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1.
An Acad Bras Cienc ; 92(1): e20190261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401838

RESUMO

Cytarabine is effectively used in the treatment of adult acute leukemia, but it has a dose-limiting side effect of fatal pulmonary oedema because it increases the vascular permeability of the alveolar capillaries. The aim of the present study was to conduct a radiological, biochemical and histopathological investigation of the effect of rutin on cytarabine-associated pulmonary oedema in rats. Rats were treated with a combination of rutin+cytarabine by administering oral rutin at a dose of 50 mg/kg; other rat groups were orally administered the same volume of physiological saline. One hour after administration of rutin or saline, the rutin+cytarabine and cytarabine groups received an intraperitoneal injection of cytarabine (200 mg/kg). This administration procedure was repeated once a day for 14 days. Radiologically, 50% of the animals given cytarabine alone showed lung oedema, but the rutin+cytarabine group showed no oedema. The inclusion of rutin decreased the amounts of cytarabine-associated malondialdehyde, tumour necrosis factor-α, and nuclear factor-κB in the lung tissue. Rutin also inhibited the reduction of total glutathione by nitric oxide. These findings suggest that rutin may be a beneficial adjunct that can minimise the development of cytarabine-associated pulmonary oedema.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Citarabina/efeitos adversos , Edema Pulmonar/tratamento farmacológico , Rutina/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Masculino , NF-kappa B/análise , Oxidantes/sangue , Estresse Oxidativo/efeitos dos fármacos , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/patologia , Ratos , Ratos Wistar , Rutina/farmacologia , Fator de Necrose Tumoral alfa/análise
2.
Acta Cir Bras ; 34(12): e201901204, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32074166

RESUMO

PURPOSE: To examine the therapeutic effect of external adenosine on an acetic acid-induced acute ulcerative colitis model in rats. METHODS: Thirty male mature rats were divided into three groups as control, acute colitis (AC) and AC+adenosine group (AC+AD). AC was induced by rectal administration of 4% acetic acid (AA). 5mg/kg/day adenosine was performed i.p for 4 weeks to AC+AD group. Rectum and colon were excised for microscopic and histopathological histopathologic evaluations, and immunohistochemical analysis of nuclear factor kappa B (NF-kB). Blood samples were collected for biochemical detection of TNF-α, Pentraxin-3 and malondialdehyde (MDA) levels. RESULTS: AC group had generalized hyperemia and hemorrhage with increased macroscopic and histopathological scores compared with control (P <0.0001) while adenosine treatment decreased these scores significantly (P <0.001), with reduced distribution of disrupted epithelium, leukocyte infiltrates, and focal hemorrhage. AC group showed significantly increased immunoexpression of NF-kB in rectum, plasma and tissue levels of TNF-α, plasma Pentraxin-3 and MDA levels (P <0.0001) while adenosine reduced these levels (P < 0.05). CONCLUSION: Adenosine appears to promote healing of colon and rectum exposed to AA-induced AC, suggesting a boosting effect of adenosine on the intestinal immune system to cure ulcerative colitis.


Assuntos
Adenosina/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Ácido Acético , Doença Aguda , Animais , Proteína C-Reativa/análise , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colo/patologia , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Masculino , Malondialdeído/sangue , NF-kappa B/análise , Ratos Sprague-Dawley , Reto/patologia , Valores de Referência , Reprodutibilidade dos Testes , Componente Amiloide P Sérico/análise , Substâncias Reativas com Ácido Tiobarbitúrico , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise
3.
J Appl Oral Sci ; 27: e20180713, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31691738

RESUMO

Vitamin D has been known to have important regulatory functions in inflammation and immune response and shows inhibitory effects on experimental periodontitis in animal models. However, the potential mechanism has yet to be clarified. Recent studies have highlighted Aryl hydrocarbon receptor (AhR) and its downstream signaling as a crucial regulator of immune homeostasis and inflammatory regulation. OBJECTIVE: This study aimed to clarify the effect of 1,25-dihydroxyvitamin D3 (VD3) on experimental periodontitis and AhR/nuclear factor-κB (NF-κB)/NLR pyrin domain-containing 3 (NLRP3) inflammasome pathway in the gingival epithelium in a murine model. METHODOLOGY: We induced periodontitis in male C57BL/6 wild-type mice by oral inoculation of Porphyromonas gingivalis (P. gingivalis), and subsequently gave intraperitoneal VD3 injection to the mice every other day for 8 weeks. Afterwards, we examined the alveolar bone using scanning electron microscopy (SEM) and detected the gingival epithelial protein using western blot analysis and immunohistochemical staining. RESULTS: SEM images demonstrated that alveolar bone loss was reduced in the periodontitis mouse model after VD3 supplementation. Western blot analyses and immunohistochemical staining of the gingival epithelium showed that the expression of vitamin D receptor, AhR and its downstream cytochrome P450 1A1 were enhanced upon VD3 application. Additionally, VD3 decreased NF-κB p65 phosphorylation, and NLRP3, apoptosis-associated speck-like protein, caspase-1, interleukin-1ß (IL-1ß) and IL-6 protein expression. CONCLUSIONS: These results implicate the alleviation of periodontitis and the alteration of AhR/NF-κB/NLRP3 inflammasome pathway by VD3 in the mouse model. The attenuation of this periodontal disease may correlate with the regulation of AhR/NF-κB/NLRP3 inflammasome pathway by VD3.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Calcitriol/farmacologia , NF-kappa B/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Periodontite/tratamento farmacológico , Periodontite/metabolismo , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Perda do Osso Alveolar , Animais , Western Blotting , Conservadores da Densidade Óssea/análise , Calcitriol/análise , Caspase 1/análise , Gengiva/efeitos dos fármacos , Gengiva/metabolismo , Gengiva/patologia , Imuno-Histoquímica , Interleucina-1beta/análise , Interleucina-6/análise , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/análise , Proteína 3 que Contém Domínio de Pirina da Família NLR/análise , Periodontite/patologia , Porphyromonas gingivalis , Receptores de Hidrocarboneto Arílico/análise , Valores de Referência , Reprodutibilidade dos Testes , Resultado do Tratamento
4.
Life Sci ; 239: 117088, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31759039

RESUMO

AIMS: Diabetic nephropathy (DN) is a common chronic microvascular complication of both types of diabetes mellitus, which leads to renal dysfunction and subsequent need of dialysis and organ transplantation. Advanced glycation end products (AGEs) are metabolic consequence of hyperglycemia and are main contributory factor in the DN pathogenesis through mediating establishment of oxidative status and chronic inflammatory milieu. This study aimed to explore the impact of vanillin on preventing the progression of DN. MAIN METHODS: Experimental DN model was established in rats utilizing streptozotocin. Serum concentration of AGEs and Interleukin-6 (IL-6) and transforming growth factor ß1 (TGFß1) levels in kidney homogenate were assessed using ELISA technique. Also, we evaluated the expression of nuclear factor kappa B (NF-κB) using immunohistochemistry. KEY FINDINGS: Treatment with vanillin for 8 weeks significantly ameliorated DN. Vanillin significantly decreased hyperglycemia and improved kidney function reflected by decreased serum levels of blood urea nitrogen, creatinine, and decreased proteinuria. Also, vanillin significantly decreased malondialdehyde content and elevated superoxide dismutase activity in renal tissues. Moreover, vanillin decreased renal expression of NF-κB and renal concentrations of IL-6, TGFß1 and collagen. In addition, vanillin significantly decreased serum AGEs concentration. Also, vanillin attenuated histological abnormalities in kidney architecture. SIGNIFICANCE: Vanillin, which is a cheap and abundant natural product, exhibited anti-AGEs, antioxidant, anti-inflammatory and anti-fibrotic activities. These activities might be helpful and potent mechanisms in preventing the progression of DN.


Assuntos
Benzaldeídos/farmacologia , Nefropatias Diabéticas/tratamento farmacológico , Produtos Finais de Glicação Avançada/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Benzaldeídos/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Interleucina-6/análise , Interleucina-6/sangue , Rim/metabolismo , Masculino , NF-kappa B/análise , NF-kappa B/sangue , Estresse Oxidativo/efeitos dos fármacos , Proteinúria/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Estreptozocina/farmacologia , Fator de Crescimento Transformador beta1/análise , Fator de Crescimento Transformador beta1/sangue
5.
Medicina (Kaunas) ; 55(9)2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31450841

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumors worldwide. HCC is a complex process that is associated with several etiological factors, which in turn result in aberrant activation of different cellular and molecular pathways and the disruption of balance between activation and inactivation of protooncogenes and tumor suppressor genes, respectively. Since HCC most often occurs in the setting of a diseased or cirrhotic liver and most of the patients are diagnosed at the late stage of disease, prognosis is generally poor. At present, limited treatment options with marginal clinical benefits are available. Systemic therapy, particularly in the form of conventional cytotoxic drugs, are generally ineffective. In recent years, molecular-targeted therapies have been clinically used to treat various cancers, including liver cancer. This approach inhibits the growth of tumor cells by interfering with molecules that are involved in carcinogenesis, which makes it more selective and specific than cytotoxic chemotherapy. Many clinical trials have been carried out while using molecular targeted drugs in advanced HCC with many more in progress. The clinical trials in HCC to date have evaluated a single-targeted therapy alone, or two or more targeted therapies in parallel. The aim of this review is to provide insight of various molecular mechanisms, leading to HCC development and progression, and also the range of experimental therapeutics for patients with advanced HCC. The review will summarize different clinical trials data the successes and failures of these treatments, as well as the most effective and approved drugs designed against HCC.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/fisiopatologia , Transdução de Sinais/fisiologia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Humanos , Incidência , Interleucina-6/análise , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/fisiopatologia , NF-kappa B/análise , Fatores de Risco , Fator de Crescimento Transformador alfa/análise , Fator de Necrose Tumoral alfa/análise
6.
Mol Med Rep ; 20(3): 2476-2483, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322196

RESUMO

Atopic dermatitis (AD) is an inflammatory skin disorder caused by immunological dysregulation and genetic factors. Whether the expression levels of cytokine and skin barrier protein were altered by S100 calcium binding protein A8 (S100A8) and S100A9 in human keratinocytic HaCaT cells was examined in the present study. Alterations of cytokine expression were examined by ELISA following treatment with S100A8/9 and various signal protein­specific inhibitors. Activation of the mitogen activated protein kinase (MAPK) pathway and nuclear factor (NF)­κB was evaluated by using western blotting and an NF­κB activity test, respectively. The expression levels of interleukin (IL)­6, IL­8 and monocyte chemoattractant protein­1 increased following treatment with S100A8 and S100A9, and the increase was significantly blocked by specific signaling pathway inhibitors, including toll­like receptor 4 inhibitor (TLR4i), rottlerin, PD98059, SB203580 and BAY­11­7085. Extracellular signal­regulated kinase (ERK) and p38 MAPK pathways were activated in a time­dependent manner following treatment with S100A8 and S100A9. Phosphorylation of ERK and p38 MAPK were blocked by TLR4i and rottlerin. S100A8 and S100A9 induced translocation of NF­κB in a time­dependent manner, and the activation of NF­κB was inhibited by TLR4i, rottlerin, PD98059 and SB203580. In addition, S100A8 and S100A9 decreased the expression of skin barrier proteins, filaggrin and loricrin. These results may help to elucidate the pathogenic mechanisms of AD and develop clinical strategies for controlling AD.


Assuntos
Calgranulina A/imunologia , Calgranulina B/imunologia , Citocinas/imunologia , Queratinócitos/imunologia , Proteínas de Membrana/imunologia , Proteínas S100/imunologia , Linhagem Celular , Citocinas/análise , Dermatite Atópica/imunologia , Humanos , Sistema de Sinalização das MAP Quinases , Proteínas de Membrana/análise , NF-kappa B/análise , NF-kappa B/imunologia , Proteínas S100/análise
7.
BMC Gastroenterol ; 19(1): 133, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345163

RESUMO

BACKGROUND: The aim of the present study was to evaluate the effects of curcumin supplementation on inflammatory indices, and hepatic features in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Fifty patients with NAFLD were randomized to receive lifestyle modification advice plus either 1500 mg curcumin or the same amount of placebo for 12 weeks. RESULTS: Curcumin supplementation was associated with significant decrease in hepatic fibrosis (p < 0.001), and nuclear factor-kappa B activity (p < 0.05) as compared with the baseline. Hepatic steatosis and serum level of liver enzymes, and tumor necrosis-α (TNF-α) significantly reduced in both groups (p < 0.05). None of the changes were significantly different between two groups. CONCLUSION: Our results indicated that curcumin supplementation plus lifestyle modification is not superior to lifestyle modification alone in amelioration of inflammation. TRIAL REGISTRATION: IRCT20100524004010N24, this trial was retrospectively registered on May 14, 2018.


Assuntos
Curcumina/administração & dosagem , Inflamação , Fígado , Hepatopatia Gordurosa não Alcoólica , Comportamento de Redução do Risco , Anti-Inflamatórios não Esteroides/administração & dosagem , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Testes de Função Hepática/métodos , Masculino , Pessoa de Meia-Idade , NF-kappa B/análise , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/psicologia , Hepatopatia Gordurosa não Alcoólica/terapia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise
8.
Balkan Med J ; 36(4): 245-250, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31140237

RESUMO

Background: Nuclear factor-kB is highly activated in cardiovascular disorders. However, few articles have targeted at the role of nuclear factor-kB inhibitor in heart failure. Aims: To evaluate the effects of nuclear factor-kB inhibitor pyrrolidine dithiocarbamate on cardiocyte apoptosis and cardiac function in a rat heart failure model. Study Design: Animal experiment. Methods: A stable and reproducible rat heart failure model (n=64) was prepared by injecting homologous microthrombotic particles into the left ventricle of Sprague­Dawley rats while obstructing the ascending aorta to produce coronary microembolization. Rats with heart failure were randomized into untreated (HFu) and pyrrolidine dithiocarbamate-treated (HFp) groups; the latter received an intraperitoneal injection of pyrrolidine dithiocarbamate (100 mg/kg/day) 1 h prior to surgery as well as on postoperative days 1-7. The sham group comprised 32 Sprague­Dawley rats. Eight rats from each group were sacrificed on days 1, 3, 7, and 14 postoperatively. Masson's trichrome staining was used to determine the micro-fibrotic area to indicate the severity of myocardial loss. Terminal transferase uridine triphosphate nick end labeling staining was used to detect apoptotic cardiomyocytes. Echocardiography and hemodynamics were performed to evaluate left ventricular function. Results: Rats with heart failure exhibited pathological changes evidenced by patchy myocardial fibrosis, remarkably elevated severity of myocardial loss, and persistently reduced left ventricular function. At the end of the study, compared with the HFu group, myocardial infarct size was reduced by 28% (p=0.001), cardiocyte apoptosis was suppressed (7.17%±1.47% vs 2.83%±0.75%, p<0.001), cardiac function parameters such as left ventricular ejection fraction (80%±4% vs 61%±6%), left ventricular + dP/dt max (4828±289 vs 2918±76 mmHg.s−1), left ventricular - dP/dt max (4398±269 vs 2481±365 mmHg.s−1), and left ventricular systolic pressure (126±13 vs 100±10 mmHg) were significantly increased, and left ventricular end-diastolic pressure was reduced (18±2 vs 13±1 mmHg) (p<0.001, for all) in the HFu group. Conclusion: Our rat model can adequately mimic heart failure via coronary vessel embolization. Moreover, pyrrolidine dithiocarbamate treatment can reduce cardiocyte apoptosis and improve cardiac function, which may be beneficial for patients with heart failure secondary to myocardial infarction.


Assuntos
Apoptose/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/patologia , NF-kappa B/efeitos dos fármacos , Pirrolidinas/farmacologia , Tiocarbamatos/farmacologia , Animais , Apoptose/fisiologia , Modelos Animais de Doenças , Embolia , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , NF-kappa B/análise , Pirrolidinas/metabolismo , Pirrolidinas/uso terapêutico , Ratos/genética , Ratos/metabolismo , Ratos Sprague-Dawley , Tiocarbamatos/metabolismo , Tiocarbamatos/uso terapêutico
9.
Anal Chim Acta ; 1068: 80-86, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31072480

RESUMO

Effective detection of the intracellular expression level of transcription factors is important for biological research and medical diagnosis. This study proposes a rapid and simple fluorescence sensing strategy for highly sensitive detection of a transcription factor, nuclear factor-kappa B (NF-κB). NF-κB binds to double-stranded DNA duplex, one of which is then protected from Exonuclease III (Exo III) digestion. An Exo III-mediated hydrolysis cycle on TaqMan probes is then triggered to achieve highly sensitive detection of NF-κB. This method can detect NF-κB with concentration as low as 45.6 pM. Furthermore, sequence-specific binding of NF-κB to DNA provides good selectivity. This method can be used for the direct quantification of nuclear proteins extracted from cells. More importantly, by simply replacing the sequence of the probe binding site, this method can also be used for reliable quantification of other DNA-binding proteins and is thus a universal sensing protocol. This strategy can be a powerful technology in the areas of disease diagnosis and pharmaceutical research.


Assuntos
Técnicas Biossensoriais , Exodesoxirribonucleases/metabolismo , NF-kappa B/análise , Diterpenos de Caurano/farmacologia , Humanos , NF-kappa B/antagonistas & inibidores , Espectrometria de Fluorescência
10.
An Acad Bras Cienc ; 91(1): e20170831, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30916148

RESUMO

Medicinal plants have long been used as an alternative to traditional drugs for the treatment of inflammatory conditions due to the classical side effects and restricted access of various commercially available drugs, such as steroids (GCs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Sambucus australis is a Brazilian herb that is commonly used to treat inflammatory diseases; however, few studies have examined the use of this species in the treatment of inflammatory conditions. The present study aims to evaluate the potential anti-inflammatory activity of S. australis in vitro. We established spleen cell cultures stimulated with pokeweed mitogen (PWM) to evaluate the production of proinflammatory cytokines, such as IL-4, IL-5, IFN-y, and IL-10 (by ELISA), and the expression of the transcription factor NF-kB (by RT-PCR). In addition, we evaluated the levels of nitric oxide in macrophage cultures and the membrane-stabilizing activity of S. australis methanolic extract (EMSA). Treatment with EMSA at concentrations of 100, 50, 25 and 12.5 µg/ml significantly decreased IL-4 (p<0.001) and IL-5 (p<0.001) levels. Treatment with 100 µg/ml EMSA reduced IFN-у (p<0.001) levels. Moreover, at 100 mg/ml, EMSA also increased IL-10 production and reduced NF-kB expression (p<0.01). In macrophage cultures stimulated with LPS, EMSA decreased nitric oxide levels (p<0.001) at all concentrations tested (100, 50, 25 and 12.5 µg/ml). Additionally, EMSA had a protective effect in the erythrocyte membrane stabilization assay. Taken together, these results suggest that S. australis has anti-inflammatory potential in vitro, characterized by the reduction of both inflammatory cytokines and the expression of NF-kB along with the up-regulation of IL-10.


Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Inflamação/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/química , Sambucus/química , Animais , Células Cultivadas , Citocinas/análise , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos BALB C , NF-kappa B/análise , Folhas de Planta/química
11.
Physiol Res ; 68(3): 431-443, 2019 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-30904007

RESUMO

A-kinase interacting protein 1 (AKIP1) has been shown to interact with a broad range of proteins involved in various cellular processes, including apoptosis, tumorigenesis, and oxidative stress suggesting it might have multiple cellular functions. In this study, we used an epitope-tagged AKIP1 and by combination of immunochemical approaches, microscopic methods and reporter assays we studied its properties. Here, we show that various levels of AKIP1 overexpression in HEK-293 cells affected not only its subcellular localization but also resulted in aggregation. While highly expressed AKIP1 accumulated in electron-dense aggregates both in the nucleus and cytosol, low expression of AKIP1 resulted in its localization within the nucleus as a free, non-aggregated protein. Even though AKIP1 was shown to interact with p65 subunit of NF-kappaB and activate this transcription factor, we did not observe any effect on NF-kappaB activation regardless of various AKIP1 expression level.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Núcleo Celular/metabolismo , Citosol/metabolismo , Mitocôndrias/metabolismo , NF-kappa B/metabolismo , Proteínas Nucleares/biossíntese , Frações Subcelulares/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Núcleo Celular/química , Citosol/química , Regulação da Expressão Gênica , Células HEK293 , Humanos , Mitocôndrias/química , NF-kappa B/análise , Proteínas Nucleares/genética , Frações Subcelulares/química
12.
Med Sci Monit ; 25: 1656-1662, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30828084

RESUMO

BACKGROUND Bulleyaconitine A (BLA) has been widely used as analgesic against chronic inflammatory pain in China. However, its potential therapeutic role in asthma remains unclear. The purpose of this study was to investigate the effect of BLA on airway inflammation in mice with allergic asthma. MATERIAL AND METHODS Specific-pathogen-free (SPF) female Balb/c mice were randomly divided into the following 6 groups: (1) Control group (NC), (2) Asthma group (AS), (3) BLA-L group, (4) BLA-M group, (5) BLA-H group, and (6) Dexamethasone group. An asthma mouse model was established by administration of ovalbumin (OVA) and mice were sacrificed within 24 h after the last challenge. Enzyme-linked immunosorbent assay (ELISA) method was used to determine the relative expression levels of IgE and IgG in mouse serum. In addition, bronchoalveolar lavage fluid (BALF) was collected and IL-4, TNF-α, and MCP-1 levels were determined by ELISA. Furthermore, eosinophils, lymphocytes, and macrophages in BALF were classified and analyzed, and inflammatory cell infiltration in the airways of mice was determined by hematoxylin-eosin (HE) staining. The expression of NF-κB1 and PKC-δ in mouse lung tissue was determined by Western blot analysis. RESULTS The levels of serum IgE and IgG in BLA- or Dex- treated mice were significantly reduced compared to those in the asthma (AS) group (P<0.01), whereas the levels of cytokines IL-4, TNF-α, and MCP-1 were significantly decreased (P<0.01). HE-staining showed that BLA significantly reduced inflammatory cell infiltration and mucus secretion in lung tissue. Moreover, BLA inhibited the expression of NF-κB1 and PKC-d via the NF-κB signaling pathway in the lung. CONCLUSIONS Our data show that BLA activates PKC-δ/NF-κB to reduce airway inflammation in allergic asthma mice.


Assuntos
Aconitina/análogos & derivados , Asma/tratamento farmacológico , Aconitina/farmacologia , Animais , Antiasmáticos/farmacologia , Asma/induzido quimicamente , Líquido da Lavagem Broncoalveolar , Quimiocina CCL2/análise , China , Citocinas/metabolismo , Modelos Animais de Doenças , Eosinófilos/metabolismo , Feminino , Inflamação/tratamento farmacológico , Interleucina-4/análise , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/análise , Ovalbumina/farmacologia , Proteína Quinase C-delta/análise , Fator de Necrose Tumoral alfa/análise
13.
Geriatr Gerontol Int ; 19(5): 419-422, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30811775

RESUMO

AIM: The aging process is associated with increased production of free radicals, but regular exercise training might create a balance between oxidative stress and the anti-oxidant system. The aim of the present study was to investigate the effect of resistance training (RT) on the serum levels of tumor necrosis factor-α, malondialdehyde, total anti-oxidant capacity and nuclear factor-κB in young and older adult women. METHODS: A total of 44 women were divided into four groups: older-training, older-control, young-training and young-control. The experimental groups carried out 12 weeks of RT with an intensity of 75% one repetition maximum. RESULTS: After finishing the RT program, total anti-oxidant capacity and nuclear factor-κB in both the young and older adult training groups were significantly increased, whereas malondialdehyde in the young and the older exercising groups decreased. In addition, malondialdehyde in both the older and young groups, and total anti-oxidant capacity in only the young group, were respectively lower and higher compared with their inactive counterparts. No significant changes in tumor necrosis factor-α occurred in training groups after the 12-week intervention, but the older and younger training groups had a significant difference with the young control group in the post-test. CONCLUSIONS: It seems that the strengthening of the anti-oxidant system resulting from regular RT in older adults is similar to those of young people. Geriatr Gerontol Int 2019; 19: 419-422.


Assuntos
Envelhecimento/metabolismo , Antioxidantes , Exercício Físico/fisiologia , Estresse Oxidativo/fisiologia , Treinamento de Resistência/métodos , Idoso , Antioxidantes/análise , Antioxidantes/metabolismo , Feminino , Humanos , Malondialdeído/análise , NF-kappa B/análise , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise , Saúde da Mulher , Adulto Jovem
14.
J Intern Med ; 285(3): 301-316, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30644612

RESUMO

AIMS: There are limited data on the role of human monocyte subsets in ST-elevation myocardial infarction (STEMI). The study aimed to establish the relationship between monocyte subsets, their phagocytic and nuclear factor κB (NFκB) activity and outcomes in STEMI. METHODS: Monocyte subsets and their phagocytic activity and intracellular levels of inhibitory κB kinase ß (IKKß, marker of NFκB activity) were measured by flow cytometry in 245 patients with STEMI, median follow-up of 46 months. RESULTS: Mon2 (CD14++CD16+CCR2+) counts were independently predictive of major adverse cardiovascular events (MACE) [4th quartile HR 3.42 (95% CI 1.43-8.16), P = 0.006 and 3rd quartile HR 2.88 (95% CI 1.19-7.00), P = 0.02 vs. 1st quartile]. Mon2 subset was the only subset associated with higher occurrence of heart failure (4th quartile vs. 1st quartile, sevenfold, P = 0.001 on univariate analysis; fivefold, P = 0.04 on multivariable analysis). On receiver operating characteristic, analysis including of Mon2 improved prognostic value of troponin T and creatine kinase for MACE and heart failure (HF). Higher intracellular Mon2 IKKß levels were associated with 10-fold lower occurrence of HF on multivariable analysis (4th vs. 1st quartiles, P = 0.03). Abnormal Mon1 and Mon2 phagocytic capacities were related to HF development, but the association was dependent on the infarct size and other prognosticators. High Mon2 levels were associated with lower ejection fraction after STEMI onset (P = 0.001) and at 6-month follow-up (P < 0.001). CONCLUSIONS: Abnormal Mon2 characteristics have a unique association with poor outcome in patients with STEMI. The relation of Mon2 with occurrence of HF is strongly and independently related to their functional status, which may have potential therapeutic implications.


Assuntos
Insuficiência Cardíaca , Quinase I-kappa B , Monócitos , NF-kappa B , Infarto do Miocárdio com Supradesnível do Segmento ST , Biomarcadores/análise , Biomarcadores/metabolismo , Contagem de Células/métodos , Correlação de Dados , Feminino , Citometria de Fluxo , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Humanos , Quinase I-kappa B/análise , Quinase I-kappa B/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/classificação , Monócitos/fisiologia , NF-kappa B/análise , NF-kappa B/metabolismo , Avaliação de Resultados em Cuidados de Saúde , Fagocitose , Prognóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Volume Sistólico
15.
Cell Prolif ; 52(2): e12547, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30657238

RESUMO

OBJECTIVE: Chinese Herb QingBai decoction (QBD) has been approved affective in the treatment of IBD patients in clinic. However, the underlying mechanism remains unknown. We aim to investigate the effect of QBD on the mouse model of ulcerative colitis and its possible mechanism. METHODS: C57/bL mice were given 5% DSS to induce colitis and were divided as QBD and mesalazine group. Weight, faeces and mental status were recorded each day and the histopathological changes (goblet cells etc) of the colon were observed after sacrificed. Fluorescein isothiocyanate-dextran 4000 was measured to reflect the intestinal mucosal permeability. In addition, cell junction-related proteins and possible signal pathways were investigated. RESULTS: QingBai decoction could significantly alleviate the inflammation and the protection effect of colitis is comparable as those in mesalazine enema group. It was found that the permeability reduced significantly with QBD treatment vs the control group, while no significant difference between the mesalazine and QBD groups. QBD treatment could upregulate the expression of tight junction complex(ZO-1, claudin-1 and occludin)and muc-2 expression. It significantly reduced the production and secretion of serials proinflammatory cytokines (IL-1ß, IL-6, Kc and TNF-α) compared with the control group. Meanwhile, NF-κB and Notch pathways were regulated. CONCLUSION: QingBai decoction can effectively alleviate intestinal inflammation and mucosal barrier function in colitis mice, and the mechanism may be related to the inhibition of inflammatory cascade as well as enhanced mucus layer barrier and mechanical barrier function by NF-κB and Notch signalling.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Absorção Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , NF-kappa B/imunologia , Animais , Apoptose/efeitos dos fármacos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Citocinas/análise , Citocinas/imunologia , Sulfato de Dextrana , Modelos Animais de Doenças , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Intestinos/imunologia , Intestinos/patologia , Camundongos Endogâmicos C57BL , NF-kappa B/análise , Permeabilidade/efeitos dos fármacos , Receptores Notch/análise , Receptores Notch/imunologia , Transdução de Sinais/efeitos dos fármacos
16.
J Agric Food Chem ; 67(7): 1889-1901, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30661353

RESUMO

Chronic inflammation and proliferation play important roles in atherosclerosis progression. This study aimed to identify the mechanisms responsible for the anti-inflammatory and antiproliferative effects of melatonin on tumor necrosis factor-α (TNF-α)- and platelet-derived growth factor-BB (PDGF-BB)-treated rat aortic smooth muscle cells (RASMCs). Melatonin reduced TNF-α-induced RASMC inflammation by decreasing vascular cell adhesion molecule-1 (VCAM-1) expression and nuclear factor-kappa B (NF-κB) P65 activity by inhibiting P38 mitogen-activated protein kinase phosphorylation ( P < 0.05). Additionally, melatonin inhibited PDGF-BB-induced RASMC proliferation by reducing mammalian target of rapamycin (mTOR) phosphorylation ( P < 0.05) but not migration in vitro. Melatonin also reduced TNF-α- and PDGF-BB-induced reactive oxygen species (ROS) production ( P < 0.05). Furthermore, melatonin treatment (prevention and treatment groups) significantly repressed high cholesterol diet-stimulated atherosclerotic lesions in vivo (19.59 ± 4.11%, 20.28 ± 5.63%, 32.26 ± 12.06%, respectively, P < 0.05). Taken together, the present study demonstrated that melatonin attenuated TNF-α-induced RASMC inflammation and PDGF-BB-induced RASMC proliferation in cells and reduced atherosclerotic lesions in mice. These results showed that melatonin has anti-inflammatory and antiproliferative properties and may be a novel therapeutic target in atherosclerosis.


Assuntos
Anti-Inflamatórios/farmacologia , Apolipoproteínas E/deficiência , Aterosclerose/prevenção & controle , Melatonina/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Animais , Aorta , Becaplermina/antagonistas & inibidores , Becaplermina/farmacologia , Proliferação de Células/efeitos dos fármacos , Masculino , Camundongos , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/química , Miócitos de Músculo Liso/patologia , NF-kappa B/análise , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Ratos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/farmacologia , Molécula 1 de Adesão de Célula Vascular/análise
17.
Exp Parasitol ; 196: 12-21, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30465732

RESUMO

Helminths and their products are strong candidates for the treatment of autoimmunological disorders and allergies. Being a key population of antigen-presenting cells, dendritic cells play a crucial role in the therapeutic potential of worms. The study compares the effects of live pre-male and pre-female L4 stage Heligmosomoides polygyrus administration on the maturation and activation of the JAWS II line of immature dendritic cells. On stimulation with L4 stage H. polygyrus, JAWS II cells acquire semi-mature status and induce Th2 and regulatory responses in vitro. The strongest immunosuppressive effect on JAWS II cells was observed following stimulation with both sexes of nematodes together; this was manifested as immature dendritic cell morphology, proliferation inhibition, cell cycle change, decreased translocation of NF-κB into the nucleus, and lower expression of surface cellular costimulatory molecules CD80, CD86 and MHC I. However, greater production of proinflammatory (IL-12p70, TNF-α, IL-6) and Th2 response-promoting cytokines (IL-4) was observed by JAWS II following exposure to both sexes compared to male or female larvae alone. Sex had no influence on the viability, apoptosis process or endocytosis abilities of the JAWS II cell line. The findings indicate that the presence of only a single sex of the parasite influences a developed response, resulting in reduced proinflammatory and an antiparasitic reaction.


Assuntos
Células Dendríticas/parasitologia , Nematospiroides dubius/fisiologia , Animais , Apoptose , Células da Medula Óssea/imunologia , Células da Medula Óssea/parasitologia , Células da Medula Óssea/fisiologia , Ciclo Celular , Linhagem Celular , Quimiocinas/análise , Citocinas/análise , Células Dendríticas/imunologia , Células Dendríticas/fisiologia , Endocitose , Feminino , Larva/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/análise , Nematospiroides dubius/crescimento & desenvolvimento , Fatores Sexuais , Organismos Livres de Patógenos Específicos
18.
An Acad Bras Cienc ; 91(1): e20180106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30569967

RESUMO

Our aim is to investigate the potentially preventive effects of Aliskiren in a carrageenan-induced lung pleurisy model and to compare the standard anti-inflammatory agents, indomethacin and dexamethasone. The pleurisy model was induced through the injection of carrageenan (0.2 ml-%2) into the pleural cavity. After the experiment, serum and lung tissues were collected and biochemical, molecular and pathological examinations were performed. In our study, pleural inflammation decreased superoxide dismutase activity and the glutathione level and increased the malondialdehyde level in the lung of rats, while Aliskiren increased the superoxide dismutase activity and glutathione level and decreased the malondialdehyde level. In addition, carrageenan-induced pleurisy caused a significant increase in pro-inflammatory cytokines mRNA expressions (TNF-α, IL-1ß, and NF-KB), while Aliskiren administration decreased their expressions as well as the standard treatments, indomethacin and dexamethasone, did. Aliskiren administration at the 200 mg/kg dose protected the lungs in the pathological evaluation, especially against inflammatory cell infiltration and edematous lesions. It appears that Aliskiren protects the lung from carrageenan-induced pleurisy damage by regulating inflammation and antioxidant-oxidant balance via Renin Angiotensin Aldosterone System inhibition.


Assuntos
Amidas/farmacologia , Anti-Inflamatórios/farmacologia , Fumaratos/farmacologia , Pleurisia/prevenção & controle , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Carragenina , Modelos Animais de Doenças , Glutationa/análise , Interleucina-1beta/análise , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Malondialdeído/análise , NF-kappa B/análise , Estresse Oxidativo/efeitos dos fármacos , Pleurisia/induzido quimicamente , Pleurisia/patologia , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/análise
19.
J Mol Med (Berl) ; 97(1): 63-75, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30456449

RESUMO

Valproic acid (VPA) is a histone deacetylase inhibitor used clinically for neurological disorders. It is also potentially useful as anti-fibrotic therapy as it reduced collagen deposition in the post-operative conjunctiva. In this study, we further evaluated the effects of VPA on post-operative inflammation using the mouse model of conjunctival scarring. VPA, injected into the subconjunctiva immediately after surgery, did not cause any adverse tissue response when examined by live microscopy and produced an apparent reduction of proinflammatory and proangiogenic markers in immunohistological examinations. In-depth analyses of the treated operated tissues revealed that VPA selectively inhibited the CD45highF4/80low macrophage subset as well as the production of specific proinflammatory cytokines/ chemokines, including CXCL1, IL-5, IL-6, and IL-10 which were reduced by ≥ 2.0-fold. VPA also specifically reduced tissue NF-кB2 p100 protein by mean 3.87-fold. On conjunctival fibroblasts, VPA treatment resulted in decreased secretion of specific cytokines, including CCL2, VEGF-A, and IL-15. In the presence of TNF-α, VPA inhibited the induction of specific cytokines/chemokines, notably CCL5 and VEGF-A, as well as NF-кB2 p100. In corroboration, VPA suppressed TNF-α stimulation of NF-кB reporter transcription by 1.51-fold. These data indicate that VPA can modulate both proinflammatory cellular and molecular targets in a selective manner and may therefore attenuate surgery-induced conjunctival inflammation. These and previous findings suggest that, by suppressing key mediators of both inflammation and fibrosis, VPA is a useful therapeutic for improving surgical outcome involving the conjunctiva. KEY MESSAGES: VPA inhibited recruitment of a CD45highF4/80low macrophage subset. VPA reduced chemokine and cytokine levels in treated tissues. VPA selectively suppressed tissue NF-кB2 p100 levels. VPA suppressed TNF-α induction of chemokines, cytokines and NF-кB2 p100 expression. VPA suppressed TNF-α stimulation of NF-кB reporter.


Assuntos
Anti-Inflamatórios/uso terapêutico , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/cirurgia , Ácido Valproico/uso terapêutico , Animais , Células Cultivadas , Túnica Conjuntiva/patologia , Citocinas/análise , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Glaucoma/patologia , Glaucoma/cirurgia , Inflamação/tratamento farmacológico , Inflamação/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/análise , Cuidados Pós-Operatórios
20.
Biosensors (Basel) ; 8(4)2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30544696

RESUMO

Nuclear factor kappa B (NF-κB), regulating the expression of several genes that mediate the inflammatory responses and cell proliferation, is one of the therapeutic targets for chronic inflammatory disease and cancer. A novel molecular binding scheme for the detection of NF-κB was investigated for its affinity to Ig-κB DNA composed by dye and quencher fluorophores, and this specificity is confirmed by competing with the DNA sequence that is complementary to the Ig-κB DNA. We create a normalization equation to remove the negative effects from the various initial fluorophore concentrations and the background noise. We also found that a periodic shaking at a frequency could help to stabilize the DNA⁻protein binding. The calibration experiment, using purified p50 (NF-κB), shows that this molecular probe biosensor has a detection limit on the order of nanomolar. The limit of detection is determined by the binding performance of dye and quencher oligonucleotides, and only a small portion of probes are stabilized by DNA-binding protein NF-κB. The specificity experiment also shows that p50/p65 heterodimer has the highest affinity for Ig-κB DNA; p65 homodimer binds with intermediate affinity, whereas p50 shows the lowest binding affinity, and Ig-κB DNA is not sensitive to BSA (bovine albumin serum). The experiment of HeLa nuclear extract shows that TNF-α stimulated HeLa nuclear extract has higher affinity to Ig-κB DNA than non-TNF-stimulated HeLa nuclear extract (4-h serum response). Therefore, the molecular binding scheme provides a rapid, quantitative, high throughput, and automated measurement of the DNA-binding protein NF-κB at low cost, which is beneficial for automated drug screening systems.


Assuntos
Técnicas Biossensoriais/métodos , DNA/metabolismo , NF-kappa B/análise , Núcleo Celular/metabolismo , DNA/química , Células HeLa , Humanos , Imunoglobulinas/genética , Limite de Detecção , NF-kappa B/metabolismo
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