Journal of Pharmaceutical Analysis最新文献

{"title":"Automated closed-cell production platform solves dilemma of industrial-scale manufacturing for mesenchymal stromal cell-based therapy","authors":"Yirui Feng , Bin Wang","doi":"10.1016/j.jpha.2023.08.017","DOIUrl":"10.1016/j.jpha.2023.08.017","url":null,"abstract":"","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 11","pages":"Pages 1233-1234"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2095177923002083/pdfft?md5=e61e1902e1f22b7af34490c04dca4377&pid=1-s2.0-S2095177923002083-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136129473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rg5 enhances the radiosensitivity of lung adenocarcinoma via reducing HSP90-CDC37 interaction and promoting client protein degradation","authors":"Hansong Bai ,&nbsp;Jiahua Lyu ,&nbsp;Xinyu Nie ,&nbsp;Hao Kuang ,&nbsp;Long Liang ,&nbsp;Hongyuan Jia ,&nbsp;Shijie Zhou ,&nbsp;Churong Li ,&nbsp;Tao Li","doi":"10.1016/j.jpha.2023.06.004","DOIUrl":"10.1016/j.jpha.2023.06.004","url":null,"abstract":"<div><p>Ginsenoside Rg5 is a rare ginsenoside showing promising tumor-suppressive effects. This study aimed to explore its radio-sensitizing effects and the underlying mechanisms. Human lung adenocarcinoma cell lines A549 and Calu-3 were used for in vitro and in vivo analysis. Bioinformatic molecular docking prediction and following validation by surface plasmon resonance (SPR) technology, cellular thermal shift assay (CETSA), and isothermal titration calorimetry (ITC) were conducted to explore the binding between ginsenoside Rg5 and 90 kD heat shock protein alpha (HSP90α). The effects of ginsenoside Rg5 on HSP90-cell division cycle 37 (CDC37) interaction, the client protein stability, and the downstream regulations were further explored. Results showed that ginsenoside Rg5 could induce cell-cycle arrest at the G1 phase and enhance irradiation-induced cell apoptosis. It could bind to HSP90α with a high affinity, but the affinity was drastically decreased by HSP90α Y61A mutation. Co-immunoprecipitation (Co-IP) and ITC assays confirmed that ginsenoside Rg5 disrupts the HSP90-CDC37 interaction in a dose-dependent manner. It reduced irradiation-induced upregulation of the HSP90-CDC37 client proteins, including SRC, CDK4, RAF1, and ULK1 in A549 cell-derived xenograft (CDX) tumors. Ginsenoside Rg5 or MRT67307 (an IKKε/TBK1 inhibitor) pretreatment suppressed irradiation-induced elevation of the LC3-II/β ratio and restored irradiation-induced downregulation of p62 expression. In A549 CDX tumors, ginsenoside Rg5 treatment suppressed LC3 expression and enhanced irradiation-induced DNA damage. In conclusion, ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma. It interacts with HSP90α and reduces the binding between HSP90 and CDC37, thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 11","pages":"Pages 1296-1308"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2095177923001168/pdfft?md5=646857b6b2c92590301f0177fbcaf1a0&pid=1-s2.0-S2095177923001168-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47046785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosensors for waterborne virus detection: Challenges and strategies","authors":"Xixi Song,&nbsp;Zina Fredj,&nbsp;Yuqiao Zheng,&nbsp;Hongyong Zhang,&nbsp;Guoguang Rong,&nbsp;Sumin Bian,&nbsp;Mohamad Sawan","doi":"10.1016/j.jpha.2023.08.020","DOIUrl":"10.1016/j.jpha.2023.08.020","url":null,"abstract":"<div><p>Waterborne viruses that can be harmful to human health pose significant challenges globally, affecting health care systems and the economy. Identifying these waterborne pathogens is essential for preventing diseases and protecting public health. However, handling complex samples such as human and wastewater can be challenging due to their dynamic and complex composition and the ultralow concentration of target analytes. This review presents a comprehensive overview of the latest breakthroughs in waterborne virus biosensors. It begins by highlighting several promising strategies that enhance the sensing performance of optical and electrochemical biosensors in human samples. These strategies include optimizing bioreceptor selection, transduction elements, signal amplification, and integrated sensing systems. Furthermore, the insights gained from biosensing waterborne viruses in human samples are applied to improve biosensing in wastewater, with a particular focus on sampling and sample pretreatment due to the dispersion characteristics of waterborne viruses in wastewater. This review suggests that implementing a comprehensive system that integrates the entire waterborne virus detection process with high-accuracy analysis could enhance virus monitoring. These findings provide valuable insights for improving the effectiveness of waterborne virus detection, which could have significant implications for public health and environmental management.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 11","pages":"Pages 1252-1268"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2095177923002095/pdfft?md5=f154207aa61bcaf9953cdad76608b13f&pid=1-s2.0-S2095177923002095-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44612267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development status of novel spectral imaging techniques and application to traditional Chinese medicine","authors":"Qi Wang ,&nbsp;Yong Zhang ,&nbsp;Baofeng Yang","doi":"10.1016/j.jpha.2023.07.007","DOIUrl":"10.1016/j.jpha.2023.07.007","url":null,"abstract":"<div><p>Traditional Chinese medicine (TCM) is a treasure of the Chinese nation, providing effective solutions to current medical requisites. Various spectral techniques are undergoing continuous development and provide new and reliable means for evaluating the efficacy and quality of TCM. Because spectral techniques are noninvasive, convenient, and sensitive, they have been widely applied to in vitro and in vivo TCM evaluation systems. In this paper, previous achievements and current progress in the research on spectral technologies (including fluorescence spectroscopy, photoacoustic imaging, infrared thermal imaging, laser-induced breakdown spectroscopy, hyperspectral imaging, and surface enhanced Raman spectroscopy) are discussed. The advantages and disadvantages of each technology are also presented. Moreover, the future applications of spectral imaging to identify the origins, components, and pesticide residues of TCM in vitro are elucidated. Subsequently, the evaluation of the efficacy of TCM in vivo is presented. Identifying future applications of spectral imaging is anticipated to promote medical research as well as scientific and technological explorations.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 11","pages":"Pages 1269-1280"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2095177923001466/pdfft?md5=f171a00d7057fabeca7f331f55ed76b0&pid=1-s2.0-S2095177923001466-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42628384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Canonical transient receptor potential channel 1 aggravates myocardial ischemia-and-reperfusion injury by upregulating reactive oxygen species","authors":"Hui-Nan Zhang ,&nbsp;Meng Zhang ,&nbsp;Wen Tian ,&nbsp;Wei Quan ,&nbsp;Fan Song ,&nbsp;Shao-Yuan Liu ,&nbsp;Xiao-Xiao Liu ,&nbsp;Dan Mo ,&nbsp;Yang Sun ,&nbsp;Yuan-Yuan Gao ,&nbsp;Wen Ye ,&nbsp;Ying-Da Feng ,&nbsp;Chang-Yang Xing ,&nbsp;Chen Ye ,&nbsp;Lei Zhou ,&nbsp;Jing-Ru Meng ,&nbsp;Wei Cao ,&nbsp;Xiao-Qiang Li","doi":"10.1016/j.jpha.2023.08.018","DOIUrl":"10.1016/j.jpha.2023.08.018","url":null,"abstract":"<div><p>The canonical transient receptor potential channel (TRPC) proteins form Ca²⁺-permeable cation channels that are involved in various heart diseases. However, the roles of specific TRPC proteins in myocardial ischemia/reperfusion (I/R) injury remain poorly understood. We observed that TRPC1 and TRPC6 were highly expressed in the area at risk (AAR) in a coronary artery ligation induced I/R model. <em>Trpc1</em>^−/− mice exhibited improved cardiac function, lower serum Troponin T and serum creatine kinase level, smaller infarct volume, less fibrotic scars, and fewer apoptotic cells after myocardial-I/R than wild-type or <em>Trpc6</em>^−/− mice. Cardiomyocyte-specific knockdown of <em>Trpc1</em> using adeno-associated virus 9 mitigated myocardial I/R injury. Furthermore, <em>Trpc1</em> deficiency protected adult mouse ventricular myocytes (AMVMs) and HL-1 cells from death during hypoxia/reoxygenation (H/R) injury. RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species (ROS) generation in <em>Trpc1</em>^−/− cardiomyocytes. Among these genes, oxoglutarate dehydrogenase-like (<em>Ogdhl</em>) was markedly downregulated. Moreover, <em>Trpc1</em> deficiency impaired the calcineurin (CaN)/nuclear factor-kappa B (NF-κB) signaling pathway in AMVMs. Suppression of this pathway inhibited <em>Ogdhl</em> upregulation and ROS generation in HL-1 cells under H/R conditions. Chromatin immunoprecipitation assays confirmed NF-κB binding to the <em>Ogdhl</em> promoter. The cardioprotective effect of <em>Trpc1</em> deficiency was canceled out by overexpression of <em>NF</em><em>-</em><em>κB</em> and <em>Ogdhl</em> in cardiomyocytes. In conclusion, our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R, leading to increased Ca²⁺ influx into associated cardiomyocytes. Subsequently, this upregulates <em>Ogdhl</em> expression through the CaN/NF-κB signaling pathway, ultimately exacerbating ROS production and aggravating myocardial I/R injury.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 11","pages":"Pages 1309-1325"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2095177923002125/pdfft?md5=cdeedb4a5fc21b418ff326b95ef21b6c&pid=1-s2.0-S2095177923002125-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48803947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N, S, Br co-doped carbon dots: One-step synthesis and fluorescent detection of 6-mercaptopurine in tablet","authors":"Qi Wang, Ying Cheng, Lifeng Ding, Shengling Li, Jie Zhang, Yulan Niu, Ziye Jing","doi":"10.1016/j.jpha.2023.11.001","DOIUrl":"https://doi.org/10.1016/j.jpha.2023.11.001","url":null,"abstract":"Scheme of synthesis of N, S, Br-CDs and fluorescent detection of 6-MP. • A suitable detection method for 6-mercaptopurine (6-MP) was developed. • N, S, Br-carbon dots (N, S, Br-CDs) synthesized by one-step hydrothermal method. • The as-synthesized N, S, Br-CDs exhibited favorable fluorescence. • The fluorescence intensity of the N, S, Br-CDs was quenched by 6-MP. • The developed method is suitable for detecting 6-MP in real pharmaceutical samples.","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"20 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135454746","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":"Recent advancements in single-cell metabolic analysis for pharmacological research","authors":"Ying Hou,&nbsp;Hongren Yao,&nbsp;Jin-Ming Lin","doi":"10.1016/j.jpha.2023.08.014","DOIUrl":"10.1016/j.jpha.2023.08.014","url":null,"abstract":"<div><p>Cellular heterogeneity is crucial for understanding tissue biology and disease pathophysiology. Pharmacological research is being advanced by single-cell metabolic analysis, which offers a technique to identify variations in RNA, proteins, metabolites, and drug molecules in cells. In this review, the recent advancement of single-cell metabolic analysis techniques and their applications in drug metabolism and drug response are summarized. High-precision and controlled single-cell isolation and manipulation are provided by microfluidics-based methods, such as droplet microfluidics, microchamber, open microfluidic probe, and digital microfluidics. They are used in tandem with variety of detection techniques, including optical imaging, Raman spectroscopy, electrochemical detection, RNA sequencing, and mass spectrometry, to evaluate single-cell metabolic changes in response to drug administration. The advantages and disadvantages of different techniques are discussed along with the challenges and future directions for single-cell analysis. These techniques are employed in pharmaceutical analysis for studying drug response and resistance pathway, therapeutic targets discovery, and in vitro disease model evaluation.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 10","pages":"Pages 1102-1116"},"PeriodicalIF":8.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44867724","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":"Potentials of ribosomopathy gene as pharmaceutical targets for cancer treatment","authors":"Mengxin Wang, Stephen Vulcano, Changlu Xu, Renjian Xie, Weijie Peng, Jie Wang, Qiaojun Liu, Lee Jia, Zhi Li, Yumei Li","doi":"10.1016/j.jpha.2023.10.001","DOIUrl":"https://doi.org/10.1016/j.jpha.2023.10.001","url":null,"abstract":"Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality. Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic, collectively known as ribosomopathy genes. Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer. Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development. The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established. This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile, to excavate the potential role of these genes, which have not or rarely been reported in cancer, in the disease development across cancers. We plan to establish a theoretical framework between the ribosomopathy gene and cancer development, to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"2021 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135760593","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":"Histone deacetylase inhibitor pracinostat suppresses colorectal cancer by inducing CDK5-Drp1 signaling-mediated peripheral mitofission","authors":"Xiao-Ling Liang ,&nbsp;Lan Ouyang ,&nbsp;Nan-Nan Yu ,&nbsp;Zheng-Hua Sun ,&nbsp;Zi-Kang Gui ,&nbsp;Yu-Long Niu ,&nbsp;Qing-Yu He ,&nbsp;Jing Zhang ,&nbsp;Yang Wang","doi":"10.1016/j.jpha.2023.06.005","DOIUrl":"10.1016/j.jpha.2023.06.005","url":null,"abstract":"<div><p>Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells. Pharmacological induction of excessively asymmetric mitofission-associated cell death (MFAD) by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy. By screening a series of pan-inhibitors, we identified pracinostat, a pan-histone deacetylase (HDAC) inhibitor, as a novel MFAD inducer, that exhibited a significant anticancer effect on colorectal cancer (CRC) in vivo and in vitro. Pracinostat increased the expression of cyclin-dependent kinase 5 (CDK5) and induced its acetylation at residue lysine 33, accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynamin-related protein 1 (Drp1)-mediated mitochondrial peripheral fission. CRC cells with high level of CDK5 (CDK5-high) displayed midzone mitochondrial division that was associated with oncogenic phenotype, but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells. Mechanistically, pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor (MFF) to mitochondrial fission 1 protein (FIS1). Thus, our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells, which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 10","pages":"Pages 1168-1182"},"PeriodicalIF":8.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43502588","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":"Monoclonal antibody targeting mu-opioid receptor attenuates morphine tolerance via enhancing morphine-induced receptor endocytosis","authors":"Jia-Jia Zhang ,&nbsp;Chang-Geng Song ,&nbsp;Miao Wang ,&nbsp;Gai-Qin Zhang ,&nbsp;Bin Wang ,&nbsp;Xi Chen ,&nbsp;Peng Lin ,&nbsp;Yu-Meng Zhu ,&nbsp;Zhi-Chuan Sun ,&nbsp;Ya-Zhou Wang ,&nbsp;Jian-Li Jiang ,&nbsp;Ling Li ,&nbsp;Xiang-Min Yang ,&nbsp;Zhi-Nan Chen","doi":"10.1016/j.jpha.2023.06.008","DOIUrl":"10.1016/j.jpha.2023.06.008","url":null,"abstract":"<div><p>Morphine is a frequently used analgesic that activates the mu-opioid receptor (MOR), which has prominent side effects of tolerance. Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance, currently, there is no effective therapy to treat morphine tolerance. In the current study, we aimed to develop a monoclonal antibody (mAb) precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms. We successfully prepared a mAb targeting MOR, named 3A5C7, by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization, and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation. Treatment of two cell lines, HEK293T and SH-SY5Y, with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2 (GRK2)/β-arrestin2-dependent mechanism, as demonstrated by immunofluorescence staining, flow cytometry, Western blotting, coimmunoprecipitation, and small interfering ribonucleic acid (siRNA)-based knockdown. This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR. We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid. Western blot, enzyme-linked immunosorbent assays, and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase, the in vitro biomarker of morphine tolerance, via the GRK2/β-arrestin2 pathway. Furthermore, in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alleviated morphine tolerance in mice, and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence. Finally, intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway. Collectively, our study provided a therapeutic mAb, 3A5C7, targeting MOR to treat morphine tolerance, mediated by enhancing morphine-induced MOR endocytosis. The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 10","pages":"Pages 1135-1152"},"PeriodicalIF":8.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43084226","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}