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1.
Dev Comp Immunol ; 119: 104020, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33476669

RESUMO

Mitogen-activated protein kinase 4 (MKK4), a member of the MAP kinase family, play important roles in response to many environmental and cellular stresses in mammals. In this study, three MKK4 subtypes, EcMKK4-1, EcMKK4-2 and EcMKK4-3, were obtained from grouper Epinephelus coioides. The open reading frame (ORF) of EcMKK4s are obtained and the EcMKK4s proteins contain highly conserved domains: a S_TKc domain, a canonical diphosphorylation group and two conserved MKKK ATP binding motifs, Asp-Phe-Gly (DFG) and Ala-Pro-Glu (APE). EcMKK4s could be found both in the cytoplasmic and nuclear. The EcMKK4s mRNA were detected in all E. coioides tissues examined with the different expression levels, and the expression were up-regulated during SGIV (Singapore grouper iridescent virus) or Vibrio alginolyticus infection. EcMKK4 could significantly reduce the activation of AP-1 reporter gene. The results suggested that EcMKK4s might play important roles in pathogen-caused inflammation.

2.
Quant Imaging Med Surg ; 10(10): 1973-1983, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33014729

RESUMO

Background: Sexual orientation has been suggested to affect executive function, of which the neurobiological basis is still largely unknown. In this study, we explored the interrelationship between neuropsychological characteristics in homosexual and heterosexual men and their anatomical connectome by graph theoretical analysis. Methods: Fifty-three homosexual and 47 heterosexual males underwent diffusion tensor magnetic resonance imaging (MRI) and neuropsychological assessments. Whole-brain anatomical networks were constructed using white matter tractography, performed on the diffusion tensor imaging data. Neuropsychological tests included the Wisconsin Card Sorting Test (WCST), the Continuous Performance Test (CPT) and the Trail-Making Test (TMT). Results: The cognitive performance of homosexual men was significantly poorer than their heterosexual counterparts in terms of WCST total correct responses. Anatomical connectome analysis revealed a lower (P=0.001) anatomical connectivity between left PoCG and left SMG (P=0.003) in homosexual men as compared to heterosexual men. Linear regression analyses showed that the WCST total correct responses score was significantly linked with sexual orientation (P=0.001). The anatomical connectivity strength between left PoCG and left SMG was also shown to be significantly correlated with sexual orientation (P=0.039) and education (P=0.047). Conclusions: Our study demonstrated the differences in the performance of WCST and anatomical connectome of large-scale brain networks between homosexual and heterosexual men, extending our understanding of the brain's circuitry and the characteristics of executive function in men of different sexual orientation.

4.
Medicine (Baltimore) ; 96(25): e7228, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28640119

RESUMO

The present study aimed to explore the possible associations between the dorsolateral prefrontal cortex (DLPFC) metabolites and the cognitive function in first-episode schizophrenia (FES).This study included 58 patients with FES (29 males and 29 females; mean age, 22.66 ±â€Š7.64 years) recruited from the First Affiliated Hospital, College of Medicine, Zhejiang University, and 43 locally recruited healthy controls (16 males and 27 females; mean age, 23.07 ±â€Š7.49 years). The single-voxel proton magnetic resonance spectroscopy was used to measure the levels of N-acetylaspartate (NAA); complex of glutamate, glutamine, and γ-aminobutyric acid (Glx); choline-containing compounds; and myo-inositol in the DLPFC. The ratios of metabolites to creatine (Cr) were calculated. The cognitive function was assessed by Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Correlation analysis was used to assess the relationships between the DLPFC metabolites and the cognitive function.Compared with the healthy controls, the patients with FES showed significantly reduced scores in each part of the MCCB, significantly reduced NAA/Cr, and significantly increased Glx/Cr in the left DLPFC. Poor performance in verbal learning and visual learning was correlated to the reduced NAA/Cr ratio in the left DLPFC.These findings suggest that a lower NAA/Cr ratio in the left DLPFC is associated with the cognitive deficits in patients with FES, and may be an early biochemical marker for the cognitive impairment in schizophrenia.


Assuntos
Disfunção Cognitiva/metabolismo , Córtex Pré-Frontal/metabolismo , Esquizofrenia/metabolismo , Psicologia do Esquizofrênico , Biomarcadores/metabolismo , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Córtex Pré-Frontal/diagnóstico por imagem , Espectroscopia de Prótons por Ressonância Magnética , Esquizofrenia/diagnóstico por imagem , Adulto Jovem
5.
Sci Rep ; 7: 40530, 2017 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-28074937

RESUMO

This study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD). A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited. The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated. The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected. In results, blood proportion of cytotoxic T cells significantly decreased in BD patients than in either MD patients or HCs. The plasma level of IL-6 increased in patients with BD and MD. The expression of TIM-3 on cytotoxic T cells significantly increased, whereas the expression of PD-L2 on monocytes significantly decreased in patients with BD than in HCs. These findings extended our knowledge of the immune dysfunction in patients with affective disorders.


Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/imunologia , Citocinas/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Antígeno B7-H1/metabolismo , Estudos de Casos e Controles , Demografia , Feminino , Humanos , Células Matadoras Naturais/imunologia , Ativação Linfocitária/imunologia , Masculino
6.
Sci Rep ; 6: 30537, 2016 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-27460201

RESUMO

The clinical and cognitive responses to repetitive transcranial magnetic stimulation (rTMS) in bipolar II depressed patients remain unclear. In this study, thirty-eight bipolar II depressed patients were randomly assigned into three groups: (i) left high-frequency (n = 12), (ii) right low-frequency (n = 13), (iii) sham stimulation (n = 13), and underwent four-week rTMS with quetiapine concomitantly. Clinical efficacy was evaluated at baseline and weekly intervals using the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive functioning was assessed before and after the study with the Wisconsin Card Sorting Test (WCST), Stroop Word-Color Interference Test (Stroop), and Trail Making Test (TMT). Thirty-five patients were included in the final analysis. Overall, the mean scores of both the HDRS-17 and the MADRS significantly decreased over the 4-week trial, which did not differ among the three groups. Exploratory analyses revealed no differences in factor scores of HDRS-17s, or in response or remission rates. Scores of WCST, Stroop, or TMT did not differ across the three groups. These findings indicated active rTMS combined with quetiapine was not superior to quetiapine monotherapy in improving depressive symptoms or cognitive performance in patients with bipolar II depression.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/terapia , Fumarato de Quetiapina/uso terapêutico , Estimulação Magnética Transcraniana/métodos , Adolescente , Adulto , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Resultado do Tratamento
7.
Ecotoxicology ; 24(7-8): 1486-97, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26013101

RESUMO

Bacteria play important roles in the structure and function of marine food webs by utilizing nutrients and degrading the pollutants, and their distribution are determined by surrounding water chemistry to a certain extent. It is vital to investigate the bacterial community's structure and identifying the significant factors by controlling the bacterial distribution in the paper. Flow cytometry showed that the total bacterial abundance ranged from 5.27 × 10(5) to 3.77 × 10(6) cells/mL. Molecular fingerprinting technique, denaturing gradient gel electrophoresis (DGGE) followed by DNA sequencing has been employed to investigate the bacterial community composition. The results were then interpreted through multivariate statistical analysis and tended to explain its relationship to the environmental factors. A total of 270 bands at 83 different positions were detected in DGGE profiles and 29 distinct DGGE bands were sequenced. The predominant bacteria were related to Phyla Protebacteria species (31 %, nine sequences), Cyanobacteria (37.9 %, eleven sequences) and Actinobacteria (17.2 %, five sequences). Other phylogenetic groups identified including Firmicutes (6.9 %, two sequences), Bacteroidetes (3.5 %, one sequences) and Verrucomicrobia (3.5 %, one sequences). Conical correspondence analysis was used to elucidate the relationships between the bacterial community compositions and environmental factors. The results showed that the spatial variations in the bacterial community composition was significantly related to phosphate (P = 0.002, P < 0.01), dissolved organic carbon (P = 0.004, P < 0.01), chemical oxygen demand (P = 0.010, P < 0.05) and nitrite (P = 0.016, P < 0.05). This study revealed the spatial variations of bacterial community and significant environmental factors driving the bacterial composition shift. These results may be valuable for further investigation on the functional microbial structure and expression quantitatively under the polluted environments in the world.


Assuntos
Bactérias/classificação , Microbiota , Água do Mar/química , Água do Mar/microbiologia , Bactérias/genética , Bactérias/isolamento & purificação , Baías , China , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Eletroforese em Gel de Gradiente Desnaturante , Dados de Sequência Molecular , Análise Multivariada , Filogenia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Análise de Sequência de DNA , Análise Espacial
8.
Cell Physiol Biochem ; 34(2): 506-18, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25116350

RESUMO

BACKGROUND/AIM: P21, a multifunctional cell cycle-regulatory molecule, regulates apoptotic cell death. In this study we examined the effect of altered p21 expression on the sensitivity of acute myeloid leukemia cells in response to HDAC inhibitor SAHA treatment and investigated the underlying mechanism. METHODS: Stably transfected HL60 cell lines were established in RPMI-1640 with supplementation of G-418. Cell viability was measured by MTT assay. Western blot was applied to assess the protein expression levels of target genes. Cell apoptosis was monitored by AnnexinV-PE/7AAD assay. RESULTS: We showed HL60 cells that that didn't up-regulate p21 expression were more sensitive to SAHA-mediated apoptosis than NB4 and U937 cells that had increased p21 level. Enforced expression of p21 in HL60 cells reduced sensitivity to SAHA and blocked TRAIL-mediated apoptosis. Conversely, p21 silencing in NB4 cells enhanced SAHA-mediated apoptosis and lethality. Finally, we found that combined treatment with SAHA and rapamycin down-regulated p21 and enhanced apoptosis in AML cells. CONCLUSION: We conclude that up-regulated p21 expression mediates resistance to SAHA via inhibition of TRAIL apoptotic pathway. P21 may serve as a candidate biomarker to predict responsiveness or resistance to SAHA-based therapy in AML patients. In addition, rapamycin may be an effective agent to override p21-mediated resistance to SAHA in AML patients.


Assuntos
Apoptose/fisiologia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Leucemia Mieloide Aguda/patologia , Ligante Indutor de Apoptose Relacionado a TNF/fisiologia , Regulação para Cima , Sequência de Bases , Western Blotting , Caspase 8/metabolismo , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Células HL-60 , Humanos , Leucemia Mieloide Aguda/metabolismo , Interferência de RNA , Sirolimo/farmacologia
9.
J Transl Med ; 12: 200, 2014 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-25082261

RESUMO

BACKGROUND: Platinum-based chemotherapy improves survival among patients with non-small cell lung cancer (NSCLC), but the efficiency is limited due to resistance. In this study, we aimed to identify the expression of Aurora-A and its correlation with cisplatin resistance and prognosis in NSCLC. METHODS: We used immunohistochemical analysis to determine the expression of Aurora-A protein in 102 NSCLC patients treated by surgery and adjuvant cisplatin-based chemotherapy. The prognostic significances were assessed by Kaplan-Meier survival estimates and Cox models. The potential role of Aurora-A in the regulation of cisplatin resistance in NSCLC cells was examined by transfections using expression vector and small interfering RNA or using small-molecule inhibitors. RESULTS: Aurora-A expression was significantly associated with clinical stage (p = 0.018), lymph node metastasis (p = 0.038) and recurrence (p = 0.005), and was an independent prognostic parameter in multivariate analysis. High level of Aurora-A expression predicted poorer overall survival (OS) and progression-free survival (PFS). In vitro data showed that Aurora-A expression was elevated in cisplatin-resistant lung cancer cells, and overexpression or knockdown of Aurora-A resulted in increased or decreased cellular resistance to cisplatin. Furthermore, inhibition of Aurora-A reversed the migration ability of cisplatin-resistant cells. CONCLUSIONS: The current findings suggest that high Aurora-A expression is correlated with cisplatin-based chemotherapeutic resistance and predicts poor patient survival in NSCLC. Aurora-A might serve as a predictive biomarker of drug response and therapeutic target to reverse chemotherapy resistance.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aurora Quinase A/fisiologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Aurora Quinase A/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Células Tumorais Cultivadas
10.
PLoS One ; 8(2): e56919, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23437271

RESUMO

Triple negative breast cancer (TNBC) acquires an unfavorable prognosis, emerging as a major challenge for the treatment of breast cancer. In the present study, 122 TNBC patients were subjected to analysis of Aurora-A (Aur-A) expression and survival prognosis. We found that Aur-A high expression was positively associated with initial clinical stage (P = 0.025), the proliferation marker Ki-67 (P = 0.001), and the recurrence rate of TNBC patients (P<0.001). In TNBC patients with Aur-A high expression, the risk of distant recurrence peaked at the first 3 years and declined rapidly thereafter, whereas patients with Aur-A low expression showed a relatively constant risk of recurrence during the entire follow-up period. Univariate and multivariate analysis showed that overexpression of Aur-A predicted poor overall survival (P = 0.002) and progression-free survival (P = 0.012) in TNBC. Furthermore, overexpression of Aur-A, associated with high Ki-67, predicted an inferior prognosis compared with low expression of both Aur-A and Ki-67. Importantly, we further found that Aur-A was overexpressed in TNBC cells, and inhibition of this kinase inhibited cell proliferation and prevented cell migration in TNBC. Our findings demonstrated that Aur-A was a potential therapeutic target for TNBC and inhibition of Aur-A kinase was a promising regimen for TNBC cancer therapy.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Adulto , Idoso , Aurora Quinases , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Feminino , Humanos , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Piperazinas/farmacologia , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Recidiva
11.
Arch Gerontol Geriatr ; 56(1): 38-43, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22698678

RESUMO

To evaluate the psychometric properties of the Chinese Montreal Cognitive Assessment (MoCA-C) and assess cross-cultural differences in a community-based cohort residing in the Eastern China. The study included 72 patients with Alzheimer's disease (AD), 84 patients with mild cognitive impairment (MCI) and 146 cognitively normal controls. Sensitivities and specificities were calculated using the recommended cut-off scores. Receiver operator characteristic (ROC) curve analyses were performed to determine optimal sensitivity and specificity. Criterion validity, inter-rater, test-retest reliability and internal consistencies of the MoCA-C were examined, and clinical observations made. The influence of age, education level and gender on MoCA score was examined. Using the recommended cut-off score of 26, the area under the ROC (AUC) for predicting MCI groups using the MoCA-C was 0.930 (95%CI: 0.894; 0.965). The MoCA-C demonstrated 92% sensitivity and 85% specificity in screening for MCI. Cultural differences from the original MoCA affected the test response rate. The MoCA-C appears to have utility as a cognitive screen for early detection of AD and for MCI and warrants further investigation regarding its applicability in primary care settings in elderly Chinese people. It will be necessary to revise the contents of the questionnaire to account for by local characteristics.


Assuntos
Transtornos Cognitivos/diagnóstico , Comparação Transcultural , Testes Neuropsicológicos/normas , Fatores Etários , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/etnologia , Doença de Alzheimer/psicologia , China , Transtornos Cognitivos/etnologia , Transtornos Cognitivos/psicologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores Sexuais
12.
J Manipulative Physiol Ther ; 35(6): 428-36, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22921320

RESUMO

OBJECTIVE: The purpose of this study was to determine influences of cervical spine positions, turning times, and cervical segments on cadaver intradiscal pressure (IDP) during cervical spinal manipulative therapy (SMT). METHODS: We simulated cervical SMT with stretching and rotation on 7 fresh adult cadaver specimens in the material test system machine. The changes in IDP for cervical intervertebral disks (C3/4, C4/5, and C5/6) during 4 different stages of cervical SMT (physiologic state, end of the traction stage, turning stage, and finish time) were monitored. Five different cervical positions (extension 20°, extension 10°, neutral position, flexion 10°, flexion 20°) and 3 different turning times (0.06, 0.11, 0.16 second) of IDP were monitored, using micropressure sensors. RESULTS: The variable tendency of cervical IDP presents a "V"-shaped curve during SMT. The 4 stages of SMT had significantly different IDP (F=5498.956; P<.001). There were also significant differences in IDP between 5 cervical positions ([F=1371.216; P<.001], [flexion 20°>flexion 10°>neutral position>extension 10°>extension 20°]), 3 turning times ([F=419.530; P<.001], [0.06>0.11>0.16 seconds]), and 3 cervical segments ([F=84.282; P<.001], [C3/4

Assuntos
Vértebras Cervicais/fisiologia , Manipulação da Coluna/métodos , Postura/fisiologia , Amplitude de Movimento Articular/fisiologia , Adulto , Fenômenos Biomecânicos , Cadáver , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pressão , Rotação , Sensibilidade e Especificidade , Fatores de Tempo , Suporte de Carga
13.
Cancer Sci ; 103(8): 1586-94, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22587416

RESUMO

Previously, we and others showed that hypoxia-inducible factor-1α (HIF-1α) and transcriptionally upregulated Aurora-A were required for disease progression in several tumors. Here, we address the clinicopathologic value of Aurora-A and HIF-1α in locally advanced nasopharyngeal carcinoma (NPC). Aurora-A and HIF-1α expression was semiquantitatively evaluated by immunohistochemistry staining in 144 cases from a randomized controlled trial. Of these patients, 69 received neoadjuvant chemotherapy plus concurrent chemoradiotherapy, and acted as the training set, and 75 cases treated with neoadjuvant chemotherapy plus radiotherapy were used as the testing set to validate the prognostic effect of Aurora-A and HIF-1α. We found that Aurora-A and HIF-1α were highly expressed in NPC, but were deficient in normal adjacent epithelia. In the testing set, Aurora-A overexpression predicted a shortened 5-year overall survival (59.1% vs 82.5%, P = 0.024), progression-free survival (44.8% vs 79.8%, P = 0.004), and distant metastasis-free survival (43.0% vs 17.3%, P = 0.016). Multivariate regression analysis confirmed that Aurora-A was indeed an independent prognostic factor for death, recurrence, and distant metastasis both in the testing set and overall patients. Moreover, a positive correlation between Aurora-A and HIF-1α was detected (P = 0.037). Importantly, although HIF-1α did not show any prognostic effect for patient outcome, the subset with Aurora-A and HIF-1α co-overexpression had the poorest overall, progression-free, and distant metastasis-free survival (all P < 0.05). Our results confirmed that Aurora-A was an independent prognostic factor for NPC. Aurora-A combined with HIF-1α refined the risk definition of the patient subset, thus potentially directing locally advanced NPC patients for more selective therapy.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Aurora Quinases , Western Blotting , Quimiorradioterapia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Neoplasias Nasofaríngeas/terapia , Prognóstico , Tolerância a Radiação , Análise de Sobrevida , Transcrição Genética/fisiologia , Resultado do Tratamento
14.
Aust N Z J Psychiatry ; 46(3): 257-64, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22391283

RESUMO

OBJECTIVES: To evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) started with citalopram in first-episode young major depressive patients. METHODS: In a 2-week double-blind study with a 2-week extended antidepressant phase, 60 first-episode young major depressive patients were randomly assigned to citalopram in combination with 2 weeks of either active or sham rTMS treatment. During the following 2 weeks, the patients continued only the citalopram treatment. The 17-item Hamilton depression rating scale (HAMD-17) and Montgomery-Asberg depression rating scale (MADRS) were used to assess the severity of depression. Moreover, the Wisconsin Card Sorting Test (WCST), Trail-Making Test (TMT), and Stroop Color-Word Test (SCWT) were used to assess executive function. RESULTS: (1) There was a significantly greater number of early improvers (a reduction of HAMD-17 score ≥ 20% within the first 2 weeks) observed in the active rTMS group compared to the sham group (57% vs. 29%, χ(2)=4.667, p=0.031). (2) There was no significant difference observed in responder rates (46% vs. 36%, χ(2)=0.295, p=0.586) or in remission rates (39% vs. 29%, χ(2)=0.319, p=0.572) between the two groups at 4 weeks. (3) There was a significant difference seen in both HAMD-17 and MADRS scores between the two groups at 2 and 4 weeks. The active rTMS group showed a significantly faster score reduction compared to the sham group at 2 weeks (HAMD-17, t=13.444, p=0.001; MADRS, t=30.123, p=0.000), which was maintained at 4 weeks on both scales (HAMD-17, t=46.915, p=0.000; MADRS, t=39.996, p=0.000). (4) The patients did not deteriorate in executive performance, and even improved in categories on WCST and completed TMT faster in the active group. CONCLUSIONS: RTMS accelerated the rapidity of the antidepressant response in first-episode young depressive patients. Our results call for future rTMS studies with larger sample sizes, high intensity of stimuli, and longer duration to draw more definitive conclusions.


Assuntos
Citalopram/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/terapia , Intervenção Médica Precoce/métodos , Estimulação Magnética Transcraniana/psicologia , Adolescente , Adulto , Antidepressivos/uso terapêutico , Terapia Combinada/métodos , Terapia Combinada/psicologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Método Duplo-Cego , Diagnóstico Precoce , Função Executiva/efeitos dos fármacos , Função Executiva/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Estimulação Magnética Transcraniana/métodos
15.
Autophagy ; 8(3): 389-400, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22240664

RESUMO

Recent studies have suggested that dysregulation of autophagy plays a pivotal role in tumorigenesis. Here, we determined the prognostic value of autophagy-related protein Beclin 1 in gastric cancer. A total of 153 primary gastric cancer patients were subjected to analysis of Beclin 1 expression and survival prognosis. Among them, 68 patients were assigned randomly and used as a training set to generate a cutoff score for Beclin 1 expression by receive operating characteristic (ROC) curve analysis. The ROC-generated cutoff score was subjected to analyze the association of Beclin 1 with clinical characteristics and patient outcome. In a testing set (n = 85) and overall patients (n = 153), both univariate and multivariate analysis found that low expression of Beclin 1 predicted adverse overall survival and progression-free survival for gastric cancer patients. Furthermore, in each stage of gastric cancer patients, Beclin 1 expression was a prognostic indicator in patients with stage II, III and IV. Importantly, a reverse relationship between Beclin 1 and Bcl-xL expression was demonstrated. In patients of elevated Bcl-xL expression, a subset with lower Beclin 1 expression displayed an inferior overall survival and progression-free survival than those with higher Beclin 1 expression. Thus, our data demonstrated that low expression of Beclin 1, associated with high Bcl-xL, played as an independent biomarker, contributing to a more aggressive cancer cell phenotype and poor prognosis for gastric tumor.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Proteína bcl-X/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína Beclina-1 , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC
16.
BMC Cancer ; 11: 397, 2011 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-21933426

RESUMO

BACKGROUND: 14-3-3Æ¡ is an intracellular, phosphoserine binding protein and proposed to be involved in tumorigenesis. However, the expression dynamics of 14-3-3Æ¡ and its clinicopathological/prognostic significance in human tumors are still controversial. METHODS: The method of immunohistochemistry (IHC) and Western blot were utilized to examine the protein expression of 14-3-3Æ¡ in gastric cancer and paired normal adjacent gastric mucosal tissues. Receive operating characteristic (ROC) curve analysis was employed to determine a cutoff score for 14-3-3Æ¡ expression in a training set (n = 66). For validation, the ROC-derived cutoff score was subjected to analysis of the association of 14-3-3Æ¡ expression with patient outcome and clinical characteristics in a testing set (n = 86) and overall patients (n = 152). RESULTS: The expression frequency and expression levels of 14-3-3Æ¡ were significantly higher in gastric cancer than in normal gastric mucosal tissues. Correlation analysis demonstrated that high expression of 14-3-3Æ¡ in gastric cancer was significantly correlated with clinical stage and tumor invasion. Furthermore, in the testing set and overall patients, Kaplan-Meier analysis showed that elevated 14-3-3Æ¡ expression predicted poorer overall survival (OS) and progression-free survival (PFS). Importantly, high 14-3-3Æ¡ expression was also associated with shortened survival time in stage III and stage IV gastric cancer patients. Multivariate analyses revealed that 14-3-3Æ¡ expression was an independent prognostic parameter in gastric cancer. CONCLUSIONS: These findings provide evidence that high expression of 14-3-3Æ¡ may be important in the tumor progression and servers as an independent molecular marker for poor prognosis of gastric cancer. Thus, overexpression of 14-3-3Æ¡ identifies patients at high risk and is a novel therapeutic molecular target for this tumor.


Assuntos
Proteínas 14-3-3/biossíntese , Biomarcadores Tumorais/biossíntese , Exonucleases/biossíntese , Neoplasias Gástricas/metabolismo , Proteínas 14-3-3/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Western Blotting , Progressão da Doença , Intervalo Livre de Doença , Exonucleases/genética , Exorribonucleases , Feminino , Seguimentos , Mucosa Gástrica/química , Mucosa Gástrica/metabolismo , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Neoplasias Gástricas/genética , Análise Serial de Tecidos , Regulação para Cima
17.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(3): 286-90, 2011 May.
Artigo em Chinês | MEDLINE | ID: mdl-21671489

RESUMO

OBJECTIVE: To assess the early therapeutic and cognitive effect of repetitive transcranial magnetic stimulation (rTMS) combined with antidepressant medication in treatment of first-episode patients with major depression. METHODS: Sixty first-episode depressed inpatients aged 18-45 y, who met the DSM-IV clinical criteria for major depressive episode were randomly assigned to citalopram treatment (20 mg/d) in combination with a two-week period of either rTMS (study group)or sham procedure (control group) on left dorsal-lateral prefrontal cortex (10 Hz, 90% motor threshold). The Hamilton Depression Rating Scale (HAMD) was used to assess the severity of depression. The Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT) were used to assess cognitive function of depression. RESULT: The response rate was significantly greater in the study group compared to the control group after treatment (57% compared with 29%,P<0.05). The HAMD scores significantly declined after treatment in two groups, and the study group showed lower scores compared to the control group after 2 weeks (P<0.01). Neuropsychological assessments showed that there was no significant difference between the two groups except for the significant improvement in the categories on WCST in study group compared to the baseline (P<0.05) and the control group (P<0.05)after 2 weeks treatment. No serious event occurred in the patients during the rTMS study. CONCLUSION: 10 Hz rTMS enhances early effects of citalopram and improves cognitive function in first-episode major depressive patients.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/terapia , Estimulação Magnética Transcraniana , Adolescente , Adulto , Citalopram/uso terapêutico , Terapia Combinada , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
18.
J Transl Med ; 9: 71, 2011 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-21595920

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is an immunophenotypically heterogeneous malignant disease, in which CD34 positivity is associated with poor prognosis. CD34+ AML cells are 10-15-fold more resistant to daunorubicin (DNR) than CD34- AML cells. Curcumin is a major component of turmeric that has shown cytotoxic activity in multiple cancers; however, its anti-cancer activity has not been well studied in DNR-insensitive CD34+ AML cells. The aim of this study was to therefore to explore curcumin-induced cytotoxicity in DNR-insensitive CD34+ AML cell lines (KG1a, Kasumi-1), DNR-sensitive U937 AML cells, and primary CD34+ AML bone-marrow-derived cells. METHODS: Primary human CD34+ cells were isolated from peripheral blood mononuclear cells or bone marrow mononuclear cells using a CD34 MicroBead kit. The growth inhibitory effects of curcumin were evaluated by MTT and colony-formation assays. Cell cycle distribution was examined by propidium iodide (PI) assay. Apoptosis was analyzed by Wright-Giemsa, Hoechst 33342 and Annexin-V/PI staining assays. The change in mitochondrial membrane potential (MMP) was examined by JC-1 staining and flow cytometry. Expression of apoptosis-related proteins was determined by reverse transcription-polymerase chain reaction and Western blotting. Short interfering RNA (siRNA) against Bcl-2 was used in CD34+ KG1a and Kasumi-1 cells incubated with/without DNR. RESULTS: Curcumin inhibited proliferation and induced apoptosis and G1/S arrest in both DNR-insensitive KG1a, Kasumi-1 and DNR-sensitive U937 cells. Curcumin-induced apoptosis was associated with reduced expression of both Bcl-2 mRNA and protein, subsequent loss of MMP, and activation of caspase-3 followed by PARP degradation. Curcumin synergistically enhanced the cytotoxic effect of DNR in DNR-insensitive KG1a and Kasumi-1 cells, consistent with decreased Bcl-2 expression. Accordingly, siRNA against Bcl-2 increased the susceptibility of KG1a and Kasumi-1 cells to DNR-induced apoptosis. More importantly, curcumin suppressed Bcl-2 expression, selectively inhibited proliferation and synergistically enhanced the cytotoxicity of DNR in primary CD34+ AML cells, while showing limited lethality in normal CD34+ hematopoietic progenitors. CONCLUSION: Curcumin down-regulates Bcl-2 and induces apoptosis in DNR-insensitive CD34+ AML cell lines and primary CD34+ AML cells.


Assuntos
Antígenos CD34/metabolismo , Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Daunorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Leucemia Mieloide Aguda/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Adolescente , Adulto , Idoso , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Fase G1/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/genética , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Pessoa de Meia-Idade , Poli(ADP-Ribose) Polimerases/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Fase S/efeitos dos fármacos
19.
Autophagy ; 6(3): 395-404, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20150769

RESUMO

Recent studies have suggested that autophagy plays a pivotal role in regulation of cancer development and progression. High expression of the autophagy-related Beclin 1 protein predicted favorable patient outcome in several tumors. Here, a randomized controlled trial (RCT)-derived 128 nasopharyngeal carcinoma (NPC) patients were subjected to analysis of Beclin 1 expression and survival probability. In this RCT, 61 patients treated with induction chemotherapy plus concurrent chemoradiotherapy were used as a training set to generate a Beclin 1 cutoff score for patient outcome by receiver operating characteristic (ROC) curve analysis. For validation, the ROC-derived cutoff point was subjected to analysis of the association of Beclin 1 expression with patient outcome and clinical characteristics in testing set. The testing set comprised of 67 patients received induction chemotherapy plus radiotherapy. In the testing set and overall patients, our univariate and multivariate analysis showed that higher Beclin 1 expression, defined by the training set ROC analysis-generated cutoff score, predicted poorer overall survival, progression-free survival and distant metastasis-free survival. However, we failed to detect a correlation between Beclin 1 and local failure-free survival. Moreover, a positive relationship between Beclin 1 and HI F-1alpha expression was found. Importantly, among patients with elevated HI F-1alpha expression, a subset with lower Beclin 1 expression displayed a significant overall survival advantage than those with higher expression (p = 0.036). Contrary to previous studies, our results demonstrated that high autophagic Beclin 1 expression was an inferior prognostic marker for NPC. HI F-1alpha-associated Beclin 1 high expression might facilitate NPC cells surviving from chemoradiotherapy, suggesting a novel therapeutic molecular target for NPC.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/metabolismo , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Proteína Beclina-1 , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Resultado do Tratamento , Adulto Jovem
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 18(1): 103-6, 2010 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-20137127

RESUMO

This study was aimed to investigate the role of bone marrow microenvironment in the regulation of activator protein 1 (AP-1) expression in multiple myeloma (MM) cells. The primary myeloma cells (CD138(+) cells) from 8 patients with MM were sorted by using immunomagnetic beads and were cocultured with osteoclasts in alpha-MEM supplemented with 10% fetal bovine serum, antibiotics, RNAKL (50 ng/ml) and macrophage colony-stimulating factor (25 ng/ml) for 10 to 14 days at 2.5 x 10(6) cells/ml. The expression levels of genes c-jun, junD fos and fosB were detected by real-time PCR. The results showed that the osteoclasts were observed after coculture of mononuclear cells in peripheral blood of MM patients with osteoclasts for 10 - 14 days. As compared with control (without coculture with osteoclasts), the viability of MM cells cocultured with osteoclasts obviously increased, the expression levels of c-jun, junD, fos and fosB decreased to 25.7% - 1.66%, 68.49% - 8.54%, 10.35% - 0.19% and 36.63% - 3.44% of the control respectively. It is concluded that the bone marrow microenvironment can inhibit the expression of c-jun, junD, fos and fosB promote myeloma cell proliferation and maintain cell survival.


Assuntos
Medula Óssea/patologia , Mieloma Múltiplo/genética , Fator de Transcrição AP-1/genética , Idoso , Medula Óssea/metabolismo , Técnicas de Cocultura , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Osteoclastos/citologia , Células Tumorais Cultivadas
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