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Do statins reduce hepatitis C RNA titers during routine clinical use?

World Journal of Gastroenterology 2009年第40期15卷 5020-5027页

作者： Kimberly A Forde Connie Law Rose O’Flynn david e Kaplan Philadelphia Veterans Administration Medical Center Department of Medicine Division of GastroenterologyUniversity of Pennsylvania Department of Pharmacy Philadelphia Veterans Administration Medical Center

AIM: To compare hepatitis C virus (HCV) titers in patients with chronic hepatitis C with and without exposure to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).MeTHODS: Medical records were reviewed for 6463 patients with documented HCV infection at a single center between March 2004 and September 2006. Patients with confi rmed viremia and meeting inclusion criteria were assigned to one of three groups: Group A (n = 50), dyslipidemic patients with statin usage during HCV RNA polymerase chain reaction (PCR) determination; Group B (n = 49), dyslipidemic patients with prior or future statin usage but not at the time of HCV RNA PCR determination; and Group C (n = 102), patients without statin usage during the study period. The primary analysis explored the effect of statin therapy on HCV viremia. Secondary analyses assessed class effect, dose response, and effect of other lipid-lowering therapies on HCV viral ***: Median HCV RNA titers did not signif icantly differ among the three groups (Group A: 4 550 000 IU/mL, Group B: 2 850 000 IU/mL, Group C: 3 055 000 IU/mL).For those subjects with longitudinal assessment of HCV viremia prior to and while on statins, there were no signif icant differences between pre- and post-HCV viral titers. Additionally, no differences in HCV titers were observed at any dose level of the most prescribed statin, simvastatin. However, hypertriglyceridemia independently correlated with HCV titers, and niacin exposure was associated with signif icantly lower viral titers (P ere was no apparent effect of statins on HCV viral replication in this analysis. Further investigation is warranted to explore the possible antiviral properties of triglyceride-lowering agents and their potential role as adjuncts to standard HCV therapy.

关键词： Hepatitis C 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor Statins Geranylgeranyl Prenylation

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Origins and evolution of plant diversity in the Hengduan Mountains, China

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Plant Diversity 2017年第4期39卷 161-166页

作者： Hang Sun Jianwen Zhang Tao Deng david e. Boufford Key Laboratory for Plant Diversity and Biogeography of east Asia Kunming Institute of BotanyChinese Academy of SciencesKunming 650201YunnanChina Harvard University Herbaria 22 Divinity AvenueCambridgeMA 02138-2020USA

*** The Hengduan Mountains region(HDM)in southwest China,one of the earth's 34 biodiversity hotspots,is characterized by its unique geology,dramatic topography,a climate where snow and below freezing temperatures can occur on any day of the year,by its location at elevations averaging between(1400e)2000 and4500(e5300)meters above sea level(m a.s.l.),and by one of

关键词： Origins and evolution of plant diversity in the Hengduan Mountains,China HDM QTP

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New Species of Meconopsis(Papaveraceae) from Laojun Shan and Yao Shan,Northern Yunnan,China

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植物分类与资源学报 2012年第2期34卷 145-149页

作者： YOSHIDA Toshio BOUFFORD david e Hoshiya 330-6 Oamishirasato-machiSambu-gunChiba 299-3222Japan Harvard University Herbaria 22 Divinity AvenueCambridgeMA 02138-2020U.S.A.

Two new species,Meconopsis muscicola and ***(Papaveraceae),are described and *** separating them from similar species are discussed and photos showing their diagnostic features are provided.

关键词： Meconopsis M.muscicola M.yaoshanensis New species Yunnan Laojun Shan Yao Shan

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Combinatorial nanodot stripe assay to systematically study cell haptotaxis

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Microsystems & Nanoengineering 2020年第1期6卷 37-48页

作者： Mcolisi Dlamini Timothy eKennedy david Juncker Biomedical engineering Department McGill University3775 University StreetMontrealQC H3A 2B4Canada McGill Genome Centre 740 Dr.Penfield AvenueMontrealQC H3A 0G1Canada McGill Program in Neuroengineering MontrealQCCanada Department of Neurology and Neurosurgery McGill University3801 University StreetMontréalQC H3A 2B4Canada

Haptotaxis is critical to cell guidance and development and has been studied in vitro using either gradients or stripe assays that present a binary choice between full and zero coverage of a protein ***,stripes offer only a choice between extremes,while for gradients,cell receptor saturation,migration history,and directional persistence confound the interpretation of cellular ***,we introduce nanodot stripe assays(NSAs)formed by adjacent stripes of nanodot arrays with different surface ***-one pairwise combinations were designed using 0,1,3,10,30,44 and 100%stripes and were patterned with 200×200,400×400 or 800×800 nm 2 *** studied the migration choices of C2C12 myoblasts that express neogenin on NSAs(and three-step gradients)of *** reference surface between the nanodots was backfilled with a mixture of polyethylene glycol and poly-D-lysine to minimize nonspecific cell ***,cell response was independent of nanodot *** to a 0%stripe,cells increasingly chose the high-density stripe with up to~90%of cells on stripes with 10%coverage and *** preference for higher *** netrin-1 coverage was observed only for coverage ratios>2.3,with cell preference plateauing at~80%for ratios≥*** combinatorial NSA enables quantitative studies of cell haptotaxis over the full range of surface coverages and ratios and provides a means to elucidate haptotactic mechanisms.

关键词： filled coverage dot

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Interactions between rodents and weeds in a lowland rice agro-ecosystem:the need for an integrated approach to management

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Integrative Zoology 2019年第4期14卷 396-409页

作者： Nyo Me HTWe Grant R.SINGLeTON david e.JOHNSON Plant Protection Division Department of AgricultureMinistry of AgricultureLivestock and IrrigationMyanmar International Rice Research Institute DAPO Box 7777Metro ManilaPhilippines Natural Resources Institute University of GreenwichChatham MaritimeKentUK

Rodents and weeds are important pests to rice crops in Southeast *** interaction between these 2 major pests is poorly *** temperate cereal systems,seeds of grass weeds can be an important food source for rodents and weed cover along crop margins provides important refuge for *** 2012 and 2013,a replicated study(n=4)in Bago,Myanmar compared 4 treatments(rodents and weeds;no rodents and weeds;rodents and no weeds;no rodents and no weeds)each of 0.25 ha in transplanted *** were managed with hand weeding in the wet season,and hand weeding and herbicides in the dry *** fences were installed to exclude *** examined the weed cover and relative abundance of weed species,rodent damage,rodent population dynamics and rice yield loss caused by rodents and *** dominant rodent species was Bandicota *** the dry season,Cyperus difformis was dominant at the tillering stage and echinochloa crus-galli was the dominant weed species at the booting *** the wet season ***-galli was a dominant weed throughout the *** by rodents was higher in the dry *** were larger economic benefits for best weed management and effective rodent control in the dry season(258 US$/ha)than in the wet season(30 US$/ha).Concurrent control of weeds in and around rice fields combined with coordinated community trapping of rodents during the early tillering stage and ripening stage of rice are recommended management options.

关键词： Bandicota bengalensis Myanmar rice rodents weeds

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A good gut feeling on Sarml-mediated axon degeneration

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Protein & Cell 2021年第8期12卷 596-598页

作者： Victoria e.von Saucken david J.Simon Department of Biochemistry Weill Cornell Medical College1300 York AvenueNew YorkNY 10065USA Tri-lnstitutional MD-PhD Program Weill Cornell MedicineRockefeller UniversityMemorial Sloan Kettering Cancer Center1300 York AvenueNew YorkNY 10065USA

Axons,the cable-like projections of neurons,experience a wide range of stressors throughout their *** result of any one of these challenges can be catastrophic,promoting degeneration of the *** degeneration is an active signaling process observed in traumatic brain injury,chemotherapy-induced peripheral neuropathies,and neu-rodegenerative disease(Simon and Watkins,2018;Coleman and Hoeke,2020).

关键词： degeneration chemotherapy traumatic

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Ca^(2+)-induced myelin pathology precedes axonal spheroid formation and is mediated in part by store-operated Ca^(2+)entry after spinal cord injury

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Neural Regeneration Research 2023年第12期18卷 2720-2726页

作者： Spencer Ames Kia Adams Mariah e.Geisen david P.Stirling Kentucky Spinal Cord Injury Research Center Department of Neurological Surgery Anatomical Sciences and Neurobiology Microbiology and Immunology University of LouisvilleSchool of MedicineLouisvilleKYUSA

The formation of axonal spheroid is a common feature following spinal cord *** further understand the source of Ca^(2+)that mediates axonal spheroid formation,we used our previously characterized ex vivo mouse spinal cord model that allows precise perturbation of extracellular Ca^(2+).We performed twophoton excitation imaging of spinal cords isolated from Thy1YFP+transgenic mice and applied the lipophilic dye,Nile red,to record dynamic changes in dorsal column axons and their myelin sheaths *** selectively released Ca^(2+)from internal stores using the Ca^(2+)ionophore ionomycin in the presence or absence of external Ca^(2+).We reported that ionomycin dose-dependently induces pathological changes in myelin and pronounced axonal spheroid formation in the presence of normal 2 m M Ca^(2+)artificial cerebrospinal *** contrast,removal of external Ca^(2+)significantly decreased ionomycin-induced myelin and axonal spheroid formation at 2 hours but not at 1 hour after *** mice that express a neuron-specific Ca^(2+)indicator in spinal cord axons,we confirmed that ionomycin induced significant increases in intra-axonal Ca^(2+),but not in the absence of external Ca^(2+).Periaxonal swelling and the resultant disruption in the axo-myelinic interface often precedes and is negatively correlated with axonal spheroid *** with YM58483(500 n M),a well-established blocker of store-operated Ca^(2+)entry,significantly decreased myelin injury and axonal spheroid ***,these data reveal that ionomycin-induced depletion of internal Ca^(2+)stores and subsequent external Ca^(2+)entry through store-operated Ca^(2+)entry contributes to pathological changes in myelin and axonal spheroid formation,providing new targets to protect central myelinated fibers.

关键词： axonal degeneration axonal spheroid formation ionomycin store-operated calcium entry myelin Nile red peri-axonal swelling

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Multidisciplinary perspectives on mechanisms of activity of popular immune-enhancing herbal supplements used by athletes

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Frontiers in Biology 2013年第1期8卷 78-100页

作者： david S. SeNCHINA Justus e. HALLAM david J. CHeNeY Department of Biology Drake University Des Moines IA 50311 USA Department of Kinesiology Iowa State-University Ames IA 50011 USA Mayo Clinic Rochester MN 55905 USA

This paper examines cellular and molecular mechanisms that may underpin the purported effects of five herbal supplements in the context of athlete immune function. Ginseng and echinacea are used frequently by athletes, whereas astragalus and elderberry are used infrequently and pequi is just emerging as a possible supplement. In vivo studies of these products on athlete immune function have yielded heterogeneous results, likely due to experimental design differences. Ginseng, echinacea, elderberry, and pequi are considered asterids sensu lato. Ginseng appears to exert strongest effects on components of adaptive immunity, in particular maintaining Thl/Th2 balance of CD4^4 T cells and their downstream effects, via its ginsenosides, flavonoids, and polysaccharides. echinacea alkamides, caffeic acid derivatives, and polysacchardies may target both innate and adaptive immunity, though perhaps the former more consistently. elderberry harbors anthocyanins and lectins which may modulate innate immunity. Data on pequi is limited but suggests that carotenoids, phenols, and fatty acids may alter circulating leukocyte populations. More phylogenetically distant, astragalus is a rosid sensu lato and may influence the innate immune system through flavonoids, polysaccharides, and saponins. Supplements generally demonstrate no effects on physiologic parameters such as lactate, oxygen dynamics, or athletic performance. Bioavailability studies indicate that purported bioactive molecules of these supplements may reach circulation in low but therapeutically-relevant quantities. Difficulties in cross- comparisons due to study design differences, coupled with an overall dearth of research on the topic, currently hamper any formal conclusions regarding the efficacy of these supplements as immunoregulators for athletes.

关键词： athlete dietary supplement exercise herb immunity mechanism

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Application of artificial intelligence in predicting the dynamics of bottom hole pressure for under-balanced drilling:extra tree compared with feed forward neural network model

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Petroleum 2022年第2期8卷 227-236页

作者： emmanuel e.Okoro Tamunotonjo Obomanu Samuel e.Sanni david I.Olatunji Paul Igbinedion Petroleum engineering Department Covenant UniversityOtaNigeria Petroleum engineering Department Federal Polytechnic of Oil and GasBonnyNigeria Chemical engineering Department Covenant UniversityOtaNigeria

This study used six fields data alongside correlation heat map to evaluate the field parameters that affect the accuracy of bottom hole pressure(BHP)*** six oil field data were acquired using measurement while drilling device to collect surface measurements of the downhole pressure data while *** the two case studies,measured field data of the wellbore filled with gasified mud system was utilized,and the wellbores were drilled using rotary jointed drill *** Randomized Tree and feed forward neural network algorithms were used to develop models that can predict with high accuracy,BHP from measured field *** modeling purpose,an extensive data from six fields was used,and the proposed model was further validated with two data from two new *** gathered data encompasses a variety of well data,general information/data,depths,hole size,and *** developed model was compared with data obtained from two new fields based on its capability,stability and *** result and model’s performance from the error analysis revealed that the two proposed extra Tree and Feed Forward models replicate the bottom hole pressure data with R2 greater than *** high values of R^(2) for the two models suggest the relative reliability of the modelling *** magnitudes of mean squared error and mean absolute percentage error for the predicted BHPs from both models range from 0.33 to 0.34 and 2.02%-2.14%,for the extra tree model and 0.40-0.41 and 3.90%e3.99%for Feed Forward model respectively;the least errors were recorded for the extra Tree ***,the mean absolute error of the extra Tree model for both fields(9.13-10.39 psi)are lower than that of the Feed Forward model(10.98-11 psi),thus showing the higher precision of the extra Tree model relative to the Feed Forward *** has shown that underbalanced operation does not guarantee the improvement of horizontal well’s extension ability,because it mainly depends on t

关键词： Artificial intelligence Bottom hole pressure extra tree Predictive model Oil and gas Feed forward algorithms

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Protein kinase small molecule inhibitors for rheumatoid arthritis: Medicinal chemistry/clinical perspectives

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World Journal of Orthopedics 2014年第4期5卷 496-503页

作者： Charles J Malemud david e Blumenthal The Arthritis Research Laboratory Department of Medicine Division of Rheumatic Diseases Case Western Reserve University Cleveland OH 44106-5076 United States Department of Anatomy Case Western Reserve University Cleveland OH 44106-5076 United States School of Medicine Division of Rheumatology Veteran’s Administration Medical Center Cleveland OH 44106 United States

Medicinal chemistry strategies have contributed to the development, experimental study of and clinical trials assessment of the first type of protein kinase small molecule inhibitor to target the Janus kinase/Signal Transducers and Activators of Transcription(JAK/STAT) signaling pathway. The orally administered small molecule inhibitor, tofacitinib, is the first drug to target the JAK/STAT pathway for entry into the armamentarium of the medical therapy of rheumatoid arthritis. The introduction of tofacitinib into general rheumatologic practice coupled with increasing understanding that additional cellular signal transduction pathways including the mitogen-activated protein kinase and phosphatidylinositide-3-kinase/Akt/mammalian target of rapa-mycin pathways as well as spleen tyrosine kinase also contribute to immune-mediated inflammatory in rheumatoid arthritis makes it likely that further development of orally administered protein kinase small molecule inhibitors for rheumatoid arthritis will occur in the near future.

关键词： Clinical trials Protein kinase Signal transduction Small molecule inhibitor Rheumatoid arthritis

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