Current drug metabolism最新文献

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Influence of SLCO1B1 Polymorphisms on the Pharmacokinetics of Mycophenolic Acid in Renal Transplant Recipients. SLCO1B1多态性对肾移植受者霉酚酸药代动力学的影响
IF 2.3 4区 医学
Current drug metabolism Pub Date : 2023-01-01 DOI: 10.2174/1389200224666230124121304
Jiawen Liu, Yongqian Zhu, Jiexiu Zhang, Jintao Wei, Ming Zheng, Zeping Gui, Hao Chen, Li Sun, Zhijian Han, Jun Tao, Xiaobin Ju, Ruoyun Tan, Min Gu, Zijie Wang
{"title":"Influence of SLCO1B1 Polymorphisms on the Pharmacokinetics of Mycophenolic Acid in Renal Transplant Recipients.","authors":"Jiawen Liu,&nbsp;Yongqian Zhu,&nbsp;Jiexiu Zhang,&nbsp;Jintao Wei,&nbsp;Ming Zheng,&nbsp;Zeping Gui,&nbsp;Hao Chen,&nbsp;Li Sun,&nbsp;Zhijian Han,&nbsp;Jun Tao,&nbsp;Xiaobin Ju,&nbsp;Ruoyun Tan,&nbsp;Min Gu,&nbsp;Zijie Wang","doi":"10.2174/1389200224666230124121304","DOIUrl":"https://doi.org/10.2174/1389200224666230124121304","url":null,"abstract":"<p><strong>Objective: </strong>This study was designed to analyze the correlation between single nucleotide polymorphisms (SNP) related to drug metabolism and pharmacokinetics of mycophenolic acid (MPA) during long-term follow-up.</p><p><strong>Materials and method: </strong>A retrospective cohort study involving 71 renal transplant recipients was designed. Blood samples were collected to extract total DNAs, followed by target sequencing based on next-generation sequencing technology. The MPA area under the curve (AUC) was calculated according to the formula established in our center. The general linear model and linear regression model were used to analyze the association between SNPs and MPA AUC.</p><p><strong>Results: </strong>A total of 689 SNPs were detected in our study, and 90 tagger SNPs were selected after quality control and linkage disequilibrium analysis. The general linear model analysis showed that 9 SNPs significantly influenced MPA AUC. A forward linear regression was conducted, and the model with the highest identical degree (r<sup>2</sup>=0.55) included 4 SNPs (<i>SLCO1B1</i>: rs4149036 [P < 0.0001], ABCC2: rs3824610 [P = 0.005], POR: rs4732514 [P = 0.006], ABCC2: rs4148395 [P = 0.007]) and 6 clinical factors (age [P < 0.0001], gender [P < 0.0001], the incident of acute rejection (AR) [P = 0.001], albumin [P < 0.0001], duration after renal transplantation [P = 0.01], lymphocyte numbers [P = 0.026]). The most relevant SNP to MPA AUC in this model was rs4149036. The subgroup analysis showed that rs4149036 had a significant influence on MPA AUC in the older group (P = 0.02), high-albumin group (P = 0.01), male group (P = 0.046), and both within-36-month group (P = 0.029) and after-36-month group (P = 0.041). The systematic review included 4 studies, and 2 of them showed that the mutation in <i>SLCO1B1</i> resulted in lower MPA AUC, which was contrary to our study.</p><p><strong>Conclusion: </strong>A total of 4 SNPs (rs4149036, rs3824610, rs4148395, and rs4732514) were identified to be significantly correlated with MPA AUC. Rs4149036, located in <i>SLCO1B1</i>, was suggested to be the most relevant SNP to MPA AUC, which had a stronger influence on recipients who were elder, male, or with high serum albumin. Furthermore, 6 clinical factors, including age, gender, occurrence of acute rejection, serum albumin, time from kidney transplantation, and blood lymphocyte numbers, were found to affect the concentration of MPA.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"24 2","pages":"114-123"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1
DNA-based Nanomaterials in the Immunotherapy. 免疫治疗中基于DNA的纳米材料。
IF 2.3 4区 医学
Current drug metabolism Pub Date : 2023-01-01 DOI: 10.2174/1389200224666230413082047
Hongxiao Huang, Shaojingya Gao, Xiaoxiao Cai
{"title":"DNA-based Nanomaterials in the Immunotherapy.","authors":"Hongxiao Huang,&nbsp;Shaojingya Gao,&nbsp;Xiaoxiao Cai","doi":"10.2174/1389200224666230413082047","DOIUrl":"10.2174/1389200224666230413082047","url":null,"abstract":"<p><strong>Background: </strong>Nucleic acid is a genetic material that shows great potential in a variety of biological applications. With the help of nanotechnology, the fabrication of DNA-based nanomaterials has emerged. From genetic DNA to non-genetic functional DNA, from single-layer and flat structure to multi-layer and complex structure, and from two-dimensional to three-dimensional structure, DNA-based nanomaterials have been greatly developed, bringing significant changes to our lives. In recent years, the research of DNA-based nanomaterials for biological applications has developed rapidly.</p><p><strong>Methods: </strong>We extensively searched the bibliographic database for a research article on nanotechnology and immunotherapy and further discussed the advantages and drawbacks of current DNA-based nanomaterials in immunotherapy. By comparing DNA-based nanomaterials with traditional biomaterials applied in immunotherapy, we found that DNA-based nanomaterials are a promising candidate material in Immunotherapy.</p><p><strong>Results: </strong>Due to the unrivaled editability and biocompatibility, DNA-based nanomaterials are not only investigated as therapeutic particles to influence cell behavior but also as drug delivery systems to treat a variety of diseases. Moreover, when DNA-based nanomaterials are loaded with therapeutic agents, including chemical drugs and biomolecules, which significantly enhance the therapeutic effects, DNA-based nanomaterials have great potential in immunotherapy.</p><p><strong>Conclusion: </strong>This review summarizes the structural development history of DNA-based nanomaterials and their biological applications in immunotherapy, including the potential treatment of cancer, autoimmune diseases, and inflammatory diseases.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"367-384"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9317666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Recent Advances in Novel Recombinant RNAs for Studying Post-transcriptional Gene Regulation in Drug Metabolism and Disposition. 用于研究药物代谢和处置中转录后基因调控的新型重组 RNA 的最新进展。
IF 2.1 4区 医学
Current drug metabolism Pub Date : 2023-01-01 DOI: 10.2174/1389200224666230425232433
Mei-Juan Tu, Ai-Ming Yu
{"title":"Recent Advances in Novel Recombinant RNAs for Studying Post-transcriptional Gene Regulation in Drug Metabolism and Disposition.","authors":"Mei-Juan Tu, Ai-Ming Yu","doi":"10.2174/1389200224666230425232433","DOIUrl":"10.2174/1389200224666230425232433","url":null,"abstract":"<p><p>Drug-metabolizing enzymes and transporters are major determinants of the absorption, disposition, metabolism, and excretion (ADME) of drugs, and changes in ADME gene expression or function may alter the pharmacokinetics/ pharmacodynamics (PK/PD) and further influence drug safety and therapeutic outcomes. ADME gene functions are controlled by diverse factors, such as genetic polymorphism, transcriptional regulation, and coadministered medications. MicroRNAs (miRNAs) are a superfamily of regulatory small noncoding RNAs that are transcribed from the genome to regulate target gene expression at the post-transcriptional level. The roles of miRNAs in controlling ADME gene expression have been demonstrated, and such miRNAs may consequently influence cellular drug metabolism and disposition capacity. Several types of miRNA mimics and small interfering RNA (siRNA) reagents have been developed and widely used for ADME research. In this review article, we first provide a brief introduction to the mechanistic actions of miRNAs in post-transcriptional gene regulation of drug-metabolizing enzymes, transporters, and transcription factors. After summarizing conventional small RNA production methods, we highlight the latest advances in novel recombinant RNA technologies and applications of the resultant bioengineered RNA (BioRNA) agents to ADME studies. BioRNAs produced in living cells are not only powerful tools for general biological and biomedical research but also potential therapeutic agents amenable to clinical investigations.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"24 3","pages":"175-189"},"PeriodicalIF":2.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10825985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10132015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Quantification of Vitamin D at Different Levels of Clinical Worsening of COVID-19. COVID-19临床恶化不同程度患者维生素D的定量分析
IF 2.3 4区 医学
Current drug metabolism Pub Date : 2023-01-01 DOI: 10.2174/1389200224666230109162132
Lai Yu Tsun, Thaciane Alkmim Bibo, Fernando Luiz Affonso Fonseca, Glaucia Luciano da Veiga, Ana Carolina Macedo Gaiatto, Nicolle de Godoy Moreira E Costa, Joyce Regina Raimundo, Matheus Moreira Perez, Thaís Gascón, Fulvio Alexandre Scorza, Carla Alessandra Scorza, Helena Nader, Manoel João Batista Castello Girão, Beatriz da Costa Aguiar Alves, Edimar Cristiano Pereira
{"title":"Quantification of Vitamin D at Different Levels of Clinical Worsening of COVID-19.","authors":"Lai Yu Tsun,&nbsp;Thaciane Alkmim Bibo,&nbsp;Fernando Luiz Affonso Fonseca,&nbsp;Glaucia Luciano da Veiga,&nbsp;Ana Carolina Macedo Gaiatto,&nbsp;Nicolle de Godoy Moreira E Costa,&nbsp;Joyce Regina Raimundo,&nbsp;Matheus Moreira Perez,&nbsp;Thaís Gascón,&nbsp;Fulvio Alexandre Scorza,&nbsp;Carla Alessandra Scorza,&nbsp;Helena Nader,&nbsp;Manoel João Batista Castello Girão,&nbsp;Beatriz da Costa Aguiar Alves,&nbsp;Edimar Cristiano Pereira","doi":"10.2174/1389200224666230109162132","DOIUrl":"https://doi.org/10.2174/1389200224666230109162132","url":null,"abstract":"<p><strong>Introduction and aim: </strong>Vitamin D is the name given to a group of lipid-soluble steroidal substances of physiological importance in the body, especially in bone metabolism. The active form of vitamin D is believed to have immunomodulatory effects on immune system cells, especially T lymphocytes, as well as on the production and action of several cytokines and on the expression of potent antimicrobial peptides in epithelial cells that line the respiratory tract, playing an important role in protecting the lung from infections. The aim of this study was to assess vitamin D levels in patients with COVID-19 in healthcare service and to verify that these levels are adequate to protect the progression of this infection.</p><p><strong>Methods: </strong>The aim of this observational study was to evaluate the serum concentration of vitamin D in 300 patients suspected of being infected with COVID-19, treated at Basic Health Units (BHUs) and at the Hospital Complex in the municipality of São Bernardo do Campo.</p><p><strong>Results: </strong>294 patients were included, 195 (66%) of which tested positive for COVID-19 and 99 (34%) negative for COVID-19. Among the patients in the positive group, 163 patients were in the mild group (84%); 22 patients in the moderate group (11%); 8 patients in the severe group (4%), and 2 patients in the deceased group (1%).</p><p><strong>Conclusion: </strong>For the patients in this study, no association was observed for the protective factor of vitamin D against COVID-19 infection, and its role in controlling the clinical staging of the disease was not verified.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"23 14","pages":"1124-1129"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10856861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
A Systematic Review of Linezolid Pharmacokinetics/Pharmacodynamics in Patients Undergoing Continuous Renal Replacement Therapy: Does One Size Fit All? 连续肾替代治疗患者利奈唑胺药代动力学/药效学的系统评价:一个标准适合所有患者吗?
IF 2.3 4区 医学
Current drug metabolism Pub Date : 2023-01-01 DOI: 10.2174/1389200224666221228144117
Yao Liu, Xu-Hua Ge, Hong-Li Guo, Feng Chen, Yong Zhang, Jing Xu, Xing Ji, Hong-Jun Miao
{"title":"A Systematic Review of Linezolid Pharmacokinetics/Pharmacodynamics in Patients Undergoing Continuous Renal Replacement Therapy: Does One Size Fit All?","authors":"Yao Liu,&nbsp;Xu-Hua Ge,&nbsp;Hong-Li Guo,&nbsp;Feng Chen,&nbsp;Yong Zhang,&nbsp;Jing Xu,&nbsp;Xing Ji,&nbsp;Hong-Jun Miao","doi":"10.2174/1389200224666221228144117","DOIUrl":"https://doi.org/10.2174/1389200224666221228144117","url":null,"abstract":"<p><strong>Background: </strong>Selection of the optimal antimicrobial posology in critically ill patients remains a challenge, especially in patients with sepsis who undergo continuous renal replacement therapy (CRRT). This systematic review aimed to analyze factors that influence the extracorporeal removal of linezolid.</p><p><strong>Methods: </strong>A comprehensive search was performed to identify studies published up to March 2022 in PubMed, MEDLINE and EMBASE databases. Studies involving adults receiving CRRT and treatment with linezolid were considered eligible if the CRRT setting and linezolid's pharmacokinetic parameters were clearly mentioned.</p><p><strong>Results: </strong>Six out of 110 potentially relevant studies were included. A total of 101 treatments were identified among 97 enrolled patients. Our analysis showed that continuous veno-venous hemodiafiltration (CVVHDF) was the most frequential used modality (52 cases). Despite distribution volume, the clearance (CL) of linezolid in these studies had large variability. Extracorporeal linezolid removal may be markedly impacted by CRRT dose. There is significant between-subject variability in the probability of pharmacokinetics-pharmacodynamics (PK-PD) target attainment of patients treated with CRRT.</p><p><strong>Conclusion: </strong>Dose adjustment, shortening the dosing interval, and continuous infusion were proposed as regimen optimization. Therapeutic drug monitoring is recommended due to the high variability of linezolid exposure among patients with CRRT, specifically for those whose bodyweight is high, renal function is preserved, and the MIC of infection bacteria is above 2 μg/mL.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"24 1","pages":"70-77"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9842265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1
Worldwide Prevalence of Polypharmacy: A Systematic Review. 世界范围内多药治疗的流行率:一项系统综述。
IF 2.3 4区 医学
Current drug metabolism Pub Date : 2023-01-01 DOI: 10.2174/1389200224666230727093010
Beatriz Dias Januário, Natália Silva Mafra, Humberto de Souza Silva, Isabella Monteiro Carvalho, Ana Luiza Sobreira Sena, Ana Paula Gomes Soares Pereira, Newton Santos de Faria Júnior, Helton Oliveira Campos
{"title":"Worldwide Prevalence of Polypharmacy: A Systematic Review.","authors":"Beatriz Dias Januário,&nbsp;Natália Silva Mafra,&nbsp;Humberto de Souza Silva,&nbsp;Isabella Monteiro Carvalho,&nbsp;Ana Luiza Sobreira Sena,&nbsp;Ana Paula Gomes Soares Pereira,&nbsp;Newton Santos de Faria Júnior,&nbsp;Helton Oliveira Campos","doi":"10.2174/1389200224666230727093010","DOIUrl":"10.2174/1389200224666230727093010","url":null,"abstract":"<p><strong>Introduction: </strong>The present study has compiled the prevalence of polypharmacy worldwide and assessed the prevalence of polypharmacy in different populations, including community-dwelling individuals, hospitalized patients, and institutionalized patients.</p><p><strong>Methods: </strong>This systematic review was conducted and reported according to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. A systematic search of electronic databases, including PubMed, Web of Science, and Scielo, was performed in March 2021 without any date and language restrictions. Combinations of the following keywords were used for the search strategy: polypharmacy OR multiple medications OR multiple medicines OR multiple drug AND prevalence. Based on the search and inclusion criteria, two hundred and eight studies (73,076,167 individuals) were selected for inclusion in the systematic review. It was observed that there is a wide variation in the prevalence of polypharmacy between studies.</p><p><strong>Results: </strong>The prevalence of polypharmacy was found to be 30.2%, 61.7%, and 56.9% for community-dwelling individuals, hospitalized patients, and institutionalized patients, respectively.</p><p><strong>Conclusion: </strong>Based on the analyses, this systematic review has demonstrated a wide variation in the prevalence of polypharmacy between studies and countries and a high prevalence of polypharmacy in institutionalized and hospitalized patients.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"568-586"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9879273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Psychoactive Substances, New Behaviours, New Drug-drug Interactions: Pharmacology of a Slam Session. 新的精神活性物质,新的行为,新的药物-药物相互作用:一个大满贯会议的药理学。
IF 2.3 4区 医学
Current drug metabolism Pub Date : 2023-01-01 DOI: 10.2174/1389200224666230228103922
Benoit Schreck, Marion Istvan, Marylène Guerlais, Edouard-Jules Laforgue, Marie Gérardin, Marie Grall-Bronnec, Aurélie Aquizerate, Caroline Victorri-Vigneau
{"title":"New Psychoactive Substances, New Behaviours, New Drug-drug Interactions: Pharmacology of a Slam Session.","authors":"Benoit Schreck,&nbsp;Marion Istvan,&nbsp;Marylène Guerlais,&nbsp;Edouard-Jules Laforgue,&nbsp;Marie Gérardin,&nbsp;Marie Grall-Bronnec,&nbsp;Aurélie Aquizerate,&nbsp;Caroline Victorri-Vigneau","doi":"10.2174/1389200224666230228103922","DOIUrl":"https://doi.org/10.2174/1389200224666230228103922","url":null,"abstract":"<p><strong>Background: </strong>Slamming has been increasing internationally for ten years, mostly among men who have sex with men. Slamming consists of injecting psychostimulants (including new psychoactive substances-NPS) intravenously to increase sexual performance.</p><p><strong>Objective: </strong>The objective of our work was to analyse drug-drug interactions related to slamming.</p><p><strong>Methods: </strong>Drawing upon a reported case of a slam session describing hour by hour the intake of substances, we performed a drug-interaction analysis using international references and a comprehensive literature review. High doses of sildenafil, GBL and 3-MMC were reported during the 40-hour session described. The specific drug-interaction research was performed using 9 references and 65 of the 209 records identified in the literature review.</p><p><strong>Results: </strong>Pharmacological data regarding nonmedicated substances were scarce. Regarding pharmacodynamics, the risk was high at the cardiovascular level and was related to the vasodilatation effect of sildenafil and the adrenergic and serotoninergic properties of stimulants; this risk may increase with usual treatment (involving other vasodilators or central depressants). Regarding pharmacokinetics, the major interactions concerned metabolism by CYP3A4 and CYP2C9, leading to interactions, particularly with HIV medication.</p><p><strong>Conclusion: </strong>This innovative work provides pharmacological information on drugs that are commonly used in slamming, allowing the development of effective medical-management protocols and the provision of risk-reduction counselling.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"24 2","pages":"80-91"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9921258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Folate Targeting Peptide Conjugates for Inflammatory Response Suppression. 叶酸靶向肽偶联物抑制炎症反应。
IF 2.3 4区 医学
Current drug metabolism Pub Date : 2023-01-01 DOI: 10.2174/1389200224666230419090052
Elizabeth Ruff, Scott Poh
{"title":"Folate Targeting Peptide Conjugates for Inflammatory Response Suppression.","authors":"Elizabeth Ruff,&nbsp;Scott Poh","doi":"10.2174/1389200224666230419090052","DOIUrl":"https://doi.org/10.2174/1389200224666230419090052","url":null,"abstract":"<p><strong>Background and objective: </strong>Protein kinases known as mitogen-activated protein kinases (MAPKs) are responsible for regulating a wide variety of physiological cell responses by generating and release of inflammatory mediators. Suppressing these inflammatory mediators can be utilized to control the propagation of inflammation. During the course of this research, we created folate-targeted MK2 inhibitor conjugates and analyzed the antiinflammatory effects of these compounds.</p><p><strong>Methods: </strong>Using RAW264.7 cells, which are generated from murine macrophages, as an in vitro model. We synthesize and evaluated a folate linked peptide MK2 inhibitor. The cytotoxicity was assessed using the ELISA kits, CCK- 8 test kit, NO concentration and inflammatory factors TNF-, IL-1, and IL-6.</p><p><strong>Results: </strong>The cytotoxicity assay results suggested that the concentration for MK2 inhibitors less than 50.0 μM be non-toxic. The ELISA Kits also demonstrated that MK2 peptide inhibitor treatment significantly decreased the content of NO, TNF-, IL-1, and IL-6 in LPS-stimulated RAW264.7 cells. It was also demonstrated that a folate-targeted MK2 inhibitor was more effective than a non-targeted inhibitor.</p><p><strong>Conclusion: </strong>This experiment demonstrates that LPS-induced macrophages can produce oxidative stress and inflammatory mediators. According to our research, pro-inflammatory mediators can be reduced by targeting folate receptor- positive (FR+) macrophages with an FR-linked anti-inflammatory MK2 peptide inhibitor in vitro, and the uptake was FR-specific.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"24 4","pages":"283-289"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10472891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
The Influences and Mechanisms of High-altitude Hypoxia Exposure on Drug Metabolism. 高原缺氧暴露对药物代谢的影响及其机制。
IF 2.3 4区 医学
Current drug metabolism Pub Date : 2023-01-01 DOI: 10.2174/1389200224666221228115526
Anpeng Zhao, Wenbin Li, Rong Wang
{"title":"The Influences and Mechanisms of High-altitude Hypoxia Exposure on Drug Metabolism.","authors":"Anpeng Zhao,&nbsp;Wenbin Li,&nbsp;Rong Wang","doi":"10.2174/1389200224666221228115526","DOIUrl":"https://doi.org/10.2174/1389200224666221228115526","url":null,"abstract":"<p><strong>Background: </strong>The special environment of high-altitude hypoxia not only changes the physiological state of the body but also affects the metabolic process of many drugs, which may affect the safety and efficacy of these drugs. The number of drugs is huge, so it is not wise to blindly repeat the pharmacokinetic studies of all of them on the plateau. Mastering the law of drug metabolism on the plateau is conducive to the comprehensive development of rational drug use on the plateau. Therefore, it is very important to determine the impacts and elucidate the mechanism of drug metabolism in hypobaric hypoxia conditions.</p><p><strong>Methods: </strong>In this review, we searched published studies on changes in drug metabolism in hypoxia conditions to summarize and analyze the mechanisms by which hypoxia alters drug metabolism.</p><p><strong>Results: </strong>Although the reported effects of high-altitude hypoxia on drug metabolism are sometimes controversial, metabolism kinetics for most of the tested drugs are found to be affected. Mechanism studies showed that the major reasons causing metabolism changes are: regulated drug-metabolizing enzymes expression and activity mediated by HIF-1, nuclear receptors and inflammatory cytokines, and change in direct or indirect effects of intestinal microflora on drug metabolism by itself or the host mediated by microflora-derived drug-metabolizing enzymes, metabolites, and immunoregulation.</p><p><strong>Conclusion: </strong>Altered enzyme expression and activity in the liver and altered intestinal microflora are the two major reasons to cause altered drug metabolism in hypoxia conditions.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"24 3","pages":"152-161"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10095164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1
Application of Nucleic Acid Nanomaterials in the Treatment of Endocrine and Metabolic Diseases. 核酸纳米材料在内分泌和代谢疾病治疗中的应用。
IF 2.3 4区 医学
Current drug metabolism Pub Date : 2023-01-01 DOI: 10.2174/1389200224666230410111015
Qiang Zhu, Yuping Xie, Ting Fu, Chengji Shi, Long Bai, Lin Liu, Jingang Xiao
{"title":"Application of Nucleic Acid Nanomaterials in the Treatment of Endocrine and Metabolic Diseases.","authors":"Qiang Zhu,&nbsp;Yuping Xie,&nbsp;Ting Fu,&nbsp;Chengji Shi,&nbsp;Long Bai,&nbsp;Lin Liu,&nbsp;Jingang Xiao","doi":"10.2174/1389200224666230410111015","DOIUrl":"10.2174/1389200224666230410111015","url":null,"abstract":"<p><p>Endocrine and metabolic diseases are the most prevalent chronic diseases globally, posing the greatest hazard to human health. Although various medications are applied in treating endocrine and metabolic illnesses, numerous obstacles exist to overcome. Nucleic acid nanomaterials are novel materials synthesized and engineered in the laboratory. In this case, Nucleic acids are employed as non-biological nanomaterials instead of serving as carriers of genetic information in live cells. Because of their high biocompatibility and editability, nucleic acid nanomaterials were frequently employed in disease diagnosis and therapy. In this review, recent developments and new viewpoints on nucleic acid nanomaterials are highlighted in the fields of diabetes mellitus and other endocrine and metabolic diseases.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"385-392"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9273336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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