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1.
Appl Opt ; 63(9): 2306-2313, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38568586

RESUMO

In recent years, significant advancements have been made in the field of computational imaging, particularly due to the application of deep learning methods to imaging problems. However, only a few studies related to deep learning have examined the impact of diffraction distance on image restoration. In this paper, the effect of diffraction distance on image restoration is investigated based on the PhysenNet neural network. A theoretical framework for diffraction images at various diffraction distances is provided along with the applicable propagators. In the experiment, the PhysenNet network is selected to train on diffraction images with different distances and the impact of using different propagators on network performance is studied. Optimal propagators required to recover images at different diffraction distances are determined. Insights obtained through these experiments can expand the scope of neural networks in computational imaging.

2.
Am Heart J ; 273: 111-120, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38677504

RESUMO

BACKGROUND: The Fontan operation is used to palliate single ventricle congenital heart defects (CHD) but poses significant morbidity and mortality risks. We present the design, planned analyses, and rationale for a long-term Fontan cohort study aiming to examine the association of patient characteristics at the time of Fontan with post-Fontan morbidity and mortality. METHODS AND RESULTS: We used the Pediatric Cardiac Care Consortium (PCCC), a US-based, multicenter registry of pediatric cardiac surgeries to identify patients who underwent the Fontan procedure for single ventricle CHD between 1 and 21 years of age. The primary outcomes are in-hospital Fontan failure (death or takedown) and post-discharge mortality through 2022. A total of 1461 (males 62.1%) patients met eligibility criteria and were included in the analytical cohort. The median age at Fontan evaluation was 3.1 years (IQR: 2.4-4.3). While 95 patients experienced in-hospital Fontan failure (78 deaths and 17 Fontan takedown), 1366 (93.5%) survived to discharge with Fontan physiology and formed the long-term analysis cohort. Over a median follow-up of 21.2 years (IQR: 18.4-24.5) 184 post-discharge deaths occurred. Thirty-year post Fontan survival was 75.0% (95% CI: 72.3%-77.8%) for all Fontan types with higher rates for current techniques such as lateral tunnel and extracardiac conduit 77.1% (95% CI: 73.5-80.8). CONCLUSION: The PCCC Fontan study aims to identify predictors for post-Fontan morbidity and mortality, enabling risk- stratification and informing surveillance practices. Additionally, the study may guide therapeutic interventions aiming to optimize hemodynamics and enhance Fontan longevity for individual patients.

3.
Am Heart J ; 268: 9-17, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37967642

RESUMO

BACKGROUND: Cardiovascular conditions are considered risk factors for poor outcomes associated with COVID-19. However, the effect of the COVID-19 pandemic on the mortality of patients with congenital heart disease (CHD) is unclear. Our study aims to examine the trends in mortality risk of CHD patients during the COVID-19 pandemic. METHODS: This is a retrospective cohort study from the Pediatric Cardiac Care Consortium, a US-based registry of interventions for CHD. We included patients having US residence and direct identifiers; death events were captured by matching with the National Death Index. The observation window (2017-2022) was divided into pre-COVID-19 and COVID-19 era defined around the national onset of COVID-19 disease in 2020. Stratified Cox model was used to assess all-cause mortality between the pre- and the COVID-19 era. RESULTS: Among 45,130 patients with CHD (median age in 2017: 23.3 years, IQR: 19.0-28.4), 503 deaths occurred during the pandemic with 44 deaths (8.7%) attributed to COVID-19 (COVID-19 mortality rate of 0.09%). The overall risk of death for patients with all types of CHD during the pandemic was significantly higher compared to the pre-COVID-19 era (aHR 1.28, 95%CI: 1.08-1.53), with a differential trend towards increased risk in patients with two-ventricle (aHR 1.44, 95% CI: 1.19-1.76) vs unchanged risk for those with single ventricle CHD (aHR = 0.83, 95% CI: 0.57-1.21). Adjusted subgroup analysis revealed a higher risk of death during the pandemic for CHD patients with male and chromosomal abnormalities. The excess deaths during the pandemic were attributed to COVID-19 itself rather than CHD or cardiovascular conditions. CONCLUSION: In this large CHD cohort study, there was a higher risk of death among CHD patients with male and chromosomal abnormalities. A differential trend towards higher risk for those with two vs. unchanged risk for single ventricle CHD was presented. The excess mortality was attributed to the COVID-19 itself and not to conditions potentially related to deferral of care. These results justify targeted protective measures towards the CHD population and may provide guidance for public health and medical care response in future epidemics.


Assuntos
COVID-19 , Doenças Cardiovasculares , Cardiopatias Congênitas , Humanos , Masculino , Criança , Adulto Jovem , Adulto , Estudos de Coortes , Pandemias , Estudos Retrospectivos , Aberrações Cromossômicas
4.
J Trace Elem Med Biol ; 72: 126992, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35550984

RESUMO

OBJECTIVE: Previous studies found that arsenic exposures have been linked to prostate cancer risk. However, this finding has been inconsistent. The purpose of this paper was to estimate the effects of arsenic exposures on prostate cancer risk. METHOD: We conducted a meta-analysis of epidemiologic studies of arsenic exposures and prostate cancer risk. We searched for both arsenic exposure and prostate cancer studies published until January 2021 from the following electronic databases: PubMed, Scopus, and Web of Science. Multilevel meta-analysis via random-effects modeling was used to examine the association between arsenic exposures and prostate cancer risk. RESULTS: There were 12 studies included with an effect size of 23. Arsenic exposure was determined from water and soil (n = 8), urinary measurements (n = 2), or self-reported questionnaire (n = 2). Overall, arsenic exposure was found to be statistically significantly associated with prostate cancer risk (Relative risk [RR] = 1.18, 95% confidence interval [CI]: 1.06 - 1.30). In the sub-analysis, arsenic exposure from water and soil was found to be statistically significantly associated with prostate cancer risk (RR= 1.22, 95% CI: 1.05 - 1.41). CONCLUSION: Data suggest that arsenic exposures may play a role in increasing prostate cancer risk. Further prospective studies are warranted to verify the association between arsenic exposure and prostate cancer risk.


Assuntos
Arsênio , Neoplasias da Próstata , Arsênio/análise , Arsênio/toxicidade , Humanos , Masculino , Estudos Prospectivos , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/epidemiologia , Solo , Água
5.
Front Psychol ; 13: 822564, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265017

RESUMO

In this study, we used data from the second wave of Midlife in the United States (MIDUS) Study, MIDUS Biomarkers and MIDUS 3. We applied the serial mediation model to explore the serial mediating effects of perceived stress and depressive symptoms on the relationship between sleep quality and life satisfaction. A total of 945 participants were included in our study. The total indirect effect of sleep quality on life satisfaction through perceived stress, depressive symptoms and the combination of perceived stress and depressive symptoms accounted for within the overall model was 45.5%. At the intervention level, programs designed to improve the level of life satisfaction among adults should focus on perceived stress and depressive symptoms. The prevention of perceived stress and depression contributes to improving life satisfaction and wellbeing. The serial mediation results should be confirmed by further longitudinal study.

6.
Cancer ; 128(9): 1832-1839, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35195279

RESUMO

BACKGROUND: Exposures to arsenic (As) and cadmium (Cd) have been associated with higher prostate cancer (PC) mortality; however, these associations have been inconsistent. The authors investigated whether higher ambient air concentrations of As and Cd are associated with lower overall and PC-specific survival among PC cases in Pennsylvania. METHODS: Incident PC cases of patients, aged 40 years or older, with a clinical diagnosis and nonmetastatic disease were identified in the 2004 to 2014 Pennsylvania Cancer Registry. Demographic, clinical, and pathologic information were extracted from the Pennsylvania Cancer Registry. The 3- and 5-year average and cumulative air concentrations of As and Cd were extracted from the Environmental Protection Agency's Toxics Release Inventory database. Spatial-temporal hierarchical accelerated failure time models were used to examine the associations between air concentrations of As and Cd and overall and PC-specific survival for the total population and stratified by geographical region defined by rurality and Appalachia status, after adjusting for confounders. RESULTS: There were 78,914 PC cases included. Increasing 3- and 5-year average and cumulative air concentrations of As and Cd were significantly associated with lower overall and PC-specific survival among cases, after adjusting for confounders, for the total population, and stratified by geographical region for most of the estimates. CONCLUSIONS: Data suggest that increasing ambient air exposures to As and Cd may play a role in overall and PC-specific mortality risk among PC cases. Exposures to As and Cd are modifiable and may provide insight into potential strategies to improve PC health outcomes. LAY SUMMARY: Arsenic and cadmium exposures linked to increased prostate cancer deaths remain unclear. We investigated whether air levels of arsenic and cadmium reported to be released from industries decrease overall and prostate cancer-specific survival among prostate cancer cases identified in the 2004 to 2014 Pennsylvania Cancer Registry. Among the 78,914 prostate cancer cases, increasing air levels of arsenic and cadmium are found to be associated with lower overall and prostate cancer-specific survival for the total population and within rural and urban Appalachia and urban non-Appalachia counties in Pennsylvania. Reducing exposures to arsenic and cadmium have the potential to decrease prostate cancer deaths.


Assuntos
Arsênio , Neoplasias da Próstata , Cádmio , Humanos , Masculino , Pennsylvania/epidemiologia , Próstata , Neoplasias da Próstata/epidemiologia
8.
BMJ Open ; 10(10): e039464, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046473

RESUMO

OBJECTIVES: Breast cancer is the most prevalent cancer and the second leading cause of cancer-related deaths among women after cervical cancer in much of sub-Saharan Africa. This study aims to examine the prevalence and sociodemographic-socioeconomic factors associated with breast cancer screening among women of reproductive age in sub-Saharan Africa. DESIGN: A weighted population-based cross-sectional study using Demographic and Health Surveys (DHS) data. We used all available data on breast cancer screening from the DHS for four sub-Saharan African countries (Burkina Faso, Ivory Coast, Kenya and Namibia). Breast cancer screening was the outcome of interest for this study. Multivariable Poisson regression was used to identify independent factors associated with breast cancer screening. SETTING: Four countries participating in the DHS from 2010 to 2014 with data on breast cancer screening. PARTICIPANTS: Women of reproductive age 15-49 years (N=39 646). RESULTS: The overall prevalence of breast cancer screening was only 12.9% during the study period, ranging from 5.2% in Ivory Coast to 23.1% in Namibia. Factors associated with breast cancer screening were secondary/higher education with adjusted prevalence ratio (adjusted PR)=2.33 (95% CI: 2.05 to 2.66) compared with no education; older participants, 35-49 years (adjusted PR=1.73, 95% CI : 1.56 to 1.91) compared with younger participants 15-24 years; health insurance coverage (adjusted PR=1.57, 95% CI: 1.47 to 1.68) compared with those with no health insurance and highest socioeconomic status (adjusted PR=1.33, 95% CI : 1.19 to 1.49) compared with lowest socioeconomic status. CONCLUSION: Despite high breast cancer mortality rates in sub-Saharan Africa, the prevalence of breast cancer screening is substantially low and varies gradually across countries and in relation to factors such as education, age, health insurance coverage and household wealth index level. These results highlight the need for increased efforts to improve the uptake of breast cancer screening in sub-Saharan Africa.


Assuntos
Neoplasias da Mama , Detecção Precoce de Câncer , Adolescente , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Burkina Faso/epidemiologia , Côte d'Ivoire/epidemiologia , Estudos Transversais , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Quênia/epidemiologia , Pessoa de Meia-Idade , Namíbia/epidemiologia , Prevalência , Adulto Jovem
9.
PLoS One ; 15(7): e0235379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628722

RESUMO

AIM: To estimate the pooled prevalence and incidence of suicidal ideation, attempts, and deaths in people with sleep apnea. METHOD: We will identify epidemiological studies reporting the prevalence or incidence rate of suicide in people with sleep apnea. We will search the following databases: PubMed (MEDLINE), Scopus, Cochrane Library, OVID (HEALTH STAR), OVID (MEDLINE) and Joana Briggs Institute EBF Database. No age, geographical location, study-design or language limits will be applied. This protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. Two reviewers (YY and YP) will independently screen citations, abstracts and will identify full-text articles for inclusion, extract data, and appraise the quality and bias of included studies. Discrepancies will be resolved by consulting with a third researcher (MC). Study quality will be assessed by the Newcastle-Ottawa Scale. The primary outcomes will be the overall prevalence or incidence of suicidal ideation, attempts and completion and the risk of suicide in people with sleep apnea. For pooling of the studies, we will use a random-effects model with a logit transformation. The DerSimonian and Laird (DL) random-effects method will be used to estimate the pooled inter-study variance. We will assess the between-study heterogeneity using I2 statistics, and Cochrane's Q statistic (significance level < 0.05). If the I2 is high (>75%), we will perform subgroup meta-analyses and conduct a meta-regression analysis to explore sources of study heterogeneity using study level median age, study-level proportions of race, gender, depression and quality scores. We will report effect estimates as suicide risk per 1000 individuals. Egger's test and funnel plots will be used to assess publication bias, and adjusted estimates using trim and fill methods will be reported if publication bias is suspected. ETHICS AND DISSEMINATION: No ethics clearance is required as no primary data will be collected. The results of this systematic review and meta-analysis will be presented at scientific conferences and published in a peer-review journal. The results may shed more light on the burden of suicide risk among individuals with sleep apnea and may guide future population-specific interventions. TRIAL REGISTRATION: PROSPERO registration number: CRD42020165404.


Assuntos
Projetos de Pesquisa , Síndromes da Apneia do Sono/complicações , Ideação Suicida , Tentativa de Suicídio/estatística & dados numéricos , Suicídio Consumado/estatística & dados numéricos , Humanos , Incidência , Metanálise como Assunto , Prevalência , Pesquisa Qualitativa , Síndromes da Apneia do Sono/psicologia , Tentativa de Suicídio/psicologia , Revisões Sistemáticas como Assunto
10.
PLoS One ; 15(5): e0233615, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470055

RESUMO

BACKGROUND: Despite the high prevalence of childhood protein-energy malnutrition and vitamin A deficiency in sub-Saharan Africa, their association has not been explored in this region. A better understanding of the epidemiologic link could help define effective preventive strategies. We aimed to explore the association of vitamin A deficiency (VAD) with stunting, wasting, and underweight among preschool children in Uganda. METHOD: We analyzed a population-based, cross-sectional data of 4,765 children aged 6-59 months who participated in 2016 Demographic and Health Surveys conducted in Uganda. We utilized generalized linear mixed-effects models with logit link function, adjusting for potential confounders to estimate associations between VAD and stunting, wasting, and underweight. RESULTS: The prevalence of VAD was 8.9% (95% CI: 8.1% to 9.6%, n = 424). Twenty-seven percent were stunted (95% CI: 26.1% to 28.6, n = 1302), 4% wasted (95% CI: 3.6% to 4.7%, n = 196), and 17% underweight (95% CI: 16.0% to 18.2%, n = 813). After adjusting for household factors (e.g., wealth index, education and working status of parents, owning land for agriculture, livestock, herds, or farm animals), vitamin A supplementation, and community factors (e.g., population density, crop growing season lengths, place of residence), children with VAD had 43% higher odds of stunted growth than those without VAD (adjusted odds ratio, 1.43 (95% CI: 1.08 to 1.89, p = 0.01). No association was observed between VAD and wasting or underweight. CONCLUSION: Vitamin A deficiency was associated with higher odds of stunting, and the association was independent of the individual, household, and community-level variables.


Assuntos
Transtornos do Crescimento/complicações , Deficiência de Vitamina A/complicações , Pré-Escolar , Estudos Transversais , Transtornos do Crescimento/epidemiologia , Humanos , Lactente , Razão de Chances , Prevalência , Magreza/complicações , Magreza/epidemiologia , Uganda/epidemiologia , Deficiência de Vitamina A/epidemiologia , Síndrome de Emaciação/complicações , Síndrome de Emaciação/epidemiologia
11.
J Affect Disord ; 265: 85-90, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31957696

RESUMO

BACKGROUND: Fatigue influences doctors' physical and mental health seriously, additionally, the topic has received wide attention recently. This study aimed to identify the association among resilience, perceived organizational support (POS) and fatigue, and to further explore whether POS could be a moderator in the association between resilience and fatigue in Chinese doctors. METHODS: A cross-sectional study was conducted in Liaoning Province in China in 2018. Out of 1000 randomly selected doctors, 866 completed the Chalder Fatigue Scale, the Connor-Davidson Resilience Scale, Survey of Perceived Organizational Support, and the questions about demographic characteristics and job condition variables. The association among resilience, POS and resilience × POS interaction with physical and mental fatigue were examined by hierarchical multiple regression. Simple slope analysis was conducted to visualize the interaction. RESULTS: The association between resilience and physical fatigue was gradually increased in the low (1 standard deviation [SD] below the mean, ß = -0.127, P< 0.05), mean (ß = -0.292, P < 0.05) and high (1 SD above the mean, ß = -0.457, P < 0.05) groups of POS. Additionally, the association was also different in the low (1 SD below the mean, ß = -0.240, P < 0.01), mean (ß = -0.357, P < 0.01) and high (1 SD above the mean, ß = -0.474, P < 0.01) groups of POS. LIMITATIONS: Due to the cross-sectional design, the study cannot draw any conclusion of causal relationships among study variables. CONCLUSIONS: POS could moderate the association among resilience, physical and mental fatigue. More interventions related to resilience and POS will be helpful to alleviate fatigue among Chinese doctors.


Assuntos
Médicos , Resiliência Psicológica , China , Estudos Transversais , Humanos , Saúde Mental , Inquéritos e Questionários
12.
Can J Diabetes ; 42(6): 652-658, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29936075

RESUMO

OBJECTIVES: It is unclear whether liver enzymes or the interactions of various liver enzymes is a predictor of type 2 diabetes mellitus (T2DM), which is independent of fatty liver. METHODS: A total of 48,001 subjects participated in baseline examinations. Among the subjects, 33,355 were followed for an average of 2.2 years. Cox proportional hazard models were used to examine the adjusted associations of AST, GGT and ALT with T2DM. RESULTS: The cumulative incidence of T2DM was 8.05% to 9.02% for fatty liver and 2.25% to 4.10% for non-fatty liver, both showing statistically significant differences. Compared with the normal liver enzyme levels in the group with fatty liver, the adjusted incident hazard ratios in T2DM were: ALT 1.23 (95% CI 1.10 to 1.50); AST 1.30 (95% CI 1.07-1.59); and GGT 1.34 (95% CI 1.08 to 1.65). In addition, compared with the normal liver enzyme levels in the group with non-fatty liver, the adjusted incident hazard ratios in type 2 diabetes were: ALT 1.27 (95% CI 1.02 to 1.59); AST 1.33 (95% CI 1.02 to 1.59); and GGT 1.53 (95% CI 1.19 to 1.98). There are significant interactions of T2DM hazard ratios between GGT and ALT and between GGT and AST in addition to ALT and AST. CONCLUSIONS: Our results suggest that the incidence of T2DM in the group with fatty liver is significantly higher than that in the normal population, and the rise of serum AST, GGT and ALT levels are risk factors independent of fatty liver for the development of T2DM after adjusting for confounding factors.


Assuntos
Diabetes Mellitus Tipo 2/enzimologia , Fígado Gorduroso/enzimologia , Fígado/enzimologia , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , China/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Fígado Gorduroso/epidemiologia , Feminino , Glutamil Aminopeptidase/sangue , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores Socioeconômicos
13.
PLoS One ; 9(11): e113913, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25426938

RESUMO

The high expression of PACAP (pituitary adenylate cyclase-activating polypeptide)-preferring receptor PAC1 is associated with nerve injury and tumors. Our previous report (Yu R, et al. PLoS One 2012; 7: e51811) confirmed the dimerization of PAC1 and found that the M-PAC1 mutation in the N-terminal first Cys/Ala lost the ability to form dimers. In this study, Chinese hamster ovary (CHO-K1) cells overexpressing wild-type PAC1 (PAC1-CHO) had significantly higher anti-apoptotic activities against serum withdrawal-induced apoptosis associated with a lower caspase 3 activity and a higher Bcl-2 level in a ligand-independent manner than those of CHO cells overexpressing the mutant M-PAC1 (M-PAC1-CHO). PAC1-CHO had significantly higher ß-catenin, cyclin D1 and c-myc levels corresponding to the Wnt/ß-catenin signal than did M-PAC1-CHO. In addition, the Wnt/ß-catenin pathway inhibitor XAV939 significantly inhibited the anti-apoptotic activities of PAC1-CHO. Top-flash assays demonstrated that PAC1-CHO had a significantly stronger Wnt/ß-catenin signal than did M-PAC1-CHO. Acetylcysteine (NAC) as an inhibitor of the dimerization of PAC1 inhibited the anti-apoptotic activities that were endowed by PAC1 and decreased the Wnt/ß-catenin signal in Top-flash assays. In the PAC1 Tet (tetracycline)-on inducible gene expression system by doxycycline (Dox), higher expression levels of PAC1 resulted in higher anti-apoptotic activities that were associated with a stronger Wnt/ß-catenin signal. A similar correlation was also found with the down-regulation of PAC1 in the Neuro2a neuroblastoma cell. BiFC combined with fluorescence confocal imaging indicated that during serum-withdrawal-induced apoptosis, PAC1 dimers displayed significant endocytosis. These findings indicate that PAC1 has ligand-independent and dimer-dependent intrinsic/basal activity, conferring cells with anti-apoptotic activities against serum withdrawal, which is involved in the Wnt/ß-catenin signal and is associated with the endocytosis of PAC1 dimers. The discovery and study of the dimer-dependent basal activity of PAC1 not only help us understand the physiological and pathological role of PAC1 but also promote the development of drugs targeting PAC1.


Assuntos
Apoptose , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Proteínas Wnt/metabolismo , Via de Sinalização Wnt , Animais , Células CHO , Cricetinae , Cricetulus , Endocitose , Camundongos , Mutação , Multimerização Proteica , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , beta Catenina/metabolismo
14.
Sheng Wu Gong Cheng Xue Bao ; 30(4): 636-43, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25195253

RESUMO

PAC1 is the neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) preferring receptor, which belongs to class B G protein-coupled receptors (GPCR) family. PAC1 mediates the most effects of PACAP as neurotransmitter, neuroregulator and neuroprotectant, while its high expression has close relationship with some physiological and pathological processes such as nerve-injury and tumor. To further understand the function of PAC1, a cell line that expressed inducible PAC1 was constructed to achieve Doxycycline (Dox) dependent expression of PAC1 in CHO (Chinese hamster ovary) cell using the improved Tet (tetracycline)-on Advanced System. First, the PAC1-EYFP fusion gene composed of PAC1 gene and gene encoding EYFP (enhanced yellow fluorescent protein) was sub-cloned to the tetracycline response element pTRE-Tight vector to construct the recombinant vector pEYFP-PAC1-EYFP by double enzyme digestion. Second, the tetracycline regulation components pTet-On advanced vector and the response element pTRE-PAC1-EYFP vector were both introduced into CHO cells successively and the positive clones were screened with G418 and hygromycin respectively. Third, the controlled expression of PAC1-EYFP in CHO was induced by tetracycline analogues Dox in different concentrations and the different levels of receptor PAC1-EYFP were detected. The results of fluorescence analysis and western blotting show that the cell strain with Dox dependent expression of PAC1-EYFP named PAC1-Tet-CHO was obtained. Moreover, in PAC1-Tet-CHO cells the expression of PAC1-EYFP was induced by Dox in a dose-dependent manner. The inducible expression of PAC1 still was stable after sub-culturing for more than 10 passages. It was also found by MTT assay that the higher expression level of PAC1 endowed the cells with higher proliferative viabilities. The construction of controlled expression system of PAC1 will lay a foundation for the further research on PAC1 profiles.


Assuntos
Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/biossíntese , Animais , Western Blotting , Células CHO , Clonagem Molecular , Cricetinae , Cricetulus , Vetores Genéticos
15.
Peptides ; 60: 41-50, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25086267

RESUMO

A novel peptide VIP-TAT with a cell penetrating peptide TAT at the C-terminus of VIP was constructed and prepared using intein mediated purification with an affinity chitin-binding tag (IMPACT) system to enhance the brain uptake efficiency for the medical application in central nervous system. It was found by labeling VIP-TAT and VIP with fluorescein isothiocyanate (FITC) that the extension with TAT increased the brain uptake efficiency of VIP-TAT significantly. Then short-term and long-term treatment with scopolamine (Scop) was used to evaluate the effect of VIP-TAT or VIP on Scop induced amnesia. Both short-term and long-term administration of VIP-TAT inhibited the latent time reduction in step-through test induced by Scop significantly, but long-term administration of VIP aggravated the Scop induced amnesia. Long-term i.p. injection of VIP-TAT was shown to have positive effect by inhibiting the oxidative damage, apoptosis and the cholinergic system activity reduction that induced by Scop, while VIP exerted negative effect in brain opposite to that in periphery system. The in vitro data showed that VIP-TAT had not only protective but also proliferative effect on Neuro2a cells which was inhibited by PAC1 antagonist PACAP(6-38). Competition binding assay and cAMP assay confirmed that VIP-TAT had higher affinity and activation for PAC1 than VIP. So it was concluded that the significantly stronger protective effect of VIP-TAT against Scop induced amnesia than VIP was due to (1) the enhanced brain uptake efficiency of VIP-TAT and (2) the increased affinity and activation of VIP-TAT for receptor PAC1.


Assuntos
Amnésia/tratamento farmacológico , Receptores Tipo II de Peptídeo Intestinal Vasoativo/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Escopolamina/antagonistas & inibidores , Peptídeo Intestinal Vasoativo/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia , Produtos do Gene tat do Vírus da Imunodeficiência Humana/farmacologia , Amnésia/induzido quimicamente , Animais , Apoptose/efeitos dos fármacos , Células CHO , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cricetulus , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos , Fragmentos de Peptídeos/farmacologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/química , Relação Estrutura-Atividade , Peptídeo Intestinal Vasoativo/administração & dosagem , Peptídeo Intestinal Vasoativo/química , Produtos do Gene tat do Vírus da Imunodeficiência Humana/administração & dosagem , Produtos do Gene tat do Vírus da Imunodeficiência Humana/química
16.
Artigo em Chinês | MEDLINE | ID: mdl-16737588

RESUMO

OBJECTIVE: To explore the mechanisms of aluminum (Al)-induced neurotoxicity by studying the effect of aluminum on lipid peroxidation in rat's brain and its sex related difference. METHODS: Forty SD rats, both male and female, were exposed to aluminum through intraperitoneal injection of AlCl3 solution for 60 days at different dose. After exposure, the step down test was performed to examine the learning and memory abilities of rats, and the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in rat's cerebrum were detected by chemical method. The changes of ultrastructure in cortex were observed by transmission electron microscopy. RESULTS: The differences between the changes of all indexes of female and male rats in the same dose-group wasn't statistically significant (P > 0.05). Compared with the rats in the control group, the learning and memory abilities of the Al-exposed rats were significantly decreased (P < 0.05). The content of MDA was increased (P < 0.01) while the activity of SOD was decreased (P < 0.05). The membrane structure of neurons in cerebrum cortex of the Al-exposed rats were broken, dissolved and gone. CONCLUSION: Aluminum can accelerate lipid peroxidation in rat's brain, which may be one of the important intoxication mechanisms of aluminum. However, the sex-related difference of this effect have not yet been observed.


Assuntos
Alumínio/toxicidade , Encéfalo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/ultraestrutura , Relação Dose-Resposta a Droga , Feminino , Aprendizagem/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fatores Sexuais
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