Wei Niu, Xiaxia Du, Yang Song, Lianyi Guo, Baohai Liu, Xin Tong
{"title":"A novel exploration of <i>COL11A1</i>'s role in regulating myeloid-derived suppressor cell activation within the colon cancer microenvironment.","authors":"Wei Niu, Xiaxia Du, Yang Song, Lianyi Guo, Baohai Liu, Xin Tong","doi":"10.1016/j.jpha.2024.101181","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101181","url":null,"abstract":"<p><p>This study aimed to elucidate the role of collagen type XI alpha 1 (<i>COL11A1</i>)-positive cancer-associated fibroblasts (CAFs) in modifying the tumor microenvironment of colon cancer (CC) and facilitating immune evasion through interactions with myeloid-derived suppressor cells (MDSCs). Using single-cell transcriptomic sequencing, we analyzed the interplay between <i>COL11A</i> <i>1</i>-positive CAFs and MDSCs in the CC microenvironment, focusing on how <i>COL11A1</i> impacts MDSC differentiation and activation. The results demonstrate that <i>COL11A1</i> expression in fibroblasts significantly enhances matrix metalloproteinase (<i>MMP</i>)3 and <i>MMP13</i> expression, leading to paracrine induction of MDSC differentiation and activation, which promotes immune evasion and tumor growth. Additionally, we observed that <i>COL11A1</i> knockout (COL11A1<sup>KO</sup>) suppresses tumor growth and hinders immune evasion. These findings underscore the essential role of <i>COL11A</i> <i>1</i>-positive CAFs in establishing an immunosuppressive tumor microenvironment conducive to CC progression. By elucidating the molecular pathway through which <i>COL11A1</i> influences MDSC activity, this research suggests new therapeutic avenues for targeting the tumor microenvironment in CC, particularly through modulating <i>COL11A1</i> expression in CAFs.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101181"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056377","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}
Laura Wiltschko, Paula Fischer, Simon Schwingenschuh, Reingard Raml, Georg Raber, Thomas Birngruber, Eva Roblegg
{"title":"Open flow microperfusion to assess local drug concentrations in the buccal mucosa.","authors":"Laura Wiltschko, Paula Fischer, Simon Schwingenschuh, Reingard Raml, Georg Raber, Thomas Birngruber, Eva Roblegg","doi":"10.1016/j.jpha.2024.101135","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101135","url":null,"abstract":"<p><p>Image 1.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101135"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12002812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996719","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}
Ying Zhao, Hui Ji, Feng Han, Qing-Feng Xu, Hui Zhang, Di Liu, Juan Wei, Dan-Hong Xu, Lai Jiang, Jian-Kui Du, Ping-Bo Xu, Yu-Jian Liu, Xiao-Yan Zhu
{"title":"Inhibition of KLK8 promotes pulmonary endothelial repair by restoring the VE-cadherin/Akt/FOXM1 pathway.","authors":"Ying Zhao, Hui Ji, Feng Han, Qing-Feng Xu, Hui Zhang, Di Liu, Juan Wei, Dan-Hong Xu, Lai Jiang, Jian-Kui Du, Ping-Bo Xu, Yu-Jian Liu, Xiao-Yan Zhu","doi":"10.1016/j.jpha.2024.101153","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101153","url":null,"abstract":"<p><p>Image 1.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101153"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061628","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}
Zhenzhen Xue, Yudong Shang, Lan Yang, Tao Li, Bin Yang
{"title":"A tailored database combining reference compound-derived metabolite, metabolism platform and chemical characteristic of Chinese herb followed by activity screening: Application to Magnoliae Officinalis Cortex.","authors":"Zhenzhen Xue, Yudong Shang, Lan Yang, Tao Li, Bin Yang","doi":"10.1016/j.jpha.2024.101066","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101066","url":null,"abstract":"<p><p>A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex (MOC) was developed and implemented to rapidly profile and discover bioactive metabolites <i>in vivo</i> derived from traditional Chinese medicine (TCM). The strategy possessed four characteristics: 1) The tailored database consisted of metabolites derived from big data-originated reference compound, metabolites predicted <i>in silico</i>, and MOC chemical profile-based pseudomolecular ions. 2) When profiling MOC-derived metabolites <i>in vivo</i>, attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds, as reported by most papers, but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites. 3) Metabolite traceability was performed, especially to distinguish isomeric prototypes-derived metabolites, prototypes of MOC compounds as well as phase I metabolites derived from other MOC compounds. 4) Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification. Using this strategy, 134 metabolites were swiftly characterized after the oral administration of MOC to rats, and several metabolites were reported for the first time. Furthermore, 17 potential active metabolites were discovered by targeting the motilin, dopamine D2, and the serotonin type 4 (5-HT<sub>4</sub>) receptors, and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model. This study extends the application of mass spectrometry (MS) to rapidly profile TCM-derived metabolites <i>in vivo</i>, which will help pharmacologists rapidly discover potent metabolites from a complex matrix.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101066"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059411","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 ceramide-induced microglial pyroptosis: Icariin is a promising therapy for Alzheimer's disease.","authors":"Hongli Li, Qiao Xiao, Lemei Zhu, Jin Kang, Qiong Zhan, Weijun Peng","doi":"10.1016/j.jpha.2024.101106","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101106","url":null,"abstract":"<p><p>Alzheimer's disease (AD), a progressive dementia, is one of the most common neurodegenerative diseases. Clinical trial results of amyloid-β (Aβ) and tau regulators based on the pretext of straightforward amyloid and tau immunotherapy were disappointing. There are currently no effective strategies for slowing the progression of AD. Herein, we spotlight the dysregulation of lipid metabolism, particularly the elevation of ceramides (Cers), as a critical yet underexplored facet of AD pathogenesis. Our study delineates the role of Cers in promoting microglial pyroptosis, a form of programmed cell death distinct from apoptosis and necroptosis, characterized by cellular swelling, and membrane rupture mediated by the NLRP3 inflammasome pathway. Utilizing both <i>in vivo</i> experiments with amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and <i>in vitro</i> assays with BV-2 microglial cells, we investigate the activation of microglial pyroptosis by Cers and its inhibition by icariin (ICA), a flavonoid with known antioxidant and anti-inflammatory properties. Our findings reveal a significant increase in Cers levels and pyroptosis markers (NOD-like receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, gasdermin D (gasdermin D (GSDMD)), and interleukin-18 (IL-18)) in the brains of AD model mice, indicating a direct involvement of Cers in AD pathology through the induction of microglial pyroptosis. Conversely, ICA treatment effectively reduces these pyroptotic markers and Cer levels, thereby attenuating microglial pyroptosis and suggesting a novel therapeutic mechanism of action against AD. This study not only advances our understanding of the pathogenic role of Cers in AD but also introduces ICA as a promising candidate for AD therapy, capable of mitigating neuroinflammation and pyroptosis through the cyclooxygenase-2 (COX-2)-NLRP3 inflammasome-gasdermin D (GSDMD) axis. Our results pave the way for further exploration of Cer metabolism disorders in neurodegenerative diseases and highlight the therapeutic potential of targeting microglial pyroptosis in AD.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101106"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047593","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":"Identifying purgative targets of sennoside A via <i>in situ</i> biotransformation of prodrug-based probes.","authors":"Zhen Liu, Xinyue Geng, Xinyue Liu, Mengru Li, Xiang Li, Zhixin Zhang, Gan Luo, Ying Wang, Xiaoyan Gao","doi":"10.1016/j.jpha.2024.101078","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101078","url":null,"abstract":"<p><p>•A strategy for <i>in situ</i> metabolically synthesized active drug-based probes was proposed.•The potential purgative targets of SA were successfully hooked and identified.•The work provided a new insight for studying the direct targets of unstable active drugs.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101078"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12019458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036697","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}
Lei Xu, Tao Zhang, Baojie Zhu, Honglin Tao, Yue Liu, Xianfeng Liu, Yi Zhang, Xianli Meng
{"title":"Mitochondrial quality control disorder in neurodegenerative disorders: Potential and advantages of traditional Chinese medicines.","authors":"Lei Xu, Tao Zhang, Baojie Zhu, Honglin Tao, Yue Liu, Xianfeng Liu, Yi Zhang, Xianli Meng","doi":"10.1016/j.jpha.2024.101146","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101146","url":null,"abstract":"<p><p>Neurodegenerative disorders (NDDs) are prevalent chronic conditions characterized by progressive synaptic loss and pathological protein alterations. Increasing evidence suggested that mitochondrial quality control (MQC) serves as the key cellular process responsible for clearing misfolded proteins and impaired mitochondria. Herein, we provided a comprehensive analysis of the mechanisms through which MQC mediates the onset and progression of NDDs, emphasizing mitochondrial dynamic stability, the clearance of damaged mitochondria, and the generation of new mitochondria. In addition, traditional Chinese medicines (TCMs) and their active monomers targeting MQC in NDD treatment have been demonstrated. Consequently, we compiled the TCMs that show great potential in the treatment of NDDs by targeting MQC, aiming to offer novel insights and a scientific foundation for the use of MQC stabilizers in NDD prevention and treatment.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101146"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061648","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":"Raman analysis of lipids in cells: Current applications and future prospects.","authors":"Yixuan Zhou, Yuelin Xu, Xiaoli Hou, Daozong Xia","doi":"10.1016/j.jpha.2024.101136","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101136","url":null,"abstract":"<p><p>Lipids play an important role in the regulation of cell life processes. Although there are various lipid detection methods, Raman spectroscopy, a non-invasive technique, provides the detailed chemical composition of lipid profiles without a complex sample preparation procedure and possesses greater potential in basic biology, clinical diagnosis and disease therapy. In this review, we summarized the characteristics and advantages of Raman-based techniques and their primary contribution to illustrating cellular lipid metabolism.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101136"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11999598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001087","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":"Luteolin and its antidepressant properties: From mechanism of action to potential therapeutic application.","authors":"Jiayu Zhou, Ziyi Wu, Ping Zhao","doi":"10.1016/j.jpha.2024.101097","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101097","url":null,"abstract":"<p><p>Luteolin is a natural flavonoid compound exists in various fruits and vegetables. Recent studies have indicated that luteolin has variety pharmacological effects, including a wide range of antidepressant properties. Here, we systematically review the preclinical studies and limited clinical evidence on the antidepressant and neuroprotective effects of luteolin to fully explore its antidepressant power. Network pharmacology and molecular docking analyses contribute to a better understanding of the preclinical models of depression and antidepressant properties of luteolin. Seventeen preclinical studies were included that combined network pharmacology and molecular docking analyses to clarify the antidepressant mechanism of luteolin and its antidepressant targets. The antidepressant effects of luteolin may involve promoting intracellular noradrenaline (NE) uptake; inhibiting 5-hydroxytryptamine (5-HT) reuptake; upregulating the expression of synaptophysin, postsynaptic density protein 95, brain-derived neurotrophic factor, B cell lymphoma protein-2, superoxide dismutase, and glutathione <i>S</i>-transferase; and decreasing the expression of malondialdehyde, caspase-3, and amyloid-beta peptides. The antidepressant effects of luteolin are mediated by various mechanisms, including anti-oxidative stress, anti-apoptosis, anti-inflammation, anti-endoplasmic reticulum stress, dopamine transport, synaptic protection, hypothalamic-pituitary-adrenal axis regulation, and 5-HT metabolism. Additionally, we identified insulin-like growth factor 1 receptor (IGF1R), AKT serine/threonine kinase 1 (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor alpha (ESR1), and epidermal growth factor receptor (EGFR) as potential targets, luteolin has an ideal affinity for these targets, suggesting that it may play a positive role in depression through multiple targets, mechanisms, and pathways. However, the clinical efficacy of luteolin and its potential direct targets must be confirmed in further multicenter clinical case-control and molecular targeting studies.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101097"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056900","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":"Probing the biological efficacy and mechanistic pathways of natural compounds in breast cancer therapy via the Hedgehog signaling pathway.","authors":"Yining Cheng, Wenfeng Zhang, Qi Sun, Xue Wang, Qihang Shang, Jingyang Liu, Yubao Zhang, Ruijuan Liu, Changgang Sun","doi":"10.1016/j.jpha.2024.101143","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101143","url":null,"abstract":"<p><p>Breast cancer (BC) is one of the most prevalent malignant tumors affecting women worldwide, with its incidence rate continuously increasing. As a result, treatment strategies for this disease have received considerable attention. Research has highlighted the crucial role of the Hedgehog (Hh) signaling pathway in the initiation and progression of BC, particularly in promoting tumor growth and metastasis. Therefore, molecular targets within this pathway represent promising opportunities for the development of novel BC therapies. This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC. By conducting a comprehensive review of various natural compounds, including polyphenols, terpenes, and alkaloids, we reveal both common and unique regulatory mechanisms that influence this pathway. This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC. Furthermore, by exploring the structure-activity relationships between these compounds and their molecular targets, we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway. These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics. Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101143"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040542","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}