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1.
FEBS J ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32243091

RESUMO

Cholesterol efflux from macrophages is the initial step of reverse cholesterol transport, an important process for high-density lipoprotein-mediated atheroprotection. G protein-coupled receptor (GPR) 120, which functions as long-chain fatty acid receptor, is well known for its anti-inflammatory and insulin-sensitizing function in macrophages. However, the role of GPR120 on macrophage foam cell formation, the hallmark of atherosclerotic plaques, has not been verified. In this study, we found for the first time that stimulation of GPR120 by its agonist GW9508 elevated the expression of ATP-binding cassette transporters (ABC) A1 and ABCG1 in THP-1 macrophage-derived foam cells and Raw264.7 macrophages, and promoted ABCA1- and ABCG1-mediated cholesterol efflux and reduced cellular cholesteryl ester (CE) content as well. In addition, GPR120 activation was accompanied with the stimulation of AMPK pathway in macrophages; however, the effect of GPR120 on macrophage cholesterol efflux was largely abolished by AMPK inhibition. Moreover, the AMPK activity and the expression of ABCA1 and ABCG1 were markedly abrogated by knockdown of GPR120, or application of phospholipase C (PLC) inhibitor, calcium chelator, or CaMKK inhibitor. Because only free cholesterol can be effluxed from macrophages, we found that activation of AMPK could lead to increase both neutral CEs hydrolysis by upregulation of neutral cholesterol ester hydrolase expression and acid CEs hydrolysis by activation of ULK1. In conclusion, these results demonstrated that GPR120 facilitated ABCA1- and ABCG1-mediated cholesterol efflux through activation of PLC/Ca2+ /CaMKK/AMPK signaling pathway, which induced CE hydrolysis and elevated the expression of ABCA1 and ABCG1 in macrophages.

2.
Virus Res ; 286: 197980, 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32311386

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) has caused tremendous amounts of economic losses to the swine industry for more than three decades, but its control is still unsatisfactory. A significant amount of information is available for host cell-virus interactions during infection, and it is evident that PRRSV has evolved to equip various strategies to disrupt the host antiviral system and provide favorable conditions for survival. The current study reviews viral strategies for modulations of cellular processes including innate immunity, apoptosis, microRNAs, inflammatory cytokines, and other cellular pathways.

4.
Nano Lett ; 20(2): 1417-1427, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31930919

RESUMO

Labeling viruses with high-photoluminescence quantum dots (QDs) for single virus tracking provides a visual tool to aid our understanding of viral infection mechanisms. However, efficiently labeling internal viral components without modifying the viral envelope and capsid remains a challenge, and existing strategies are not applicable to most viruses. Here, we have devised a strategy using the clustered regularly interspaced short palindromic repeats (CRISPR) imaging system to label the nucleic acids of Pseudorabies virus (PRV) with QDs. In this strategy, QDs were conjugated to viral nucleic acids with the help of nuclease-deactivated Cas9/gRNA complexes in the nuclei of living cells and then packaged into PRV during virion assembly. The processes of PRV-QD adsorption, cytoplasmic transport along microtubules, and nuclear entry were monitored in real time in both Vero and HeLa cells, demonstrating the utility and efficiency of the strategy in the study of viral infection.

5.
J Virol ; 94(6)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-31896589

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV), an important pathogen that affects the pig industry, is a highly genetically diverse RNA virus. However, the phylogenetic and genomic recombination properties of this virus have not been completely elucidated. In this study, comparative analyses of all available genomic sequences of North American (NA)-type PRRSVs (n = 355, including 138 PRRSV genomes sequenced in this study) in China and the United States during 2014-2018 revealed a high frequency of interlineage recombination hot spots in nonstructural protein 9 (NSP9) and the GP2 to GP3 regions. Lineage 1 (L1) PRRSV was found to be susceptible to recombination among PRRSVs both in China and the United States. The recombinant major parent between the 1991-2013 data and the 2014-2018 data showed a trend from complex to simple. The major recombination pattern changed from an L8 to L1 backbone during 2014-2018 for Chinese PRRSVs, whereas L1 was always the major backbone for US PRRSVs. Intralineage recombination hot spots were not as concentrated as interlineage recombination hot spots. In the two main clades with differential diversity in L1, NADC30-like PRRSVs are undergoing a decrease in population genetic diversity, NADC34-like PRRSVs have been relatively stable in population genetic diversity for years. Systematic analyses of insertion and deletion (indel) polymorphisms of NSP2 divided PRRSVs into 25 patterns, which could generate novel references for the classification of PRRSVs. The results of this study contribute to a deeper understanding of the recombination of PRRSVs and indicate the need for coordinated epidemiological investigations among countries.IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine diseases. However, the phylogenetic and genomic recombination properties of the PRRS virus (PRRSV) have not been completely elucidated. In this study, we systematically compared differences in the lineage distribution, recombination, NSP2 polymorphisms, and evolutionary dynamics between North American (NA)-type PRRSVs in China and in the United States. Strikingly, we found high frequency of interlineage recombination hot spots in nonstructural protein 9 (NSP9) and in the GP2 to GP3 region. Also, intralineage recombination hot spots were scattered across the genome between Chinese and US strains. Furthermore, we proposed novel methods based on NSP2 indel patterns for the classification of PRRSVs. Evolutionary dynamics analysis revealed that NADC30-like PRRSVs are undergoing a decrease in population genetic diversity, suggesting that a dominant population may occur and cause an outbreak. Our findings offer important insights into the recombination of PRRSVs and suggest the need for coordinated international epidemiological investigations.

6.
J Agric Food Chem ; 68(1): 88-96, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31826619

RESUMO

Solanum rostratum is a worldwide malignant invasive weed, causing serious harm to the ecological environment and biodiversity. Strong chemical defense against herbivorous insects is supposed to be one of the successful invasive mechanisms of this exotic plant. However, the real defense components and their action mechanisms and distributions are still unknown. To address these problems, we bioassay-guided isolated compounds from the aerial part of S. rostratum and determined their structures using high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance, and electronic circular dichroism calculation. One new and seven known compounds were identified, and all of the isolates exhibited different levels of antifeedant activities, especially compounds 1 and 4. Consistently, compounds 1 and 4 displayed potent inhibitory effects on antifeedant-related enzymes (AchE and CarE). The action mechanisms of active compounds 1 and 4 were revealed by molecular docking and molecular dynamic simulation studies. Furthermore, the distributions of the active compounds in leaves, stems, and flowers were also analyzed by liquid chromatography-mass spectrometry.


Assuntos
Comportamento Alimentar/efeitos dos fármacos , Inseticidas/farmacologia , Mariposas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plantas Daninhas/química , Solanum/química , Animais , Flores/química , Flores/metabolismo , Inseticidas/química , Inseticidas/isolamento & purificação , Inseticidas/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Mariposas/fisiologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Plantas Daninhas/metabolismo , Metabolismo Secundário , Solanum/metabolismo , Espectrometria de Massas por Ionização por Electrospray
7.
Pharm Res ; 37(1): 4, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823030

RESUMO

PURPOSE: The discovery of nano drug delivery system has rendered a great hope for improving cancer therapy. However, there are some inevitable obstacles that constrain its development, such as the physical and biological barriers, the toxicity of carrier materials and the physiological toxicity of drugs. Here, we report a polymeric prodrug micelle (PPM) with pH/redox dual-sensitivity, which was prepared using methoxy poly (ethylene glycol) (mPEG) with favorable biosafety to improve cancer therapy. METHOD: The tumor microenvironment stimuli-responsive PPMs were prepared and characterized in vitro and in vivo. RESULTS: Our data displayed that the PPMs with excellent biocompatibility exhibited the stimuli-responsive drug release behavior under the microenvironment of cancer cells, superior cellular internalization and lower cytotoxicity. A new method to control drug release behavior was proposed by comparing the release behavior of PPMs formed by PEG of different molecular weight. Furthermore, the fabricated PPMs exhibited the "oral-like" blood concentration curve, improved biodistribution, reduced tissue toxicity and excellent antitumor efficiency in vivo. Consistently, these results indicated that PPMs improved chemotherapeutic efficiency and reduced side effects of the model drug doxorubicin (DOX). CONCLUSION: The prepared pH/redox dual-sensitive PPM enhanced the chemotherapy effect on the tumor site while reducing the physiological toxicity of DOX. Graphical Abstract.


Assuntos
Portadores de Fármacos/química , Micelas , Polietilenoglicóis/química , Pró-Fármacos/química , Microambiente Tumoral , Células A549 , Animais , Antineoplásicos/administração & dosagem , Preparações de Ação Retardada , Doxorrubicina/administração & dosagem , Humanos , Masculino , Camundongos Endogâmicos BALB C , Pró-Fármacos/administração & dosagem , Ratos Sprague-Dawley
8.
Vet Microbiol ; 239: 108486, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31767088

RESUMO

Porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) was first detected in the United States of America (USA) in 1999, several strains were also recognized soon later, and these isolates are typically called North American (NA) PRRSV-1. However, few reports have characterized PRRSV-1 viruses in the USA. We explored the genetic characteristics and diversity of PRRSV-1 viruses circulating in the USA. PRRSV-1 PCR-positive samples collected from seven states in 2010-2018 (n = 27) were subjected to next-generation sequencing. The 27 PRRSV-1 viruses had 88.4-91.3% nucleotide identity to the PRRSV-1 Lelystad-virus strain (the type 1 prototype strain) and 87.4-89.8% to the previously reported NA PRRSV-1 viruses. Individual proteins had several unique genetic characteristics and only one of the 27 tested samples had the characteristic 17-amino acid (aa) deletion in Nsp2, a genetic marker of NA PRRSV-1 viruses described previously. Fourteen isolates displayed a 3-aa C-terminal truncation in the highly conserved Nsp12 gene; 16 samples had a 21- or 18-aa C-terminal truncation in GP3 gene; and one was observed with a 1-aa deletion at the overlapping region of GP3 and GP4. In addition, the GP5 protein in most isolates, excluding one exception, demonstrated similar genetic variation as other reported NA PRRSV-1 isolates. All tested isolates clustered within subtype 1 together with other available NA PRRSV-1 viruses. Collectively, our results provide up-to-date information on PRRSV-1 viruses circulating in the USA in the past 9 years although the number of PRRSV-1 isolates included in this study is limited. These PRRSV-1 viruses have undergone gradual genetic variation and exhibited some previously undescribed genetic characteristics and diversity, which complicates the diagnosis and control of NA PRRSV-1.


Assuntos
Variação Genética , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Animais , Suínos , Estados Unidos
9.
Math Biosci Eng ; 16(6): 6874-6891, 2019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31698593

RESUMO

Honey has been one previous natural food in human history. However, as the supply cannot satisfy the market demand, many incidents of adulterated and fraudulent honey have been reported. In Taiwan, some common adulterated honey and fraudulent honey incidents include (1) mixing honey with fructose, (2) importing cheap honey abroad but labeling them as domestic honey, and (3) labeling cheaper honey (for example, nectar and lychee honey) as high-price honey (for example, longan honey). It is very difficult for consumers to tell the genuineness of the labeling of honey. To protect consumers and honest honey producers, we aim at exploring and developing an efficient and convenient technology that can effectively classify honey. We analyze the infrared spectra of honey samples and apply machine learning technologies to classify honey. The experimental results confirm that this technology can effectively distinguish several main honey types in Taiwan. This technology has the advantages of non-destruction, immediacy, and low manpower. It can serve as an effective tool to fast screen honey products.

10.
Transbound Emerg Dis ; 66(6): 2592-2600, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31379138

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) is an agent of porcine reproductive and respiratory syndrome (PRRS), which causes substantial economic losses to the swine industry. PRRSV displays rapid variation, and five lineages coexist in mainland China. Lineage 3 PRRSVs emerged in mainland China in 2005 and prevailed in southern China after 2010. In the present study, two lineage 3 PRRSV strains, which are named SD110-1608 and SDWH27-1710, were isolated from northern China in 2017. To explore the characteristics and origins of the two strains, we divided lineage 3 into five sublineages (3.1-3.5) based on 146 open reading frame (ORF) 5 sequences. Both strains and the strains isolated from mainland China were classified into sublineage 3.5. Lineage 3 PRRSVs isolated from Taiwan and Hong Kong were classified into sublineages 3.1-3.3 and sublineage 3.4, respectively. Recombination analysis revealed that SD110-1608 and SDWH27-1710 were derived from recombination of QYYZ (major parent strain) and JXA1 (minor parent strain). Sequence alignment showed that SD110-1608 and SDWH27-1710 shared a 36-aa insertion in Nsp2 with QYYZ isolated from Guangdong Province in 2010. Based on the evolutionary relationship among GP2a, GP3, GP4, GP5 and N proteins between sublineages 3.2 (FJ-1) and 3.5 (FJFS), we speculated that sublineage 3.5 (mainland China) originated from sublineage 3.2 (Taiwan, China). This study provides important information regarding the classification and transmission of lineage 3 PRRSVs.


Assuntos
Variação Genética , Genoma Viral , Vírus da Síndrome Respiratória e Reprodutiva Suína/classificação , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Recombinação Genética , Animais , China , Filogenia , Síndrome Respiratória e Reprodutiva Suína/virologia , Alinhamento de Sequência , Suínos
11.
Psychol Med ; : 1-8, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31084640

RESUMO

BACKGROUND: Pharmacological treatments targeting the neuroendocrine stress response may hold special promise in secondary prevention of posttraumatic stress disorder (PTSD). However, findings from clinical trials have been inconsistent and the efficacy of specific drugs, their temporal window of efficacy, effective doses and the characteristics of likely treatment responders remain unclear. METHOD: Using an experimental human model of distressing involuntary memory formation, we compare the effects of two drugs that have theoretical or empirical support as secondary preventive agents in PTSD. Eighty-eight healthy women (average age: 23.5 years) received oral propranolol (80 mg), hydrocortisone (30 mg), or matched placebo immediately after viewing a 'trauma film'. They then completed daily, time-stamped intrusion diaries for 1 week, at the end of which, voluntary memory was tested. RESULTS: While neither drug affected voluntary memory for the trauma narrative, propranolol treatment was associated with 42% fewer, and hydrocortisone with 55% fewer intrusions across the week, relative to placebo. Additionally, propranolol reduced general trauma-like symptoms, and post-drug cortisol levels were negatively correlated with intrusion frequency in the hydrocortisone group. CONCLUSIONS: Overall, this study shows substantial reductions in intrusive memories and preserved voluntary narrative-declarative memory following either propranolol or hydrocortisone in an experimental model of psychological trauma. As such, despite some inconsistencies in clinical trials, our findings support continued investigation of propranolol and hydrocortisone as secondary preventive agents for re-experiencing symptoms of PTSD. The findings also suggest that it is critical for future research to identify the conditions governing the preventive efficacy of these drugs in PTSD.

12.
Respir Med ; 150: 85-94, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30961957

RESUMO

BACKGROUND: There is a controversy in terms of the efficacy of vitamin D supplementation in improving asthma symptom control. Moreover, whether there is a difference in the treatment effect with respect to baseline vitamin D status remains unknown. This meta-analysis was to assess the correlations of vitamin D status with asthma-related respiratory outcomes. METHODS: PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials of vitamin D supplementation in patients with asthma. Primary outcomes were the rate of asthma exacerbation and predicted percentage of forced expiratory volume in first second (FEV1%). Secondary outcomes were asthma control test (ACT) scores, fractional exhaled nitric oxide (FeNO), interleukin-10 (IL-10) and adverse events. RESULTS: A total of 14 randomized controlled trials (1421 participants) fulfilled the inclusion. Vitamin D supplementation was associated with a significant reduction in the rate of asthma exacerbation by 27% (RR: 0.73 95%Cl (0.58-0.92)). In subgroup analysis, the protective effect of exacerbation was restricted in patients with vitamin D insufficiency (vitamin D < 30 ng/ml) (RR: 0.76 95%Cl (0.61-0.95)). An improvement of FEV1% was demonstrated in patients with vitamin D insufficiency and air limitation (FEV1% < 80%) (MD: 8.3 95%Cl (5.95-10.64). No significant difference was observed in ACT scores, FeNO, IL-10 and adverse events. CONCLUSIONS: Vitamin D supplementation reduced the rate of asthma exacerbation, especially in patients with vitamin D insufficiency. Additionally, the benefit of vitamin D had a positive effect on pulmonary function in patients with air limitation and vitamin D insufficiency.


Assuntos
Asma/tratamento farmacológico , Avaliação de Sintomas/métodos , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Adolescente , Adulto , Idoso , Asma/metabolismo , Asma/fisiopatologia , Criança , Pré-Escolar , Progressão da Doença , Expiração , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Lactente , Interleucina-10/análise , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/análise , Ensaios Clínicos Controlados Aleatórios como Assunto , Testes de Função Respiratória/métodos , Avaliação de Sintomas/estatística & dados numéricos , Resultado do Tratamento , Vitamina D/efeitos adversos , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/epidemiologia , Vitaminas/efeitos adversos
13.
Front Psychiatry ; 10: 92, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30918487

RESUMO

Background: Post-traumatic stress disorder (PTSD) and substance consumption commonly co-occur in victims of sexual assault. Substance consumption can occur pre- andi/or post-assault. Pre-assault substance consumption may have an impact on the subsequent development of PTSD. This review aims to provide an overview of current understanding of the effects of acute substance intoxication and chronic pre-assault problematic substance use on symptoms of PTSD amongst individuals who were victims of sexual assault. Methods: PsycINFO, EMBASE, and MEDLINE were searched using terms related to PTSD, sexual assault, and substance consumption. These yielded 2,121 articles, 268 of which were retrieved for more detailed evaluation and 13 of these met inclusion criteria and were appraised in full. Results: Overall, the reviewed papers supported our hypothesis that acute substance intoxication and chronic pre-assault problematic substance use are associated with fewer initial PTSD symptoms but less improvement over time, resulting in slower overall PTSD recovery. They also highlighted post-assault characterological self-blame and negative social reactions as mediators of recovery in the context of pre-assault substance consumption. Conclusions: Acute substance intoxication and chronic pre-assault problematic substance use appear to have an impact on the development of PTSD symptoms amongst victims of sexual assault. The importance of developing early interventions and routine screening and assessment for PTSD and pre-assault substance consumption is emphasized. The limited research on male victims and on substances other than alcohol is highlighted.

14.
Eur J Pharm Sci ; 131: 50-57, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30735825

RESUMO

The aim of the present study was to develop a new marker for correcting water flux in the in situ single-pass intestinal perfusion (SPIP) model. The new marker was designed and synthesized based on the application of both polyethylene glycol-4000 (PEG-4000) and phenol red as non-absorbable markers. The new marker mPEG-PR was obtained by combining phenol red with polyethylene glycol monomethyl ether-4000 (mPEG-4000) and verified by nuclear magnetic resonance (NMR), ultraviolet (UV) spectra, gel permeability chromatograph (GPC) and differential scanning calorimetry (DSC). mPEG-PR fully took the advantages of phenol red and PEG including the low permeability and the simple measuring method which were assessed by the in vitro and the in situ models. In the everted gut sac (EGS) studies, the permeability of mPEG-PR was significantly reduced by nearly 4 times compared with phenol red, and the absorptive percentage of mPEG-PR was <0.1% in 105 min. In addition, the solution with verapamil or without Ca2+ could help improve the absorption of phenol red but did not influence the absorption of mPEG-PR. The results of isosorbide dinitrate as a model drug in the in situ SPIP study showed that both the mPEG-PR marker and the gravimetric method were useful for correcting water flux, which had smaller coefficients of variation than the phenol red marker and the non-corrected method. In conclusion, mPEG-PR could potentially be applied as an accurate and convenient marker for correcting water volume in the intestinal perfusion study.


Assuntos
Corantes/administração & dosagem , Dinitrato de Isossorbida/administração & dosagem , Fenolsulfonaftaleína/administração & dosagem , Polietilenoglicóis/administração & dosagem , Animais , Absorção Intestinal , Masculino , Ratos Sprague-Dawley
15.
Vet Res ; 49(1): 103, 2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-30290850

RESUMO

In the original publication of this article [1], the author found the brand of vimentin antibody was wrong in Fig. 3. The legend of Fig. 3, 'mouse anti-vimentin mAb (Cell Signaling Technology) at 4 °C overnight' should be 'mouse anti-vimentin mAb (Sigma-Aldrich) at 4 °C overnight'.

16.
Vet Microbiol ; 222: 46-54, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30080672

RESUMO

The recent rapid evolution of PRRSVs has resulted in certain biological characteristic changes, such as the fact that an increasing number of field PRRSVs can be isolated from PAMs but not from Marc-145 cells. In this study, we first isolated Marc-145-unadaptive field PRRSV strains from PAMs; sequence analysis showed that these PRRSVs belong to the HP-PRRSV (lineage 8) branch or NADC30-Like (lineage 1) branch. We further found major variations in ORF2-4 regions. To explore the viral adaptation mechanisms in detail, we constructed a full-length cDNA clone of MY-376, a Marc-145-unadaptive PRRSV. Construction of serially chimeric viruses of HuN4-F112 (a Marc-145-adaptive strain) and MY-376 demonstrated that variation in the minor envelope protein (GP2a and GP3) complex is a main determinant of PRRSV tropism for Marc-145 cells.


Assuntos
Células Epiteliais/virologia , Variação Genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/isolamento & purificação , Proteínas do Envelope Viral , Animais , Técnicas de Cultura de Células , Linhagem Celular , DNA Complementar , Fases de Leitura Aberta/genética , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/química , Suínos , Proteínas do Envelope Viral/genética , Tropismo Viral
17.
Psychophysiology ; 55(11): e13213, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30069970

RESUMO

The stimulus-preceding negativity (SPN) is a reliable index of incentive anticipation. However, it remains controversial whether the anticipatory process indexed by the SPN is modulated by incentive valence. The present study investigated the effect of valence on the SPN in a gambling task that required participants to make a binary (gain vs. loss) prediction after their choice on trials with different reward probabilities. Behaviorally, the participants exhibited a positive bias in their prediction. Electrophysiologically, a valence asymmetry was observed for the SPN. Specifically, the SPN was more pronounced when the participants made a gain relative to loss prediction, which was specific over the left hemisphere. Moreover, the SPN showed an uncertainty effect with enhanced amplitudes before uncertain versus certain outcomes, which tended to be pronounced during gain compared to loss anticipation. These findings indicated that the SPN is more sensitive to positive relative to negative valence, which may be mediated by the mesocorticolimbic dopaminergic pathway.© 2018 Society for Psychophysiological Research.


Assuntos
Antecipação Psicológica/fisiologia , Córtex Cerebral/fisiologia , Comportamento de Escolha/fisiologia , Emoções/fisiologia , Potenciais Evocados/fisiologia , Motivação/fisiologia , Recompensa , Incerteza , Adolescente , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Adulto Jovem
18.
Drug Dev Ind Pharm ; 44(12): 1990-1999, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30058391

RESUMO

The purpose of this research was to develop multiple-unit gastric floating mini-tablets and to evaluate the possibility of using these mini-tablets as a delivery system to improve the drug absorption for drugs with a narrow absorption window. Mini-tablets were prepared using hydroxypropyl methylcellulose (HPMC K100M) and carbopol 971P as release retarding agents and sodium bicarbonate (NaHCO3) as gas-forming agent. The properties of the prepared mini-tablets in terms of floating characteristic parameters and in vitro release were evaluated. Furthermore, in vivo gastric retention study in rats and in vivo pharmacokinetic study in rabbits of the optimized formulation were performed. The optimized mini-tablets containing 45% HPMC K100M, 15% stearyl alcohol, 13% carbopol 971P, and 12% NaHCO3 were found to float immediately within 1 min and duration more than 9 h. The in vivo gastric retention study results indicated that the mini-tablets could retain in the stomach for more than 6.67 h. Furthermore, the AUC0-t of the floating mini-tablets (6849.83 ± 753.80 h ng·mL-1) was significantly higher than that of marketed sustained-release tablets XATRAL®XL (4970.16 ± 924.60 h ng·mL-1). All these results illustrated that the gastric floating mini-tablets might be a promising drug delivery system for drugs with a narrow absorption window.


Assuntos
Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Desenho de Fármacos , Liberação Controlada de Fármacos , Quinazolinas/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Química Farmacêutica , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Excipientes/química , Mucosa Gástrica/metabolismo , Absorção Gastrointestinal , Masculino , Quinazolinas/administração & dosagem , Quinazolinas/química , Coelhos , Ratos , Ratos Sprague-Dawley , Solubilidade , Espectroscopia de Luz Próxima ao Infravermelho , Comprimidos , Fatores de Tempo
19.
Vet Res ; 49(1): 75, 2018 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-30053894

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important globally distributed and highly contagious pathogen that has restricted cell tropism in vivo and in vitro. In the present study, we found that annexin A2 (ANXA2) is upregulated expressed in porcine alveolar macrophages infected with PRRSV. Additionally, PRRSV replication was significantly suppressed after reducing ANXA2 expression in Marc-145 cells using siRNA. Bioinformatics analysis indicated that ANXA2 may be relevant to vimentin, a cellular cytoskeleton component that is thought to be involved in the infectivity and replication of PRRSV. Co-immunoprecipitation assays and confocal analysis confirmed that ANXA2 interacts with vimentin, with further experiments indicating that the B domain (109-174 aa) of ANXA2 contributes to this interaction. Importantly, neither ANXA2 nor vimentin alone could bind to PRRSV and only in the presence of ANXA2 could vimentin interact with the N protein of PRRSV. No binding to the GP2, GP3, GP5, nor M proteins of PRRSV was observed. In conclusion, ANXA2 can interact with vimentin and enhance PRRSV growth. This contributes to the regulation of PRRSV replication in infected cells and may have implications for the future antiviral strategies.


Assuntos
Anexina A2/metabolismo , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Vimentina/metabolismo , Replicação Viral , Animais , Ligação Proteica , Suínos
20.
FASEB J ; 32(8): 4293-4301, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29509513

RESUMO

Several groups have used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) for DNA virus editing. In most cases, one single-guide RNA (sgRNA) is used, which produces inconsistencies in gene editing. In this study, we used a swine herpesvirus, pseudorabies virus, as a model to systematically explore the application of CRISPR/Cas9 in DNA virus editing. In our current report, we demonstrated that cotransfection of 2 sgRNAs and a viral genome resulted in significantly better knockout efficiency than the transfection-infection-based approach. This method could result in 100% knockout of ≤3500 bp of viral nonessential large fragments. Furthermore, knockin efficiency was significantly improved by using 2 sgRNAs and was also correlated with the number of background viruses. We also demonstrated that the background viruses were all 2-sgRNA-mediated knockout mutants. Finally, this study demonstrated that the efficacy of gene knockin is determined by the replicative kinetics of background viruses. We propose that CRISPR/Cas9 coupled with 2 sgRNAs creates a powerful tool for DNA virus editing and offers great potential for future applications.-Tang, Y.-D., Guo, J.-C., Wang, T.-Y., Zhao, K., Liu, J.-T., Gao, J.-C., Tian, Z.-J., An, T.-Q., Cai, X.-H. CRISPR/Cas9-mediated 2-sgRNA cleavage facilitates pseudorabies virus editing.


Assuntos
Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Vírus de DNA/genética , RNA Guia/genética , Animais , Linhagem Celular , Chlorocebus aethiops , Edição de Genes/métodos , Técnicas de Inativação de Genes/métodos , Genoma Viral/genética , Herpesvirus Suídeo 1/genética , Transfecção/métodos , Células Vero
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