Journal of Pharmaceutical Analysis最新文献

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Discovery of potent anti-MRSA components from Dalbergia odorifera through UPLC-Q-TOF-MS and targeting PBP2a protein through in-depth transcriptomic, in vitro, and in-silico studies 通过UPLC-Q-TOF-MS,并通过深入的转录组学、体外和体内研究,从达尔文香豆中发现针对PBP2a蛋白的强效抗MRSA成分
IF 8.8 1区 医学
Journal of Pharmaceutical Analysis Pub Date : 2024-01-23 DOI: 10.1016/j.jpha.2024.01.006
Jiajia Wu, Syed Shams ul Hassan, Xue Zhang, Tao Li, Abdur Rehman, Shikai Yan, Huizi Jin
{"title":"Discovery of potent anti-MRSA components from Dalbergia odorifera through UPLC-Q-TOF-MS and targeting PBP2a protein through in-depth transcriptomic, in vitro, and in-silico studies","authors":"Jiajia Wu, Syed Shams ul Hassan, Xue Zhang, Tao Li, Abdur Rehman, Shikai Yan, Huizi Jin","doi":"10.1016/j.jpha.2024.01.006","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.01.006","url":null,"abstract":"Abstract not available","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"230 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139554917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Platelet membrane biomimetic nanomedicine induces dual glutathione consumption for enhancing cancer radioimmunotherapy 血小板膜生物仿生纳米药物可诱导谷胱甘肽双重消耗,增强癌症放射免疫疗法的效果
IF 8.8 1区 医学
Journal of Pharmaceutical Analysis Pub Date : 2024-01-17 DOI: 10.1016/j.jpha.2024.01.003
Xiaopeng Li, Yang Zhong, Pengyuan Qi, Daoming Zhu, Chenglong Sun, Nan Wei, Yang Zhang, Zhanggui Wang
{"title":"Platelet membrane biomimetic nanomedicine induces dual glutathione consumption for enhancing cancer radioimmunotherapy","authors":"Xiaopeng Li, Yang Zhong, Pengyuan Qi, Daoming Zhu, Chenglong Sun, Nan Wei, Yang Zhang, Zhanggui Wang","doi":"10.1016/j.jpha.2024.01.003","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.01.003","url":null,"abstract":"<p>Radiotherapy (RT) is one of the most common treatments for cancer. However, intracellular glutathione (GSH) plays a key role in protecting cancer from radiation damage. Herein, we have developed a platelet membrane biomimetic nanomedicine (PMD) that induces double GSH consumption to enhance tumor radioimmunotherapy. This biomimetic nanomedicine consists of an external platelet membrane and internal organic mesoporous silica nanoparticles (MON) loaded with 2-deoxy-D-glucose (2-DG). Thanks to the tumor-targeting ability of the platelet membranes, PMD can target and aggregate to the tumor site, which is internalized by tumor cells. Within tumor cells overexpressing GSH, MON reacts with GSH to degrade and release 2-DG. This step initially depletes the intracellular GSH content. The subsequent release of 2-DG inhibits glycolysis and adenosine triphosphate (ATP) production, ultimately leading to secondary GSH consumption. This nanodrug combines dual GSH depletion, starvation therapy, and RT to promote immunogenic cell death and stimulate the systemic immune response. In the bilateral tumor model in vivo, distal tumor growth was also well suppressed. The proportion of mature dendritic cells (DC) and CD8<sup>+</sup>T cells in the mice was increased. This indicates that PMD can promote anti-tumor radioimmunotherapy and has good prospects for clinical application.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"17 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139496301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of GC × GC fingerprints from medicinal materials using a novel contour detection algorithm: A case of Curcuma wenyujin 使用新型轮廓检测算法分析药材的 GC × GC 指纹:以莪术为例
IF 8.8 1区 医学
Journal of Pharmaceutical Analysis Pub Date : 2024-01-14 DOI: 10.1016/j.jpha.2024.01.004
Xinyue Yang, Yingyu Sima, Xuhuai Luo, Yaping Li, Min He
{"title":"Analysis of GC × GC fingerprints from medicinal materials using a novel contour detection algorithm: A case of Curcuma wenyujin","authors":"Xinyue Yang, Yingyu Sima, Xuhuai Luo, Yaping Li, Min He","doi":"10.1016/j.jpha.2024.01.004","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.01.004","url":null,"abstract":"<p>This study introduces an innovative contour detection algorithm, PeakCET, designed for rapid and efficient analysis of natural product image fingerprints using comprehensive two-dimensional gas chromatogram (GC × GC). This method innovatively combines contour edge tracking with affinity propagation (AP) clustering for peak detection in GC × GC fingerprints, a first in this field. Contour edge tracking significantly reduces false positives caused by \"burr\" signals, while AP clustering enhances detection accuracy in the face of false negatives. The efficacy of this approach is demonstrated using three medicinal products derived from <em>Curcuma wenyujin</em>. PeakCET not only performs contour detection but also employs inter-group peak matching and peak-volume percentage calculations to assess the compositional similarities and differences among various samples. Furthermore, this algorithm compares the GC × GC fingerprints of <em>Radix</em>/<em>Rhizoma Curcumae Wenyujin</em> with those of products from different botanical origins. The findings reveal that genetic and geographical factors influence the accumulation of secondary metabolites in various plant tissues. Each sample exhibits unique characteristic components alongside common ones, and variations in content may influence their therapeutic effectiveness. This research establishes a foundational data-set for the quality assessment of <em>Curcuma</em> products and paves the way for the application of computer vision techniques in two-dimensional (2D) fingerprint analysis of GC × GC data.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"249 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139460418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeted delivery of rosuvastatin enhances treatment of HHcy-induced atherosclerosis using macrophage membrane-coated nanoparticles 利用巨噬细胞膜包被纳米粒子靶向输送罗伐他汀,提高对 HHcy 诱导的动脉粥样硬化的治疗效果
IF 8.8 1区 医学
Journal of Pharmaceutical Analysis Pub Date : 2024-01-13 DOI: 10.1016/j.jpha.2024.01.005
Dayue Liu, Anning Yang, Yulin Li, Zhenxian Li, Peidong You, Hongwen Zhang, Shangkun Quan, Yue Sun, Yaling Zeng, Shengchao Ma, Jiantuan Xiong, Yinju Hao, Guizhong Li, Bin Liu, Huiping Zhang, Yideng Jiang
{"title":"Targeted delivery of rosuvastatin enhances treatment of HHcy-induced atherosclerosis using macrophage membrane-coated nanoparticles","authors":"Dayue Liu, Anning Yang, Yulin Li, Zhenxian Li, Peidong You, Hongwen Zhang, Shangkun Quan, Yue Sun, Yaling Zeng, Shengchao Ma, Jiantuan Xiong, Yinju Hao, Guizhong Li, Bin Liu, Huiping Zhang, Yideng Jiang","doi":"10.1016/j.jpha.2024.01.005","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.01.005","url":null,"abstract":"<p>Rosuvastatin (RVS) is an excellent drug with anti-inflammatory and lipid-lowering properties in the academic and medical fields. However, this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia (HHcy), including high oral dosage, poor targeting, and long-term toxic side effects. In this study, we applied nanotechnology to construct a biomimetic nano-delivery system, macrophage membrane (Møm)-coated RVS-loaded Prussian blue (PB) nanoparticles (MPR NPs), for improving the bioavailability and targeting capacity of RVS, specifically to the plaque lesions associated with HHcy-induced atherosclerosis. <em>In vitro</em> assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4 (TLR4)/hypoxia-inducible factor-1α (HIF-1α/nucleotide-binding and oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathways, reducing pyroptosis and inflammatory response in macrophages. Additionally, MPR NPs reversed the abnormal distribution of ABCA1/ABCG1 caused by HIF-1α, promoting cholesterol efflux and reducing lipid deposition. <em>In vivo</em> studies using apolipoprotein E knockout (<em>ApoE</em><sup>−/−</sup>) mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable biosecurity, the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes. These findings suggest that the synthesis of Møm-coated RVS-loaded PB NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"1 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139460267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Baicalin alleviates chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor 黄芩苷通过直接靶向β2-肾上腺素能受体缓解慢性压力诱导的乳腺癌转移
IF 8.8 1区 医学
Journal of Pharmaceutical Analysis Pub Date : 2024-01-04 DOI: 10.1016/j.jpha.2024.01.002
Qi Jia, Yinyin Zhou, Li Song, Ximeng Shi, Xuan Jiang, Ruizhi Tao, Aiyun Wang, Yuanyuan Wu, Zhonghong Wei, Yinan Zhang, Xiaoman Li, Yin Lu
{"title":"Baicalin alleviates chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor","authors":"Qi Jia, Yinyin Zhou, Li Song, Ximeng Shi, Xuan Jiang, Ruizhi Tao, Aiyun Wang, Yuanyuan Wu, Zhonghong Wei, Yinan Zhang, Xiaoman Li, Yin Lu","doi":"10.1016/j.jpha.2024.01.002","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.01.002","url":null,"abstract":"<p>Recent studies have shown that stress can substantially facilitate breast cancer metastasis, which can be ameliorated by nonselective β1/β2-adrenergic receptor (β1/β2-AR) blocker. However, several side effects were identified. Thus, it is extremely warranted to explore more effective and better-tolerated β2-AR blocker. Currently, we demonstrated that baicalin (BA), a major bioactive component of <em>Scutellaria baicalensis</em> Georgi, could significantly attenuate stress hormones especially epinephrine (Epi)-induced breast cancer cell migration and invasion <em>in vitro.</em> Mechanistically, we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability (DARTS) combined with mass spectrum assay, and BA photoaffinity probe with pull-down assay, which was further confirmed by a couple of biophysical and biochemical assays. Furthermore, we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR, subsequently inhibit cAMP-PKA-FAK pathway, and thus impede epithelial-mesenchymal transition (EMT), thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft <em>in vivo</em> orthotopic and tail vein mouse model. These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"78 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139092199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In situ visualization of the cellular uptake and sub-cellular distribution of mussel oligosaccharides 贻贝寡糖的细胞摄取和亚细胞分布原位可视化
IF 8.8 1区 医学
Journal of Pharmaceutical Analysis Pub Date : 2024-01-04 DOI: 10.1016/j.jpha.2023.12.022
Zhenjie Yu, Huarong Shao, Xintian Shao, Linyan Yu, Yanan Gao, Youxiao Ren, Fei Liu, Caicai Meng, Peixue Ling, Qixin Chen
{"title":"In situ visualization of the cellular uptake and sub-cellular distribution of mussel oligosaccharides","authors":"Zhenjie Yu, Huarong Shao, Xintian Shao, Linyan Yu, Yanan Gao, Youxiao Ren, Fei Liu, Caicai Meng, Peixue Ling, Qixin Chen","doi":"10.1016/j.jpha.2023.12.022","DOIUrl":"https://doi.org/10.1016/j.jpha.2023.12.022","url":null,"abstract":"<p>Unlike chemosynthetic drugs designed for specific molecular and disease targets, active small-molecule natural products typically have a wide range of bioactivities and multiple targets, necessitating extensive screening and development. To address this issue, we propose a strategy for the direct in situ microdynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action. As a proof-of-concept, we investigated the behavior of mussel oligosaccharide (MOS-1) by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells. We recorded the entire dynamic process of the localization of fluorescein isothiocyanate (FITC)-mussel oligosaccharide (MOS-1) to the lysosomes and visualized the distribution of the drug within the cell. Remarkably, lysosomes containing FITC-MOS-1 actively recruited lipid droplets, leading to fusion events and increased cellular lipid consumption. These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases. Furthermore, in a high-fat HepG2 cell model and in high-fat diet-fed <em>ApoE</em><sup><em>−/−</em></sup> mice, MOS-1 significantly promoted triglyceride degradation, reduced lipid droplet accumulation, lowered serum triglyceride levels, and mitigated liver damage and steatosis. Overall, our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase as this methodology contributes to the rapid identification of drug indications. Collectively, this methodology is significant for the screening and development of selective small-molecule drugs, and is expected to expedite the identification of candidate molecules with medicinal effects.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"35 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139092371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Renal tubular epithelial cell quality control mechanisms as therapeutic targets in renal fibrosis 作为肾脏纤维化治疗靶点的肾小管上皮细胞质量控制机制
IF 8.8 1区 医学
Journal of Pharmaceutical Analysis Pub Date : 2024-01-03 DOI: 10.1016/j.jpha.2024.01.001
Yini Bao, Qiyuan Shan, Keda Lu, Qiao Yang, Ying Liang, Haodan Kuang, Lu Wang, Min Hao, Mengyun Peng, Shuosheng Zhang, Gang Cao
{"title":"Renal tubular epithelial cell quality control mechanisms as therapeutic targets in renal fibrosis","authors":"Yini Bao, Qiyuan Shan, Keda Lu, Qiao Yang, Ying Liang, Haodan Kuang, Lu Wang, Min Hao, Mengyun Peng, Shuosheng Zhang, Gang Cao","doi":"10.1016/j.jpha.2024.01.001","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.01.001","url":null,"abstract":"<p>Renal fibrosis is a devastating consequence of progressive chronic kidney disease, representing a major public health challenge worldwide. The underlying mechanisms in the pathogenesis of renal fibrosis remain unclear, and effective treatments are still lacking. Renal tubular epithelial cells (RTECs) maintain kidney function, and their dysfunction has emerged as a critical contributor to renal fibrosis. Cellular quality control comprises several components, including telomere homeostasis, ubiquitin-proteasome system, autophagy, mitochondrial homeostasis (mitophagy and mitochondrial metabolism), endoplasmic reticulum (unfolded protein response), and lysosomes. Failures in the cellular quality control of RTECs, including deoxyribonucleic acid (DNA), protein, and organelle damage, exert profibrotic functions by leading to senescence, defective autophagy, endoplasmic reticulum stress, mitochondrial and lysosomal dysfunction, apoptosis, fibroblast activation, and immune cell recruitment. In this review, we summarize recent advances in understanding the role of quality control components and intercellular crosstalk networks in RTECs, within the context of renal fibrosis.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"4 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139374202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation 槲皮素治疗非传染性疾病潜力的新视角:以Nrf2为靶点对抗氧化应激和炎症
IF 8.8 1区 医学
Journal of Pharmaceutical Analysis Pub Date : 2024-01-03 DOI: 10.1016/j.jpha.2023.12.020
Li Zhang, Li Yue Xu, Fei Tang, Dong Liu, Xiao Lan Zhao, Jing Nan Zhang, Jia Xia, Jiao Jiao Wu, Yu Yang, Cheng Peng, Hui Ao
{"title":"New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation","authors":"Li Zhang, Li Yue Xu, Fei Tang, Dong Liu, Xiao Lan Zhao, Jing Nan Zhang, Jia Xia, Jiao Jiao Wu, Yu Yang, Cheng Peng, Hui Ao","doi":"10.1016/j.jpha.2023.12.020","DOIUrl":"https://doi.org/10.1016/j.jpha.2023.12.020","url":null,"abstract":"<p>Non-communicable diseases (NCDs), including cardiovascular diseases, cancer, metabolic diseases, and skeletal diseases, pose significant challenges to public health worldwide. The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage. Nuclear factor erythroid 2-related factor 2 (Nrf2), a critical transcription factor, plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury. Therefore, <em>Nrf2</em>-targeting therapies hold promise for preventing and treating NCDs. Quercetin (Que) is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties. It modulates the <em>Nrf2</em> signaling pathway to ameliorate oxidative stress and inflammation. Que modulates mitochondrial function, apoptosis, autophagy, and cell damage biomarkers to regulate oxidative stress and inflammation, highlighting its efficacy as a therapeutic agent against NCDs. Here, we discussed, for the first time, the close association between NCD pathogenesis and the <em>Nrf2</em> signaling pathway, involved in neurodegenerative diseases, cardiovascular disease, cancers, organ damage, and bone damage. Furthermore, we reviewed the availability, pharmacokinetics, pharmaceutics, and therapeutic applications of Que in treating NCDs. In addition, we focused on the challenges and prospects for its clinical use. Que represents a promising candidate for the treatment of NCDs due to its <em>Nrf2</em>-targeting properties.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"58 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139096700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dynamic gut microbiome-metabolome in c-BSA induced experimental immune-complex glomerulonephritis and effect of losartan and MMF on microbiota modulation c-BSA 诱导的实验性免疫复合物肾小球肾炎中肠道微生物组代谢组的动态变化以及洛沙坦和 MMF 对微生物组调节的影响
IF 8.8 1区 医学
Journal of Pharmaceutical Analysis Pub Date : 2023-12-30 DOI: 10.1016/j.jpha.2023.12.021
Wenying Shi, Zhaojun Li, Weida Wang, Xikun Liu, Haijie Wu, Xiaoguang Chen, Xunrong Zhou, Sen Zhang
{"title":"Dynamic gut microbiome-metabolome in c-BSA induced experimental immune-complex glomerulonephritis and effect of losartan and MMF on microbiota modulation","authors":"Wenying Shi, Zhaojun Li, Weida Wang, Xikun Liu, Haijie Wu, Xiaoguang Chen, Xunrong Zhou, Sen Zhang","doi":"10.1016/j.jpha.2023.12.021","DOIUrl":"https://doi.org/10.1016/j.jpha.2023.12.021","url":null,"abstract":"<p>Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis (ICGN). However, an in-depth study on this topic is currently lacking. Herein, we report an ICGN model to address this gap. ICGN was induced via the intravenous injection of cationized bovine serum albumin into Sprague-Dawley rats for two weeks, after which mycophenolate mofetil (MMF) and losartan were administered orally. Two and six weeks after ICGN establishment, fecal samples were collected and 16S ribosomal DNA (rDNA) sequencing and untargeted metabolomic were conducted. Fecal microbiota transplantation (FMT) was conducted to determine whether gut normalization caused by MMF and losartan contributed to their renal protective effects. A gradual decline in microbial diversity and richness was accompanied by a loss of renal function. Approximately 18 genera were found to have significantly different relative abundances between the early and later stages, and <em>Marvinbryantia</em> and <em>Allobaculum</em> were markedly upregulated in both stages. Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN, characterized by the overproduction of indole and kynurenic acid, while the serotonin pathway was reduced. Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces. FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes ratio but did not improve renal function. These findings indicate that ICGN induces serous gut dysbiosis, wherein an altered tryptophan metabolism may contribute to its progression. MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis, which partially contributed to their renoprotective effects.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"12 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139070539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Discrimination of Polysorbate 20 by High-Performance Liquid Chromatography-Charged Aerosol Detection and Characterization for Components by Expanding Compound Database and Library 用高效液相色谱法检测聚山梨醇酯 20,并通过扩展化合物数据库和资料库确定成分特征
IF 8.8 1区 医学
Journal of Pharmaceutical Analysis Pub Date : 2023-12-30 DOI: 10.1016/j.jpha.2023.12.019
Shi-Qi Wang, Xun Zhao, Li-Jun Zhang, Yue-Mei Zhao, Lei Chen, Jin-Lin Zhang, Bao-Cheng Wang, Sheng Tang, Tom Yuan, Yaozuo Yuan, Mei Zhang, Hian Kee Lee, Hai-Wei Shi
{"title":"Discrimination of Polysorbate 20 by High-Performance Liquid Chromatography-Charged Aerosol Detection and Characterization for Components by Expanding Compound Database and Library","authors":"Shi-Qi Wang, Xun Zhao, Li-Jun Zhang, Yue-Mei Zhao, Lei Chen, Jin-Lin Zhang, Bao-Cheng Wang, Sheng Tang, Tom Yuan, Yaozuo Yuan, Mei Zhang, Hian Kee Lee, Hai-Wei Shi","doi":"10.1016/j.jpha.2023.12.019","DOIUrl":"https://doi.org/10.1016/j.jpha.2023.12.019","url":null,"abstract":"<p>Analyzing polysorbate 20 (PS20) composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance. The similar structures and polarities of PS20 components make accurate separation, identification, and quantification challenging. In this work, a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography (HPLC) with charged aerosol detection (CAD) to separate 18 key components with multiple esters. The separated components were characterized by ultra-high-performance LC-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) with an identical gradient as the HPLC-CAD analysis. The polysorbate compound database and library were expanded over 7-time compared to the commercial database. The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship. UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources. The method observed the impact of 4 degradation conditions on peak components, identifying stable components and their tendencies to change. HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences, distinguishing quasi products.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"32 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139070762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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