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1.
Front Aging Neurosci ; 15: 1195424, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37674782

RESUMO

Aims: Our aim was to differentiate patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) from cognitively normal (CN) individuals and predict the progression from MCI to AD within a 3-year longitudinal follow-up. A newly developed Holo-Hilbert Spectral Analysis (HHSA) was applied to resting state EEG (rsEEG), and features were extracted and subjected to machine learning algorithms. Methods: A total of 205 participants were recruited from three hospitals, with CN (n = 51, MMSE > 26), MCI (n = 42, CDR = 0.5, MMSE ≥ 25), AD1 (n = 61, CDR = 1, MMSE < 25), AD2 (n = 35, CDR = 2, MMSE < 16), and AD3 (n = 16, CDR = 3, MMSE < 16). rsEEG was also acquired from all subjects. Seventy-two MCI patients (CDR = 0.5) were longitudinally followed up with two rsEEG recordings within 3 years and further subdivided into an MCI-stable group (MCI-S, n = 36) and an MCI-converted group (MCI-C, n = 36). The HHSA was then applied to the rsEEG data, and features were extracted and subjected to machine-learning algorithms. Results: (a) At the group level analysis, the HHSA contrast of MCI and different stages of AD showed augmented amplitude modulation (AM) power of lower-frequency oscillations (LFO; delta and theta bands) with attenuated AM power of higher-frequency oscillations (HFO; beta and gamma bands) compared with cognitively normal elderly controls. The alpha frequency oscillation showed augmented AM power across MCI to AD1 with a reverse trend at AD2. (b) At the individual level of cross-sectional analysis, implementation of machine learning algorithms discriminated between groups with good sensitivity (Sen) and specificity (Spec) as follows: CN elderly vs. MCI: 0.82 (Sen)/0.80 (Spec), CN vs. AD1: 0.94 (Sen)/0.80 (Spec), CN vs. AD2: 0.93 (Sen)/0.90 (Spec), and CN vs. AD3: 0.75 (Sen)/1.00 (Spec). (c) In the longitudinal MCI follow-up, the initial contrasted HHSA between MCI-S and MCI-C groups showed significantly attenuated AM power of alpha and beta band oscillations. (d) At the individual level analysis of longitudinal MCI groups, deploying machine learning algorithms with the best seven features resulted in a sensitivity of 0.9 by the support vector machine (SVM) classifier, with a specificity of 0.8 yielded by the decision tree classifier. Conclusion: Integrating HHSA into EEG signals and machine learning algorithms can differentiate between CN and MCI as well as also predict AD progression at the MCI stage.

2.
Proteomics Clin Appl ; 17(6): e2200081, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37376802

RESUMO

PURPOSE: Stroke is the sudden death of brain cells in a localized area due to an inadequate blood flow or blood vessel rupture, and it seriously affects the quality of life. The metabolite biomarkers are needed for predicting the functional outcome of acute ischemic stroke (AIS). EXPERIMENTAL DESIGN: To identify biomarkers for AIS, untargeted LC/MS metabolomics was performed on plasma samples from subjects with favorable prognosis (mRS ≤ 2) and unfavorable prognosis (mRS > 2). The identified markers were further absolutely quantified by a targeted MRM approach. RESULTS: There were 10 upregulated and 26 downregulated markers. Among these candidates, one was successfully identified as glycocholic acid and then absolutely quantified in plasma samples. Glycocholic acid could discriminate between subjects with favorable and unfavorable prognosis with an area under the curve (AUC) of 0.68 and odds ratio of 5.88. CONCLUSIONS AND CLINICAL RELEVANCE: Glycocholic acid was identified as a potential plasma metabolite marker of non-progressive outcomes after ischemic stroke and could serve as predictive prognostic markers for clinical acute stroke outcomes.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Prognóstico , Qualidade de Vida , Cromatografia Líquida , Espectrometria de Massas em Tandem , Acidente Vascular Cerebral/diagnóstico , Biomarcadores , Ácido Glicocólico , Metabolômica
3.
Int J Mol Sci ; 21(21)2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33114317

RESUMO

Melanoma is notoriously resistant to current cancer therapy. However, the chemoresistance mechanism of melanoma remains unclear. The present study unveiled that chemotherapy drug cisplatin induced the formation of giant cells, which exhibited enlargement in cell diameter and nucleus in mice and human melanoma cells. Giant cells were positive with melanoma maker S100 and cancer stem cell markers including ABCB5 and CD133 in vitro and in vivo. Moreover, giant cells retained the mitotic ability with expression of proliferation marker Ki-67 and exhibited multiple drug resistance to doxorubicin and actinomycin D. The mitochondria genesis/activities and cellular ATP level were significantly elevated in giant cells, implicating the demand for energy supply. Application of metabolic blockers such as sodium azide or 2-deoxy glucose abolished the cisplatin-induced giant cells formation and expression of cancer stemness markers. The present study unveils a novel chemoresistance mechanism of melanoma cells via size alteration and the anti-neoplastic strategy by targeting giant cells.


Assuntos
Trifosfato de Adenosina/metabolismo , Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Células Gigantes/patologia , Melanoma/tratamento farmacológico , Antígeno AC133/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Animais , Linhagem Celular Tumoral , Cisplatino/farmacologia , Desoxiglucose/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Gigantes/efeitos dos fármacos , Células Gigantes/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Proteínas S100/metabolismo , Azida Sódica/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Free Radic Biol Med ; 155: 29-36, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32450129

RESUMO

Stroke is a major public health problem and ranks third most common cause of death in adults worldwide. Thrombolysis with recombinant tissue plasminogen activator and endovascular thrombectomy are the main revascularization therapies for acute ischemic stroke. However, ischemia-reperfusion injury, mainly caused by oxidative/nitrosative stress injury, after revascularization therapy can result in worsening outcomes. For better clinical prognosis, more and more studies have focused on the pharmaceutical neuroprotective therapies against free radical damage. The impact of vitamin C (ascorbic acid) on oxidative stress-related diseases is moderate because of its limited oral bioavailability and rapid clearance. However, recent evidence of the clinical benefit of parenteral vitamin C administration has emerged, especially in critical care. In this study we demonstrated that parenteral administration of vitamin C significantly improved neurological deficits and reduced brain infarction and brain edema by attenuating the transient middle cerebral artery occlusion (tMCAO)-induced nitrosative stress, inflammatory responses, and the resultant disruptions of blood brain barrier and cerebral neuronal apoptosis. These results suggest that parenteral administration of vitamin C has potential as an adjuvant agent with intravenous thrombolysis or endovascular thrombectomy in acute treatment of ischemic stroke.


Assuntos
Isquemia Encefálica , Fármacos Neuroprotetores , Acidente Vascular Cerebral , Animais , Apoptose , Ácido Ascórbico/farmacologia , Barreira Hematoencefálica , Encéfalo , Isquemia Encefálica/tratamento farmacológico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Ratos , Ativador de Plasminogênio Tecidual
5.
Phys Chem Chem Phys ; 21(38): 21561-21567, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31538155

RESUMO

We theoretically investigated hydrogen evolution reaction (HER) on the XRD observed (100), (110), (111), and (210) surfaces of pyrite structure CoS2. The random structure searching method was employed in this work to thoroughly and less-biasedly identify the active sites for each considered surface. We calculated the free energy of hydrogen adsorption, and found that (110) and (210) surfaces are more active than the conventionally assumed (100) facet. While the lowest energy active site on the (100) and (210) surfaces is the five-coordinated transition metal site that is commonly seen in other HER catalysts, the lowest energy active site on the (110) surface is the two-coordinated S site, which is a S tetrahedron with two corners missing. Besides those lowest energy active sites, both (110) and (210) have more than one species of active site on the surface, including not fully coordinated transition metals and sulfur. We further explored the reaction for MnS2, FeS2, and NiS2, and analyzed the density of states. Our results showed both CoS2 and NiS2 (110) and (210) surfaces are catalytically reactive for HER.

6.
Rehabil Nurs ; 42(2): 80-89, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-25424728

RESUMO

PURPOSE: Female stroke victims have a higher survival rate and experience a greater loss of quality of life than do male stroke victims. The aim of this study was to evaluate the determinants of health-related quality of life in middle-aged women stroke survivors. DESIGN: This study is a cross-sectional design. METHODS: This cross-sectional research uses a descriptive, prospective, and correlational study design to investigate the associations between latent variables. Participants included women stroke survivors, aged 45-65 years, who were patients at a medical center in Taiwan. Participants completed an interview and a six-part questionnaire comprising the Short-Form Health Survey (SF-36), National Institutes of Health Stroke Scale, Modified Rankin Scale, Burden Scale, Chinese Health Questionnaire, and five items that pertain to the survivor's cognitive appraisal of coping. Structural equation modeling (SEM), with the use of the partial least squares (PLS) method, was used to examine the proposed conceptual model. FINDINGS: A total of 48 dyad samples (48 female stroke survivors, mean age = 55.29; 48 caregivers, mean age = 42.71) participated in the study. Overall, women's physical functioning (PF; stroke severity), cognitive appraisal of coping, and caregiver's psychosocial functioning were the predictors, explaining 43.3% of the variance in women's health-related quality of life. CONCLUSIONS AND CLINICAL RELEVANCE: We found that female stroke survivors' level of stroke severity and negative appraisal-impact of stroke are significant predictors of the stroke survivor's quality of life. In addition to assisting women in their PF rehabilitation, rehabilitation nurses also should help to develop survivors' self-care confidence as a means to avoid the recurrence of stroke.


Assuntos
Qualidade de Vida/psicologia , Acidente Vascular Cerebral/psicologia , Sobreviventes/psicologia , Atividades Cotidianas , Idoso , Cuidadores/psicologia , Cuidadores/normas , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/instrumentação , Psicometria/métodos , Enfermagem em Reabilitação/métodos , Acidente Vascular Cerebral/complicações , Inquéritos e Questionários , Taiwan
7.
Mol Neurobiol ; 53(6): 3702-3713, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26126515

RESUMO

A diet consisting of high levels of saturated fat has been linked to a dramatic rise in obesity. Long-term exposure to high fat, "Western diet" (WD), is detrimental to ischemic brain injury. Adiponectin receptor 1 (ADR-1) activation is also shown to exacerbate ischemic neuronal death. However, it is not known whether increasing percentages of adiponectin (APN)-containing neurons attenuates ischemic neuronal apoptosis by modulating ADRS. To explore the role of APN and its ADRs in the development of acute cerebral injury, we subjected WD and control diet (CD) rats to 1 h of middle cerebral artery occlusion followed by 23 h of reperfusion. Compared with CD rats, WD rats exhibited higher levels of brain infarct, neurologic deficits, brain edema, and apoptosis of APN-containing neurons; upregulation of both ADR-1 and P38 mitogen-activated protein kinase (P38MAPK); and downregulation of ADR-2 in ischemic brain tissues including frontal cortex, striatum, and hippocampus. Increasing percentages of APN-containing neurons by baculovirus-mediated administration of APN, in addition to reducing apoptosis of APN-containing neurons in ischemic brain tissues, significantly attenuated brain infarct and edema, neurologic deficits, and altered expression of ADR-1, P38MAPK, and ADR-2 in both WD and CD group rats. These data suggest a negative correlation between percentages of APN-containing neurons and cerebral ischemic injury. Obesity could exacerbate rat cerebral ischemic injury by enhancing apoptosis of APN-containing neurons in ischemic brain tissues probably via modulating ADRs and P38MAPK.


Assuntos
Adiponectina/metabolismo , Apoptose , Isquemia Encefálica/patologia , Progressão da Doença , Neurônios/metabolismo , Neurônios/patologia , Obesidade/patologia , Animais , Antígenos Nucleares/metabolismo , Baculoviridae/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Edema Encefálico/complicações , Edema Encefálico/patologia , Infarto Encefálico/complicações , Infarto Encefálico/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/metabolismo , Contagem de Células , Regulação para Baixo , Indóis/metabolismo , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Injeções Intraventriculares , Masculino , Proteínas do Tecido Nervoso/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Ratos Sprague-Dawley , Receptores de Adiponectina/metabolismo , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
Mol Neurobiol ; 53(7): 4961-71, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26374550

RESUMO

Ischemic stroke, caused by obstruction of blood flow to the brain, would initiate microglia activation which contributes to neuronal damage. Therefore, inhibition of microglia-mediated neuroinflammation could be a therapeutic strategy for ischemic stroke. This study was aimed to elucidate the anti-inflammatory effects of alpha-lipoic acid and etanercept given either singly or in combination in rats subjected to middle cerebral artery occlusion. Both α-lipoic acid and etanercept markedly reduced cerebral infarct, blood-brain barrier disruption, and neurological motor deficits with the former drug being more effective with the dosage used. Furthermore, when used in combination, the reduction was more substantial. Remarkably, a greater diminution in the serum levels of tumor necrosis factor-alpha as well as the brain levels of microglial activation (e.g., microgliosis, amoeboid microglia, and microglial overexpression of tumor necrosis factor-α) was observed with the combined drug treatment as compared to the drugs given separately. We conclude that inhibition of peripheral tumor necrosis factor-alpha as well as downregulation of brain microglial activation by alpha-lipoic acid or etanercept protect rat brain against ischemic stroke. Moreover, when both drugs were used in combination, the stroke recovery was promoted more extensively.


Assuntos
Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Etanercepte/administração & dosagem , Acidente Vascular Cerebral/metabolismo , Ácido Tióctico/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismo , Animais , Antioxidantes/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Isquemia Encefálica/patologia , Isquemia Encefálica/prevenção & controle , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Quimioterapia Combinada , Masculino , Fármacos Neuroprotetores/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/prevenção & controle , Fator de Necrose Tumoral alfa/antagonistas & inibidores
9.
J Clin Nurs ; 24(21-22): 3155-64, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26265435

RESUMO

AIMS AND OBJECTIVES: This study identified the factors that affect health-related quality of life at one and six months post-stroke in women who have undergone a mild stroke and that affect their informal caregivers' psychological health status. BACKGROUND: Middle-aged women perform the main care roles in a family. When they suffer a stroke, it upsets the equilibrium of their family life. DESIGN: This is a longitudinal design. METHODS: This prospective follow-up study recruited 41 middle-aged women stroke survivors (mean age = 54.95, SD = 9.63) and their informal caregivers (mean age = 41.56, SD = 15.93). The Short-Form Health Survey (SF-36) was used to assess stroke survivor's health-related quality of life, and the Chinese Health Questionnaire was used to measure the level of depression of the stroke survivor's informal caregiver. Data were analysed through descriptive statistics, Wilcoxon signed-rank tests and the generalised estimating equation approach for modelling repeatedly measures. RESULTS: All stroke survivors showed significant improvement in the physical component summary of the health-related quality of life at one and six months after stroke, but there was no significant difference in the mental component summary. In addition, there was no significant difference in the health of the informal caregivers of the women over time. Generalised estimating equation analysis showed that the most important determinant of mental component summary of health-related quality of life among women stroke survivors was cognitive appraisal. The informal caregivers' most important determinants of health status, as measured by level of depression, were their sense of coherence, burden and patients' mental component summary of the health-related quality of life. CONCLUSION: This study highlights the impact of cognitive appraisal in determining health-related quality of life of women stroke survivors and how it affects their caregivers' mental health. RELEVANCE TO CLINICAL PRACTICE: The findings of this study may contribute to home care nurses' understanding the importance of the psychosocial impact of the stroke for the survivor and their ability to help the surviving women to promote the confidence needed for self-care, which will contribute to their quality of life and affect their caregivers' health.


Assuntos
Cuidadores/psicologia , Transtornos Cognitivos/psicologia , Avaliação em Enfermagem , Acidente Vascular Cerebral/psicologia , Adulto , Transtornos Cognitivos/complicações , Transtornos Cognitivos/enfermagem , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/enfermagem , Inquéritos e Questionários , Sobreviventes/psicologia , Saúde da Mulher
10.
Psychiatry Res ; 220(1-2): 335-41, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25169892

RESUMO

Obsessive-compulsive disorder (OCD) is a chronic debilitating anxiety disorder significant in intrusive thoughts and compensation repetitive behaviors. Few studies have reported on this condition Asia. This study estimated the prevalence, incidence and psychiatric comorbidities of OCD in Taiwan. We identified study subjects for 2000-2008 with a principal diagnosis of OCD according to the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic criteria by using National Health Research Institute database. These patients received either outpatient or inpatient care for their condition. Rates were directly age- and sex-adjusted to the 2004 Taiwan population distribution. The estimated mean annual incidence was 27.57 per 10(5) inhabitants and the one year prevalence was 65.05 per 10(5) inhabitants. Incidence and prevalence increased with age, peaking at age 18-24 years in males and at 35-44 years in females. About 53% of adults (≥18 years) and 48% of child and adolescent patients (6-17 years) had one or more comorbid psychiatric conditions. The most common comorbid diagnosis was depressive disorders for both adult and child-adolescent patients. We found a lower prevalence and incidence of clinically diagnosed OCD than that of community studies. Many Asian patients with OCD also had various psychiatric comorbidities, a clinically relevant finding.


Assuntos
Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/psicologia , Vigilância da População , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Comorbidade , Bases de Dados Factuais , Transtorno Depressivo/diagnóstico , Feminino , Seguimentos , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico , Vigilância da População/métodos , Prevalência , Estudos Prospectivos , Sistema de Registros , Taiwan/epidemiologia , Adulto Jovem
11.
J Pediatr ; 164(1): 136-141.e1, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24112864

RESUMO

OBJECTIVE: To delineate the relationship between traumatic brain injury (TBI) and mood disorders from population-based data in Taiwan. STUDY DESIGN: This prospectively followed cohort study involved a subset of the National Health Insurance Research Database containing complete inpatient and outpatient data of 1 million randomly drawn beneficiaries. We included 10- to 24-year-old patients (n = 15,203) receiving the diagnosis of TBI in ambulatory visits or hospitalization from 2000-2004 and their age- and sex-matched comparison insureds using health service in the same year (n = 76,015). Diagnosis of mood disorders was recorded within 5 years after the traumatic event or index use of health service. Baseline demographics, clinical characteristics, and premorbid psychiatric conditions were compared using χ(2) analysis. Increased risk during the 5-year follow-up period was represented by crude and adjusted hazard ratios with 95% CI using a Cox proportional hazard regression. RESULTS: A total of 451/15,203 patients with TBI (2.97%) received a diagnosis of mood disorders in the 5-year follow-up period compared with 1153/97,445 individuals (1.52%) without antecedent TBI. After adjusting for select premorbid comorbidities, TBI remained a significant predisposing factor with a 1.96-fold (95% CI 1.74-2.22) increase in risk of mood disorders. CONCLUSIONS: Our findings show a higher likelihood of manifesting mood disorders in adolescents and young adults who sustained a prior TBI. Health professionals should carefully monitor both the physical and psychological impacts of head trauma.


Assuntos
Lesões Encefálicas/complicações , Transtornos do Humor/epidemiologia , Vigilância da População/métodos , Adolescente , Adulto , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/epidemiologia , Criança , Comorbidade , Feminino , Seguimentos , Humanos , Incidência , Masculino , Transtornos do Humor/etiologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taiwan/epidemiologia , Índices de Gravidade do Trauma , Adulto Jovem
12.
J Neurol Neurosurg Psychiatry ; 83(11): 1080-5, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22842203

RESUMO

OBJECTIVE: The relationship between traumatic brain injury (TBI) and the risk of dementia remains controversial. This population based study was designed to estimate and compare the risk of dementia in TBI and non-TBI individuals during the 5 year period after TBI. METHODS: This study was a retrospective cohort study. Data were obtained from the Longitudinal Health Insurance Database 2000. We included 44,925 patients receiving ambulatory or hospital care and 224,625 non-TBI patients; patients were matched for sex, age and year of index use of healthcare. Patients <15 years of age and those admitted to the intensive care unit were excluded. Each individual was studied for 5 years to identify the subsequent development of dementia. Data were analysed by Cox proportional hazard regression. RESULTS: During the 5 year follow-up period, 1196 TBI (2.66%) and 224,625 non-TBI patients (1.53%) patients developed dementia. During the 5 year follow-up period, TBI was independently associated with a 1.68 (range 1.57-1.80) times greater risk of dementia after adjusting for sociodemographic characteristics and selected comorbidities. CONCLUSIONS: The findings of this study suggest an increased risk of dementia among individuals with TBI. We suggest the need for more intensive medical monitoring and health education in individuals with TBI.


Assuntos
Lesões Encefálicas/epidemiologia , Bases de Dados Factuais/estatística & dados numéricos , Demência/epidemiologia , Adolescente , Adulto , Idoso , Lesões Encefálicas/complicações , Comorbidade , Demência/complicações , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
13.
Int J Mol Sci ; 13(4): 4351-4366, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22605982

RESUMO

Ultraviolet C (UVC) is a DNA damage inducer, and 20 J/m(2) of UVC irradiation caused cell growth inhibition and induced cell death after exposure for 24-36 h. The growth of NIH 3T3 cells was significantly suppressed at 24 h after UVC irradiation whereas the proliferation of A431 cells was inhibited until 36 h after UVC irradiation. UVC irradiation increased COX-2 expression and such up-regulation reached a maximum during 3-6 h in NIH 3T3 cells. In contrast, UVC-induced COX-2 reached a maximum after 24-36 h in A431 cells. Measuring prostaglandin E2 (PGE2) level showed a biphasic profile that PGE2 release was rapidly elevated in 1-12 h after UVC irradiation and increased again at 24 h in both cell lines. Treatment with the selective COX-2 inhibitor, SC-791, during maximum expression of COX-2 induction, attenuated the UVC induced-growth inhibition in NIH 3T3 cells. In contrast, SC-791 treatment after UVC irradiation enhanced death of A431 cells. These data showed that the patterns of UVC-induced PGE2 secretion from NIH 3T3 cells and A431 cells were similar despite the differential profile in UVC-induced COX-2 up-regulation. Besides, COX-2 might play different roles in cellular response to UVC irradiation in various cell lines.


Assuntos
Ciclo-Oxigenase 2/biossíntese , Dinoprostona/biossíntese , Isoxazóis/farmacologia , Sulfonamidas/farmacologia , Raios Ultravioleta/efeitos adversos , Células 3T3 , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Inibidores de Ciclo-Oxigenase 2/farmacologia , Dinoprostona/metabolismo , Humanos , Camundongos , Regulação para Cima/efeitos da radiação
14.
J Neurotrauma ; 29(7): 1518-29, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22332641

RESUMO

Magnesium sulfate and nimesulide are commonly used drugs with reported neuroprotective effects. Their combination as stroke treatment has the potential benefits of decreasing individual drug dosage and fewer adverse effects. This study evaluated their synergistic effects and compared a low-dose combination with individual drug alone and placebo. Sprague-Dawley rats underwent 90 min of focal ischemia with intraluminal suture occlusion of the middle cerebral artery followed by reperfusion. The rats were randomly assigned to receive one of the following treatments: placebo, magnesium sulfate (MgSO4; 45 mg/kg) intravenously immediately after the induction of middle cerebral artery occlusion, nimesulide (6 mg/kg) intraperitoneally before reperfusion, and combined therapy. Three days after the ischemia-reperfusion insult, therapeutic outcome was assessed by 2,3,5-triphenyltetrazolium chloride staining and a 28-point neurological severity scoring system. Cyclooxygenase-2, prostaglandin E2, myeloperoxidase, and caspase-3 expression after treatment were evaluated using Western blot analyses and immunohistochemical staining, followed by immunoreactive cell analysis using tissue cytometry. Only the combination treatment group showed a significant decrease in infarction volume (10.93±6.54% versus 26.43±7.08%, p<0.01), and neurological severity score (p<0.05). Low-dose MgSO4 or nimesulide showed no significant neuroprotection. There was also significant suppression of cyclooxygenase-2, prostaglandin E2, myeloperoxidase, and caspase-3 expression in the combination treatment group, suggesting that the combination of the two drugs improved the neuroprotective effects of each individual drug. MgSO4 and nimesulide have synergistic effects on ischemia-reperfusion insults. Their combination helps decrease drug dosage and adverse effects. Combined treatment strategies may help to combat stroke-induced brain damage in the future.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Modelos Animais de Doenças , Sulfato de Magnésio/farmacologia , Sulfonamidas/farmacologia , Animais , Anticonvulsivantes/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Inibidores de Ciclo-Oxigenase/farmacologia , Sinergismo Farmacológico , Ratos , Ratos Sprague-Dawley
15.
Am J Med Sci ; 344(5): 383-90, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22245947

RESUMO

INTRODUCTION: Heatstroke has been defined as a form of hyperthermia associated with a systemic inflammatory response that leads to multiple organ dysfunction syndrome (MODS). It has also been documented that heat shock protein 70 (HSP70) preconditioning is able to induce thermotolerance. Here, the authors further investigated whether hypobaric hypoxia preconditioning (HHP) improved the MODS in heatstroke by up-regulation of HSP70. METHODS: Anesthetized rats were randomly assigned to (a) non-HHP + nonheated group, (b) non-HHP + heated group, (c) HHP + heated group and (d) HHP + HSP70 antibodies (Abs) + heated groups. All heated groups were exposed to heat stress (43°C, 70 minutes) to induce heatstroke. For HHP, animals were exposed to 0.66 atmosphere absolute (18.3% O2) for 5 hours daily for consecutive 5 days per week for 2 weeks before the start of heat exposure. RESULTS: HHP significantly (i) attenuated hypotension, (ii) reduced plasma index of the toxic oxidizing radicals and the organ injury indicator, (iii) attenuated plasma systemic inflammatory response molecules, (iv) reduced an index of infiltration of polymorphonuclear neutrophils in the lung like myeloper-oxidase activity, (v) promoted plasma levels of an anti-inflammatory cytokine, interleukin-10, (vi) promoted the survival time to fourfold compared with non-HHP group and (vii) promoted the overexpression of HSP70 in different organs (eg, the lung) during heatstroke. The beneficial effects of HHP could be significantly attenuated by HSP70 Ab preconditioning. CONCLUSION: Our results show that HHP protects rats from heat-induced MODS via up-regulating HSP70. Thus, HHP could be a novel strategy for the prevention of heatstroke animals or patients before heat exposure.


Assuntos
Proteínas de Choque Térmico HSP70/biossíntese , Golpe de Calor/prevenção & controle , Hipóxia/patologia , Animais , Encéfalo/metabolismo , Proteínas de Choque Térmico HSP70/imunologia , Proteínas de Choque Térmico HSP70/metabolismo , Golpe de Calor/sangue , Golpe de Calor/patologia , Interleucina-10/sangue , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
16.
Nat Prod Res ; 26(13): 1218-23, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22043982

RESUMO

A novel homosesquiterpenoid, burmanol (1), along with 16 known compounds, including one triterpenoid, one quinol, two chlorophylls, two coumarins, two steroids, three lignans and five benzenoids were obtained from the stems of Cinnamomum burmanii (Lauraceae). The structures of these compounds were determined on the basis of spectroscopic analysis.


Assuntos
Cinnamomum/química , Caules de Planta/química , Sesquiterpenos/análise , Clorofila/análise , Cumarínicos/análise , Lignanas , Estrutura Molecular , Sesquiterpenos/química , Esteroides/análise , Triterpenos/análise
17.
J Nutr Biochem ; 22(1): 46-52, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20303727

RESUMO

Nucleophosmin (NPM/B23) is a nucleolar phosphoprotein involved in cellular response to many different stimuli. Herein, we studied the molecular mechanism of NPM/B23 induction by curcumin, a natural AP-1 inhibitor with antitumor properties. Exposure to 5-30 µM curcumin significantly and dose-dependently increased the level of NPM/B23 in non-transformed NIH 3T3 cells but not HeLa cells and F9 cells. Besides, the transformed F9 and HeLa cells are more sensitive to curcumin-induced cell death and growth inhibition than NIH 3T3 cells. Overexpression of c-Jun, but not c-Fos, decreased ∼40% of NPM/B23 and enhanced the sensitivity of NIH 3T3 cells to 30 µM curcumin. Furthermore, down-regulation of NPM/B23 by transfection with NPM/B23 antisense plasmid enhanced the sensitivity to curcumin-induced cell death and growth inhibition. These results indicated that NPM/B23 expression regulates cellular sensitivity to curcumin. Besides, NPM/B23 knockdown may facilitate as a novel strategy to promote the sensitivity of cancer cells to curcumin.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Curcumina/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Fator de Transcrição AP-1/antagonistas & inibidores , Regulação para Cima/efeitos dos fármacos , Animais , Anticarcinógenos/farmacologia , Linhagem Celular Transformada , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células-Tronco de Carcinoma Embrionário , Células HeLa , Humanos , Camundongos , Células NIH 3T3 , Neoplasias/prevenção & controle , Proteínas Nucleares/genética , Nucleofosmina , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/metabolismo , Concentração Osmolar , Proteínas Proto-Oncogênicas c-jun/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-jun/genética , Proteínas Proto-Oncogênicas c-jun/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo
18.
Int J Food Microbiol ; 144(1): 104-10, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20884069

RESUMO

Exopolysaccharides (EPSs) are a metabolite of probiotics which have gained wide interest recently, but little is known about their function. EPS was isolated from Bifidobacterium longum BCRC 14634 and sterilized by 0.22 µm filter. The proliferation of J77A.1 macrophages and their secretion of the anti-inflammatory cytokine interleukin-10 (IL-10) was elevated after treatment with heat-killed B. longum or 5 µg/mL EPS. The endotoxin, lipopolysaccharides (LPS), a potent inducer of pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), significantly suppressed the growth of J77A.1 cells, and induced the secretion of TNF-α from J774A.1 cells. Furthermore, 24h pretreatment with 5 µg/ml EPS suppressed 100 ng/ml LPS-induced cell growth inhibition and release of TNF-α from J774A.1 cells. Additional experiments showed that 80 µg/mL EPS had antimicrobial activity against 7 species of food-spoilage and infection bacteria. Our results suggest that EPS from B. longum might be useful as a mild immune modulator for macrophages, contributing to the capacity of B. longum to fight against gastrointestinal infections, and even some food-spoilage microbe.


Assuntos
Anti-Infecciosos/farmacologia , Bifidobacterium/química , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Polissacarídeos Bacterianos/farmacologia , Probióticos , Animais , Anti-Infecciosos/imunologia , Anti-Infecciosos/metabolismo , Bifidobacterium/imunologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-10/imunologia , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Camundongos , Polissacarídeos Bacterianos/isolamento & purificação , Fator de Necrose Tumoral alfa/imunologia
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