RESUMEN
Myasthenia gravis (MG) is a kind of chronic autoimmune disease which can weaken patients' motor function and, furthermore, produce negative impact on the health-related quality of life (HRQoL). The primary purpose of this research was to evaluate factors that might affect the HRQoL of MG patients. A cross-sectional clinical research was carried out including 188 successive patients with MG. Myasthenia Gravis Foundation of America (MGFA) classification and Quantitative Myasthenia Gravis (QMG) score were applied to assess the severity of the disease. The Medical Outcome Survey 36-Item Short-Form Health Survey (SF-36) was used to estimate the HRQoL. Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were utilized to measure the depression and anxiety symptom. Factors may influence the HRQoL of MG patients include age, educational level, occupation, the situation of the thymus, the type of MG and generalized myasthenia gravis (GMG), the severity of the disease and the psychological disorder. Higher QMG and HARS scores were two significant factors that can prognosticate lower Physical Composite Score (PCS) and Mental Composite Score (MCS), while older age was just a significant factor which has prognostic value for lower PCS. The results of this research may have a potential guiding significance for the clinical treatment strategy and improve the quality of life in patients with MG consequently. In addition to the treatment of physical symptoms, the psychological symptoms such as anxiety and depression should be concerned as well.
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Actividades Cotidianas/psicología , Ansiedad/psicología , Depresión/psicología , Miastenia Gravis/psicología , Calidad de Vida/psicología , Adulto , Ansiedad/diagnóstico , China , Estudios Transversales , Depresión/diagnóstico , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
In order to obtain bioactive α-bungarotoxin (αBtx) using recombinant protein technique, a codon-optimized synthetic gene was expressed in fusion with the N-terminal 10-His-tag and C-terminal Strep-tag in Escherichia coli. Further optimization through site-directed mutagenesis enabled moderate expression of the protein without the N-terminal His-tag or the C-terminal Strep-tag. Two such recombinant αBtx (rαBtx) were obtained, both with an additional methionine and a glycine at the N-terminal and one with (G4S1)2-Strep-tag at the C-terminal. The rαBtx proteins were refolded using a novel protocol, which efficiently produced final products with activity similar to its natural counterpart. The protocol could easily be scale up, which produced 0.3-1mg of pure and highly active rαBtx per liter of E. coli culture.
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Bungarotoxinas/química , Codón , Genes Sintéticos , Proteínas Recombinantes de Fusión/química , Animales , Secuencia de Bases , Bungarotoxinas/biosíntesis , Bungarotoxinas/genética , Bungarotoxinas/aislamiento & purificación , Clonación Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Expresión Génica , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Plásmidos/química , Plásmidos/metabolismo , Replegamiento Proteico , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , Serpientes/metabolismoRESUMEN
The development and progression of esophageal cancer is associated with multiple alterations in the genome, including loss of the tumor suppressor phosphatase and tensin homolog deleted from the chromosome 10 (PTEN) gene. The purpose of this study was to determine the effects of adenovirus-mediated MMAC/PTEN expression on the growth and survival of human esophageal cancer cells in vitro and in vivo. We found that compared to control cells, overexpression of PTEN significantly suppressed growth and induced apoptosis in esophageal cancer cell lines Eca-109 and TE-1 via downregulation of Bcl-2 expression and changes in cell-cycle progression. Adenovirus PTEN also inhibited the growth of subcutaneous tumor xenografts by significantly reducing tumor size in vivo. Thus our results confirm the proposed functional role of MMAC/PTEN as a regulator of esophageal cancer progression in vivo and in vitro. PTEN might be an important biological marker and potential therapeutic target in the treatment of human esophageal cancer.
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Monoéster Fosfórico Hidrolasas/genética , Monoéster Fosfórico Hidrolasas/fisiología , Adenoviridae/genética , Adenoviridae/metabolismo , Infecciones por Adenoviridae/genética , Infecciones por Adenoviridae/terapia , Animales , Apoptosis/genética , Apoptosis/fisiología , Carcinoma/genética , Carcinoma/terapia , Línea Celular Tumoral , Regulación hacia Abajo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Genes Supresores de Tumor , Humanos , Ratones , Ratones Desnudos , Neoplasias/genética , Neoplasias/terapia , Fosfohidrolasa PTEN , Monoéster Fosfórico Hidrolasas/metabolismo , Distribución AleatoriaRESUMEN
Background and Purpose: Patients' self-perceived burden (SPB) is associated with distress, which has a potentially negative influence on disease rehabilitation and quality of life. Stroke represents a significant health and social burden. The aim of the study was to assess, compare, and identify predictors of SPB in stroke survivors during the first 3 months post-stroke. Methods: A prospective longitudinal study was used. Consecutive stroke inpatients were recruited from the neurology department of three general hospitals in Xi'an, China. Patients were surveyed using the Self-perceived Burden Scale (SPBS) on the fourth day of admission (Acute phase, Time 1, T1) and 1 month (Time 2, T2) and 3 months (Time 3, T3) post-stroke. Results: Considerable burden was experienced by 84.15-91.50% of patients in the first 3 months post-stroke. The mean score of physical burden was the highest. Over time, physical, emotional, and economic burden all declined. The following characteristics had significant association with increased patient SPB at T1, T2, and T3: age, self-evaluated economic pressure, comorbidity, and functional status (P < 0.01). Patients' knowledge about stroke was only significantly associated with SPB at T3 (P < 0.01). Conclusions: Patients experienced a high degree of SPB in the early stage after stroke. Addressing the characteristics and predicting factors as well as the development of a targeted intervention for SPB may improve survival and post-stroke disability.
RESUMEN
Acute exacerbation of generalized myasthenia gravis (GMG) can cause swallowing impairment, respiratory failure, or death. It is important to identify immunological factors that might be regarded reliably as an index of the patient's clinical condition, response to treatment, and measure of certain immune aberrations of MG. In this study we investigated correlations between complement component C3, acetylcholine receptor antibody (AChRab) titer, and clinical severity of GMG. AChRab titer and C3 concentration were determined by radioimmunoassay and nephelometry, respectively. The clinical severity of GMG was assessed by the quantitative MG score (QMGS) according to Besinger and colleagues. Our findings indicate that the C3 level correlates with clinical severity of AChRab-positive GMG.
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Complemento C3/metabolismo , Miastenia Gravis/sangre , Miastenia Gravis/patología , Adolescente , Adulto , Autoanticuerpos/sangre , Biomarcadores/sangre , Complemento C3/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Receptores Colinérgicos/sangre , Adulto JovenRESUMEN
Factor rotation is conducted to aid interpretation in exploratory factor analysis (EFA). Target rotation allows researchers to directly examine the match between the rotated factor loading matrix and their expected factor loading pattern. In some EFA applications, however, researchers have expectations on both the factor loading pattern and the factor correlation pattern. We propose to extend target rotation such that target values can be specified for both factor loadings and factor correlations. We illustrate extended target rotation with a memory study and a personality study with the multitrait-multimethod design. We also explore the statistical properties of extended target rotation using simulated data. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Asunto(s)
Interpretación Estadística de Datos , Análisis Factorial , Modelos Estadísticos , Psicología/métodos , Humanos , Memoria a Corto Plazo/fisiología , Personalidad/fisiologíaRESUMEN
BACKGROUND: To observe the suppressive effects of exogenous p27 gene on human lung cancer cell line A549. METHODS: An adenovirus expression vector (pAd CMV-p27) containing 570 bp human full-length p27 cDNA was transfected into human lung cancer cell line A549. Expression of exogenous p27 gene was detected by dot-blot hybridization and laser co-focal system. MTT was adopted to measure the effects of exogenous p27 gene on cell cycle progression and cell features of the infected A549. RESULTS: The mRNA and protein expression level of p27 was remarkably increased after transfecting with exogenous p27 gene. The apoptosis of infected A549 occurred and the progression of cell cycle was arrested in G1 phase. CONCLUSIONS: p27(kipl) gene transfer may play a therapeutic role in the treatment of lung cancer.
RESUMEN
Follicular helper CD4+ T (TFH) cells are the specialized providers of B cell help in germinal centers (GCs). Formation of GCs in thymi is the primary thymi characteristic in MG patients. TFH cells are involved in the pathogenic process of many autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and autoimmune thyroid disease. The role thymic TFH cells played in MG with thymoma has not been elucidated. Here, we analyzed surface markers CXCR5, Bcl-6, ICOS and IL-21 on TFH cells in thymus derived from thymoma patients with ocular MG (OMG), generalized MG (GMG) or without MG using immunohistochemical staining, immunofluorescence, western blotting, and real-time PCR analysis. We show that clinical severity of MG is correlated with higher mRNA expression of the four markers. Indeed, results show higher expression of all four markers in thymoma with GMG patients compared with both OMG and non-MG patients. We found no significant difference in the expression of CXCR5, Bcl-6 and ICOS in OMG compared with non-MG patients. Regression analysis shows a positive correlation between thymic CXCR5, BCL-6, ICOS and IL-21 levels and quantitative MG score (QMGS) in GMG patients. In addition, we found no significant correlation between TFH cell expression and QMGS in OMG patients. Our findings show that higher expression of TFH cells in the thymoma is related to the clinical severity of MG and suggests a role in the pathogenesis of MG. However, the real source of these TFH cells is still uncertain and needs further study.
Asunto(s)
Linfocitos T CD4-Positivos/patología , Miastenia Gravis/patología , Timoma/patología , Timo/patología , Neoplasias del Timo/patología , Linfocitos T CD4-Positivos/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Humanos , Proteína Coestimuladora de Linfocitos T Inducibles/genética , Proteína Coestimuladora de Linfocitos T Inducibles/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Miastenia Gravis/cirugía , Proteínas Proto-Oncogénicas c-bcl-6 , ARN Mensajero/metabolismo , Receptores CXCR5/genética , Receptores CXCR5/metabolismo , Índice de Severidad de la Enfermedad , Timectomía , Timoma/cirugía , Timo/cirugía , Neoplasias del Timo/cirugíaRESUMEN
Differential expressions of immune molecules have been shown in the thymi with pathological results, including myasthenia gravis (MG). CD25 is an activation marker expressed on T cells. CXCL13 mediates the homing and motility of B cells in secondary lymphoid tissues. Herein, we investigated the expressions of CD25 and CXCL13 in the thymi of thymic hyperplasia patients with MG or with non-MG. A total of 34 thymic hyperplasia patients with MG (20 generalized MG (GMG) and 14 ocular MG (OMG) and six thymic hyperplasia patients without MG were enrolled and analyzed using immunohistochemical staining and real-time polymerase chain reaction for CD25 and CXCL13. Our study demonstrated a higher expression of both CD25 and CXCL13 in hyperplastic thymi with OMG or GMG compared to those with non-MG. According to the immunohistochemical results, we observed that CD25 expression was significantly lower in atrophic thymi and non-MG hyperplastic thymi, compared with that in infant thymi (P = 0.002 and 0.005, respectively). In contrast to CD25 expression, we did not observe differential expression of CXCL13 among three control groups. And a similar CD25 mRNA expression was found in real-time polymerase chain reaction (PCR) results. We observed that both hyperplastic thymi with OMG or GMG expressed significantly higher levels of CD25 than those with non-MG (P = 0.007 and 0.001, respectively). And an increase of CD25 expression was observed in hyperplastic thymi with GMG compared to those with OMG (P = 0.030). Similarly, CXCL13 expression was significantly higher in hyperplastic thymi with GMG or with OMG than those with non-MG (P = 0.001 and 0.050, respectively). No significant CXCL13 expression difference was found between hyperplastic thymi with GMG and those with OMG (P > 0.05). The real-time PCR results showed a similar tendency of CD25 mRNA expression among the thymi of non-MG, OMG, and GMG patients, but the difference did not reach significance (P > 0.05). An obvious increased expression of CXCL13 was found in hyperplastic thymi with GMG patients, compared to those with non-MG and OMG patients (P = 0.003 and 0.071, respectively). There was no difference found between hyperplastic thymi with non-MG and with OMG. Regression analysis showed a positive correlation between thymic CD25 level and MG symptom severity (F = 28.240; P = 0.000, r = 0.523). Similarly, a positive correlation was found between thymic CXCL13 expression and MG disease severity (F = 36.093; P = 0.000, r = 0.671). Taken together, our findings suggest CD25 and CXCL13 participate in the pathogenesis of MG and may influence the clinical symptoms of MG.
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Miastenia Gravis/diagnóstico , Adulto , Estudios de Casos y Controles , Quimiocina CXCL13/genética , Quimiocina CXCL13/metabolismo , Femenino , Humanos , Lactante , Subunidad alfa del Receptor de Interleucina-2/genética , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Masculino , Persona de Mediana Edad , Miastenia Gravis/complicaciones , Miastenia Gravis/metabolismo , Timo/metabolismo , Timo/patología , Hiperplasia del Timo/complicaciones , Hiperplasia del Timo/diagnóstico , Transcripción GenéticaRESUMEN
BACKGROUND: Increasing evidence supports a link between expressions of CD4, CD25, Foxp3, and CXCL13 in thymic hyperplasia with myasthenia gravis (MG) patients. Herein, we investigated the expressions of these molecules in thymoma patients with ocular MG (OMG) or generalized MG (GMG). METHODS: A total of 58 thymoma patients with MG (23 GMG and 35 OMG) and 73 thymoma patients without MG were analyzed using immunohistochemistry for CD4, CD25, Foxp3 and CXCL13. RESULTS: OMG was more frequent than GMG in late-onset thymoma males (P=0.037), but no difference was observed in females (P=0.128). There was no significant difference of Foxp3 expression among all types of thymoma from patients with OMG and Non-MG. Compared to patients with OMG, a decreased Foxp3 expression was seen in types AB, B1 and B2 thymoma with GMG, with the decrease in the former two types reaching significance (P=0.001, 0.043, respectively). However, a significantly increased expression of CXCL13 was observed in types B1 and B2 thymoma patients with GMG (P=0.027, 0.048, respectively, compared to those with OMG). Furthermore, the CXCL13 expression in type AB thymoma patients with GMG was higher than those with Non-MG (P=0.003).There were no differences among expressions of CD4, CD25, Foxp3, and CXCL13 in type A and B3 thymoma patients, regardless of with OMG, GMG or Non-MG. CONCLUSION: Differential expressions of Foxp3 and CXCL13 in various types of thymoma patients with OMG or GMG might suggest the differential immunological processes underlying the two subtype of MG.