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1.
Carcinogenesis ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32188964

RESUMO

The difference of the patients bearing hepatocellular carcinoma (HCC) with and without cirrhosis at clinical level has not been completely determined. This study compared their differences in clinicopathological traits and prognostic factors for recurrence-free survival (RFS) and overall survival (OS). Animal model was established to validate the result of clinical observation. As a result, 82 patients bearing HCC with no cirrhosis (HCC-NC) and 146 patients bearing HCC with cirrhosis (HCC-C) were included. HCC-NC exhibited shorter prothrombin time and higher plasma albumin than HCC-C. In HCC-NC, satellite nodule was an independent risk factor for OS, and high γ-GT was an independent risk factor for RFS. In HCC-C, female sex was an independent risk factor for OS. Stratified analysis showed the OS and RFS of HCC-NC were better than HCC-C in conditions like without cancer embolus (in the portal vein or bile duct), without lymphadenopathy in hepatic portal, without satellite nodule, and with small or high-differentiated tumor. Animal model analysis showed HCC-NC had a higher liver/body weight, lower tumor count, and lower max tumor volume than HCC-C. In conclusion, clinicopathological traits and risk factors influencing postoperative OS and RFS differed between patients with HCC-C and HCC-NC.

2.
J Asian Nat Prod Res ; 22(2): 167-178, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30507305

RESUMO

In this study, we developed a novel liquid fermentation medium of Cordyceps militaris using pupa powder and wheat bran as nitrogen resources instead of the traditionally used peptone. This process not only reduced the cost by approximately 50%, but increased production by over 30%. Then, we explored a method to extract and purify cordycepin by combining hydrothermal reflux extraction with macroporous resin adsorption, which is inexpensive and suitable for the industrial production. The optimum conditions for hydrothermal reflux were extracting three times at 95 °C with 1:10 sample-to-water ratio, and the cordycepin purity with macroporous resin HPD-100 reached 95.23%.[Formula: see text].


Assuntos
Cordyceps , Desoxiadenosinas , Fermentação , Estrutura Molecular
3.
Mol Cell Biochem ; 461(1-2): 81-89, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31342299

RESUMO

In pathogenesis of Parkinson's disease (PD), mitochondrial dysfunction causes substantial reactive oxygen species (ROS) production and oxidative stress, leading to dopaminergic (DA) neuronal cell death. Mitochondrial toxins, including MPP+ (1-methyl-4-phenylpyridinium ion) and rotenone, induce oxidative injury in cultured DA neuronal cells. The current study tested the potential effect of SC79, a first-in-class small-molecule Akt activator, against the process. In SH-SY5Y cells and primary murine DA neurons, SC79 significantly attenuated MPP+- and rotenone-induced viability reduction, cell death, and apoptosis. SC79 activated Akt signaling in DA neuronal cells. Akt inhibition (by LY294002 and MK-2206) or CRISPR-Cas9-mediated Akt1 knockout completely abolished SC79-induced DA neuroprotection against MPP+. Further studies demonstrated that SC79 attenuated MPP+- and rotenone-induced ROS production, mitochondrial depolarization, and lipid peroxidation in SH-SY5Y cells and primary DA neurons. Moreover, upregulation of Nrf2-dependent genes (HO1 and NQO1) and Nrf2 protein stabilization were detected in SC79-treated SH-SY5Y cells and primary DA neurons. Together we show that SC79 protects DA neuronal cells from mitochondrial toxins possibly via activation of Akt-Nrf2 signaling.


Assuntos
1-Metil-4-fenilpiridínio/toxicidade , Acetatos/farmacologia , Benzopiranos/farmacologia , Neurônios Dopaminérgicos/patologia , Ativadores de Enzimas/farmacologia , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Rotenona/toxicidade , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neurônios Dopaminérgicos/efeitos dos fármacos , Humanos , Camundongos Endogâmicos C57BL , Neuroproteção/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
4.
Cancer Lett ; 443: 13-24, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30503558

RESUMO

Advanced stage nasopharyngeal carcinoma (NPC) has a poor prognosis. Triptonide ("TN") is a small molecule monomer extract from the ancient Chinese herb Tripterygium wilfordii Hook. We show that TN, at nanomolar concentrations, potently inhibited survival and proliferation of multiple established and primary human NPC cells. TN induced NPC cell cycle arrest and apoptosis activation. NPC cell migration and invasion were also inhibited by TN. Importantly, TN was non-cytotoxic to nasopharyngeal epithelial cells. TN treatment in NPC cells disrupted LncRNA THOR ("Lnc-THOR")-IGF2BP1 association, causing depletion of Lnc-THOR and downregulation of IGF2BP1 mRNA targets (Myc, IGF2 and Gli1). Lnc-THOR or IGF2BP1 knockout by CRISPR/Cas9 gene-editing methods mimicked and abolished TN's actions in NPC cells. Conversely, ectopic Lnc-THOR overexpression inhibited TN-induced cytotoxicity in NPC cells. Significantly, Lnc-THOR, IGF2BP1 and its mRNA targets are elevated in human NPC tissues and cells, but almost undetectable in nasopharyngeal epithelial tissues and cells. In vivo, intraperitoneal TN administration significantly inhibited subcutaneous NPC xenograft growth in mice. Similarly, Lnc-THOR-knockout HONE-1 xenografts grew significantly slower than control tumors. Thus, TN inhibits human NPC cell growth in vitro and in vivo via disrupting Lnc-THOR-IGF2BP1 signaling.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Triterpenos/administração & dosagem , Animais , Antineoplásicos Fitogênicos/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Injeções Intraperitoneais , Masculino , Camundongos , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética , Triterpenos/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Int J Biol Macromol ; 125: 87-91, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30529348

RESUMO

In this paper, the catalytic performance of non-purified esterase from wheat bran immobilized on glass fibre membrane carrier is established, the immobilization conditions observed were enzyme 1 mL, phosphate buffer 3 mL (pH 7.0), immobilization time 1 h, immobilization temperature 29 °C. After carrier functionalization some characteristics of immobilized enzyme were studied, the results showed that immobilized enzyme presenting improved characteristic than that of free enzyme. The optimum pH for free and immobilized enzymes were found to be 8 and 7, respectively. As for optimum temperature for free and immobilized enzymes were observed to be 30 °C and 40 °C, respectively. When the enzyme was immobilized on glass fibre membranes, its Km increased about 7 times. In addition, storage and thermal stability of the free wheat esterase were increased by as a result of membrane immobilization, after 12 days of storage, the immobilized enzyme still retained about 91.10% of its original activity at 4 °C, indicating a great potential in industrial application.


Assuntos
Enzimas Imobilizadas , Esterases/química , Vidro , Triticum/química , Ativação Enzimática , Estabilidade Enzimática , Enzimas Imobilizadas/química , Esterases/isolamento & purificação , Esterases/metabolismo , Concentração de Íons de Hidrogênio , Cinética , Extração Líquido-Líquido , Temperatura Ambiente
6.
Theranostics ; 8(17): 4695-4709, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30279732

RESUMO

VEGF binding to VEGFR2 leads to VEGFR2 endocytosis and downstream signaling activation to promote angiogenesis. Methods: Using genetic strategies, we tested the requirement of α subunits of heterotrimeric G proteins (Gαi1/3) in the process. Results: Gαi1/3 are located in the VEGFR2 endocytosis complex (VEGFR2-Ephrin-B2-Dab2-PAR-3), where they are required for VEGFR2 endocytosis and downstream signaling transduction. Gαi1/3 knockdown, knockout or dominant negative mutation inhibited VEGF-induced VEGFR2 endocytosis, and downstream Akt-mTOR and Erk-MAPK activation. Functional studies show that Gαi1/3 shRNA inhibited VEGF-induced proliferation, invasion, migration and vessel-like tube formation of HUVECs. In vivo, Gαi1/3 shRNA lentivirus inhibited alkali burn-induced neovascularization in mouse cornea. Further, oxygen-induced retinopathy (OIR)-induced retinal neovascularization was inhibited by intravitreal injection of Gαi1/3 shRNA lentivirus. Moreover, in vivo angiogenesis by alkali burn and OIR was significantly attenuated in Gαi1/3 double knockout mice. Significantly, Gαi1/3 proteins are upregulated in proliferative retinal tissues of proliferative diabetic retinopathy (PDR) patients. Conclusion: These results provide mechanistic insights into the critical role played by Gαi1/3 proteins in VEGF-induced VEGFR2 endocytosis, signaling and angiogenesis.


Assuntos
Endocitose , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Neovascularização Fisiológica , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Técnicas de Silenciamento de Genes , Técnicas de Inativação de Genes , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Modelos Animais , Modelos Teóricos , Ligação Proteica
7.
J Food Sci Technol ; 55(7): 2786-2794, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30042595

RESUMO

Volatile oil in Chrysanthemum morifolium Ramat (C. morifolium) was extracted by the method of water vapor distillation and its chemical components was identified by gas-chromatography coupled with mass spectrometry (GC-MS). The volatile oil are evaluated for antibacterial activity against Escherichia coli, Staphylococcus aureus, Salmonella enteritids, Pseudomonas aeruginosa and Bacillus subtilis. Effects of surfactant, temperature, pH and ultraviolet light on antibacterial activity stability of volatile oil were analyzed too. Total 56 compounds were identified in C. morifolium volatile oil. The main constituents in C. morifolium volatile oil were monoterpenes and sesquiterpenes compounds, including hydrocarbons, esters, aldehydes, ketones, phenols and organic acids. α-curcumene was the most abundant volatile component (12.55%). The volatile oil showed promising antibacterial activity against 5 selected strains. The inhibitory effect on P. aeruginosa exhibited maximum inhibition zone diameter 20.43 mm, and E. coli showed 12.29 mm. The volatile oil treated with surfactant Tween 20 showed the strongest antibacterial activity, followed by Tween 80 and the SDS lowest, which showed the lowest. pH also had different effect on antibacterial activity stability of the C. morifolium volatile oil. No significant difference effect on antibacterial activity stability of volatile oil was observed with temperature and UV treatment.

8.
Cell Physiol Biochem ; 48(2): 450-460, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30016785

RESUMO

BACKGROUND/AIMS: Glioma causes significant human mortalities annually. Molecularly-targeted therapy is a focus of glioma research. METHODS: Grb2-associated binding 1 (Gab1) expression and microRNA-29a-3p ("miR-29a-3p") expression in human glioma cells and tissues were tested by Western blotting assay and qRT-PCR assay. shRNA/siRNA strategy was applied to silence Gab1 in human glioma cells. miR-29a or anti-sense miR-29a construct was transfected to human glioma cells. Cell proliferation was tested by BrdU ELISA assay and cell counting assay. RESULTS: We show that expression of Gab1 was significantly elevated in human glioma tissues and cells, which correlated with downregulation of its putative microRNA: miR-29a-3p. In A172 glioma cells and primary human glioma cells, Gab1 shRNA/siRNA inhibited Akt-Erk activation and cell proliferation. Forced-expression of miR-29a-3p downregulated Gab1, inhibiting glioma cell proliferation, whereas miR-29a-3p was in-effective on cell proliferation in Gab1-silenced A172 cells. Furthermore, introduction of a 3'-untranslated region (3'-UTR) mutant Gab1 (UTR-G160A) blocked miR-29a-3p-induced inhibition on Akt signaling and A172 cell proliferation. CONCLUSIONS: miR-29a-3p downregulation leads to Gab1 upregulation to promote glioma cell proliferation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Glioma/patologia , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Antagomirs/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glioma/metabolismo , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais
9.
Proc Natl Acad Sci U S A ; 115(15): E3549-E3558, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29507199

RESUMO

Stress-related alterations in brain-derived neurotrophic factor (BDNF) expression, a neurotrophin that plays a key role in synaptic plasticity, are believed to contribute to the pathophysiology of depression. Here, we show that in a chronic mild stress (CMS) model of depression the Gαi1 and Gαi3 subunits of heterotrimeric G proteins are down-regulated in the hippocampus, a key limbic structure associated with major depressive disorder. We provide evidence that Gαi1 and Gαi3 (Gαi1/3) are required for the activation of TrkB downstream signaling pathways. In mouse embryonic fibroblasts (MEFs) and CNS neurons, Gαi1/3 knockdown inhibited BDNF-induced tropomyosin-related kinase B (TrkB) endocytosis, adaptor protein activation, and Akt-mTORC1 and Erk-MAPK signaling. Functional studies show that Gαi1 and Gαi3 knockdown decreases the number of dendrites and dendritic spines in hippocampal neurons. In vivo, hippocampal Gαi1/3 knockdown after bilateral microinjection of lentiviral constructs containing Gαi1 and Gαi3 shRNA elicited depressive behaviors. Critically, exogenous expression of Gαi3 in the hippocampus reversed depressive behaviors in CMS mice. Similar results were observed in Gαi1/Gαi3 double-knockout mice, which exhibited severe depressive behaviors. These results demonstrate that heterotrimeric Gαi1 and Gαi3 proteins are essential for TrkB signaling and that disruption of Gαi1 or Gαi3 function could contribute to depressive behaviors.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/metabolismo , Subunidade alfa Gi2 de Proteína de Ligação ao GTP/biossíntese , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/biossíntese , Hipocampo/metabolismo , Animais , Dendritos/metabolismo , Dendritos/patologia , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/patologia , Depressão/patologia , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/patologia , Regulação para Baixo , Feminino , Subunidade alfa Gi2 de Proteína de Ligação ao GTP/genética , Subunidade alfa Gi2 de Proteína de Ligação ao GTP/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Neurônios/patologia , Transdução de Sinais/efeitos dos fármacos , Estresse Fisiológico/fisiologia
10.
Oncogene ; 37(21): 2890-2902, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29520106

RESUMO

We previously identified a pivotal role for G protein α inhibitory subunit 1 (Gαi1) in mediating PI3K-Akt signaling by receptor tyrosine kinases (RTKs). Here, we examined the expression and biological function of Gαi1 in human glioma. Gαi1 mRNA and protein expression were significantly upregulated in human glioma tissues, which correlated with downregulation of an anti-Gαi1 miRNA: microRNA-200a ("miR-200a"). Forced-expression of miR-200a in established (A172/U251MG lines) and primary (patient-derived) human glioma cells resulted in Gαi1 downregulation, Akt inactivation and proliferation inhibition. Reduction of Gαi1 expression by shRNA, dominant negative mutant interference, or complete Gαi1 depletion inhibited Akt activation and cell proliferation. Notably, miR-200a was unable to inhibit glioma cell proliferation when Gαi1 was silenced or mutated. Co-immunoprecipitation studies, in human glioma cells and tissues, show that Gαi1 forms a complex with multiple RTKs (EGFR, PDGFRα, and FGFR) and the adapter protein Gab1. In vivo, the growth of subcutaneous and orthotopic glioma xenografts in nude mice was largely inhibited by expression of Gαi1 shRNA or miRNA-200a. Collectively, miR-200a downregulation in human glioma leads to Gαi1 over-expression, Akt activation and glioma cell proliferation.


Assuntos
Neoplasias Encefálicas/genética , Regulação para Baixo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Glioma/genética , MicroRNAs/genética , Animais , Neoplasias Encefálicas/metabolismo , Proliferação de Células , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Humanos , Camundongos , Transplante de Neoplasias , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas
11.
Mol Cancer Ther ; 17(6): 1229-1239, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29592879

RESUMO

We here evaluated the antiesophageal cancer cell activity by the antifungal drug itraconazole. Our results show that µg/mL concentrations of itraconazole potently inhibited survival and proliferation of established (TE-1 and Eca-109) and primary human esophageal cancer cells. Itraconazole activated AMPK signaling, which was required for subsequent esophageal cancer cell death. Pharmacologic AMPK inhibition, AMPKα1 shRNA, or dominant negative mutation (T172A) almost completely abolished itraconazole-induced cytotoxicity against esophageal cancer cells. Significantly, itraconazole induced AMPK-dependent autophagic cell death (but not apoptosis) in esophageal cancer cells. Furthermore, AMPK activation by itraconazole induced multiple receptor tyrosine kinases (RTKs: EGFR, PDGFRα, and PDGFRß), lysosomal translocation, and degradation to inhibit downstream Akt activation. In vivo, itraconazole oral gavage potently inhibited Eca-109 tumor growth in SCID mice. It was yet ineffective against AMPKα1 shRNA-expressing Eca-109 tumors. The in vivo growth of the primary human esophageal cancer cells was also significantly inhibited by itraconazole administration. AMPK activation, RTK degradation, and Akt inhibition were observed in itraconazole-treated tumors. Together, itraconazole inhibits esophageal cancer cell growth via activating AMPK signaling. Mol Cancer Ther; 17(6); 1229-39. ©2018 AACR.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Neoplasias Esofágicas/metabolismo , Itraconazol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/genética , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Neoplasias Esofágicas/genética , Feminino , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Pessoa de Meia-Idade , Proteólise , Proteínas Proto-Oncogênicas c-akt/metabolismo , Taquicininas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Oncotarget ; 8(21): 35061-35068, 2017 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-28456783

RESUMO

We have previously shown that Gαi3 is elevated in human glioma, mediating Akt activation and cancer cell proliferation. Here, we imply that Gαi3 could also be important for irradiation resistance. In A172 human glioma cells, Gαi3 knockdown (by targeted shRNAs) or dominant-negative mutation significantly potentiated irradiation-induced cell apoptosis. Reversely, forced over-expression of wild-type or constitutively-active Gαi3 inhibited irradiation-induced A172 cell apoptosis. Irradiation in A172 cells induced Gαi3 translocation to cell nuclei and association with local protein DNA-dependent protein kinase (DNA-PK) catalytic subunit. This association was important for DNA damage repair. Gαi3 knockdown, depletion (using Gαi3 knockout MEFs) or dominant-negative mutation potentiated irradiation-induced DNA damages. On the other hand, expression of the constitutively-active Gαi3 in A172 cells inhibited DNA damage by irradiation. Together, these results indicate a novel function of Gαi3 in irradiation-resistance in human glioma cells.


Assuntos
Neoplasias Encefálicas/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Glioma/metabolismo , Tolerância a Radiação , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Dano ao DNA , Proteína Quinase Ativada por DNA/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Glioma/genética , Glioma/radioterapia , Humanos , Transporte Proteico
14.
J Sep Sci ; 39(17): 3318-26, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27384745

RESUMO

An automated online solid-phase extraction with restricted-access material combined with high-performance liquid chromatography and tandem mass spectrometry was developed and validated for the simultaneous quantification of vanillin and its vanillic acid metabolite in human plasma. After protein precipitation by methanol, which contained the internal standards, the supernatant of plasma samples was injected to the system, the endogenous large molecules were flushed out, and target analytes were trapped and enriched on the adsorbent, resulting in a minimization of sample complexity and ion suppression effects. Calibration curves were linear over the concentrations of 5-1000 ng/mL for vanillin and 10-5000 ng/mL for vanillic acid with a coefficient of determination >0.999 for the determined compounds. The lower limits of quantification of vanillin and vanillic acid were 5.0 and 10.0 ng/mL, respectively. The intra- and inter-run precisions expressed as the relative standard deviation were 2.6-8.6 and 3.2-10.2%, respectively, and the accuracies expressed as the relative error were in the range of -6.1 to 7.3%. Extraction recoveries of analytes were between 89.5 and 97.4%. There was no notable matrix effect for any analyte concentration. The developed method was proved to be sensitive, repeatable, and accurate for the quantification of vanillin and its vanillic acid metabolite in human plasma.


Assuntos
Automação/métodos , Benzaldeídos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Plasma/química , Espectrometria de Massas em Tandem/métodos , Ácido Vanílico/sangue , Humanos
15.
Mol Neurobiol ; 53(4): 2510-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26063590

RESUMO

This study examined the association between elevated plasma homocysteine (Hcy) levels and the risk of acute cerebral infarction in patients with carotid artery lesions. A total of 78 patients were divided into two groups, the high Hcy group (n = 38; Hcy levels >15 umol/L) and the low Hcy group (n = 40; Hcy levels ≤15 umol/L). High-resolution B-mode ultrasounds were performed to assess intima media thickness (IMT), infarcts, plaques, and stenosis in the extracranial carotid artery of these patients. All patients underwent 3 T MR scanners to evaluate cerebral artery stenosis in the intracranial cerebral artery. The plasma Hcy levels did not show any statistically significant differences when comparisons were based on gender, age, blood pressure, diabetes, hyperlipidemia, and systolic and diastolic pressures. Importantly, the incidence of carotid plaque and severe stenosis of intracranial and extracranial artery were significantly higher in the high Hcy group compared to the low Hcy group. Pearson's test indicated that plasma Hcy levels positively correlated with IMT, total number of plaques and unstable plaques. Overall, the elevated plasma Hcy levels correlated with increased frequency of carotid plaque formation, extra- and intracranial arterial stenosis, and the degree of stenosis. In conclusion, we find a significant correlation between elevated plasma Hcy levels and the increased incidence of acute cerebral infarction in patients with carotid artery lesions.


Assuntos
Artérias Carótidas/patologia , Infarto Cerebral/sangue , Homocisteína/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Arteriosclerose/sangue , Arteriosclerose/patologia , Espessura Intima-Media Carotídea , Estenose das Carótidas/sangue , Estenose das Carótidas/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
16.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 32(5): 390-394, 2016 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-29931840

RESUMO

OBJECTIVE: To establish a model of oxidative stress injury in cultured rat aortic endothelial cells, and to provide a basis for the research of cell injury and apoptosis. METHODS: The rats were decapitated to get the aorta in thoracic operation under aseptic conditions. By subculture after tissue block culture method to get sufficient aortic endothelial cells, cultured in 96-well plates or grow on cover glass for the following test. Without H2O2 group as a control group, with different doses of H2O2 (100,200,300,400,500 µmol/L) treated endothelialcells in 12 h to screen the optimal dose. Based on the results, with the same dose of H2O2 (100 or 200 µmol/L) acted on endothelial cells respectively in different time (3, 6, 9, 12 and 24 h) to screen the optimal duration. Each group was made in sextuplicate. The establishment of the model was evaluated by immunofluorescence,cell viability testing, biochemical indicators detection (lactate dehydrogenase(LDH), nitric oxide(NO), malondialdehyde(MDA), superoxidedismutase(SOD))and apoptosis index testing. RESULTS: Endothelial cells were cultured successfully and verified by immunofluorescence staining of intracellular antigen Ⅷ collagen. With the increase of H2O2 doses at the same action time 12 h, the cell viability was significantly decreased (77.63%±5.20% to 40.90%±2.10%). The same dose(100 µmol/L group and 200 µmol/L group)with the action time increasing, the cellviability was significantly decreased (100 µmol/L group was 86.83%±12.11% to 44.26%±5.70%, 200 µmol/L group was 78.28%±11.98% to 34.45%±5.87%). At dose of H2O2 was 100 µmol/L and treated in 3,6,9,12 and 24 h, LDH-L and MDA were significantly increased after 9 h while NO and SOD were significantly decreased. In H2O2 dose of 100 µmol/L and action time 12 h, flow cytometry showed endothelial cellapoptosis rate was 16.92%±2.37%, significantly higher than the control group of 2.68%±0.47%(P<0.01); TUNEL detected endothelial cell apoptosis index was17.65%±2.36%, which was significantly higher than that in the control group of 3.23%±0.57%(P<0.01). CONCLUSIONS: The method was successfullyestablished a model of oxidative stress injury in cultured rat aortic endothelial cells, explore the moderate conditions that induced cells injury and apoptosis which could be a basis for the research.


Assuntos
Apoptose , Células Endoteliais/patologia , Estresse Oxidativo , Animais , Células Cultivadas , Células Endoteliais/enzimologia , Peróxido de Hidrogênio , L-Lactato Desidrogenase/metabolismo , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Ratos , Superóxido Dismutase/metabolismo
17.
Artigo em Chinês | MEDLINE | ID: mdl-26387175

RESUMO

OBJECTIVE: To observe the protective effects of histone deacetylase inhibitor on stress-induced myocardial injury. METHODS: Healthy male Wistar rats were randomly divided into 3 groups( n = 6), and the stress-induced myocardial injury model was established with chronic restraint stress method. The protective effects of histone deacetylase inhibitor on stress-induced myocardial injury were observed with Trichostatin A (TSA) intervention. Histone acetylation levels in myocardium of rats were detected by Western blot method, spectrophotometry method was used to dynamically determine the activity of rat serum lactate dehydrogenase (LDH), serum creatine kinase isoenzyme-MB (CK-MB) and Caspase 3, and nagar Olsen staining were used to observe the early myocardial damage. RESULTS: Restraint stress could significantly reduce the level of histone acetylation of myocardium in rats, and TSA intervention could inhibit the stress-induced reduction of myocardial levels of histone acetylation. Restraint stress could cause the significant increase of serum LDH activity ( P < 0.05), serum CK-MB activity ( P < 0.05), and the Caspase 3 activity of myocardial tissue (P < 0.05), and early myocardial damage also occurred during restraint stress. ISA intervention could significantly reduce the serum LDH activity (P < 0.05), the serum CK-MB activity (P < 0.05), the activity of myocardial tissue caspase 3 induced by restraint stress (P < 0.05), and the stress-induced myocardial injury was also attenuated by TSA intervention. CONCLUSION: The histone deacetylase inhibitor TSA can protect stress-induced myocardial injury.


Assuntos
Cardiotônicos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Miocárdio/patologia , Estresse Fisiológico , Acetilação , Animais , Caspase 3/sangue , Creatina Quinase Forma MB/sangue , L-Lactato Desidrogenase/sangue , Masculino , Ratos , Ratos Wistar , Restrição Física
18.
Ther Drug Monit ; 37(6): 776-82, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26035137

RESUMO

BACKGROUND: Free drug analysis is increasingly becoming popular in therapeutic drug monitoring (TDM). Centrifugal ultrafiltration (CF-UF) is the primary method to separate free drug from that of bound drug. However, the volume ratio of ultrafiltrate to sample solution (Vu/Vs) affects the accuracy of CF-UF, which highly depends on the different plasma conditions. Plasma protein concentrations in patients are different from those observed in healthy subjects, and there are also significant differences among patients with different diseases. Only very few studies have reported on the effect of protein concentration on the analysis methodology of free drug by CF-UF. METHODS: In this study, valproic acid was used as the representative drug, and plasma samples with different albumin concentrations were analyzed by CF-UF and hollow fiber centrifugal ultrafiltration (HFCF-UF). RESULTS: There was no significant difference of free drug concentrations by HFCF-UF and CF-UF when plasma albumin concentrations ranged 40-60 g/L. However, at low albumin concentrations (<40 g/L), a considerable difference was detected, and the difference was increased with the decrease of plasma albumin concentration. When the albumin concentration was as low as 10 g/L, the free drug concentration was 17.3 mcg/mL by CF-UF, whereas it was 10.2 mcg/mL by HFCF-UF. CONCLUSIONS: The accuracy of free drug measurement by CF-UF was albumin concentration dependent. However, such an effect was not observed when samples were prepared by HFCF-UF, which was more suitable for TDM of plasma samples from different patients. Therefore, this method could be readily applied to the measurement of free valproic acid plasma concentrations for TDM in patients.


Assuntos
Monitoramento de Medicamentos/métodos , Albumina Sérica/metabolismo , Ultrafiltração/métodos , Ácido Valproico/farmacocinética , Adolescente , Adulto , Idoso , Centrifugação/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
J Exp Clin Cancer Res ; 34: 57, 2015 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-26024660

RESUMO

BACKGROUND: The primary glioblastoma multiforme (GBM) is the most malignant form of astrocytic tumor with an average survival of approximately 12-14 months. The search for novel and more efficient chemo-agents against this disease is urgent. Salinomycin induces broad anti-cancer effects; however, its role in GBM and the underlying mechanism are not clear. RESULTS: Here we found that salinomycin induced both apoptosis and necrosis in cultured glioma cells, and necrosis played a major role in contributing salinomycin's cytotoxicity. Salinomycin induced p53 translocation to mitochondria, where it formed a complex with cyclophilin-D (CyPD). This complexation was required for mitochondrial permeability transition pore (mPTP) opening and subsequent programmed necrosis. Blockade of Cyp-D by siRNA-mediated depletion or pharmacological inhibitors (cyclosporin A and sanglifehrin A) significantly suppressed salinomycin-induced glioma cell necrosis. Meanwhile, p53 stable knockdown alleviated salinomycin-induced necrosis in glioma cells. Reactive oxygen species (ROS) production was required for salinomycin-induced p53 mitochondrial translocation, mPTP opening and necrosis, and anti-oxidants n-acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) inhibited p53 translocation, mPTP opening and glioma cell death. CONCLUSIONS: Thus, salinomycin mainly induces programmed necrosis in cultured glioma cells.


Assuntos
Ciclofilinas/metabolismo , Glioma/induzido quimicamente , Piranos/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Apoptose , Morte Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Glioma/genética , Humanos , Transdução de Sinais
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(1): 14-8, 2015 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-25993811

RESUMO

The hydrotalcite with the properties of flame-retardant, eliminating smoke, filling and thermostability is a new kind of inorganic flame retardant. In the work, the MgAl hydrotalcite as flame retardant with Mg/Al molar ratio of 4 (MgAl-LDH) was prepared by using urea as the precipitating agent. The thermolysis behavior of the MgAl-LDH flame retardant was investigated by X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR) and thermogravimetry-differential scanning calorimetry (TG-DSC) as well as self deconvolution and curve-fitting analyses. Thermal phase transition of the MgAl-LDH was clarified, especially the characteristics of the hydroxyl groups (-OH) in the brucite-like layers and the changes in coordinate of the carbonate (CO3(2-)) from the interlayers. Based on thermodynamic data, thermal decomposition process was discussed. By.XRD analysis; it was found that the phase change took place when the decomposition temperature increased. The MgAl-LDH was decarbonated basically to MgAl mixed metal oxides (Mg-Al-O) at 500 °C, and impurity MgAl204 phase formed at 600 °C. According to the analyses of FT-IR, TG-DSC and curve-fitting technique, the hydroxyl groups (-OH) in the brucite-like layers possessed three the ligands such as [Al-OH-Al], [Al-OH-Mg] and [Mg-OH-Mg] modes. Dehydroxylation of the brucite-like layers based on the binding forces, where the [Mg-OH-Mg] among the three modes was the most difficult to be re- moved during the pyrolysis process. In the same way, the CO3(2-) ligands also possessed three modes such as H2O-bridged CO3(2-), monodentate and bidentate coordination modes. Based on the thermodynamic analysis, the thermodynamic properties of the hydrotalcite as flame retardant were evaluated, and the expressions of the Gibbs free energy, (ΔrGθT), as a function of temperature, were derived for the Mg8Al2 (OH)20CO3 crystal. Thermodynamic analysis showed that the removal of -OH from the brucite-like layers was spontaneous process, when the Gibbs free energy (ΔrGθT) was under zero at the temperature (T) above 228. 65 °C. The result and datum were close to the experimental result from the TG-DSC analyses, indicating that the relationship between the Gibbs free energy (ΔrGθT) and temperature (T) from thermodynamic analysis was reliable.

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