RESUMO
Periodontal disease is a chronic disease with a high prevalence, and in order to secure natural materials to prevent oral diseases, new materials that protect periodontal tissue from inflammation are being sought. Genes were identified using real-time quantitative polymerase chain reaction (RT-qPCR), and proteins were confirmed using Western blot. Dichlorodihydrofluorescein diacetate (DCF-DA) analysis was used, and the antibacterial effects were confirmed through Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) analysis. To confirm this effect in vivo, Sprague-Dawley rats, in which periodontitis was induced using ligation or Lipopolysaccharide of Porphyromonas gingivalis (PG-LPS), were used. In vitro experiments using human periodontal ligament (HPDL) cells stimulated with PG-LPS showed that Ginsenoside Rg6 (G-Rg6) had anti-inflammatory, antibacterial, antioxidant, and osteoblast differentiation properties. In vivo, G-Rg6 was effective in Sprague-Dawley rats in which periodontitis was induced using ligation or PG-LPS. Therefore, Ginsenoside Rg6 shows potential effectiveness in alleviating periodontitis.
Assuntos
Ginsenosídeos , Lipopolissacarídeos , Periodontite , Ratos , Humanos , Animais , Lipopolissacarídeos/toxicidade , Ratos Sprague-Dawley , Inflamação/tratamento farmacológico , Antibacterianos , Porphyromonas gingivalis , Periodontite/tratamento farmacológicoRESUMO
BACKGROUND: Eating behavior is determined by both homeostatic and hedonic values. OBJECTIVE: We investigated the association of hedonic value with striatal dopamine transporter (DAT) availability sub-regionally. METHOD: An intravenous bolus injection of 18F-FP-CIT was administered after the infusion of glucose or placebo, and the emission data were acquired over 90 min. DAT availability and binding potential (BPND) were measured via the simplified reference tissue method. Subjects were assessed with sensory taste test of sucrose solutions. The "most liked" sucrose concentration (%) was determined as the hedonic rating for sucrose. RESULTS: Twenty healthy males participated in this study. After glucose loading, BPNDs of putamen significantly increased, and those of caudate nucleus showed the increasing trend, while those of ventral striatum were not significantly different. After glucose loading, the "most liked" sucrose concentration (%) was negatively associated with BPNDs of caudate nucleus and showed the trend of positive association with those from ventral striatum. Slopes of regression lines were significantly different according to the sub-regions of striatum. CONCLUSION: We have highlighted that striatal DAT increased after glucose loading in dorsal striatum, not in ventral striatum. These changes of striatal DAT were sub-regionally associated with the hedonic rating of sucrose from each subject.
Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina , Sacarose , Corpo Estriado/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Glucose/metabolismo , Humanos , Masculino , Sacarose/metabolismoRESUMO
Several next-generation (universal) influenza vaccines and broadly neutralizing antibodies (bNAbs) are in clinical development. Some of these mediate inhibitions of virus replication at the postentry stage or use Fc-dependent mechanisms. Nonneutralizing antibodies have the potential to mediate enhancement of viral infection or disease. In the current study, two monoclonal antibodies (MAbs) 72/8 and 69/1, enhanced respiratory disease (ERD) in mice following H3N2 virus challenge by demonstrating increased lung pathology and changes in lung cytokine/chemokine levels. MAb 78/2 caused changes in the lung viral loads in a dose-dependent manner. Both MAbs increased HA sensitivity to trypsin cleavage at a higher pH range, suggesting MAb-induced conformational changes. pHrodo-labeled virus particles' entry and residence time in the endocytic compartment were tracked during infection of Madin-Darby canine kidney (MDCK) cells. Both MAbs reduced H3N2 virus residence time in the endocytic pathway, suggesting faster virus fusion kinetics. Structurally, 78/2 and 69/1 Fabs bound the globular head or base of the head domain of influenza hemagglutinin (HA), respectively, and induced destabilization of the HA stem domain. Together, this study describes Mab-induced destabilization of the influenza HA stem domain, faster kinetics of influenza virus fusion, and ERD in vivo. The in vivo animal model and in vitro assays described could augment preclinical safety evaluation of antibodies and next-generation influenza vaccines that generate antibodies which do not block influenza virus-receptor interaction.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Anticorpos Antivirais/efeitos adversos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Pulmão/virologia , Infecções por Orthomyxoviridae/virologia , Internalização do Vírus/efeitos dos fármacos , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/metabolismo , Anticorpos Antivirais/química , Anticorpos Antivirais/metabolismo , Sítios de Ligação , Cães , Endocitose/efeitos dos fármacos , Endocitose/imunologia , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/patogenicidade , Pulmão/imunologia , Pulmão/patologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/patologia , Ligação Proteica , Proteólise , Carga Viral/efeitos dos fármacos , Vírion/efeitos dos fármacos , Vírion/imunologia , Vírion/patogenicidade , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Plasmodium vivax malaria has a persistent liver stage that causes relapse, and introducing tafenoquine to suppress relapse could aid in disease eradication. Therefore, we assessed the impact of tafenoquine introduction on P. vivax malaria incidence and performed a cost-benefit analysis from the payer's perspective. METHODS: We expanded the previously developed P. vivax malaria dynamic transmission model and calibrated it to weekly civilian malaria incidences in 2014-2018. Primaquine and tafenoquine scenarios were considered by assuming different relapse probabilities, and relapse and total P. vivax malaria cases were predicted over the next decade for each scenario. We then estimated the number of cases prevented by replacing primaquine with tafenoquine. The cost and benefit of introducing tafenoquine were obtained using medical expenditure from a nationwide database, and a cost-benefit analysis was conducted. A probabilistic sensitivity analysis was performed to assess the economic feasibility robustness of tafenoquine introduction under uncertainties of model parameters, costs, and benefits. RESULTS: Under 0.04 primaquine relapse probability, the introduction of tafenoquine with relapse probability of 0.01 prevented 129 (12.27%) and 35 (77.78%) total and relapse cases, respectively, over the next decade. However, under the same relapse probability as primaquine, introducing tafenoquine had no additional preventative effect. The 14-day primaquine treatment cost was $3.71. The tafenoquine and the glucose-6-phosphate dehydrogenase rapid diagnostic testing cost $57.37 and $7.76, totaling $65.13. The average medical expenditure per malaria patient was estimated at $1444.79. The cost-benefit analysis results provided an incremental benefit-cost ratio (IBCR) from 0 to 3.21 as the tafenoquine relapse probability decreased from 0.04 to 0.01. The probabilistic sensitivity analysis showed an IBCR > 1, indicating that tafenoquine is beneficial, with a probability of 69.1%. CONCLUSION: Tafenoquine could reduce P. vivax malaria incidence and medical costs and bring greater benefits than primaquine.
Assuntos
Antimaláricos , Malária Vivax , Aminoquinolinas , Antimaláricos/uso terapêutico , Análise Custo-Benefício , Humanos , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Malária Vivax/prevenção & controle , Primaquina/uso terapêutico , RecidivaRESUMO
BACKGROUND: The reproduction number is one of the most crucial parameters in determining disease dynamics, providing a summary measure of the transmission potential. However, estimating this value is particularly challenging owing to the characteristics of epidemic data, including non-reproducibility and incompleteness. METHODS: In this study, we propose mathematical models with different population structures; each of these models can produce data on the number of cases of the influenza A(H1N1)pdm09 epidemic in South Korea. These structured models incorporating the heterogeneity of age and region are used to estimate the reproduction numbers at various terminal times. Subsequently, the age- and region-specific reproduction numbers are also computed to analyze the differences illustrated in the incidence data. RESULTS: Incorporation of the age-structure or region-structure allows for robust estimation of parameters, while the basic SIR model provides estimated values beyond the reasonable range with severe fluctuation. The estimated duration of infectious period using age-structured model is around 3.8 and the reproduction number was estimated to be 1.6. The estimated duration of infectious period using region-structured model is around 2.1 and the reproduction number was estimated to be 1.4. The estimated age- and region-specific reproduction numbers are consistent with cumulative incidence for corresponding groups. CONCLUSIONS: Numerical results reveal that the introduction of heterogeneity into the population to represent the general characteristics of dynamics is essential for the robust estimation of parameters.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Influenza Humana/transmissão , Adolescente , Adulto , Número Básico de Reprodução/estatística & dados numéricos , Epidemias , Humanos , Incidência , Modelos Teóricos , República da Coreia/epidemiologia , Adulto JovemRESUMO
INTRODUCTION: The objectives were to visualize the incisive canal (IC) remodelling following maximum incisor retraction and to evaluate its impact on canal-invasion-associated apical root resorption. METHODS: Pre- and post-treatment CBCT images of 34 adult orthodontic patients (age 18-47 years) with a large amount of maxillary incisor retraction (>4 mm) using temporary anchorage devices (TADs) were retrospectively evaluated. Maxillary regional superimpositions and 3D models of the IC along with central incisors were used to measure the changes in IC dimension, IC invasion by the roots and IC remodelling. In addition, the association of the amount of apical root resorption with the root-IC relationship and IC remodelling were evaluated. RESULTS: IC invasion by the incisor roots following maximum retraction was seen in 53% (18 out of 34) of the cases. IC with larger volume and area showed more invasions compared with those with smaller volume and area (P < .01). The amount of root resorption was significantly higher with IC invasion than without invasion (2.39 mm vs 0.82 mm, P < .0001). IC remodelling following maximum retraction was seen in 24% of the subjects. IC remodelling group demonstrated less apical root resorption than the non-remodelling group (0.98 mm vs 3.27 mm, P < .0001). CONCLUSION: IC with larger volume and surface area before treatment were more likely to show canal invasion by the incisor roots after maximum retraction. IC invasion resulted in apical root resorption. However, approximately one-fourth of cases showed remodelling of the IC, which reduced the amount of root resorption.
Assuntos
Reabsorção da Raiz , Adolescente , Adulto , Humanos , Incisivo/diagnóstico por imagem , Maxila/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Reabsorção da Raiz/diagnóstico por imagem , Raiz Dentária , Adulto JovemRESUMO
Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract disease in infants. Previously, we elucidated the antibody repertoire following primary RSV infection in infants. Whole genome-fragment phage display libraries (GFPDL) expressing linear and conformational epitopes from RSV bound 100-fold more phages within attachment protein (G) following primary RSV infection. The G-reactive epitopes spanned the N- and C-termini of G ectodomain, in addition to the central conserved domain (CCD). In the current study, we examined the contribution of antigenic regions of G outside of the CCD to RSV-specific immunity. We evaluated the immunogenicity, neutralization and protective efficacy of all RSV-G antigenic sites identified following primary RSV infection using recombinant E. coli expressed G ectodomain (REG), CCD-deleted G ectodomain (REG ΔCCD), N- and C-terminal G subdomains, and antigenic site peptides. The REG ΔCCD, N- and C-terminal subdomains and peptides generated antibody titers in rabbits and mice that bound fully glycosylated Recombinant Mammalian expressed G ectodomain (RMG) and intact RSV virion particles but minimal in vitro neutralization titers compared with the intact G ectodomain. Vaccinated mice were challenged intranasally with RSV-A2 Line 19F. Viral replication in nasal cavity and lungs was significantly reduced in vaccinated animals compared to unimmunized controls. Control of viral loads post-RSV challenge correlated with serum antibody binding to the virus particles. In addition, very low Th2/Th1 cytokine ratios were found in the lungs of REG ΔCCD vaccinated mice after challenge. These data demonstrate the presence of multiple protective sites in RSV G protein outside of the CCD that could contribute to the development of a bacterially produced unglycosylated G protein as safe and protective vaccine against RSV disease.
Assuntos
Anticorpos Neutralizantes , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/imunologia , Células A549 , Animais , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/genética , Anticorpos Neutralizantes/imunologia , Células Cultivadas , Sequência Conservada/genética , Cisteína/química , Cisteína/genética , Mapeamento de Epitopos , Epitopos/química , Epitopos/genética , Epitopos/imunologia , Feminino , Humanos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Domínios Proteicos/genética , Domínios Proteicos/imunologia , Coelhos , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/patologia , Vacinas contra Vírus Sincicial Respiratório/síntese química , Vacinas contra Vírus Sincicial Respiratório/química , Vacinas contra Vírus Sincicial Respiratório/genética , Vírus Sincicial Respiratório Humano/química , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/imunologia , Proteínas do Envelope Viral/genética , Proteínas Virais de Fusão/química , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/imunologiaRESUMO
Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity are emerging as attractive therapeutic strategies for the management of severe vascular inflammatory diseases. Recently, we found that JH-4, a synthesized decursin derivative, exhibited a strong anti-Hutchinson-Gilford progeria syndrome by efficiently blocking progerin-lamin A/C binding. In this study, we examined the effects of JH-4 on HMGB1-mediated septic responses and the survival rate in a mouse sepsis model. The anti-inflammatory activities of JH-4 were monitored based on its effects on lipopolysaccharide- or cecal ligation and puncture (CLP)-mediated release of HMGB1. The antiseptic activities of JH-4 were determined by measuring permeability, leukocyte adhesion, migration, and the activation of proinflammatory proteins in HMGB1-activated human umbilical vein endothelial cells and mice. JH-4 inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. JH-4 also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with JH-4 reduced CLP-induced release of HMGB1, sepsis-related mortality, and pulmonary injury in vivo. Our results indicate that JH-4 is a possible therapeutic agent to treat various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.
Assuntos
Anti-Infecciosos Locais/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Benzopiranos/uso terapêutico , Butiratos/uso terapêutico , Proteína HMGB1/metabolismo , Extratos Vegetais/uso terapêutico , Sepse/tratamento farmacológico , Sepse/mortalidade , Angelica/química , Animais , Anti-Infecciosos Locais/farmacologia , Anti-Inflamatórios/farmacologia , Benzopiranos/farmacologia , Butiratos/farmacologia , Permeabilidade Capilar/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Proteína HMGB1/antagonistas & inibidores , Proteína HMGB1/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Leucócitos/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/farmacologia , Sepse/metabolismo , Taxa de SobrevidaRESUMO
During Bacillus subtilis sporulation, segregating sister chromosomes are anchored to cell poles and the chromosome is remodeled into an elongated structure called the axial filament. Data indicate that a developmentally regulated protein called RacA is involved in these functions. To gain insight into how RacA performs these diverse processes we performed a battery of structural and biochemical analyses. These studies show that RacA contains an N-terminal winged-helix-turn-helix module connected by a disordered region to a predicted coiled-coil domain. Structures capture RacA binding the DNA using distinct protein-protein interfaces and employing adjustable DNA docking modes. This unique DNA binding mechanism indicates how RacA can both specifically recognize its GC-rich centromere and also non-specifically bind the DNA. Adjacent RacA molecules within the protein-DNA structure interact leading to DNA compaction, suggesting a mechanism for axial filament formation. We also show that the RacA C-domain coiled coil directly contacts the coiled coil region of the polar protein DivIVA, which anchors RacA and hence the chromosome to the pole. Thus, our combined data reveal unique DNA binding properties by RacA and provide insight into the DNA remodeling and polar anchorage functions of the protein.
Assuntos
Bacillus subtilis/genética , Bacillus subtilis/metabolismo , DNA/metabolismo , Cinetocoros/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , DNA/química , Cinetocoros/química , Modelos Moleculares , Conformação Molecular , Simulação de Acoplamento Molecular , Domínios e Motivos de Interação entre Proteínas , Esporos Bacterianos , Relação Estrutura-AtividadeRESUMO
Highly selective cytochrome P450 CYP2J2 (CYP2J2) inhibitors suitable for reaction phenotyping are currently not available. (7S)-(+)-(4-Nitro-phenyl)-acrylic acid, 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester (LKY-047), a decursin derivative, was synthesized, and its inhibitor potencies toward CYP2J2 as well as other cytochrome P450 (P450) enzymes in human liver microsomes (HLM) were evaluated. LKY-047 was demonstrated to be a strong competitive inhibitor of CYP2J2-mediated astemizole O-demethylase and terfenadine hydroxylase activity, with Ki values of 0.96 and 2.61 µM, respectively. It also acted as an uncompetitive inhibitor of CYP2J2-mediated ebastine hydroxylation with a Ki value of 3.61 µM. Preincubation of LKY-047 with HLMs and NADPH did not alter inhibition potency, indicating that it is not a mechanism-based inhibitor. LKY-047 was found to be a selective CYP2J2 inhibitor with no inhibitory effect on other human P450s, such as CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A (IC50 > 50 µM). These in vitro data support the use of LKY-047 as a selective CYP2J2 inhibitor with potential application in the identification of P450 isoforms responsible for drug metabolism in reaction phenotyping assays.
Assuntos
Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Citocromo P-450 CYP2J2 , Humanos , Hidroxilação/efeitos dos fármacos , Inativação Metabólica/efeitos dos fármacos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , NADP/metabolismo , Isoformas de Proteínas/metabolismoRESUMO
We synthesized (+)-decursin derivatives substituted with cinnamoyl- and phenyl propionyl groups originating from (+)-CGK062 and screened them using a cell-based assay to detect relative luciferase reporter activity. Of this series, compound 8b, in which a 3-acetoxy cinnamoyl group was introduced, most potently inhibited (97.0%) the Wnt/ß-catenin pathway. Specifically, compound 8b dose-dependently inhibited Wnt3a-induced expression of the ß-catenin response transcription (CRT) and increased ß-catenin degradation in HEK293 reporter cells. Furthermore, compound 8b suppressed expression of the downstream ß-catenin target genes cyclin D1 and c-myc and suppressed PC3 cell growth in a concentration-dependent manner.
Assuntos
Benzopiranos/farmacologia , Butiratos/farmacologia , Proteínas Wnt/antagonistas & inibidores , beta Catenina/antagonistas & inibidores , Benzopiranos/síntese química , Benzopiranos/química , Butiratos/síntese química , Butiratos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade , Proteínas Wnt/metabolismo , beta Catenina/metabolismoRESUMO
The efficient time schedule and prioritization of vaccine supplies are important in mitigating impact of an influenza pandemic. In practice, there are restrictions associated with limited vaccination coverage and the maximum daily vaccine administration. We extend previous work on optimal control for influenza to reflect these realistic restrictions using mixed constraints on state and control variables. An optimal control problem is formulated with the aim of minimizing the number of infected individuals while considering intervention costs. Time-dependent vaccination is computed and analysed using a model incorporating heterogeneity in population structure under different settings of transmissibility levels, vaccine coverages, and time delays.
RESUMO
In this Letter, we investigated the barrier protective effects of 3-N-(MeO)n-cinnamoyl carbazoles (BS 1; n=1, BS 2; n=2, BS 3; n=3) and 3-O-(MeO)3-cinnamoyl carbazole (BS 4) against high-mobility group box 1 (HMGB1)-mediated vascular disruptive responses in human umbilical vein endothelial cells (HUVECs) and in mice for the first time. Data showed that BS 2, BS 3, and BS 4, but not BS 1, inhibited HMGB1-mediated vascular disruptive responses and transendothelial migration of human neutrophils to HUVECs. BS 2, BS3, and BS 4 also suppressed HMGB1-induced hyperpermeability and leukocyte migration in mice. Interestingly, the barrier protective effects of BS 3 and BS 4 were better than those of BS 2. These results suggest that the number of methoxy groups substituted on the cinnamamide or cinnamate moiety of the 9H-3-carbazole derivative is an important pharmacophore for the barrier protective effects of these compounds.
Assuntos
Carbazóis/química , Carbazóis/farmacologia , Proteína HMGB1/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Animais , Carbazóis/síntese química , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Leucócitos/metabolismo , Camundongos , Estrutura Molecular , Permeabilidade/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Quorum sensing (QS) controls certain behaviors of bacteria in response to population density. In gram-negative bacteria, QS is often mediated by N-acyl-L-homoserine lactones (acyl-HSLs). Because QS influences the virulence of many pathogenic bacteria, synthetic inhibitors of acyl-HSL synthases might be useful therapeutically for controlling pathogens. However, rational design of a potent QS antagonist has been thwarted by the lack of information concerning the binding interactions between acyl-HSL synthases and their ligands. In the gram-negative bacterium Burkholderia glumae, QS controls virulence, motility, and protein secretion and is mediated by the binding of N-octanoyl-L-HSL (C8-HSL) to its cognate receptor, TofR. C8-HSL is synthesized by the acyl-HSL synthase TofI. In this study, we characterized two previously unknown QS inhibitors identified in a focused library of acyl-HSL analogs. Our functional and X-ray crystal structure analyses show that the first inhibitor, J8-C8, binds to TofI, occupying the binding site for the acyl chain of the TofI cognate substrate, acylated acyl-carrier protein. Moreover, the reaction byproduct, 5'-methylthioadenosine, independently binds to the binding site for a second substrate, S-adenosyl-L-methionine. Closer inspection of the mode of J8-C8 binding to TofI provides a likely molecular basis for the various substrate specificities of acyl-HSL synthases. The second inhibitor, E9C-3oxoC6, competitively inhibits C8-HSL binding to TofR. Our analysis of the binding of an inhibitor and a reaction byproduct to an acyl-HSL synthase may facilitate the design of a new class of QS-inhibiting therapeutic agents.
Assuntos
4-Butirolactona/análogos & derivados , Proteínas de Bactérias/antagonistas & inibidores , Burkholderia/metabolismo , Ligação Proteica , Percepção de Quorum/fisiologia , S-Adenosilmetionina/metabolismo , Fatores de Transcrição/antagonistas & inibidores , 4-Butirolactona/metabolismo , Proteínas de Bactérias/metabolismo , Cristalografia por Raios X , Fluorescência , Homosserina/análogos & derivados , Homosserina/metabolismo , Lactonas/metabolismo , Especificidade por Substrato , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Green teas can be grouped based on their flavor profiles. The country of origin appears to have a strong influence on the flavor of green tea probably because similar processing methods are widely used within each particular country and flavor is dependent, in part, on processing. The aim of this article is to determine what flavor differences exist among a wide range of green teas (n = 138) produced in various countries. RESULTS: In this study we found that roast-processed teas were mostly responsible for brown-related flavors and steam-processed teas were responsible for green-related flavors. The prices of the green teas did not differentiate the flavors of the samples. Often highly priced green teas were grouped with low-priced green teas from the same manufacturer or country of origin according to their flavor attributes. CONCLUSIONS: Differences in the tea plant varieties or cultivars likely affects flavors in green tea. However, those were not known for many samples in this research and more study will be needed to determine the effects of specific differences in varieties or cultivars.
Assuntos
Camellia sinensis/química , Manipulação de Alimentos , Qualidade dos Alimentos , Folhas de Planta/química , Chá/química , África Oriental , Ásia , Camellia sinensis/crescimento & desenvolvimento , Análise por Conglomerados , Custos e Análise de Custo , Dieta/economia , Dieta/etnologia , Humanos , Kansas , Folhas de Planta/crescimento & desenvolvimento , Análise de Componente Principal , Reprodutibilidade dos Testes , Paladar , Chá/economiaRESUMO
This study compared check-all-that-apply (CATA) and rating methods using simple flavor foods and determined the discrimination ability of two consumer-based methods. Orange juice (simple flavor and liquid) and yogurt (simple flavor and semi-solid) samples were used. Six samples with different flavors and textures were evaluated for each food group. One hundred twenty consumers participated in each food session. CATA and rating were performed in two visits at weekly intervals. Consumers in each session distinguished the sample characteristics, and similar results were obtained using the CATA and rating methods. Although the number of characteristics with a significant difference in the rating method was relatively higher than that of CATA, some attributes with low frequency and intensity values may not have a significant effect on sample discrimination. Therefore, the types of questionnaire should be selected considering the test objectives and how similar the samples were. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01413-y.
RESUMO
Four frozen dumplings were prepared using air-frying, microwaving, pan-frying, and steaming for consumer acceptability and texture perception measure. Cluster analysis was performed and two groups resulted. Neutral consumers who generally rated 'like slightly' and 'neither like nor dislike' were influenced by the combinations of dumpling and cooking methods. Dumpling likers who rated higher than 'like moderately' were influenced by cooking methods. When divided into clusters, each effect was significant. For dumplings, consumers preferred three products over one. Regarding cooking methods, neutral consumers preferred pan-frying and air-frying. However, dumpling likers preferred pan-frying. Chewy, soft, crisp, and sticky characteristics positively influenced on acceptability. In addition, dumpling shells and fillings were analyzed to measure crispness and firmness, respectively, using a texture analyzer. Cooking methods influenced skin crispness but dumplings influenced filling firmness. Although correlation was very low between consumer texture perception and analytical measure, using both would be beneficial in further understanding. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01389-9.
RESUMO
BACKGROUND: In South Korea, the National Immunization Program has included one-dose varicella vaccination for 1-year-olds since 2005. This study examines the potential impact of introducing a two-dose varicella vaccination for children, along with zoster vaccination for adults, using either the zoster vaccine live (ZVL) or recombinant zoster vaccine (RZV). METHODS: The investigation considered four strategies in a base case scenario. The first involved introducing zoster vaccination for 60-year-olds, with a 60 % coverage. The second strategy combined zoster vaccination with a second-dose varicella vaccination for 4-year-olds, with a 90 % coverage. An age-structured model spanning 50 years was employed, assuming a zoster vaccine catch-up campaign over the initial 5 years. Cost-effectiveness analyses were conducted, assessing incremental cost-effectiveness ratios (ICERs), incremental net monetary benefits (INMBs), and net loss under different ages at zoster vaccination (50, 60, 65, and 70 years) and varying willingness-to-pay (WTP) levels from â©40 million ($34,998) to â©84 million ($74,000). RESULTS: All strategies were cost-effective and significantly reduced herpes zoster (HZ) incidence, preventing approximately 3,077,000 to 7,609,000 cases, depending on the chosen strategy. The combined strategy prevented around 4,950,000 varicella and 653,000 HZ cases additionally. RZV outperformed ZVL by preventing twice as many HZ cases and offering greater QALY gains. However, ZVL was more cost-effective due to its lower cost. Probabilistic sensitivity analyses revealed that RZV became more cost-effective at higher WTP thresholds, exceeding â©60.9 million ($53,193) in terms of ICER and â©62.5 million ($54,591) for INMBs and net loss. The optimal age for zoster vaccination was 60 years concerning ICER but 50 years regarding INMB. CONCLUSIONS: Combining RZV with a two-dose varicella vaccination strategy reduced the disease burden and improved QALY more effectively, though ZVL remained more cost-effective at lower WTP levels. Decisions regarding vaccination policies should be balanced between the public health needs and WTP levels.
Assuntos
Vacina contra Varicela , Varicela , Análise Custo-Benefício , Vacina contra Herpes Zoster , Herpes Zoster , Modelos Teóricos , Vacinação , Humanos , Herpes Zoster/prevenção & controle , Herpes Zoster/epidemiologia , Herpes Zoster/economia , República da Coreia/epidemiologia , Varicela/prevenção & controle , Varicela/epidemiologia , Varicela/economia , Vacina contra Varicela/economia , Vacina contra Varicela/administração & dosagem , Vacina contra Varicela/imunologia , Vacina contra Herpes Zoster/economia , Vacina contra Herpes Zoster/administração & dosagem , Pessoa de Meia-Idade , Pré-Escolar , Idoso , Vacinação/economia , Vacinação/métodos , Masculino , Feminino , Programas de Imunização/economia , Criança , Lactente , Adulto , Incidência , Herpesvirus Humano 3/imunologiaRESUMO
Understanding how shear affects whey protein stability is crucial to deal with typical industrial issues occurring at the bulk solution/surface interface, such as fouling during heat treatments. However, at the state of the art, this effect remains unclear, contrary to that of temperature. This article presents a novel strategy to study the impact of shear rate and concentration on the accumulation of whey protein surficial deposits. It consists in applying a range of shear rates (0-200 s-1) at controlled temperature (65 °C) on whey protein solutions (5-10 wt%) by a parallel plate rheometer equipped with a glass disc, thus allowing the off-line characterization of the deposits by microscopy. Our results highlight an unequivocal effect of increasing shear stress. At 5 wt%, it fosters the formation of primary deposits (≈ 10 µm), whereas at 10 wt% it results in the development of complex branched structures (≈ 50 µm) especially for shear rates ranging from 140 s-1 to 200 s-1. Based on the classification by size of the observed populations, we discuss possible hypotheses for the deposit growth kinetics, involving the interplay of different physico-chemical protein-surface interactions and paving the way to future further investigations.
Assuntos
Reologia , Proteínas do Soro do Leite , Proteínas do Soro do Leite/química , Estresse Mecânico , Resistência ao Cisalhamento , Propriedades de Superfície , CinéticaRESUMO
Vaccinating young children against rotavirus (RV) is a promising preventive strategy against rotavirus gastroenteritis (RVGE). We evaluated the relative risk reduction of RVGE induced by universal vaccination in Vietnam through dynamic model analysis. We developed an age-stratified dynamic Vaccinated-Susceptible-Infectious-Recovered-Susceptible model to analyze RV transmission and assess vaccine effectiveness (VE). We assumed 3 different vaccine efficacies: 55%, 70%, and 85%. For model calibration, we used a database of patients under 5 years of age admitted to Ho Chi Minh No.1 Hospital with RVGE between January 2013 and December 2018. Assuming a vaccination rate of 95%, the number of RVGE hospitalizations after 5 years from universal RV vaccination decreased from 92,502 cases to 45,626 with 85% efficacy, to 54,576 cases with 70% efficacy, and to 63,209 cases with 55% efficacy. Additionally, RVGE hospitalizations after 10 years decreased from 177,950 to 89,517 with 85% efficacy and to 121,832 cases with 55% efficacy. The relative risk reductions of RVGE after 10 years were 49.7% with 85% efficacy, 40.6% with 70% efficacy, and 31.5% with 55% efficacy. The VE was 1.10 times (95% CI, 1.01-1.22) higher in the 4-months to 1-year-old age group than in the other age groups (P = 0.038), when applying 85% efficacy with 95% coverage. In conclusion, despite its relatively lower efficacy compared to high-income countries, RV vaccination remains an effective intervention in Southwestern Vietnam. In particular, implementing universal RV vaccination with higher coverage would result in a decrease in RVGE hospitalizations among Vietnamese children under 5 years of age.