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Progression of Platelet Counts in Treatment Naïve HIV/HCV Co-Infection

World Journal of AIDS 2013年第1期3卷 36-40页

作者： Jonathan E. Schelfhout Danijela A. Stojanovic amy houtchens Heidi M. Crane Edward R. Cachay Elizabeth R. Brown Sonia M. Napravnik Mari M. Kitahata Michael S. Saag Peter W. Hunt Teresa L. Kauf Joseph A. C. Delaney Department of Epidemiology University of Washington Seattle WA Department of Medicine University of Alabama at Birmingham Birmingham USA Department of Medicine University of California at San Diego San Diego USA Department of Medicine University of California at San Francisco San Francisco USA Department of Medicine University of North Carolina Chapel Hill USA Division of Allergy & Infectious Disease Department of Medicine University of Washington Seattle USA Food and Drug Administration Silver Spring USA Vaccine and Infectious Disease and Public Health Sciences Divisions Fred Hutchinson Cancer Research Center Seattle USA

Background: Previous research has suggested an association between infection with hepatitis C virus (HCV) or with human immunodeficiency virus (HIV) and low platelet counts. This study estimates platelet count changes over time in HIV/HCV co-infected participants and compares them with the changes in platelet count among HIV mono-infected participants to test if HIV/HCV co-infection is associated with lower platelet counts. Methods: This retrospective cohort study included all HIV treatment naive patients from four sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort with platelet count measurements between 2002 and 2009. We conducted a mixed effects linear regression modeling the mean change in platelet count per year while adjusting for age, sex, race, baseline CD4 cell count, and site. Index date was the first platelet count after 2002, and participants were censored upon initiation of treatment for HIV or HCV. Results: There were 929 HIV/HCV co-infected and 3558 HIV mono-infected participants with a mean follow-up time of 1.2 years. HIV/HCV co-infected participants had on average a slighter lower platelet count at baseline (234,040 vs. 242,780/μL;p-value = 0.004), and a more rapid mean reduction per year (7230 vs. 3580/μL;p-value 0.001) after adjusting for age, sex, baseline CD4 count. Conclusions: In treatment naive participants, HIV/HCV co-infection is associated with a more rapid decline in platelet count compared with HIV mono-infection.

关键词： HCV HIV AIDS Co-Infection Platelet Count Thrombocytopenia

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Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： Yi Zhang Zhongwu Liu Michael Chopp Michael Millman Yanfeng Li Pasquale Cepparulo amy Kemper Chao Li Li Zhang Zheng Gang Zhang Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA Department of Pathology Henry Ford HospitalDetroitMIUSA Division of Pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression *** EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal *** analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-sEVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

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Updates on esophageal and gastric cancers

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World Journal of Gastroenterology 2006年第20期12卷 3237-3242页

作者： amy Gallo Charles Cha Resident Department of Surgery Yale University School of Medicine333 Cedar St.FMB 121New HavenCT 06520United States Department of Surgery Yale University of School of Medicine 333 Cedar St.FMB 121New HavenCT 06520United States

Esophageal and gastric cancers are both common and deadly. Patients present most often after disease progression and survival is therefore poor. Due to demographic variability and recent changes in disease incidence, much emphasis has been placed on studying risk factors for both esophageal and gastric cancers. However, with increasing understanding of these diseases, low survival rates persist and continued intensive studies are necessary to optimize treatment plans. This review article discusses updates in the evolving epidemiology, clinical presentation, risk factors, and diagnostic and treatment modalities of esophageal and gastric cancers.

关键词： Gastric cancer Esophageal cancer Surgery Treatment

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Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check

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Frontiers of Medicine 2020年第3期14卷 273-283页

作者： amy Lee Fa-Chyi Lee Department of Biology University of California San DiegoSan DiegoCA 92093USA Division of Hematology/Oncology Department of Internal MedicineUniversity of California IrvineOrangeCA 92868USA

In terms of global cancer-related deaths,hepatocellular carcinoma (HCC) has the fourth highest mortality *** until 2017,treatment of advanced HCC was largely limited to sorafenib,an oral tyrosine kinase inhibitor,with little to no success in the development of alternative treatment ***,in the past two years,there has been an unprecedented increase in both the number and type of treatment options available for *** of 2019,the US FDA has approved four oral tyrosine kinase inhibitors,two immune checkpoint inhibitors,and one anti-angiogenesis antibody for the treatment of *** with this new variety,systemic treatment of advanced HCC remains largely unsatisfactory,and the median survival rate stands at approximately one *** expected breakthrough of using immune checkpoint inhibitors in advanced HCC did not materialize in *** use of immune checkpoint inhibitors in conjunction with oral tyrosine kinase inhibitors or antiangiogenesis medications is the current clinical research trend,the results of which are eagerly *** limited progress in survival,HCC research is currently experiencing a period of growth and innovation,and there is hope for significant advances in the treatment of advanced HCC as the field continues to develop.

关键词： hepatocellular carcinoma tyrosine kinase inhibitor check point inhibitor anti-angiogenesis

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Dynamic change of Adamalysin 19 (ADAM19) in human placentas and its effects on cell invasion and adhesion in human trophoblastic cells

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Science China(Life Sciences) 2009年第8期52卷 710-718页

作者： SANG QingXiang amy Department of Chemistry and Biochemistry and Institute of Molecular Biophysics Florida State University

Human ADAM19 is a recently identified member of the ADAM *** is highly expressed in human placentas,but its dynamic change and function at the human feto-maternal interface during placentation remain to be *** this present study,the spatial and temporal expression and cellular localization of ADAM19 in normal human placentas were first demonstrated,and the effects of ADAM19 on trophoblast cell adhesion and invasion were further investigated by using a human choriocarcinoma cell line(JEG-3) as an in vitro *** data demonstrated that ADAM19 was widely distributed in villous cytotrophoblast cells,syncytiotrophoblast cells,column trophoblasts,and villous capillary endothelial cells during early *** mRNA and protein level of ADAM19 in placentas was high at gestational weeks 8-9,but diminished significantly at mid-and term *** JEG-3 cells,the overexpression of ADAM19 led to diminished cell invasion,as well as increases in cell adhesiveness and the expression of E-cadherin,with no changes in β-catenin expression *** data indicate that ADAM19 may participate in the coordinated regulation of human trophoblast cell behaviors during the process of placentation.

关键词： ADAM19 human trophoblast cells invasion adhesion

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Stochastic SIS metapopulation models for the spread of disease among species in a fragmented landscape

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International Journal of Biomathematics 2016年第4期9卷 97-119页

作者： amy J. Ekanayake Department of Mathematics Western Illinois University 1 University Circle Maeomb Illinois 61455 USA

Two stochastic models are derived for a susceptible-infectious-susceptible epidemic spreading through a metapopulation： a continuous time Markov chain （CTMC） model and an It6 stochastic differential equation （SDE） model. The stochastic models are numerically compared. Close agreement suggests that computationally intense CTMC simulations can be approximated by simpler SDE simulations. Differential equations for the moments of the SDE probability distribution are also derived, the steady states are solved numerically using a moment closure technique, and these results are compared to simulations. The moment closure technique only coarsely approximates simulation results. The effect of model parameters on stability of the disease-free equilibrium is also numerically investigated.

关键词： Epidemic metapopulation Ito stochastic differential equation Markov chain moment closure.

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Lifespan Modulation in Mice and the Confounding Effects of Genetic Background

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Journal of Genetics and Genomics 2014年第9期41卷 497-503页

作者： Lorna Mulvey amy Sinclair Colin Selman Institute of Biodiversity Animal Health and Comparative MedicineCollege of MedicineVeterinary and Life SciencesGraham Kerr BuildingUniversity of Glasgow

We are currently in the midst of a revolution in ageing research, with several dietary, genetic and pharmacological interventions now known to modulate ageing in model organisms. Excitingly, these interventions also appear to have beneficial effects on late-life health. For example, dietary restriction （DR） has been shown to slow the incidence of age-associated cardiovascular disease, metabolic disease, cancer and brain ageing in non-human primates and has been shown to improve a range of health indices in humans. While the idea thai DR＇s ability to extend lifespan is often thought of as being universal, studies in a range of organisms, including yeast, mice and monkeys, suggest that this may not actually be the case. The precise reasons underlying these differential effects of DR on lifespan are currently unclear, but genetic background may be an important factor in how an individual responds to DR. Similarly, recent findings also suggest that the responsiveness of mice to specific genetic or pharmacological interventions that modulate ageing may again be influenced by genetic background. Consequently, while there is a clear driver to develop interventions to improve late-life health and vitality, under- standing precisely how these act in response to particular genotypes is critical if we are to translate these findings to humans. We will consider of the role of genetic background in the efficacy of various lifespan interventions and discuss potential routes of utilising genetic heterogeneity to further understand how particular interventions modulate lifespan and healthspan.

关键词： Ageing Dietary restriction Genotype Longevity

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Contribution of NMDA receptors to dorsolateral prefrontal cortical networks in primates

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Neuroscience Bulletin 2015年第2期31卷 191-197页

作者： Min Wang amy F T Arnsten Department of Neurobiology Yale Medical School

Cognitive disorders such as schizophrenia and Alzheimer＇s disease are associated with dysfunction of the highly evolved dorsolateral prefrontal cortex （dlPFC）, and with changes in glutamatergic N-methyI-D-aspartate receptors （NMDARs）. Recent research on the primate dlPFC discovered that the pyramidal cell circuits that generate the persistent firing underlying spatial working memory communicate through synapses on spines containing NMDARs with NR2B subunits （GluN2B） in the post-synaptic density. This contrasts with synapses in the hippocampus and primary visual cortex, where GluN2B receptors are both synaptic and extrasynaptic. Blockade of GluN2B in the dlPFC markedly reduces the persistent firing of the Delay cells needed for neuronal representations of visual space. Cholinergic stimulation of nicotinic （17 receptors within the glutamate synapse is necessary for NMDAR actions. In contrast, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors have only subtle effects on the persistent firing of Delay cells, but contribute substantially to the firing of Cue and Response cells. Systemic administration of the NMDAR antagonist ketamine reduces the persistent firing of Delay cells, but increases the firing of some Response cells. The reduction in persistent firing produced by ketamine may explain why this drug can mimic or worsen the cognitive symptoms of schizophrenia. Similar actions in the medial PFC circuits representing the emotional aspects of pain may contribute to the rapid analgesic and anti-depressant actions of ketamine.

关键词： glutamate Alzheimer's disease schizophrenia depression ketamine

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Heightened condition dependent expression of structural coloration in the faces,but not wings,of male and female flies

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Current Zoology 2022年第5期68卷 600-607页

作者： Thomas E White amy Locke Tanya Latty School of Life and Environmental Sciences The University of SydneySydney 2106Australia

Structurally colored sexual signals are a conspicuous and widespread class of ornament used in mate choice,though the extent to which they encode information on the quality of their bearers is not fully *** predicts that signaling traits under strong sexual selection as honest indicators should evolve to be more developmentally integrated and exaggerated than nonsexual traits,thereby leading to heightened condition ***,we test this prediction through examination of the sexually dimorphic faces and wings of the cursorial fly Lispe *** and females possess structural UV-white and golden faces,respectively,and males present their faces and wings to females during close-range,ground-based courtship displays,thereby creating the opportunity for mutual *** a field-collected sample of individuals,we found that the appearance of the faces of both sexes scaled positively with individual condition,though along separate *** in better condition expressed brighter faces as modeled according to conspecific flies,whereas condition scaled with facial saturation in *** found no such relationships for their wing interference pattern nor abdomens,with the latter included as a nonsexual *** results suggest that the structurally colored faces,but not the iridescent wings,of male and female *** are reliable guides to individual quality and support the broader potential for structural colors as honest *** also highlight the potential for mutual mate choice in this system,while arguing for 1 of several alternate signaling roles for wing interferences patterns among the myriad taxa which bear them.

关键词： honest signal iridescent mate choice sexual selection wing interference pattern

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A sting in the tail： the N-terminal domain of the androgen receptor as a drug target

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Asian Journal of Andrology 2016年第5期18卷 687-694页

作者： amy E Monaghan Iain J McEwan School of Medicine Medical Sciences and Nutrition Institute of Medical Sciences University of Aberdeen Foresterhill Aberdeen AB25 2ZD United Kingdom.

The role of androgen receptor （AR） in the initiation and progression of prostate cancer （PCa） is well established. Competitive inhibition of the AR ligand-binding domain （LBD） has been the staple of antiandrogen therapies employed to combat the disease in recent years. However, their efficacy has often been limited by the emergence of resistance, mediated through point mutations, and receptor truncations. As a result, the prognosis for patients with malignant castrate resistant disease remains poor. The amino-terminal domain （NTD） of the AR has been shown to be critical for AR function. Its modular activation function （AF-1） is important for both gene regulation and participation in protein-protein interactions. However, due to the intrinsically disordered structure of the domain, its potential as a candidate for therapeutic intervention has been dismissed in the past. The recent emergence of the small molecule EPI-O01 has provided evidence that AR-NTD can be targeted therapeutically, independent of the LBD. Targeting of AR-NTD has the potential to disrupt multiple intermolecular interactions between AR and its coregulatory binding partners, in addition to intramolecular cross-talk between the domains of the AR. Therapeutics targeting these protein-protein interactions or NTD directly should also have efficacy against emerging AR splice variants which may play a role in PCa progression. This review will discuss the role of intrinsic disorder in AR function and illustrate how emerging therapies might target NTD in PCa.

关键词： androgen receptor inhibitor intrinsically disordered structure N-terminal domain prostate cancer small molecules

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