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1.
Development ; 149(15)2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35876688

RESUMO

Epithelial tube formation requires Rho1-dependent actomyosin contractility to generate the cellular forces that drive cell shape changes and rearrangement. Rho1 signaling is activated by G-protein-coupled receptor (GPCR) signaling at the cell surface. During Drosophila embryonic salivary gland (SG) invagination, the GPCR ligand Folded gastrulation (Fog) activates Rho1 signaling to drive apical constriction. The SG receptor that transduces the Fog signal into Rho1-dependent myosin activation has not been identified. Here, we reveal that the Smog GPCR transduces Fog signal to regulate Rho kinase accumulation and myosin activation in the medioapical region of cells to control apical constriction during SG invagination. We also report on unexpected Fog-independent roles for Smog in maintaining epithelial integrity and organizing cortical actin. Our data support a model wherein Smog regulates distinct myosin pools and actin cytoskeleton in a ligand-dependent manner during epithelial tube formation.


Assuntos
Proteínas de Drosophila , Animais , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Ligantes , Morfogênese , Miosinas , Receptores Acoplados a Proteínas G/genética , Smog
2.
J Cell Mol Med ; 28(13): e18526, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38957036

RESUMO

A genome-wide association study (GWAS) is a powerful tool in investigating genetic contribution, which is a crucial factor in the development of complex multifactorial diseases, such as type 2 diabetes mellitus. Type 2 diabetes mellitus is a major healthcare burden in the Western Pacific region; however, there is limited availability of genetic-associated data for type 2 diabetes in Southeast Asia, especially among the Kinh Vietnamese population. This lack of information exacerbates global healthcare disparities. In this study, 997 Kinh Vietnamese individuals (503 with type 2 diabetes and 494 controls) were prospectively recruited and their clinical and paraclinical information was recorded. DNA samples were collected and whole genome genotyping was performed. Standard quality control and genetic imputation using the 1000 Genomes database were executed. A polygenic risk score for type 2 diabetes was generated in different models using East Asian, European, and mix ancestry GWAS summary statistics as training datasets. After quality control and genetic imputation, 107 polymorphisms reached suggestive statistical significance for GWAS (≤5 × 10-6) and rs11079784 was one of the potential markers strongly associated with type 2 diabetes in the studied population. The best polygenic risk score model predicting type 2 diabetes mellitus had AUC = 0.70 (95% confidence interval = 0.62-0.77) based on a mix of ancestral GWAS summary statistics. These data show promising results for genetic association with a polygenic risk score estimation in the Kinh Vietnamese population; the results also highlight the essential role of population diversity in a GWAS of type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/genética , Estratificação de Risco Genético , Herança Multifatorial/genética , Projetos Piloto , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , População do Sudeste Asiático/genética , Vietnã/epidemiologia
3.
Funct Integr Genomics ; 24(2): 70, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565780

RESUMO

Salinization is one of the leading causes of arable land shrinkage and rice yield decline, recently. Therefore, developing and utilizing salt-tolerant rice varieties have been seen as a crucial and urgent strategy to reduce the effects of saline intrusion and protect food security worldwide. In the current study, the CRISPR/Cas9 system was utilized to induce targeted mutations in the coding sequence of the OsDSG1, a gene involved in the ubiquitination pathway and the regulation of biochemical reactions in rice. The CRISPR/Cas9-induced mutations of the OsDSG1 were generated in a local rice cultivar and the mutant inheritance was validated at different generations. The OsDSG1 mutant lines showed an enhancement in salt tolerance compared to wild type plants at both germination and seedling stages indicated by increases in plant height, root length, and total fresh weight as well as the total chlorophyll and relative water contents under the salt stress condition. In addition, lower proline and MDA contents were observed in mutant rice as compared to wild type plants in the presence of salt stress. Importantly, no effect on seed germination and plant growth parameters was recorded in the CRISRP/Cas9-induced mutant rice under the normal condition. This study again indicates the involvement of the OsDSG1 gene in the salt resistant mechanism in rice and provides a potential strategy to enhance the tolerance of local rice varieties to the salt stress.


Assuntos
Oryza , Tolerância ao Sal , Tolerância ao Sal/genética , Sistemas CRISPR-Cas , Oryza/metabolismo , Estresse Salino , Mutação
4.
MMWR Morb Mortal Wkly Rep ; 73(10): 219-224, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483842

RESUMO

During March-April 2023, a total of 51 persons reported mild to severe gastrointestinal illness after eating at restaurant A in Bozeman, Montana. The outbreak resulted in multiple severe outcomes, including three hospitalizations and two deaths. After an inspection and temporary restaurant closure, the Montana Department of Public Health and Human Services and Montana's Gallatin City-County Health Department collaborated with CDC to conduct a matched case-control study among restaurant patrons to help identify the source of the outbreak. Consumption of morel mushrooms, which are generally considered edible, was strongly associated with gastrointestinal illness. A dose-response relationship was identified, and consumption of raw morel mushrooms was more strongly associated with illness than was consumption of those that were at least partially cooked. In response to the outbreak, educational public messaging regarding morel mushroom preparation and safety was shared through multiple media sources. The investigation highlights the importance of prompt cross-agency communication and collaboration, the utility of epidemiologic studies in foodborne disease outbreak investigations, and the need for additional research about the impact of morel mushroom consumption on human health. Although the toxins in morel mushrooms that might cause illness are not fully understood, proper preparation procedures, including thorough cooking, might help to limit adverse health effects.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Doenças Transmitidas por Alimentos , Humanos , Montana/epidemiologia , Estudos de Casos e Controles , Doenças Transmitidas por Alimentos/epidemiologia , Surtos de Doenças , Restaurantes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia
5.
BMC Plant Biol ; 23(1): 533, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37919649

RESUMO

BACKGROUND: Powdery mildew is a major disease that causes great losses in soybean yield and seed quality. Disease-resistant varieties, which are generated by reducing the impact of susceptibility genes through mutation in host plants, would be an effective approach to protect crops from this disease. The Mildew Locus O (MLO) genes are well-known susceptibility genes for powdery mildew in plant. In this study, we utilized the CRISPR/Cas9 system to induce targeted mutations in the soybean GmMLO genes to improve powdery mildew resistance. RESULTS: A dual-sgRNA CRISPR/Cas9 construct was designed and successfully transferred into the Vietnamese soybean cultivar DT26 through Agrobacterium tumefaciens-mediated transformation. Various mutant forms of the GmMLO genes including biallelic, chimeric and homozygous were found at the T0 generation. The inheritance and segregation of CRISPR/Cas9-induced mutations were confirmed and validated at the T1 and T2 generations. Out of six GmMLO genes in the soybean genome, we obtained the Gmmlo02/Gmmlo19/Gmmlo23 triple and Gmmlo02/Gmmlo19/Gmmlo20/Gmmlo23 quadruple knockout mutants at the T2 generation. When challenged with Erysiphe diffusa, a fungus that causes soybean powdery mildew, all mutant plants showed enhanced resistance to the pathogen, especially the quadruple mutant. The powdery mildew severity in the mutant soybeans was reduced by up to 36.4% compared to wild-type plants. In addition, no pleiotropic effect on soybean growth and development under net-house conditions was observed in the CRISPR/Cas9 mutants. CONCLUSIONS: Our results indicate the involvement of GmMLO02, GmMLO19, GmMLO20 and GmMLO23 genes in powdery mildew susceptibility in soybean. Further research should be conducted to investigate the roles of individual tested genes and the involvement of other GmMLO genes in this disease infection mechanism. Importantly, utilizing the CRISPR/Cas9 system successfully created the Gmmlo transgene-free homozygous mutant lines with enhanced resistance to powdery mildew, which could be potential materials for soybean breeding programs.


Assuntos
Sistemas CRISPR-Cas , Glycine max , Glycine max/genética , RNA Guia de Sistemas CRISPR-Cas , Melhoramento Vegetal , Mutação , Fungos , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Resistência à Doença/genética
6.
Planta ; 257(3): 57, 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36795295

RESUMO

MAIN CONCLUSION: Induced mutations in the SC-uORF of the tomato transcription factor gene SlbZIP1 by the CRISPR/Cas9 system led to the high accumulation of sugar and amino acid contents in tomato fruits. Tomato (Solanum lycopersicum) is one of the most popular and consumed vegetable crops in the world. Among important traits for tomato improvement such as yield, biotic and abiotic resistances, appearance, post-harvest shelf life and fruit quality, the last one seems to face more challenges because of its genetic and biochemical complexities. In this study, a dual-gRNAs CRISPR/Cas9 system was developed to induce targeted mutations in uORF regions of the SlbZIP1, a gene involved in the sucrose-induced repression of translation (SIRT) mechanism. Different induced mutations in the SlbZIP1-uORF region were identified at the T0 generation, stably transferred to the offspring, and no mutation was found at potential off-target sites. The induced mutations in the SlbZIP1-uORF region affected the transcription of SlbZIP1 and related genes in sugar and amino acid biosynthesis. Fruit component analysis showed significant increases in soluble solid, sugar and total amino acid contents in all SlbZIP1-uORF mutant lines. The accumulation of sour-tasting amino acids, including aspartic and glutamic acids, raised from 77 to 144%, while the accumulation of sweet-tasting amino acids such as alanine, glycine, proline, serine, and threonine increased from 14 to 107% in the mutant plants. Importantly, the potential SlbZIP1-uORF mutant lines with desirable fruit traits and no impaired effect on plant phenotype, growth and development were identified under the growth chamber condition. Our result indicates the potential utility of the CRISPR/Cas9 system for fruit quality improvement in tomato and other important crops.


Assuntos
Solanum lycopersicum , Fatores de Transcrição , Fatores de Transcrição/genética , Aminoácidos/metabolismo , Açúcares/metabolismo , Solanum lycopersicum/genética , Sistemas CRISPR-Cas , Frutas/genética , Frutas/metabolismo
7.
BMC Public Health ; 23(1): 445, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36882752

RESUMO

BACKGROUND: University students are vulnerable to changes due to COVID-19 pandemic. Although warning has been made about the impact of this crisis on students' mental health, there are barely any sufficient study. This work investigated how the pandemic affected the mental health of students at the Vietnam National University of Ho Chi Minh City (VNU-HCMC) and efficiency of available mental health supportive methods. METHODS: An online survey was conducted among students at Vietnam National University of Ho Chi Minh City (VNU-HCMC) from October 18, 2021, to October 25, 2021. Microsoft Excel 16.51 (Microsoft, USA) and R language, Epi packages 2.44 and 4.1.1 (rdrr.io) were used for data analysis. RESULTS: Thirty-seven thousand one hundred fifty students participated in the survey, including 48.4% female and 51.6% male. Online learning pressure was mainly recorded (65.1%). Many students suffered from sleeping disorders (56.2%). Some reported being victims of abuse (5.9%). Female students expressed a significantly higher level of distress than males, particularly the feeling of ambiguity about the purpose of life (p-value < 0.0001, OR: 0.94, 95% CI: [0.95-0.98]). Third-year students suffered higher stress levels than others, especially in online learning (68.8%, p-value < 0.05). Mental health statuses among students of different lockdown status regions were not significantly different. Therefore, lockdown status did not affect the stress levels of students which suggested that poor mental health outcomes seemed to root in the suspension of everyday university life rather than the prohibition of going out. CONCLUSIONS: During COVID-19, students experienced lots of stress and mental problems. These findings underscore the importance of academic and innovative activities, bringing attention to the needs of interactive study and extra-curricular activities.


Assuntos
COVID-19 , Saúde Mental , Estudantes , Feminino , Humanos , Masculino , Controle de Doenças Transmissíveis , COVID-19/epidemiologia , Estudos Transversais , Pandemias , População do Sudeste Asiático , Vietnã/epidemiologia , Estudantes/psicologia
8.
Proc Natl Acad Sci U S A ; 117(29): 17278-17287, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32631999

RESUMO

The prefrontal cortex (PFC) plays a critical role in curbing impulsive behavior, but the underlying circuit mechanism remains incompletely understood. Here we show that a subset of dorsomedial PFC (dmPFC) layer 5 pyramidal neurons, which project to the subthalamic nucleus (STN) of the basal ganglia, play a key role in inhibiting impulsive responses in a go/no-go task. Projection-specific labeling and calcium imaging showed that the great majority of STN-projecting neurons were preferentially active in no-go trials when the mouse successfully withheld licking responses, but lateral hypothalamus (LH)-projecting neurons were more active in go trials with licking; visual cortex (V1)-projecting neurons showed only weak task-related activity. Optogenetic activation and inactivation of STN-projecting neurons reduced and increased inappropriate licking, respectively, partly through their direct innervation of the STN, but manipulating LH-projecting neurons had the opposite effects. These results identify a projection-defined subtype of PFC pyramidal neurons as key mediators of impulse control.


Assuntos
Comportamento Impulsivo/fisiologia , Inibição Psicológica , Córtex Pré-Frontal/fisiologia , Células Piramidais/fisiologia , Animais , Gânglios da Base/fisiologia , Comportamento Animal/fisiologia , Interneurônios/fisiologia , Camundongos , Neurônios/fisiologia , Optogenética , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/patologia , Células Piramidais/patologia , Núcleo Subtalâmico/diagnóstico por imagem , Núcleo Subtalâmico/fisiologia , Córtex Visual
9.
Transgenic Res ; 31(1): 73-85, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34532833

RESUMO

Overexpression of GA20 oxidase gene has been a recent trend for improving plant growth and biomass. Constitutive expression of GA20ox has successfully improved plant growth and biomass in several plant species. However, the constitutive expression of this gene causes side-effects, such as reduced leaf size and stem diameter, etc. To avoid these effects, we identified and employed different tissue-specific promoters for GA20ox overexpression. In this study, we examined the utility of At1g promoter to drive the expression of GUS (ß-glucuronidase) reporter and AtGA20ox genes in tobacco and Melia azedarach. Histochemical GUS assays and quantitative real-time-PCR results in tobacco showed that At1g was a root-preferential promoter whose expression was particularly strong in root tips. The ectopic expression of AtGA20ox gene under the control of At1g promoter showed improved plant growth and biomass of both tobacco and M. azedarach transgenic plants. Stem length as well as stem and root fresh weight increased by up to 1.5-3 folds in transgenic tobacco and 2 folds in transgenic M. azedarach. Both tobacco and M. azedarach transgenic plants showed increases in root xylem width with xylem to phloem ratio over 150-200% as compared to WT plants. Importantly, no significant difference in leaf shape and size was observed between At1g::AtGA20ox transgenic and WT plants. These results demonstrate the great utility of At1g promoter, when driving AtGA20ox gene, for growth and biomass improvements in woody plants and potentially some other plant species.


Assuntos
Regulação da Expressão Gênica de Plantas , Nicotiana , Biomassa , Glucuronidase/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Regiões Promotoras Genéticas/genética , Nicotiana/genética , Nicotiana/metabolismo
10.
Epidemiol Infect ; 150: e167, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36093606

RESUMO

In this study, we tested the validity across two scales addressing conspiratorial thinking that may influence behaviours related to public health and the COVID-19 pandemic. Using the COVIDiSTRESSII Global Survey data from 12 261 participants, we validated the 4-item Conspiratorial Thinking Scale and 3-item Anti-Expert Sentiment Scale across 24 languages and dialects that were used by at least 100 participants per language. We employed confirmatory factor analysis, measurement invariance test and measurement alignment for internal consistency testing. To test convergent validity of the two scales, we assessed correlations with trust in seven agents related to government, science and public health. Although scalar invariance was not achieved when measurement invariance test was conducted initially, we found that both scales can be employed in further international studies with measurement alignment. Moreover, both conspiratorial thinking and anti-expert sentiments were significantly and negatively correlated with trust in all agents. Findings from this study provide supporting evidence for the validity of both scales across 24 languages for future large-scale international research.


Assuntos
COVID-19 , Idioma , Atitude , Humanos , Pandemias , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
11.
J Fish Dis ; 45(9): 1389-1401, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35696542

RESUMO

Tilapia Lake Virus (TiLV) is reported as a threat to tilapia aquaculture in 16 countries on four continents with outbreaks causing up to 90% mortality. This research is one of the first studies on TiLVs from Vietnam. We propagated successfully one TiLV isolate HB196-VN-2020 from a diseased tilapia sample using an E-11 cell line and evaluated its virulence in two different weights of red hybrid tilapia and three serial 10-fold diluted viral titers. Smaller fish (4.5 ± 1.98 g) were proved to be more susceptible to TiLV infection at the viral titre of 9.1 × 105 TCID50 fish-1 than larger fish (20.8 ± 7.5 g) with the mortalities of 92.5% and 12.5%, respectively. Reassortant detection analysis revealed seven potential reassortment events among 23 TiLV genomes, indicating the mixed infection of multiple TiLV isolates at the farms and the fish movement among different regions. Seven maximum likelihood phylogenetic trees based on the individual segments or the concatenated coding regions of some segments showed the genetically distant relationship of the Southern Vietnamese isolate RIA2-VN-2019 with the 21 reference isolates, and suggest the different origins of two Vietnamese TiLV isolates (RIA2-VN-2019 and HB196-VN-2020). However, additional sequences from various sampling locations and times are required to better understand the impacts of genetic diversity and reassortments on the evolution, migration and natural selection of TiLVs in Vietnam and other countries.


Assuntos
Doenças dos Peixes , Tilápia , Vírus , Animais , Filogenia , Vietnã/epidemiologia
12.
Asia Pac J Clin Nutr ; 30(4): 588-594, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34967187

RESUMO

BACKGROUND AND OBJECTIVES: The number of older adults is increasing rapidly in Vietnam. They suffer from various health problems, including malnutrition and dysphagia. By using a simple screening questionnaire such as the Mini Nutritional Assessment - Short Form (MNA-SF) and 10-item Eating Assessment Tool (EAT-10), nutritional and dysphagic status were screened in this study. The study aimed to determine the prevalence of and relationship between malnutrition and dysphagia in Vietnamese older adult inpatients. METHODS AND STUDY DESIGN: The study was designed as a cross-sectional study and conducted in three large hospitals in northern Vietnam. The data about nutritional status and dysphagia status of 1007 older inpatients were collected by dietitians. RESULTS: There were 71.6% of subjects at malnourished (MNA-SF score <8) and risk of malnutrition (MNA-SF score: 8-11). The prevalence of dysphagia by EAT-10 was 24.6%. The risk of dysphagia was independently associated with higher risk of malnutrition, with an odds ratio of 3.21 (95% CI: 1.93-5.31, p<0.001). In addition, malnutrition was also an independent predictor for risk of dysphagia, with an odds ratio of 3.09 (95% CI: 1.84- 5.17, p<0.001). CONCLUSIONS: Malnutrition and dysphagia prevalence were high; and malnutrition and dysphagia have a strong relationship among older adult inpatients in Vietnam. Therefore, nutritional and dysphagia screening at hospital admission are very important and recommended.


Assuntos
Transtornos de Deglutição , Desnutrição , Idoso , Povo Asiático , Estudos Transversais , Transtornos de Deglutição/complicações , Transtornos de Deglutição/epidemiologia , Avaliação Geriátrica , Humanos , Pacientes Internados , Desnutrição/epidemiologia , Avaliação Nutricional , Estado Nutricional
13.
Health Qual Life Outcomes ; 18(1): 254, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727479

RESUMO

BACKGROUND: Cardiovascular diseases (CVDs) have been the global health problems that cause a substantial burden for the patients and the society. Assessing the Quality of Life (QOL) of CVD patients is critical in the effectiveness evaluation of CVD treatments as well as in determining potential areas for enhancing health outcomes. Through the adoption of a combination of bibliometric approach and content analysis, publications trend and the common topics regarding interventions to improve QOL of CVD patients were searched and characterized to inform priority setting and policy development. METHODS: Bibliographic data of publications published from 1990 to 2018 on interventions to improve QOL of CVD patients were retrieved from Web of Science. Network graphs illustrating the terms co-occurrence clusters were created by VOSviewer software. Latent Dirichlet Allocation approach was adopted to classify papers into major research topics. RESULTS: A total of 6457 papers was analyzed. We found a substantial increase in the number of publications, citations, and the number of download times of papers in the last 5 years. There has been a rise in the number of papers related to intervention to increase quality of life among patients with CVD during 1990-2018. Conventional therapies (surgery and medication), and psychological, behavioral interventions were common research topics. Meanwhile, the number of papers evaluating economic effectiveness has not been as high as that of other topics. CONCLUSIONS: The research areas among the scientific studies emphasized the importance of interdisciplinary and inter-sectoral approaches in both evaluation and intervention. Future research should be a focus on economic evaluation of intervention as well as interventions to reduce mental issues among people with CVD.


Assuntos
Doenças Cardiovasculares/terapia , Publicações Periódicas como Assunto , Qualidade de Vida , Bibliometria , Doenças Cardiovasculares/psicologia , Saúde Global , Humanos , Fator de Impacto de Revistas
14.
Qual Life Res ; 29(9): 2333-2343, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32347440

RESUMO

PURPOSE: The number of patients with depressive disordered globally increased and affects people of all ages and countries and has a significant and negative impact on the quality of life (QoL). Depression if left untreated may lead to severe consequences. However, there are several types of effective treatments, but often patients need support from health staff to find suitable treatments. This study aims to examine the global trend of the publications as well as the development of interventions for depressing treatment. METHODS: We download and analyzed 15,976 scientific research from the Web of Science from 1990 to 2018. A text mining based on Latent Dirichlet and terms' co-occurrence in titles and abstracts to identify hidden research topics and research landscapes. RESULTS: We found that the number of papers related to non-pharmacological treatment (such as cognitive-behavioral, mindfulness, or family and social support) to improve the QoL of patients with depression has increased. The number of papers on this serious health issue in low-middle income countries (LMICs) was not as high as in high-income countries (HICs). CONCLUSION: It is necessary to increase support of the treatment of depression in LMICs as well as applied non-pharmacological interventions to patients with depression.


Assuntos
Depressão/terapia , Transtorno Depressivo/terapia , Qualidade de Vida/psicologia , Terapia Cognitivo-Comportamental , Humanos , Atenção Plena , Apoio Social , Resultado do Tratamento
15.
Adv Exp Med Biol ; 1292: 13-25, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-29687285

RESUMO

BACKGROUND: Cancer is one of the leading causes of death in the world. A great deal of effort has been made to discover new agents for cancer treatment. Xao tam phan (Paramignya trimera) is a traditional medicine of Vietnam used in cancer treatment for a long time, yet there is not much scientific evidence proving its anticancer potency. The study aimed to evaluate the toxicity of Paramignya trimera extract (PTE) on multicellular tumor spheres (MCTS) of MCF-7 cells using hanging drop technique. METHODS: Firstly, MCF-7 cells were seeded on hanging drop plates, spheroid size was tracked, and growth curve was measured by MTT assay and AlamarBlue® assay. The necrotic core of MCTS was evaluated by propidium iodide (PI) staining. Toxicity of doxorubicin (DOX) and tirapazamine (TPZ) was then tested on 3D model compared to 2D culture condition. RESULTS: The results showed that the IC50 of DOX on 3D MCF-7 cells was nearly 50 times greater than monolayer MCF-7 cells. In contrast, TPZ (an agent which is specifically toxic under hypoxic conditions) had significantly lower IC50 in 3D condition than in 2D. The toxicity tests for PTE showed that PTE strongly inhibited MCF-7 cells in both 2D and 3D conditions. Interestingly, the IC50 of PTE in 3D model was remarkably lower than in 2D (IC50 value was 168.9 ± 11.65 µg/ml compared to 260.8 ± 16.54 µg/ml, respectively). The invasion assay showed that PTE completely inhibited invasion of MCF-7 cells at 250 µg/mL concentration. Also, flow cytometry results indicated that PTE effectively induced apoptosis in MCF-7 spheroids in 3D condition at 250 µg/mL concentration. CONCLUSION: The results from this study emphasize the promise of PTE in cancer therapy.


Assuntos
Neoplasias da Mama/patologia , Técnicas de Cultura de Células/métodos , Metanol/química , Modelos Biológicos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/toxicidade , Humanos , Células MCF-7
16.
J Gen Virol ; 100(6): 975-984, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31090533

RESUMO

The development of live-attenuated vaccines against Dengue virus (DENV) has been problematic. Dengvaxia, licensed in several countries where DENV is endemic, has shown low efficacy profiles and there are safety concerns prohibiting its administration to children younger than 9 years old, and the live-attenuated tetravalent vaccine (LATV) developed by NIAID has proven too reactogenic during clinical trialing. In this work we examined whether the combination of TV005, a LATV-derived formulation, with Tetra DIIIC, a subunit vaccine candidate based on fusion proteins derived from structural proteins from all four DENV serotypes, can overcome the respective limitations of these two vaccine approaches. Rhesus macaques were first primed with one or two doses of Tetra DIIIC and then boosted with TV005, following the time course of the appearance of virus-binding and neutralizing antibodies, and evaluating protection by means of a challenge experiment with wild-type viruses. Although the two evaluated prime-boost regimes were equivalent to a single administration of TV005 in terms of the development of virus-binding and neutralizing antibodies as well as the protection against viral challenge, both regimes reduced vaccine viremia to undetectable levels. Thus, the combination of Tetra DIIIC with TV005 offers a potential solution to the reactogenicity problems, which have beset the development of the latter vaccine candidate.


Assuntos
Vírus da Dengue/imunologia , Dengue/imunologia , Proteínas Recombinantes de Fusão/imunologia , Vacinas Atenuadas/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Linhagem Celular , Chlorocebus aethiops , Dengue/virologia , Feminino , Imunização/métodos , Imunização Secundária/métodos , Macaca mulatta , Masculino , Células Vero
17.
Harm Reduct J ; 16(1): 6, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30654814

RESUMO

BACKGROUND: Despite existing efforts to provide antiretroviral treatment (ART) for all HIV-diagnosed people, stigma deprives them of the highest attainable health status and challenges the effectiveness of ART program in Vietnam. This study aimed to assess five dimensions of HIV-related stigma and explore its associated factors among ART patients in a multisite survey. Implications of this study support the development of HIV policies to improve patients' access, utilization, and outcomes of ART program toward the 90-90-90 goal in Vietnam. METHODS: A total of 1133 ART patients who were recruited by convenience sampling method from 8 ART clinics in Hanoi and Nam Dinh in a cross-sectional study from January to August 2013. Multivariate logistic regression was employed to identify factors associated with stigmatization. RESULTS: The majority of participants reported experiencing stigmatization due to shame (36.9%), blame/judge (21.6%), and discrimination (23.4%). Further, 91.5% of participants disclosed their HIV status with others. The likelihood of experiencing stigmatization did not only associate with the patients' socioeconomic status (e.g., age, occupation, education) and HIV status disclosure, but also their health problems. Those with anxiety or depression and perceived lower quality of life were more likely to experience stigma. CONCLUSIONS: To maximize the efficiency of the ART program, it is essential to develop interventions that reduce stigma involving individuals, families, and communities, and recognize and address complex health problems especially those patients showing depressive symptoms. Increasing quality of life of HIV-positive patients by providing vocational training, financial, family, and peer support will reduce the likelihood of experiencing stigma.


Assuntos
Síndrome da Imunodeficiência Adquirida/psicologia , Terapia Antirretroviral de Alta Atividade/tendências , Infecções por HIV/psicologia , Estereotipagem , Abuso de Substâncias por Via Intravenosa/epidemiologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/terapia , Adulto , Estudos Transversais , Depressão/complicações , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Vergonha , Fatores Socioeconômicos , Abuso de Substâncias por Via Intravenosa/complicações , Resultado do Tratamento , Vietnã/epidemiologia , Adulto Jovem
18.
Orbit ; 38(4): 269-273, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30125147

RESUMO

Orbital blowout fractures result from trauma which breaks the bony orbital wall while sparing the rim. Previous research into fracture mechanism has focused on bony anatomy. This study evaluates the role of preorbital and intraorbital soft tissue volume in fracture risk. A retrospective case-control study was conducted on 51 cases of adults with unilateral orbital blowout fracture, matched to 51 controls who had experienced orbital trauma by comparable mechanisms without sustaining a fracture. Axial Computed Tomography (CT) images with orbital fine cuts were assessed on a 3D post-processing workstation to measure the volume of the pre- and intraorbital soft tissues, then compared between the two groups using Mann-Whitney U analysis. In the case group, there were 40 males (78%), injured by assault (66%), fall (12%), motor vehicle collision (10%), or other cause (12%). The control group included 33 males (65%), injured by assault (55%), fall (22%), motor vehicle (4%), or other cause (20%). There was no significant difference in mechanism rates between case and control groups. Median preorbital volumes were 12.5 cm3 in the case group and14.1 cm3 in controls (p = 0.02). Median intraorbital volumes were 24.4 cm3 in the case group and 25.9 cm3 in controls (p = 0.003). CT volumetric analysis shows that patients who sustained blowout fractures have lower preorbital and intraorbital soft tissue volume than those who did not fracture. This underscores the significant role that soft tissues play in dissipating impact forces, both anterior to the orbital rim and within the orbit itself.


Assuntos
Órbita/diagnóstico por imagem , Fraturas Orbitárias/diagnóstico por imagem , Fraturas Orbitárias/epidemiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , População Urbana/estatística & dados numéricos , Adulto Jovem
19.
J Inherit Metab Dis ; 40(3): 395-401, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28220263

RESUMO

Beta-ketothiolase (T2) deficiency is an inherited disease of isoleucine and ketone body metabolism caused by mutations in the ACAT1 gene. Between 2005 and 2016, a total of 41 patients with T2 deficiency were identified at a medical center in northern Vietnam, with an estimated incidence of one in 190,000 newborns. Most patients manifested ketoacidotic episodes of varying severity between 6 and 18 months of age. Remarkably, 28% of patients showed high blood glucose levels (up to 23.3 mmol/L). Ketoacidotic episodes recurred in 43% of patients. The age of onset, frequency of episodes, and identified genotype did not affect patient outcomes that were generally favorable, with the exception of seven cases (five died and two had neurological sequelae). Custom-tailored acute and follow-up management was critical for a positive clinical outcome. Two null mutations, c.622C>T (p.Arg208*) and c.1006-1G>C (p.Val336fs), accounted for 66% and 19% of all identified ACAT1 mutant alleles, respectively. Most patients showed characteristic biochemical abnormalities. A newborn screening program could be expected to have a high yield in Vietnam. Investigation findings of haplotypes linked to the most common ACAT1 mutation (c.622C>T) are consistent with an ancient common founder of mutation-bearing chromosomes belonging to the Kinh ethnic population. The direct management and long-term follow-up of a large number of T2-deficient patients enabled us to study the natural history of this rare disease.


Assuntos
Acetil-CoA C-Aciltransferase/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/genética , Acetil-CoA C-Aciltransferase/genética , Alelos , Feminino , Haplótipos/genética , Humanos , Recém-Nascido , Masculino , Mutação/genética , Triagem Neonatal/métodos , Vietnã
20.
J Nanosci Nanotechnol ; 17(4): 2740-742, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-29664594

RESUMO

This study investigated the mechanical properties and initial cell response of bioactive glass infiltrated zirconia before and after sandblasting. One hundred zirconia specimens were divided into the following four groups: untreated zirconia (ZR), sandblasted zirconia (ZS), glass infiltrated zirconia (ZG), and sandblasted glass infiltrated zirconia (ZGS). Surface roughness, biaxial flexural strength, hardness and osteoblast cells proliferation were evaluated. ZGS group showed a slight decrease in hardness. However it has improvement in flexural strength (686.2 MPa). After sandblasting, the ZGS group had the highest surface roughness (R a = 1.24 µm) with enhanced osteoblast cells response. Our results indicated that sandblasting method can improve the mechanical properties of bioactive glass infiltrated zirconia with better osteoblast cell response. This new surface is promising for zirconia dental implant application in the future.


Assuntos
Materiais Dentários/química , Vidro/química , Zircônio/química , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Materiais Dentários/farmacologia , Testes de Dureza , Teste de Materiais , Camundongos , Osteoblastos/efeitos dos fármacos , Propriedades de Superfície , Zircônio/farmacologia
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