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1.
Rhinology ; 61(3): 214-220, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36715355

RESUMEN

BACKGROUND: Bilateral symmetrical pain in the midfacial region without evidence of sinonasal disease is termed midfacial segment pain (MSP), about which little is known. The present study explored the prevalence of facial pain and the risk factors for MSP. METHODS: We analysed cross-sectional data from the Korea National Health and Nutrition Examination Survey (KNHANES). Those who reported facial pain or pressure lasting at least three months with no evidence of a sinonasal disease on nasal endoscopy were considered to have MSP. The participants were categorised according to the presence of facial pain and chronic rhinosinusitis. Basic demographic data and medical conditions, including hypertension, diabetes mellitus, and dyslipidemia, were compared between subject groups. We also evaluated psychological stress, depressive episodes, and suicidal thoughts, as well as physician-diagnosed nasal diseases, including chronic rhinitis and symptomatic nasal septal deviation. Univariate and multivariate logistic regression analyses were performed to determine risk factors for MSP. RESULTS: Of 31,999 participants, the prevalence of facial pain was 0.59%. A total of 58 (0.18%) respondents had MSP, of whom 40 (73.5%) were female. On univariate analysis, female sex, chronic rhinitis, and psychological stress were more prevalent in the subjects with MSP than the control subjects. However, in the multivariate analysis, only chronic rhinitis and psychological stress remained significant, while the female sex exhibited only marginal significance. CONCLUSION: Chronic rhinitis and psychological stress may be significant risk factors for MSP.


Asunto(s)
Rinitis , Humanos , Femenino , Masculino , Rinitis/diagnóstico , Encuestas Nutricionales , Estudios Transversales , Factores de Riesgo , Enfermedad Crónica , Dolor Facial
2.
Cell Death Differ ; 22(9): 1517-25, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25721045

RESUMEN

Glioblastomas (GBMs) maintain their cellular heterogeneity with glioma stem cells (GSCs) producing a variety of tumor cell types. Here we interrogated the oncogenic roles of Lim domain only 2 (LMO2) in GBM and GSCs in mice and human. High expression of LMO2 was found in human patient-derived GSCs compared with the differentiated progeny cells. LMO2 is required for GSC proliferation both in vitro and in vivo, as shRNA-mediated LMO2 silencing attenuated tumor growth derived from human GSCs. Further, LMO2 is sufficient to induce stem cell characteristics (stemness) in mouse premalignant astrocytes, as forced LMO2 expression facilitated in vitro and in vivo growth of astrocytes derived from Ink4a/Arf null mice and acquisition of GSC phenotypes. A subset of mouse and human GSCs converted into vascular endothelial-like tumor cells both in vitro and in vivo, which phenotype was attenuated by LMO2 silencing and promoted by LMO2 overexpression. Mechanistically, the action of LMO2 for induction of glioma stemness is mediated by transcriptional regulation of Jagged1 resulting in activation of the Notch pathway, whereas LMO2 directly occupies the promoter regions of the VE-cadherin gene for a gain of endothelial cellular phenotype. Subsequently, selective ablation of human GSC-derived VE-cadherin-expressing cells attenuated vascular formation in mouse intracranial tumors, thereby significantly prolonging mouse survival. Clinically, LMO2 expression was elevated in GBM tissues and inversely correlated with prognosis of GBM patients. Taken together, our findings describe novel dual roles of LMO2 to induce tumorigenesis and angiogenesis, and provide potential therapeutic targets in GBMs.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/patología , Glioblastoma/irrigación sanguínea , Glioblastoma/patología , Proteínas con Dominio LIM/biosíntesis , Proteínas con Dominio LIM/genética , Células Madre Neoplásicas/patología , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas/genética , Animales , Apoptosis/fisiología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Glioblastoma/genética , Glioblastoma/metabolismo , Xenoinjertos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células Madre Neoplásicas/metabolismo , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo
3.
Osteoporos Int ; 25(4): 1313-9, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24345885

RESUMEN

UNLABELLED: Osteoporosis and high-risk osteopenia (high-risk of osteoporotic fractures) are highly prevalent in South Korean postmenopausal women and men aged 50 years and over. INTRODUCTION: This study determined the percentages of the population at high risk of osteoporotic fractures according to the World Health Organization (WHO) criteria and the Fracture Risk Assessment (FRAX) model. METHODS: Data collected from the 2010 Fifth Korean National Health and Nutrition Examination Survey, a cross-sectional survey of the general South Korean general population, were analyzed. The percentages of the population with high-risk osteopenia according to the US National Osteoporosis Foundation (NOF) and Japanese treatment guidelines were subsequently determined and compared. RESULTS: Based on the WHO criteria and FRAX model, 37.7% of the menopausal women and 12.7% of the men aged 50 years and older are at high risk of osteoporotic fracture. According to the Japanese and NOF guidelines, 10.9 (10.6% of men and 11.2% of women) and 10.7% (10.6% of men and 10.9% of women), respectively, of the study population with osteopenia are at high risk of fracture. By age group, 49.3% of Korean women aged 55 years and older, 67.7% of Korean women aged 65 years and older, and 33.5% of Korean men aged 75 years and older are at high risk. CONCLUSION: As a very large percentage of the South Korean postmenopausal population has osteoporosis or high-risk osteopenia, greater effort at identifying and treating this population should be expended to prevent osteoporotic fracture.


Asunto(s)
Fracturas Osteoporóticas/epidemiología , Distribución por Edad , Anciano , Densidad Ósea/fisiología , Enfermedades Óseas Metabólicas/epidemiología , Enfermedades Óseas Metabólicas/fisiopatología , Estudios Transversales , Femenino , Cuello Femoral/fisiopatología , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Osteoporosis/epidemiología , Osteoporosis/fisiopatología , Osteoporosis Posmenopáusica/epidemiología , Osteoporosis Posmenopáusica/fisiopatología , Fracturas Osteoporóticas/fisiopatología , República de Corea/epidemiología , Medición de Riesgo/métodos , Distribución por Sexo
4.
Cell Death Differ ; 19(7): 1196-207, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22240897

RESUMEN

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5), promote the selective clearing of various malignancies by inducing apoptosis, holding the promise as a potent therapeutic agent for anticancer. Though DR4 and DR5 have high sequence similarity, differential regulation of both receptors in human tumor cells remains largely unexplored. Here, we repot that golgi-specific Asp-His-His-Cys (DHHC) zinc finger protein (GODZ) regulates TRAIL/DR4-mediated apoptosis. Using the SOS protein recruitment-yeast two-hybrid screening, we isolated GODZ that interacted with the death domain of DR4. GODZ binds to DR4, but not to DR5, through the DHHC and the C-terminal transmembrane domain. Expression level of GODZ affects apoptosis of tumor cells triggered by TRAIL, but not that induced by TNF-α/cycloheximide (CHX) or DNA-damaging drugs. In parallel, GODZ functions to localize DR4 to the plasma membrane (PM) via DHHC motif. Also, introduction of mutation into the cysteine-rich motif of DR4 results in its mistargeting and attenuates TRAIL- or GODZ-mediated apoptosis. Interestingly, GODZ expression is highly downregulated in Hep-3B tumor cells, which show resistance to TRAIL. However, reconstitution of GODZ expression enhances the targeting of DR4 to cell surface and sensitizes Hep-3B cells to TRAIL. Taken together, these data establish that GODZ is a novel DR4-selective regulator responsible for targeting of DR4 to the PM, and thereby for TRAIL-induced apoptosis.


Asunto(s)
Glicoproteínas de Membrana/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Secuencias de Aminoácidos , Animales , Apoptosis/efectos de los fármacos , Células COS , Línea Celular Tumoral , Membrana Celular/metabolismo , Chlorocebus aethiops , Cicloheximida/farmacología , Regulación hacia Abajo , Células HEK293 , Células HeLa , Humanos , Glicoproteínas de Membrana/antagonistas & inhibidores , Glicoproteínas de Membrana/genética , Mutagénesis Sitio-Dirigida , Estructura Terciaria de Proteína , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/genética , Proteína Son Of Sevenless Drosofila/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Dedos de Zinc
5.
Oncogene ; 27(31): 4344-52, 2008 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-18362888

RESUMEN

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a potent inducer of apoptosis in tumor cells and holds a promise as a therapeutic agent against cancer. To elucidate the death signaling evoked by TRAIL, we performed a functional genetic screening and rescued TRAIL-resistant Jurkat clones harboring ribosomal protein S6 (rpS6) cDNA in anti-sense frame. Reduction of rpS6 expression in Jurkat and HeLa cells attenuated apoptosis induced by TRAIL, but not those by other cell death signals, including tumor necrosis factor-alpha and cycloheximide, etoposide, doxorubicin, tunicamycin and staurosporine. Death receptor (DR) 4, but not DR5, was downregulated in rpS6 knockdown cells. Conversely, the sensitivity to TRAIL was increased by the ectopic expression of wild-type rpS6 and further by phospho-defective rpS6 mutant (S6-SS235,6AA), but not by phospho-mimic rpS6 mutant (S6-SS235,6DD). Also, unphosphorylatable rpS6 knock-in mouse embryo fibroblasts (rpS6(P-/-) MEFs) were more sensitive to TRAIL than control MEFs. In addition, SKHep-1 tumor cells, which express less phospho-rpS6 and are more sensitive to TRAIL than other tumor cells, became effectively desensitized to TRAIL after rpS6 knockdown. These results suggest that rpS6, especially in its unphosphorylated form, is a selective mediator of TRAIL-induced apoptosis.


Asunto(s)
Apoptosis , Proteína S6 Ribosómica/fisiología , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Animales , Antineoplásicos/farmacología , ADN Complementario/metabolismo , Células HeLa , Humanos , Células Jurkat , Ratones , Ratones Transgénicos , Fosforilación , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Transducción de Señal
6.
J Microencapsul ; 21(5): 539-52, 2004 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15513760

RESUMEN

The chitosan microspheres were prepared by a membrane emulsification method with variations of the N2 gas pressure and the chitosan concentration. The pressure of N2 gas was varied within the range from 0.2 x 10(5) to 0.8 x 10(5) Pa at chitosan concentration 1.5 wt%. In addition, the concentration of chitosan was varied between 0.5 approximately 2.0 wt% at 0.4 x 10(5) Pa of N2 gas pressure. Using this method, it is possible to prepare stable emulsions with a very narrow droplet size distribution in comparison with conventional methods. The average size of the microspheres was dependent on the N2 gas pressure and the concentration, that is it was increased with the pressure and the concentration. The modelling of the size for the microspheres according to the concentration was carried out using Macleod's relation and Parkins & Brown equation. The former shows the relationship between density and surface tension and the latter demonstrates the correlation between the volume of the microspheres and the interfacial tension. The modelling results were in good agreement with the experimental data to predict the microspheres size with the variation of concentration.


Asunto(s)
Quitosano , Composición de Medicamentos/métodos , Emulsiones , Microscopía Electrónica de Rastreo , Microesferas , Modelos Teóricos , Tamaño de la Partícula
7.
Nature ; 404(6781): 982-6, 2000 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-10801124

RESUMEN

Inorganic zeolites are used for many practical applications that exploit the microporosity intrinsic to their crystal structures. Organic analogues, which are assembled from modular organic building blocks linked through non-covalent interactions, are of interest for similar applications. These range from catalysis, separation and sensor technology to optoelectronics, with enantioselective separation and catalysis being especially important for the chemical and pharmaceutical industries. The modular construction of these analogues allows flexible and rational design, as both the architecture and chemical functionality of the micropores can, in principle, be precisely controlled. Porous organic solids with large voids and high framework stability have been produced, and investigations into the range of accessible pore functionalities have been initiated. For example, catalytically active organic zeolite analogues are known, as are chiral metal-organic open-framework materials. However, the latter are only available as racemic mixtures, or lack the degree of framework stability or void space that is required for practical applications. Here we report the synthesis of a homochiral metal-organic porous material that allows the enantioselective inclusion of metal complexes in its pores and catalyses a transesterification reaction in an enantioselective manner. Our synthesis strategy, which uses enantiopure metal-organic clusters as secondary building blocks, should be readily applicable to chemically modified cluster components and thus provide access to a wide range of porous organic materials suitable for enantioselective separation and catalysis.

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