检索结果-南通市图书馆

Biochemical mechanisms in drug-induced liver injury:Certainties and doubts

World Journal of Gastroenterology 2009年第39期15卷 4865-4876页

作者： Ignazio Grattagliano Leonilde Bonfrate Catia V Diogo Helen H wang David QH Wang Piero Portincasa Clinica Medica "A.Murri" Dipartimento di Medicina Interna e Medicina PubblicaUniversity of Bari Medical School Department of Zoology Center for Neurosciences and Cell BiologyUniversity of Coimbra Department of Medicine Liver Center and Gastroenterology DivisionBeth Israel Deaconess Medical CenterHarvard Medical School and Harvard Digestive Diseases Center

Drug-induced liver injury is a significant and still unresolved clinical problem.Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development.Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites.Aging,preexisting liver disease,enzyme induction or inhibition,genetic variances,local O2 supply and,above all,the intrinsic molecular properties of the drug may affect this process.Necrotic death follows antioxidant consumption and oxidation of intracellular proteins,which determine increased permeability of mitochondrial membranes,loss of potential,decreased ATP synthesis,inhibition of Ca2+-dependent ATPase,reduced capability to sequester Ca2+ within mitochondria,and membrane bleb formation.Conversely,activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis.Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage.Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis,in which different HLA genotypes might play a major role.This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage.Future perspectives including new frontiers for research are discussed.

关键词：生化机制肝损伤药物性免疫系统激活肝细胞损伤毒性机制肝脏疾病抗氧化剂

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

Therapy of gallstone disease:What it was,what it is,what it will be

引用

World Journal of Gastrointestinal Pharmacology and Therapeutics 2012年第2期3卷 7-20页

作者： Piero Portincasa Agostino Di Ciaula Leonilde Bonfrate David QH Wang Department of Biomedical Sciences and Human Oncology Clinica Medica "A.Murri"University of Bari Medical SchoolPiazza Giulio Cesare 11Policlinico70124 BariItaly Division of Internal Medicine Hospital of Bisceglievia Bovio 27970052 Bisceglie (Bari)Italy Division of Gastroenterology and Hepatology Department of Internal MedicineEdward Doisy Research CenterSaint Louis University School of MedicineSt.LouisMO 63104United States

Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic factors.Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones,new perspectives regarding medical therapy of cholelithiasis are currently under discussion,also taking into account the pathogenesis of gallstones,the natural history of the disease and the analysis of the overall costs of therapy.A careful selection of patients may lead to successful nonsurgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones.The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations,suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe),or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis,might be proposed as additional approaches for treating cholesterol gallstones.In this review we discuss old,recent and future perspectives on medical treatment of cholesterol cholelithiasis.

关键词： Gallstones Dissolution therapy Cholecystectomy Bile acids Ezetimibe Statins Gallbladder Bile Nuclear receptors

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

Silybin counteracts lipid excess and oxidative stress in cultured steatotic hepatic cells

引用

World Journal of Gastroenterology 2016年第26期22卷 6016-6026页

作者： Giulia Vecchione Elena Grasselli Adriana Voci Francesca Baldini Ignazio Grattagliano David QH Wang Piero Portincasa Laura Vergani DISTAV Department of Earth Environment and Life Sciences University of Genova Department of Biomedical Sciences and Human Oncology University School of Medicine Department of Internal Medicine Division of Gastroenterology and Hepatology Saint Louis University School of Medicine

AIM: To investigate in vitro the therapeutic effect and mechanisms of silybin in a cellular model of hepatic steatosis.METHODS: Rat hepatoma Fa O cells were loaded with lipids by exposure to 0.75 mmol/L oleate/palmitate for 3 h to mimic liver steatosis. Then, the steatotic cells were incubated for 24 h with different concentrations(25 to 100 μmol/L) of silybin as phytosome complex with vitamin E. The effects of silybin on lipid accumulation and metabolism, and on indices of oxidative stress were evaluated by absorption and fluorescence microscopy, quantitative real-time PCR, Western blot, spectrophotometric and fluorimetric assays.RESULTS: Lipid-loading resulted in intracellular triglyceride(TG) accumulation inside lipid droplets, whose number and size increased. TG accumulation was mediated by increased levels of peroxisome proliferator-activated receptors(PPARs) and sterol regulatory element-binding protein-1c(SREBP-1c). The lipid imbalance was associated with higher production of reactive oxygen species(ROS) resulting in increased lipid peroxidation, stimulation of catalase activity and activation of nuclear factor kappa-B(NF-κB). Incubation of steatotic cells with silybin 50 μmol/L significantly reduced TG accumulation likely by promoting lipid catabolism and by inhibiting lipogenic pathways, as suggested by the changes in carnitine palmitoyltransferase 1(CPT-1), PPAR and SREBP-1c levels. The reduction in fat accumulation exerted by silybin in the steatotic cells was associated with the improvement of the oxidative imbalance caused by lipid excess as demonstrated by the reduction in ROS content, lipid peroxidation, catalase activity and NF-κB activation.CONCLUSION: We demonstrated the direct antisteatotic and anti-oxidant effects of silybin in steatotic cells, thus elucidating at a cellular level the encouraging results demonstrated in clinical and animal studies.

关键词： Non-alcoholic fatty liver disease Steatotic hepatocytes Silybin Lipid metabolism Oxidative stress Li

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

A silybin-phospholipids complex counteracts rat fatty liver degeneration and mitochondrial oxidative changes

引用

World Journal of Gastroenterology 2013年第20期19卷 3007-3017页

作者： Ignazio Grattagliano Catia V Diogo Maria Mastrodonato Ornella de Bari Michele Persichella David QH Wang Adriana Liquori Domenico Ferri Maria Rosaria Carratù Paulo J Oliveira Piero Portincasa Section of Internal Medicine Department of Interdisciplinary MedicineUniversity of Bari70124 BariItaly Center for Neuroscience and Cell Biology Largo Marques de PombalUniversity of CoimbraP-3004-517 CoimbraPortugal Laboratory of Histology and Comparative Anatomy Department of Animal and Environmental BiologyUniversity of Bari70125 BariItaly Division of Gastroenterology and Hepatology Department of Internal MedicineEdward Doisy Research CenterSaint Louis University School of MedicineSaint LouisMO 63104United States Department of Pharmacology and Human Physiology University of Bari70124 BariItaly

AIM:To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidative alterations and lipids accumulation in fatty hepatocytes.METHODS:Silybin-phospholipid complex containing vitamin E(Realsil) was daily administered by gavage(one pouch diluted in 3 mL of water and containing 15 mg vitamin E and 47 mg silybin complexed with phospholipids) to rats fed a choline-deprived(CD) or a high fat diet [20% fat,containing 71% total calories as fat,11% as carbohydrate,and 18% as protein,high fat diet(HFD)] for 30 d and 60 d,respectively.The control group was fed a normal semi-purified diet containing adequate levels of choline(35% total calories as fat,47% as carbohydrate,and 18% as protein).Circulating and hepatic redox active and nitrogen regulating molecules(thioredoxin,glutathione,glutathione peroxidase),NO metabolites(nitrosothiols,nitrotyrosine),lipid peroxides [malondialdehyde-thiobarbituric(MDA-TBA)],and pro-inflammatory keratins(K-18) were measured on days 0,7,14,30,and 60.Mitochondrial respiratory chain proteins and the extent of hepatic fatty infiltration were evaluated.RESULTS:Both diet regimens produced liver steatosis(50% and 25% of liver slices with CD and HFD,respectively) with no signs of necro-inflammation:fat infiltration ranged from large droplets at day 14 to disseminated and confluent vacuoles resulting in microvesicular steatosis at day 30(CD) and day 60(HFD).In plasma,thioredoxin and nitrosothiols were not significantly changed,while MDA-TBA,nitrotyrosine(from 6 ± 1 nmol/L to 14 ± 3 nmol/L day 30 CD,P < 0.001,and 12 ± 2 nmol/L day 60 HFD,P < 0.001),and K-18(from 198 ± 20 to 289 ± 21 U/L day 30 CD,P < 0.001,and 242 ± 23 U/L day 60 HFD,P < 0.001) levels increased significantly with ongoing steatosis.In the liver,glutathione was decreased(from 34.0 ± 1.3 to 25.3 ± 1.2 nmol/mg prot day 30 CD,P < 0.001,and 22.4 ± 2.4 nmol/mg prot day 60 HFD,P < 0.001),while thioredoxin and glutathione peroxidase were initially increased and then decreased.Nitrosothiols were constantly increas

关键词： Fatty liver Glutathione Lipid peroxidation Nitrosothiols Nitrotyrosine Thioredoxin

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

Precision antiplatelet therapy for the prevention of ischaemic stroke

引用

Stroke & Vascular Neurology 2022年第2期7卷 89-91页

作者： david wang Neurovascular Division Department of NeurologyBarrow Neurological InstituteSt.Joseph's Hospital and Medical CenterPhoenixArizonaUSA

Stroke happens to people of all ages and has become the leading cause of disability in the world.1 It is also the leading cause of death in China and fifth-leading cause of death in the USA.23 Prevention of stroke is the best treatment.The use of antiplatelet therapy is one of the main prevention strategies.Aspirin is the only antiplatelet drug indicated for primary or secondary stroke prevention.Since the invention of aspirin nearly 120 years ago,more antiplatelet agents are available.Clinicians can select one antiplatelet drug or the combination for a specific patient with a specific subtype of ischaemic stroke.This kind of precision antiplatelet therapy can maximise the benefit and lower the risk of haemorrhagic complications.

关键词： prevention death Aspirin

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

Burst mode enabled ultrafast laser inscription inside gallium arsenide

引用

International Journal of Extreme Manufacturing 2022年第4期4卷 179-187页

作者： Andong wang Pol Sopeña david Grojo Aix-Marseille University CNRSLP3UMR734113009 MarseilleFrance

Ultrafast laser inscription(ULI)inside semiconductors offers new perspectives for 3D monolithic structures to be fabricated and new functionalities to be added in electronic and photonic microdevices.However,important challenges remain because of nonlinear effects such as strong plasma generation that distort the energy delivery at the focal point when exposing these materials to intense infrared light.Up to now,the successful technological demonstrations have primarily concentrated on silicon(Si).In this paper,we target at another important semiconductor:gallium arsenide(GaAs).With nonlinearities higher than those of Si,3D-machining of GaAs with femtosecond pulses becomes even harder.However,we show that the difficulty can be circumvented by burst-mode irradiation.We generate and apply trains of pulses at terahertz repetition rates for efficient pulse-to-pulse accumulation of laser-induced free carriers in the focal region,while avoiding an overdose of prefocal excitations.The superior performance of burst-mode irradiation is confirmed by a comparative study conducted with infrared luminescence microscopy.The results indicate a successful reduction of the plasma density in the prefocal region so that higher pulse energy reaches the focal spot.The same method is applied to identify optimum irradiation conditions considering particular cases such as asymmetric pulse trains and aberrated beams.With 64-pulse trains,we successfully manage to cross the writing threshold providing a solution for ULI inside GaAs.The application potential is finally illustrated with a stealth dicing demonstration by taking benefit of the burst mode.The irradiation method opens wide possibilities for 3D structuring inside GaAs by ULI.

关键词： laser processing ultrafast laser inscription THz-repetition-rate burst semiconductors gallium arsenide

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

On the complexity of computing Markov perfect equilibrium in general-sum stochastic games

引用

National Science Review 2023年第1期10卷 288-301页

作者： Xiaotie Deng Ningyuan Li david Mguni Jun wang Yaodong Yang Center on Frontiers of Computing Studies School of Computer Science Peking University Center for Multi-Agent Research Institute for AI Peking University Huawei UK Computer Science University College London

Similar to the role of Markov decision processes in reinforcement learning,Markov games(also called stochastic games) lay down the foundation for the study of multi-agent reinforcement learning and se quential agent interactions.We introduce approximate Markov perfect equilibrium as a solution to the computational problem of finite-state sto chastic games repeated in the infinite horizon and prove its PPAD-completeness.This solution concept preserves the Markov perfect property and opens up the possibility for the success of multi-agent reinforcement learning algorithms on static two-player games to be extended to multi-agent dynamic games,expanding the reign of the PPAD-complete class.

关键词： Markov game multi-agent reinforcement learning Markov perfect equilibrium PPAD-completeness stochastic game

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Ultrafast Laser Writing Deep inside Silicon with THz-Repetition-Rate Trains of Pulses

引用

Research 2020年第1期2020卷 1478-1488页

作者： Andong wang Amlan Das david Grojo Aix-Marseille Univ. CNRSLP3 UMR 734113009 MarseilleFrance

Three-dimensional laser writing inside silicon remains today inaccessible with the shortest infrared light pulses unless complex schemes are used to circumvent screening propagation nonlinearities.Here,we explore a new approach irradiating silicon with trains of femtosecond laser pulses at repetition rates up to 5.6 THz that is order of magnitude higher than any source used for laser processing so far.This extremely high repetition rate is faster than laser energy dissipation from microvolume inside silicon,thus enabling unique capabilities for pulse-to-pulse accumulation of free carriers generated by nonlinear ionization,as well as progressive thermal bandgap closure before any diffusion process comes into play.By space-resolved measurements of energy delivery inside silicon,we evidence changes in the interplay between detrimental nonlinearities and accumulation-based effects.This leads to a net increase on the level of space-time energy localization.The improvement is also supported by experiments demonstrating high performance for 3D laser writing inside silicon.In comparison to repeated single pulses,irradiation with trains of only four-picosecond pulses with the same total energy leads to an apparent decrease of the energy threshold for modification and drastic improvements on the repeatability,uniformity,and symmetricity of the produced features.The unique benefits of THz bursts can provide a new route to meet the challenge of 3D inscription inside narrow bandgap materials.

关键词： repetition Deep shortest

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

Comparative Analysis of Vaccine Inequity and COVID-19 Transmission Amid the Omicron Variant Among Countries--Six Countries,Asia-Pacific Region,2022

引用

China CDC weekly 2023年第33期5卷 731-736,I0001-I0006页

作者： Jingli Yang Hannah McClymont david JWarne Liping wang Wenbiao Hu School of Public Health and Social Work Queensland University of TechnologyBrisbaneAustralia College of Earth and Environmental Sciences Lanzhou UniversityLanzhou CityGansu ProvinceChina School of Mathematical Sciences Queensland University of TechnologyBrisbaneAustralia Centre for Data Science Queensland University of TechnologyBrisbaneAustralia Division of Infectious Diseases Chinese Center for Diseases Control and PreventionBeijingChina.

What is already known about this topic?The coronavirus disease 2019(COVID-19)persists as a significant global public health crisis.The predominant strain,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),notably the Omicron variant,continues to undergo mutations.While vaccination is heralded as the paramount solution to cease the pandemic,challenges persist in providing equitable access to COVID-19 vaccines.What is added by this report?The distribution of vaccine coverage exhibited disparities between high-income and middle-income countries,with middle-income countries evidencing lower levels of vaccination.The data further suggested that countries with lesser vaccination levels tended to display a higher case fatality rate.Findings indicated that an increase in population-wide vaccination was effective in mitigating COVID-19 related mortalities.What are the implications for public health practice?The findings of this research underscore the pressing necessity for equitable access to vaccines to effectively mitigate the COVID-19 pandemic within the Asia-Pacific region.

关键词： COV income vaccination

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

Quantification of perfluorinated compounds in atmospheric particulate shows potential connection with environmental event

引用

Journal of Environmental Sciences 2024年第2期136卷 237-247页

作者： Hua Tang Ying wang Shengling Si Hongli Li david Da Yong Chen National Institute of Metrology 18 BeisanhuandongluChaoyang DistrictBeijing 100029China School of Chemistry and Materials Science Nanjing Normal UniversityNanjing 210023China Si Chuan Zhong Ce Biao Wu Technology Co.Ltd. Sichuan 610052China Department of Chemistry University of British ColumbiaVancouver V6T 1Z1BCCanada

A method of quantification of perfluorinated compounds(PFCs)from atmospheric particulate matter(APM)is described.A single step pretreatment method,selective pressurized liquid extraction(SPLE),was developed to reduce the high matrix background and avoid contamination from commonly used multiple sample pretreatment steps.An effective sorbent was selected to purify the PFCs during SPLE,followed by liquid chromatography-tandem mass spectrometry(LC–MS/MS),for quantification of PFCs.Conditions affecting the SPLE efficiency,including temperature,static extraction time,and number of extraction cycles used,were studied.The optimum conditions were found to be 120℃,10 min,and 3 cycles,respectively.LC-MS/MS method was developed to obtain the optimal sensitivity specific to PFCs.The method detection limits(MDLs)were 0.006 to 0.48 ng/g for the PFCs studied and the linear response range was from 0.1 to 100 ng/g.To ensure accurate values were obtained,each step of the experiment was evaluated and controlled to prevent contamination.The optimized method was tested by performing spiking experiments in natural particulate matter matrices and good rates of recovery and reproducibility were obtained for all target compounds.Finally,the method was successfully used to measure 16 PFCs in the APM samples collected in Beijing over five years from 2015 to 2019.It is observed that some PFCs follow the trend of total PFC changes,and can be attributed to the environment influencing events and policy enforcement,while others don't seem to change as much with time of the year or from year to year.

关键词： Selective pressurized liquid extraction Liquid chromatography-mass spectrometry Perfluorinated compounds Atmospheric particulate matter Pollution control

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：