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1.
Eur Rev Med Pharmacol Sci ; 26(19): 7084-7090, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36263556

RESUMO

OBJECTIVE: Based on the Huimin policy of Weihai Social Security Bureau, this project aims to investigate feasibility of screening through screening of serum tumor markers (TM) in the middle-aged and elderly population in Weihai area. According to the joint mode of examination institution and clinical department (oncology), we provide dynamic follow-up for subjects for early intervention of abnormal tumor screening and high-risk population, through which we can cut off pathogenic pathway of cancer and improve early diagnosis of cancer and enhance the cure rate. PATIENTS AND METHODS: We continued to track subjects whose TM was not reduced to normal until it was normal or diagnosed, collecting the blood samples of eligible patients that we removed high-risk factors from the subjects so that TM could be lowered to normal. RESULTS: A total of 83,049 blood samples were detected in our hospital, and 89 patients were diagnosed with newly diagnosed tumor. The positive expression rate of CEA in lung cancer patients was 91.4%. CONCLUSIONS: The diagnosis of tumor relies not only on TM, but also on observation of clinical symptoms, continuous observation of TM dynamic changes and individualized comprehensive analysis.  The main purpose of this policy is not only to find patients with "early tumor", but also to cut off the pathogenic pathway of cancer, achieve purpose of tertiary prevention and significantly save medical costs. The examination mechanism and the clinical-related departments are connected, and the pattern of screening, tracking and analysis of abnormal results in large samples is in line with the present situation of China and is worthy of clinical promotion.


Assuntos
Biomarcadores Tumorais , Neoplasias Pulmonares , Pessoa de Meia-Idade , Humanos , Idoso , Antígeno Carcinoembrionário , Detecção Precoce de Câncer , Neoplasias Pulmonares/diagnóstico , China
2.
Neoplasma ; 67(1): 78-84, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31777262

RESUMO

Accumulating evidence indicates that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) is involved in cancer, while the clinical significance and the exact role of eEF1A1 in renal cell carcinoma (RCC) remain obscure. The aim of the present study was to evaluate the clinical significance of eEF1A1 in RCC and to investigate its effective mechanisms in order to identify a potential therapeutic target. The expression levels of eEF1A1 in RCC were explored by immunohistochemistry in tissues from 184 patients. eEF1A1 was knocked down, and cell proliferation and apoptosis were then investigated. The MAPK pathway-related proteins were detected by western blot. Our results revealed that eEF1A1 was highly expressed in RCC tissues and associated with poor prognosis. Knockdown of eEF1A1 attenuated proliferation and promoted the apoptosis of RCC cells. Furthermore, eEF1A1 knockdown decreased the phosphorylation level of AKT and ERK. In conclusion, eEF1A1 may serve as a valuable prognostic biomarker and promising therapeutic target of RCC.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Fator 1 de Elongação de Peptídeos/genética , Apoptose , Carcinoma de Células Renais/genética , Proliferação de Células , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Renais/genética , Prognóstico
3.
Zhonghua Xin Xue Guan Bing Za Zhi ; 47(7): 539-543, 2019 Jul 24.
Artigo em Chinês | MEDLINE | ID: mdl-31365994

RESUMO

Objective: To investigate the risk factors of postoperative acute kidney injury (AKI) in patients aged between 40 and 50 years old undergoing cardiac valvular surgery and the impact on outcome. Methods: The clinical data of 286 patients aged between 40 and 50 years old undergoing cardiac valve surgery in Guangdong Provincial People's Hospital from January 2012 to December 2016 were analyzed retrospectively. Preoperative coronary angiography was performed in all patients. All patients enrolled were divided into AKI group and non-AKI group according to the existence or not of postoperative AKI. Patients with AKI were further divided into AKI stage 1, stage 2, and stage 3 groups according to KDIGO guideline. Demographic characteristics, preoperative clinical data including serum creatinine, estimated glomerular filtration rate, hemoglobin, uric acid, urinary protein, presence or absence of chronic kidney disease, left ventricular ejection fraction, pulmonary artery pressure, New York Heart Association (NYHA) functional classification, preoperative co-morbidity (hypertension, diabetes, anemia, cerebrovascular disease, peripheral artery disease), preoperative medication(vasoactive drugs, diuretic, renin-angiotensin system inhibitor (RASI), surgical data (contrast dosage in coronary angiography, type of cardiac valve surgery) were recorded and analyzed in this retrospective study. The risk factors for postoperative AKI and its impact on clinical outcomes (mortality, hospitalization expenses and Intensive Care Unit stay duration) were evaluated. Logistic regression analysis was used to determine the risk factors for postoperative AKI and the adjusted variables with P<0.2 were selected for the multivariate logistic regression analysis to define the independent determinants for AKI. Results: AKI was defined in 106 out of 286 enrolled patients, including 96 patients with AKI stage 1, 10 patients with AKI stage 2 and no patients with AKI stage 3. The proportion of coexisting cerebrovascular diseases was higher in AKI group than in non-AKI group (9(8.49%) and 5(2.78%), χ(2)=4.677, P=0.031), while there was no difference among other baseline data between the two groups. Multivariate logistic regression analysis showed that preoperative complications of cerebral vascular disease was an independent risk factor of postoperative AKI (OR=3.578, 95%CI 1.139-11.242, P=0.029). Five out of 106 AKI patients died during hospitalization while there was only 1 patient died among 180 patients without AKI. Patients with AKI after cardiac valve operation experienced higher mortality than patients without AKI (χ(2)=5.625, P=0.028). Further analysis showed that there was no difference in hospitalization mortality between patients with AKI stage 2 and stage (χ(2)=0.686, P=0.408) while the hospitalization mortality in patients with AKI stage 2 was higher than those without AKI (χ(2)=8.113, P=0.004). The hospitalization expenses in patients with AKI were 10.38(8.59,12.54) ×10(4) RMB, significantly higher than that in patients without AKI (9.72(8.03,11.93) ×10(4) RMB)(P=0.043). There was no difference in hospitalization expenses between patients with AKI stage 1 and without AKI (P=0.635). The hospitalization expenses in patients with AKI stage 2 was higher than those without AKI (P=0.023). Intensive Care Unit stay duration in patients with AKI was 3(1,4) days, significantly higher than those without AKI (P=0.044). There was no difference in Intensive Care Unit stay duration in patients with AKI stage 1 and without AKI (P=0.978), while Intensive Care Unit stay duration in patients with AKI stage 2 was significantly longer than those without AKI (P=0.006). Conclusions: Preoperative complications of cerebral vascular disease is an independent risk factor of postoperative AKI. Non-senile patients with AKI after cardiac valvular surgery is associated with a higher proportion of mortality, hospitalization expenses and Intensive Care Unit stay duration as compared patients without postoperative AKI.


Assuntos
Injúria Renal Aguda , Adulto , Valvas Cardíacas , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco
4.
Zhonghua Nei Ke Za Zhi ; 58(7): 501-507, 2019 Jul 01.
Artigo em Chinês | MEDLINE | ID: mdl-31269566

RESUMO

Objective: To evaluate the clinical manifestations, metal metabolism, imaging characteristics and treatment response in patients with delayed Wilson disease (WD). Methods: Patients with untreated WD (40 with delayed onset and 40 with non-delayed onset) were enrolled. Twenty healthy people were included as normal controls. All patients were evaluated with modified Young scale neural symptom scores, grade of Child liver function and mental symptoms rating scale, magnetic resonance imaging (MRI) scan, magnetic sensitive imaging (susceptibility weighted imaging, SWI), metal metabolism. Corrected phase (CP) was measured at SWI. After 2 week treatment, neurologic symptoms, liver function, and metal metabolism were reviewed. Results: The total score of neurological symptoms in WD patients with delayed onset was lower than that of non-delayed onset (13.00±6.87 vs. 21.13±5.53, P=0.033). The scores of SCL-90 and HAMA depression scales in patients with delayed onset were lower than those of non-delayed onset. On T(2) weighted imaging, areas including substantia nigra and thalamus, the caudate nucleus, globus pallidus, putamen presented high signal rate in patients with delated onset than those with non-delayed (P=0.022, 0.037, 0.022, 0.037, 0.029 respectively). The SWI CP values of cangbai sphere and shell nucleus in patients with delayed onset were lower than those with non-delayed onset. Patients with delayed onset had higher urinary copper than those with non-delayed onset before and after treatment (P=0.040, 0.036). After treatment, the score of abnormal tremor and gait in patients with delayed onset was decreased (P=0.037, 0.044), while as the occurrence of neurological symptoms was increased by 10%, and the liver function level in patients with delayed WD was decreased in 3 cases. Conclusions: The brain of WD patients with delayed onset is mainly composed of metal deposits, however the cell damage is not apparent. Clinical symptoms are characterized by significant liver injury, but relatively mild neurological and psychiatric symptoms. Patients with delayed WD have higher urinary copper excretion than those with non-delayed WD. Chelating agents improves the neurological symptoms in patients with delayed onset.


Assuntos
Encéfalo/diagnóstico por imagem , Cobre/metabolismo , Degeneração Hepatolenticular/patologia , Encéfalo/metabolismo , Estudos de Casos e Controles , Criança , Cobre/urina , Degeneração Hepatolenticular/metabolismo , Humanos , Imageamento por Ressonância Magnética , Tálamo
5.
Zhonghua Yi Xue Za Zhi ; 99(11): 806-811, 2019 Mar 19.
Artigo em Chinês | MEDLINE | ID: mdl-30893721

RESUMO

Objective: To study the clinical symptoms, copper metabolism and imaging characteristics of Wilson disease (WD) carriers and to explore the treatment strategy of WD carriers. Methods: Forty WD carriers, 40 WD patients and 20 normal controls from the First Affiliated Hospital of Sun Yat-sen University from July 2007 to May 2018 were included. The modified Young scale was used for neural symptom scoring, and Child grading of liver function, mental symptoms rating scale, magnetic resonance imaging (MRI) scan, susceptibility weighted imaging (SWI) inspection, metal metabolism tests were also applied to all the included subjects. Corrected phase (CP) was measured by SWI. WD carriers were divided into symptomatic group and asymptomatic group. Symptomatic WD carriers were treated with penicillamine for 2 weeks and zinc gluconate for 3 months, then their neurological symptoms, liver function grade, metal metabolism index were rechecked. Results: Six WD carriers presented with some clinical symptoms, including 5 with neurological symptoms and 4 with liver dysfunction. The score of Hamilton anxiety (HAMA) scale of symptomatic WD carriers was higher than that of normal control group (P=0.021). 85% of carriers had ceruloplasmin level less than 0.26 g/L. 80% of carriers had serum copper between normal controls and WD patients. The free copper level of WD carriers was lower than that of WD patients (P=0.012, 0.019). Urinary copper in symptomatic WD carriers was higher than normal controls (P=0.047). The CP values of thalamus, globus pallidus and putamen in symptomatic WD carriers were lower than those in normal control group. After treatment with penicillamine in symptomatic WD carriers, urinary copper was higher than that before treatment (P=0.036). After treatment, the liver enzymes of symptomatic WD carriers returned to normal, and the score of modified Young scale was lower than before treatment (P=0.031). Conclusions: Mild copper metabolism abnormality is seen in WD carriers. A few carriers have neurological symptoms such as limb tremors, or liver symptoms such as abnormal liver enzymes. Abnormal copper metabolism is more serious in symptomatic WD carriers than in asymptomatic WD carriers. Symptomatic WD carriers can be treated with zinc gluconate.


Assuntos
Degeneração Hepatolenticular , Ceruloplasmina , Cobre , Humanos , Imageamento por Ressonância Magnética
6.
Zhonghua Yi Xue Za Zhi ; 97(3): 176-181, 2017 Jan 17.
Artigo em Chinês | MEDLINE | ID: mdl-28162166

RESUMO

Objective: To evaluate the difference of metal metabolism, damage to structure and functional activity in brains between hepatic and cerebral type Wilson disease (WD). Methods: Forty patients with WD, including 20 with cerebral type and 20 with hepatic type, and 20 age-matched healthy controls in the First Affiliated Hospital, Sun Yat-sen University between Jul 2013 and May 2016 were enrolled.All study subjects underwent diffusion tensor imaging (DTI), resting state functional MRI (rs-fMRI) and susceptibility weighted imaging (SWI) of the brain.Six regions of interest (ROIs) were chosen.The values of fractional anisotropy (FA), λ in ROIs were determined on DTI, FA and fiber volumes between ROIs were also determined on DTI.The values of amplitude of low frequency fluctuation (ALFF) and regional homogeneity (REHO) in ROIs were determined on rs-fMRI.The values of corrected phase (CP) were calculated on SWI.The copper and iron content were measured.The difference of imaging and metal metrics between cerebral type and hepatic type WD were evaluated. Results: DTI metrics differed between patients with the cerebral and hepatic types of WD.ALFF values in the caudate nucleus, and thalamus were lower (P=0.037, 0.040), and REHO values in the caudate nucleus were lower (P=0.029), in patients of cerebral type than in hepatic type patients.CP values of the right caudate nucleus and left putamen in cerebral type WD patients were lower than in hepatic type patients (P=0.020, 0.23). The serum iron content of hepatic type WD patients was higher than the normal (P=0.013), and the urine copper content was higher than the cerebral type patients (P=0.021). Conclusions: Metal deposition and damage to the structure and functional activity in the brain may occur in hepatic type WD patients.The structural and functional activity damage of the brain in hepatic type is less severe than that in cerebral type patients, while the metal deposition is not significant different between hepatic and cerebral type.


Assuntos
Encéfalo/patologia , Degeneração Hepatolenticular/patologia , Anisotropia , Encéfalo/metabolismo , Imagem de Tensor de Difusão , Degeneração Hepatolenticular/metabolismo , Humanos , Imageamento por Ressonância Magnética
7.
8.
Br J Dermatol ; 177(3): 809-817, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28132413

RESUMO

BACKGROUND: The tryptophan-depleting enzyme indoleamine-2,3-dioxygenase (IDO) is critical for the regulation of immunotolerance and plays an important role in immune-associated skin diseases. OBJECTIVES: To analyse the level of IDO in condyloma acuminata (CA) and its role in this condition. METHODS: IDO expression was assessed in the skin and peripheral blood of healthy controls and patients with CA. To assess the role of skin IDO in immunity, the ability of isolated epidermal cells to metabolize tryptophan and the influence on polyclonal T-cell mitogen (PHA)-stimulated T-cell proliferation were explored. RESULTS: IDO median fluorescence intensities in peripheral blood mononuclear cells from patients with CA were similar to those from healthy controls. Immunohistochemistry showed that IDO+ cells were rare in normal skin and the control skin of patients with CA, but were greatly accumulated in wart tissue. Most fluorescence signals of IDO+ cells did not overlap with those of CD1a+ Langerhans cells. Human papillomavirus (HPV) DNA probe in situ hybridization showed a large number of IDO+ cells in the HPV- site. Keratinocytes in the skin of healthy controls and the circumcised skin of patients with CA could minimally transform tryptophan into kynurenine, but IDO-competent epidermal cells from warts could transform tryptophan. In addition, these IDO-competent epidermal cells could inhibit PHA-stimulated T-cell proliferation. The addition of an IDO inhibitor, 1-methyl-d-tryptophan, restored the inhibited T-cell proliferation. CONCLUSIONS: Abnormally localized high IDO expression might be involved in the formation of a local immunotolerant microenvironment.


Assuntos
Doenças do Ânus/enzimologia , Condiloma Acuminado/enzimologia , Doenças Urogenitais Femininas/enzimologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Doenças Urogenitais Masculinas/enzimologia , Adulto , Doenças do Ânus/imunologia , Estudos de Casos e Controles , Proliferação de Células/fisiologia , Células Cultivadas , Condiloma Acuminado/imunologia , Feminino , Doenças Urogenitais Femininas/imunologia , Humanos , Tolerância Imunológica/fisiologia , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Leucócitos Mononucleares/enzimologia , Masculino , Períneo , Linfócitos T/virologia , Triptofano/metabolismo
9.
Genet Mol Res ; 15(3)2016 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-27706597

RESUMO

Maternal post-traumatic stress disorder (PTSD) increases the risk of adverse neurodevelopmental outcomes in the child. Epigenetic alternations may play an essential role in the negative effects of PTSD. This study was aimed to investigate the possible epigenetic alterations of maternal PTSD, which underpins the developmental and behavioral impact. 24 pregnant Sprague-Dawley (SD) rats were randomly grouped into PTSD and control groups. Open-field tests (OFTs), elevated pull maze (EPM) assays, gene expression profile chip tests, and methylated DNA immunoprecipitation sequencing (MeDIP-Seq) were performed on the offsprings 30 days after birth. The results showed that PTSD offsprings had lower body weights and OFT scores than control offsprings. Enzyme-linked immunosorbent assays showed that serotonin receptor (5-HT) and dopamine levels were significantly lower in PTSD offsprings than in control offsprings. In contrast, corticosterone levels were higher in the PTSD group than in the control group. In a comparison of the PTSD group versus the control group, 4,160 significantly differentially methylated loci containing 30,657 CpGs were identified; 2,487 genes, including 13 dysmethylated genes, were validated by gene expression profiling, showing a negative correlation between methylation and gene expression (R = -0.617, P = 0.043). In conclusion, maternal PTSD could delay the physical and behavioral development of offsprings, and the underlying mechanism could contribute to changes in neurotransmitters and gene expression, owing to dysregulation of whole-genome methylation. These findings could support further clinical research on appropriate interventions for maternal PTSD to prevent methylation dysregulation and developmental retardation.


Assuntos
Deficiências do Desenvolvimento/metabolismo , Epigênese Genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Transtornos de Estresse Pós-Traumáticos/complicações , Animais , Peso Corporal , Corticosterona/sangue , Metilação de DNA , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/psicologia , Feminino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ratos Sprague-Dawley , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transcriptoma , Aumento de Peso
10.
Zhonghua Yi Xue Za Zhi ; 96(30): 2404-9, 2016 Aug 09.
Artigo em Chinês | MEDLINE | ID: mdl-27545032

RESUMO

OBJECTIVE: To investigate the effect of proteinuria on in-hospital severe adverse events and prognosis of the patients with heart failure(HF). METHODS: Clinical data of 520 patients with severe HF( NYHA 3-4 grades) in our department were analyzed retrospectively. Proteinuria was diagnosed on admission using the spot dipstick urinalysis. Clinical characteristics were compared between the patients with and without proteinuria. Univariate and multivariate Logistic regression analysis were used to evaluate the correlations of proteinuria with in-hospital adverse events and prognosis. RESULTS: On admission, proteinuria was found in 57.7% (300/520) of the enrolled patients with severe HF. The age, proportions of the HF patients coexistent with hypertention, diabetes mellitus and aneamia, and receiving vasoactive drugs, levels of NT-proBNP, creatinine, C-reactive protein and fasting blood glucose, were significantly higher, while the levels of eGFR, hemoglobin and hematocrit significantly lower in the proteinuria group than those in the non- proteinuria group. The multivariate analysis revealed that proteinuria was an independent risk factor for mechanical ventilation (MV) (OR=2.916, 95% CI: 1.712-4.968, P<0.001), cardiopulmonary resuscitation (CPR) (OR=1.956, 95% CI: 0.997-3.843, P=0.049) and in-hospital mortality (OR=2.490, 95% CI: 1.188-5.218, P=0.016). CONCLUSIONS: The severe HF patients with proteinuria often present with severe critical conditions. Proteinuria should be a potential marker for in-hospital adverse events and prognosis of severe hospitalized HF patients.


Assuntos
Insuficiência Cardíaca , Biomarcadores , Proteína C-Reativa , Creatinina , Hemoglobinas , Mortalidade Hospitalar , Hospitais , Humanos , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Prognóstico , Proteinúria , Estudos Retrospectivos
11.
Int J Biol Sci ; 12(9): 1041-51, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27570478

RESUMO

A major feature of early age-related macular degeneration (AMD) is the thickening of Bruch's membrane in the retina and an alteration in its composition with increased lipid deposition. In certain pathological conditions proteoglycans are responsible for lipid retention in tissues. Growth factors are known to increase the length of glycosaminoglycan chains and this can lead to a large increase in the interaction between proteoglycans and lipids. Using choroidal endothelial cells, we investigated the effects of a number of AMD relevant growth factors TGFß, thrombin, PDGF, IGF and VEGF on proteoglycan synthesis. Cells were characterized as of endothelial origin using the specific cell markers endothelial nitric oxide synthesis and von Willebrand factor and imaged using confocal microscopy. Cells were treated with growth factors in the presence and absence of the appropriate inhibitors and were radiolabeled with [35S]-SO4. Proteoglycans were isolated by ion exchange chromatography and sized using SDS-PAGE. Radiosulfate incorporation was determined by the cetylpyridinium chloride (CPC) precipitation technique. To measure cellular glycosaminoglycan synthesizing capacity we added xyloside and assessed the xyloside-GAGs by SDS-PAGE. TGFß, thrombin, PDGF & IGF dose-dependently stimulated radiosulfate incorporation and GAG elongation as well as xyloside-GAG synthesis, however VEGF treatment did not stimulate any changes in proteoglycan synthesis. VEGF did not increase pAKT but caused a large increase in pERK relative to the response to PDGF. Thus, AMD relevant agonists cause glycosaminoglycan hyperelongation of proteoglycans synthesised and secreted by retinal choroidal endothelial cells. The absence of a response to VEGF is intriguing and identifies proteoglycans as a novel potential target in AMD. Future studies will examine the relevance of these changes to enhanced lipid binding and the development of AMD.


Assuntos
Glicosaminoglicanos/metabolismo , Retina/citologia , Retina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Western Blotting , Linhagem Celular , Eletroforese em Gel de Poliacrilamida , Células Endoteliais/metabolismo , Haplorrinos , Fosfoproteínas/metabolismo , Proteoglicanas/metabolismo , RNA Mensageiro/metabolismo , Trombina/metabolismo
12.
Genet Mol Res ; 15(2)2016 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-27323037

RESUMO

We evaluated the application of three machine learning algorithms, including logistic regression, support vector machine and back-propagation neural network, for diagnosing congenital heart disease and colorectal cancer. By inspecting related serum tumor marker levels in colorectal cancer patients and healthy subjects, early diagnosis models for colorectal cancer were built using three machine learning algorithms to assess their corresponding diagnostic values. Except for serum alpha-fetoprotein, the levels of 11 other serum markers of patients in the colorectal cancer group were higher than those in the benign colorectal cancer group (P < 0.05). The results of logistic regression analysis indicted that individual detection of serum carcinoembryonic antigens, CA199, CA242, CA125, and CA153 and their combined detection was effective for diagnosing colorectal cancer. Combined detection had a better diagnostic effect with a sensitivity of 94.2% and specificity of 97.7%; combining serum carcinoembryonic antigens, CA199, CA242, CA125, and CA153, with the support vector machine diagnosis model and back-propagation, a neural network diagnosis model was built with diagnostic accuracies of 82 and 75%, sensitivities of 85 and 80%, and specificities of 80 and 70%, respectively. Colorectal cancer diagnosis models based on the three machine learning algorithms showed high diagnostic value and can help obtain evidence for the early diagnosis of colorectal cancer.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Aprendizado de Máquina , Adulto , Idoso , Algoritmos , Antígeno Ca-125/sangue , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Redes Neurais de Computação , Máquina de Vetores de Suporte
13.
Cell Death Dis ; 7: e2078, 2016 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-26821070

RESUMO

Pluripotency makes human pluripotent stem cells (hPSCs) promising for regenerative medicine, but the teratoma formation has been considered to be a major obstacle for their clinical applications. Here, we determined that the downregulation of miR-302 suppresses the teratoma formation, hampers the self-renewal and pluripotency, and promotes hPSC differentiation. The underlying mechanism is that the high endogenous expression of miR-302 suppresses the AKT1 expression by directly targeting its 3'UTR and subsequently maintains the pluripotent factor OCT4 at high level. Our findings reveal that miR-302 regulates OCT4 by suppressing AKT1, which provides hPSCs two characteristics related to their potential for clinical applications: the benefit of pluripotency and the hindrance of teratoma formation. More importantly, we demonstrate that miR-302 upregulation cannot lead OCT4 negative human adult mesenchymal stem cells (hMSCs) to acquire the teratoma formation in vivo. Whether miR-302 upregulation can drive hMSCs to acquire a higher differentiation potential is worthy of deep investigation.


Assuntos
MicroRNAs/fisiologia , Fator 3 de Transcrição de Octâmero/metabolismo , Células-Tronco Pluripotentes/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células-Tronco Adultas/citologia , Células-Tronco Adultas/metabolismo , Células-Tronco Adultas/fisiologia , Animais , Ciclo Celular/genética , Diferenciação Celular/fisiologia , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , MicroRNAs/genética , MicroRNAs/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Teratoma/genética , Teratoma/patologia , Transfecção
14.
Int J Dev Neurosci ; 38: 17-22, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25068645

RESUMO

Machado-Joseph disease (MJD) is caused by a (CAG)n trinucleotide repeat expansion that is translated into an abnormally long polyglutamine tract. This disease is considered the most common form of spinocerebellar ataxia (SCA). In the present study, we developed stable inducible cell lines (PC12Tet-On-Ataxin-3-Q28/84) expressing ataxin-3 with either normal or abnormal CAG repeats under doxycycline control. The expression of acetyl histone H3 and the induction of c-Fos in response to cAMP were strongly suppressed in cells expressing the protein with the expanded polyglutamine tract. Treatment with valproic acid, a histone deacetylase inhibitor (HDACi), attenuated mutant ataxin-3-induced cell toxicity and suppression of acetyl histone H3, phosphorylated cAMP-responsive element binding protein (p-CREB) as well as c-Fos expression. These results indicate that VPA can stimulate the up-regulation of gene transcription through hyperacetylation. Thus, VPA might have a therapeutic effect on MJD.


Assuntos
Proteína de Ligação a CREB/metabolismo , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Histonas/metabolismo , Ácido Valproico/farmacologia , Animais , Ataxina-3 , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Fator de Crescimento Neural/farmacologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Células PC12 , Peptídeos/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transfecção , Expansão das Repetições de Trinucleotídeos/genética
15.
J Sports Med Phys Fitness ; 53(6): 665-70, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24247190

RESUMO

AIM: AIM of the study was to examine the relationships between biochemical and physiological changes induced by exercise in postmyocardial infarction patients (PMIP) during the early stages of cardiac rehabilitation. METHODS: Forty-nine male non-blockade recent PMIP, aged 63.8 ± 4.7 years, performed a graded exercise test on a motorised treadmill until volitional cessation or reaching any of the American College of Sports Medicine criteria. Blood pressure and rate-pressure product (RPP) were recorded every three minutes. A 12-lead electrocardiogram was monitored continuously and heart rate (HR) was taken from this. Blood samples were obtained by two methods; those used for testing blood lactate (BL) were taken from an already warmed finger tip before and during exercise, and the others used for enzymatic analysis based on lactate dehydrogenase (LDH), lactate dehydrogenase isoenzyme 1 (LDH-1), creatine kinase (CK) and creatine kinase polypeptide sub-unit MB (CK-MB) were collected by venipuncture from the antecubital vein pre and immediate post exercise test. RESULTS: Highly significant correlations existed between exercise-induced changes in HR, RPP, BL and ST segment level with increased enzymes activity in serum, and 73.1% to 90.1% of the variance in percentage increase of the enzyme activity could be predicted from the variance in percentage increase of HR during exercise. However, the mechanism of these relationships may differ. CONCLUSION: Since the rise in serum enzymes during submaximal exercise is primarily attributed to changes in membrane permeability in fatigued muscle, these relationships provide useful guidance to health professionals obtaining biochemical information about muscle fatigue.


Assuntos
Teste de Esforço , Infarto do Miocárdio/sangue , Infarto do Miocárdio/fisiopatologia , Pressão Sanguínea/fisiologia , Eletrocardiografia , Frequência Cardíaca/fisiologia , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/reabilitação
16.
Artigo em Inglês | MEDLINE | ID: mdl-23304210

RESUMO

We aimed to investigate the mechanism of shaking as a prenatal stressor impacting the development of the offspring and Chinese medicines correcting the alterations. Pregnant rats were randomized into earthquake simulation group (ESG), herbal group (HG) which received herbal supplements in feed after shaking, and control group (CG). Findings revealed body weight and open field test (OFT) score of ESG offspring were statistically inferior to the CG and HG offspring. The corticosterone levels of ESG were higher than those of CG but not than HG. The dopamine level of ESG was slightly lower than that of the CG and of HG was higher than that of ESG. The 5-HT of ESG was higher than CG and HG. The growth hormone level of the ESG was significantly lower than ESG but not than CG. Gene expression profile showed 81 genes upregulated and 39 genes downregulated in ESG versus CG, and 60 genes upregulated and 28 genes downregulated in ESG versus HG. Eighty-four genes were found differentially expressed in ESG versus CG comparison and were normalized in ESG versus HG. We conclude that maternal shaking negatively affected physical and nervous system development, with specific alterations in neurohormones and gene expression. Chinese herbal medicine reduced these negative outcomes.

17.
J Nanosci Nanotechnol ; 7(4-5): 1568-72, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17450927

RESUMO

Field-effect transistors have been fabricated using single-walled carbon nanotubes (SWCNTs) and double-walled carbon nanotubes (DWCNTs), and their electrical transport properties have been studied comparatively. While a semiconducting SWCNT exhibits better field-effect characteristics than a DWCNT counterpart, the DWCNT shows more complicated response to external gate modulation. Depending on the nature of the two shells of a DWCNT, i.e., whether the shell is semiconducting (S) or metallic (M), a DWCNT device can be described as either S-S, or S-M, or M-S, or M-M. It was found that the S-S and M-M or M-S devices show similar field-effect characteristics to those found in SWCNT devices. But for S-M DWCNT devices, distinct field-effect characteristic was found and attributed to the combined effects of intershell interactions and screening by free carriers of the inner metallic shell. The S-M DWCNT devices thus provide a perfect system for studying the important intershell interaction, and information on the effect of this interaction on the electrical properties of a multi-walled carbon nanotube can be obtained by a comparative study of S-M DWCNT and S-SWCNT devices.


Assuntos
Nanotecnologia/métodos , Nanotubos de Carbono/química , Química/métodos , Eletroquímica/métodos , Elétrons , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Silício/química , Transistores Eletrônicos
18.
J Phys Chem B ; 110(43): 21408-11, 2006 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-17064086

RESUMO

Field effect transistors have been fabricated using Bi2S3 nanowires. Whether the contact is ohmic or non-ohmic, the current of Bi2S3 nanowires was found to increase remarkably in H2 compared to that in a vacuum. Carrier density and mobility within the nanowires and the contact barriers between the nanowires and the electrodes have been extracted using field effect and two-probe current-voltage curves. It was found that H2 enhances electronic mobility and carrier density within the nanowires dramatically. The effect of H2 on the contact barriers was observed to be negligible compared to the other two effects.

19.
J Phys Chem B ; 109(37): 17361-5, 2005 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-16853219

RESUMO

Field-effect transistors (FETs) have been fabricated using double-walled carbon nanotubes (DWCNTs), and electrical transport measurements have been carried out on 125 DWCNT FETs. Among these devices, 52 were found to show basically semiconducting field-effect characteristics, 44 show metallic characteristics, and 29 show neither pure semiconducting nor metallic characteristics. These 3 distinct types of field-effect characteristics were identified as resulting from the semiconducting (S)-S, metallic (M)-M or M-S, and S-M combinations of the two shells of the DWCNT. While the S-S and M-M or M-S DWCNT devices exhibit similar field-effect characteristics to those by single-walled carbon nanotube (SWCNT) devices, the S-M device responds uniquely to the external gate voltage. In particular, it was found that free charges in the inner metallic shell may screen the outer semiconducting shell from the gate effect and that the screening is directly related to the intershell interaction, which increases with increasing temperature and tube diameter. The screening is disadvantageous to the performance of DWCNT FETs, and a similar effect is expected to occur in MWCNTs.

20.
Micron ; 35(6): 495-502, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15120136

RESUMO

A four nanoprobe system has been installed inside a FEI XL30 F scanning electron microscope (SEM), and shown to be fully compatible with the normal functions of the SEM and also a Gatan cold stage (model C1003, -185-400 degrees C). With some selected examples of applications, we have shown that this nanoprobe system may be used effectively for gripping, moving and manipulating nanoobjects, e.g. carbon nanotubes, setting up electric contacts for electronic measurements, tailoring the structure of the nanoobject by cutting, etc. and even for making unexpected nanostructures, e.g. a nanohook. Applications in other areas have also been speculated, limitations or disadvantages of the current design of the probe system were discussed, and methods for possible improvement were suggested.

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