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1.
Nutr Health ; : 2601060231209555, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280233

RESUMO

Background: The energy balance between inputs and outputs is essential to avoid a reduction in performance, recovery difficulties, hormonal problems, an increased risk of fatigue, injuries and illnesses. Aim: The purpose of the study is to evaluate whether the energy intake assumed by non-professional sportsmen of the new fitness disciplines on the basis of the guidelines present in the literature, meets the needs required by their sporting activity. Methods: The sample consist of 20 non-competitive adult sportsmen (n.10 females; n.10 males) that were voluntarily enrolled in a gym, belonging to the various fitness disciplines: bodybuilders (n = 2); calisthenics (n = 3); crossfitters (n = 15). The subjects underwent an anamnestic-nutritional interview and used a photographic atlas to estimate the energy intake in the training day (in terms of macronutrients, micronutrients and H2O). Results: The results of the study reported: a lower energy intake, the breakdown of macronutrients was suitable for the nutritional indications reported by bibliographic sources, with the exception for protein intake that was higher than the other macronutrients; a lower intake of fibers, mono/polyunsaturated fatty acids; an higher intake of simple sugars, proteins and H2O, and by a normal parameters of carbohydrates, fats and saturated fatty acids. Conclusions: Generally the study has shown that the sample energy intake is extremely low in the training day. Therefore, it is useful to educate sportsmen, coaches and families in order to avoid deficiencies/excess of calories and nutrients which may not be functional for the sporting activity performed.

2.
Int J Mol Sci ; 24(3)2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36768382

RESUMO

Cholesterol accumulation in macrophages leads to the formation of foam cells and increases the risk of developing atherosclerosis. We have verified whether hydroxytyrosol (HT), a phenolic compound with anti-inflammatory and antioxidant properties, can reduce the cholesterol build up in THP-1 macrophage-derived foam cells. We have also investigated the potential mechanisms. Oil Red O staining and high-performance liquid chromatography (HPLC) assays were utilized to detect cellular lipid accumulation and cholesterol content, respectively, in THP-1 macrophages foam cells treated with HT. The impact of HT on cholesterol metabolism-related molecules (SR-A1, CD36, LOX-1, ABCA1, ABCG1, PPARγ and LRX-α) in foam cells was assessed using real-time PCR (RT-qPCR) and Western blot analyses. Finally, the effect of HT on the adhesion of THP-1 monocytes to human vascular endothelial cells (HUVEC) was analyzed to study endothelial activation. We found that HT activates the PPARγ/LXRα pathway to upregulate ABCA1 expression, reducing cholesterol accumulation in foam cells. Moreover, HT significantly inhibited monocyte adhesion and reduced the levels of adhesion factors (ICAM-1 and VCAM-1) and pro-inflammatory factors (IL-6 and TNF-α) in LPS-induced endothelial cells. Taken together, our findings suggest that HT, with its ability to interfere with the import and export of cholesterol, could represent a new therapeutic strategy for the treatment of atherosclerotic disease.


Assuntos
Células Espumosas , PPAR gama , Humanos , Células Espumosas/metabolismo , PPAR gama/metabolismo , Células Endoteliais/metabolismo , Colesterol/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Receptores X do Fígado/metabolismo
3.
Int J Mol Sci ; 23(24)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36555859

RESUMO

Living organisms do not disregard the laws of thermodynamics and must therefore consume energy for their survival. In this way, cellular energy exchanges, which aim above all at the production of ATP, a fundamental molecule used by the cell for its metabolisms, favor the formation of waste products that, if not properly disposed of, can contribute to cellular aging and damage. Numerous genes have been linked to aging, with some favoring it (gerontogenes) and others blocking it (longevity pathways). Animal model studies have shown that calorie restriction (CR) may promote longevity pathways, but given the difficult application of CR in humans, research is investigating the use of CR-mimetic substances capable of producing the same effect. These include some phytonutrients such as oleuropein, hydroxytyrosol, epigallo-catechin-gallate, fisetin, quercetin, and curcumin and minerals such as magnesium and selenium. Some of them also have senolytic effects, which promote the apoptosis of defective cells that accumulate over the years (senescent cells) and disrupt normal metabolism. In this article, we review the properties of these natural elements that can promote a longer and healthier life.


Assuntos
Produtos Biológicos , Senoterapia , Humanos , Animais , Produtos Biológicos/farmacologia , Envelhecimento , Senescência Celular , Quercetina/farmacologia
4.
J Am Coll Nutr ; 39(2): 178-186, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31393225

RESUMO

Background: The amount of healthy subjects adopting a gluten-free diet (GFD) for nonmedical reasons actually surpasses the numbers of those who are dealing with a permanent gluten-related disorder.Objective: The study aimed to better clarify the interactions between a GFD and physical and psychological well-being.Methods: Sixty healthy subjects with normal weight were enrolled. Thirty subjects (15 female) were submitted to a normocaloric GFD and considered as the experimental group (EG), and 30 subjects (15 female) were submitted to a normocaloric diet (CG) for 6 months. The hematochemical and psychological parameters before and after the diet were recorded.Results: Significant improvement was demonstrated in red blood count, hemoglobin, total cholesterol, and high-density lipoprotein parameters in the EG after the gluten-free diet. However, a significant increase of α-amylase pancreatic activity and reduction of vitamin B12 and magnesium levels in the EG were observed. Regarding the psychological parameters, the GFD significantly improved scores assessing body satisfaction, but increased social insecurity.Conclusions: The study is the first to consider significant modulation in hematochemical parameters as well as psychological ones by gluten avoidance in healthy individuals. Although these subjects were not characterized by intestinal mucosa damage, some of the effects were similar to those observed in celiac disease patients who began to adhere to a GFD.


Assuntos
Dieta Livre de Glúten/estatística & dados numéricos , Nível de Saúde , Adulto , Afeto , Contagem de Células Sanguíneas , Pressão Sanguínea , Imagem Corporal/psicologia , Doença Celíaca/dietoterapia , Dieta , Dieta Livre de Glúten/psicologia , Ingestão de Energia , Feminino , Voluntários Saudáveis , Humanos , Itália , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Inquéritos e Questionários
5.
Int J Mol Sci ; 20(13)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269760

RESUMO

Chenopodium quinoa Wild is a "pseudocereal" grain which attracts a lot of attention in the scientific community as it has a positive effect on health. Here, we investigate the presence of biologically active O-prenylated phenylpropanoids in the ethanol extract of commercially available quinoa seeds. We claim that 4'-Geranyloxyferulic acid (GOFA) was the only phytochemical product found that belongs to quinoa's group secondary metabolites. We studied the changes in the oxidative and inflammatory status of the cellular environment in HCT 116 cell line processed with quinoa extract and its component GOFA; the implementation was done through the analysis of the antioxidant enzymes (SOD and CAT), the pro-inflammatory components (iNOS, IL-6 and TNF-α), and the products of intermediary metabolism (ONOO-, O2-). Moreover, the l-arginine uptake was proposed as a target of the tested compounds. We demonstrated that the GOFA, through a decrease of the CAT-2B expression, leads to a reduction of the l-arginine uptake, downregulating the harmful iNOS and restoring the altered redox state. These results propose a new molecular target involved in the reduction of the critical inflammatory process responsible for the cancer progression.


Assuntos
Anticarcinógenos/farmacologia , Arginina/metabolismo , Transportador 2 de Aminoácidos Catiônicos/metabolismo , Ácidos Cumáricos/farmacologia , Óxido Nítrico/metabolismo , Anticarcinógenos/química , Chenopodium quinoa/química , Ácidos Cumáricos/química , Células HCT116 , Humanos , Inflamação/metabolismo , Inflamação/prevenção & controle , Neoplasias/metabolismo , Neoplasias/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Sementes/química
6.
J Cell Mol Med ; 22(5): 2750-2759, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29512923

RESUMO

Gastroesophageal reflux disease (GERD), a clinical condition characterized by reflux of gastroduodenal contents in the oesophagus, has proved to demonstrate a strong link between oxidative stress and the development of GERD. Proton pump inhibitors (PPIs) have been universally accepted as first-line therapy for management of GERD. The potential benefits of electrolysed reduced water (ERW), rich in molecular hydrogen, in improving symptoms and systemic oxidative stress associated with GERD was assessed. The study was performed on 84 GERD patients undergoing control treatment (PPI + tap water) or experimental treatment (PPI + ERW) for 3 months. These patients were subjected to the GERD-Health Related Quality of Life Questionnaire as well as derivatives reactive oxigen metabolites (d-ROMs) test, biological antioxidant potential (BAP) test, superoxide anion, nitric oxide and malondialdehyde assays, which were all performed as a proxy for the oxidative/nitrosative stress and the antioxidant potential status. Spearman's correlation coefficient was used to evaluate the correlation between scores and laboratory parameters. Overall results demonstrated that an optimal oxidative balance can be restored and GERD symptoms can be reduced rapidly via the integration of ERW in GERD patients. The relative variation of heartburn and regurgitation score was significantly correlated with laboratory parameters. Thus, in the selected patients, combination treatment with PPI and ERW improves the cellular redox state leading to the improvement of the quality of life as demonstrated by the correlation analysis between laboratory parameters and GERD symptoms.


Assuntos
Refluxo Gastroesofágico/sangue , Refluxo Gastroesofágico/terapia , Hidrogênio/uso terapêutico , Água/farmacologia , Adulto , Idoso , Antioxidantes/metabolismo , Humanos , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Inibidores da Bomba de Prótons/uso terapêutico , Qualidade de Vida , Adulto Jovem
7.
Int J Mol Sci ; 18(4)2017 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-28333102

RESUMO

Polyphenols compounds are a group molecules present in many plants. They have antioxidant properties and can also be helpful in the management of sepsis. Licochalcone C (LicoC), a constituent of Glycyrrhiza glabra, has various biological and pharmacological properties. In saying this, the effect of LicoC on the inflammatory response that characterizes septic myocardial dysfunction is poorly understood. The aim of this study was to determine whether LicoC exhibits anti-inflammatory properties on H9c2 cells that are stimulated with lipopolysaccharide. Our results have shown that LicoC treatment represses nuclear factor-κB (NF-κB) translocation and several downstream molecules, such as inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Moreover, LicoC has upregulated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) signaling pathway. Finally, 2-(4-Morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002), a specific PI3K inhibitor, blocked the protective effects of LicoC. These findings indicate that LicoC plays a pivotal role in cardiac dysfunction in sepsis-induced inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Chalconas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular , Molécula 1 de Adesão Intercelular/metabolismo , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos
8.
J Cell Physiol ; 231(11): 2439-51, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26895796

RESUMO

Several studies have shown that xanthones obtained from Garcinia Mangostana (GM) have remarkable biological activities. α-mangostin (α-MG) is the main constituent of the fruit hull of the GM. Several findings have suggested that SIRT-1, a nuclear histone deacetylase, could influence cellular function by the inhibition of NF-kB signaling. ROS can inhibit SIRT-1 activity by initiating oxidative modifications on its cysteine residues, and suppression of SIRT-1 enhances the NF-κB signaling resulting in inflammatory responses. The goals of the present study were to evaluate the quantity of α-MG in the methanolic extract of GM (Vithagroup Spa) and to investigate the activity of this xanthone in U937 cell line and in human monocytes from responsive to inflammatory insult analyzing the possible changes on the activation of SIRT-1 protein via NF-Kb. Cells were treated with the methanolic extract of GM and/or LPS. The chromatographic separation of α-MG was performed by an HPLC analysis. EX 527, a specific SIRT-1 inhibitor, was used to determine if SIRT-1/NfkB signaling pathway might be involved in α-MG action on cells. Our results show that α-MG inhibits p65 acetylation and down-regulates the pro-inflammatory gene products as COX-2, iNOS via SIRT-1 activation. Cells treated with EX 527 showed an up-regulation of NFkB acetylation and an over expression of inducible enzymes and their product of catalysis (NO and PGE2). These results suggest that α-MG may be useful for the development of alternative pharmacological strategies aimed at reducing the inflammatory process. J. Cell. Physiol. 231: 2439-2451, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Inflamação/patologia , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Xantonas/farmacologia , Acetilação/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Citoproteção/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Garcinia/química , Humanos , Lipopolissacarídeos , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Superóxidos/metabolismo , Células U937 , Xantonas/química
9.
Int J Mol Sci ; 17(9)2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27598129

RESUMO

It is known that increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) can exert harmful effects, altering the cellular redox state. Electrolyzed Reduced Water (ERW) produced near the cathode during water electrolysis exhibits high pH, high concentration of dissolved hydrogen and an extremely negative redox potential. Several findings indicate that ERW had the ability of a scavenger free radical, which results from hydrogen molecules with a high reducing ability and may participate in the redox regulation of cellular function. We investigated the effect of ERW on H2O2-induced U937 damage by evaluating the modulation of redox cellular state. Western blotting and spectrophotometrical analysis showed that ERW inhibited oxidative stress by restoring the antioxidant capacity of superoxide dismutase, catalase and glutathione peroxidase. Consequently, ERW restores the ability of the glutathione reductase to supply the cell of an important endogenous antioxidant, such as GSH, reversing the inhibitory effect of H2O2 on redox balance of U937 cells. Therefore, this means a reduction of cytotoxicity induced by peroxynitrite via a downregulation of the NF-κB/iNOS pathway and could be used as an antioxidant for preventive and therapeutic application. In conclusion, ERW can protect the cellular redox balance, reducing the risk of several diseases with altered cellular homeostasis such as inflammation.


Assuntos
Antioxidantes/farmacologia , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Água/farmacologia , Antioxidantes/química , Linhagem Celular Tumoral , Eletrólise/métodos , Humanos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Pesquisa Translacional Biomédica/métodos , Água/química
10.
J Cell Mol Med ; 19(7): 1548-56, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25807993

RESUMO

Polyphenols are the major components of many traditional herbal remedies, which exhibit several beneficial effects including anti-inflammation and antioxidant properties. Src homology region 2 domain-containing phosphatase-1 (SHP-1) is a redox sensitive protein tyrosine phosphatase that negatively influences downstream signalling molecules, such as mitogen-activated protein kinases, thereby inhibiting inflammatory signalling induced by lipopolysaccharide (LPS). Because a role of transforming growth factor ß-activated kinase-1 (TAK1) in the upstream regulation of JNK molecule has been well demonstrated, we conjectured that SHP-1 could mediate the anti-inflammatory effect of verbascoside through the regulation of TAK-1/JNK/AP-1 signalling in the U937 cell line. Our results demonstrate that verbascoside increased the phosphorylation of SHP-1, by attenuating the activation of TAK-1/JNK/AP-1 signalling. This leads to a reduction in the expression and activity of both COX and NOS. Moreover, SHP-1 depletion deletes verbascoside inhibitory effects on pro-inflammatory molecules induced by LPS. Our data confirm that SHP-1 plays a critical role in restoring the physiological mechanisms of inducible proteins such as COX2 and iNOS, and that the down-regulation of TAK-1/JNK/AP-1 signalling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of inflammatory diseases.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Glucosídeos/farmacologia , Inflamação/enzimologia , Inflamação/patologia , Fenóis/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Morte Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Ciclo-Oxigenase 2/metabolismo , Ativação Enzimática/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Glucosídeos/química , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Dados de Sequência Molecular , Óxido Nítrico Sintase Tipo II/metabolismo , Fenóis/química , Fosforilação/efeitos dos fármacos , Transdução de Sinais , Fator de Transcrição AP-1/metabolismo , Tirosina/metabolismo , Células U937
11.
Brain Behav Immun ; 46: 261-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25712259

RESUMO

Several studies have focused on the relationship between hormonal changes and affective states in sporting contexts relating to an agonistic outcome. More recently, pro-inflammatory cytokines have also been successfully associated with affective state modulation. The aim of this study was to investigate whether athletes who won or lost show different levels of steroid hormones (testosterone and cortisol), pro-inflammatory cytokine IL-1ß, or expressions of anger and anxiety during six training fights in seasonal competitions down to the main seasonal competition. In 25 male kick-boxing athletes (age±SD, 28.68±5.34), anger states (RS score) and anxiety states (AS score) were assessed by STAXI-2 and STAI-Y, respectively. Cortisol (C), testosterone (T) and IL-1ß salivary levels were measured by the ELISA method. The saliva samples were taken in the afternoon, 30min prior to the start and 30min from the end of both simulated and official competitions. The results showed that the RS score, T, T/C ratio salivary levels increased during the season, whereas the AS score, C and IL-1ß suggested an opposite trend. Close to an official competition, the RS score, T, T/C ratio and IL-1ß salivary concentrations were significantly higher, and then decreased during competition. By contrast, the AS score and C levels significantly increased throughout the official competition. In addition, significant differences were found for hormones and IL-1ß concentrations as well as psychometric assessment close to the outcome of an official match. Athletes who lost showed an higher AS score and C level, while those who won were characterized by an higher level during the pre-competition RS score, T, T/C ratio, and IL-1ß. Note that these factors were positively and significantly correlated at the pre-official competition time, while in a linear regression analysis, IL-1ß, T and T/C ratio concentrations explained 43% of the variance in the RS score observed at the same time (adjusted R(2)=0.43, ANOVA P<.05). Our data suggest that the beginning of an agonistic event could trigger emotional responses which correspond to different biological processes instead that of a simulated fight. In particular, IL-1ß could be a potential new biological marker of anger and the combined measurement of these factors may be a useful way of understanding athletes' change in relation to their performance.


Assuntos
Ira/fisiologia , Ansiedade/psicologia , Atletas , Comportamento Competitivo/fisiologia , Hidrocortisona/análise , Interleucina-1beta/análise , Testosterona/análise , Adulto , Afeto/fisiologia , Ansiedade/fisiopatologia , Humanos , Masculino , Saliva/química , Estações do Ano , Esportes , Adulto Jovem
12.
Mol Pharm ; 12(1): 66-74, 2015 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-25375771

RESUMO

A novel cyclic prodrug of S-allyl-glutathione (CP11), obtained by using an acyloxy-alkoxy linker, was estimated for its pharmacokinetic and biological properties. The stability of CP11 was evaluated at pH 1.2, 7.4, in simulated fluids with different concentrations of enzymes, and in human plasma. The anti-inflammatory ability of CP11 was assessed in U937 cells, an immortalized human monocyte cell line. Results showed that CP11 is stable at acidic pH showing a possible advantage for oral delivery due to the longer permanence in the stomach. Having a permeability coefficient of 2.49 × 10(-6) cm s(-1), it was classified as discrete BBB-permeable compound. Biological studies revealed that CP11 is able to modulate inflammation mediated by LPS in U937 cells preventing the increase of ROS intracellular levels through interaction with the MAPK pathway.


Assuntos
Inibidores Enzimáticos/química , Glutationa/química , Glutationa/síntese química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Pró-Fármacos/química , Espécies Reativas de Oxigênio/metabolismo , Permeabilidade da Membrana Celular , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Lipopolissacarídeos/química , Modelos Químicos , Monócitos/citologia , Permeabilidade , Temperatura , Células U937
13.
Eur J Ophthalmol ; : 11206721241236919, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38444247

RESUMO

BACKGROUND: recently much studies evidenced the potential role of photo-biomodulation (PBM) in patients affected by Age-related Macular Degeneration (AMD). We designed a new wearable device for self-medication that employs the same broadband red light described in literature, but with extremely low irradiance. AIM: to demonstrate the safety and effectiveness of low-fluence light stimulations emitted by a LED source with appropriate wavelengths through our new device in improving short-term visual function in patients affected by severe non neovascular AMD. MATERIALS AND METHODS: we prospectively enrolled patients affected by severe non-neovascular AMD with a relative sparing of the foveal region. All the patients were randomly assigned in placebo or in treatment group. The treatment consisted of 10 sessions of 10-min each, using the new device comprised of micro-LEDs that emitted light onto an amorphous support assembled within Metallic eyeglasses. The placebo group blindly underwent the same number of PBM sessions with the micro-LED turned off. Before and after each placebo/treatment sessions all the patients received: optical coherence tomography (OCT), Best-Corrected Visual Acuity (BCVA) and Microperimetry (MP). RESULTS: no significant differences in the anatomical parameters were observed in the two groups. The MP mean sensitivity and the central visual function both far and near significantly improved in the treated group (respectively p < 0.001, p < 0.001). CONCLUSIONS: our pivotal demonstrated that the LED PBM delivered through our new device is a safe and effective tool for improving short-term visual function in patients affected by severe non-neovascular AMD.

14.
Biochim Biophys Acta ; 1820(12): 2095-104, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22951221

RESUMO

BACKGROUND: Previous reports suggest that NO may contribute to the pathophysiology of septic shock. Recently, we have synthesized and characterized a series of benzyl- and dibenzyl derivative of N-(3-aminobenzyl)acetamidine, a potent and selective inhibitor of iNOS, in vitro assay. We evaluated the molecular mechanisms by which these compounds are involved in the regulation of NOSs expression. METHODS: H9c2 cells were stimulated with lipopolysaccharide (LPS) in the presence or absence of acetamidine-derivative. The NOSs mRNA and protein, and activation of signaling pathways (Akt and NF-κB) were assayed. RESULTS: The induction of endotoxic shock in H9c2 with LPS caused an increase of inducible NOS and a down-regulation of constitutive NOS. The molecular mechanism involved in the modulation of NOSs expression in H9c2 cells upon LPS stimulation resulted in the modification of the redox state responsible for NF-kB nuclear translocation via NIK -IKKα/ß-IkBα, simultaneously to the inactivation of the PI3K/Akt pathway. The compounds acted as an anti-inflammatory modulator. CONCLUSION: These results suggest that LPS regulates the opposite NOS expression in H9c2 cells by modifying the redox state of these cells responsible for the NF-kB nuclear translocation via NIK-IKKα/ß-IkBα, simultaneous to the inactivation of the PI3K/Akt pathway. The new molecule acts as an anti-inflammatory modulator in LPS-induced inflammation in H9c2 cells by the restoration of eNOS and nNOS expressions, mechanistically involving the PI3K/Akt pathway. GENERAL SIGNIFICANCE: This study delineates the underlying mechanisms of opposite NOSs expression in H9c2 cells stimulated with LPS.


Assuntos
Amidinas/farmacologia , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Mioblastos Cardíacos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citometria de Fluxo , Humanos , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Inflamação/induzido quimicamente , Inflamação/patologia , Mioblastos Cardíacos/citologia , Mioblastos Cardíacos/efeitos dos fármacos , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Nitritos/metabolismo , Oxirredução , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Mensageiro/genética , Ratos , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos
15.
Electrophoresis ; 34(15): 2275-80, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23712818

RESUMO

Analytical methods for quantification of 5'-methylcytosine in genomes are important tools to investigate epigenetic changes in gene expression during development, differentiation, aging, or cancer. Here, we report a novel genomic methylation content assay based on enzymatic hydrolysis of DNA and MEKC separation of 5'-deoxyribonucleoside monophosphates (dNMP) using the cationic surfactant CTAB as pseudostationary phase. Calf Thymus DNA was used during method development to determine electrophoretic parameters and electrolyte composition for a complete separation between 2'-deoxycytosine-5'-monophosphate and 2'-deoxy-5'-methylcytosine 5'-monophosphate (d5mCMP). Methylated and not methylated oligonucleotides were used to confirm the identity of each peak and evaluate analytical parameters of the method. The LOD of the method was found to be 12.5 pmol/µL for d5mCMP.


Assuntos
Cromatografia Capilar Eletrocinética Micelar/métodos , Metilação de DNA , DNA/metabolismo , Espectrofotometria Ultravioleta/métodos , Animais , Bovinos , Cetrimônio , Compostos de Cetrimônio , Monofosfato de Citidina/análogos & derivados , Monofosfato de Citidina/análise , Monofosfato de Citidina/química , DNA/genética , Hidrólise , Limite de Detecção , Reprodutibilidade dos Testes
16.
Aggress Behav ; 39(2): 141-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23208827

RESUMO

Recently, several studies reported a relationship between immune system activation and anger expression. Consequently, the aim of this study was to explore immunitary molecular mechanisms that potentially underlie anger expression. To this end, we applied the Frustration-Aggression Theory in a contact sport model, utilizing the nearing of sporting events to trigger anger feelings. In parallel, we evaluated the activation of immune system at mRNA levels. We enrolled 20 amateur rugby players (age ± SD, 27.2 ± 4.5) who underwent psychological assessment to evaluate anger, with the State-Trait Anger Expression Inventory-2 (STAXI-2), before rugby matches; at the same time blood samples were taken to analyze the variations of gene expression by microarray. During the 2 hr before each game, a significant increase was verified in the Rage State (RS) score compared to the score ascertained 72 hr before. At the same time, we found modulation in expression profile, in particular increased expression of gene that encodes interleukin l-ß (IL-1ß). In a regression analysis, RS score was related to IL-1ß, and the potential risk factors age, body mass index, smoking, and drinking. The levels of cytokine were positively and independently related to RS score. Our results suggest that the nearing of sporting event can trigger anger state feelings and activate immune system in rugby players. We propose the IL-1ß as a potential biological marker of anger. However, further research is necessary to clarify the correlation between cytokine and anger.


Assuntos
Ira/fisiologia , Atletas/psicologia , Futebol Americano/fisiologia , Interleucina-1beta/sangue , Adulto , Fatores Etários , Agressão/fisiologia , Consumo de Bebidas Alcoólicas/psicologia , Índice de Massa Corporal , Futebol Americano/psicologia , Humanos , Masculino , Fatores de Risco , Fumar/psicologia , Inquéritos e Questionários
17.
Int J Mol Sci ; 14(12): 24412-21, 2013 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-24351825

RESUMO

There is growing evidence that increased levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) may contribute to endothelial dysfunction. Studies in animal models as well as in humans have suggested that the increase in ADMA occurs at a time when vascular disease has not yet become clinically evident. ADMA competitively inhibits NO elaboration by displacing L-arginine from NO synthase. In a concentration-dependent manner, it thereby interferes not only with endothelium-dependent, NO-mediated vasodilation, but also with other biological functions exerted by NO. The upshot may be a pro-atherogenic state. Recently, several studies have investigated the effect of various therapeutical interventions on ADMA plasma concentrations.


Assuntos
Arginina/análogos & derivados , Doenças Cardiovasculares/metabolismo , Animais , Arginina/metabolismo , Doenças Cardiovasculares/patologia , Humanos , Inflamação , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Risco
18.
Healthcare (Basel) ; 11(9)2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37174763

RESUMO

The investigation of this observational case-control study aimed at determining the effectiveness of a combined treatment of extremely low-frequency electromagnetic fields (ELF) with a soft elastic knee brace versus ELF alone in knee osteoarthritis (KOA) with respect to a reduction in pain and functional recovery. We hypothesized that the combined use of ELF and a soft elastic knee brace may provide better results. Thirty-five patients (N = 35, divided into Group 1 = ELF and Group 2 = ELF with the soft elastic knee brace) were analyzed. The rehabilitative protocol consisted of 10 sessions of antiphlogistic and antiedema programs (first cycle) for 2 weeks, followed by twelve sessions of bone repair and connective tissue repair programs (second cycle) in patients with knee osteoarthritis (KOA) for 4 weeks. Patient evaluations were conducted at baseline (T0) and after 2 (T1) and 4 (T2) weeks of treatment. A follow-up evaluation was conducted 6 weeks after treatment (T3). The LIMFA© Therapy System was used to create multifrequency magnetoelectric fields with an intensity of 100 µT and a low-frequency field. The Incrediwear Cred 40 knee sleeve (Incred) was used for alleviating knee pain. The Visual Analogue Scale (VAS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Lysholm score (Ls) were used as outcome measures. The results showed that pain at rest (Vr), pain in motion (Vm), KOOS, and Ls were significantly affected by ELF over time. In conclusion, Group 2 had a better response in terms of pain resolution at rest (p < 0.05) and a concurrent better response at T3 in terms of functional recovery (p < 0.05).

19.
Biomolecules ; 13(12)2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-38136598

RESUMO

Several studies have already demonstrated the biocompatibility of a tooth as a grafting material in the regeneration of bone tissue, showing its osteoconductive potential, while no studies have verified whether the osteoinductive potential of a tooth remains constant or is altered after its treatment with the Tooth Transformer (TT) device. The aim of the study was to demonstrate that the treatment with the TT device did not alter the osteoinductivity of an extracted tooth that was stored dry. Twelve extracted human teeth were collected from real patients. Caries, tartar and filling materials were removed from each tooth; each tooth was coarsely cut and stored at room temperature (RT) until use. Each sample was shredded, demineralized and disinfected, using the TT device. Protein extraction was carried out for each sample, and Western Blot analysis was performed to test the presence of mineralization protein LIM-1 and transforming growth factor-ß. The presence of the human Bone Morphogenetic Protein 2 (BMP-2) and human collagen Type I (COL-I) was found in dry tooth samples processed with the TT device and subjected to Enzyme-Linked Immunosorbent Assay (ELISA) testing. The treatment of chemical demineralization using the TT device does not alter the osteoinductive potential of a dry tooth.


Assuntos
Proteínas Morfogenéticas Ósseas , Fator de Crescimento Transformador beta , Humanos , Regeneração Óssea , Colágeno Tipo I , Western Blotting
20.
Nitric Oxide ; 27(3): 143-9, 2012 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-22721692

RESUMO

While thymopentin has been used for many years in the experimental treatment of Sézary syndrome (SS), a rare and very aggressive lymphoma, its mechanism of action is still not known. Herein we show that this peptide acts as an inhibitor of isolated iNOS and nNOS isoforms, and reduces iNOS protein/mRNA levels and iNOS activity in blood cells obtained from both healthy donors and SS patients. Similar results were obtained with TPN-2, the N(ω)-nitro analogue of the Arg-Lys motif present in thymopentin. Additional investigations are necessary to confirm the role and the relative importance of the two mechanisms of iNOS down-regulation in the therapeutic action of these peptides against SS.


Assuntos
Leucócitos Mononucleares/enzimologia , Macrófagos/enzimologia , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo II/sangue , Síndrome de Sézary/tratamento farmacológico , Síndrome de Sézary/enzimologia , Timopentina/farmacologia , Análise de Variância , Animais , Estudos de Casos e Controles , Bovinos , Regulação para Baixo/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Modelos Moleculares , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/genética , Proteínas Recombinantes/antagonistas & inibidores , Síndrome de Sézary/sangue
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