Image 1.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 7","pages":"101615"},"PeriodicalIF":8.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498659","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}

{"title":"Self-assembled multifunctional hairpin probe for ultrasensitive and mismatch-selective miRNA detection.","authors":"Baoqiang Chen, Yiping Fan, Qi Wang, Jianguo Xu, Yi Wang, Bingyong Lin, Lee Jia, Longhua Guo","doi":"10.1016/j.jpha.2026.101561","DOIUrl":"10.1016/j.jpha.2026.101561","url":null,"abstract":"<p><p>Sensitive, specific, and stable detection of microRNAs (miRNAs) in complex biological environments remains a formidable challenge in molecular diagnostics. We introduce a novel bidirectional palindromic assembled multifunctional hairpin probe (A-MF-HP)-a molecular tool that integrates target recognition, cascade signal amplification, and fluorescence reporting into a single, compact system. Two palindromic arms drive autonomous, bidirectional self-assembly into a nuclease-resistant architecture, enabling robust operation in serum-rich environments. Upon recognition of miRNA-21, a structural switch in one hairpin triggers polymerase extension, nicking, and strand displacement all without auxiliary probes. This initiates a self-propagating disassembly cascade, unfolding additional hairpins and exponentially amplifying the signal. Under the optimized conditions, the platform demonstrates femtomolar-level sensitivity (about 1× 10^-15 M) across a six-order dynamic range, with single-nucleotide mismatch discrimination and negligible cross-reactivity to unrelated miRNAs. Notably, A-MF-HP retains full functionality after 12 h in 10% human serum, and clinical application to blood samples from lung cancer patients revealed marked fluorescence elevation compared to healthy controls. By uniting biostability, multifunctionality, and autonomous amplification in a single programmable probe, this novel strategy addresses limitations commonly observed in multi-component isothermal amplification assays, such as poor nuclease tolerance and dependence on multiple separate probes, offering a powerful diagnostic tool for miRNA profiling in biomedical and clinical settings.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 7","pages":"101561"},"PeriodicalIF":8.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498652","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}

{"title":"Sweat as a diagnostic biofluid: analytical advances and future directions.","authors":"Dayanne Mozaner Bordin, Janice Irene McCauley, Eduardo Geraldo de Campos, David Bishop, Bruno Spinosa De Martinis","doi":"10.1016/j.jpha.2025.101473","DOIUrl":"10.1016/j.jpha.2025.101473","url":null,"abstract":"<p><p>The use of sweat as an alternative specimen for biological analyses is well recognised and has been successfully applied in forensic toxicology and clinical health assessments. Compared to conventional matrices such as urine and blood, sweat samples are easy to obtain, are less invasive and present a reduced number of endogenous interferents. Advanced analytical techniques in sweat analysis have considerably expanded capabilities in the isolation of drugs, detection of complex metabolites and identification of biomarkers. The ability to detect a broader range of substances with greater sensitivity and accuracy, improved speed and efficiency and enhanced reliability present opportunities for non-invasive chemical sensing in sweat for a much broader scope of metabolites than traditionally recognised. The year 2023 was marked by an evolutionary step in artificial intelligence (AI), opening the door for improved pattern analysis and classification algorithms to improve diagnostic precision and therapeutic accuracy. It is anticipated that when combined with advances in the performance and miniaturization of integrated circuits, stretchable electronics, wireless connectivity and longer battery life, a substantial impact is expected on the development of wearable biosensor devices to provide meaningful information to the physiology of end-users, expanding its role in personalized medicine and health monitoring. Therefore, the aim of this review is to provide an integrative overview of sweat as a diagnostic and monitoring biofluid by first discussing traditional methods in clinical and forensic applications. Recent advancements in sweat biomarker detection are then highlighted, followed by an evaluation of sweat's potential for real-time physiological monitoring.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 7","pages":"101473"},"PeriodicalIF":8.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148595450","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}

{"title":"Lappaconitine hydrobromide prevents NLRP3-GSDMD-mediated pyroptosis to alleviate sepsis-induced acute lung injury by enhancing NR1H3.","authors":"Yuejia Lan, Qingrui Zhong, Hongkai Huang, Xiao Deng, Lu Yang, Jiayi Sun, Mingyang Liu, Xianli Meng, Jiasi Wu","doi":"10.1016/j.jpha.2026.101631","DOIUrl":"10.1016/j.jpha.2026.101631","url":null,"abstract":"<p><p>Evidence indicates that nuclear receptor subfamily 1 group H member 3 (NR1H3) activation mitigates sepsis-induced acute lung injury (SALI) by reducing inflammatory response. Nevertheless, the mechanisms underlying NR1H3-inflammation interactions in addressing SALI remain unclear. Moreover, limited phytochemicals have been documented to ameliorate SALI via this pathway. Here, we discovered that NR1H3 activation directly suppresses the clustering of toll-like receptor 4 (TLR4) to lipid rafts, which acts as a part of the priming of NLR family pyrin domain containing 3 (NLRP3) inflammasome. This process results in the suppression of NLRP3 inflammasome assembly and activation, consequently alleviating gasdermin-D (GSDMD)-mediated pyroptosis. Furthermore, through dual-luciferase reporter gene testing, drug binding assays, gene expression analysis, and biochemical evaluation, we determined lappaconitine hydrobromide (LAH) as a novel NR1H3 agonist that effectively suppresses TLR4-NLRP3 signaling pathway. Our results showed LAH attenuates inflammatory lung injury in both lipopolysaccharide (LPS) and cecal slurry (CS)-induced SALI mouse models. <i>In vivo</i> and <i>in vitro</i> experiments revealed that LAH suppresses NLRP3 signaling activation and pyroptosis. Additionally, RNA sequencing (RNA-seq) and bioinformatics analysis demonstrated that the differentially expressed genes (DEGs) linked to interleukin-1 beta (IL-1β) production, modulation of inflammatory response, and control of innate immune response were markedly enriched in LAH, and core genes amongst the DEGs included NR1H3. Mechanistically, LAH reduces inflammation and pyroptosis through modulation of NR1H3-NLRP3-GSDMD axis in mice. This finding was further substantiated by the suppression of NR1H3 <i>in vitro</i>. Our findings offer novel perspectives on the NR1H3-inflammation interaction in SALI regulation and indicate the therapeutic promise of LAH as an NR1H3 agonist for SALI management via NLRP3 suppression.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 7","pages":"101631"},"PeriodicalIF":8.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148595427","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}

{"title":"Classification of pulmonary inflammation stages and assessment of multicomponent drug intervention based on spatiotemporal imaging variations utilizing RhB-conjugated poly-L-lysine nanoparticles.","authors":"Man Zhang, Shanshan Zhai, He Gao, Tong Sun, Kaixin Liu, Wenshuang Wang, Yuanyuan Hou, Gang Bai","doi":"10.1016/j.jpha.2026.101582","DOIUrl":"10.1016/j.jpha.2026.101582","url":null,"abstract":"<p><p>Acute pulmonary inflammation, a major cause of morbidity and mortality, involves complex immune responses and increased vascular permeability. Conventional imaging techniques for assessing pneumonia and monitoring vascular leakage have limitations in spatial resolution and practicality. Rhodamine B-conjugated poly-L-lysine (RhB-PLL) self-assembled nanoparticles (NPs) were synthesized for targeting mitochondria and sensing vascular permeability. Dynamic spatiotemporal imaging analysis stratifies the progression of acute pneumonia into four distinct stages. Six phosphatidylcholine (PC) metabolites, exhibiting stage-dependent variations, were proposed as potential biomarkers to support RhB-PLL detection. Subsequently, Fuzheng Jiedu decoction (FZJD) was used as a model to validate the rationale of syndrome-specific treatment for pneumonia. Three simplified prescriptions derived from FZJD showed unique advantages at different stages. Xiaochaihu decoction (XCH) relieved inflammation and oxidative stress in mild to moderate cases; Sanren decoction (SR) reduced vascular leakage and prevented pulmonary edema in moderate to severe cases; Maxingshigan decoction (MXSG) improved mitochondrial function and prevented microcirculatory disorders in severe to critical cases. The combined prescription, FZJD, mitigated disease progression in mild to moderate cases and demonstrated the benefits of overall intervention. This conclusion was further substantiated by metabolomics cluster analysis. Real-time RhB-PLL multimodal imaging enables precise visualization and detection of inflammation progress, facilitates therapy assessment, and enhances the understanding of multicomponent drug combinations.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 7","pages":"101582"},"PeriodicalIF":8.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611709","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}

{"title":"Discovery of mitochondrial modulators using target-aggregated machine learning.","authors":"Lizhuo Wang, Peng Yang, Sirui Wu, Fanding Xu, Wu Su, Le Shi, Hui Guo, Li Cui, Jiankang Liu, Zhiwei Yang, Jiangang Long","doi":"10.1016/j.jpha.2026.101579","DOIUrl":"10.1016/j.jpha.2026.101579","url":null,"abstract":"<p><p>Image 1.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 7","pages":"101579"},"PeriodicalIF":8.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611647","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}

{"title":"GSH-triggered release of anabasine in mitochondria for synergistic chemotherapy assisted by OATP transportation.","authors":"Miao Zhang, Ling-Li Wang, Si-Ling Chen, Yan-Ping Liu, Ming-Hua Zheng, Jing-Yi Jin","doi":"10.1016/j.jpha.2026.101565","DOIUrl":"10.1016/j.jpha.2026.101565","url":null,"abstract":"<p><p>Image 1.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 6","pages":"101565"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13311262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355330","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}

{"title":"Targeting posttranslational modifications of oxidative stress pathways for the treatment of diabetic nephropathy.","authors":"Li Zhou, Xin-Lei Shen, Qing-Ru Zhu, Wen-Kai Yu, Hang-Chao Li, Gang Cao, Yi-Ni Bao","doi":"10.1016/j.jpha.2026.101558","DOIUrl":"10.1016/j.jpha.2026.101558","url":null,"abstract":"<p><p>Diabetic nephropathy (DN), a major microvascular complication of diabetes, is the leading cause of chronic kidney disease (CKD). Oxidative stress has emerged as a central driver of DN, making its associated signaling pathways promising therapeutic targets. When reactive oxygen species (ROS) exceed the cell's antioxidant capacity, they disrupt homeostasis and trigger inflammation, apoptosis, necrosis, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. In the kidneys, these events accelerate fibroblast activation and collagen deposition, leading to fibrosis, glomerulosclerosis, and progressive loss of function. Recent studies identify post-translational modifications (PTMs) as key regulators in this process. By altering protein structure, function, and interactions, PTMs modulate many of the pathological mechanisms underlying DN. Targeting oxidative stress pathways regulated by PTMs therefore offers a promising therapeutic approach. In this review, we first introduce the role of PTMs in DN and outline the contribution of oxidative stress to disease progression. We then examine how PTMs regulate oxidative stress pathways, highlight novel modifications with potential relevance to DN, and discuss emerging therapeutic strategies targeting these pathways.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 6","pages":"101558"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393207","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}

{"title":"Targeting angiogenesis in diabetic wound healing: New insight from chemical architecture to functional outcomes.","authors":"Junren Chen, Siqi Qin, Ziwei Xing, Cheng Peng, Dan Li","doi":"10.1016/j.jpha.2025.101475","DOIUrl":"10.1016/j.jpha.2025.101475","url":null,"abstract":"<p><p>Diabetic wound healing (DWH) is a multifaceted process hindered by impaired angiogenesis that usually leads to increased risks of infection and amputation. Targeting impeded angiogenic signals to restore the microenvironment favoring vascular network re-establishment is a promising therapeutic strategy for diabetic wound. Natural products have emerged as potential therapeutic agents for diabetic wounds by regulating endotheliocytes functions and their cross-talks with immune cells and fibroblasts, while the similarities and differences of the chemical structures greatly determine their distinct efficient and underlying mechanisms in diabetic wound angiogenesis. In this review, relevant literature was retrieved from PubMed, Google Scholar, and Web of Science databases, covering publications from 2020 to 2025. This paper reviews the role of angiogenesis in DWH and the action of natural products in DWH by targeting angiogenesis, particularly highlighting their chemical architecture driven specific biological activity on angiogenesis, with the aim of providing references for angiogenesis-based therapeutic strategies for diabetic ulcers and promoting the development of angiogenesis-targeting agents.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 6","pages":"101475"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148427349","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}