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1.
Hum Brain Mapp ; 45(1): e26531, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37986643

RESUMO

Magnetic resonance spectroscopy (MRS) is the primary method that can measure the levels of metabolites in the brain in vivo. To achieve its potential in clinical usage, the reliability of the measurement requires further articulation. Although there are many studies that investigate the reliability of gamma-aminobutyric acid (GABA), comparatively few studies have investigated the reliability of other brain metabolites, such as glutamate (Glu), N-acetyl-aspartate (NAA), creatine (Cr), phosphocreatine (PCr), or myo-inositol (mI), which all play a significant role in brain development and functions. In addition, previous studies which predominately used only two measurements (two data points) failed to provide the details of the time effect (e.g., time-of-day) on MRS measurement within subjects. Therefore, in this study, MRS data located in the anterior cingulate cortex (ACC) were repeatedly recorded across 1 year leading to at least 25 sessions for each subject with the aim of exploring the variability of other metabolites by using the index coefficient of variability (CV); the smaller the CV, the more reliable the measurements. We found that the metabolites of NAA, tNAA, and tCr showed the smallest CVs (between 1.43% and 4.90%), and the metabolites of Glu, Glx, mI, and tCho showed modest CVs (between 4.26% and 7.89%). Furthermore, we found that the concentration reference of the ratio to water results in smaller CVs compared to the ratio to tCr. In addition, we did not find any time-of-day effect on the MRS measurements. Collectively, the results of this study indicate that the MRS measurement is reasonably reliable in quantifying the levels of metabolites.


Assuntos
Encéfalo , Giro do Cíngulo , Humanos , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/metabolismo , Reprodutibilidade dos Testes , Espectroscopia de Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Ácido Glutâmico/metabolismo , Creatina/metabolismo , Inositol/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Ácido Aspártico/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Colina/metabolismo
2.
Neural Plast ; 2020: 8882207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082780

RESUMO

The current study is aimed at establishing links between brain network examination and neural plasticity studies measured by optical neuroimaging. Sixteen healthy subjects were recruited from the University of Macau to test the Granger Prediction Estimation (GPE) method to investigate brain network connectivity during figurative language comprehension. The method is aimed at mapping significant causal relationships across language brain networks, captured by functional near-infrared spectroscopy measurements (fNIRS): (i) definition of regions of interest (ROIs) based on significant channels extracted from spatial activation maps; (ii) inspection of significant causal relationships in temporal resolution, exploring the experimental task agreement; and (iii) early identification of stronger causal relationships that guide neuromodulation intervention, targeting impaired connectivity pathways. Our results propose top-down mechanisms responsible for perceptive-attention engagement in the left anterior frontal cortex and bottom-up mechanism in the right hemispheres during the semantic integration of figurative language. Moreover, the interhemispheric directional flow suggests a right hemisphere engagement in decoding unfamiliar literal sentences and fine-grained integration guided by the left hemisphere to reduce ambiguity in meaningless words. Finally, bottom-up mechanisms seem activated by logographic-semantic processing in literal meanings and memory storage centres in meaningless comprehension. To sum up, our main findings reveal that the Granger Prediction Estimation (GPE) integrated strategy proposes an effective link between assessment and intervention, capable of enhancing the efficiency of the treatment in language disorders and reducing the neuromodulation side effects.


Assuntos
Encéfalo/fisiologia , Compreensão/fisiologia , Idioma , Adulto , Feminino , Humanos , Masculino , Vias Neurais/fisiologia , Neuroimagem/métodos , Imagem Óptica/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto Jovem
3.
Biomed Chromatogr ; 32(6): e4197, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29359465

RESUMO

rCCK8PE38 is a novel immunotoxin that targets choleystokinin B receptor, which is over-expressed in some tumor tissues. Although we constructed a prokaryotic expression vector to express rCCK8PE38 in our laboratory, thorough purification was necessary to quantitatively assess its anti-tumor effect. In this study, we established a purification protocol to obtain rCCK8PE38 with high purity from E. coli. Three different types of chromatography, hydrophobic chromatography, ion exchange chromatography and size exclusion chromatography, were used in combination. The purification technological parameters of each chromatography type were optimized. The whole process of purification was arranged to minimize the purification steps and achieve purity and bioactivity. Finally, through this optimized scheme, we obtained a recombinant protein with a purity of >95%; then, the protein was stored at -80°C after lyophilization. The purified protein was used in a tumor inhibition experiment and was effective in killing tumor cells that over-expressed choleystokinin B receptor. The results of this study may provide some valuable information about protein purification and lay the foundation for further clinical experiments with rCCK8PE38.


Assuntos
Antineoplásicos/isolamento & purificação , Imunotoxinas/isolamento & purificação , Proteínas Recombinantes/isolamento & purificação , Sulfato de Amônio/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Precipitação Química , Cromatografia Líquida , Escherichia coli/genética , Humanos , Imunotoxinas/química , Imunotoxinas/genética , Imunotoxinas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
4.
Carcinogenesis ; 38(12): 1241-1248, 2017 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-29029037

RESUMO

Recent studies indicate that abnormal levels of low-density lipoprotein (LDL), which is an important component of dyslipidaemia, are associated with alterations to cancer risk, including that of renal cell carcinoma (RCC). Single nucleotide polymorphisms at microRNA-binding sites contribute to cancer susceptibility and progression by affecting the messenger RNA (mRNA) function of target genes. In this case-control study, we examined the frequency of six potentially functional single nucleotide polymorphisms in the LDL receptor gene (LDLR) in 1004 clear cell RCC (ccRCC) patients and 1065 cancer-free subjects. Logistic regression analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs). The association between genetic variants and levels of LDLR mRNA and protein was also evaluated. Compared with the CC genotype, multivariate logistic regression analysis showed that the LDLR rs2738464 variant GG genotype was associated with a significantly decreased ccRCC risk (P = 0.002, OR: 0.605, 95% CI: 0.439-0.833). Further functional experiments showed that the rs2738464 variant G allele affected miR-330 regulation of the LDLR 3'-untranslated region (UTR), increasing LDLR mRNA levels in patient kidney tissues. These findings suggest that LDLR rs2738464 may affect the affinity of miR-330 binding to the LDLR 3'-UTR, thus regulating LDLR expression and contributing to ccRCC risk.


Assuntos
Carcinoma de Células Renais/genética , Predisposição Genética para Doença/genética , Neoplasias Renais/genética , Receptores de LDL/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genótipo , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único
5.
Pharmacogenet Genomics ; 25(11): 521-30, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26287940

RESUMO

BACKGROUND AND AIM: Genetic variants in the mammalian target of rapamycin (mTOR) gene have become an interesting topic for the study of genetic susceptibility to cancer, but their associations with the risk of gastric cancer have not been fully investigated. MATERIALS AND METHODS: In a hospital-based case-control study of 1002 gastric cancer patients and 1003 cancer-free controls, we genotyped four potentially functional single nucleotide polymorphisms (SNPs) (rs1034528G>C, rs17036508T>C, rs3806317A>G, and rs2295080T>G) of mTOR and assessed their associations with the risk of gastric cancer using univariate and multivariate logistic regression analyses. We also used the multifactorial dimension reduction analysis to explore possible interactions and the false-positive report probabilities to assess significant findings. RESULTS: We found that rs1034528 CG/CC and rs3806317 GA/GG variant genotypes were associated with an increased risk of gastric cancer under a dominant model (adjusted odds ratio=1.27 and 1.22, respectively). In the combined analysis of all four SNPs under investigation, patients with 3-4 risk genotypes of mTOR had a significantly increased risk of gastric cancer (adjusted odds ratio=1.46, 95% confidence interval=1.19-1.79) compared with those with 0-2 risk genotypes. Stratified analysis indicated that this risk was more pronounced in subgroups of men, never-smokers, never-drinkers, and clinical stages III+IV. The multifactorial dimension reduction analysis suggested some evidence of interactions between the combined genotypes and other risk factors for gastric cancer. CONCLUSION: These findings suggest that potentially functional SNPs of mTOR may individually or collectively contribute to the risk of gastric cancer. Larger studies with diverse ethnic populations are warranted to validate our findings.


Assuntos
Adenocarcinoma/genética , Povo Asiático/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Serina-Treonina Quinases TOR/genética , Estudos de Casos e Controles , Linhagem Celular , China , Feminino , Expressão Gênica , Genes Dominantes , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , RNA Mensageiro/genética , Fatores de Risco
6.
Tumour Biol ; 36(9): 6919-27, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25854172

RESUMO

The kinesin-like factor 1 B (KIF1B) gene plays an important role in the process of apoptosis and the transformation and progression of malignant cells. Genetic variations in KIF1B may contribute to risk of epithelial ovarian cancer (EOC). In this study of 1,324 EOC patients and 1,386 cancer-free female controls, we investigated associations between two potentially functional single nucleotide polymorphisms in KIF1B and EOC risk by the conditional logistic regression analysis. General linear regression model was used to evaluate the correlation between the number of variant alleles and KIF1B mRNA expression levels. We found that the rs17401966 variant AG/GG genotypes were significantly associated with a decreased risk of EOC (adjusted odds ratio (OR) = 0.81, 95 % confidence interval (CI) = 0.68-0.97), compared with the AA genotype, but no associations were observed for rs1002076. Women who carried both rs17401966 AG/GG and rs1002076 AG/AA genotypes of KIF1B had a 0.82-fold decreased risk (adjusted 95 % CI = 0.69-0.97), compared with others. Additionally, there was no evidence of possible interactions between about-mentioned co-variants. Further genotype-phenotype correlation analysis indicated that the number of rs17401966 variant G allele was significantly associated with KIF1B mRNA expression levels (P for GLM = 0.003 and 0.001 in all and Chinese subjects, respectively), with GG carriers having the lowest level of KIF1B mRNA expression. Taken together, the rs17401966 polymorphism likely regulates KIF1B mRNA expression and thus may be associated with EOC risk in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Cinesinas/genética , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Adulto , Idoso , Alelos , Povo Asiático , Carcinoma Epitelial do Ovário , Feminino , Regulação Neoplásica da Expressão Gênica , Genótipo , Humanos , Cinesinas/biossíntese , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/biossíntese , Fatores de Risco
7.
Carcinogenesis ; 34(4): 770-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23299407

RESUMO

Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is an anti apoptotic and pro-oncogenic signaling molecule involved in the process of immunity, carcinogenesis and tumor progression. Single nucleotide polymorphisms (SNPs) at microRNA-binding sites may change messenger RNA target gene function, thus leading to cancer susceptibility and tumor progression. In this study of 1584 cervical cancer cases and 1394 cancer-free female controls, we investigated associations between three potentially functional SNPs in TNFAIP8 family genes and cervical cancer risk as well as platinum resistance and clinical outcomes in Eastern Chinese women. We found that the TNFAIP8-rs11064 variant GG genotype was associated with an increased risk of cervical cancer compared with AA/AG genotypes (adjusted odds ratio = 2.16, 95% confidence interval = 1.16-4.03, P = 0.015). Further in vitro and ex vivo functional experiments demonstrated that the TNFAIP8-rs11064 variant G allele weakened the binding affinity of miR-22 to the TNFAIP8 3'-untranslated region (UTR) in four cancer cell lines, resulting in increased production of the TNFAIP8 protein in the patients' cervical tissues. In the survival subset, the high TNFAIP8 protein expression was significantly associated with both resistance to cisplatin and nedaplatin, recurrence and death from cervical cancer. Taken together, in the absence of information on human papillomavirus (HPV) infection, the TNFAIP8-rs11064 SNP may function by affecting the affinity of miR-22 binding to the 3'-UTR of TNFAIP8 and regulating TNFAIP8 expression, thus contributing to cervical cancer risk. Additionally, the increased TNFAIP8 protein expression may predict platinum resistance and clinical outcomes in cervical cancer patients. Larger, prospective studies with detailed HPV infection data are warranted to validate our findings.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , MicroRNAs/metabolismo , Neoplasias do Colo do Útero/genética , Regiões 3' não Traduzidas , Proteínas Reguladoras de Apoptose/biossíntese , Estudos de Casos e Controles , Linhagem Celular Tumoral , China , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/uso terapêutico , Paclitaxel/uso terapêutico , Polimorfismo de Nucleotídeo Único , Risco , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/mortalidade
8.
Int J Cancer ; 133(8): 1765-75, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23400628

RESUMO

XPC polymorphisms may alter DNA repair capacity, thus leading to genetic instability and carcinogenesis. Numerous studies have investigated the associations of XPC Lys939Gln (rs2228001) and Ala499Val (rs2228000) polymorphisms with cancer susceptibility; however, the findings are inconclusive. We searched literature from MEDLINE and EMBASE for eligible publications that assessed the associations between these two polymorphisms and cancer risk. We also assessed genotype-mRNA expression correlation data from HapMap for rs2228001 and rs2228000 in normal cell lines derived from 270 subjects with different ethnicities. The final analysis included 62 published studies of 25,708 cases and 30,432 controls for the Lys939Gln and 34 studies with 14,877 cases and 17,888 controls for the Ala499Val. Overall, Lys939Gln was significantly associated with an increased overall cancer risk (Gln/Gln vs. Lys/Lys: OR = 1.16, 95% CI = 1.07 - 1.25, p < 0.001; recessive model: OR = 1.14, 95% CI = 1.06 - 1.22, p < 0.001; dominant model: OR = 1.06, 95% CI = 1.01 - 1.11, p = 0.015 and Gln vs. Lys: OR = 1.07, 95% CI = 1.03 - 1.10, p < 0.001) and further stratifications showed an increased risk for bladder, lung and colorectal cancer, Asian populations and population-based studies. Likewise, Ala499Val was also significantly associated with an increased overall cancer risk (Val/Val vs. Ala/Ala: OR = 1.21, 95% CI = 1.07 - 1.36, p = 0.003 and recessive model: OR = 1.20, 95% CI = 1.08 - 1.34, p = 0.001) and further stratification showed an increased risk for breast and bladder cancer, particularly in Asian populations. Interestingly, significantly correlation between XPC genotypes and mRNA expression was found only for Asian populations as well. Despite some limitations, this meta-analysis established some solid statistical evidence for an association between XPC polymorphisms and cancer risk, which warrants further validation in single large studies.


Assuntos
Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Transformação Celular Neoplásica/genética , Feminino , Estudos de Associação Genética , Humanos , Masculino , Fatores de Risco
9.
Hum Genet ; 132(3): 301-12, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23180271

RESUMO

Interleukin 6 (IL6) encodes a cytokine protein, which functions in inflammation, maintains immune homeostasis and plays important roles in cervical carcinogenesis. Single nucleotide polymorphisms (SNPs) in IL6 that cause variations in host immune response may contribute to cervical cancer risk. In this two-stage case-control study with a total of 1,584 cervical cancer cases and 1,768 cancer-free female controls, we investigated associations between two IL6 SNPs and cervical cancer risk in Eastern Chinese women. In both Study 1 and Study 2, we found a significant association of the IL6-rs2069837 SNP with an increased risk of cervical cancer as well as in their combined data (OR 1.27 and 1.19, 95% CI 1.08-1.49 and 1.04-1.36, P = 0.004 and 0.014 for dominant and additive genetic models, respectively). Furthermore, rs2069837 variant AG/GG carriers showed significantly higher levels of IL6 protein than did rs2069837 AA carriers in the target tissues. Using multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses, we observed some evidence of interactions of the IL6 rs2069837 SNP with age at primiparity and menopausal status in cervical cancer risk. We concluded that the IL6-rs2069837 SNP may be a marker for susceptibility to cervical cancer in Eastern Chinese women by a possible mechanism of altering the IL6 protein expression. Although lacked information on human papillomavirus (HPV) infection, our study also suggested possible interactions between IL6 genotypes and age at primiparity or menopausal status in cervical carcinogenesis. However, larger, independent studies with detailed HPV infection data are warranted to validate our findings.


Assuntos
Povo Asiático/genética , Interleucina-6/genética , Interleucina-6/imunologia , Polimorfismo de Nucleotídeo Único , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/imunologia , Adulto , Fatores Etários , Idoso , Povo Asiático/estatística & dados numéricos , Carcinoma/genética , Carcinoma/imunologia , Estudos de Casos e Controles , China/epidemiologia , Simulação por Computador , Fatores de Confusão Epidemiológicos , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Menopausa , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paridade , Fatores de Risco , Neoplasias do Colo do Útero/patologia
10.
Mol Carcinog ; 52 Suppl 1: E70-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23423739

RESUMO

Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions, and genetic variations in this complex may affect cancer risk. In this study, we examined the associations between eight potential functional single nucleotide polymorphisms in the mTORC1 genes (rs2536T>C and rs1883965G>A for mTOR, rs3160T>C, and rs26865A>G for mLST8, rs3751934C>A, rs1062935T>C, rs3751932T>C, and rs12602885G>A for Raptor, not included in published gastric cancer genome-wide association studies) and gastric cancer risk in 1125 gastric cancer cases and 1196 cancer-free controls. We performed conditional logistic regression and multifactor dimensionality reduction (MDR) analyses to assess their associations with gastric cancer risk. We also used false-positive report probabilities (FPRP) for assessing significant findings. We found that only the rs1883965A variant genotypes were associated with an increased risk of gastric cancer (AG vs. GG: adjusted odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.00-1.59; AA vs. GG: adjusted OR = 1.85, 95% CI = 0.67-5.16 and dominant model: adjusted OR = 1.28, 95% CI = 1.03-1.61). Patients with ≥1 risk genotypes of mTOR had significant increased risk (adjusted OR = 1.25, 95% CI = 1.04-1.49), compared with those having zero risk genotypes. In the stratified analysis, the risk effect of the rs1883965 AG/AA genotypes was evident in subgroups of ever-smokers, non-gastric cardia adenocarcinoma and clinical stage I + II, which were noteworthy findings as evaluated by FPRP. The MDR analysis identified smoking status and rs1883965 as the strongest two-factors for gastric cancer risk. These data support the hypothesis that functional polymorphisms of mTOR may contribute to gastric cancer risk. Clearly, our results require validation in larger studies with different ethnic populations.


Assuntos
Adenocarcinoma/etiologia , Povo Asiático/genética , Biomarcadores Tumorais/genética , Predisposição Genética para Doença , Complexos Multiproteicos/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias Gástricas/etiologia , Serina-Treonina Quinases TOR/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Proteína Regulatória Associada a mTOR , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Homólogo LST8 da Proteína Associada a mTOR
11.
BMC Cancer ; 13: 19, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23320911

RESUMO

BACKGROUND: MicroRNA (miRNA)-related single nucleotide polymorphisms (SNPs) may compromise miRNA binding affinity and modify mRNA expression levels of the target genes, thus leading to cancer susceptibility. However, few studies have investigated roles of miRNA-related SNPs in the etiology of cervical carcinoma. METHODS: In this case-control study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between two miR-218-related SNPs involved in the LAMB3-miR-218 pathway and the risk of cervical carcinoma in Eastern Chinese women. RESULTS: We found that the pri-miR-218 rs11134527 variant GG genotype was significantly associated with a decreased risk of cervical carcinoma compared with AA/AG genotypes (adjusted OR=0.77, 95% CI=0.63-0.95, P=0.015). However, this association was not observed for the miR-218 binding site SNP (rs2566) on LAMB3. Using the multifactor dimensionality reduction analysis, we observed some evidence of interactions of these two SNPs with other risk factors, especially age at primiparity and menopausal status, in the risk of cervical carcinoma. CONCLUSIONS: The pri-miR-218 rs11134527 SNP was significantly associated with the risk of cervical carcinoma in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.


Assuntos
Povo Asiático/genética , Carcinoma/genética , Predisposição Genética para Doença/genética , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Adulto , Estudos de Casos e Controles , China , Feminino , Genótipo , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco
12.
Brain Behav ; 13(10): e3219, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37587620

RESUMO

INTRODUCTION: Brain age, the estimation of a person's age from magnetic resonance imaging (MRI) parameters, has been used as a general indicator of health. The marker requires however further validation for application in clinical contexts. Here, we show how brain age predictions perform for the same individual at various time points and validate our findings with age-matched healthy controls. METHODS: We used densely sampled T1-weighted MRI data from four individuals (from two densely sampled datasets) to observe how brain age corresponds to age and is influenced by acquisition and quality parameters. For validation, we used two cross-sectional datasets. Brain age was predicted by a pretrained deep learning model. RESULTS: We found small within-subject correlations between age and brain age. We also found evidence for the influence of field strength on brain age which replicated in the cross-sectional validation data and inconclusive effects of scan quality. CONCLUSION: The absence of maturation effects for the age range in the presented sample, brain age model bias (including training age distribution and field strength), and model error are potential reasons for small relationships between age and brain age in densely sampled longitudinal data. Clinical applications of brain age models should consider of the possibility of apparent biases caused by variation in the data acquisition process.

13.
Eur J Med Chem ; 252: 115282, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36989812

RESUMO

The function of the p53 protein is impaired by the overexpression of its negative regulator murine double minute 2 protein (MDM2) and homologous protein MDMX. Disruption of the p53-MDM2/MDMX interaction to restore the transcriptional function of p53 is considered a promising strategy for cancer therapy. To design dual MDM2/MDMX inhibitors, the binding modes of MDM2 or MDMX with their inhibitors are elucidated. Several hot-spot residues of MDM2 or MDMX are identified by molecular dynamics simulations, alanine scanning and MM-GBSA calculations. Then, focusing on the interaction with hot-spot residues, two series of derivatives bearing 1,3-diketone and α-aminoketone scaffolds are designed and synthesized. Among these compounds, C16 is identified as the most potent compound with low micromolar binding affinities with MDM2 and MDMX. C16 also displays moderate antiproliferative activities against MDM2-overexpressing and MDMX-overexpressing cells, with IC50 values of 0.68 µM in HCT116 cells and 0.54 µM in SH-SY5Y cells. Furthermore, C16 inhibits cell migration and invasion, reactivates the function of p53, arrests the cell cycle and induces cellular apoptosis in HCT116 and SH-SY5Y cells. Collectively, C16 can be developed as a dual MDM2 and MDMX inhibitor for cancer therapy.


Assuntos
Antineoplásicos , Neuroblastoma , Camundongos , Animais , Humanos , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Proteínas de Ciclo Celular/metabolismo , Antidepressivos , Ligação Proteica
14.
Hum Genet ; 131(7): 1235-44, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22371296

RESUMO

DNA repair genes play an important role in maintaining stability and integrity of genomic DNA. Polymorphisms in nucleotide excision repair genes may cause variations in DNA repair capacity phenotype and thus contribute to cancer risk. In this case-control study of 1,125 gastric cancer cases and 1,196 cancer-free controls, we investigated the association between three functional single nucleotide polymorphisms (SNPs, rs2296147T > C, rs2094258C > T and rs873601G > A) in the xeroderma pigmentosum group G (XPG) gene and gastric cancer risk. We used the Taqman assays to genotype these three SNPs and logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that only the rs873601A variant genotypes were associated with a significant higher risk for gastric adenocarcinoma (adjusted OR = 1.30, 95% CI = 1.03-1.64 for AA vs. GG and adjusted OR = 1.23, 95% CI = 1.01-1.49 for AA vs. GG/AG). Stratification analysis indicated that this risk was more pronounced in subgroups of older age (>59 years), males, ever-smokers, and patients with NGCA. All these were not found for the other two SNPs (rs2296147T > C and rs2094258C > T). We then performed expression analysis using gastric cancer adjacent normal tissues from 141 patients and found that the A variant allele was associated with non-significantly reduced expression of XPG mRNA (P(trend) = 0.107). Further analysis using mRNA expression data from the HapMap suggested that the A allele was associated with significantly reduced expression of XPG mRNA in normal cell lines for 45 Chinese (P(trend) = 0.003) as well as for 261 subjects with different ethnicities (P(trend) = 0.001). These support the hypothesis that functional XPG variants may contribute to the risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.


Assuntos
Povo Asiático/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Predisposição Genética para Doença , Proteínas Nucleares/genética , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/genética , Fatores de Transcrição/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Linhagem Celular , China , Reparo do DNA , Feminino , Genótipo , Projeto HapMap , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adulto Jovem
15.
Front Public Health ; 10: 883566, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35419339

RESUMO

Population aging is getting enlarged in the upcoming decades. Meanwhile, old-aged longevity and dependency are getting large due to improvement in life expectancy. In literature, it is claimed that old-aged dependency affects the wellbeing of society. Thus, the study intends to explore the impact of population aging on human wellbeing. The study adopts the Autoregressive Distributed Lag (ARDL) approach for empirical analysis by using time-series series data from 1990 to 2020. The study findings reveal that an increase in population aging reports a significant and decreasing impact on human wellbeing. However, an increase in health expenditure reports a significant and increasing impact on human wellbeing. Thus, China must pay attention to population aging to improve human health.


Assuntos
Envelhecimento , Expectativa de Vida , Idoso , China/epidemiologia , Gastos em Saúde , Humanos , Pessoa de Meia-Idade , Fatores de Tempo
16.
Front Hum Neurosci ; 16: 1021503, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325431

RESUMO

Our understanding of the cognitive functions of the human brain has tremendously benefited from the population functional Magnetic Resonance Imaging (fMRI) studies in the last three decades. The reliability and replicability of the fMRI results, however, have been recently questioned, which has been named the replication crisis. Sufficient statistical power is fundamental to alleviate the crisis, by either "going big," leveraging big datasets, or by "going small," densely scanning several participants. Here we reported a "going small" project implemented in our department, the Bergen breakfast scanning club (BBSC) project, in which three participants were intensively scanned across a year. It is expected this kind of new data collection method can provide novel insights into the variability of brain networks, facilitate research designs and inference, and ultimately lead to the improvement of the reliability of the fMRI results.

17.
Cogn Neurodyn ; 16(2): 471-481, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35401873

RESUMO

In previous word reading studies, lexicality has been used as a variable to examine the impacts of word form and meaning information on the many stages of word recognition process. Yet the neural dynamics associated with lexicality effect of various information processing for Chinese visual word recognition has not been well elucidated. In this study, Chinese native speakers were instructed to read Chinese disyllabic compound words, morphological legal (pseudo-words) and illegal non-words with their brain potentials recorded. Event-related potentials (ERP) results showed that N200 was related to Chinese orthographic processing, where three lexical conditions elicited comparable patterns. A semantic discrimination was found for N400 between pseudo-words/non-words and real words, which is in favor of the lexical view of the N400 effect. Further, a later ERP component P600 exhibited the difference between the non-words and pseudo-words, reflecting a re-analysis of word meaning or grammatical operation on Chinese morphological legality. Therefore, we argue that Chinese morphological information might have an independent representation (the P600 effect) in mental lexicon.

18.
Cortex ; 154: 184-196, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35780754

RESUMO

Although the role of morphology in alphabetic language processing has been extensively studied, it is still unclear how morphology is enabled and constrained in morpho-syllabic languages like Chinese. This study aims to inspect the time courses and patterns of brain activation associated with Chinese morphological constraint encoding. Chinese native speakers were recruited to perform visual lexical decisions on real Chinese compound words, pseudowords, and nonwords, whilst behavioral, electroencephalographic, and functional near infrared spectroscopy data were simultaneously recorded. For the first time, both morphological and semantic effects were examined to reveal the corresponding spatio-temporal brain activation patterns based on multimodal data. Brain activation differences between pseudowords and real words indexed morphological sensitivity, whereas differences between real words or pseudowords and nonwords characterized semantic effects. Electrophysiological data showed that semantic processing occurred earlier (N400, 300-450 msec) than morphological processing (450-570 msec), while brain activation patterns revealed a differentiation between morphological parsing (specified in the left inferior frontal gyrus) and semantic analysis (in a broader fronto-temporal network). These findings offer new evidence that morphological constraints are encoded at a late stage of compound word processing in Chinese and suggest that the left prefrontal cortex plays an essential role in this process.


Assuntos
Eletroencefalografia , Leitura , Encéfalo , Mapeamento Encefálico , China , Potenciais Evocados , Feminino , Humanos , Idioma , Imageamento por Ressonância Magnética , Masculino , Semântica
19.
Cytokine ; 56(3): 695-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21978540

RESUMO

Published data on the association between microRNA-146a (miR-146a) G/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 23 studies including 10,585 cases and 12,183 controls were used in the meta-analysis. Overall, no significant associations were found between miR-146a G/C polymorphism and cancer risk when all studies pooled into the meta-analysis (GC vs. CC: OR=1.08, 95% CI=0.94-1.24; GG vs. CC: OR=1.13, 95% CI=0.93-1.37; dominant model: OR=1.09, 95% CI=0.94-1.26). In the subgroup analysis by ethnicity, still no significant associations were found. In the subgroup analysis by cancer type, statistically significantly increased risks were found for papillary thyroid carcinoma (GC vs. CC: OR=3.44, 95% CI=1.86-6.34; GG vs. CC: OR=2.20, 95% CI=1.22-3.99; dominant model: OR=2.68, 95% CI=1.48-4.83). In the subgroup analysis by population-based controls or hospital-based controls, no statistically significantly increased risks were found. Despite some limitations, this meta-analysis suggests that the miR-146a G allele is a low-penetrant risk factor for papillary thyroid carcinoma development.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , MicroRNAs/genética , Neoplasias/genética , Polimorfismo de Nucleotídeo Único/genética , Humanos , Razão de Chances , Viés de Publicação
20.
Neuroscience ; 459: 50-58, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33556458

RESUMO

The neural cognitive mechanism in processing static facial expressions (FEs) has been well documented, whereas the one underlying perceiving dynamic faces remains unclear. In this study, Fourier transformation and time-frequency analysis of Electroencephalography (EEG) data were carried out to detect the brain activation underlying dynamic or static FEs while twenty-one participants were viewing dynamic or static faces flicking at 10 Hz. In particular, steady-state visual evoked potentials (SSVEPs) were quantified through spectral power analysis of EEG recordings. Besides, Granger causality (GC) analysis (GCA) was also performed to capture the causal cortical network dynamics during dynamic or static FEs of emotion. It was discovered that the dynamic (from neural to happy (N2H) or vice versa (H2N)) FEs elicited larger SSVEPs than the static ones. Additionally, GCA demonstrated that the H2N case, in which happy FEs were being gradually changed into neutral ones, exhibited larger GC measure during the late processing stage than that from the early stage. Consequently, enhanced SSVEPs and effective brain connectivity for dynamic FEs illustrated that participants might need consume more attentional resources to process the dynamic faces, particularly for the change from happy to neutral faces. The new neural index might facilitate us to better understand the cognitive processing of dynamic and static FEs.


Assuntos
Potenciais Evocados Visuais , Expressão Facial , Eletroencefalografia , Emoções , Estimulação Luminosa
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