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1.
Spine J ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31759132

RESUMO

BACKGROUND CONTEXT: Although quantitative measurements improve the assessment of disc degeneration, acquirement of quantitative measurements relies on manual segmentation on lumbar magnetic resonance images (MRIs), which may introduce subjective bias. To date, only a few semi-automatic systems have been developed to quantify important components on MRIs. PURPOSE: To develop a deep learning based program (Spine Explorer) for automated segmentation and quantification of the vertebrae and intervertebral discs on lumbar spine MRIs. STUDY DESIGN: Cross-sectional study PATIENT SAMPLE: The study was extended on the Hangzhou Lumbar Spine Study, a population-based study of mainland Chinese with focuses on lumbar degenerative changes. From this population-based database, 50 sets lumbar MRIs were randomly selected as training dataset, and another 50 as test dataset. OUTCOME MEASURES: Regions of vertebrae and discs were manually segmented on T2W sagittal MRIs to train a convolutional neural network for automated segmentation. Intersection-over-union (IU) was calculated to evaluate segmentation performance. Computational definitions were proposed to acquire quantitative morphometric and signal measurements for lumbar vertebrae and discs. MRIs in the test dataset were automatically measured with Spine Explorer and manually with ImageJ. METHODS: Intra-class correlation coefficient (ICC) was calculated to examine inter-software agreements. Correlations between disc measurements and Pfirrmann score as well as age were examined to assess measurement validity. RESULTS: The trained Spine Explorer automatically segments and measures a lumbar MRI in half a second, with mean IU of 94.7% and 92.6% for the vertebra and disc, respectively. For both vertebra and disc measurements acquired with Spine Explorer and ImageJ, the agreements were excellent (ICC=0.81∼1.00). Disc measurements significantly correlated to Pfirrmann score, and greater age was associated with greater anterior disc bulging area (r=0.35∼0.44) and fewer signal measurements (r=-0.62∼-0.77) as automatically acquired with Spine Explorer. CONCLUSIONS: Spine Explorer is an efficient, accurate, and reliable tool to acquire comprehensive quantitative measurements for lumbar vertebra and disc. Implication of such deep learning based program can facilitate clinical studies of the lumbar spine.

2.
Acad Radiol ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31767534

RESUMO

RATIONALE AND OBJECTIVES: To study the MRI characteristics of early extrapancreatic necrosis and compare them with those of peripancreatic fluid collections in acute pancreatitis (AP). MATERIALS AND METHODS: This retrospective study enrolled 70 AP patients who had extrapancreatic collections visible on MRI within 1 week of onset. Extrapancreatic collections were divided into extrapancreatic necrosis and peripancreatic fluid collections based on follow-up MRI, CT, or pathology. The number and area of extrapancreatic collections, extrapancreatic inflammation on MRI (EPIM) score, MR severity index score and clinical characteristics were evaluated and compared between the two groups. RESULTS: Of the seventy AP patients, 32 (45.7%) had extrapancreatic necrosis, and 38 (54.3%) had peripancreatic fluid collections. The number and area of extrapancreatic collections, MR severity index score, EPIM score, and prevalence of associated hemorrhage were significantly higher in extrapancreatic necrosis patients than in those with peripancreatic fluid collections (p < 0.001). Among the single indicators, the accuracy of the area of extrapancreatic collections (AUC = 0.871) was comparable to that of the EPIM score for predicting extrapancreatic necrosis and was significantly higher than that of the other two indicators. The combination of all indicators showed the highest predictive accuracy (AUC = 0.949), and combinations of two or more indicators demonstrated significantly higher predictive accuracy for extrapancreatic necrosis than any single indicator (p < 0.05) except for the area of extrapancreatic collections (p > 0.05). CONCLUSION: The MRI characteristics have the potential to differentiate early extrapancreatic necrosis from peripancreatic fluid collections and help indicate extrapancreatic necrosis.

3.
ACS Sens ; 4(9): 2536-2545, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31503452

RESUMO

Pollutant detection is of great importance for quality control of drinking water and environmental protection. The common methods of pollutant detection suffer from time-consuming procedures, bulky and expensive instruments, and complicated sample pretreatment. Herein, a type of conceptually new self-amplified fluorescent nanoparticle (SAFN) is constructed based on aggregation-induced emission (AIE) luminogens for rapid and visual detection of xylene in aqueous media. AIE luminogens are self-assembled into SAFNs in aqueous media, which emit efficiently due to the aggregation of luminogen molecules. The SAFNs of AIE luminogens stick xylene molecules from aqueous media through multiple interactions including hydrophobic and π-π interactions. Upon capturing xylene, SAFNs swell, which quench the fluorescence of the whole SAFNs, showing the self-amplification effect. Such a self-amplification effect is entirely different from that of conjugated polymers in the literature. Importantly, fluorescence quenching of SAFNs by xylene can be readily observed by the naked eye, which enables visual xylene sensing. The SAFNs enable rapid and visual detection of xylene in aqueous media with a low detection limit (5 µg/L) in the order of seconds. Given high sensitivity, rapid response, simple and easy operation, and low cost, SAFNs of AIE luminogens present a promising platform for visual detection of organic pollutants in aqueous media.

4.
Spine J ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31442618

RESUMO

BACKGROUND CONTEXT: Modic changes (MCs) have long been suspected as a pathologic cause of back pain. Although much attention has been focused on clinical perspectives, the etiology of MCs remains unclear. Although some studies have reported that sex, body mass index (BMI), cigarette smoking, and physical loading may associate with MCs, the observed associations are inconsistent among studies. PURPOSE: To investigate associations between MCs and lifestyle and lifetime occupational exposures using a general population sample. STUDY DESIGN: Cross-sectional study. PATIENT SAMPLE: The study was an extension of the Hangzhou Lumbar Spine Study, a population-based study of mainland Chinese focusing on lumbar degenerative changes. A total of 644 randomly selected subjects from a typical community in Hangzhou, Eastern China participated. OUTCOME MEASURES: The presence and type of MCs in the lumbosacral spine were evaluated on sagittal magnetic resonance images. Demographics, lifestyle factors, and occupational exposures were measured using a structured interview. METHODS: Univariate and multivariate logistic regressions were used to examine the associations of MCs with various environmental exposures. RESULTS: Among the 644 subjects (52.6±13.9 years; range 20-88 years) included in this study, 44.7% had MCs. In univariate regression analyses, the presence of MCs was associated with greater age, higher BMI, greater cigarette smoking, regular exercise, and absence of daily vehicle vibration. Modic changes were not univariately associated with sex or alcohol consumption. In addition, all occupational loading measurements were associated with the occurrence of MCs in univariate analyses, except work time spent in vehicles and work-related back injuries. However, in multivariate regression analyses, no statistically significant associations between the occurrence of MCs and lifestyle or lifetime occupational exposures were observed after adjusting for age, sex, and BMI. CONCLUSIONS: Age is an important determinant of MCs, with BMI and sex also playing a role. Lifestyle and occupational factors appear to have minor effects, if any, on the pathogenesis of MCs in the lumbar spine.

5.
Artigo em Inglês | MEDLINE | ID: mdl-30972672

RESUMO

Soil-exchangeable aluminum (Al) has toxic effects on living organisms in acidic soils. Earthworm presence and activity can alter soil pH, which has a significant influence on Al toxicity. However, the effects of earthworms on soil Al toxicity and fractions are still largely unknown. This laboratory study focused on the effects of three earthworm species (endogeics Pontoscolex corethrurus and Amynthas robustus, anecis Amynthas aspergillum) on soil acidification, Al fraction distribution, and base cation release. Three native earthworm species and a soil (latosolic red soil) collected from a botanical garden in South China were incubated under laboratory conditions. After 40 days of incubation, six Al fractions in soil, namely exchangeable (AlEx), weakly organically bound (AlOrw), organically bound (AlOr), amorphous (AlAmo), Al occluded in crystalline iron oxides (AlOxi), and amorphous aluminosilicate and gibbsite (AlAag) fractions, were extracted using a sequential procedure. Soil pH; organic carbon; total nitrogen; total Al (AlTotal); exchangeable K, Na, Ca, Mg contents; and CEC were determined as well. Compared to control soil, pH values increased by 0.79, 0.41, and 0.57 units in casts in the presence of P. corethrurus, A. robustus, and A. aspergillum, and 0.70, 0.32, and 0.50 units in non-ingested soil, respectively. Compared to control soil, the 61.7%, 30.7%, and 36.1% of AlEx contents in casts and 68.5%, 25.9%, and 39.0% of AlEx in non-ingested soil significantly decreased with the addition of P. corethrurus, A. robustus, and A. aspergillum, respectively. Moreover, compared to control soil, the 78.7%, 37.7%, and 40.1% of exchangeable Ca2+ and 12.3%, 24.7%, and 26.8% of exchangeable Mg2+ contents in casts significantly increased with the presence of P. corethrurus, A. robustus, and A. aspergillum, respectively. Soil treated with P. corethrurus had higher soil pH values, exchangeable Ca2+ contents, and lower AlEx than those with A. robustus and A. aspergillum. Results of principal component analyses showed that P. corethrurus, A. robustus, and A. aspergillum casts and non-ingested soil differ for soil pH, Al fractions, and exchangeable base cations release. These results indicate that earthworms, especially P. corethrurus, can reduce soil Al toxicity, increase soil pH, and affect the release of exchangeable base cations.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30838490

RESUMO

This study focused on the study of earthworm survival, growth, reproduction, enzyme activities, and protein contents to evaluate and predict the effects of different soil pH levels and determine the optimal risk assessment indicators for the effects. Survival rate, growth rate, and cocoon number as well as four enzyme (glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)) activities and two proteins (total protein (TP) and metallothionein (MT)) contents in earthworms were determined to characterize the responses of earthworm activity to five soil pH levels. These biological datasets (survival, growth, and reproduction) were compared with biochemical indexes (GSH-PX, SOD, POD, CAT, TP, and MT), mainly using biphasic dose-response models. The results indicated that the soil pH value had significant inhibitory effects on the survival, growth, and reproduction of earthworms beginning with 3.0, 4.0, and 5.2, respectively. The dose-response models (J-shaped and inverted U-shaped curves) statistics indicated that the critical values (ECZEP) of the GSH-PX, SOD, POD, CAT, TP, and MT inhibited by soil acid stress were 3.46, 3.76, 3.35, 3.54, 3.50, and 3.96 (average 3.60), respectively. In the present study, the fitting curve analysis showed that the responses of the CAT activities and TP and MT contents in earthworm in response to soil pH have the behavior of hormesis.

7.
Eur Radiol ; 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30413966

RESUMO

OBJECTIVES: To predict the recurrence of acute pancreatitis (AP) by constructing a radiomics model of contrast-enhanced computed tomography (CECT) at AP first attack. METHODS: We retrospectively enrolled 389 first-attack AP patients (271 in the primary cohort and 118 in the validation cohort) from three tertiary referral centers; 126 and 55 patients endured recurrent attacks in each cohort. Four hundred twelve radiomics features were extracted from arterial and venous phase CECT images, and clinical characteristics were gathered to develop a clinical model. An optimal radiomics signature was chosen using a multivariable logistic regression or support vector machine. The radiomics model was developed and validated by incorporating the optimal radiomics signature and clinical characteristics. The performance of the radiomics model was assessed based on its calibration and classification metrics. RESULTS: The optimal radiomics signature was developed based on a multivariable logistic regression with 10 radiomics features. The classification accuracy of the radiomics model well predicted the recurrence of AP for both the primary and validation cohorts (87.1% and 89.0%, respectively). The area under the receiver operating characteristic curve (AUC) of the radiomics model was significantly better than that of the clinical model for both the primary (0.941 vs. 0.712, p = 0.000) and validation (0.929 vs. 0.671, p = 0.000) cohorts. Good calibration was observed for all the models (p > 0.05). CONCLUSIONS: The radiomics model based on CECT performed well in predicting AP recurrence. As a quantitative method, radiomics exhibits promising performance in terms of alerting recurrent patients to potential precautions. KEY POINTS: • The incidence of recurrence after an initial episode of acute pancreatitis is high, and quantitative methods for predicting recurrence are lacking. • The radiomics model based on contrast-enhanced computed tomography performed well in predicting the recurrence of acute pancreatitis. • As a quantitative method, radiomics exhibits promising performance in terms of alerting recurrent patients to the potential need to take precautions.

8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 35(3): 371-375, 2018 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-29896734

RESUMO

OBJECTIVE: To report on prenatal diagnosis and follow up of two patients with paternal uniparental disomy of chromosome 6 (pUPD6). METHODS: Fetal cells were subjected to in situ culturing and G-banded chromosomal analysis. DNA samples of the fetuses and their parents were also analyzed with single nucleotide polymorphism microarray (SNP array). RESULTS: Both fetuses had a normal male karyotype. SNP array analysis showed both have carried pUPD6. CONCLUSION: pUPD6 can lead to transient neonatal diabetes mellitus type 1. Homozygous status of recessive mutations, disorder of gene imprinting, and its influence on placental function are the main factors to be considered during prenatal diagnosis and genetic counseling for pUPD6.

9.
Hum Reprod ; 33(4): 757-767, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29579270

RESUMO

STUDY QUESTION: Do specific factors affect the segregation patterns of a quadrivalent structure and can the quadrivalent affect genome stability during meiosis? SUMMARY ANSWER: Meiotic segregation patterns can be affected by the carrier's gender and age, location of breakpoints and chromosome type, and the quadrivalent structure can increase genome instability during meiosis. WHAT IS KNOWN ALREADY: Carriers of reciprocal translocations have an increased genetic reproductive risk owing to the complex segregation patterns of a quadrivalent structure. However, the results of previous studies on the factors that affect segregation patterns seem to be contradictory, and the effect of a quadrivalent on genome stability during meiosis is unknown. STUDY DESIGN, SIZE, DURATION: We designed a retrospective study to analyze the segregation patterns of 24 chromosomes from reciprocal translocation and non-translocation patients. Data for 356 reciprocal translocation carriers and 53 patients with the risk to transmit monogenic inherited disorders (RTMIDs) undergoing PGD-single nucleotide polymorphism array analysis were collected. The study was performed between March 2014 and July 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Segregation patterns of a quadrivalent in 1842 blastocysts from 466 assisted reproduction cycles of reciprocal translocation carriers were analyzed according to the location of chromosome breakpoints, the carrier's gender and age, and chromosome type. In addition, to analyze the effect of quadrivalent structure on genome stability, segregation products of chromosomes which are not involved in the translocation from translocation carriers were compared with those of 23 pairs of chromosomes in 318 blastocysts from 72 assisted reproduction cycles of patients with RTMIDs. MAIN RESULTS AND THE ROLE OF CHANCE: The percentage of adjacent-2 products with severe asymmetric quadrivalent was significantly higher than those with mild asymmetric quadrivalent (P = 0.020) while, in contrast, the incidence of 4:0/others was lower (P = 0.030). The frequencies of adjacent-1, adjacent-2 and 3:1 products differed between male and female carriers (P < 0.001, P = 0.015 and P = 0.001, respectively), and also for adjacent-1 and 4:0/others products in young versus older carriers (P = 0.04 and P = 0.002, respectively). In addition, adjacent-1 products of a quadrivalent with an acrocentric chromosome were significantly higher than those of a quadrivalent without an acrocentric chromosome (P = 0.001). Moreover, a quadrivalent could significantly increase the frequencies of abnormal chromosomes compared to patients with RTMIDs (P = 0.048, odds ratio (OR) = 1.43, 95% CI = 1.01-2.43), especially for the male carriers (P = 0.018, OR = 1.58, 95% CI = 1.08-2.25). In contrast, for older carriers, no difference was found in both aneuploidy and segmental anomalies compared to patients with RTMIDs. LIMITATIONS, REASONS FOR CAUTION: The study contained appropriate controls, yet the analysis was limited by a small number of control patients and embryos. WIDER IMPLICATIONS OF THE FINDINGS: Until now, there had been no definite report about the effect of quadrivalents on genome stability in reciprocal translocation carriers compared with control samples, and in the present study the large sample size ensured a detailed analysis of factors with a possible impact on segregation patterns. These data provide a better insight into the meiotic mechanisms involved in non-disjunction events in gametes from reciprocal translocation carriers. In addition, our results will help to provide each reciprocal translocation carrier couple undergoing PGD with more appropriate genetic counseling and a better understanding of the large numbers of abnormal embryos with chromosome aneuploidy. STUDY FUNDING/COMPETING INTEREST(S): The research was supported by the Research Funding of Shanghai Ji Ai Genetics & IVF Institute and the authors declare a lack of competing interests in this study.

10.
Basic Res Cardiol ; 110(3): 22, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25820907

RESUMO

Patients with coronary artery disease show high serum levels of interleukin (IL)-27, a novel member of the IL-6 family. However, the function of IL-27 in hearts suffering ischemia/reperfusion (IR) injury is unclear. Here, we showed increased expression of mRNA for the IL-27 subunits, EBI3 and p28, in rat hearts after 40 min of coronary ligation and release for 7 days. This increase was associated with a peak in the release of the cardiac enzyme, creatine kinase-MB, on day 2 post-release. Moreover, levels of IL-27 receptor subunit gp130 mRNA, but not those of subunit WSX-1 mRNA, decreased in post-ischemic hearts. These results suggest that increased IL-27 production may compensate for receptor downregulation during myocardial recovery. Lactate dehydrogenase release and crystal violet staining revealed that IL-27 or IL-6 significantly attenuated severe hypoxia (SH, 2 % O2)-induced cell damage in H9c2 cardiomyoblasts and primary rat neonatal cardiomyocytes. Incubating cardiomyocytes with IL-27 or IL-6 resulted in time-dependent activation of signal transducers and activators of transcription 3 (STAT3). Interestingly, IL-27-induced STAT3 activation was attenuated by pre-treatment with a gp130-neutralizing antibody. Blocking gp130 also reduced the cytoprotective effects of IL-27 or IL-6. Moreover, IL-27-mediated protection against SH was blocked by stattic, a small-molecule inhibitor of STAT3. IL-27 markedly improved post-ischemic recovery and reduced tissue damage in isolated perfused hearts when administered 5 min before reperfusion. These results indicate that IL-27 protects the myocardium against IR injury and facilitates the recovery of damaged cardiomyocytes via the gp130/STAT3 pathway.


Assuntos
Receptor gp130 de Citocina/metabolismo , Interleucinas/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/fisiologia , Animais , Western Blotting , Modelos Animais de Doenças , Reação em Cadeia da Polimerase , Ratos , Ratos Wistar
11.
Reprod Biomed Online ; 29(4): 490-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25131559

RESUMO

The effect of quadrivalent geometry on meiotic behaviour was evaluated. Segregation patterns of 404 cleavage stage embryos from 40 reciprocal translocation carriers undergoing 75 PGD cycles were analysed according to the asymmetric degree of quadrivalent. The percentage of alternate products with severe asymmetric quadrivalents was significantly lower than patients with mild asymmetric quadrivalents (22.5% versus 38.7%, P = 0.001). The incidence of 3:1 products was significantly higher in patients with severe compared with mild asymmetric quadrivalents (23.1% versus 12.2%, P = 0.004). The incidence of adjacent 1 (25.8% versus 24.3%), 2 (11.5% versus 12.6%) and 4:0/other segregation products (17.0% versus 12.2%) were not statistically significantly different between embryos from patients with severe or mild asymmetric quadrivalents. After adjusting for the confounder of sex using a logistic regression model, the odds of alternate embryos is about one-half for carriers classified as severe (OR 0.456, 95% CI 0.291 to 0.705), and the odds of 3:1 embryos is 2.2 times higher for carriers with severe asymmetric quadrivalents (OR 2.235, 95% CI 1.318 to 3.846). Our results suggest that the meiotic segregation pattern is related to the degree of asymmetry of specific quadrivalents. Severe asymmetric quadrivalents increases the risk of abnormal embryos.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/diagnóstico , Divisão Celular Assimétrica , Blastômeros/patologia , Segregação de Cromossomos , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Diagnóstico Pré-Implantação , Translocação Genética , Transtornos 46, XX do Desenvolvimento Sexual/genética , Transtornos 46, XX do Desenvolvimento Sexual/patologia , Transtornos 46, XX do Desenvolvimento Sexual/prevenção & controle , Adulto , Blastômeros/citologia , China , Estudos de Coortes , Criopreservação , Transtorno 46,XY do Desenvolvimento Sexual/genética , Transtorno 46,XY do Desenvolvimento Sexual/patologia , Transtorno 46,XY do Desenvolvimento Sexual/prevenção & controle , Ectogênese , Transferência Embrionária , Características da Família , Feminino , Heterozigoto , Humanos , Masculino , Injeções de Esperma Intracitoplásmicas , Vitrificação
12.
Med Sci Monit ; 20: 577-81, 2014 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-24714517

RESUMO

BACKGROUND: Axillary lymph nodes (ALN) are the most commonly involved site of disease in breast cancer that has spread outside the primary lesion. Although sentinel node biopsy is a reliable way to manage ALN, there are still no good methods of predicting ALN status before surgery. Since morbidity in breast cancer surgery is predominantly related to ALN dissection, predictive models for lymph node involvement may provide a way to alert the surgeon in subgroups of patients. MATERIAL AND METHODS: A total of 1325 invasive breast cancer patients were analyzed using tumor biological parameters that included age, tumor size, grade, estrogen receptor, progesterone receptor, lymphovascular invasion, and HER2, to test their ability to predict ALN involvement. A support vector machine (SVM) was used as a classification model. The SVM is a machine-learning system developed using statistical learning theories to classify data points into 2 classes. Notably, SVM models have been applied in bioinformatics. RESULTS: The SVM model correctly predicted ALN metastases in 74.7% of patients using tumor biological parameters. The predictive ability of luminal A, luminal B, triple negative, and HER2 subtypes using subgroup analysis showed no difference, and this predictive performance was inferior, with only 60% accuracy. CONCLUSIONS: With an SVM model based on clinical pathologic parameters obtained in the primary tumor, it is possible to predict ALN status in order to alert the surgeon about breast cancer counseling and in decision-making for ALN management.


Assuntos
Axila/patologia , Neoplasias da Mama/patologia , Linfonodos/patologia , Metástase Linfática/diagnóstico , Feminino , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Máquina de Vetores de Suporte
13.
J Formos Med Assoc ; 111(5): 275-83, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22656398

RESUMO

BACKGROUND/PURPOSE: Umbilical cord blood is rich in primitive natural killer (NK) cells, which are activated by interleukin (IL)-12. It was previously reported that a novel IL-12 family cytokine, IL-27 comprised of EBI3 and p28, was elevated in maternal serum during normal pregnancy. Thus, we compared the immune regulatory functions of IL-27 and IL-12 on mononuclear cells derived from cord blood and adult peripheral blood. METHODS: After stimulation with IL-27, IL-12, and IL-27 combined with IL-12, the cytotoxicity against BJAB lymphoma cells by blood mononuclear cells was performed. Then immunofluorescence staining, reverse transcriptase-polymerase chain reaction and Western blotting were used to detect the effects of IL-27 and IL-12 in isolated NK cells. RESULTS: IL-27, IL-12, and IL-27 combined with IL-12 enhanced the cytotoxicity of adult peripheral blood cells and cord blood cells, but the proliferation of distinct subpopulations of cells was not evident. Similar results were also obtained with purified cord blood NK cells. Interestingly, distinct from IL-12, IL-27 could induce aggregation and morphological changes of umbilical cord blood cells. Finally, IL-27 combined with IL-12 could stimulate increased IL-27 receptor (gp130 and WSX-1) transcripts in purified cord blood NK cells. However, the activation of signal transducer and activator of transcription 3 (STAT3) in NK cells was only detected in the presence of IL-27, but not IL-12 alone. CONCLUSION: From previous results, we summarize our current understanding of the augmentation of distinct regulation of NK cells by IL-27 and IL-12.


Assuntos
Sangue Fetal/imunologia , Interleucina-12/imunologia , Interleucinas/imunologia , Células Matadoras Naturais/metabolismo , Ativação Linfocitária , Fator de Transcrição STAT3/metabolismo , Biomarcadores/metabolismo , Western Blotting , Linhagem Celular Tumoral , Testes Imunológicos de Citotoxicidade , Citotoxicidade Imunológica , Humanos , Interleucina-12/metabolismo , Interleucinas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
BMC Cell Biol ; 10: 9, 2009 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-19187526

RESUMO

BACKGROUND: Nrf1 [p45 nuclear factor-erythroid 2 (p45 NF-E2)-related factor 1], a member of the CNC-bZIP (CNC basic region leucine zipper) family, is known to be a transcriptional activator by dimerization with distinct partners, such as Maf, FosB, c-Jun, JunD, etc. The transcriptional roles of CNC-bZIP family are demonstrated to be involved in globin gene expression as well as the antioxidant response. For example, CNC-bZIP factors can regulate the expression of detoxification proteins through AREs, such as expression of human gamma-glutamylcysteine synthetases (GCS), glutathione S-transferases (GST), UDP-glucuronosyl transferase (UDP-GT), NADP (H) quinone oxidoreductase (NQOs), etc. To further explore other factor(s) in cells related to the function of Nrf1, we performed a yeast two-hybrid screening assay to identify any Nrf1-interacting proteins. In this study, we isolated a cDNA encoding residues 126-475 of MCRS2 from the HeLa cell cDNA library. Some functions of MCRS1 and its splice variant-MSP58 and MCRS2 have been previously identified, such as transforming, nucleolar sequestration, ribosomal gene regulation, telomerase inhibition activities, etc. Here, we demonstrated MCRS2 can function as a repressor on the Nrf1-mediated transactivation using both in vitro and in vivo systems. RESULTS: To find other proteins interacting with the CNC bZIP domain of Nrf1, the CNC-bZIP region of Nrf1 was used as a bait in a yeast two-hybrid screening assay. MCRS2, a splicing variant of p78/MCRS1, was isolated as the Nrf1-interacting partner from the screenings. The interaction between Nrf1 and MCRS2 was confirmed in vitro by GST pull-down assays and in vivo by co-immunoprecipitation. Further, the Nrf1-MCRS2 interaction domains were mapped to the residues 354-447 of Nrf1 as well as the residues 314-475 of MCRS2 respectively, by yeast two-hybrid and GST pull-down assays. By immunofluorescence, MCRS2-FLAG was shown to colocalize with HA-Nrf1 in the nucleus and didn't result in the redistribution of Nrf1. This suggested the existence of Nrf1-MCRS2 complex in vivo. To further confirm the biological function, a reporter driven by CNC-bZIP protein binding sites was also shown to be repressed by MCRS2 in a transient transfection assay. An artificial reporter gene activated by LexA-Nrf1 was also specifically repressed by MCRS2. CONCLUSION: From the results, we showed MCRS2, a new Nrf1-interacting protein, has a repression effect on Nrf1-mediated transcriptional activation. This was the first ever identified repressor protein related to Nrf1 transactivation.


Assuntos
Proteínas Nucleares/metabolismo , Fator 1 Nuclear Respiratório/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Repressoras/metabolismo , Transativadores/metabolismo , Células Cultivadas , DNA Complementar/genética , DNA Complementar/metabolismo , Imunofluorescência , Genes Reporter , Células HeLa , Humanos , Proteínas Nucleares/genética , Fator 1 Nuclear Respiratório/genética , Proteínas de Ligação a RNA/genética , Proteínas Repressoras/genética , Transativadores/genética , Ativação Transcricional , Transfecção
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