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1.
Tumour Biol ; 41(4): 1010428319846803, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31018830

RESUMO

Mesenchymal stem cells have therapeutic properties that are related to their potentials for trans-differentiation, immunomodulation, anti-inflammatory, inhibitory effect on tumor proliferation, and induction of apoptosis. This study was performed to analyze the role of mesenchymal stem cells as an alternative for cellular signaling growth factors involved in the pathogenesis of leukemogenesis in rats. Treatment of rats with 7,12-dimethyl benz [a] anthracene induced leukemogenesis appeared as a significant decrease in hematological parameters with concomitant significant increase in bone marrow oxidative and inflammatory indices (transforming growth factor beta and interleukin-6) in comparison with normal groups. On the contrary, Western immunoblotting showed a significant increase in the signaling growth factors: PI3K, AKT, mTOR proteins and a significant decrease in PTEN in 7,12-dimethyl benz [a] anthracene-treated group. In addition, a significant increase in the transcript levels of B cell lymphoma-2 protein gene in the 7,12-dimethyl benz [a] anthracene group, while that of C-X-C motif chemokine receptor-4 and B cell lymphoma-2 protein associated x-protein were significantly downregulated compared to controls. Meanwhile, therapeutic mesenchymal stem cells treatment predict a significant improvement versus 7,12-dimethyl benz [a] anthracene group through the modulation of growth factors that confront bone marrow dysplasia. In the same direction treatment of 7,12-dimethyl benz [a] anthracene group with mesenchymal stem cells, it induced apoptosis and increased the homing efficacy to bone marrow. In conclusion, mesenchymal stem cells improve hematopoiesis and alleviate inflammation, and modulated PI3K/AKT signaling pathway contributed to experimental leukemogenesis.


Assuntos
Leucemia/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Proteína Oncogênica v-akt/genética , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Apoptose/genética , Células da Medula Óssea/patologia , Diferenciação Celular/genética , Proliferação de Células/genética , Modelos Animais de Doenças , Humanos , Leucemia/induzido quimicamente , Leucemia/genética , Leucemia/patologia , PTEN Fosfo-Hidrolase , Fosfatidilinositol 3-Quinases/genética , Ratos , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Fator de Crescimento Transformador beta/genética
2.
Mar Drugs ; 14(11)2016 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-27834847

RESUMO

Penitrem A (PA) is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K) channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety. Astaxanthin (AST) is a marine natural xanthophyll carotenoid with documented antioxidant activity. Unlike other common antioxidants, AST can cross blood brain barriers (BBBs), inducing neuroprotective effects. Docosahexaenoic acid (DHA) is polyunsaturated ω-3 fatty acid naturally occurring in fish and algae. DHA is essential for normal neurological and cellular development. This study evaluated the protective activity of AST and DHA against PA-induced toxicity, in vitro on Schwann cells CRL-2765 and in vivo in the worm Caenorhbitidis elegans and Sprague Dawley rat models. PA inhibited the viability of Schwann cells, with an IC50 of 22.6 µM. Dose-dependent treatments with 10-100 µM DHA significantly reversed the PA toxicity at its IC50 dose, and improved the survival of Schwann cells to 70.5%-98.8%. Similarly, dose-dependent treatments with 10-20 µM AST reversed the PA toxicity at its IC50 dose and raised these cells' survival to 61.7%-70.5%. BK channel inhibition in the nematode C. elegans is associated with abnormal reversal locomotion. DHA and AST counteracted the in vivo PA BK channel antagonistic activity in the C. elegans model. Rats fed a PA-contaminated diet showed high levels of glutamate (GLU), aspartate (ASP), and gamma amino butyric acid (GABA), with observed necrosis or absence of Purkinjie neurons, typical of PA-induced neurotoxicity. Dopamine (DA), serotonin (5-HT), and norepinephrine (NE) levels were abnormal, Nitric Oxide (NO) and Malondialdehyde (MDA) levels were significantly increased, and total antioxidant capacity (TAC) level in serum and brain homogenates was significantly decreased in PA-treated rats. DHA and AST treatments effectively counteracted the toxic effects of PA and normalized most biochemical parameters in rats. DHA and AST can be useful food additives to prevent and reverse PA food-induced toxicity.


Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/antagonistas & inibidores , Micotoxinas/efeitos adversos , Animais , Antioxidantes/farmacologia , Produtos Biológicos/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Locomoção/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Xantofilas/farmacologia
3.
Egypt J Immunol ; 21(2): 75-83, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25812354

RESUMO

Tuberculosis (TB) remains one of the major challenges to the global public health. The most powerful tools in any TB control program are prompt diagnosis and successful treatment of patients with active contagious disease. For almost 100 years the tuberculin skin test (TST) has been used to support the diagnosis of active and latent TB infection. The TST has a number of limitations, most notable low specificity in BCG vaccinated individuals due to cross-reactive components in PPD and the Mycobacterium bovis BCG vaccine strain and an intensive search for new and more specific diagnostic antigens has therefore been ongoing. The current diagnostic techniques utilize production of Interferon-gamma (IFN-γ) in response to novel M. tuberculosis (MTB) synthetic overlapping peptides mixtures to detect MTB infection. The aim of this study was to evaluate human immune responses to two novel Mycobacterium tuberculosis latency associated antigens Rv2659 Pepmix and Rv2660 Pepmix in comparison with ESAT-6 Pepmix. We compared the production of IFN-γ by ELISA following overnight stimulation with the antigens among the different groups of our study, TST negative healthy subjects (n = 16), TST positive healthy subjects (n = 16) and active pulmonary TB patients (n = 30). Our results showed that in TB patients, a positive IFN-γ response was observed to ESAT-6 by 73% of the donors, 47% responded to Rv2659 and 57% responded to Rv2660 when compared to TST negative controls. In conclusion, the ESAT-6 pepmix is recognized in a greater proportion of TB patients compared to Rv2659 and Rv2660, and levels of IFN-γ in response to ESAT-6 are higher than the levels observed in response to Rv2659 and Rv2660.


Assuntos
Antígenos de Bactérias/farmacologia , Proteínas de Bactérias/farmacologia , Interferon gama/imunologia , Mycobacterium tuberculosis/imunologia , Peptídeos/farmacologia , Linfócitos T/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium bovis/imunologia , Linfócitos T/patologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/patologia
4.
Photodiagnosis Photodyn Ther ; 10(4): 446-59, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24284098

RESUMO

BACKGROUND: Indocyanine green (ICG) is a promising photosensitive agent for photodynamic therapy (PDT) of tumors. Encapsulating ICG dye in polymeric nanoparticles based on PEBBLE technology forming (ICG-PEBBLE) could improve the aqueous stability of the entrapped ICG molecules. The study objective is to investigate the PDT effect of free ICG-PEBBLE and its Anti-EGFR conjugate. METHODS: Skin squamous cell carcinoma was induced in CD1 mice by dimethylbenzanthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) followed by a PDT protocol for four weeks. RESULTS: PDT using ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR decreased skin tumor sizes. Our findings revealed that the inflammatory mediators tumor necrosis factor (TNF-α), nitric oxide (NO), cycloxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), the angiogenic mediator vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) were decreased, while apoptosis, caspase-3 and histone acetylation were induced in tumor bearing groups after PDT using both of ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR. CONCLUSION: The present study indicated the effectiveness of PDT using ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR as an inhibitor modality for tumor size, apoptosis, angiogenesis and tumor inflammation. The conjugating of ICG-PEBBLE to anti-EGFR was found to be more effective in inhibiting VEGF and in increasing caspase-3 compared to free ICG-PEBBLE, but there were no other preferential PDT efficacy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Receptores ErbB/metabolismo , Verde de Indocianina/administração & dosagem , Nanocápsulas/uso terapêutico , Fotoquimioterapia/métodos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Animais , Receptores ErbB/antagonistas & inibidores , Feminino , Camundongos , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/química , Siloxanas/química , Neoplasias Cutâneas/patologia , Resultado do Tratamento
5.
Photodiagnosis Photodyn Ther ; 10(2): 173-85, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23769284

RESUMO

BACKGROUND: Photodynamic therapy (PDT) is a therapeutic modality involving the use of a photosensitizer agent activated by light of appropriate wavelength to selectively destroy tumor cells. Indocyanine green (ICG) is a promising photosensitive agent for PDT of tumor cells. The main disadvantage of using ICG in PDT is the instability of ICG in aqueous solutions. Encapsulating ICG dye in a biocompatible matrix based on PEBBLE technology showed an improvement of aqueous stability comparing with free ICG dye. The main objective of this study is to investigate the photodynamic effect of ICG-ormosil PEBBLEs on two different cell lines: human breast adenocarcinoma cells (MCF-7) and hepatocellular carcinoma cells (HepG2). METHODS: ICG-embedded ormosil PEBBLEs were synthesized based on a sol-gel process, and characterized by transmission electron microscopy and other fluorescence tests. The cell viability was evaluated by MTT and trypan blue assays. Apoptosis, necrosis, and DNA damage (comet assay), were evaluated by fluorescence microscopic tests. RESULTS: The results declared that ICG-ormosil PEBBLEs and free ICG both have the same cytotoxic and phototoxic effect on MCF-7 and HepG2 cell lines, where the apoptotic mode of cell death is preferentially occurred in case of PDT using ICG-ormosil PEBBLEs. Both ICG and ICG-ormosil PEBBLEs induced DNA damage after laser exposure. These results would suggest that entrapping ICG in Polymeric nanoparticles forming ICG-ormosil PEBBLEs improve the aqueous stability of the photosensitizer and in the same time retain its photodynamic activity, suggesting that it is preferred to use ICG-ormosil PEBBLEs instead of free ICG dye.


Assuntos
Verde de Indocianina/química , Nanocápsulas/uso terapêutico , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Fotoquimioterapia/métodos , Polímeros/química , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Hep G2 , Humanos , Verde de Indocianina/uso terapêutico , Células MCF-7 , Nanocápsulas/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Siloxanas/química , Resultado do Tratamento
6.
Clin Biochem ; 42(13-14): 1401-6, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19559018

RESUMO

OBJECTIVES: To investigate the possibility of depending on adiponectin and leptin as early predictors of microvascular complications in type 1 diabetic subjects. DESIGN AND METHODS: We studied 63 type 1 diabetic subjects from the National Institute of Diabetes (30 normoalbuminuric and 33 microalbuminuric). Clinical, demographic characteristics and kidney function tests were monitored. Plasma levels of adiponectin, leptin, interlukein-6 (IL-6), and the high sensitive C-reactive protein (CRP) were measured in these subjects. RESULTS: Microalbuminuric subjects showed a significant elevation in adiponectin levels and a significant decrease in leptin levels as compared to normoalbuminuric subjects. Adiponectin showed a significant positive correlation with microalbuminuria concentrations while leptin showed a significant negative correlation with both fasting blood glucose and glycated hemoglobin A(1c). CONCLUSION: The results of this study introduced the possibility of depending on adiponectin and leptin as early, reliable, and sensitive predictors for the microvascular complications monitored by microalbuminuria concentration and glycemic control indices.


Assuntos
Adiponectina/sangue , Diabetes Mellitus Tipo 1/sangue , Leptina/sangue , Doenças Vasculares/sangue , Adolescente , Albuminúria/sangue , Albuminúria/complicações , Albuminúria/diagnóstico , Biomarcadores/sangue , Glicemia/análise , Proteína C-Reativa/análise , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/complicações , Diagnóstico Precoce , Ensaio de Imunoadsorção Enzimática , Jejum/sangue , Feminino , Hemoglobina A Glicada/análise , Humanos , Interleucina-6/sangue , Testes de Função Renal , Masculino , Valor Preditivo dos Testes , Análise de Regressão , Doenças Vasculares/complicações , Doenças Vasculares/diagnóstico
7.
J Clin Lipidol ; 3(4): 269-74, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21291823

RESUMO

BACKGROUND: Adipose tissue is known to produce and secrete a variety of bioactive substances known as adipocytokines. Adiponectin and leptin are considered to be among the most important adipocytokines: OBJECTIVES: We sought to explore the relationships between adipocytokines (adiponectin and leptin), plasma lipoprotein lipid, and diabetic control indices in type 1 diabetic subjects. SUBJECTS AND METHODS: In this study 63 clinically diagnosed type 1 diabetic subjects and 30 age- and sex-matched healthy control subjects were analyzed. Age, sex, diabetic duration, family history of diabetes, daily insulin dose, weight, height, body mass index, and systolic and diastolic blood pressure were recorded. Fasting blood glucose, glycated hemoglobin A(1c), total hemoglobin, plasma lipoprotein, lipid and plasma concentrations of adiponectin and leptin were measured in type 1 diabetic subjects and control subjects. RESULTS: In this study a significant increase in triglycerides and high-density lipoprotein cholesterol in plasma of type 1 diabetics was found as compared with normal control subjects. In type 1diabetic subjects, plasma adiponectin was significantly elevated, whereas leptin showed a significant decrease as compared to a normal control group. Leptin concentrations showed a positive correlation with body mass index and systolic blood pressure but a negative correlation with both fasting blood glucose and glycated hemoglobinA(1c). CONCLUSION: The results of this study suggest that blood leptin but not adiponectin concentrations have a significant correlation with indices of glycemic control.

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