检索结果-南通市图书馆

Sulfation of chondroitin and bile acids converges to antagonize Wnt/β-catenin signaling and inhibit APC deficiency-induced gut tumorigenesis

引用

Acta Pharmaceutica Sinica B 2024年第3期14卷 1241-1256页

作者： Pengfei Xu Yue Xi Jong-Won Kim Junjie Zhu Min Zhang Meishu Xu Songrong Ren Da Yang xiaochao ma Wen Xie Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Department of Hepatobiliary and Pancreatic Surgery Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China Department of Pharmacology&Chemical Biology University of PittsburghPittsburghPA 15261USA

Sulfation is a crucial and prevalent conjugation reaction involved in cellular processes and mammalian physiology.3’-Phosphoadenosine 5’-phosphosulfate(PAPS)synthase 2(PAPSS2)is the primary enzyme to generate the universal sulfonate donor PAPS.The involvement of PAPSS2-mediated sulfation in adenomatous polyposis coli(APC)mutation-promoted colonic carcinogenesis has not been reported.Here,we showed that the expression of PAPSS2 was decreased in human colon tumors along with cancer stages,and the lower expression of PAPSS2 was correlated with poor prognosis in advanced colon cancer.Gut epithelial-specific heterozygous Apc deficient and Papss2-knockout(Apc^(Δgut-Het)Papss2^(Δgut))mice were created,and the phenotypes were compared to the spontaneous intestinal tumorigenesis of Apc^(Δgut-Het)mice.Apc^(Δgut-Het)Papss2^(Δgutmice) were more sensitive to gut tumorigenesis,which was mechanistically accounted for by the activation of Wnt/β-catenin signaling pathway due to the suppression of chondroitin sulfation and inhibition of the farnesoid X receptor(FXR)-transducin-like enhancer of split 3(TLE3)gene regulatory axis.Chondroitin sulfate supplementation in Apc^(Δgut-Het)Papss2^(Δgutmice) alleviated intestinal tumorigenesis.In summary,we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids-FXR-TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/β-catenin signaling.Chondroitin sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis.

关键词： Colon cancer APC Wnt/b-catenin PAPSS2 Chondroitin sulfate Sulfation Bile acids FXR

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Activation of PXR causes drug interactions with Paxlovid in transgenic mice

引用

Acta Pharmaceutica Sinica B 2023年第11期13卷 4502-4510页

作者： Saifei Lei Alice Guo Jie Lu Qian Qi Aaron S.Devanathan Junjie Zhu xiaochao ma Center for Pharmacogenetics Department of Pharmaceutical SciencesSchool of PharmacyUniversity of PittsburghPittsburghPA 15261USA School of Nursing University of PennsylvaniaPhiladelphiaPA 19104USA Department of Pharmacy and Therapeutics School of PharmacyUniversity of PittsburghPittsburghPA 15261USA

Paxlovid is a nirmatrelvir(NMV)and ritonavir(RTV)co-packaged medication used for the treatment of coronavirus disease 2019(COVID-19).The active component of Paxlovid is NMV and RTV is a pharmacokinetic booster.Our work aimed to investigate the drug/herb-drug interactions associated with Paxlovid and provide mechanism-based guidance for the clinical use of Paxlovid.By using recombinant human cytochrome P450s(CYPs),we confirmed that CYP3A4 and 3A5 are the major enzymes responsible for NMV metabolism.The role of CYP3A in Paxlovid metabolism were further verified in Cyp3a-null mice,which showed that the deficiency of CYP3A significantly suppressed the metabolism of NMV and RTV.Pregnane X receptor(PXR)is a ligand-dependent transcription factor that upregulates CYP3A4/5 expression.We next explored the impact of drug-and herb-mediated PXR activation on Paxlovid metabolism in a transgenic mouse model expressing human PXR and CYP3A4/5.We found that PXR activation increased CYP3A4/5 expression,accelerated NMV metabolism,and reduced the systemic exposure of NMV.In summary,our work demonstrated that PXR activation can cause drug interactions with Paxlovid,suggesting that PXR-activating drugs and herbs should be used cautiously in COVID-19 patients receiving Paxlovid.

关键词： Paxlovid Nirmatrelvir Ritonavir Pregnane X receptor CYP3A4/5 Rifampicin Rhynchophylline Drug/herb-drug interactions

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Chemical basis of pregnane X receptor activators in the herbal supplement Gancao (licorice)

引用

Liver Research 2022年第4期6卷 251-257页

作者： Anqi Cheng Saifei Lei Junjie Zhu Jie Lu mary F.Paine Wen Xie xiaochao ma Center for Pharmacogenetics Department of Pharmaceutical SciencesSchool of PharmacyUniversity of PittsburghPittsburghPAUSA Department of Pharmaceutical Sciences College of Pharmacy and Pharmaceutical SciencesWashington State UniversitySpokaneWAUSA

Background and aims:The herbal supplement Gancao,also known as licorice,belongs to the genus Glycyrrhiza and has been used worldwide for its hepatoprotective effect.Recent studies have raised concerns about potential herb-drug interactions associated with Gancao via pregnane X receptor(PXR)-mediated induction of hepatic cytochrome P4503A4(CYP3A4).The current work aimed to determine the phytochemicals in Gancao that activate PXR and induce CYP3A4.Methods:DPX2 cells were used for cell-based PXR reporter assays.The phytochemicals in Gancao extract were identified using a metabolomics approach.The effects of PXR activators identified from in vitro studies were further investigated in PXR-and CYP3A4-humanized mouse models.Results:Gancao was verified to be a PXR-activating herb.Two major phytochemicals in Gancao,gly-cyrrhizin(GZ)and glycyrrhetinic acid(GA),did not activate PXR in the cell-based reporter assays.However,glabridin was shown to activate PXR in a dose-dependent manner.In vivo studies confirmed that GZ is not a PXR activator and glabridin is a weak PXR activator.Although GA did not active PXR in vitro,it induced CYP3A4 expression in a PXR-dependent manner in the PXR-and CYP3A4-humanized mice.

关键词： Gancao Licorice Glabridin Pregnane X receptor(PXR) Cytochrome P4503A4(CYP3A4) Herb-drug interactions

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Isoniazid metabolism and hepatotoxicity

引用

Acta Pharmaceutica Sinica B 2016年第5期6卷 384-392页

作者： Pengcheng Wang Komal Pradhan Xiao-bo Zhong xiaochao ma Center for Pharmacogenetics Department of Pharmaceutical SciencesSchool of PharmacyUniversity of Pittsburgh Department of Pharmaceutical Sciences School of PharmacyUniversity of Connecticut

Isoniazid(INH) is highly effective for the management of tuberculosis.However,it can cause liver injury and even liver failure.INH metabolism has been thought to be associated with INH-induced liver injury.This review... 详细信息

关键词： Isoniazid Metabolism Hepatotoxicity Anti-tuberculosis N-Acetyltransferase 2 Amidase

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Clinical perspectives of isoniazid-induced liver injury

引用

Liver Research 2021年第2期5卷 45-52页

作者： Saifei Lei Ruizhi Gu xiaochao ma Center for Pharmacogenetics Department of Pharmaceutical SciencesSchool of PharmacyUniversity of PittsburghPittsburghPAUSA

Isoniazid(INH)is a synthetic anti-mycobacterial agent used to treat active or latent tuberculosis(TB).INH has been in clinical use for nearly 70 years and remains broadly utilized at the front line of anti-TB treatment.However,the potential for liver damage and even fulminant liver failure during INH-based TB treatment presents a major challenge for TB control programs worldwide.In this review,we discuss the hepatotoxic effects of INH and provide an overview of the mechanisms and their applications in prediction and prevention of INH hepatotoxicity in clinical practice.

关键词： Hepatotoxicity Liver injury Isoniazid(INH) Tuberculosis(TB)

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

LC–MS-based metabolomics in profiling of drug metabolism and bioactivation

引用

Acta Pharmaceutica Sinica B 2012年第2期2卷 118-125页

作者： Feng Li Frank JGonzalez xiaochao ma Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKansas 66160USA Laboratory of Metabolism Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMaryland 20892USA

Since metabolism significantly affects drug safety and efficacy,determining the metabolic profile of a drug is a critical part of drug development.The application of an LC–MS-based metabolomic approach has gained more widespread use in identifying drug metabolites,developing metabolic maps and lending clues to mechanisms of bioactivation.Thus,the LC–MS-based metabolomic approach is a powerful tool for profiling of drug metabolism and bioactivation.

关键词： Metabolomics Drug metabolism Reactive metabolites Multivariate data analysis

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

放电等离子烧结Cu-15Ni-8Sn/石墨自润滑复合材料摩擦磨损性能研究

引用

摩擦学学报（中英文） 2024年第4期44卷 509-518页

作者：马文林刘益超王小超苏博兰州交通大学机电工程学院甘肃兰州730070 中国科学院兰州化学物理研究所中国科学院材料磨损与防护重点实验室甘肃兰州730000

以Cu-15Ni-8Sn合金为基体,石墨为润滑剂,采用放电等离子烧结技术制备了Cu-15Ni-8Sn/石墨自润滑复合材料.使用扫描电子显微镜、X射线衍射仪和万能试验机研究了复合材料的微观组织、物相组成和室温力学性能,通过球-盘式摩擦试验机测试复... 详细信息

以Cu-15Ni-8Sn合金为基体,石墨为润滑剂,采用放电等离子烧结技术制备了Cu-15Ni-8Sn/石墨自润滑复合材料.使用扫描电子显微镜、X射线衍射仪和万能试验机研究了复合材料的微观组织、物相组成和室温力学性能,通过球-盘式摩擦试验机测试复合材料的摩擦磨损性能,利用三维轮廓仪测量材料磨损体积,借助扫描电子显微镜对磨痕形貌进行表征.结果表明:向Cu-15Ni-8Sn基体材料中添加石墨后,材料的硬度明显降低;随着石墨含量的提高,复合材料的抗压强度逐渐降低.当添加质量分数为3%的石墨时,Cu-15Ni-8Sn/石墨自润滑复合材料的耐磨性最好,磨损率最小为3.0×10^(-6)mm^(3)/(N·m),其磨损机理主要以磨粒磨损为主.

关键词：自润滑复合材料 Cu-15Ni-8Sn 放电等离子烧结抗压强度磨粒磨损

来源：

维普期刊数据库

同方期刊数据库博看期刊评论

在线全文

学校读者我要写书评

暂无评论

Pregnane X receptor in drug-induced liver injury: Friend or foe?

引用

Liver Research 2018年第4期2卷 173-179页

作者： Amina I.Shehu xiaochao ma Center for Pharmacogenetics Department of Pharmaceutical SciencesSchool of PharmacyUniversity of PittsburghPittsburghPAUSA

The pregnane X receptor(PXR)is a ligand activated nuclear receptor that is highly expressed in the liver and regulates many cellular functions including drug metabolism,endobiotic metabolism,oxidative stress response,apoptosis,inflammation,cell proliferation and regeneration.PXR activation promotes drug-induced liver injury(DILI)through its ability to increase the expression of phaseⅠand phaseⅡdrug metabolizing enzymes.The PXR also increases lipid synthesis and fatty acid uptake into the liver,leading to lipid accumulation and steatosis.In recent years,PXR has been explored as an important target in DILI and liver diseases.This review will highlight the roles of PXR in modulating DILI.PXR polymorphisms that have been associated with DILI will also be discussed.

关键词： Pregnane X receptor(PXR) Drug-induced liver injury(DILI) Drug metabolism Endobiotic metabolism Oxidative stress response Apoptosis Inflammation Cell proliferation Cell regeneration

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice

引用

Acta Pharmaceutica Sinica B 2020年第1期10卷 171-185页

作者： Pei Wang Xueyan Shao Yifan Bao Junjie Zhu Liming Chen Lirong Zhang xiaochao ma Xiao-bo Zhong Department of Pharmacology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001China Department of Pharmaceutical Sciences School of PharmacyUniversity of ConnecticutStorrsCT 06269USA Department of Pharmaceutical Sciences School of PharmacyUniversity of PittsburghPittsburghPA 15261USA

The prevalence of obesity-associated conditions raises new challenges in clinical medication.Although altered expression of drug-metabolizing enzymes(DMEs)has been shown in obesity,the impacts of obese levels(overweight,obesity,and severe obesity)on the expression of DMEs have not been elucidated.Especially,limited information is available on whether parental obese levels affect ontogenic expression of DMEs in children.Here,a high-fat diet(HFD)and three feeding durations were used to mimic different obese levels in C57BL/6 mice.The hepatic expression of five nuclear receptors(NRs)and nine DMEs was examined.In general,a trend of induced expression of NRs and DMEs(except for Cyp2c29 and 3a11)was observed in HFD groups compared to low-fat diet(LFD)groups.Differentialeffects of HFD on the hepatic expression of DMEs were found in adult mice at different obese levels.Family-based dietary style of an HFD altered the ontogenic expression of DMEs in the offspring older than 15 days.Furthermore,obese levels of parental mice affected the hepatic expression of DMEs in offspring.Overall,the results indicate that obese levels affected expression of the DMEs in adult individuals and that of their children.Drug dosage might need to be optimized based on the obese levels.

关键词： Diet-induced obesity Overweight High-fat diet Drug-metabolizing enzymes Nuclear receptors Ontogenic expression

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

含氮碱基缓蚀剂在铜研磨抛光后清洗液中的应用

引用

集成电路应用 2024年第2期41卷 48-51页

作者：史筱超马丽王溯上海市集成电路关键工艺材料重点实验室上海201616 上海新阳半导体材料股份有限公司上海201616

阐述对比不同缓蚀剂配方对铜dummy片表面腐蚀抑制的影响,并辅助不同温度、时间、浓度下的不同缓蚀剂腐蚀速率,提出含有含氮碱基缓蚀剂配方的优势。对比不同缓释剂配方的清洗效果、表面粗糙度、对PVA清洗刷表面划伤的影响,进一步验证含... 详细信息

阐述对比不同缓蚀剂配方对铜dummy片表面腐蚀抑制的影响,并辅助不同温度、时间、浓度下的不同缓蚀剂腐蚀速率,提出含有含氮碱基缓蚀剂配方的优势。对比不同缓释剂配方的清洗效果、表面粗糙度、对PVA清洗刷表面划伤的影响,进一步验证含有含氮碱基缓蚀剂配方的PCMP样品,在碱性条件下表现最佳。可将晶圆表面铜层清洗干净,且对铜表面腐蚀起到有效抑制作用,降低表面粗糙度,延长Q-Time时间。分析PCMP处理后的晶圆表面SP2和XPS表征,验证Cu_(2)O可以有效延长Q-time时间。

关键词：集成电路制造 PCMP 缓蚀剂腐蚀晶圆清洗

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：