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1.
J Cell Mol Med ; 28(7): e18194, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38506086

RESUMO

Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease. If not treated, it can lead to liver damage, cirrhosis and even liver cancer. However, advances in treatment have remained relatively slow, and there is thus an urgent need to develop appropriate treatments. Hedan tablet (HDP) is used to treat metabolic syndrome. However, scientific understanding of the therapeutic effect of HDP on NASH remains limited. We used HDP to treat a methionine/choline-deficient diet-induced model of NASH in rats to elucidate the therapeutic effects of HDP on liver injury. In addition, we used untargeted metabolomics to investigate the effects of HDP on metabolites in liver of NASH rats, and further validated its effects on inflammation and lipid metabolism following screening for potential target pathways. HDP had considerable therapeutic, anti-oxidant, and anti-inflammatory effects on NASH. HDP could also alter the hepatic metabolites changed by NASH. Moreover, HDP considerable moderated NF-κB and lipid metabolism-related pathways. The present study found that HDP had remarkable therapeutic effects in NASH rats. The therapeutic efficacy of HDP in NASH mainly associated with regulation of NF-κB and lipid metabolism-related pathways via arachidonic acid metabolism, glycine-serine-threonine metabolism, as well as steroid hormone biosynthesis.


Assuntos
Medicamentos de Ervas Chinesas , Hepatopatia Gordurosa não Alcoólica , Ratos , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , NF-kappa B/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
2.
J Affect Disord ; 316: 233-242, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35981627

RESUMO

BACKGROUND: Parkinson's disease (PD) is a neurological disorder. Recently, celastrol (Cel) has been reported to have neuroprotective properties. We investigated the protective effects of Cel on PD in a cell model with 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells and further addressed the underlying protective mechanisms of Cel. METHODS: PC12 cells were treated with 6-OHDA, and Cel was added to the medium at various concentrations. The CCK-8 assay, Hoechst/PI staining, and flow cytometry analysis were performed to detect cellular viability and apoptosis. Mitochondrial membrane potential (MMP) was examined by JC-1 staining. ROS level was quantified by ROS staining. The effects of Cel on the expression of miR-146a and PI3K/Akt/mTOR pathway were then clarified using real-time PCR and Western blotting. Moreover, a miR-146a mimic was synthesized and transfected into PC12 cells to further determine the mechanisms of Cel's neuronal protection against 6-OHDA-induced neurotoxicity. RESULTS: Cel greatly improved cell viability and lessened apoptosis. Flow cytometry showed that Cel especially inhibited early apoptosis. Cel also obviously restored the MMP and decreased ROS level destroyed by 6-OHDA. Moreover, 6-OHDA increased the expression of miR-146a and decreased pAkt/mTOR protein levels, whereas Cel reversed these changes. In particular, miR-146a targeted and inhibited the expression of PI3K, an upstream molecule of Akt/mTOR. Transfection of 6-OHDA-treated neurons with miR-146a mimic notably attenuated Cel's protective effects. LIMITATIONS: There were no animal experiments in our study. CONCLUSIONS: Cel exerts neuroprotective activity against 6-OHDA-caused neurotoxicity by regulating miR-146a/PI3K/Akt/mTOR pathway, which provides a potential application of Cel for treating neurodegenerative diseases.


Assuntos
Neoplasias das Glândulas Suprarrenais , MicroRNAs , Fármacos Neuroprotetores , Doença de Parkinson , Feocromocitoma , Animais , Apoptose , MicroRNAs/genética , MicroRNAs/metabolismo , Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , Triterpenos Pentacíclicos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Espécies Reativas de Oxigênio , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismo
3.
Plant Physiol Biochem ; 185: 112-122, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35671588

RESUMO

The effectiveness of iron is reduced in saline conditions, which can easily lead to iron deficiency and inhibit photosynthesis in rice. In this study, 4-week-old Fe-deficient rice seedlings were treated under saline sodic stress (50 mM) to different concentrations (0, 0.2%, 0.4%, 0.8%, 1.6%, and 3.2%) of foliar iron fertilizer (FeEDDHA). Differences in prompting fluorescence and the MR820 signal of rice leaves after 7 days of treatment were probed using the JIP-test. The results show that the performances of the two rice varieties were in general agreement. Under iron deficiency and soda salinity stress conditions, rice growth was inhibited, and the pigment content, specific energy flux, quantum yield, performance of the active PSII reaction center (PIABS) and the oxidation (Vox) and reduction rates (Vred) of PSI were reduced. These indicators first increase and then decrease with increasing iron fertiliser concentrations. The best results were obtained with the Fe3 treatment (0.8%). Fluorescence parameters such as the relative variable fluorescence (WK and VJ) and the quantum yield of energy dissipation (φDo) showed opposite trends. This suggests that iron deficiency/excess and soda saline stress disrupt the electron and energy transport in the photosystem. Appropriate iron fertilization concentration can repair the photosynthetic electron transport chain, improve electron transport efficiency and promote balanced energy distribution. Therefore, we suggest that moderate amounts of Fe are beneficial for improving the electron and energy transport properties of the photosystem, while spraying high concentrations of Fe fertilizer has a negative effect on improving salt tolerance in rice.


Assuntos
Deficiências de Ferro , Oryza , Clorofila , Fertilizantes , Fluorescência , Ferro/farmacologia , Oryza/metabolismo , Fotossíntese , Complexo de Proteína do Fotossistema II/metabolismo , Folhas de Planta/metabolismo , Plântula/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-35399623

RESUMO

Many studies have found that the dysfunction in gut microbiota and the metabolic dysfunction can promote nonalcoholic fatty liver disease (NAFLD) development. Er-Chen decoction (EC) can be used in the treatment of NAFLD. However, the mechanism of this hepatoprotection is still unknown. In this study, we constructed a rat model with NAFLD fed with high-fat chow and administered EC treatment. The therapeutic effects of EC on NAFLD were evaluated by measuring transaminases, blood lipid levels, and pathological changes in the liver. In addition, we measured the effects of EC on liver inflammatory response and oxidative stress. The changes in gut microbiota after EC treatment were studied using 16S rRNA sequencing. Serum untargeted metabolomics analysis was also used to study the metabolic regulatory mechanisms of EC on NAFLD. The results showed that EC decreased the serum transaminases and lipid levels and improved the pathological changes in NAFLD rats. Furthermore, EC enhanced the activities of SOD and GSH-Px and decreased MDA level in the liver. EC treatment also decreased the gene and protein levels of IL-6, IL-1ß, and TNF-α in the liver and serum. The 16S rRNA sequencing and untargeted metabolomics indicated that EC treatment affected the gut microbiota and regulated serum metabolism. Correlation analysis showed that the effects of EC on taurine and hypotaurine metabolism, cysteine and methionine metabolism, and vitamin B6 metabolism pathways were associated with affecting in the abundance of Lactobacillus, Dubosiella, Lachnospiraceae, Desulfovibri, Romboutsia, Akkermansia, Intestinimonas, and Candidatus_saccharimonas in the gut. In conclusion, our study confirmed the protective effect of EC on NAFLD. EC could treat NAFLD by inhibiting oxidative stress, reducing inflammatory responses, and improving the dysbiosis of gut microbiota and the modulation of the taurine and hypotaurine metabolism, cysteine and methionine metabolism, and vitamin B6 metabolism pathways in serum.

5.
J Biomed Nanotechnol ; 17(7): 1284-1292, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446132

RESUMO

This study aimed to introduce nano-gold PCR for detection of TERT methylation, and explore the correlation between TERT methylation and prognosis of hepatocellular carcinoma (HCC). From March 2016 to March 2018, 154 HBV carriers treated in our hospital were enrolled in the study and divided into HCC (68 cases), cirrhosis (45 cases) and chronic hepatitis (CH) groups (41 cases) based on clinical disease. HCC patients were further divided into methylation (30 cases) and non-methylation (38 cases) subgroup based on methylation status of the TERT. TERT methylation of HCC specimens were 44.12% and 35.24% by nano-PCR and conventional PCR, respectively. The TERT methylation and TERT expression in HCC specimens were higher than for cirrhosis and CH specimens. A significant positive correlation was observed between TERT methylation and TERT expression. AFP, Edmondson classification, tumor size, hilar lymph node and intrahepatic metastasis, and TNM staging in the methylation group were higher than in non-methylation group. Further, overall survival and progression-free survival were significantly shorter. Nano-gold PCR is more sensitive in detecting TERT methylation. As CHB progresses, TERT methylation increases. Greater methylation of the gene is associated with worse prognosis in HCC patients.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Telomerase , Carcinoma Hepatocelular/genética , Metilação de DNA , Ouro , Vírus da Hepatite B/genética , Hepatite B Crônica/genética , Humanos , Neoplasias Hepáticas/genética , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Telomerase/genética
6.
J Chromatogr A ; 1653: 462428, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34329956

RESUMO

Three novel hypercrosslinked polymers (HCPs) were synthesized via Friedel-Crafts reaction employing 1,3,5-tris(bromomethyl)-2,4,6-trimethylbenzene as alkylating agent, and triphenylbenzene, tetraphenylethylene and p-quaterphenyl as the aromatic units, respectively. The prepared HCPs were applied as solid-phase microextraction coatings for direct immersion extraction of polycyclic aromatic hydrocarbons (PAHs) and their oxygenated and nitrated derivatives in environmental water samples. The key factors affecting the extraction efficiency including extraction time, extraction temperature, stirring rate, ionic strength and desorption conditions, were carefully studied. Coupled with gas chromatography mass spectrometry analysis, a new method for determining PAHs and their derivatives was developed. Under the optimized conditions, the limits of detection (S/N=3) and limits of quantitation (the lowest concentration for quantification) of the method were in the range of 2.5-25.0 and 7.5-75.0 ng L-1, respectively. The recoveries of spiked samples were in the range of 73.1-118.3% with relative standard deviations less than 13.0%. The developed method was applied for the simultaneous determination of nine PAHs and their derivatives in environmental water samples, showing good accuracy and reliability.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Hidrocarbonetos Policíclicos Aromáticos , Microextração em Fase Sólida , Poluentes Químicos da Água , Limite de Detecção , Hidrocarbonetos Policíclicos Aromáticos/análise , Polímeros , Reprodutibilidade dos Testes , Poluentes Químicos da Água/análise
7.
Chin J Physiol ; 64(1): 24-31, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33642341

RESUMO

Accumulating evidence has already indicated that traditional Chinese medicine (TCM) possesses tremendous potential for treating neurodegenerative diseases. Astragalus, also named Huangqi, is a famous traditional medical herb that can be applied to treat cerebral ischemia and prevent neuronal degeneration. Nevertheless, the underlying mechanisms remain largely unexplored. In the present study, Astragalus-containing serum (ASMES) was prepared and added into the culture medium of PC12 cells to explore its neuroprotective effect on 6-hydroxydopamine (6-OHDA)-caused neuronal toxicity. Our data showed that ASMES significantly ameliorated the cellular viability of cultured PC12 cells against the neurotoxicity induced by 6-OHDA (P < 0.05). Moreover, ASMES significantly decreased the cell apoptosis triggered by 6-OHDA (P < 0.01). Furthermore, 2',7'-dichlorofluorescin diacetate assay was performed to detect the changes in oxidative stress, and we showed that 6-OHDA elevated the production of reactive oxygen species (ROS), whereas ASMES significantly reversed these changes (P < 0.01). Besides, mitochondrial membrane potential (MMP) assay showed that ASMES could restore 6-OHDA-damaged MMP in cultured PC12 cells (P < 0.05). In conclusion, Astragalus could protect PC12 cells from 6-OHDA-caused neuronal toxicity, and possibly, the ROS-mediated apoptotic pathway participated in this process. Collectively, our findings provided valuable insights into the potential in treatment of neurodegenerative diseases.


Assuntos
Fármacos Neuroprotetores , Animais , Apoptose , Sobrevivência Celular , Potencial da Membrana Mitocondrial , Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , Células PC12 , Ratos , Espécies Reativas de Oxigênio
9.
Mikrochim Acta ; 187(9): 521, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32856135

RESUMO

Graphene-carbon nanosphere composite (G@CNS) was prepared via a simple hydrothermal method. The G@CNS nanocomposite was characterized by X-ray diffraction, scanning electron microscope, surface area, and porosity analysis. The G@CNS was applied as a new sorbent for solid-phase extraction of five carbamate pesticides (tsumacide, carbaryl, isoprocarb, bassa, diethofencarb) prior to quantitative determination by high-performance liquid chromatography with ultraviolet detection at 208 nm. Some experimental parameters including desorption conditions, sample pH, sample volume, and loading rate were studied carefully. Under the optimized condition, the method provided good linearity ranging from 0.3 to 100.0 ng mL-1 with low limits of detection of 0.10-0.20 ng mL-1 for grape juice, 0.10-0.30 ng mL-1 for blend fruit juice, and 0.10-0.20 ng mL-1 for water sample. Good method recoveries (80.2-110%) with relative standard deviations less than 7.2% and high enrichment factors (167-293) were achieved. Results demonstrated that this novel G@CNS can serve as a promising alternative sorbent for more applications. In this work, a graphene-carbon nanosphere (G@CNS) composite was synthesized via a simple hydrothermal method. Then, the G@CNS was served as a novel sorbent for solid-phase extraction of five carbamate pesticides (tsumacide, carbaryl, isoprocarb, bassa, diethofencarb) in juice and environmental water samples, followed by their quantitative analysis with high-performance liquid chromatography-ultraviolet detection.

10.
Biomed Res Int ; 2018: 2396109, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29854733

RESUMO

The in vitro antioxidant and antimicrobial activity of the essential oil from Melaleuca alternifolia (M. alternifolia) was evaluated in this report. The antioxidant potential of the essential oil from M. alternifolia was evaluated by the DPPH (2,2-diphenyl-1-picrylhydrazyl) method, thiobarbituric acid reactive species (TBARS) assay, and the hydroxyl radical scavenging activity method. The essential oil from M. alternifolia was able to reduce DPPH with an EC50 (concentration for 50% of maximal effect) of 48.35 µg/ml, inhibit the lipid peroxidation with an IC50 (50% inhibitory concentration) of 135.9 µg/ml, and eliminate hydroxyl radicals with an EC50 of 43.71 µg/ml. Antimicrobial screening, minimum inhibitory concentration, and minimum bactericidal concentration assays showed that the essential oil from M. alternifolia inhibited strongly the growth of different types of microorganisms, including Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Penicillium italicum Wehmer, and Penicillium digitatum Sacc. Thus, the essential oil of M. alternifolia possesses antioxidant and antimicrobial activity and could be suitable for use as a natural preservative ingredient in food, agriculture, and pharmaceutical industries.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Melaleuca/química , Óleos Voláteis/farmacologia , Bactérias/efeitos dos fármacos , Compostos de Bifenilo/química , Sequestradores de Radicais Livres/química , Fungos/efeitos dos fármacos , Radical Hidroxila/química , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Picratos/química
11.
Biomed Pharmacother ; 99: 715-724, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29710469

RESUMO

Hydroxytyrosol (HT) is a natural polyphenol antioxidant that exists in olive oil. In the study of multifunctional hypolipidemic of nicotinic derivatives, we found that hydroxytyrosol nicotinate (HT-N) incorporation of niacin with HT displayed ?-glucosidase inhibitory activities in vitro, such as yeast ?-glucosidase (IC50?=?117.72??M) and rat intestinal ?-glucosidases maltase (IC50?=?31.86??M) and sucrase (IC50?=?22.99??M), and had a good control of postprandial blood glucose (PBG). HT-N shown significantly hypoglycemic action by 16.9% and protection of pancreatic tissue in type 2 diabetic mellitus (T2DM) mouse model. HT-N also shown a potent antioxidant activity and property of anti-glycation in vitro, which were benefit for ameliorating diabetic complications. Moreover, HT-N exhibited much significant hypolipidemia, lowering plasma triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 34.6%, 45.8% and 32.1% respectively, in hyperlipidemic mice induced by Triton WR 1339. The results indicated that HT-N has hypolipidemic, hypoglycemic and antioxidant actions. All these properties could be conducive to amelioration of oxidative stress, hyperlipidemia, and diabetes that HT-N may serve as a multifunctional potential therapeutic strategy in diabetic patients with hyperlipidemia.


Assuntos
Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Niacina/farmacologia , Álcool Feniletílico/análogos & derivados , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/farmacologia , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Hipolipemiantes/administração & dosagem , Hipolipemiantes/química , Concentração Inibidora 50 , Lipídeos/sangue , Masculino , Camundongos , Niacina/administração & dosagem , Niacina/química , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Ratos
12.
Exp Ther Med ; 15(3): 2851-2859, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29599829

RESUMO

The present study aimed to determine whether the expression of microRNA (miR)-10b was correlated with the molecular subtypes of early invasive ductal carcinoma of the breast. In situ hybridization was used to detect the expression of miR-10b in 193 patients diagnosed with early invasive ductal carcinoma. Immunohistochemistry was performed to evaluate the expression of estrogen receptor (ER)-α, progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2). The positive expression rate of miR-10b in patients with early invasive ductal carcinoma with ER-α (+) or PR (+) was decreased compared with ER-α (-) or PR (-) patients (P<0.05). Furthermore, the positive expression rate of miR-10b in patients with Her-2 (-) was significantly increased compared with patients that were Her-2 (+) (P=0.031). The positive expression rate of miR-10b in the luminal B subtype was significantly decreased compared with that in the luminal A, Her-2 and basal-like subtypes (P=0.037). In patients that were identified as miR-10b (+), the median disease-free survival time was significantly increased in patients that were ER-α (+)/PR (+)/Her-2 (-) compared with patients that were ER-α (-)/PR (-)/Her-2 (+) (P<0.05). In addition, the median disease-free survival time was significantly decreased in Her-2 overexpression and basal-like subtypes when compared with luminal A and B subtypes (P<0.05). The molecular subtype was an independent prognostic factor for early invasive ductal carcinoma (odds ratios for luminal B, Basal-like, and Her-2 overexpression were 2.900, 5.232 and 4.214, respectively; all P<0.05). Positive expression of miR-10b may also be a prognostic risk factor (odds ratio >1), though this was not statistically significant (P>0.05). The present findings indicated that miR-10b-positive expression was correlated with the expression of ER-α, Her-2 and the molecular subtypes of early invasive ductal carcinoma of the breast.

13.
Radiother Oncol ; 129(1): 154-160, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29122362

RESUMO

BACKGROUND AND PURPOSE: The benefit of consolidation chemotherapy for locally advanced squamous cell carcinoma of the esophagus is unknown. The aim of this study was to investigate the efficacy of consolidation chemotherapy with cisplatin and 5-fluorouracil (5-FU) after concurrent chemoradiotherapy (CCRT) with the same agents in patients with stage II-III disease. MATERIAL AND METHODS: Data for patients with stage II-III squamous cell carcinoma of the esophagus treated with CCRT were retroactively reviewed. Patients who received CCRT alone (observation group) were compared with those who underwent CCRT followed by consolidation chemotherapy (consolidation group) with regard to progression-free survival, overall survival, treatment failure and toxicity. Differences in baseline characteristics were adjusted using the propensity score matching method. RESULTS: From September 2006 to September 2012, 812 patients were recruited (n = 272 for observation; n = 540 for consolidation). Among them, 290 (35.7%) had clinical stage II disease and 522 (64.3%) had stage III disease. In the overall study cohort, the median progression-free survival (22.1 months vs. 22.0 months, P = 0.917) and median overall survival (33.8 months vs. 31.3 months, P = 0.591) were comparable between the observation group and consolidation group. Comparisons of the observation and consolidation group in the matched population (262 patients in each group) showed median progression-free survival of 23.0 months and 25.4 months (hazard ratio [HR], 0.93; 95% CI [confidence interval], 0.74-1.15; P = 0.491), and median overall survival of 34.6 months and 35.0 months (HR, 0.92; 95% CI, 0.80-1.27; P = 0.919), respectively. There were no significant differences in local/regional failure and persistence disease (50.4% vs. 48.5%) and distant failure (10.7% vs. 8.8%) between the two groups. CONCLUSIONS: Compared to CCRT alone, consolidation chemotherapy did not further prolong progression-free survival and overall survival for patients with stage II-III squamous cell carcinoma of the esophagus. The role of consolidation therapy needs to be studied further.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Adulto , Idoso , Cisplatino/administração & dosagem , Quimioterapia de Consolidação/métodos , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos
14.
Free Radic Biol Med ; 110: 188-195, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28603086

RESUMO

To balance the production and decomposition of reactive oxygen species, living organisms have generated antioxidant enzymes and non-enzymatic antioxidant defense systems. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) are two important antioxidant enzymes. Apart from their catalytic functions, they protect each other, resulting in more efficient removal of reactive oxygen species, protection of cells against injury, and maintenance of the normal metabolism of reactive oxygen species. SOD catalyzes the dismutation of the superoxide anion (O2•-) to oxygen (O2) and hydrogen peroxide (H2O2). H2O2 is then detoxified to water by GPx. In this study, human GPx1Ser and the Alvinella pompejana SOD (ApSOD) gene were used to design and generate several recombinant proteins with both GPx and SOD activities by combining traditional fusion protein technology, a cysteine auxotrophic expression system, and a single protein production (SPP) system. Among the fusion proteins, Se-hGPx1Ser-L-ApSOD exhibited the highest SOD and GPx activities. Additional research was conducted to better understand the properties of Se-hGPx1Ser-L-ApSOD. The synergism of Se-hGPx1Ser-L-ApSOD was evaluated by using an in vitro model. This research may facilitate future studies on the cooperation and catalytic mechanisms of GPx and SOD. We believe that the bifunctional enzyme has potential applications as a potent antioxidant.


Assuntos
Antioxidantes/química , Glutationa Peroxidase/química , Peróxido de Hidrogênio/química , Proteínas Recombinantes de Fusão/química , Superóxido Dismutase/química , Superóxidos/química , Animais , Antioxidantes/metabolismo , Clonagem Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Cinética , Modelos Moleculares , Poliquetos/química , Poliquetos/enzimologia , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Especificidade por Substrato , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo , Glutationa Peroxidase GPX1
15.
Int J Pharm ; 527(1-2): 31-41, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28487188

RESUMO

To develop embolic microspheres with MRI detectability, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized and mixed with monomer of acrylic acid to prepare SPIONs-loaded polymerized microspheres (SPMs) by inverse suspension polymerization method. The SPMs were evaluated for the ability of embolization by investigating the morphology, particle size, elasticity and renal arterial embolization to rabbits. Meanwhile, the loading of SPIONs was verified by optical microscope, transmission electron microscope, Fourier transform infrared spectrum, vibrating sample magnetometer, X-ray diffraction and X-ray photoelectron spectroscopy, and the content of SPIONs in SPMs was measured quantitatively. Furthermore, the MRI detectability of SPMs was testified in gel phantom, mice and rabbits respectively by a clinical 3.0T MRI scanner. The results revealed the SPMs were potential MRI detectable embolic microspheres for improving the effectiveness and safety of embolotherapy in the future.


Assuntos
Resinas Acrílicas/química , Embolização Terapêutica , Nanopartículas de Magnetita/química , Microesferas , Animais , Imageamento por Ressonância Magnética , Masculino , Camundongos , Coelhos
16.
Oncol Rep ; 36(6): 3233-3240, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27748853

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the second cause of cancer-related deaths around the world. Pterostilbene (PTE), is a natural analog of resveratrol, possessing diverse pharmacological activities. In the present study, we aimed to examine the effect of PTE on tumor growth in mouse models of HCC and to elucidate the possible molecular mechanism in vivo and in vitro. We showed that PTE dose-dependently suppressed tumor growth in mice induced by diethylnitrosamine plus carbon tetrachloride, as evidenced by a decrease in the number of tumors and in the maximum size of the tumors. PTE concentration-dependently inhibited cell viability and proliferation in HepG2 cells. PTE increased caspase-3 activities and apoptosis in liver tumor tissues and cells, indicating the activation of the mitochondrial apoptotic pathway. PFTα, superoxide dismutase 2 (SOD2) lentivirus and N-acetylcysteine (NAC) significantly inhibited PTE-induced inhibition of tumor growth and cell proliferation and increase in apoptosis. PTE dose-dependently increased reactive oxygen species (ROS) levels both in liver tumor tissues and cells, which were inhibited by PFTα, SOD2 lentivirus and NAC. PTE resulted in a significant decrease in SOD2 expression in liver tumor tissues and cells, which were inhibited by PFTα, but not NAC, indicating that PTE-induced ROS generation was attributed to p53-mediated downregulation of SOD2. Collectively, PTE increased p53 expression, decreased SOD2 expression, and resulted in an increase in the ROS levels and the activation of the mitochondrial apoptotic pathway, leading to inhibition of tumor growth and cell proliferation. These data demonstrated that the p53/SOD2/ROS pathway is critical for PTE-mediated inhibition of tumor growth and HCC cell proliferation.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Estilbenos/farmacologia , Animais , Carcinoma Hepatocelular/patologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos C57BL , Mitocôndrias , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Carga Tumoral , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Int J Pharm ; 511(2): 831-9, 2016 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-27426106

RESUMO

To monitor the spatial distribution of embolic particles inside the target tissues during and after embolization, blank poly (acrylic acid) microspheres (PMs) were initially prepared by inverse suspension polymerization method and then loaded with superparamagnetic iron oxide (SPIO) nanoparticles by in situ precipitation method to obtain magnetic resonance imaging (MRI) detectable SPIO-loaded poly (acrylic acid) microspheres (SPMs). The loading of SPIO nanoparticles in SPMs was confirmed by vibrating sample magnetometer, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and infrared spectrum, respectively. The results showed that SPMs exhibited excellent superparamagnetism and the SPIO embedded in SPMs were proved to be inverse spinel magnetite. The content of SPIO loaded in wet SPMs of subgroups of 100-300, 300-500, 500-700 and 700-900µm was measured to be 11.84±0.07, 10.20±0.05, 9.98±0.00 and 8.79±0.01mg/ml, corresponding to the weight percentage in freeze-dried SPMs to be 18.07±0.28%, 18.54±0.13%, 18.66±0.01% and 18.50±0.07%, respectively. The SPMs were spherical in shape, had smooth surface, and were within the size range of clinical demands for embolization. The compression tests indicated that SPMs were more rigid than PMs and commercially used Embospheres (P<0.01). The MRI detectability of SPMs was evaluated with the SPMs embedded in gel phantom in vitro and injected subcutaneously into the back of mice in vivo. Both the results demonstrated that the SPMs could provide distinct negative contrast enhancement and be sensitively detected by T2-weighted MR imaging. All the results show that SPMs are potential MRI detectable embolic microspheres for the future embolotherapy.


Assuntos
Resinas Acrílicas/química , Embolização Terapêutica/métodos , Microesferas , Animais , Meios de Contraste/administração & dosagem , Meios de Contraste/química , Elasticidade , Injeções Subcutâneas , Fenômenos Magnéticos , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Masculino , Camundongos , Tamanho da Partícula , Imagens de Fantasmas
18.
Oncol Lett ; 11(2): 1531-1536, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26893775

RESUMO

The aim of the present study was to investigate the role of estrogen receptor (ER) ß in the prognosis of ERα-positive breast cancer in postmenopausal women, and its effect on the efficacy of endocrine therapy. Tissue specimens from 195 patients with postmenopausal breast cancer were analyzed. ERß expression levels were detected using immunohistochemical staining. Kaplan-Meier analysis was performed to assess patient survival, and the difference in survival was analyzed using the log-rank test. Cox regression was utilized to evaluate prognostic factors. The results revealed that the disease-free survival rate decreased dramatically as ERß expression levels increased in all postmenopausal ERα-positive breast cancer patients, and ERß expression was identified to be an indicator of poor prognosis in cases of this disease. Similarly, in postmenopausal ERα-positive breast cancer patients undergoing endocrine therapy, high ERß expression levels reduced the disease-free survival rate and were correlated with poor patient prognosis. However, in such patients who were not treated with endocrine therapy, disease-free survival rate and prognosis were not significantly affected by ERß expression. In conclusion, ERß overexpression led to endocrine therapy resistance and poor prognosis in postmenopausal ERα-positive breast cancer patients, suggesting that ERß may affect breast cancer prognosis via an increase in endocrine therapy resistance.

19.
Exp Ther Med ; 10(4): 1423-1428, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26622501

RESUMO

ß-catenin, cyclin D1 and estrogen receptor (ER)-ß are closely associated with the pathogenesis of breast cancer. In the present study, tissue samples were collected from 226 patients with breast cancer. Subsequently, immunohistochemical analysis was performed to detect the expression of ß-catenin, cyclin D1 and ER-ß, and the Kaplan-Meier method was used for survival analysis. The abnormal expression rate of ß-catenin was 75.2%, while the cyclin D1 positive expression rate was 77.0% and the ER-ß positive expression rate was 43.4%. In the tissue samples exhibiting abnormal expression of ß-catenin, the positive expression rate of cyclin D1 (85.9%) was significantly higher compared with the samples that expressed ß-catenin normally (50.0%). Furthermore, the positive expression rate of ER-ß (35.7%) in the ß-catenin normal expression tissues was significantly lower compared with that in the ß-catenin abnormal expression tissues (45.9%). In the tissues with positive cyclin D1 expression, the positive expression rate of ER-ß (48.4%) was significantly higher compared with the cyclin D1 negative expression samples (26.9%). In addition, patients with normal expression of ß-catenin and positive expression of cyclin D1 exhibited longer tumor-free survival times. Therefore, an association exists among the abnormal expression of ß-catenin and the positive expression of cyclin D1 and ER-ß, which may contribute to the development of breast cancer.

20.
Exp Ther Med ; 9(6): 2147-2150, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26136950

RESUMO

The aim of the present study was to investigate the expression of estrogen receptor ß (ERß) in triple-negative and triple-positive breast cancer patients, and evaluate its utility as a prognostic factor. Between January 2000 and December 2010, primary tumor tissue samples were collected from 234 subjects, including 107 triple-negative and 127 triple-positive breast cancer patients. The samples were embedded in paraffin and immunohistochemical staining was conducted to determine the expression levels of ERß. The Kaplan-Meier method was used to analyze patient survival rates. ERß expression was observed in 38/107 patients (35.5%) with triple-negative breast cancer and 63/127 patients (49.6%) with triple-positive breast cancer. The ERß expression rate was significantly decreased in the patients with triple-negative breast cancer, as compared with those with triple-positive breast cancer (P=0.03). Analysis of the survival rates indicated that patients with triple-negative breast cancer and positive ERß expression exhibited poor disease progression-free survival (DFS) compared with those with negative ERß expression (P=0.021). However, no statistically significant difference was observed in the DFS between the triple-positive breast cancer patients with positive and negative ERß expression. Therefore, the expression of ERß varies between triple-negative and triple-positive breast cancer patients. In addition, positive expression of ERß indicates a poor prognosis in triple-negative breast cancer patients; however, this is not the case for triple-positive breast cancer patients.

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