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Rac1 regulates the release of Weibel-Palade Bodies in human aortic endothelial cells

Chinese Medical journal 2004年第8期117卷 1143-1150页

作者：杨水祥闫娟 Shailesh S.Deshpande Kaikobad Irani charles j.Lowenstein Cardiovascular Center Tongren Hospital Capital University of Medical SciencesBeijing100730China Division of Cardiology Department of Medicine Department of PathologyJohns Hopkins UniversitySchool of MedicineBaltimoreMaryland 21205USA

Background The release of Weibel-Palade Bodies (WPB) is a form of endothelial cell activation But the signal transduction pathway leading to WPB release is not yet defined We hypothesized that small G-protein rac1 and reactive oxygen species (ROS) mediate the ligand induced release of Weibel-Palade Bodies Methods We tested this hypothesis by using wild-type and mutant adenoviral rac1 expression vectors, and by manipulating the production and destruction of superoxide and hydrogen peroxide in human aortic endothelial cells (HAEC) KH*2/5DResults Thrombin (1 0 Unit, 30 min) induced the increase of WPB release by 3 7-fold in HAEC, and that H 2O 2 (0 1 mmol/L, 30 min) induced by 4 5-fold These results correlated with thrombin-stimulated activation of rac-GTP binding activity by 3 5-fold, and increase of ROS production by 3 4-fold The dominant negative adenoviral rac-N17 gene transfer dramatically inhibited the release of WPB by 64 2% (control) and 77 3% (thrombin-stimulation), and decreased ROS production by 65 5% (control) and 83 6% (thrombin-stimulation) compared with non-infected cells, respectively Anti-oxidants, catalase and N-acetyl-cysteine significantly decreased the release of WPB by 34% and 79% in control cells, and further decreased by 63 6% and 46 7% in rac-N17 transferred cells compared with non-infected cells We also confirmed that rac1 was located upstream of ROS in the WPB release pathway KH*2/5DConclusions Small G-protein rac1 medicates ligand-induced release of Weibel-Palade Bodies in human aortic endothelial cells, and the signal pathway of WPB release is a rac1-dependent ROS regulating mechanism

关键词： Weibel-Palade Bodies von Willebrand factor P-selectin rac thrombin exocytosis reactive oxygen species

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Effect of Mild Sonication Conditions on the Attributes of <i>Lactobacillus delbrueckii</i>ssp. <i>bulgaricus</i>LB-12

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Advances in Microbiology 2012年第2期2卷 104-111页

作者： Marvin Moncada Kayanush j. Aryana charles Boeneke School of Animal Sciences Louisiana State University Agricultural Center Baton Rouge USA School of Animal Sciences Louisiana State University Agricultural Center Baton Rouge USA Department of Food Science Louisiana State University Agricultural Center Baton Rouge USA

Lactobacillus delbrueckii ssp. bulgaricus is a widely used bacterium for the production of some fermented dairy products. Mild sonication intensity condition is a non-destructive technique that uses sound waves to cause cavitation in aqueous solutions and may improve the permeability of membranes, speed up the transfer of substrates and promote cellular growth and propagation. The objective was to determine the effect of mild sonication intensities at different temperatures on growth, bile tolerance and protease activity of Lactobacillus delbrueckii ssp. bulgaricus LB-12. The treatments were four sonication intensities (8.07, 14.68, 19.83 and 23.55 W/cm2) randomized at three different temperatures (4℃, 22℃ and 40℃). The energy input (1500 j) was kept constant in all treatments. Control samples did not receive any sonication treatment. Growth and bile tolerance were determined every 2 h for 12 h of incubation. Protease activity was determined at 0, 12 and 24 h. Mild sonication conditions included 1) mild sonication intensities, 2) temperatures and 3) times, all three of which played a role in influencing the desirable attributes of Lactobacillus delbrueckii ssp. bulgaricus LB-12. Of all the mild sonication intensities studied, 14.68 W/cm2 had the best overall influence at certain time points forimproving the bile tolerance and growth at 4℃ and protease activity at 40℃. Mild sonication intensity of 23.55 W/cm2 had the best overall influence at certain time points for protease activity of at 22℃. Some mild sonication conditions could be recommended for improvement of some characteristics of Lactobacillus delbrueckii ssp. bulgaricus LB-12.

关键词： Sonication Starter Culture Lactobacillus bulgaricus

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Transdermal Delivery of Gabapentin: Effect of Cosolvent and Microemulsion on Permeation through the Rat Skin

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Pharmacology & Pharmacy 2014年第5期5卷 471-478页

作者： Chika j. Mbah charles O. Nnadi Department of Pharmaceutical and Medicinal Chemistry Faculty of Pharmaceutical Sciences University of Nigeria Nsukka Nigeria

The objective of the present study was to examine the influence of cosolvent system and micro-emulsion formulation on in-vitro skin permeation of gabapentin, furthermore, to characterize the physicochemical properties of drug-loaded oil-in-water (o/w) and water-in-oil (w/o) cremophor 40-based microemulsions in comparison to the blank counterparts. The cosolvent system prepared by homogenous mixing is composed of ethanol-water and propylene glycol-water mixture (90:10, 80:20, 70:30 v/v) respectively. The microemulsion consisted of coconut oil, water and mixture of cremophor 40 (surfactant) and ethanol (cosurfactant) and was prepared by aqueous phase titration method. Physicochemical properties of microemulsions were determined using reported procedures. Transdermal flux for gabapentin was studied in-vitro using modified Franz diffusion cells. The physicochemical properties of drug-loaded microemulsions and their blank counterparts were generally alike, however, slight variation in pH and viscosity was observed probably due to the intrinsic properties of the drug. The ethanol-water system (70:30 v/v) gave higher flux for gabapentin when compared to propylene glycol-water system (70:30 v/v). The w/o microemulsion formulations resulted in, higher flux for gabapentin when compared to o/w formulations. FTIR spectra of the untreated stratum corneum, when compared to cosolvent system and microemulsion treated stratum corneum, suggest the mechanism of permeation to be disruption of lipid bilayers and keratin denaturation of the stratum corneum. The results show that incorporation of gabapentin into microemulsions did not change the microemulsion type. The in vitro permeation data obtained from experimental work suggest that the cosolvent system (ethanol-water 70:30 v/v) and w/o microemulsion formulations respectively, can be successfully used as potential vehicles in developing transdermal therapeutic systems for gabapentin.

关键词： Transdermal Delivery Cosolvent System Microemulsion Gabapentin

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Aged rat heart: Modulation of age-related respiratory defects decreases ischemic-reflow injury

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Health 2013年第1期5卷 1-7页

作者： Edward j. Lesnefsky charles L. Hoppel Center for Mitochondrial Diseases Departments of Medicine and Pharmacology Case Western Reserve University Cleveland USA Departments of Medicine Biochemistry and Physiology Virginia Commonwealth University and McGuire Veterans Affairs Medical Center Richmond USA

Myocardial injury increases in the elderly heart during ischemia and reperfusion. Mitochondria, the key targets and sources of injury during ischemia and reperfusion, sustain ischemic damage to the electron transport chain that is superimposed upon age-related defects. In the adult heart, interventions to activate endogenous cytoprotective signaling systems meet in mitochondria to decrease cardiac injury. Unfortunately, these systems are largely ineffective in the aged heart. Thus, new treatment concepts are needed to reduce injury in the aged heart. Our group chose a strategy to directly treat the effector of cardiac injury in the aged heart, the mitochondria. We further utilized a novel approach to ask if the reversal of aging defects in cardiac mitochondria before ischemia could decrease ischemia-reperfusion injury in the heart. Three hours following treatment with the small molecule, nutriceutical acetylcarnitine (AcCN), oxidative phosphorylation as well as age-induced defects in electron transport chain complexes III and IV was corrected in the heart. When such hearts were then exposed to ischemia and reperfusion, cardiac injury was markedly reduced. Contraction during reperfusion improved and recovery became similar to that in adult hearts. Cardiac cell death was substantially reduced. Thus, age-related defects in electron transport are a key mechanism of the increased myocardial injury in the elderly heart during ischemia and reperfusion. Modulation of aging-induced defects in mitochondrial metabolism reduces cardiac injury from ischemia and reperfusion, and is a novel strategy to protect myocardium in the elderly patient at risk for an acute myocardial infarction.

关键词： Mitochondria Cytochrome Oxidase Complex III Myocardial Infarction Aging

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Intra-arterial thrombolytics during endovascular thrombectomy for acute ischaemic stroke in the MR CLEAN Registry

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Stroke & Vascular Neurology 2023年第1期8卷 17-25页

作者： Sabine L Collette Reinoud P H Bokkers Aryan Mazuri Geert j LycklamaàNijeholt Robert j van Oostenbrugge Natalie E LeCouffe Faysal Benali charles B L M Majoie jan Cees de Groot Gert jan R Luijckx Maarten Uyttenboogaart 无 Department of Radiology Medical Imaging CentreUniversity Medical Centre GroningenUniversity of GroningenGroningenthe Netherlands Department of Radiology Haaglanden Medical CentreThe Haguethe Netherlands Department of Neurology Cardiovascular Research Institute Maastricht(CARIM)Maastricht University Medical CentreMaastrichtthe Netherlands Department of Neurology Amsterdam UMCUniversity of AmsterdamAmsterdam NeuroscienceAmsterdamthe Netherlands Department of Radiology Maastricht University Medical CentreMaastrichtthe Netherlands Department of Radiology and Nuclear Medicine Amsterdam UMCUniversity of AmsterdamAmsterdam NeuroscienceAmsterdamthe Netherlands Department of Neurology University Medical Centre GroningenUniversity of GroningenGroningenthe Netherlands On behalf of the MR CLEAN Registry investigators

Introduction The efficacy and safety of local intra-arterial(IA)thrombolytics during endovascular thrombectomy(EVT)for large-vessel occlusions is *** analysed how often IA thrombolytics were administered in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands(MR CLEAN)Registry,whether it was associated with improved functional outcome and assessed technical and safety outcomes compared with EVT without IA *** In this observational study,we included patients undergoing EVT for an acute ischaemic stroke in the anterior circulation from the MR CLEAN Registry(March 2014-November 2017).The primary endpoint was favourable functional outcome,defined as an modified Rankin Scale score≤2 at 90 *** endpoints were reperfusion status,early neurological recovery and symptomatic intracranial haemorrhage(sICH).Subgroup analyses for IA thrombolytics as primary versus adjuvant revascularisation attempt were *** Of the 2263 included patients,95(4.2%)received IA thrombolytics during *** IA thrombolytics administered were urokinase(median dose,250000 IU(IQR,193750-250000))or alteplase(median dose,20 mg(IQR,12-20)).No association was found between IA thrombolytics and favourable functional outcome(adjusted OR(aOR),1.16;95%CI 0.71 to 1.90).Successful reperfusion was less often observed in those patients treated with IA thrombolytics(aOR,0.57;95%CI 0.36 to 0.90).The odds of sICH(aOR,0.82;95%CI 0.32 to 2.10)and early neurological recovery were comparable between patients treated with and without IA *** primary and adjuvant revascularisation attempts,IA thrombolytics were more often administered for proximal than for distal *** outcomes were comparable for patients receiving IA thrombolytics as a primary versus adjuvant revascularisation *** Local IA thrombolytics were rarely used in the MR CLEAN *** the relatively small st

关键词： arterial throm acute

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Serrated flow in NaI:Tl scintillator crystals

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journal of Materials Science & Technology 2023年第22期153卷 120-127页

作者： jamieson Brechtl Xie Xie Rui Feng Gongyao Wang charles Melcher Mariya Zhuravleva Peter K.Liaw The Bredesen Center for Interdisciplinary Research and Graduate Education The University of TennesseeKnoxvilleTN 37996USA Department of Materials Science and Engineering The University of TennesseeKnoxvilleTN 37996USA Scintillation Materials Research Center The University of TennesseeKnoxvilleTN 37996USA

The serrated-flow behavior is an important phenomenon that unveils material-deformation mechanisms,as reported for various kinds of *** doped with Tl(NaI:Tl)is unique among scintillation ma-terials in that the structure contains glide planes that are linked to serration *** the present work,single crystals of NaI:Tl were subjected to room-temperature compression experiments at different strain *** serrated flow was observed,and complexity and multifractal analyses were performed to analyze the serration *** findings revealed that the strain rate had a pronounced effect on the complexity and multifractality of the serrated flow,similar to what has been found in other alloy *** results also indicate that there may be a strong link between the complexity of the serrated flow behavior and the heterogeneity of the underlying *** is expected that the present work could be a step toward a better understanding of the deformation behavior and forgeability of NaI:Tl single crystals.

关键词： Dislocations Ceramic material Mechanical testing Numerical algorithms Scintillator

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Tailoring properties of hybrid perovskites by domain-width engineering with charged walls

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npj Computational Materials 2018年第1期4卷 26-31页

作者： Lan Chen charles Paillard Hong jian Zhao jorgeÍñiguez Yurong Yang Laurent Bellaiche Physics Department and Institute for Nanoscience and Engineering University of ArkansasFayettevilleArkansas 72701USA Materials Research and Technology Department Luxembourg Institute of Science and Technology(LIST)5 Avenue des Hauts-FourneauxL-4362 Esch/AlzetteLuxembourg National Laboratory of Solid State Microstructures Jiangsu Key Laboratory of Artificial Functional Materials and Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China

Charged ferroelectric domain walls are fascinating electrical topological defects that can exhibit unusual ***,in the search for novel phenomena,we perform and analyze first-principles calculations to investigate the effect of domain width on properties of domains with charged walls in the photovoltaic material consisting of methylammonium lead iodide hybrid *** report that such domains are stable and have rather low domain wall energy for any investigated width(that is,up to 13 lattice constants).Increasing the domain width first linearly decreases the electronic band gap from≃1.4 eV to about zero(which therefore provides an efficient band-gap engineering),before the system undergoes an insulator-to-metal transition and then remains metallic(with both the tail-to-tail and head-to-head domain walls being conductive)for the largest *** these results can be understood in terms of:(i)components of polarization along the normal of the domain walls being small in magnitude;(ii)an internal electric field that is basically independent of the domain width;and(iii)rather negligible charge transfer between *** findings deepen the knowledge of charged ferroelectric domain walls and can further broaden their potential for applications,particularly in the context of halide perovskites for photovoltaics.

关键词： properties walls perovskite

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Impact of xylanases on gut microbiota of growing pigs fed corn-or wheat-based diets

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Animal Nutrition 2018年第4期4卷 339-350页

作者： Zhengxiao Zhang Hein M.Tun Ru Li Beatriz j.M.Gonzalez Hannah C.Keenes charles M.Nyachoti Elijah Kiarie Ehsan Khafipour Department of Animal Science University of Manitoba Department of Medical Microbiology and Infectious Diseases University of Manitoba Department of Animal Bioscience University of Guelph

This study investigated the effects of xylanase supplementations with cereal-based diets on nutrient digestibility and gut microbiota of growing pigs. A total of 96 individually penned pigs(initial BW = 22.7 ± 0.65 kg) were allotted to 12 treatments and subjected to a completely randomized block design experiment. Pigs in each treatment were fed an isocaloric wheat-based or corn-based diet with or without 1 of 5 types of xylanase supplements(XA, XB, XC, XD, XE). On d 42, all piglets were euthanized to obtain ileal and cecal digesta for microbial analysis, which involved high-throughput sequencing of the V1 - V3 regions of 16 S rRNA gene. Corn-and wheat-based diets differed(P jority

关键词： Piglets Microbiota Xylanase Arabinoxylans Digestibility

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喂饲酒精对大鼠肝抑制N-甲基-N′-硝基-N-亚硝基胍致突变性的影响

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中国药理学与毒理学杂志 1987年第1期1卷 110-115页

作者：周宗灿,charles S Lieber,Anthony j Garro 北京医科大学公共卫生学院美国纽约市酒精研究治疗中心纽约市立索菲·戴维斯生物医学教育学院北京 100083

本文比较了喂饲酒精4wk的Sprague-Dawley 大鼠肝匀浆上清液(S9)和对照组大鼠肝S9对直接致癌物N-甲基-N’-硝基-N-亚硝基胍(MNNG)致突变性的抑制作用。Ames试验表明,喂饲酒精可增强大鼠肝S9抑制MNNG致突变性的能力(p<0.05),并伴有某些解... 详细信息

本文比较了喂饲酒精4wk的Sprague-Dawley 大鼠肝匀浆上清液(S9)和对照组大鼠肝S9对直接致癌物N-甲基-N’-硝基-N-亚硝基胍(MNNG)致突变性的抑制作用。Ames试验表明,喂饲酒精可增强大鼠肝S9抑制MNNG致突变性的能力(p<0.05),并伴有某些解毒酶活性增加。酒精组大鼠肝S9的谷胱甘肽S-转移酶、UDP葡萄糖醛酸基转移酶及氨基比林N-脱甲基酶活性分别为对照组的1.2,1.7和1.2倍。喂饲酒精可增加肝内谷胱甘肽的浓度,但对UDP葡萄糖醛酸的含量无显著影响。本文结果提示,喂饲酒精导致大鼠肝S9对MNNG致突变性的抑制能力增加是与上述解毒酶活性及某些辅因子浓度增高有关。

关键词：酒精 N-甲基-N’-硝基-N-亚硝基胍 Ames试验谷胱甘肽 UDP葡萄糖醛酸谷胱甘肽S-转移酶 UDP葡萄糖醛酸基转移酶 N-脱甲基酶

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Management of extracranial carotid artery stenosis during endovascular treatment for acute ischaemic stroke:results from the MR CLEAN Registry

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Stroke & Vascular Neurology 2023年第3期8卷 229-237,I0074-I0085页

作者： Sabine L Collette Michael P Rodgers Marianne A A van Walderveen Kars C j Compagne Paul j Nederkoorn jeannette Hofmeijer jasper M Martens Gert j de Borst Gert jan R Luijckx charles B L M Majoie Aad van der Lugt Reinoud P H Bokkers Maarten Uyttenboogaart University Medical Centre Groningen University of GroningenGroningenThe Netherlands Leiden University Medical Centre LeidenThe Netherlands Erasmus MC University Medical CentreRotterdamThe Netherlands Amsterdam University Medical Centres University of AmsterdamAmsterdamThe Netherlands Rijnstate Hospital ArnhemThe Netherlands University Medical Centre Utrecht University of UtrechtUtrechtThe Netherlands

Background The optimal management of ipsilateral extracranial internal carotid artery(ICA)stenosis during endovascular treatment(EVT)is *** compared the outcomes of two different strategies:EVT with vs without carotid artery stenting(CAS).Methods In this observational study,we included patients who had an acute ischaemic stroke undergoing EVT and a concomitant ipsilateral extracranial ICA stenosis of≥50%or occlusion of presumed atherosclerotic origin,from the Dutch Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands(MR CLEAN)Registry(2014-2017).The primary endpoint was a good functional outcome at 90 days,defined as a modified Rankin Scale score≤*** endpoints were successful intracranial reperfusion,new clot in a different vascular territory,symptomatic intracranial haemorrhage,recurrent ischaemic stroke and any serious adverse *** Of the 433 included patients,169(39%)underwent EVT with *** 123/168(73%)patients,CAS was performed before intracranial *** 42/224(19%)patients who underwent EVT without CAS,a deferred carotid endarterectomy or CAS was *** with and without CAS were associated with similar proportions of good functional outcome(47%vs 42%,respectively;adjusted OR(aOR),0.90;95%CI,0.50 to 1.62).There were no major differences between the groups in any of the secondary endpoints,except for the increased odds of a new clot in a different vascular territory in the EVT with CAS group(aOR,2.96;95%CI,1.07 to 8.21).Conclusions Functional outcomes were comparable after EVT with and without *** during EVT might be a feasible option to treat the extracranial ICA stenosis but randomised studies are warranted to prove non-inferiority or superiority.

关键词： stenosis carotid treatment

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