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AIMS: To examine the association between 24 literature-based single nucleotide polymorphisms and diabetic kidney disease in Chinese people with type 2 diabetes. METHODS AND RESULTS: Twenty-four candidate diabetic kidney disease-susceptible single nucleotide polymorphisms were genotyped in 208 participants with type 2 diabetes and diabetic kidney disease and 200 participants with type 2 diabetes without diabetic kidney disease (case and control groups, respectively), together with 206 healthy participants using MassARRAY. Rs11643718 in the SLC12A3 gene was associated with diabetic kidney disease in the recessive model after adjusting for confounding factors, such as age and gender (adjusted odds ratio 2.056, 95% CI 1.120-3.776; P = 0.020). Meta-analyses further confirmed the association (P = 0.002). In addition, participants with the GG genotype had worse renal function and more albuminuria than those with the AA+AG genotype (P < 0.05). Renal section immunohistochemistry was conducted in participants with type 2 diabetes, diabetic kidney disease and AA+AG or GG genotypes and in participants with glomerular minor lesions. Together with data from the Nephroseq database, it was shown that the abundance of SLC12A3 was reduced in patients with the GG genotype, while elevated expression of SLC12A3 was associated with better renal function. In addition, rs10951509 and rs1345365 in ELMO1, which were determined to be in high linkage disequilibrium by SHEsis software, were also associated with diabetic kidney disease (adjusted P = 0.010 and 0.015, respectively). CONCLUSIONS: The G allele and GG genotype of SLC12A3 rs11643718 are associated with the development of diabetic kidney disease in a Chinese population with type 2 diabetes.
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Proteínas Adaptadoras Transductoras de Señales/genética , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/genética , Anciano , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Nefropatías Diabéticas/etiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Miembro 3 de la Familia de Transportadores de Soluto 12/genéticaRESUMEN
Stimulated emission depletion (STED) microscopy performed using continuous-wave (CW) lasers has been investigated and developed by Willig et al. (Nature Methods, 2007, 4(11):915) for nearly a decade. Kuang et al. (Review of Scientific Instruments, 2010, 81:053709) developed the CW STED microscopy technique with 405 nm excitation and 532 nm depletion beams. In their research, Coumarin 102 dye was adopted and was found to be depletable. In this study, a parametric investigation of the depletion of Coumarin 102 dye is carried out experimentally. The influence of the excitation and depletion beam intensities and dye concentrations on the depletion efficiency are studied in detail. The results indicate the following: (1) The highest depletion occurs for the 100 µM Coumarin 102 solution, with a 1.4 µW excitation beam and a 115.3 mW depletion beam. (2) The minimum saturation intensity (Is) of STED, that is 13 MW cm-2 , is observed when the Coumarin 102 solution concentration is 10 µM. (3) Is values calculated directly from the depletion power derived with the cross-sectional area due to the full-width-at-half-maximum (FWHM) of the depletion beam show poor accuracy, where Is may be overestimated. Thus, a correction factor for the cross-sectional area is proposed. We also find that Is is not exactly constant for a fixed excitation beam power and dye concentration. This trend indicates that the conventional suppression function η(x)=e- ln (2)ISTED(x)/Is derived from picosecond STED may cause errors in evaluating the depletion process in CW STED microscopy.
RESUMEN
OBJECTIVE: The resistance of hepatocellular carcinoma (HCC) to chemotherapy may be mediated by the c-Jun N-terminal kinase (JNK) pathway. We wished to verify the involvement of this pathway in resistance of HCC cells to cisplatin. MATERIALS AND METHODS: We used HepG2 cell line and cisplatin-resistant clone (HepG2/DDP). Expressions of drug resistance and apoptosis-related genes were analyzed by qPCR. Protein expressions were assessed by Western blot. The JNK pathway was assessed as total JNK1/2 and JNK1/2 phosphorylation. Cell growth kinetics was quantified by the CCK-8 assay, and cell apoptosis (Annexin V / propidium iodide) by flow cytometry. RESULTS: HepG2/DDP cells were more resistant and less apoptotic on cisplatin. Expression of drug-resistance genes MDR1, MRP1 and MPR2 was significantly up-regulated in HepG2/DDP cells (p < 0.05), with up-regulation of MDR1 being the highest. This was confirmed by Western blot analysis of P-glycoprotein (P-gp), MRP1 and MRP2 proteins, the proteins encoded by the above genes. Expression of anti-apoptotic genes Bcl-2 and Bcl-XL was significantly up-regulated, and expression of pro-apoptotic genes Bak and Bad was significantly reduced, in HepG2/DDP cells (p < 0.05). Cisplatin treatment of HepG2 led to increased phosphorylation of JNK1/2; the trend reversed by the inhibitor SP600125. Furthermore, cisplatin increased expression of P-gp, which was also attenuated by SP600125. Cell growth was inhibited more substantially, and cell apoptosis promoted, when HepG2 cells were exposed to both cisplatin and SP600125. CONCLUSIONS: Inhibition of the JNK signaling pathway enhances the sensitivity of HCC cells to cisplatin by down-regulating the expression of P-gp.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Antineoplásicos/farmacología , Carcinoma Hepatocelular/metabolismo , Cisplatino/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Neoplasias Hepáticas/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Cisplatino/uso terapéutico , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/fisiología , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/fisiología , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiologíaRESUMEN
OBJECTIVE: The aim of our study was to assess the performance of acoustic radiation force impulse (ARFI) imaging to differentiate benign from malignant thyroid nodules. METHODS: 182 patients who needed thyroid surgery were examined. All patients and 50 healthy volunteers underwent ARFI sonoelastography, which quantitatively analysed the elasticity and hardness of the nodule's centre and periphery. RESULTS: ARFI values showed a statistical significance between malignant nodules and benign nodules and common thyroid parenchyma, in both the centre and periphery of nodules (p < 0.01). There was no significant difference between benign nodules and common thyroid parenchyma in either the nodule's centre or periphery (p > 0.05). There was no significant difference between the nodule's centre and periphery of the elastic parameters in both the benign and malignant nodules. There was a statistically significant difference among the two areas (the central group and the peripheral group) under the receiver operating characteristic curve, and the optimal model was the peripheral group. For differentiation of malignant from benign nodules, the sensitivity and specificity were 96.3% and 96.2%, respectively, when 2.545 m s(-1) was chosen as a cut-off value in the peripheral group. CONCLUSION: ARFI imaging may be helpful to differentiate benign nodules from malignant thyroid nodules. The selecting measurement position is important in ARFI imaging, and it has good diagnostic value in clinical applications. ADVANCES IN KNOWLEDGE: This study shows the diagnostic contribution of ARFI imaging in thyroid lesions.
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Diagnóstico por Imagen de Elasticidad/métodos , Glándula Tiroides/diagnóstico por imagen , Nódulo Tiroideo/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y Especificidad , Glándula Tiroides/patología , Nódulo Tiroideo/patologíaRESUMEN
Ejaculation is a process involving sympathetic and parasympathetic effects during different stages - emission and ejection. Some conditions of ejaculation dysfunction are associated with autonomic nerves. However, the exact effects of autonomic nerves on ejaculation are not well defined. Autonomic agonists induce different recorded trace patterns of seminal vesicular contraction. The different traces contain different components of phasic and tonic contraction, which may have physiological implications. In this study, we examined isolated rat seminal vesicle (SV) contraction by phenylephrine (PE), acetylcholine, and their respective antagonists and then speculated upon physiological roles of sympathetic and parasympathetic nerves on SV during ejaculation. We found that PE and Ach both achieved good contraction of rat SV. Compared to α1b for sympathetic and M1, M2 for parasympathetic receptors, α1a and M3 are the relatively dominant subtypes on rat SV. Adrenergic and cholinergic agonists cause different trace patterns of SV contraction. We speculated that the sympathetic effect is dominant during emission to squeeze seminal fluid out and that the parasympathetic effect is dominant during ejection to provide an anti-reflux effect on the ejaculatory duct.
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Eyaculación/fisiología , Músculo Liso/inervación , Sistema Nervioso Parasimpático/fisiología , Vesículas Seminales/inervación , Sistema Nervioso Simpático/fisiología , Acetilcolina/farmacología , Agonistas Adrenérgicos/farmacología , Animales , Agonistas Colinérgicos/farmacología , Masculino , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Fenilefrina/farmacología , Ratas , Ratas Wistar , Receptor Muscarínico M1/fisiología , Receptor Muscarínico M2/fisiología , Receptor Muscarínico M3/fisiología , Receptores Adrenérgicos alfa 1/fisiología , Vasoconstrictores/farmacología , Vasodilatadores/farmacologíaRESUMEN
Circulating endothelial progenitor cells (EPCs) are bone marrow-derived cells required for endothelial repair. A low EPC number can be considered as an independent predictor of endothelial dysfunction and future cardiovascular events. Recent evidence shows that patients with hypogonadal symptoms without other confounding risk factors have a low number of circulating progenitor cells (PCs) and EPCs, thus highlighting the role of testosterone in the proliferation and differentiation of EPCs. Here, we investigate if testosterone replacement therapy (TRT) can increase circulating EPC number in men with late onset hypogonadism. Forty-six men (age range, 40-73 years; mean age, 58.3 years) with hypogonadal symptoms were recruited, and 29 men with serum total testosterone (TT) levels less than 350 ng/dL received TRT using transdermal testosterone gel (Androgel; 1% testosterone at 5 g/day) for 12 months. Circulating EPC numbers (per 100 000 monocytes) were calculated using flow cytometry. There was no significant association between serum TT levels and the number of circulating EPCs before TRT. Compared with the number of mean circulating EPCs at baseline (9.5 ± 6.2), the number was significantly higher after 3 months (16.6 ± 11.1, p = 0.027), 6 months (20.3 ± 15.3, p = 0.006) and 12 months (27.2 ± 15.5, p = 0.017) of TRT. Thus, we conclude that serum TT levels before TRT are not significantly associated with the number of circulating EPCs in men with late onset hypogonadism. However, TRT can increase the number of circulating EPCs, which implies the benefit of TRT on endothelial function in hypogonadal men.
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Células Endoteliales/efectos de los fármacos , Terapia de Reemplazo de Hormonas , Hipogonadismo/tratamiento farmacológico , Células Madre/efectos de los fármacos , Testosterona/administración & dosificación , Administración Cutánea , Adulto , Edad de Inicio , Anciano , Biomarcadores/sangre , Recuento de Células , Distribución de Chi-Cuadrado , Células Endoteliales/patología , Citometría de Flujo , Geles , Humanos , Hipogonadismo/sangre , Hipogonadismo/epidemiología , Hipogonadismo/patología , Masculino , Persona de Mediana Edad , Vigilancia de Productos Comercializados , Células Madre/patología , Taiwán/epidemiología , Testosterona/sangre , Testosterona/deficiencia , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
Even though a growing number of studies have found that patients with ankylosing spondylitis (AS) suffer from sexual problems, only very few studies have specifically addressed the relationship between AS and ED. Using a population-based data set, this case-control study aimed to examine the association of ED with a prior diagnosis of AS in Taiwan. We selected 2213 ED patients ≥40 years old and 17,704 matched controls. We considered the date of the first diagnosis of ED as the index date for cases. Multivariate logistic regression was performed to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between previously diagnosed AS and ED. A total of 224 out of the 19,917 sampled subjects (1.1%) had been diagnosed with AS before the index date. Prior AS was found in 42 (1.9%) cases and 182 (1.0%) controls. After adjusting for geographic location, urbanization level, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, depressive disorder and alcohol abuse/alcohol-dependence syndrome, multivariate logistic regression revealed that cases were more likely to have been previously diagnosed with AS than controls (OR=1.58, 95% CI=1.09-2.19, P=0.019). There was an association between ED and AS. We suggest that physicians should be attentive to sexual complaints from AS patients in order to refer them to other specialists for multidisciplinary management.
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Disfunción Eréctil/etiología , Espondilitis Anquilosante/complicaciones , Adulto , Anciano , Estudios de Casos y Controles , Comorbilidad , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Espondilitis Anquilosante/diagnóstico , Encuestas y Cuestionarios , TaiwánRESUMEN
The relationship between endogenous plasma testosterone and plasma lipids was assessed among 856 Taiwanese men â§40 years old originally recruited for an epidemiological study of testosterone deficiency syndrome. Blood samples were drawn from fasting (n = 562) and non-fasting (n = 294) subjects between 0800 to 1100 hours. With adjustment of age, body mass index and sex hormone-binding globulin, the following results were shown: (i) triglyceride (TG) levels were negatively associated with quartile levels of testosterone, and the magnitudes of associations were greater for postprandial TGs than for fasting TGs; (ii) high-density lipoprotein cholesterol (HDL-C) levels were positively related to quartile levels of testosterone, but the associations became insignificant after further control of TGs; and (iii) the calculated low-density lipoprotein cholesterol (LDL-C) levels were positively associated with quartile levels of testosterone. Similar results were obtained in multivariate linear regression analyses with additional control of hypertension and diabetes. In these Taiwanese men, the favorable association of endogenous plasma testosterone with HDL-C counterbalances the unfavorable association of it with LDL-C, while the net influence of testosterone on plasma lipids for cardiovascular system was still in the beneficial direction due to its negative association with postprandial plasma TG levels.
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Lípidos/sangre , Testosterona/sangre , Adulto , Anciano , Anciano de 80 o más Años , Ayuno/sangre , Humanos , Persona de Mediana Edad , Globulina de Unión a Hormona Sexual/metabolismo , TaiwánRESUMEN
This study aimed to investigate immunostaining patterns for major histocompatibility complex class I (MHC-I) in different types of myopathies and to assess the diagnostic value of CD8/MHC-I complex for definite polymyositis. The study included 20 cases of definite polymyositis, 20 cases of dermatomyositis and 10 cases of dystrophies with muscle inflammation (inflammatory muscular dystrophy). Immunohistochemical staining with MHC-I antibody demonstrated the presence of MHC-I along the sarcolemma of scattered or small groups of non-necrotic fibres in both polymyositis and inflammatory muscular dystrophy, whereas intense sarcolemmal immunostaining for MHC-I was diffusely present in almost all fibres in dermatomyositis. Double immunofluorescence labelling for CD8 and MHC-I detected the CD8/MHC-I complex in 20% of polymyositis cases with mononuclear cell infiltrates. No CD8/MHC-I complex was found in the dermatomyositis or inflammatory muscular dystrophy cases. The results suggest that MHC-I detection alone cannot be used as a reliable diagnostic test to differentiate polymyositis from dystrophies with secondary muscle inflammation. The CD8/MHC-I complex, although showing high specificity, is neither a sensitive nor an easy-to-handle diagnostic test for polymyositis.
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Antígenos CD8/metabolismo , Genes MHC Clase I , Polimiositis/diagnóstico , Adolescente , Adulto , Anciano , Biomarcadores/metabolismo , Biopsia , Niño , Dermatomiositis/diagnóstico , Dermatomiositis/genética , Dermatomiositis/metabolismo , Diagnóstico Diferencial , Femenino , Técnica del Anticuerpo Fluorescente Directa , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Distrofias Musculares/diagnóstico , Distrofias Musculares/genética , Distrofias Musculares/metabolismo , Polimiositis/genética , Polimiositis/metabolismo , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Adulto JovenRESUMEN
Kawasaki disease (KD) is the most common form of pediatric vasculitis. Though its etiology is unknown, researchers have suggested that it is related to genetics. The inositol 1,4,5-triphosphate receptor type 3 (ITPR3) gene has a strong association with the development of type 1 diabetes and, plays a critical role in the development of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Graves' disease. The aim of study is to examine the association of ITPR3 polymorphisms with KD risk in Taiwanese children. This study evaluates the single nucleotide polymorphisms (SNP) rs2229634 in the ITPR3 gene with KD in a case-control study involving 93 KD patients and 680 healthy, gender- and age-matched controls. The frequency of the rs2229634 T/T genotype was significantly higher in KD patients with coronary artery aneurysm (CAA) than in patients without CAA [odds ratio (OR) = 2.56, 95% confidence interval (95% CI) = 1.35-4.88, P = 0.004]. In addition, KD patients with the T/T genotype elevated mean serum levels of C-reactive protein compared with patients with the C/C or C/T genotype (12.2 mg dL(-1) vs. 8.5 mg dL(-1) , P = 0.036). In conclusion, the results of this study suggest that the rs2229634 SNP in the ITPR3 gene is associated with the risk of CAA formation in Taiwanese KD patients.
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Aneurisma Coronario/genética , Predisposición Genética a la Enfermedad , Receptores de Inositol 1,4,5-Trifosfato/genética , Síndrome Mucocutáneo Linfonodular/genética , Polimorfismo de Nucleótido Simple , Alelos , Pueblo Asiatico/genética , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Niño , Preescolar , Cromosomas Humanos Par 6/genética , Aneurisma Coronario/etiología , Frecuencia de los Genes , Marcadores Genéticos , Genotipo , Humanos , Taiwán/epidemiologíaRESUMEN
Although benzene, a well-known human carcinogen, has been shown to induce apoptosis in vitro, no studies have been carried out to confirm and characterize its role in activating apoptosis in vivo. The present study investigated the effects of benzene inhalation on the epithelial cells lining the respiratory tract including bronchioles, terminal bronchioles, respiratory bronchioles and alveoli of male Sprague-Dawley rats. Inhalation of benzene 300 ppm for 7 days induced apoptotic changes in the parenchymal components in the lung that significantly exceeded the events of programmed cell death in normal control tissues. Apoptosis was confirmed by the electrophoretic analysis of internucleosomal DNA fragmentation of benzene-exposed lung tissues, which exhibited 180-200 bp laddering subunits indicative of genomic DNA degradation. Furthermore, semi-quantitative analysis of intracellular localization of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling TUNEL) showed a significant (p < 0.001) increase in the apoptotic index calculated for bronchiolar 73.5%, terminal bronchiolar (65%), and respiratory bronchiolar 60.8% segmental epithelial components as well as alveolar (55%) epithelia. Analysis of immunohistochemical expression of apoptosis-related gene products also supported the hypothesis that benzene can induce apoptosis in chemosensitive target cells in the lung parenchyma. Quantitative immunhistochemistry showed a statistically significant increase p < 0.001 in the immunoreactive staining index for cytochrome c, Apaf-1 (apoptosis activating factor-1), DNA fragmentation factor, and representative cysteine proteases including caspase-1, caspase-2L, caspase-8 and caspase-9. Thus this is the first study of the respiratory system that demonstrates that benzene inhalation induces lung cell apoptosis as confirmed by DNA electrophoresis, in situ nick end labeling, and the upregulation of apoptosis-related gene products that facilitate caspase-cleaved enzymes which lead to cell degradation via programmed cell death. These responses may represent an important defense mechanism within the parenchymal cells of the respiratory system that reduce mutational hazard and the potential carcinogenic effects of benzene-initiated pathogenesis.