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1.
Pharm Biol ; 55(1): 1171-1176, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28228044

RESUMO

CONTEXT: Withaferin A (WFA) exhibits diverse pharmaceutical applications on human diseases, including rheumatoid arthritis, cancers and microbial infection. OBJECTIVE: We evaluated the neuroprotective role of WFA using a mouse model of spinal cord injury (SCI). MATERIALS AND METHODS: BALB/c mice were administrated 10 mg/kg of WFA. Gene expression was measured by real-time PCR, western blot and immunohistochemistry. Cell morphology and apoptosis were determined by H&E staining and TUNEL assay. Motor function was evaluated by the BBB functional scale for continuous 7 weeks. RESULTS: WFA significantly improved neurobehavioural function and alleviated histological alteration of spinal cord tissues in traumatized mice. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) significantly increased in WFA-treated mice. Meanwhile, the expression of Nogo-A and RhoA remarkably decreased in the presence of WFA. Furthermore, the apoptotic cell death was attenuated in mice treated with WFA (31.48 ± 2.50% vs. 50.08 ± 2.08%) accompanied by decreased bax and increased bcl-2. In addition, WFA decreased the expression of pro-inflammatory mediators such as IL-1ß (11.20 ± 1.96 ng/mL vs. 17.59 ± 1.42 ng/mL) and TNF-α (57.38 ± 3.57 pg/mL vs. 95.06 ± 9.13 pg/mL). The anti-inflammatory cytokines including TGF-ß1 (14.32 ± 1.04 pg/mL vs. 9.37 ± 1.17 pg/mL) and IL-10 (116.80 ± 6.91 pg/mL vs. 72.33 ± 9.35 pg/mL) were elevated after WFA administration. DISCUSSION AND CONCLUSION: This study demonstrated that WFA has a neuroprotective role by inhibition of apoptosis and inflammation after SCI in mice.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Inflamação/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Vitanolídeos/farmacologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Mediadores da Inflamação/metabolismo , Camundongos Endogâmicos BALB C , Atividade Motora/efeitos dos fármacos , Proteínas Nogo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Tempo , Proteínas rho de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP
2.
Mar Drugs ; 11(1): 67-80, 2013 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-23303301

RESUMO

This study was performed to explore other potential mechanisms underlying hemolysis in addition to pore-formation of tentacle extract (TE) from the jellyfish Cyanea capillata. A dose-dependent increase of hemolysis was observed in rat erythrocyte suspensions and the hemolytic activity of TE was enhanced in the presence of Ca2+, which was attenuated by Ca2+ channel blockers (Diltiazem, Verapamil and Nifedipine). Direct intracellular Ca2+ increase was observed after TE treatment by confocal laser scanning microscopy, and the Ca2+ increase could be depressed by Diltiazem. The osmotic protectant polyethylenglycol (PEG) significantly blocked hemolysis with a molecular mass exceeding 4000 Da. These results support a pore-forming mechanism of TE in the erythrocyte membrane, which is consistent with previous studies by us and other groups. The concentration of malondialdehyde (MDA), an important marker of lipid peroxidation, increased dose-dependently in rat erythrocytes after TE treatment, while in vitro hemolysis of TE was inhibited by the antioxidants ascorbic acid-Vitamin C (Vc)-and reduced glutathione (GSH). Furthermore, in vivo hemolysis and electrolyte change after TE administration could be partly recovered by Vc. These results indicate that lipid peroxidation is another potential mechanism besides pore-formation underlying the hemolysis of TE, and both Ca2+ channel blockers and antioxidants could be useful candidates against the hemolytic activity of jellyfish venoms.


Assuntos
Venenos de Cnidários/farmacologia , Eritrócitos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Cifozoários/química , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Diltiazem/farmacologia , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/fisiologia , Eritrócitos/metabolismo , Eritrócitos/fisiologia , Glutationa/metabolismo , Hemólise/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Nifedipino/farmacologia , Osmose/efeitos dos fármacos , Osmose/fisiologia , Polietilenoglicóis/farmacologia , Ratos , Ratos Sprague-Dawley , Verapamil/farmacologia
3.
Mar Drugs ; 11(9): 3335-49, 2013 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-23999662

RESUMO

Our previous studies demonstrated that tentacle extract (TE) from the jellyfish, Cyanea capillata, could cause a dose-dependent increase of systolic blood pressure, which seemed to be the result of direct constriction of vascular smooth muscle (VSM). The aim of this study is to investigate whether TE could induce vasoconstriction in vitro and to explore its potential mechanism. Using isolated aorta rings, a direct contractile response of TE was verified, which showed that TE could induce concentration-dependent contractile responses in both endothelium-intact and -denuded aortas. Interestingly, the amplitude of contraction in the endothelium-denuded aorta was much stronger than that in the endothelium-intact one, implying that TE might also bring a weak functional relaxation in addition to vasoconstriction. Further drug intervention experiments indicated that the functional vasodilation might be mediated by nitric oxide, and that TE-induced vasoconstriction could be attributed to calcium influx via voltage-operated calcium channels (VOCCs) from the extracellular space, as well as sarcoplasmic reticulum (SR) Ca²âº release via the inositol 1,4,5-trisphosphate receptor (IP3R), leading to an increase in [Ca²âº](c), instead of activation of the PLC/DAG/PKC pathway or the sympathetic nerve system.


Assuntos
Aorta/efeitos dos fármacos , Cifozoários/química , Vasoconstritores/química , Vasoconstritores/farmacologia , Animais , Aorta/metabolismo , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Retículo Sarcoplasmático/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
4.
Biomed Res Int ; 2022: 3742447, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757472

RESUMO

Glioma is one of the most common intracranial malignancies that plagues people around the world. Despite current improvements in treatment, the prognosis of glioma is often unsatisfactory. Necroptosis is a form of programmed cell death. As research progresses, the role of necroptosis in tumors has gradually attracted the attention of researchers. And lncRNA is regarded as a critical role in the development of cancer. Therefore, this study is aimed at establishing a prognostic model based on necroptosis-associated lncRNAs to accurately assess the prognosis and immune response of patients with glioma. The RNA sequences of glioma patients and normal brain samples were downloaded from The Cancer Genome Atlas (TCGA) and GTEx databases, respectively. The coexpression analysis was performed to identify the necroptosis-related lncRNAs. Then, we utilized LASSO analysis following univariate Cox analysis to construct a prognostic model. Subsequently, we applied the Kaplan-Meier curve, time-dependent receiver operating characteristics (ROC), and univariate and multivariate Cox regression analyses to assess the effectiveness of this model. And the functional enrichment analyses and immune-related analyses were employed to investigate the potential biological functions. A validation set was obtained from the Chinese Glioma Genome Atlas (CGGA) database. And qRT-PCR was employed to further validate the expression levels of selected necroptosis-associated lncRNAs. Seven necroptosis-related lncRNAs (FAM13A-AS1, JMJD1C-AS1, LBX2-AS1, ZBTB20-AS4, HAR1A, SNHG14, and LINC00900) were determined to construct a prognostic model. The area under the ROC curve (AUC) was 0.871, 0.901, and 0.911 at 1, 2, and 3 years, respectively. The risk score was shown to be an important independent predictor in both univariate and multivariate Cox regression analyses. Through functional enrichment analyses, we found that the differentially expressed genes (DEGs) were mainly enriched in protein binding and signaling-related biological functions and immune-associated pathways. In conclusion, we established and validated a novel necroptosis-related lncRNA signature, which could accurately predict the overall survival of glioma patients and serve as potential therapeutic targets.


Assuntos
Glioma , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Proteínas Ativadoras de GTPase/genética , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Humanos , Imunidade , Histona Desmetilases com o Domínio Jumonji/genética , Estimativa de Kaplan-Meier , Necroptose/genética , Oxirredutases N-Desmetilantes/genética , Oxirredutases N-Desmetilantes/metabolismo , Prognóstico , RNA Longo não Codificante/metabolismo
5.
Front Cell Dev Biol ; 10: 840759, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359455

RESUMO

Gliomas are the most common and aggressive malignancies of the central nervous system. Histone deacetylases (HDACs) are important targets in cancer treatment. They regulate complex cellular mechanisms that influence tumor biology and immunogenicity. However, little is known about the function of HDACs in glioma. The Oncomine, Human Protein Atlas, Gene Expression Profiling Interactive Analysis, Broad Institute Cancer Cell Line Encyclopedia, Chinese Glioma Genome Atlas, OmicShare, cBioPortal, GeneMANIA, STRING, and TIMER databases were utilized to analyze the differential expression, prognostic value, and genetic alteration of HDAC and immune cell infiltration in patients with glioma. HDAC1/2 were considerable upregulated whereas HDAC11 was significantly downregulated in cancer tissues. HDAC1/2/3/4/5/7/8/11 were significantly correlated with the clinical glioma stage. HDAC1/2/3/10 were strongly upregulated in 11 glioma cell lines. High HDCA1/3/7 and low HDAC4/5/11 mRNA levels were significantly associated with overall survival and disease-free survival in glioma. HDAC1/2/3/4/5/7/9/10/11 are potential useful biomarkers for predicting the survival of patients with glioma. The functions of HDACs and 50 neighboring genes were primarily related to transcriptional dysregulation in cancers and the Notch, cGMP-PKG, and thyroid hormone signaling pathways. HDAC expression was significantly correlated with the infiltration of B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in glioma. Our study indicated that HDACs are putative precision therapy targets and prognostic biomarkers of survival in glioma patients.

6.
Front Immunol ; 13: 1037318, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405716

RESUMO

Background: Alzheimer's disease is the most common neurodegenerative disease worldwide. Metabolic syndrome is the most common metabolic and endocrine disease in the elderly. Some studies have suggested a possible association between MetS and AD, but few studied genes that have a co-diagnostic role in both diseases. Methods: The microarray data of AD (GSE63060 and GSE63061 were merged after the batch effect was removed) and MetS (GSE98895) in the GEO database were downloaded. The WGCNA was used to identify the co-expression modules related to AD and MetS. RF and LASSO were used to identify the candidate genes. Machine learning XGBoost improves the diagnostic effect of hub gene in AD and MetS. The CIBERSORT algorithm was performed to assess immune cell infiltration MetS and AD samples and to investigate the relationship between biomarkers and infiltrating immune cells. The peripheral blood mononuclear cells (PBMCs) single-cell RNA (scRNA) sequencing data from patients with AD and normal individuals were visualized with the Seurat standard flow dimension reduction clustering the metabolic pathway activity changes each cell with ssGSEA. Results: The brown module was identified as the significant module with AD and MetS. GO analysis of shared genes showed that intracellular transport and establishment of localization in cell and organelle organization were enriched in the pathophysiology of AD and MetS. By using RF and Lasso learning methods, we finally obtained eight diagnostic genes, namely ARHGAP4, SNRPG, UQCRB, PSMA3, DPM1, MED6, RPL36AL and RPS27A. Their AUC were all greater than 0.7. Higher immune cell infiltrations expressions were found in the two diseases and were positively linked to the characteristic genes. The scRNA-seq datasets finally obtained seven cell clusters. Seven major cell types including CD8 T cell, monocytes, T cells, NK cell, B cells, dendritic cells and macrophages were clustered according to immune cell markers. The ssGSEA revealed that immune-related gene (SNRPG) was significantly regulated in the glycolysis-metabolic pathway. Conclusion: We identified genes with common diagnostic effects on both MetS and AD, and found genes involved in multiple metabolic pathways associated with various immune cells.


Assuntos
Doença de Alzheimer , Síndrome Metabólica , Doenças Neurodegenerativas , Humanos , Idoso , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Síndrome Metabólica/genética , Leucócitos Mononucleares/metabolismo , Algoritmos , Aprendizado de Máquina , Biomarcadores , Proteínas Centrais de snRNP
7.
Regul Toxicol Pharmacol ; 56(2): 148-55, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19766684

RESUMO

Safety evaluation of synthetic human brain natriuretic peptide (shBNP) was carried out in cynomolgus monkeys (Macaca fascicularis) by 2-week intravenous toxicity studies. System exposure was also assessed throughout the whole administration. Three test groups received doses of 432, 1440 and 4320 microg/kg/day of shBNP, with a high infusion rate of 36 mL/kg/hr for 30 min compared to the clinical protocol of continuous infusion over 24h. Commercially available recombinant human brain natriuretic peptide (rhBNP) of 1440 microg/kg/day was used as positive control. The 2-week repeated intravenous doses of shBNP resulted in reversible increased serum LDH and CPK in monkeys receiving 1440 and 4320 microg/kg/day dose with no pertinent histopathological changes. Some changes related to the pharmacologic effects of BNP including hypotension was observed after administration. No treatment-related mortalities or renal dysfunction were found. Controversy about the safety issue of BNP as an exogenous hormone concerning ventricular remodeling and myocardial cell apoptosis, coupled with our results, were also discussed. The no-observed-adverse-effect level (NOAEL) was considered to be 432 microg/kg /day, which is about 20 times higher than the commonly used clinical dose. The results of the present study advocate the safety of shBNP in cynomolgus monkeys at levels used in the study.


Assuntos
Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Encefálico/toxicidade , Animais , Relação Dose-Resposta a Droga , Feminino , Humanos , Infusões Intravenosas , Macaca fascicularis , Masculino , Peptídeo Natriurético Encefálico/administração & dosagem , Nível de Efeito Adverso não Observado , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/sangue , Proteínas Recombinantes/toxicidade , Medição de Risco , Fatores de Tempo
8.
Artigo em Inglês | MEDLINE | ID: mdl-18391575

RESUMO

OBJECTIVES: To study whether rotational stimulus induced pica and whether the vestibular apparatus was necessary for obtaining rotation-induced pica in mice. METHODS: Pica behavior in mice was investigated following 60 min of rotation once daily at 70 rpm (15 s on with 5 s off) for 3 consecutive days. After evaluating vestibular function and histology of vestibular epithelia, we examined rotation-induced kaolin intake, so-called pica, in sham-lesioned and chemically labyrinthectomized mice. RESULTS: The labyrinthectomized mice exhibited loss of the contact righting and swimming capability while the destruction of hair cells of vestibular epithelia was observed. Moreover, mice subjected to rotation, but not labyrinthectomized mice, showed a significant increase in kaolin intake at the last 2 rotation sessions and the first postrotation session. CONCLUSIONS: The findings indicated that a functioning vestibular system is necessary for rotation-evoking pica in mice and thus pica can be a behavioral index of motion sickness in mice.


Assuntos
Comportamento Animal , Pica/fisiopatologia , Pica/psicologia , Rotação/efeitos adversos , Vestíbulo do Labirinto/fisiopatologia , Animais , Ingestão de Alimentos , Feminino , Caulim , Camundongos , Camundongos Endogâmicos , Enjoo devido ao Movimento/psicologia , Pica/etiologia , Pica/patologia , Vestíbulo do Labirinto/patologia
9.
Am J Cancer Res ; 8(4): 624-635, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29736308

RESUMO

Gliomas are the most prevalent type of primary brain tumors in adults, accounting for more than 40% of neoplasms in the central nervous system. The spen paralogue and orthologue C-terminal domain containing 1 (SPOCD1) has been recently identified and found to discriminate progressive from non-progressive bladder cancers. In this study, we detected high-level of SPOCD1 expression in glioma and its high expression significantly associated with advanced tumor grade and poor prognosis. In vitro assays showed that knockdown of SPOCD1 significantly inhibited cell proliferation and colony formation capacities in U373 and U87 cells. In a xenograft model of glioma, SPOCD1 was also found to inhibit tumor growth. In addition, knockdown of SPOCD1 was shown to inhibit cell migration and invasion in glioma U373 and U87 cells. SPOCD1 positively regulated the expression of Pentraxin 3 (PTX3), whereas overexpression of PTX3 attenuated SPOCD1 knockdown-mediated inhibition of cell proliferation, migration and invasion in glioma cells. Our observations suggest that SPOCD1 promotes the proliferation and metastasis of glioma cells through regulating PTX3. Our data might provide novel evidence for the diagnosis and treatment of glioma in clinic.

10.
Int J Biol Macromol ; 82: 488-96, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26529191

RESUMO

A bacterium strain, designated as CMF-2, was isolated from the jellyfish Cyanea capillata and its culture supernatant exhibited a significant antimicrobial activity. The strain CMF-2 was identified as Pseudomonas sp. based on the morphological, biochemical and physiological characteristics as well as 16S rRNA sequence analysis. In this study, an antimicrobial protein, named as CAP-1, was isolated from the culture of CMF-2 through ammonium sulfate precipitation and gel filtration chromatography. According to the result of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), a major band indicated that the antimicrobial protein had a molecular mass of about 15 kDa, and it was identified as a hypothetical protein by MALDI-TOF-MS analysis and Mascot searching. CAP-1 displayed a broad antimicrobial spectrum against the indicator bacteria and fungus, including Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Candida albicans, especially some marine-derived microorganisms such as Vibrio vulnificus, Vibrio alginolyticus, Vibrio parahaemolyticus, Vibrio cholera, and Vibrio anguillarum, but showed little impact on tumor cells and normal human cells. The protein CAP-1 remained a stable antimicrobial activity in a wide range of temperature (20-80°C) and pH (2-10) conditions. These results suggested that CAP-1 might have a specific antimicrobial function not due to cytotoxicity.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/farmacologia , Pseudomonas/metabolismo , Sequência de Aminoácidos , Animais , Anti-Infecciosos/isolamento & purificação , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/isolamento & purificação , Cromatografia em Gel , Fermentação , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Filogenia , Pseudomonas/classificação , Pseudomonas/genética , Pseudomonas/isolamento & purificação , Pseudomonas/ultraestrutura , RNA Ribossômico 16S/genética , Cifozoários/microbiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Simbiose , Temperatura
11.
Toxicon ; 108: 232-9, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26546696

RESUMO

Previously, we established delayed jellyfish envenomation syndrome (DJES) models and proposed that the hemorrhagic toxins in jellyfish tentacle extracts (TE) play a significant role in the liver and kidney injuries of the experimental model. Further, we also demonstrated that metalloproteinases are the central toxic components of the jellyfish Cyanea capillata (C. capillata), which may be responsible for the hemorrhagic effects. Thus, metalloproteinase inhibitors appear to be a promising therapeutic alternative for the treatment of hemorrhagic injuries in DJES. In this study, we examined the metalloproteinase activity of TE from the jellyfish C. capillata using zymography analyses. Our results confirmed that TE possessed a metalloproteinase activity, which was also sensitive to heat. Then, we tested the effect of metalloproteinase inhibitor batimastat (BB-94) on TE-induced hemorrhagic injuries in DJES models. Firstly, using SR-based X-ray microangiography, we found that BB-94 significantly improved TE-induced hepatic and renal microvasculature alterations in DJES mouse model. Secondly, under synchrotron radiation micro-computed tomography (SR-µCT), we also confirmed that BB-94 reduced TE-induced hepatic and renal microvasculature changes in DJES rat model. In addition, being consistent with the imaging results, histopathological and terminal deoxynucleotidyl transferase-mediated UTP end labeling (TUNEL)-like staining observations also clearly corroborated this hypothesis, as BB-94 was highly effective in neutralizing TE-induced extensive hemorrhage and necrosis in DJES rat model. Although it may require further clinical studies in the near future, the current study opens up the possibilities for the use of the metalloproteinase inhibitor, BB-94, in the treatment of multiple organ hemorrhagic injuries in DJES.


Assuntos
Mordeduras e Picadas/tratamento farmacológico , Venenos de Cnidários/toxicidade , Hemorragia/prevenção & controle , Fenilalanina/análogos & derivados , Substâncias Protetoras/uso terapêutico , Cifozoários , Tiofenos/uso terapêutico , Angiografia , Animais , Marcação In Situ das Extremidades Cortadas , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Metaloproteases/antagonistas & inibidores , Metaloproteases/química , Metaloproteases/toxicidade , Camundongos , Necrose/prevenção & controle , Fenilalanina/uso terapêutico , Ratos , Ratos Sprague-Dawley , Síndrome , Microtomografia por Raio-X
12.
Int J Clin Exp Pathol ; 8(6): 6434-41, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26261519

RESUMO

Chemoresistance is a major obstacle to successful chemotherapy for glioma. Formononetin is a novel herbal isoflavonoid isolated from Astragalus membranaceus and possesses antitumorigenic properties. In the present study, we investigated the anti-proliferative effects of formononetin on human glioma cells, and further elucidated the molecular mechanism underlying the anti-tumor property. We found that formononetin enhanced doxorubicin cytotoxicity in glioma cells. Combined treatment with formononetin reversed the doxorubicin-induced epithelial-mesenchymal transition (EMT) in tumor cells. Moreover, we found that formononetin treatment significantly decreased the expression of HDAC5. Overexpression of HDAC5 diminished the suppressive effects of formononetin on glioma cell viability. Furthermore, knockdown of HDAC5 by siRNA inhibited the doxorubicin-induced EMT in glioma cells. Taken together, these results demonstrated that formononetin-combined therapy may enhance the therapeutic efficacy of doxorubicin in glioma cells by preventing EMT through inhibition of HDAC5.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Doxorrubicina/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glioma/tratamento farmacológico , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Isoflavonas/farmacologia , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glioma/enzimologia , Glioma/genética , Glioma/patologia , Histona Desacetilases/genética , Humanos , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos , Transfecção
13.
Environ Pollut ; 125(3): 305-12, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12826408

RESUMO

Amaranthus tricolor L. and Amaranthus cruentus L. were grown in pots containing 7.5 kg soils artificially contaminated with three levels of 134Cs activity: 5.55 x 10(5) Bq pot-1, 1.11 x 10(6) Bq pot(-)1, and 1.665 x 10(6) Bq pot(-1), respectively. Forty-nine days after sowing and growth, plants were harvested. The plants growing in soils with increasing 134Cs concentrations showed increasing concentration of this radionuclide in shoots. There were significant differences in uptake of 134Cs applied to soils between and within the plant species, depending on the initial 134Cs concentrations. The plant species showed different responses to the addition of (NH4)2SO4 to soils. Biomass production of both species was reduced in pots treated with (NH4)2SO4. (NH4)2SO4 application decreased the uptake of 134Cs by A. tricolor but increased the accumulation of 134Cs by A. cruentus, showing that chemicals with the highest efficiency to enhance the desorption of 134Cs might play an unexpected role in transferring the radionuclide to shoots.


Assuntos
Amaranthus/metabolismo , Radioisótopos de Césio/farmacocinética , Brotos de Planta/metabolismo , Poluentes Radioativos do Solo/farmacocinética , Amaranthus/efeitos dos fármacos , Amaranthus/crescimento & desenvolvimento , Sulfato de Amônio/farmacologia , Biomassa , Relação Dose-Resposta a Droga , Brotos de Planta/efeitos dos fármacos , Potássio/análise , Solo/análise , Especificidade da Espécie
14.
Mol Med Rep ; 10(4): 2045-50, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25050565

RESUMO

Histone deacetylases (HDACs) constitute a family of enzymes that play important roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation and apoptosis of cancer cells. However, the biological function of HDAC5 in glioma cells has not been fully understood. In the present study, we found that the mRNA and protein levels of HDAC5 are increased in human glioma tissues and cell lines. In addition, overexpression of HDAC5 promoted proliferation of glioma cells, as measured by the MTT assay. By contrast, HDAC5 gene silencing using small interfering RNA (siRNA) inhibited cell proliferation. Furthermore, we demonstrated that HDAC5 enhances Notch 1 expression at both the mRNA and the protein level in glioma cell lines. Taken together, these results demonstrated, for the first time to the best of our knowledge, that HDAC5 promotes glioma cell proliferation, and suggest that this effect involves the upregulation of Notch 1. Therefore, our study may provide a novel therapeutic target for treatment of gliomas.


Assuntos
Histona Desacetilases/metabolismo , Receptor Notch1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Glioma/metabolismo , Glioma/patologia , Histona Desacetilases/química , Histona Desacetilases/genética , Humanos , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Receptor Notch1/genética , Regulação para Cima
15.
PLoS One ; 9(5): e97509, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24824597

RESUMO

Thioredoxins (Trx proteins) are a family of small, highly-conserved and ubiquitous proteins that play significant roles in the resistance of oxidative damage. In this study, a homologue of Trx was identified from the cDNA library of tentacle of the jellyfish Cyanea capillata and named CcTrx1. The full-length cDNA of CcTrx1 was 479 bp with a 312 bp open reading frame encoding 104 amino acids. Bioinformatics analysis revealed that the putative CcTrx1 protein harbored the evolutionarily-conserved Trx active site 31CGPC34 and shared a high similarity with Trx1 proteins from other organisms analyzed, indicating that CcTrx1 is a new member of Trx1 sub-family. CcTrx1 mRNA was found to be constitutively expressed in tentacle, umbrella, oral arm and gonad, indicating a general role of CcTrx1 protein in various physiological processes. The recombinant CcTrx1 (rCcTrx1) protein was expressed in Escherichia coli BL21 (DE3), and then purified by affinity chromatography. The rCcTrx1 protein was demonstrated to possess the expected redox activity in enzymatic analysis and protection against oxidative damage of supercoiled DNA. These results indicate that CcTrx1 may function as an important antioxidant in C. capillata. To our knowledge, this is the first Trx protein characterized from jellyfish species.


Assuntos
Regulação da Expressão Gênica/fisiologia , Modelos Moleculares , Cifozoários/genética , Tiorredoxinas/genética , Tiorredoxinas/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Western Blotting , Clonagem Molecular , DNA Complementar/genética , Escherichia coli , Etiquetas de Sequências Expressas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Dados de Sequência Molecular , Fases de Leitura Aberta/genética , Oxirredução , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Cifozoários/metabolismo , Análise de Sequência de DNA , Homologia de Sequência , Tiorredoxinas/química
16.
Toxicon ; 74: 1-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23916600

RESUMO

Our previous studies have shown that tentacle extract (TE) from the jellyfish Cyanea capillata could induce a delayed jellyfish envenomation syndrome with severe multiple organ dysfunctions, among which renal injury with tubular necrosis seemed to be most serious. So, in this study, we aimed to explore the toxic effect of TE on rat renal tubular epithelial NRK-52E cells. Based on the previous findings that TE could cause oxidative damage in erythrocytes, the effects of TE on cell oxidative stress conditions, including ROS production and lipid peroxidation, and mitochondrial dysfunction associated with cell death were investigated in NRK-52E cells. The results showed that TE caused cell morphological change and decreased cell viability through induction of apoptosis and necrosis in NRK-52E cells. Meanwhile, ROS overproduction and mitochondrial membrane potential decrease were found before the cell death occurred. It was concluded that TE could induce cytotoxicity, especially apoptosis and necrosis, in NRK-52E cells, and mitochondrial dysfunction and ROS overproduction might play important roles in the process of cell injury and death.


Assuntos
Venenos de Cnidários/toxicidade , Células Epiteliais/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Cifozoários/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Túbulos Renais/citologia , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Necrose/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo
17.
Toxicon ; 61: 54-61, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23151380

RESUMO

The delayed jellyfish envenomation syndrome (DJES) with serious multiple organ dysfunction or systemic damages, generally developed 2 h after jellyfish stings, deserves special attention for it is very meaningful to the clinical interventions. To set up a DJES model as well as to obtain more details about its process, an integrative approach, including clinical chemistry, pathology and immunohistochemistry, was conducted to simultaneously monitor the effects of tentacle extract (TE) from the jellyfish Cyanea capillata on the vital target organs (heart, lung, liver and kidney). Our results showed that the TE from C. capillata could induce diverse toxic effects on these organs, among which the liver and kidney injuries seemed to be more serious than cardiopulmonary injuries and might be the leading causes of death in rats with DJES. In summary, we have established a DJES model with multiple organ dysfunction, which could facilitate the research on its underlying mechanism as well as the development of specific prevention or therapy strategies against jellyfish envenomation. The application of this model suggested that the possible mechanism of DJES might be attributed to the synergy of cytotoxicity, vasoconstriction effect and other specific target organ toxicities of jellyfish venom.


Assuntos
Venenos de Cnidários/toxicidade , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Animais , Análise Química do Sangue , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Eletrólitos/sangue , Imuno-Histoquímica , Dose Letal Mediana , Masculino , Microscopia Eletrônica de Transmissão , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/patologia , Ratos , Ratos Sprague-Dawley , Extratos de Tecidos/toxicidade
18.
Int J Phytoremediation ; 10(2): 159-70, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18709927

RESUMO

In our survey in the copper (Cu) mining area of China, a sun fern (Pteridium revolutum) was found to accumulate 30-567 mg Cu kg(-1) DW (33 samples) in its fronds with a large frond biomass. Cu translocation factors in the plants varied from 0.09 to 3.88. In a greenhouse pot experiment, the effect of an elevated CO2 concentration (700 microL L(-1)) on Cu accumulation in plants was studied using three fern species (P. revolutum, Pteridium aquilinum, and Pteris vittata) grown in the Cu-contaminated soil. P. revolutum showed a higher Cu tolerance but its Cu translocation factor was lower than 1. At the elevated CO2 concentration, frond biomass of all species was significantly increased, as was the total Cu content in the fronds of P. revolutum and P. aquilinum. Our study suggests that P. revolutum could serve as a good candidate for phytoextraction of Cu-contaminated soils and that doubling the ambient CO2 concentration will facilitate its use in phytoextraction.


Assuntos
Dióxido de Carbono/farmacologia , Cobre/metabolismo , Pteridium/efeitos dos fármacos , Pteridium/metabolismo , Poluentes do Solo/metabolismo , Biomassa , Relação Dose-Resposta a Droga , Mineração , Especificidade da Espécie
19.
Ying Yong Sheng Tai Xue Bao ; 17(3): 507-11, 2006 Mar.
Artigo em Zh | MEDLINE | ID: mdl-16724752

RESUMO

A field survey on the Petridium revolutum growing on the Cu mining spoils in Yunnan Province and related greenhouse hydroponic sand culture experiment showed that when growing on the soil with an average Cu concentration of 2 432 mg x kg(-1) DW and the maximum Cu concentration of 7 554 mg x kg(-1) DW, P. revolutum had a large amount of aboveground biomass, with the maximum dry weight of 40.05 g x plant(-1) DW and the average dry weight of 18.33 g x plant(-1) DW. The average and maximum Cu contents were 201 and 567 mg x kg(-1) DW in aboveground biomass, and 346 and 1723 kg(-1) DW in underground biomass, respectively. The transfer factor of Cu reached a maximum of 3.88, with an average of 0.81. Under quartz sand culture condition, P. revolutum could grow well when the Cu concentration in nutrient solution was 7 mg x L(-1). The accumulation of Cu by P. revolutum plant increased significantly with increasing Cu concentration, with the most of absorbed Cu concentrated in underground biomass. It was suggested that P. revolutum had a remarkable tolerance to Cu and a potential capacity of Cu accumulation, and could be used in the phytoremediation of Cu-polluted soils.


Assuntos
Cobre/análise , Mineração , Plantas/metabolismo , Poluentes do Solo/análise , Solo/análise , Biodegradação Ambiental , Cobre/farmacocinética , Poluentes do Solo/farmacocinética
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