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1.
J Vasc Interv Radiol ; 35(1): 137-141, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37820885

RESUMEN

Eleven patients (5 men, 6 women) with post-operative thoracic duct injuries and high output chylothorax were treated with thoracic duct embolization (TDE). Six patients underwent intraprocedural thoracic duct ligation at the time of original procedure. In all cases, the pleural fluid demonstrated high triglyceride levels (414 mg/dL; interquartile range [IQR], 345 mg/dL). Median daily (IQR) chest tube outputs before and after TDE were 900 mL (1,200 mL) and 325 mL (630 mL), respectively. Coil- or plug-assisted ethylene vinyl alcohol (EVOH) copolymer was used as embolic agent in all patients. Technical and clinical success rates were 100% and 82%, respectively. Nontarget venous embolization of EVOH copolymer was not identified on subsequent imaging.


Asunto(s)
Quilotórax , Embolización Terapéutica , Traumatismos Torácicos , Masculino , Humanos , Femenino , Quilotórax/diagnóstico por imagen , Quilotórax/etiología , Quilotórax/terapia , Embolización Terapéutica/métodos , Conducto Torácico/diagnóstico por imagen , Estudios Retrospectivos , Traumatismos Torácicos/terapia , Resultado del Tratamiento
2.
Environ Res ; 252(Pt 3): 118973, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38679278

RESUMEN

BACKGROUND: There is a noticeable lack of information on the levels of both non-essential and essential trace elements in women aged over 50. The main objective of this study is to investigate trace element concentrations and explore the influence of sociodemographic factors and dietary sources of exposure in this demographic. METHODS: We analyzed 19 trace elements, including manganese, cobalt, copper, zinc, molybdenum, chromium, nickel, arsenic, strontium, cadmium, tin, antimony, cesium, barium, tungsten, mercury, thallium, lead, and uranium, using ICP-MS and mercury analyzer. Urine samples were obtained from a cohort of 851 women aged over 50 who participated in the 8th KoGES-Ansung study (2017-2018). Multiple linear models were employed to explore associations between urinary trace element concentrations and sociodemographic factors and dietary sources of exposure. We used K-means clustering to discern patterns of exposure to trace elements and identify contributing factors and sources. RESULTS: Our findings indicate higher concentrations of molybdenum (Mo), arsenic (As), cadmium (Cd), and lead (Pb) in our study population compared to women in previous studies. The study population were clustered into two distinct groups, characterized by lower or higher urinary concentrations. Significant correlations between age and urinary concentrations were observed in Ni. Smoking exhibited positive associations with urinary Cd and As. Associations with dietary sources of trace elements were more distinct in women in the high-exposure group. Urinary antimony (Sb) was positively linked to mushroom and egg intake, As to mushroom and fish, and Hg to egg, dairy products, fish, seaweed, and shellfish. CONCLUSIONS: Our study underscores the significant gap in understanding urinary concentrations of trace elements in women aged over 50. With higher concentrations of certain elements compared to previous studies and significant correlations between age, smoking, and specific food sources, it is imperative to address this gap through targeted dietary source-specific risk management.


Asunto(s)
Dieta , Oligoelementos , Humanos , Femenino , Persona de Mediana Edad , Oligoelementos/orina , Estudios de Cohortes , Anciano , Exposición a Riesgos Ambientales/análisis , Agricultura , Contaminantes Ambientales/orina , Anciano de 80 o más Años , Exposición Dietética/análisis
3.
Gastroenterol Nurs ; 47(3): 195-202, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38847429

RESUMEN

Functional gastrointestinal disorders are common and have high prevalence in young adults. This study aimed to identify the prevalence and risk factors of functional gastrointestinal disorders in university students. A cross-sectional study was conducted in January 2021 at two universities in a South Korean city and included 493 participants. The Rome IV criteria (for functional dyspepsia and irritable bowel syndrome) and the Korean gastroesophageal reflux disease questionnaire (for gastroesophageal reflux disease) were used to define each disease. Data were analyzed using descriptive statistics and multivariate logistic regression. Gastroesophageal reflux disease, functional dyspepsia, and irritable bowel syndrome prevalence was 18.5%, 7.5%, and 6.5%, respectively, in university students. In multivariate analysis, school year (fourth) (odds ratio [95% confidence interval] = 2.27 [0.25, 0.78]), underlying disease (odds ratio [95% confidence interval] = 2.92 [1.42, 6.04]), physical activity less than once weekly (odds ratio [95% confidence interval] = 4.84 [1.04, 22.45]), very irregular meals (odds ratio [95% confidence interval] = 4.02 [1.54, 10.49]), overeating more than 5 times weekly (odds ratio [95% confidence interval] = 3.37 [1.19, 9.56]), and academic stress (odds ratio [95% confidence interval] = 1.02 [1.01, 1.03]) were risk factors for functional gastrointestinal disorders. Our findings indicate that a comprehensive management program focusing on eating habits and psychological factors is needed to reduce the prevalence of functional gastrointestinal disorders in university students.


Asunto(s)
Enfermedades Gastrointestinales , Estudiantes , Humanos , República de Corea/epidemiología , Femenino , Masculino , Prevalencia , Estudiantes/estadística & datos numéricos , Estudios Transversales , Factores de Riesgo , Universidades , Adulto Joven , Enfermedades Gastrointestinales/epidemiología , Adulto , Encuestas y Cuestionarios , Adolescente , Dispepsia/epidemiología
4.
J Enzyme Inhib Med Chem ; 38(1): 51-66, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36305287

RESUMEN

ARS-interacting multifunctional proteins 2 (AIMP2) is known to be a powerful tumour suppressor. However, the target AIMP2-DX2, AIMP2-lacking exon 2, is often detected in many cancer patients and cells. The predominant approach for targeting AIMP-DX2 has been attempted via small molecule mediated inhibition, but due to the lack of satisfactory activity against AIMP2-DX2, new therapeutic strategies are needed to develop a novel drug for AIMP2-DX2. Here, we report the use of the PROTAC strategy that combines small-molecule AIMP2-DX2 inhibitors with selective E3-ligase ligands with optimised linkers. Consequently, candidate compound 45 was found to be a degrader of AIMP2-DX2. Together, these findings demonstrate that our PROTAC technology targeting AIMP2-DX2 would be a potential new strategy for future lung cancer treatment.


Asunto(s)
Antineoplásicos , Neoplasias Pulmonares , Humanos , Antineoplásicos/farmacología , Línea Celular Tumoral , Pulmón , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Proteínas Nucleares/metabolismo , Proteolisis
5.
Ecotoxicol Environ Saf ; 264: 115479, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37716066

RESUMEN

Bisphenol A (BPA) is widely used in the production of plastics, food containers, and receipt ink globally. However, research has identified it as an endocrine disruptor, affecting the hormonal balance in living organisms. Bisphenol S (BPS), one of the alternative substances, was developed, but its effects on human health and the underlying mechanisms remain unclarified. Specifically, research on the effects of oral exposure to bisphenol on the lungs is lacking. We examined the potential differences in toxicity between these compounds in lung cells in vitro and in vivo. Our toxicity mechanism studies on MRC5 and A549 cells exposed to BPA or BPS revealed that BPA induced actin filament abnormalities and activated epithelial-mesenchymal transition (EMT). This finding suggests an increased potential for lung fibrosis and metastasis in lung cancer. However, given that BPS was not detected at the administered dose and under the specific experimental conditions, the probability of these occurrences is considered minimal. Additionally, animal experiments confirmed that oral exposure to BPA activates EMT in the lungs. Our study provides evidence that prolonged oral exposure to BPA can lead to EMT activation in lung tissue, similar to that observed in cell experiments, suggesting the potential to induce lung fibrosis. This research emphasizes the importance of regulating the use of BPA to mitigate its associated pulmonary toxicity. Furthermore, it is significant that within the parameters of our experimental conditions, BPS did not exhibit the toxicological pathways clearly evident in BPA.


Asunto(s)
Fibrosis Pulmonar , Animales , Humanos , Fibrosis Pulmonar/inducido químicamente , Fenoles/toxicidad , Pulmón
6.
Opt Express ; 30(26): 47017-47025, 2022 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-36558639

RESUMEN

This study proposes a liquid-crystal-based active wavelength filter for phase-sensitive optical time domain reflectometry to mitigate the amplified spontaneous emission (ASE) noise and accurately match the passband with the light source. The validity of the proposed system was verified using comparative experiments with conventional passive optical filters. The experiment showed an increase in signal-to-noise ratio (SNR) of up to 2.21 dB compared with passive filters. Additionally, the proposed system can effectively eliminate ASE noise, resulting in an SNR of 12.99 dB.

7.
Environ Res ; 209: 112885, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35131323

RESUMEN

Urine was used as a part of a human biomonitoring study based on the excretion kinetics of less-persistent contaminants, such as phthalates and bisphenol A (BPA). Despite the advantages of being non-invasive and easy to collect, urine can show a large variability of concentrations of phthalate metabolites and BPA within a person depending on sampling time. Therefore, it is essential to assess the variability of urinary concentrations for comprehensive sampling design in the context of exposure and risk assessments. In this study, 18 phthalate metabolites and eight BPs were measured in all spot urine (n = 401) collected from 12 participants for seven consecutive days to evaluate within- and between-person variabilities. The intraclass correlation coefficients (ICCs) for all spot urines were poor for monomethyl phthalate (ICC: 0.002) and BPA (0.121) but were moderate for monoethyl phthalate (0.514) and monobenzyl phthalate (0.462). Based on the results of di (2-ethylhexyl) phthalate (DEHP) metabolites, the half-life and differences in metabolic capability seem to affect the ICCs. Urinary mono (2-ethylhexyl) phthalate (MEHP), a primary metabolite of DEHP, was suggested as a short-term exposure marker of DEHP in our study. Creatinine- and specific gravity-adjusted concentrations of phthalate metabolites and BPs resulted in increased ICCs, implying requirements for randomly collected spot urine. Most analytes in the first morning voids (FMVs) were correlated significantly with those in the daily composites, suggesting the feasibility of FMVs to estimate the daily exposure dose. This study facilitates a more comprehensive sampling design and data interpretation strategy for human biomonitoring studies.


Asunto(s)
Dietilhexil Ftalato , Contaminantes Ambientales , Ácidos Ftálicos , Compuestos de Bencidrilo , Monitoreo Biológico , Dietilhexil Ftalato/orina , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/orina , Humanos , Fenoles , Ácidos Ftálicos/orina
8.
Environ Res ; 204(Pt A): 111888, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34403664

RESUMEN

BACKGROUND: Associations of heavy metal exposures with obesity and obesity-related traits have been suggested, while those with nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM) are often inconsistent. METHODS: This study included 3787 adults aged ≥19 years who participated in the Korean National Environmental Health Survey 2015-2017, and investigated the association of toxic heavy metals with metabolic diseases. Lead (Pb), mercury (Hg), and cadmium (Cd) were measured either in urine (uHg, uCd) or total blood (bPb, bHg). Body mass index (BMI) was calculated, and DM cases were identified through a self-answered medication history. Hepatic Steatosis Index (HSI) as a surrogating index of NAFLD, was calculated using hepatic enzyme measurements, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). RESULTS: Adults in the highest quartile of bPb, bHg, and uHg showed significantly elevated odds of obesity (BMI ≥25 kg/m2), compared to the lowest quartile (OR 1.58 for bPb, 1.92 for bHg, and 1.81 for uHg). HSI was positively correlated with bHg, uHg, and uCd concentrations. The odds of NAFLD (HSI ≥36) were also increased with increasing quartile of bHg, uHg, and uCd concentrations. For DM, bPb showed a significant negative association, while bHg and uCd exhibited non-monotonic and inconclusive associations. CONCLUSIONS: Among the general adult population of Korea, both Pb and Hg exposures were associated with an increased risk of obesity. In addition, both Hg and Cd exposures were associated with increased odds of NAFLD. These metals, however, were not associated with an increased risk of DM.


Asunto(s)
Diabetes Mellitus , Mercurio , Adulto , Cadmio/toxicidad , Diabetes Mellitus/inducido químicamente , Diabetes Mellitus/epidemiología , Salud Ambiental , Humanos , Plomo , Mercurio/toxicidad , Obesidad/inducido químicamente , Obesidad/epidemiología , República de Corea/epidemiología
9.
Opt Express ; 28(9): 12675-12687, 2020 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-32403760

RESUMEN

In recent years, some of the most interesting discoveries in science and engineering emerged from interdisciplinary areas that defy the traditional classification. One recent and extensively studied example is the advent of optomechanics that explores the radiation pressure-induced nonlinearity in a solid micro-resonator. Instead of using a solid resonator, we studied a liquid droplet resonator in which optical pressure could actively interact with the fluid interface. The droplet resonator supported high-quality whispering gallery modes along its equatorial plane, which produced a radiation pressure that counterbalances the interfacial tension, resulting in a droplet with damped harmonic oscillation. A major goal of this study was to demonstrate that such a novel and all-liquid platform could lead to a single-photon-level nonlinearity at room temperature. If successful, such a highly nonlinear system may lead to new research paradigms in photonics, fluid mechanics, as well as quantum information science.

10.
Pharmacol Res ; 160: 105100, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32739426

RESUMEN

Cyclin Y (CCNY) is a member of cyclin superfamily proteins involved in the regulation of the cell cycle in proliferating cells. Intriguingly, CCNY is highly expressed in terminally differentiated neuronal cells of multiple brain regions and acts as a postsynaptic protein, which plays an inhibitory role in long-term potentiation. However, the pathophysiological significance of CCNY in the nervous system remains largely unexplored. In this study, we revisited our RNA-sequencing (RNA-seq) data obtained from cultured hippocampal neurons virally overexpressing or depleting CCNY. Using RNA-seq-based bioinformatic disease analysis and synaptic gene ontology analysis, we identified that numerous genes associated with epilepsy (e.g. Chrna4, Gabrd, Nhlrc1, Reln, Samd12, Slc6a1, etc.) or neurodegenerative diseases (e.g. Psen1, Pdyn, Ndrg1, etc.) are affected by the level of CCNY expression. In agreement with the RNA-seq-based disease analysis, we found that Ccny knockout (KO) mice are more susceptible to kainic acid-induced epilepsy than wild-type mice. In addition, some epilepsy-associated genes that are regulated by CCNY levels were further validated in the brain of Ccny KO mice at the mRNA and protein levels. Collectively, our findings indicate that CCNY shifts the expression profile of epilepsy-associated genes and exerts a protective effect against kainic acid-induced epilepsy, suggesting CCNY as a potential pharmaceutical candidate for the treatment of epilepsy.


Asunto(s)
Ciclinas/genética , Epilepsia/inducido químicamente , Epilepsia/genética , Agonistas de Aminoácidos Excitadores , Ácido Kaínico , Animales , Química Encefálica/genética , Células Cultivadas , Biología Computacional , Femenino , Genotipo , Hipocampo/citología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Enfermedades Neurodegenerativas/genética , RNA-Seq , Proteína Reelina
11.
Bioorg Med Chem ; 28(23): 115797, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33075682

RESUMEN

In order to identify anti-tubercular agents with a novel scaffold, commercial libraries of small organic compounds were screened against a fluorescent strain of Mycobacterium tuberculosis H37Rv, using a dual phenotypic assay. Compounds were assessed against bacteria replicating in broth medium, as well as inside macrophages, and thienothiazolocarboxamide (TTCA) scaffold was identified as hit in both assays, with submicromolar inhibitory concentrations. Derivatives of TTCA were further synthesized and evaluated for their inhibitory effects on M.tuberculosis H37Rv. In the present study we report the structure-activity relationship of these TTCA derivatives. Compounds 28, 32 and 42 displayed good anti-tubercular activities, as well as favorable ADME and PK properties. Compound 42 exhibited excellent oral bioavailability in mice with high distribution to lungs, within 1 h. It was found to be efficacious in a dose dependent manner in a murine model of M. tuberculosis infection. Hence, compound 42 is now under evaluation as a potential lead candidate for treatment of tuberculosis.


Asunto(s)
Amidas/química , Antituberculosos/química , Tiazoles/química , Amidas/farmacocinética , Amidas/farmacología , Amidas/uso terapéutico , Animales , Antituberculosos/farmacocinética , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Estabilidad de Medicamentos , Femenino , Semivida , Humanos , Ratones , Ratones Endogámicos BALB C , Microsomas/metabolismo , Mycobacterium tuberculosis/efectos de los fármacos , Relación Estructura-Actividad , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Tuberculosis/patología
12.
Environ Res ; 189: 109901, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32980001

RESUMEN

Early life exposures to lead (Pb) and mercury (Hg) were reported to be associated with various adverse health outcomes. However, limited data was available for urinary Pb and Hg levels in young children and the proportion of children at risk by age, as well as inter- and intra-subject variations of urinary Pb and Hg levels. Therefore, we collected total 491 urine samples from 241 children by urine collection at birth and at intervals of 3 months until 27 months of age for each child (at 10 monitoring time points), measured urinary Pb and Hg levels, and then evaluated the proportion of children at risk by age and the intra-class correlation (ICC) of the urinary Pb and Hg levels. Both the urinary Pb and Hg levels were significantly different according to the monitoring time points (p < 0.0001 for both Pb and Hg). The number of children with Hg level over the Human BioMonitoring (HBM) I (7 µg/L) and II (25 µg/L) in the first urine at birth were 3 (2.2%) and 1 (0.7%), respectively, while the urinary samples at the other time points did not show Hg level over HBM I or HBM II. However, the exceedance rate for urinary Pb based on HBM values was not calculated due to unavailable HBM values. On the other hands, the proportion of the children with Pb and Hg levels over the reference value derived on the 95th percentile of representative samples (RV95) (1.7 µg/L for Canadian Pb and 0.4 µg/L for German Hg) was relatively high, ranging from 20.0% to 100.0% for Pb and from 13.6% to 100.0% for Hg. The ICC of the repeated measurements from birth to 27 months was 0 for Pb and 0.89 for Hg, while the ICC after the exclusion of the first urine at birth was 0.13 for Pb and 0.47 for Hg. Furthermore, the Pb and Hg exposures were consistent among the high-exposure group for Pb and among all population for Hg. Our data showed Korean children were exposed to relatively high levels of Pb and Hg. However, our Pb and Hg levels in children were based on only urine samples without urinary correction and without consideration of the levels in any other bio-samples such as bloods. Therefore, to explore the Pb and Hg exposures using urine samples warrant further investigation with large sample size considering urinary correction and other bio-samples in the future.


Asunto(s)
Plomo , Mercurio , Monitoreo Biológico , Canadá , Niño , Preescolar , Monitoreo del Ambiente , Humanos , Mercurio/análisis
13.
J Neurosci ; 38(14): 3571-3583, 2018 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-29530986

RESUMEN

Mutations in the cereblon (CRBN) gene cause human intellectual disability, one of the most common cognitive disorders. However, the molecular mechanisms of CRBN-related intellectual disability remain poorly understood. We investigated the role of CRBN in synaptic function and animal behavior using male mouse and Drosophila models. Crbn knock-out (KO) mice showed normal brain and spine morphology as well as intact synaptic plasticity; however, they also exhibited decreases in synaptic transmission and presynaptic release probability exclusively in excitatory synapses. Presynaptic function was impaired not only by loss of CRBN expression, but also by expression of pathogenic CRBN mutants (human R419X mutant and Drosophila G552X mutant). We found that the BK channel blockers paxilline and iberiotoxin reversed this decrease in presynaptic release probability in Crbn KO mice. In addition, paxilline treatment also restored normal cognitive behavior in Crbn KO mice. These results strongly suggest that increased BK channel activity is the pathological mechanism of intellectual disability in CRBN mutations.SIGNIFICANCE STATEMENTCereblon (CRBN), a well known target of the immunomodulatory drug thalidomide, was originally identified as a gene that causes human intellectual disability when mutated. However, the molecular mechanisms of CRBN-related intellectual disability remain poorly understood. Based on the idea that synaptic abnormalities are the most common factor in cognitive dysfunction, we monitored the synaptic structure and function of Crbn knock-out (KO) animals to identify the molecular mechanisms of intellectual disability. Here, we found that Crbn KO animals showed cognitive deficits caused by enhanced BK channel activity and reduced presynaptic glutamate release. Our findings suggest a physiological pathomechanism of the intellectual disability-related gene CRBN and will contribute to the development of therapeutic strategies for CRBN-related intellectual disability.


Asunto(s)
Cognición , Discapacidad Intelectual/genética , Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Transmisión Sináptica , Proteínas Adaptadoras Transductoras de Señales , Animales , Encéfalo/citología , Encéfalo/metabolismo , Células Cultivadas , Drosophila , Ácido Glutámico/metabolismo , Indoles/farmacología , Canales de Potasio de Gran Conductancia Activados por el Calcio/antagonistas & inhibidores , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/genética , Péptidos/farmacología , Bloqueadores de los Canales de Potasio/farmacología , Sinapsis/efectos de los fármacos , Sinapsis/metabolismo , Sinapsis/fisiología
14.
Nanotechnology ; 29(47): 475501, 2018 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-30211686

RESUMEN

We demonstrated a single-material multifunctional sensor using ZnO nanorods, which is capable of mimicking the five human senses. A simple method for the growth of ZnO nanorods and their application as a multifunctional sensor was studied. High-density ZnO nanorods were synthesized by the carbothermal transport method on a graphene catalyst. To optimize the sensing mechanisms, we investigated ZnO nanostructure growth under two oxygen flow rates. ZnO nanorods as sensors for smell, light, sound, touch, and taste, the five human senses, showed stable electrical signals under standard ambient conditions.

15.
J Neurosci ; 36(39): 10181-97, 2016 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-27683913

RESUMEN

UNLABELLED: During brain development, dynamic changes in neuronal membranes perform critical roles in neuronal morphogenesis and migration to create functional neural circuits. Among the proteins that induce membrane dynamics, cell adhesion molecules are important in neuronal membrane plasticity. Here, we report that V-set and transmembrane domain-containing protein 5 (Vstm5), a cell-adhesion-like molecule belonging to the Ig superfamily, was found in mouse brain. Knock-down of Vstm5 in cultured hippocampal neurons markedly reduced the complexity of dendritic structures, as well as the number of dendritic filopodia. Vstm5 also regulates neuronal morphology by promoting dendritic protrusions that later develop into dendritic spines. Using electroporation in utero, we found that Vstm5 overexpression delayed neuronal migration and induced multiple branches in leading processes during corticogenesis. These results indicate that Vstm5 is a new cell-adhesion-like molecule and is critically involved in synaptogenesis and corticogenesis by promoting neuronal membrane dynamics. SIGNIFICANCE STATEMENT: Neuronal migration and morphogenesis play critical roles in brain development and function. In this study, we demonstrate for the first time that V-set and transmembrane domain-containing protein 5 (Vstm5), a putative cell adhesion membrane protein, modulates both the position and complexity of central neurons by altering their membrane morphology and dynamics. Vstm5 is also one of the target genes responsible for variations in patient responses to treatments for major depressive disorder. Our results provide the first evidence that Vstm5 is a novel factor involved in the modulation of the neuronal membrane and a critical element in normal neural circuit formation during mammalian brain development.


Asunto(s)
Orientación del Axón/fisiología , Movimiento Celular/fisiología , Morfogénesis/fisiología , Neurogénesis/fisiología , Neuronas/citología , Neuronas/fisiología , Animales , Moléculas de Adhesión Celular/metabolismo , Tamaño de la Célula , Células Cultivadas , Regulación del Desarrollo de la Expresión Génica/fisiología , Proteínas de la Membrana/metabolismo , Ratones
16.
Biochem Biophys Res Commun ; 482(1): 28-34, 2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-27836539

RESUMEN

Infection with pathogens activates the endothelial cell and its sustained activation may result in impaired endothelial function. Endothelial dysfunction contributes to the pathologic angiogenesis that is characteristic of infection-induced inflammatory pathway activation. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a protein receptor which recognizes bacterial molecules and stimulates an immune reaction in various cells; however, the underlying molecular mechanisms in the regulation of inflammation-triggered angiogenesis are not fully understood. Here we report that peroxisome proliferator-activated receptor gamma (PPARγ)-mediated miR-125a serves as an important regulator of NOD1 agonist-mediated angiogenesis in endothelial cells by directly targeting NOD1. Treatment of human umbilical vein endothelial cells with natural PPARγ ligand, 15-Deoxy-Delta12,14-prostaglandin J2, led to inhibition of NOD1 expression; contrarily, protein levels of NOD1 were significantly increased by PPARγ knockdown. We report that PPARγ regulation of NOD1 expression is a novel microRNA-mediated regulation in endothelial cells. MiR-125a expression was markedly decreased in human umbilical vein endothelial cells subjected to PPARγ knockdown while 15-Deoxy-Delta12,14-prostaglandin J2 treatment increased the level of miR-125a. In addition, NOD1 is closely regulated by miR-125a, which directly targets the 3' untranslated region of NOD1. Moreover, both overexpression of miR-125a and PPARγ activation led to inhibition of NOD1 agonist-induced tube formation in endothelial cells. Finally, NOD1 agonist increased the formation of cranial and subintestinal vessel plexus in zebrafish, and this effect was abrogated by concurrent PPARγ activation. Overall, these findings identify a PPARγ-miR-125a-NOD1 signaling axis in endothelial cells that is critical in the regulation of inflammation-mediated angiogenesis.


Asunto(s)
Células Endoteliales/metabolismo , MicroARNs/metabolismo , Neovascularización Patológica/metabolismo , Proteína Adaptadora de Señalización NOD1/metabolismo , PPAR gamma/metabolismo , Vasculitis/metabolismo , Animales , Células Cultivadas , Regulación hacia Abajo , Células Endoteliales/patología , Humanos , Neovascularización Patológica/patología , Vasculitis/patología , Pez Cebra
17.
J Vasc Interv Radiol ; 28(4): 594-601, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28169138

RESUMEN

PURPOSE: To describe outcomes of patients with malignant biliary obstruction who undergo salvage percutaneous biliary drainage after occlusion of endoscopic biliary stents. MATERIALS AND METHODS: A single-center retrospective review was performed of 47 patients (25 men, 22 women) who underwent percutaneous biliary drainage for recurrent obstruction after endoscopic stent placement between 2005 and 2015. Primary malignancies were bile duct (n = 13), colorectal (n = 11), gallbladder (n = 7), pancreas (n = 5), hepatocellular (n = 4), and other (n = 7). Indication for salvage drain placement was infection (n = 19) and jaundice or need to decrease bilirubin (n = 28). Kaplan-Meier and Cox regression methods were used for survival analysis. Logistic and multivariate regressions were employed to identify factors associated with survival. RESULTS: Median survival after salvage biliary drain placement was 1.8 months (95% confidence interval [CI], 1.3-2.7). Elevated international normalized ratio (INR) ≥ 1.5 before drainage was associated with poorer survival after drainage (median survival 0.7 months vs 2.4 months, P < .01). Median survival was shorter in 28 patients (64%) with bilirubin ≤ 2 mg/dL (34.2 µmol/L) after drainage (1.2 months vs 5.4 months, P < .001). Left-sided drain placement, elevated bilirubin, and elevated INR correlated with decreased likelihood of achieving bilirubin ≤ 2 mg/dL (34.2 µmol/L) (odds ratio [OR] 0.13, 95% CI, 0.02-0.71, P = .02; OR 0.18, 95% CI, 0.05-0.69, P = .01; OR 0.10, 95% CI, 0.01-0.90, P = .04). CONCLUSIONS: Survival is limited for most patients who undergo salvage percutaneous biliary drainage. Elevated bilirubin and INR before drainage portend a poor prognosis.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica/instrumentación , Colestasis/terapia , Neoplasias del Sistema Digestivo/complicaciones , Drenaje/instrumentación , Terapia Recuperativa , Stents , Adulto , Anciano , Anciano de 80 o más Años , Bilirrubina/sangre , Biomarcadores/sangre , California , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica/mortalidad , Colestasis/diagnóstico por imagen , Colestasis/etiología , Colestasis/mortalidad , Neoplasias del Sistema Digestivo/diagnóstico por imagen , Neoplasias del Sistema Digestivo/mortalidad , Drenaje/efectos adversos , Drenaje/métodos , Drenaje/mortalidad , Femenino , Humanos , Relación Normalizada Internacional , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Terapia Recuperativa/efectos adversos , Terapia Recuperativa/mortalidad , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba
18.
Proc Natl Acad Sci U S A ; 110(47): 19083-8, 2013 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-24191027

RESUMEN

HIV-1 primarily infects activated CD4+ T cells and macrophages. Quiescent CD4+ T cells, however, possess cellular factors that limit HIV-1 infection at different postentry steps of the viral life cycle. Here, we show that the previously reported immune regulator monocyte chemotactic protein-induced protein 1 (MCPIP1) restricts HIV-1 production in CD4+ T cells. While the ectopic expression of MCPIP1 in cell lines abolished the production of HIV-1, silencing of MCPIP1 enhanced HIV-1 production. Subsequent analysis indicated that MCPIP1 imposes its restriction by decreasing the steady levels of viral mRNA species through its RNase domain. Remarkably, common T-cell stimuli induced the rapid degradation of MCPIP1 in both T-cell lines and quiescent human CD4+ T cells. Lastly, blocking the proteosomal degradation of MCPIP1 by MG132 abrogated HIV-1 production in phorbol 12-myristate 13-acetate/ionomycin-stimulated human CD4+ T cells isolated from healthy donors. Overall, MCPIP1 poses a potent barrier against HIV-1 infection at a posttranscriptional stage. Although the observed HIV restriction conferred by MCPIP1 does not seem to be overcome by any viral protein, it is removed during cellular stimulation. These findings provide insights into the mechanisms of cellular activation-mediated HIV-1 production in CD4+ T cells.


Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Infecciones por VIH/prevención & control , Ribonucleasas/metabolismo , Factores de Transcripción/metabolismo , Northern Blotting , Células HEK293 , Humanos , Immunoblotting , Leupeptinas/farmacología , Activación de Linfocitos/inmunología , Proteolisis/efectos de los fármacos , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
19.
J Phys Ther Sci ; 28(8): 2358-61, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27630432

RESUMEN

[Purpose] This study was conducted to provide basic data for solutions to reduce the turnover rate of physical therapists. It should help create efficient personnel and organization management by exploring the impact of the work environment and work-related stress on turnover intention and analyzing the correlation between them. [Subjects and Methods] A survey was conducted with 236 physical therapists working at medical institutions in the Daejeon and Chungcheong areas. For the analysis on the collected data, correlational and linear regression analyses were conducted using the SPSS 18.0 program and Cronbach's alpha coefficient. [Results] The results showed a statistically significant positive correlation between turnover intention and work-related stress but a statistically significant negative correlation respectively between turnover intention and work environment. Work-related stress (ß=0.415) had a significant positive impact on turnover intention and work environment (ß=-0.387) had a significant negative impact on turnover intention. [Conclusion] To increase satisfaction level with the profession as well as the workplace for physical therapists, improvement of the work environment was the most necessary primary improvement.

20.
Opt Express ; 23(6): 7351-65, 2015 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-25837078

RESUMEN

We report an experimental technique where one uses a standard silica fiber as a cylindrical whispering gallery mode (WGM) resonator to sense airborne nanoscale aerosols produced by electric arc welding. We find that the accumulation of aerosols on the resonator surface induces a measurable red-shift in resonance frequency, and establish an empirical relation that links the magnitude of resonance shift with the amount of aerosol deposition. The WGM quality factors, by contrast, do not decrease significantly, even for samples with a large percentage of surface area covered by aerosols. Our experimental results are discussed and compared with existing literature on WGM-based nanoparticle sensing.


Asunto(s)
Aerosoles/análisis , Electrónica/instrumentación , Nanopartículas/química , Dióxido de Silicio/química , Calibración , Microscopía Electrónica de Rastreo , Nanopartículas/ultraestructura
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