Qianlin Song, Chao Song, Xin Chen, Yunhe Xiong, Ziqi He, Xiaozhe Su, Jiawei Zhou, Hu Ke, Caitao Dong, Wenbiao Liao, Sixing Yang
{"title":"Oxalate regulates crystal-cell adhesion and macrophage metabolism via JPT2/PI3K/AKT signaling to promote the progression of kidney stones","authors":"Qianlin Song, Chao Song, Xin Chen, Yunhe Xiong, Ziqi He, Xiaozhe Su, Jiawei Zhou, Hu Ke, Caitao Dong, Wenbiao Liao, Sixing Yang","doi":"10.1016/j.jpha.2024.02.010","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.02.010","url":null,"abstract":"Oxalate is an organic dicarboxylic acid that is a common component of plant foods. The kidneys are essential organs for oxalate excretion, but excessive oxalates may induce kidney stones. Jupiter microtubule associated homolog 2 (JPT2) is a critical molecule in Ca mobilization, and its intrinsic mechanism in oxalate exposure and kidney stones remains unclear. This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones. Genetic approaches were used to control JPT2 expression in cells and mice, and the JPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics. The results showed that oxalate exposure triggered the upregulation of JPT2, which is involved in nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated Ca mobilization. Transcriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown, and these were dominated by PI3K/AKT signaling, respectively. Untargeted metabolomics indicated that JPT2 knockdown inhibited the production of succinic acid semialdehyde (SSA) in macrophages. Furthermore, JPT2 deficiency in mice inhibited kidney stones mineralization. In conclusion, this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion, and modulating macrophage metabolism and inflammatory polarization via JPT2/PI3K/AKT signaling.","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"30 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140010078","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}
{"title":"An Fe-Cu bimetallic organic framework as a microwave sensitizer for treating tumors using combined microwave thermotherapy and chemodynamic therapy","authors":"Xinyang Zhu, Chao He, Longfei Tan, Xun Qi, Meng Niu, Xianwei Meng, Hongshan Zhong","doi":"10.1016/j.jpha.2024.02.006","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.02.006","url":null,"abstract":"Microwave thermotherapy (MWTT), as a treatment for tumors, lacks specificity and requires sensitizers. Most reported microwave sensitizers are single-metal organic frameworks (MOFs), which must be loaded with ionic liquids to enhance the performance in MWTT. Meanwhile, MWTT is rarely combined with other treatment modalities. Here, we synthesized a novel Fe-Cu bimetallic organic framework FeCuMOF (FCM) by applying a hydrothermal method and further modified it with methyl polyethylene glycol (mPEG). The obtained FeCuMOF@PEG (FCMP) showed remarkable heating performance under low-power microwave irradiation; it also acted as a novel nanoparticle enzyme to catalyze hydrogen peroxide decomposition, producing abundant reactive oxygen species (ROS) to deplete glutathione and prevent ROS clearance from tumor cells during chemodynamic treatment. The FCMP was biodegradable and demonstrated excellent biocompatibility, allowing it to be readily metabolized without causing toxic effects. Finally, it was shown to act as a suitable agent for T2 magnetic resonance imaging (MRI) and . This new bimetallic nanostructure could successfully realize two tumor treatment modalities (MWTT and chemodynamic therapy) and dual imaging modes (MRI and microwave thermal imaging). Our findings represent a breakthrough for integrating the diagnosis and treatment of tumors and provides a reference for developing new microwave sensitizers.","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"257 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140010255","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}
Meiyu Qu, Qiangqiang He, Hangyang Bao, Xing Ji, Tingyu Shen, Muhammad Qasim Barkat, Ximei Wu, Ling-Hui Zeng
{"title":"Multiple roles of arsenic compounds in phase separation and membraneless organelles formation determine their therapeutic efficacy in tumors","authors":"Meiyu Qu, Qiangqiang He, Hangyang Bao, Xing Ji, Tingyu Shen, Muhammad Qasim Barkat, Ximei Wu, Ling-Hui Zeng","doi":"10.1016/j.jpha.2024.02.011","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.02.011","url":null,"abstract":"Arsenic compounds are widely used for the therapeutic intervention of multiple diseases. Ancient pharmacologists discovered the medicinal utility of such highly toxic substances, and modern pharmacologists have further recognized the specific active ingredients in human diseases. In particular, Arsenic trioxide (ATO), as a main component, has therapeutic effects on various tumors (including leukemia, hepatocellular carcinoma, lung cancer, etc.). However, its toxicity limits its efficacy, and how to control its toxicity has been an important issue. Interestingly, recently emerging evidence has pointed out the pivotal roles of arsenic compounds in phase separation and membraneless organelles formation, which may decide their toxicity and therapeutic efficacy. Here, we summarized the arsenic compounds-regulating phase separation and membraneless organelles formation. We further hypothesize their potential involvement in the therapy and toxicity of arsenic compounds, highlighting potential mechanisms underlying the clinical application of arsenic compounds.","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"30 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140009948","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}
{"title":"Signal interference between drugs and metabolites in LC-ESI-MS quantitative analysis and its evaluation strategy","authors":"Fulin Jiang, Jingyu Liu, Yagang Li, Zihan Lu, Qian Liu, Yunhui Xing, Janshon Zhu, Min Huang, Guoping Zhong","doi":"10.1016/j.jpha.2024.02.008","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.02.008","url":null,"abstract":"Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS) is a widely utilized technique for in vivo pharmaceutical analysis. Ionization interference within electrospray ion source, occurring between drugs and metabolites, can lead to signal variations, potentially compromising quantitative accuracy. Currently, method validation often overlooks this type of signal interference, which may result in systematic errors in quantitative results without matrix-matched calibration. In this study, we conducted an investigation using ten different groups of drugs and their corresponding metabolites across three LC-ESI-MS systems to assess the prevalence of signal interference. Such interferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites, thereby altering the relationship between analyte response and concentration for quantification. Finally, we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods: chromatographic separation, dilution, and stable labeled isotope internal standards correction. The above strategies were integrated into the method establishment process to improve quantitative accuracy.","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"47 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140010085","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}
Alina Cherniienko, Roman Lesyk, Lucjusz Zaprutko, Anna Pawełczyk
{"title":"IR-EcoSpectra: Exploring sustainable ex situ and in situ FTIR applications for green chemical and pharmaceutical analysis","authors":"Alina Cherniienko, Roman Lesyk, Lucjusz Zaprutko, Anna Pawełczyk","doi":"10.1016/j.jpha.2024.02.005","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.02.005","url":null,"abstract":"","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"2012 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139954673","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}
Shu Yang, Zhonghua Wang, Yanhua Liu, Xin Zhang, Hang Zhang, Zhaoying Wang, Zhi Zhou, Zeper Abliz
{"title":"Dual mass spectrometry imaging and spatial metabolomics to investigate the metabolism and nephrotoxicity of nitidine chloride","authors":"Shu Yang, Zhonghua Wang, Yanhua Liu, Xin Zhang, Hang Zhang, Zhaoying Wang, Zhi Zhou, Zeper Abliz","doi":"10.1016/j.jpha.2024.01.012","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.01.012","url":null,"abstract":"<p>Evaluating toxicity and decoding the underlying mechanisms of active compounds are crucial for drug development. In this study, we present an innovative, integrated approach that combines air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and spatial metabolomics to comprehensively investigate the nephrotoxicity and underlying mechanisms of nitidine chloride (NC), a promising anti-tumor drug candidate. Our quantitive AFADESI-MSI analysis unveiled the region specific of accumulation of NC in the kidney, particularly within the inner cortex (IC) region, following single and repeated dose of NC. High spatial resolution ToF-SIMS analysis further allowed us to precisely map the localization of NC within the renal tubule. Employing spatial metabolomics based on AFADESI-MSI, we identified over 70 discriminating endogenous metabolites associated with chronic NC exposure. These findings suggest the renal tubule as the primary target of NC toxicity and implicate renal transporters (organic cation transporters, multidrug and toxin extrusion, organic cation transporter 2), metabolic enzymes (protein arginine N-methyltransferase, nitric oxide synthase), mitochondria, oxidative stress, and inflammation in NC-induced nephrotoxicity. This study offers novel insights into NC-induced renal damage, representing a crucial step towards devising strategies to mitigate renal damage caused by this compound.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"10 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139678495","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}
{"title":"In situ repolarization of Tumor-Associated Macrophages with synergic nanoformulation to reverse immunosuppressive TME in mouse breast cancer for cancer therapy","authors":"Ruhua Luo, Zhongyu Yue, Qian Yang, Honghua Zhang, Tian Xie, Shuling Wang, Qingchang Tian","doi":"10.1016/j.jpha.2024.01.009","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.01.009","url":null,"abstract":"<p>The conversion of tumor-associated macrophages (TAMs) from M2 phenotype to M1 phenotype could reverse the immunosuppression associated with the tumor microenvironment. Here, we constructed M2 phenotype macrophage-targeted Lipo@CpG-FA by encapsulating CpG ODNs. The combination of Lipo@CpG-FA with FA-Lipo@Ele-AS1411 caused regression and inhibition of 4T1 breast cancers by reversing the M2-TAMs mediated immunosuppression and efficiently inducing effector T cell activation in the tumor microenvironment. In addition to antitumor effects, Elemene (Ele) could inhibit the effect M2 macrophage proliferation by enhancing the therapeutic effects. The application of this strategy may be potentially expanded for cancer therapy in combination with other therapeutics.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"85 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139678396","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}
Shaowei Huang, Xueqian Xie, Bo Xu, Zengfeng Pan, Junjie Liang, Meiling Zhang, Simin Pan, Xiaojing Wang, Meng Zhao, Qing Wang, Jinyan Chen, Yanyang Li, Lian Zhou, Xia Luo
{"title":"Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells","authors":"Shaowei Huang, Xueqian Xie, Bo Xu, Zengfeng Pan, Junjie Liang, Meiling Zhang, Simin Pan, Xiaojing Wang, Meng Zhao, Qing Wang, Jinyan Chen, Yanyang Li, Lian Zhou, Xia Luo","doi":"10.1016/j.jpha.2024.01.008","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.01.008","url":null,"abstract":"<p>Inhibiting the death receptor 3 (DR3) signaling pathway in group 3 innate lymphoid cells (ILC3s) presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis (UC). Paeoniflorin, a prominent component of <em>Paeonia lactiflora</em> Pall., has demonstrated the ability to restore barrier function in UC mice, but the precise mechanism remains unclear. In this study, we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s. C57BL/6 mice were subjected to random allocation into 7 distinct groups, namely the control group, the 2% dextran sodium sulfate (DSS) group, the paeoniflorin groups (25, 50, and 100 mg/kg), the anti-tumor necrosis factor-like ligand 1A (anti-TL1A) antibody group, and the IgG group. We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using western blot and flow cytometry, respectively. Meanwhile, DR3-overexpressing MNK-3 cells and 2% DSS-induced Rag1<sup>-/-</sup> mice were used for verification. The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier. Simultaneously, paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines (Interleukin-17A, Granulocyte-macrophage colony stimulating factor, and Interleukin-22). Alternatively, paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system. We additionally confirmed that paeoniflorin-conditioned medium (CM) restored the expression of tight junctions in Caco-2 cells via coculture. In conclusion, paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner, and its mechanism is associated with the inhibition of the DR3 signaling pathway.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"37 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139667375","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}
Tinatini Tchatchiashvilli, Helena Duering, Lisa Mueller-Boetticher, Christian Grune, Dagmar Fischer, Mathias W. Pletz, Oliwia Makarewicz
{"title":"PEG-PLGA nanoparticles deposited in Pseudomonas aeruginosa and Burkolderia cenocepacia","authors":"Tinatini Tchatchiashvilli, Helena Duering, Lisa Mueller-Boetticher, Christian Grune, Dagmar Fischer, Mathias W. Pletz, Oliwia Makarewicz","doi":"10.1016/j.jpha.2024.01.007","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.01.007","url":null,"abstract":"<p>In our prior research, polymer nanoparticles containing tobramycin displayed robust antibacterial efficacy against biofilm-embedded <em>Pseudomonas aeruginosa</em> and <em>Burkholderia cenocepacia</em> cells, critical pathogens in cystic fibrosis. In the current study, we investigated the deposition of a nanoparticulate carrier composed of poly(D,L-lactic-<em>co</em>-glycolic acid) (PLGA) and poly(ethylene glycol)-<em>block</em>-PLGA (PEG-PLGA) that was either covalently bonded with cyanine-5-amine or noncovalently bound with freely embedded cationic rhodamine B, which served as a drug surrogate. After exposing these nanoparticles to bacteria, we performed cell fractionation and fluorescence analysis, which highlighted the accumulation of cyanine-5-amine in the outer membranes and the accumulation of rhodamine B in the cytoplasm of cells. The results indicated that these organic nanoparticles are effective vehicles for targeted antibiotic delivery in bacterial cells, explaining the observed increase in the efficacy of encapsulated tobramycin against biofilms. This work emphasizes the potential of PEG-PLGA-based formulations for advanced drug delivery strategies.</p>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"3 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139582572","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}