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1.
Biomolecules ; 11(7)2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34356672

RESUMO

In the search for new therapeutic strategies to contrast SARS-CoV-2, we here studied the interaction of polydatin (PD) and resveratrol (RESV)-two natural stilbene polyphenols with manifold, well known biological activities-with Spike, the viral protein essential for virus entry into host cells, and ACE2, the angiotensin-converting enzyme present on the surface of multiple cell types (including respiratory epithelial cells) which is the main host receptor for Spike binding. Molecular Docking simulations evidenced that both compounds can bind Spike, ACE2 and the ACE2:Spike complex with good affinity, although the interaction of PD appears stronger than that of RESV on all the investigated targets. Preliminary biochemical assays revealed a significant inhibitory activity of the ACE2:Spike recognition with a dose-response effect only in the case of PD.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/tratamento farmacológico , Glucosídeos/farmacologia , Resveratrol/farmacologia , SARS-CoV-2/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/metabolismo , Estilbenos/farmacologia , COVID-19/metabolismo , Descoberta de Drogas , Medicamentos de Ervas Chinesas/farmacologia , Inibidores Enzimáticos/farmacologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica/efeitos dos fármacos , SARS-CoV-2/metabolismo
2.
Sci Rep ; 11(1): 12412, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127760

RESUMO

The control of Covid 19 epidemics by public health policy in Italy during the first and the second epidemic waves has been driven by using reproductive number Rt(t) to identify the supercritical (percolative), the subcritical (arrested), separated by the critical regime. Here we show that to quantify the Covid-19 spreading rate with containment measures there is a need of a 3D expanded parameter space phase diagram built by the combination of Rt(t) and doubling time Td(t). In this space we identify the Covid-19 dynamics in Italy and its administrative Regions. The supercritical regime is mathematically characterized by (i) the power law of Td vs. [Rt(t) - 1] and (ii) the exponential behaviour of Td vs. time, either in the first and in the second wave. The novel 3D phase diagram shows clearly metastable states appearing before and after the second wave critical regime. for loosening quarantine and tracing of actives cases. The metastable states are precursors of the abrupt onset of a next nascent wave supercritical regime. This dynamic description allows epidemics predictions needed by policymakers interested to point to the target "zero infections" with the elimination of SARS-CoV-2, using the Finding mobile Tracing policy joint with vaccination-campaign, in order to avoid the emergence of recurrent new variants of SARS-CoV-2 virus, accompined by recurrent long lockdowns, with large economical losses, and large number of fatalities.


Assuntos
COVID-19/prevenção & controle , Simulação por Computador , COVID-19/epidemiologia , COVID-19/patologia , COVID-19/virologia , Busca de Comunicante , Humanos , Itália/epidemiologia , Política Pública , Quarentena , SARS-CoV-2/isolamento & purificação
3.
Nutrients ; 13(3)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805648

RESUMO

BACKGROUND: Polydatin is a stilbenoid with important antioxidant, anti-inflammatory, and immunomodulating properties. The aim of this study was to assess the anti-inflammatory preventive effect of polydatin in the mouse model of acute arthritis induced by calcium pyrophosphate (CPP) crystals. METHODS: Acute arthritis was induced by the injection of a suspension of sterile CPP crystals into the ankle joint of Balb/c mice. Animals were randomized to receive polydatin or colchicine (the control drug) according to a prophylactic and a therapeutic protocol. The primary outcome was the variation of ankle swelling obtained after crystal injection and treatment, while histological parameters such as leukocyte infiltration, IL-1ß and CXCL1 levels and tissue expression were considered as secondary outcomes. RESULTS: Prophylactic treatment with PD significantly diminished ankle swelling after 48 h from crystal injection. Secondary outcomes such as leukocyte infiltration, necrosis, edema, and synovitis were also decreased. PD caused a reduction in circulating levels of IL-1ß and CXCL1, as well as their tissue expression. By contrast, the therapeutic administration of PD did not have any beneficial effect. CONCLUSIONS: PD can effectively prevent acute inflammatory response to crystals in the mouse model of CPP crystal-induced arthritis. These results suggest that this bioactive compound might be used in the prevention of crystal-induced acute attacks in humans.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/prevenção & controle , Glucosídeos/farmacologia , Estilbenos/farmacologia , Doença Aguda , Animais , Artrite Experimental/induzido quimicamente , Pirofosfato de Cálcio , Quimiocina CXCL1/efeitos dos fármacos , Interleucina-1beta/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Tarso Animal/efeitos dos fármacos
4.
Materials (Basel) ; 13(20)2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33050281

RESUMO

Diseases determining bone tissue loss have a high impact on people of any age. Bone healing can be improved using a therapeutic approach based on tissue engineering. Scientific research is demonstrating that among bone regeneration techniques, interesting results, in filling of bone lesions and dehiscence have been obtained using adult mesenchymal stem cells (MSCs) integrated with biocompatible scaffolds. The geometry of the scaffold has critical effects on cell adhesion, proliferation and differentiation. Many cytokines and compounds have been demonstrated to be effective in promoting MSCs osteogenic differentiation. Oligostilbenes, such as Resveratrol (Res) and Polydatin (Pol), can increase MSCs osteoblastic features. 3D printing is an excellent technique to create scaffolds customized for the lesion and thus optimized for the patient. In this work we analyze osteoblastic features of adult MSCs integrated with 3D-printed polycarbonate scaffolds differentiated in the presence of oligostilbenes.

6.
Foods ; 8(11)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703439

RESUMO

Resveratol (RES) and its natural precursor polydatin (PD) are polyphenols that may display a broad variety of beneficial effects including anti-inflammatory properties. This study aimed to investigate the role of RES and PD in the inflammatory process induced by monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in vitro. A monocytic cell line (THP-1) was primed for 3 hours with phorbol myristate acetate (100 ng/mL) and stimulated with synthetic MSU (0.05 mg/mL) and CPP (0.025 mg/mL) crystals. RES and PD were added to cultures concurrently with the crystals, or as 2-hour pretreatment. The effect of the two polyphenols was evaluated on intracellular and extracellular IL-1ß levels, NACHT-LRRPYD-containing protein-3 (NLRP3) inflammasome expression, reactive oxygen species (ROS) and nitric oxide (NO) production, and the assessment of crystal phagocytosis. RES and PD strongly inhibited IL-1ß induced by crystals after cell pretreatment. Cell pretreatment was effective also in reducing IL-1 mRNA expression while no effect was observed on NLRP3 gene expression. RES and PD had no effect on crystal phagocytosis when used as pretreatment. Both polyphenols were significantly effective in inhibiting ROS and NO production. Our results demonstrated that RES and PD are effective in inhibiting crystal-induced inflammation. Data obtained after cell pretreatment allow us to hypothesize that these polyphenols act on specific signaling pathways, preventing inflammation.

7.
Scientifica (Cairo) ; 2019: 9136249, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30838155

RESUMO

Background: Severe skin rash is listed among important side effects of EGFR tyrosine kinase inhibitors. Polydatin (PD), a glycosylated polyphenol, is endowed with anti-inflammatory activity in human epidermal keratinocytes. Objective: This study evaluated the effect of topical application of a moisturizer containing PD to prevent skin rash in patients with mutated non-small cell lung cancer (NSCLC) treated with afatinib. Materials and Methods: Eligible NSCLC patients with metastatic disease were treated with first-line afatinib 40 mg/die. One day before starting systemic therapy, all patients received topical administration of a 1.5% PD-based cream b.i.d. every day until the end of afatinib treatment. Results: Out of 34 treated patients, the incidence of skin rash (all grades) was 41.2% and grade 2 rash was 20.6%, and grade 3 rash was not observed in any of the patients. None of the patients discontinued therapy for toxicity. The mean duration of treatment was 6.4 months, calculated from the time treatment was started to the date treatment was stopped. Conclusion: The results showed that a PD-based cream can reduce the incidence of grade ≥2 skin toxicities in patients treated with afatinib. Clinical study registration number: Prot. No. 130/CE Lazio 1 Italy.

8.
Int J Med Sci ; 15(9): 944-952, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30008608

RESUMO

Bone loss and fractures are consequences of aging, diseases or traumas. Furthermore the increased number of aged people, due to the rise of life expectancy, needs more strategies to limit the bone loss and regenerate the lost tissue, ameliorating the life quality of patients. A great interest for non-pharmacological therapies based on natural compounds is emerging and focusing on the oligostilbene Polydatin, present in many kinds of fruits and vegetables, when resveratrol particularly in red wines. These molecules have been extensively studied due to their antioxidant and anti-inflammatory effects, showing more recently Resveratrol the ability to enhance osteogenic differentiation and bone formation. However, the clinical applications of Resveratrol are limited due to its low bioavailability and rapid metabolism, while its natural glycosilated precursor Polydatin shows better metabolic stability and major abundance in fresh fruits and vegetables. Nevertheless the role of Polydatin on osteogenic differentiation is still unexplored. Mesenchymal stem cells (MSCs) from dental tissues, such as dental bud stem cells (DBSCs), are able to differentiate toward osteogenic lineage: thus we investigated how Resveratrol and Polydatin influence the differentiation of DBSCs, eventually affecting bone formation. Our results showed that Polydatin increases MSCs osteogenic differentiation sharing similar properties with Resveratrol. These results encourage to deepen the effects of this molecule on bone health and its associated mechanisms of action, wishing for the future a successful use in bone loss prevention and therapy.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Glucosídeos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Estilbenos/farmacologia , Células Cultivadas , Criança , Humanos , Masculino , Resveratrol
9.
Oncol Rep ; 40(3): 1435-1442, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30015848

RESUMO

Oral squamous cell carcinoma (OSCC) is one of the most aggressive and deadliest tumors worldwide. The aryl hydrocarbon receptor (AHR) is a nuclear transcription factor known as a dioxin receptor and mediates the toxic effects of industrial contaminants. In addition, AHR has been implicated in multiple cellular processes and its expression has been shown to play a critical role in tumorigenesis, including human oral cancer cell lines. In the present study, we evaluated the expression of AHR/HSP-90 in 25 formalin­fixed, paraffin-embedded human oral cancer specimens by IHC analysis. CYP1A1 expression was regarded as an AHR reporter gene. The data indicated a complete correlation between AHR expression and cancer grade enabling us to propose AHR as a prognostic marker of oral cancer. Moreover, in OSCC cell line CAL27, we observed the modulatory effect of polydatin, a widespread natural substance and direct precursor of resveratrol, on AHR expression. A computational approach was performed to predict the site of interaction of polydatin on the AHR surface. Our studies confirm the involvement of AHR signaling in the clinicopathological specimens of oral cancer and suggest the use of polydatin for oral cancer prevention.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Citocromo P-450 CYP1A1/antagonistas & inibidores , Glucosídeos/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Neoplasias Bucais/metabolismo , Receptores de Hidrocarboneto Arílico/antagonistas & inibidores , Estilbenos/farmacologia , Apoptose/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Citocromo P-450 CYP1A1/metabolismo , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Gradação de Tumores , Projetos Piloto , Receptores de Hidrocarboneto Arílico/metabolismo , Células Tumorais Cultivadas
10.
Food Chem ; 239: 964-974, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-28873659

RESUMO

The inhibition properties of a number of antioxidants against peroxidation, started by a 2,2'-azobis[2-(2-imidazolin-2-yl)propane] radical initiator, of linoleic acid in sodium dodecyl sulfate micelles, have been determined in terms of oxygen consumption by a Clark electrode in an oxygen-tight cell. For the 31 antioxidants investigated at variable concentrations, the experimental results well fit the kinetic equation for competitive reactions. The ratio between the initial rates, monitored in the absence and in the presence of antioxidants, depends linearly on their concentration. From the slopes of these straight lines, an absolute scale of inhibition properties of the lipid peroxidation can be devised. Furthermore, the little difference of the time of complete oxygen consumption on concentration of different antioxidants has been found, indicating a restricted difference towards chemical structure and stoichiometric ratio. Some considerations regarding the mechanisms of inhibition of the lipid peroxidation in micelles, in view of bibliographic data, have been made.


Assuntos
Peroxidação de Lipídeos , Antioxidantes , Radicais Livres , Cinética , Micelas , Oxirredução
11.
Exp Ther Med ; 14(1): 3-9, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28672886

RESUMO

Health promotion strategies and lifestyle changes are important in disease prevention. Oral health has received a large amount of attention previously as it is a fundamental component of general health and it contributes to the quality of life. Therefore, the study of associations between diet, health and the presence of bioactive compounds in food is receiving a substantial amount of attention. In the present review the effects and targets of a natural polyohenolic stilbenoid compound; resveratrol (3,5,4'-trihydroxystilbene; RSV) is assessed, and the future prospects for RSV in promoting oral health are considered. RSV is a phytoalexin, synthesized by a wide range of plants and abundantly extracted in grape skin, it has been purported to exert a multiplicity of anti-inflammatory, anti-viral, anti-microbial, estrogenic, anticancer, cardioprotective, neuroprotective and immunomodulatory functions. In this review, following an introduction documenting the biochemistry of RSV and RSV glucosides, the bioavailability and pharmacokinetics of RSV are described. Considering its multiple properties, the present review has focused on the potential benefits of RSV as an antioxidant and chemopreventive agent.

12.
J Microbiol Methods ; 128: 34-41, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27392938

RESUMO

The principal fungal species isolated from a contaminated library environment were tested for their microbial volatile organic compound (MVOC) production ability. Aspergillus creber, A. penicillioides, Cladosporium cladosporioides, Eurotium chevalieri, E. halophilicum, Penicillium brevicompactum and P. chrysogenum were cultivated on suitable culture media inside sample bottles specifically designed and created for direct MVOC injection to a GC-MS instrument. The fungal emissions were monitored over several weeks to detect changes with the aging of the colonies, monitored also by respirometric tests. A total of 55 different MVOCs were detected and isopropyl alcohol, 3-methyl-1-butanol and 2-butanone were the principal compounds in common between the selected fungal species. Moreover, 2,4-dimethylheptane, 1,4-pentadiene, styrene, ethanol, 2-methyl-1-butanol, acetone, furan and 2-methylfuran were the most detected compounds. For the first time, the MVOC production for particular fungal species was detected. The species A. creber, which belongs to the recently revised group Aspergillus section Versicolores, was characterized by the production of ethanol, furan and 1,4-pentadiene. For the xerophilic fungus E. halophilicum, specific production of acetone, 2-butanone and 1,4-pentadiene was detected, supported also by respirometric data. The results demonstrated the potential use of this method for the detection of fungal contamination phenomena inside Cultural Heritage's preservation environments.


Assuntos
Microbiologia Ambiental , Fungos/química , Bibliotecas , Compostos Orgânicos Voláteis/análise , Aspergillus/química , Aspergillus/isolamento & purificação , Butanonas/análise , Cladosporium/química , Cladosporium/isolamento & purificação , Meios de Cultura/química , Fungos/classificação , Furanos/análise , Cromatografia Gasosa-Espectrometria de Massas , Penicillium/química , Penicillium/isolamento & purificação , Pentanóis/análise , Análise de Componente Principal
13.
J Exp Clin Cancer Res ; 35(1): 118, 2016 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-27448598

RESUMO

BACKGROUND: Human T-cell leukemia virus (HTLV-1) is a lymphotropic retrovirus associated to adult T cell leukemia (ATL) and to non-neoplastic inflammatory conditions affecting the central nervous system, lung or skin. The inflammatory disorders associated to HTLV-1 are mediated by different proinflammatory cytokines as IL-1α, IL-6, TNF-α. The release and the role of IL-17 is still debated. Aims of this study were to analyze IL-17 induction by HTLV-1 infection and to determine whether resveratrol (RES) is able to down regulate the pathway of cytokines production either in HTLV-1 chronically infected MT-2 cell line or in human CD4+ cells infected in vitro with HTLV-1. METHODS: MT-2 and HTLV-1 infected CD4+ cells were analyzed for proinflammatory cytokine production before or after RES treatment. The concentrations of IL-17, IL-1α, IL-6, and TNF-α were measured in cell culture supernatants by ELISA and SearchLight™ technology. The IL-17 mRNA expression was evaluated by RT-PCR. NF-kB activation was detected by non-radioactive, Electro Mobility Shift Assay (EMSA). HTLV-1 RNA expression was detected by Real-time-PCR (RQ-PCR). RESULTS: We found that RES is capable of inducing a dose-dependent inhibition of IL-1α, IL-6 and TNF-α production in vitro and can down regulate the expression of IL-17 at both mRNA and protein levels in HTLV-1 infected cells. This effect was associated with a dose-dependent inhibition of the of the nuclear factor kappa-B (NF-kB) activity. Conversely, RES did not apparently affect HTLV-1 proliferation. CONCLUSIONS: These results support the anti-inflammatory properties of RES, suggesting that it might be a useful therapeutic agent for the treatment of HTLV-1 related inflammatory diseases.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Linfócitos T CD4-Positivos/virologia , Regulação para Baixo , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Interleucina-17/metabolismo , Estilbenos/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linhagem Celular , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-17/genética , Interleucina-1alfa/genética , Interleucina-1alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Resveratrol , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
14.
Inflammation ; 36(1): 26-34, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22956122

RESUMO

It is well known that human keratinocytes produce the anti-microbial peptide ß-defensin 2. Its production is enhanced by pathogenic microorganisms or other environmental stressors. In this study, we evaluated the effect of resveratrol, a polyphenol found in several dietary source as grape seed, and its natural precursor, polydatin on heat-stressed human keratinocytes. By reverse transcription-polymerase chain reaction and enzyme-linked immunoadsorbent assay, we demonstrated that resveratrol used in combination with polydatin was able to modulate interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha gene expression. In addition, our data show that resveratrol and polydatin increased the heat shock protein (Hsp)70B' gene expression, a Hsp that plays an important role in the cytoprotection and repair of cells and tissues. Worthy of note, polydatin used alone or in combination with resveratrol, increased the release of human ß-defensin 2. These results highlighted the ability of polydatin and resveratrol to reinforce cytoprotective response in stress conditions and suggest their use in cosmetic or pharmaceutical preparations.


Assuntos
Glucosídeos/farmacologia , Inflamação/tratamento farmacológico , Queratinócitos/metabolismo , Estilbenos/farmacologia , beta-Defensinas/biossíntese , Linhagem Celular , Citoproteção/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/biossíntese , Proteínas de Choque Térmico HSP70/metabolismo , Resposta ao Choque Térmico , Humanos , Interleucina-6/biossíntese , Interleucina-6/metabolismo , Interleucina-8/biossíntese , Interleucina-8/metabolismo , Resveratrol , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/metabolismo , beta-Defensinas/metabolismo
15.
Biophys Chem ; 135(1-3): 76-83, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18420333

RESUMO

The antioxidant activities of trans-resveratrol (trans-3,5,4'-trihydroxystilbene) and trans-piceid (trans-5,4'-dihydroxystilbene-3-O-beta-D-glucopyranoside), its more widespread glycosilate derivative, have been compared measuring their inhibitory action on peroxidation of linoleic acid (LA) and the radical scavenging ability towards different free radicals (such as DPPH) and radical initiators. It has been found that the two stilbenes have similar antioxidant capacity, while the comparison with BHT (2,6-di-tert-butyl-4-methylphenol) and alpha-tocopherol (vitamin E, vit. E), taken as reference, points out a slower but prolonged protective action against lipid peroxidation. Furthermore, piceid appears more efficacious than resveratrol as a consequence of the reaction of the latter with its radical form. The DSC profiles of phosphatidylcholine liposomes of various chain lengths, and EPR measurements of spin labelled liposomes demonstrated that the susceptible hydroxyl group of these compounds are located in the lipid region of the bilayer close to the double bonds of polyunsaturated fatty acids, making these stilbenes particularly suitable for the prevention and control of the lipid peroxidation of the membranes.


Assuntos
Antioxidantes/farmacologia , Glucosídeos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Micelas , Estilbenos/farmacologia , Lipossomas Unilamelares/química , Antioxidantes/química , Hidroxitolueno Butilado/química , Glucosídeos/química , Modelos Biológicos , Estrutura Molecular , Resveratrol , Estilbenos/química , Vitamina E/química
16.
Int J Oncol ; 28(3): 641-8, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16465368

RESUMO

A number of previous studies investigated the in vitro effects of resveratrol on malignant human breast epithelial cell replication. The aim of the present study was to evaluate the activity of resveratrol on human metastatic breast cancer cells. The study was performed on the MCF-7 tumor cell line. Cell growth, cell cycle perturbation and apoptosis were evaluated by trypan blue dye exclusion assay, flow cytometric analysis and confocal fluorescence microscopy. TRAP assay and Western blot analysis respectively detected levels of telomerase activity and levels of hTERT in intracellular compartments of MCF-7 cells treated with resveratrol. Resveratrol has a direct inhibitory effect on cell proliferation. The results demonstrate that the drug induces apoptosis in MCF-7 cells, in a time- and concentration-related manner. Our results also show that the growth-inhibitory effect of resveratrol on malignant cells is mainly due to its ability to induce S-phase arrest and apoptosis in association with reduced levels of telomerase activity. In particular, TRAP assay and Western blot analysis respectively showed that resveratrol treatment down-regulates the telomerase activity of target cells and the nuclear levels of hTERT, the reverse transcriptase subunit of the telomerase complex. In our experimental model of breast cancer, resveratrol shows direct antiproliferative and pro-apoptotic effects. Studies on telomerase function and intracellular hTERT distribution point out that this agent is endowed with additional suppressive functions on critical tumor biological properties. These results speak in favor of a potential role of resveratrol in chemoprevention/chemotherapy of breast cancer.


Assuntos
Proliferação de Células/efeitos dos fármacos , Estilbenos/farmacologia , Telomerase/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Feminino , Citometria de Fluxo , Humanos , Microscopia Confocal , Resveratrol , Fatores de Tempo
17.
J Med Virol ; 70(1): 31-41, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12629641

RESUMO

Iacovacci et al. [(1997a) Research in Virology 148:147-151] described that the euploid diploid cells, of the normal human bone marrow-derived lymphoblastoid B-cell line TO.FE., are susceptible to hepatitis C virus (HCV) infection and support long term virus production. Transmission electron microscopy described some steps of HCV replication cycle in this in vitro infected cellular system [Serafino et al. (1997) Research in Virology 148:153-159]. In the present study, in order to identify the intracellular sites involved in HCV replication, the ultrastructural changes associated with infection in TO.FE. cells were correlated with the subcellular localisation of structural and nonstructural viral proteins. Transmission electron microscopy and confocal microscopy data indicate that these viral proteins appeared located in the Golgi apparatus and endoplasmic reticulum, suggesting an active involvement of these compartments in viral assembly and morphogenesis. Furthermore, transmission and scanning electron microscopic observations on cultures infected chronically support the hypothesis that these cellular compartments may serve as starting sites of the morphological changes associated to viral infection and replication, leading to cell-cell fusion, syncytia formation, and finally lysis of infected cells and virus release.


Assuntos
Linfócitos B/virologia , Retículo Endoplasmático/virologia , Complexo de Golgi/virologia , Hepacivirus/fisiologia , Replicação Viral , Linhagem Celular , Retículo Endoplasmático/fisiologia , Retículo Endoplasmático/ultraestrutura , Complexo de Golgi/fisiologia , Complexo de Golgi/ultraestrutura , Humanos , Técnicas In Vitro , Microscopia Eletrônica
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