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1.
Int J Mol Sci ; 22(4)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670458

RESUMO

Interferons (IFNs) are a crucial component in the innate immune response. Especially the IFN-ß signaling operates in most cell types and plays a key role in the first line of defense upon pathogen intrusion. The induction of IFN-ß should be tightly controlled, because its hyperactivation can lead to tissue damage or autoimmune diseases. Activation of the IFN-ß promoter needs Interferon Regulatory Factor 3 (IRF3), together with Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Activator Protein 1 (AP-1). Here we report that a human noncoding RNA, nc886, is a novel suppressor for the IFN-ß signaling and inflammation. Upon treatment with several pathogen-associated molecular patterns and viruses, nc886 suppresses the activation of IRF3 and also inhibits NF-κB and AP-1 via inhibiting Protein Kinase R (PKR). These events lead to decreased expression of IFN-ß and resultantly IFN-stimulated genes. nc886's role might be to restrict the IFN-ß signaling from hyperactivation. Since nc886 expression is regulated by epigenetic and environmental factors, nc886 might explain why innate immune responses to pathogens are variable depending on biological settings.

2.
Biomolecules ; 11(2)2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33562198

RESUMO

This article aimed to identify and distinguish the various responses to silver nanoparticles (NPs) of endothelial and epithelial cells. We also assessed the significantly increased gene expression levels, as shown by microarray analysis. We evaluated the median lethal dose of NPs in each cell line and found that each value was different. We also confirmed the toxicity of 5 nm silver NPs. Meanwhile, cell death was not observed in cells exposed to 100 nm silver NPs at a high concentration. We verified that 5 nm silver NPs affected the variation in gene expression in cells through microarray analysis and observed a noticeable increase in interleukin (IL)-8 and IL-11 gene expression in early stages. This study showed noticeable variation in the expression of oxidative stress-related genes in early stages. Microarray results showed considerable variation in cell death-, apoptosis-, and cell survival-related gene expression. Of note, IL-11 gene expression was particularly increased following the exposure of endothelial and epithelial cells to 5 nm silver NPs. In conclusion, this study demonstrated that intracellular genes specifically responded to silver NPs in respiratory epithelial cells and endothelial cells. Among cytokine genes, IL-11 expression was noticeably increased. Additionally, we confirmed that NP toxicity was affected by NP size and dose.

4.
Curr Biol ; 30(9): 1614-1625.e5, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32169208

RESUMO

Cells can sense and respond to various mechanical stimuli from their surrounding environment. One of the explanations for mechanosensitivity, a lipid-bilayer model, suggests that a stretch of the membrane induced by mechanical force alters the physical state of the lipid bilayer, driving mechanosensors to assume conformations better matched to the altered membrane. However, mechanosensors of this class are restricted to ion channels. Here, we reveal that integrin αIIbß3, a prototypic adhesion receptor, can be activated by various mechanical stimuli including stretch, shear stress, and osmotic pressure. The force-induced integrin activation was not dependent on its known intracellular activation signaling events and was even observed in reconstituted cell-free liposomes. Instead, these mechanical stimuli were found to alter the lipid embedding of the integrin ß3 transmembrane domain (TMD) and subsequently weaken the αIIb-ß3 TMD interaction, which results in activation of the receptor. Moreover, artificial modulation of the membrane curvature near integrin αIIbß3 can induce its activation in cells as well as in lipid nanodiscs, suggesting that physical deformation of the lipid bilayer, either by mechanical force or curvature, can induce integrin activation. Thus, our results establish the adhesion receptor as a bona fide mechanosensor that directly senses and responds to the force-modulated lipid environment. Furthermore, this study expands the lipid-bilayer model by suggesting that the force-induced topological change of TMDs and subsequent alteration in the TMD interactome is a molecular basis of sensing mechanical force transmitted via the lipid bilayer.

5.
Leuk Lymphoma ; 61(1): 66-74, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31441360

RESUMO

To identify epigenetically silenced miRNAs and to investigate their influences on predictive target oncogenes in extranodal natural killer/T-cell lymphoma (NKTCL). Decitabine treatment was performed to evaluate methylated miRNAs in NKTCL cells. The relationship between a given miRNA and its target mRNA was validated using 24 tumor tissues. miR-379, miR-134, miR-20b, miR-376a, miR-654-3p, miR-143, miR-181c, miR-1225-5p, miR-1246, and miR-1275 were epigenetically silenced in SNK6 cells. miR-134, miR-376a, miR-143 and miR-181c significantly affected cellular viability. PDGFRα was regulated by miR-34a and miR-181c. miR-143, miR-20b and miR34a regulated STAT3 expression. miR-20b and miR-143 expression showed inverse correlations with STAT3 mRNA expression in NKTCL tissues. K-RAS was regulated by miR-181c. Downregulation of cell viability by salirasib treatment was identified. miRNAs were downregulated by DNA methylation, and several microRNAs affected the viability of NKTCL cells. miR-34a and miR-181c may be involved in the oncogenic progression of NKTCL through the regulation of PDGFRα, STAT3, and K-RAS.

6.
J Exp Clin Cancer Res ; 38(1): 462, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718692

RESUMO

BACKGROUND: We investigated the role of PD-L1 in the metabolic reprogramming of non-small cell lung cancer (NSCLC). METHODS: Changes in glycolysis-related molecules and glycolytic activity were evaluated in PD-L1low and PD-L1high NSCLC cells after transfection or knockdown of PD-L1, respectively. Jurkat T-cell activation was assessed after co-culture with NSCLC cells. The association between PD-L1 and immune response-related molecules or glycolysis were analyzed in patients with NSCLC and The Cancer Genome Atlas (TCGA). RESULTS: Transfecting PD-L1 in PD-L1low cells enhanced hexokinase-2 (HK2) expression, lactate production, and extracellular acidification rates, but minimally altered GLUT1 and PKM2 expression and oxygen consumption rates. By contrast, knocking-down PD-L1 in PD-L1high cells decreased HK2 expression and glycolysis by suppressing PI3K/Akt and Erk pathways. Interferon-γ (IFNγ) secretion and activation marker expression was decreased in stimulated Jurkat T-cells when co-cultured with HK2-overexpressing vector-transfected tumor cells rather than empty vector-transfected tumor cells. Immunohistochemistry revealed that PD-L1 expression was positively correlated with HK2 expression in NSCLC (p < 0.001). In TCGA, HK2 exhibited a positive linear association with CD274 (PD-L1) expression (p < 0.001) but an inverse correlation with the expression of CD4, CD8A, and T-cell effector function-related genes in the CD274high rather than CD274low group. Consistently, there were fewer CD8+ T-cells in PD-L1positive/HK2high tumors compared to PD-L1positive/HK2low tumors in squamous cell carcinoma. CONCLUSIONS: PD-L1 enhances glycolysis in NSCLC by upregulating HK2, which might dampen anti-tumor immunity. PD-L1 may contribute to NSCLC oncogenesis by inducing metabolic reprogramming and immune checkpoint.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Hexoquinase/metabolismo , Neoplasias Pulmonares/genética , Receptor de Morte Celular Programada 1/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Transfecção
7.
Artigo em Inglês | MEDLINE | ID: mdl-30946663

RESUMO

GOAL: The Sonophoresis, which utilizes ultrasound for transdermal drug delivery (TDD), can improve the efficiency of drug delivery for a variety of drugs predominantly due to caviation effect. In order to increase the efficacy of sonophoresis, we propose an alternative cavitation seed specialized for sonophoresis, which can be concentrated on the skin surface by gravity adapting perfluorohexane as core. METHODS: An in vitro and in vivo experiments were conducted to assess the effect of the specialized cavitation seed. High performance liquid chromatography was used for in vitro experiments on porcine skin with ferulic acid and an optical imaging system was used for in vivo experiments on rat model with fluorescein isothiocyanate-dextran (FD, 150 kDa), respecitively. RESULTS: The amount of ferulic acid delivered by sonophoresis with the proposed cavitation seed was approximately 1,700 times greater than the amount delivered by diffusion. FD could be delivered to a depth of 500 »m under the skin, and the average total flux in the region of interest was increased 6.4-fold for the group using sonophoresis with the cavitation seed compared to the group using diffusion. CONCLUSION: Conclusively, sonophoresis with the proposed cavitation seed demonstrated significant improvement in TDD and the possibility of macromolecule delivery into the skin. SIGNIFICANCE: This approach has potential to be a main TDD method for variety of applications including medicine and cosmetics.

8.
Proc Natl Acad Sci U S A ; 116(17): 8289-8294, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30948645

RESUMO

DNA-reactive compounds are harnessed for cancer chemotherapy. Their genotoxic effects are considered to be the main mechanism for the cytotoxicity to date. Because this mechanism preferentially affects actively proliferating cells, it is postulated that the cytotoxicity is specific to cancer cells. Nonetheless, they do harm normal quiescent cells, suggesting that there are other cytotoxic mechanisms to be uncovered. By employing doxorubicin as a representative DNA-reactive compound, we have discovered a cytotoxic mechanism that involves a cellular noncoding RNA (ncRNA) nc886 and protein kinase R (PKR) that is a proapoptotic protein. nc886 is transcribed by RNA polymerase III (Pol III), binds to PKR, and prevents it from aberrant activation in most normal cells. We have shown here that doxorubicin evicts Pol III from DNA and, thereby, shuts down nc886 transcription. Consequently, the instantaneous depletion of nc886 provokes PKR and leads to apoptosis. In a short-pulse treatment of doxorubicin, these events are the main cause of cytotoxicity preceding the DNA damage response in a 3D culture system as well as the monolayer cultures. By identifying nc886 as a molecular signal for PKR to sense doxorubicin, we have provided an explanation for the conundrum why DNA-damaging drugs can be cytotoxic to quiescent cells that have the competent nc886/PKR pathway.


Assuntos
Apoptose/efeitos dos fármacos , DNA/metabolismo , MicroRNAs/metabolismo , RNA não Traduzido , Linhagem Celular , Doxorrubicina/farmacologia , Humanos , MicroRNAs/genética , RNA Polimerase III/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Transdução de Sinais/efeitos dos fármacos , eIF-2 Quinase/metabolismo
9.
Nutrients ; 11(1)2018 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-30583546

RESUMO

The effect of calcium consumption in the prevention of type 2 diabetes mellitus (T2DM) remains controversial, and depends on food calcium sources. This prospective study aimed to evaluate the association between calcium-rich food consumption and T2DM incidence among Korean adults. We analyzed the data of 8574 adults aged 40⁻69 years, without a history of T2DM, cardiovascular disease, and cancer at the baseline from the Korean Genome and Epidemiology Study. The consumption of calcium-rich foods was assessed using a validated semi-quantitative food frequency questionnaire. T2DM-related data were collected using biennial questionnaires, health examinations, and clinical tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. In the multivariate-adjusted model, yogurt intake was inversely associated with T2DM risk (HR: 0.73; 95% CI: 0.61⁻0.88 in the fourth quartile as compared to the first quartile). However, the intakes of other calcium-rich foods, including milk and anchovies, were not significantly associated with T2DM risk. Yogurt may provide protective effects against T2DM in Korean adults, owing to the beneficial effects of probiotics. Further prospective large-scale cohort studies should be conducted to validate these findings.


Assuntos
Cálcio na Dieta/administração & dosagem , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Idoso , Animais , Diabetes Mellitus Tipo 2/prevenção & controle , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leite , Probióticos/administração & dosagem , Modelos de Riscos Proporcionais , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de Risco , Inquéritos e Questionários , Iogurte
10.
BMB Rep ; 51(12): 623-629, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30293551

RESUMO

For mechanical force to induce changes in cellular behaviors, two main processes are inevitable; perception of the force and response to it. Perception of mechanical force by cells, or mechanosensing, requires mechanical force-induced conformational changes in mechanosensors. For this, at least one end of the mechanosensors should be anchored to relatively fixed structures, such as extracellular matrices or the cytoskeletons, while the other end should be pulled along the direction of the mechanical force. Alternatively, mechanosensors may be positioned in lipid bilayers, so that conformational changes in the embedded sensors can be induced by mechanical force-driven tension in the lipid bilayer. Responses to mechanical force by cells, or mechanotransduction, require translation of such mechanical force-induced conformational changes into biochemical signaling. For this, protein-protein interactions or enzymatic activities of mechanosensors should be modulated in response to force-induced structural changes. In the last decade, several molecules that met the required criteria of mechanosensors have been identified and proven to directly sense mechanical force. The present review introduces examples of such mechanosensors and summarizes their mechanisms of action. [BMB Reports 2018; 51(12): 623-629].


Assuntos
Mecanotransdução Celular/fisiologia , Estresse Mecânico , Animais , Moléculas de Adesão Celular/metabolismo , Proteínas do Citoesqueleto/metabolismo , Humanos , Canais Iônicos/metabolismo , Bicamadas Lipídicas/metabolismo , Poro Nuclear/metabolismo , Transdução de Sinais
11.
J Acoust Soc Am ; 144(1): EL33, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30075640

RESUMO

This study investigates focus and boundary effects on Korean nasal consonants and vowel nasalization. Under focus, nasal consonants lengthen in CVN# but shorten in #NVC, enhancing [nasal] vs [oral]. Vowels resist nasalization under focus, enhancing [oral]. Domain-initial nasal consonants denasalize, exercising no coarticulatory influence. Domain-final nasal consonants shorten counter to expectation, although vowel nasalization increases. Comparison with English data reveals similarities (focus-induced coarticulatory resistance) despite cross-linguistic differences in marking prominence, but it also suggests that prosodic-structural conditioning of non-contrastive vowel nasalization, albeit based on phonetic underpinnings of coarticulatory process, is fine-tuned in language-specific ways, resulting in cross-linguistic variation.


Assuntos
Idioma , Acústica da Fala , Percepção da Fala/fisiologia , Fala/fisiologia , Adulto , Feminino , Humanos , Masculino , Fonética , República da Coreia
12.
J Transl Med ; 16(1): 162, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29890998

RESUMO

BACKGROUND: Diffuse large B cell lymphoma (DLBCL) contains heterogeneous subtypes with various molecular dysregulation at the gene, protein and microRNA levels. Compared with the GCB subtype, the non-germinal center B-like (non-GCB)/activated B cell-like (ABC) subtype exhibits frequent progression despite standard immunochemotherapy. We aimed to investigate the effects of miR-197 on the progression and chemosensitivity of DLBCL with respect to the GCB and non-GCB/ABC subtypes. METHODS: To screen distinctively expressed microRNAs, microRNA expression patterns were analyzed in 10 DLBCL cases by microarray chip assays. Using quantitative real-time polymerase chain reaction (qRT-PCR), associations between miR-197 expression levels and clinicopathologic variables were investigated in 51 DLBCL tissue samples. The effects of miR-197 on doxorubicin chemosensitivity were investigated using the OCI-Ly1 and SUDHL9 cell lines. RESULTS: MicroRNA expression profiling by hierarchical clustering revealed that miR-197 was one of the distinctively expressed microRNAs in DLBCL. Quantitative analysis using qRT-PCR revealed that miR-197 levels were not correlated with clinicopathologic variables, including the international prognostic index, but low miR-197 levels were significantly associated with lymphoma progression defined by refractoriness, relapse or death in the rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-treated subgroup (n = 43; p = 0.004). Among the three molecular groups, i.e., the GCB, non-GCB/miR-197low and non-GCB/miR-197high groups, progression was most frequently observed in the non-GCB/miR-197low group in the full cohort (p = 0.013) and the R-CHOP cohort (p = 0.008). In survival analysis, low miR-197 levels were independently predictive of shorter progression-free survival in the R-CHOP cohort (p = 0.031; HR = 27.9) and the non-GCB subgroup (p = 0.037; HR = 21.5) but not in the GCB subgroup. Using SUDHL9 (ABC type) and OCI-Ly1 (GCB type) cells, the effects of doxorubicin on reducing cell viability were enhanced by miR-197 transfection. In apoptosis assays, miR-197 transfection enhanced doxorubicin-induced apoptosis in SUDHL9 cells but not in OCI-Ly1 cells, suggesting a chemosensitizing effect of miR-197 in ABC DLBCL. CONCLUSIONS: These results suggest the role of miR-197 as a biomarker with potential therapeutic implications.


Assuntos
Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , MicroRNAs/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Análise por Conglomerados , Estudos de Coortes , Progressão da Doença , Intervalo Livre de Doença , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise Multivariada , Adulto Jovem
13.
Nutr Diabetes ; 8(1): 20, 2018 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-29695709

RESUMO

BACKGROUND/OBJECTIVES: It remains unclear if high egg consumption has beneficial or adverse effects on cardiometabolic health. The present study prospectively evaluated the longitudinal association between egg-consumption levels and incident cardiovascular disease (CVD) among Korean adults. SUBJECTS/METHODS: We conducted a prospective cohort study of 9248 Korean adults aged 40-69 years without CVD or cancer at the baseline from the Korean Genome and Epidemiology Study, Ansung-Ansan cohort, South Korea. The egg intake of the participants was estimated using a validated semiquantitative food frequency questionnaire at the baseline and the second follow-up examination and categorized into quartiles. CVD cases were identified using biennial questionnaires and confirmed through repeated in-depth personal interviews. Hazard ratios (HR) and 95% confidence interval (CI) were analyzed using Cox proportional hazard regression. RESULTS: During the average follow-up of 7.3 years, 570 cases of CVD were newly diagnosed. After adjusting for multiple confounding variables, egg-intake levels were not associated with CVD incidence (HR: 1.14, 95% CI: 0.87-1.49, P for trend: 0.7). However, the association was modified by type 2 diabetes mellitus (T2DM) status. Egg consumption was significantly associated with an increased risk for incident CVD among participants with T2DM; individuals with the highest egg intake (4.2 ± 0.04 eggs/week) had a 2.8 times higher incidence of CVD (HR: 2.81, 95% CI: 1.25-6.30, P for trend: 0.02) than those with the lowest egg intake (0.1 ± 0.02 eggs/week). However, no association was observed among individuals without T2DM (HR: 1.03, 95% CI: 0.77-1.38, P for trend: 0.8). CONCLUSIONS: Higher egg consumption may increase the risk for CVD in Korean patients with T2DM. Our findings provide a basis for the development of an optimal dietary cholesterol intake guideline for the Korean population.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Dieta , Ovos/efeitos adversos , Comportamento Alimentar , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Inquéritos sobre Dietas , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , República da Coreia , Inquéritos e Questionários
14.
Int J Mol Sci ; 18(12)2017 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-29232921

RESUMO

Carbohydrates are the primary energy source for plant development. Plants synthesize sucrose in source organs and transport them to sink organs during plant growth. This metabolism is sensitive to environmental changes in light quantity, quality, and photoperiod. In the daytime, the synthesis of sucrose and starch accumulates, and starch is degraded at nighttime. The circadian clock genes provide plants with information on the daily environmental changes and directly control many developmental processes, which are related to the path of primary metabolites throughout the life cycle. The circadian clock mechanism and processes of metabolism controlled by the circadian rhythm were studied in the model plant Arabidopsis and in the crops potato and rice. However, the translation of molecular mechanisms obtained from studies of model plants to crop plants is still difficult. Crop plants have specific organs such as edible seed and tuber that increase the size or accumulate valuable metabolites by harvestable metabolic components. Human consumers are interested in the regulation and promotion of these agriculturally significant crops. Circadian clock manipulation may suggest various strategies for the increased productivity of food crops through using environmental signal or overcoming environmental stress.


Assuntos
Arabidopsis/crescimento & desenvolvimento , Metabolismo dos Carboidratos , Relógios Circadianos , Produtos Agrícolas/crescimento & desenvolvimento , Arabidopsis/metabolismo , Produtos Agrícolas/metabolismo , Regulação da Expressão Gênica de Plantas , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Proteínas Circadianas Period/metabolismo , Proteínas de Plantas/metabolismo , Solanum tuberosum/crescimento & desenvolvimento , Solanum tuberosum/metabolismo
15.
J Acoust Soc Am ; 142(4): EL362, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29092557

RESUMO

This study investigated articulation of preboundary lengthening (PBL) in tri-syllabic pseudo words (bábaba, babába, bababá) in American English. Results from 10 speakers showed that PBL was modulated by the degree of prominence, i.e., the less prominent, the more PBL. PBL was attracted to the penultimate stressed syllable but only when the word received no pitch accent whereas the antepenultimate syllable showed no PBL. Kinematically, PBL was accompanied by a larger movement along with an increase in peak velocity, showing a kind of boundary-related articulatory strengthening, although there was some evidence of temporal expansion possibly due to lowered stiffness.


Assuntos
Gestos , Lábio/fisiologia , Fonética , Acústica da Fala , Qualidade da Voz , Adulto , Fenômenos Biomecânicos , Fenômenos Eletromagnéticos , Feminino , Humanos , Masculino , Medida da Produção da Fala , Fatores de Tempo , Adulto Jovem
16.
Br J Nutr ; 118(6): 473-480, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28980892

RESUMO

Multiple studies have elucidated the antioxidant properties of Se, which are now well known among the nutrition and biomedical science communities. Recently, considerable interest has been focused on the possible association between Se exposure and risk of metabolic disease, such as lipid dysregulation; however, there is limited epidemiological data on this topic. The present study aimed to investigate associations between toenail Se levels and dyslipidaemia or individual lipid levels, and to examine the effect of dietary supplement use on these associations. We analysed baseline data from a cohort in the Yeungnam area, including 232 men and 269 women. Information on demographic, dietary and lifestyle characteristics was obtained through a self-reported questionnaire. Se levels in toenail specimens were measured using neutron activation analysis. Fasting blood lipid levels were measured during medical examinations. After adjusting for multiple confounding variables, we observed no association between toenail Se levels and dyslipidaemia or individual lipid profiles. However, the association was modified by dietary supplement use. Among the supplement users, higher toenail Se levels were associated with a higher prevalence of lipid dysregulation, whereas non-users exhibited a lower prevalence of lipid dysregulation. Associations between toenail Se levels, lipid levels and dyslipidaemia may be influenced by taking dietary supplements. Future large-scale, prospective cohort studies should be conducted to further evaluate the association between Se levels in the body and metabolic health effects in light of increasing rates of dietary supplement use.


Assuntos
Grupo com Ancestrais do Continente Asiático , Dislipidemias/epidemiologia , Unhas/química , Selênio/análise , Adulto , Antioxidantes/análise , Índice de Massa Corporal , Estudos Transversais , Dieta , Suplementos Nutricionais , Dislipidemias/diagnóstico , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prevalência , República da Coreia , Selênio/administração & dosagem , Fatores Socioeconômicos , Inquéritos e Questionários
17.
Nutrients ; 9(5)2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28505126

RESUMO

Meat consumption has been shown to be associated with cardiovascular disease (CVD) risk in Western societies; however, epidemiological data are limited on the Korean population. Therefore, we examined the associations between unprocessed meat consumption and CVD incidence in Korea. Data were derived from the Ansung-Ansan cohort (2001-2012), including 9370 adults (40-69 years) without CVD or cancer at baseline. Total unprocessed meat consumption was estimated as the sum of unprocessed red meat (beef, pork, and organ meat) and poultry consumption. In the fully adjusted Cox regression model, the relative risks of CVD across increasing quintiles of total unprocessed meat intake were 1.0 (reference), 0.72 (95% confidence interval (CI): 0.55, 0.95), 0.57 (95% CI: 0.42, 0.78), 0.69 (95% CI: 0.51, 0.95), and 0.69 (95% CI: 0.48, 0.97), but no significant linear trend was detected (p for trend = 0.14). Frequent poultry consumption was significantly associated with a decreased CVD risk; this association showed a dose-response relationship (p for trend = 0.04). This study showed that a moderate intake of total unprocessed meat was inversely associated with CVD risk. A significant inverse association between poultry consumption and incident CVD was observed in Korean adults, requiring further confirmation in other populations.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Doenças Cardiovasculares/epidemiologia , Dieta , Neoplasias/epidemiologia , Aves Domésticas , Carne Vermelha , Adulto , Idoso , Animais , Índice de Massa Corporal , Doenças Cardiovasculares/genética , Bovinos , Estudos Epidemiológicos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/prevenção & controle , Avaliação Nutricional , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de Risco , Fatores Socioeconômicos , Suínos
18.
Plant Cell Rep ; 35(9): 1975-85, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27300023

RESUMO

KEY MESSAGE: OsWRKY51 functions as a positive transcriptional regulator in defense signaling against Xanthomonas oryzae pv. oryzae by direct DNA binding to the promoter of defense related gene, OsPR10a. OsWRKY51 in rice (Oryza sativa L.) is induced by exogenous salicylic acid (SA) and inoculation with Xanthomonas oryzae pv. oryzae (Xoo). To examine the role of OsWRKY51 in the defense response of rice, we generated OsWRKY51 overexpressing and underexpressing transgenic rice plants. OsWRKY51-overexpressing transgenic rice lines were more resistant to Xoo and showed greater expression of defense-related genes than wild-type (WT) plants, while OsWRKY51-underexpressing lines were more susceptible to Xoo and showed less expression of defense-associated genes than WT plants. Transgenic lines overexpressing OsWRKY51 showed growth retardation compared to WT plants. In contrast, transgenic lines underexpressing OsWRKY51 by RNA interference showed similar plant height with WT plants. Transient expression of OsWRKY51-green fluorescent protein fusion protein in rice protoplasts revealed that OsWRKY51 was localized in the nucleus. OsWRKY51 bound to the W-box and WLE1 elements of the OsPR10a promoter. Based on these results, we suggest that OsWRKY51 is a positive transcriptional regulator of defense signaling and has direct DNA binding ability to the promoter of OsPR10a, although it is reported to be a negative regulator in GA signaling.


Assuntos
Oryza/imunologia , Oryza/microbiologia , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Xanthomonas/fisiologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Modelos Biológicos , Oryza/efeitos dos fármacos , Oryza/crescimento & desenvolvimento , Fenótipo , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Ligação Proteica/efeitos dos fármacos , Interferência de RNA , Ácido Salicílico/farmacologia , Frações Subcelulares/metabolismo , Fatores de Transcrição/genética , Xanthomonas/efeitos dos fármacos
19.
Oncoimmunology ; 5(3): e1108514, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27141364

RESUMO

Programmed cell death (PD)-1/PD-1 ligand-1 (PD-L1)-targeted therapy has emerged as a promising therapeutic strategy for lung cancer. However, whether EML4-ALK regulates PD-L1 expression in lung cancer remains unknown. A total of 532 pulmonary adenocarcinomas (pADCs), including 58 ALK-translocated tumors, were immunohistochemically evaluated for PD-L1 and PD-1. H23 (EGFRWild-typeEML4-ALK-PD-L1Low) and H2228 (EGFRWild-typeEML4-ALK+PD-L1High) cells were transfected with EML4-ALK or ALK short interfering RNAs and used to investigate the alterations in PD-L1 expression. PD-L1 expression was detected in 81% of ALK-translocated pADCs; this value was significantly higher than those of pADCs with EGFR mutation, KRAS mutation or lacking ALK, EGFR or KRAS mutation (p <0.005 for all). Moreover, ALK-translocated pADC with PD-L1 expression showed significantly higher numbers of tumor-infiltrating PD-1+ cells. ALK knockdown or inhibition (crizotinib treatment) in H2228 cells downregulated PD-L1 expression. Transfection of H23 cells with EML4-ALK enhanced PD-L1 expression, which was compromised by crizotinib treatment. This ALK-dependent upregulation of PD-L1 expression was mediated by STAT3 and hypoxia-inducible factor (HIF)-1α under normoxia and hypoxia. Furthermore, EML4-ALK enhanced HIF-1α expression through increasing transcription and decreasing ubiquitination of HIF-1α. In ALK-translocated pADC tissues, significant positive correlations between PD-L1 and nuclear HIF-1α (p < 0.05) or pSTAT3 expression levels (p<0.005) were observed. Among patients with ALK-translocated pADC, strong PD-L1 expression was significantly associated with shorter progression-free (p = 0.001) and overall survival (p = 0.002) after crizotinib treatment. Collectively, our findings demonstrate that ALK-derived pADCs increase PD-L1 expression via HIF-1α and/or STAT3, thus providing a rationale for PD-1/PD-L1 pathway-targeted therapy in ALK-translocated lung cancer.

20.
Exp Mol Med ; 48: e222, 2016 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-27012708

RESUMO

MicroRNAs (miRNAs) are negative regulators of gene expression, and miRNA deregulation is found in various tumors. We previously reported that suppression of adenine nucleotide translocase 2 (ANT2) by short hairpin RNA (shRNA) inhibits hepatocellular carcinoma (HCC) development by rescuing miR-636 expression. However, the tumor-suppressive mechanisms of ANT2 shRNA are still poorly understood in HCC. Here, we hypothesized that miRNAs that are specifically downregulated by ANT2 shRNA might function as oncomiRs, and we investigated the roles of ANT2 shRNA-regulated miRNAs in the pathogenesis of HCC. Our data show that miR-19a and miR-96, whose expression is regulated by ANT2 suppression, were markedly upregulated in HCC cell lines and clinical samples. Ectopic expression of miR-19a and miR-96 dramatically induced the proliferation and colony formation of hepatoma cells in vitro, whereas inhibition of miR-19a and miR-96 reduced these effects. To investigate the in vivo function, we implanted miR-96-overexpressing HepG2 cells in a xenograft model and demonstrated that the increase in miR-96 promoted tumor growth. We also found that miR-19a and miR-96 inhibited expression of tissue inhibitor of metalloproteinase-2. Taken together, our results suggest that ANT2-regulated miR-19a and miR-96 play an important role in promoting the proliferation of human HCC cells, and the knockdown of ANT2 directly downregulates miR-19a and miR-96, ultimately resulting in the suppression of tumor growth.


Assuntos
Translocador 2 do Nucleotídeo Adenina/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , RNA Interferente Pequeno/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Camundongos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Transdução de Sinais
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