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1.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(3): 289-295, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31496161

RESUMO

OBJECTIVE: To investigate the effect and mechanism of glucosides of chaenomeles speciosa (GCS) on ischemia/reperfusion-induced brain injury in mouse model. METHODS: Fifty 8-week C57BL/C mice were randomly divided into five groups with 10 in each group:sham group, model group, GCS 30 mg/kg group, GCS 60 mg/kg group and GCS 90 mg/kg group, and the GCS was administrated by gavage (once a day) for 14 d. HE staining was performed to investigate the cell morphology; the Zea-Longa scores were measured for neurological activity; TUNEL staining was performed to investigate the cell apoptosis; ELISA was used to detected the oxidative stress and inflammation; Western Blot was performed to investigate the key pathway and neurological functional molecules. RESULTS: Compared with the sham group, the brain tissues in model group were seriously damaged, presenting severe cell apoptosis, oxidative stress and inflammation, associated with increased NF-κB P65 and TNF-α levels as well as decreased myelin associate glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMgp)levels (all P<0.01). Compared with the model group, the brain tissues in GCS groups were ameliorated, and cell apoptosis, oxidative stress and inflammation were inhibited, associated with decreased NF-κB P65 and TNF-α levels as well as increased MAG and OMgp levels (all P<0.01), which were more markedly in GCS 60 mg/kg group. CONCLUSIONS: GCS can inhibit the NF-κB P65 and TNF-α, reduce the oxidative stress and inflammation, decrease the cell apoptosis in mouse ischemia/reperfusion-induced brain injury model, and 60 mg/kg GCS may be the optimal dose.


Assuntos
Lesões Encefálicas , Glucosídeos , Rosaceae , Fator de Necrose Tumoral alfa , Animais , Encéfalo/efeitos dos fármacos , Lesões Encefálicas/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Distribuição Aleatória , Rosaceae/química , Fator de Necrose Tumoral alfa/genética
2.
Chem Biol Interact ; 311: 108790, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31400342

RESUMO

Preclinical assays play a key role in research in research on the neurobiology of pain and the development of novel analgesics. Drugs available for the treatment of inflammatory pain are not fully effective and show adverse effects. Thus, we investigated the antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide (BAPD), a new analgesic drug prototype. BAPD effects were investigated using nociception models induced by chemical (glutamate), immunologic (Freund's Complete Adjuvant - CFA) and thermal stimuli in Swiss mice. Mice were orally (p.o.) treated with BAPD (0.1-50 mg/kg) 30 min prior to the glutamate and hot-plate tests and a time-course (0.5 up to 8 h) of the antinociceptive effect of BAPD (50 mg/kg, p. o.) was evaluated in a CFA model. In the CFA model, BAPD effects on cyclooxygenase-2 (COX-2), tumor necrosis factor (TNFα) and interferon-γ (INF-γ) expression, myeloperoxidase (MPO) activity, oxidative (2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels) and histological parameters were evaluated. The safety of the compound (50 and 300 mg/kg, p. o.) was verified for 72 h. BAPD reduced the licking time induced by glutamate and caused an increase in latency response to thermal stimulus. Naloxone reversed the antinociceptive effect of BAPD. Paw edema formation induced by glutamate or CFA injection was reduced by BAPD. Mechanical hyperalgesia induced by CFA was attenuated by BAPD. BAPD did not protect against the increase in MPO activity and decrease of the 2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels induced by CFA. BAPD protected against histological alterations and reduction on the levels of gene expression COX-2 and INF-γ in the paw of mice exposed to CFA. BAPD was safe at the doses and time evaluated. BAPD exerts acute antinociceptive, anti-inflammatory and anti-hyperalgesic actions, suggesting that it may represent an alternative in the future development of new therapeutic strategies.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , Interferon gama/metabolismo , Nociceptividade/efeitos dos fármacos , Receptores Opioides/metabolismo , Analgésicos/química , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 2/genética , Edema/tratamento farmacológico , Edema/patologia , Comportamento Exploratório/efeitos dos fármacos , Pé/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Interferon gama/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Dor/tratamento farmacológico , Dor/patologia , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores Opioides/genética , Testes de Toxicidade Aguda , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
3.
J Agric Food Chem ; 67(35): 9796-9804, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31393712

RESUMO

Overactivated microglia and persistent neuroinflammation hold an important role in the pathophysiology of neurodegenerative diseases. The extract of Lycoris chejuensis (CJ) and its active compound, 7-deoxy-trans-dihydronarciclasine (named E144), attenuated expressions of pro-inflammatory factors, including nitric oxide, prostaglandin E2, inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), and interleukin 6, secreted by lipopolysaccharide-activated BV-2 microglial cells, as measured by an enzyme-linked immunosorbent assay or western blotting. In contrast, CJ extract and E144 promoted the secretion of the anti-inflammatory cytokine, interleukin 10. Moreover, we found that E144 attenuated the expression of TNF-α and COX-2 in the cerebral cortex of lipopolysaccharide-treated mice and/or T2576 transgenic mice as well as reduced the reactive immune cells visualized by ionized calcium-binding adaptor molecule 1. Our results suggest the possibility of E144 to serve as a potential anti-neuroinflammatory agent by preventing excess production of pro-inflammatory factors.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/imunologia , Isoquinolinas/administração & dosagem , Lycoris/química , Extratos Vegetais/administração & dosagem , Doença de Alzheimer/genética , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Modelos Animais de Doenças , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Isoquinolinas/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/metabolismo , NF-kappa B/genética , NF-kappa B/imunologia , Extratos Vegetais/química , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
4.
Exp Parasitol ; 205: 107736, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31442455

RESUMO

Goats are frequently described as an intermediate host for the protozoan Neospora caninum, manifesting the disease mainly by recurrent abortions with placentitis and encephalitis in fetuses. Several reports of natural and experimental infections in cattle and mice show differences in the immune response, and the outcome of the infection can be variable depending on the species affected and by the behavior of the infective strain. This study describes for the first time two Neospora caninum strains isolated from naturally infected goats from the state of Minas Gerais, Brazil. One placenta and one brain from different goats were processed for a first bioassay in gerbils (Meriones unguiculatus). Subsequently, a second bioassay was performed by inoculating the processed brain samples from gerbils into Interferon gamma (IFN-γ) knockout mice (KO mice). Tachyzoites collected from the peritoneal fluid of the KO mice were inoculated into VERO cell monolayers, where they presented a very slow growth rate. The tachyzoites were also inoculated into BALB/c mice with a dose of 106 tachyzoites per animal. After a 5-week follow up, the animals infected with both of the strains developed a strong polarized Th1 response with increased serum and spleen gene expression levels of pro-inflammatory cytokines (mainly IFN-γ and TNF-α) in the first week. Tissue lesions were mild in the animals infected with both strains. Despite the strong immune response preventing an infection in the visceral organs, the parasite was able to reach the brain, causing progressive brain lesions from the second to fifth week post infection. The NC-goat1-infected mice presented with severe meningoencephalitis, but the NC-goat2-infected animals had considerable histological brain lesions only at week 5. Immunohistochemical analysis of the mouse brains revealed a different pattern of inflammatory cells compared to the naturally infected goats. A severe inflammatory infiltrate of CD3+ T lymphocytes was found in the NC-goat1-infected mice. A more discrete infiltrate of CD3+ T cells was found in the NC-goat2-infected animals. Additionally, IBA1 IHC revealed an intense microglial reaction and monocyte perivascular cuffs in the NC-goat1-infected animals and lower microglia/monocyte infiltrates in the NC-goat2-infected mice. This work contributes knowledge on the pathogenicity of new Neospora caninum strains in mice, comparable with other well-established mouse models of the disease, and demonstrates the importance of studying goats as an intermediate host of this parasite.


Assuntos
Coccidiose/veterinária , Doenças das Cabras/parasitologia , Neospora/patogenicidade , Animais , Bioensaio/veterinária , Encéfalo/parasitologia , Encéfalo/patologia , Cercopithecus aethiops , Coccidiose/parasitologia , Coccidiose/patologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Gerbillinae , Doenças das Cabras/patologia , Cabras , Imuno-Histoquímica/veterinária , Interferon gama/genética , Interferon gama/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neospora/isolamento & purificação , Pâncreas/patologia , Placenta/patologia , Gravidez , Baço/metabolismo , Baço/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Células Vero
5.
J Agric Food Chem ; 67(36): 10079-10088, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31461286

RESUMO

Geraniin has been reported to possess potent anti-inflammatory properties and to modulate the macrophage polarization. This study sought to evaluate the protective effects and underlying mechanisms of geraniin on lipopolysaccharide (LPS)-induced neuroinflammation and neurobiological alternations as well as cognitive impairment. Daily intragastrical administration with geraniin (20 mg kg-1 day-1) for 14 days significantly prolonged the duration in the target quadrant (26.53 ± 2.03 versus 37.09 ± 3.27%; p < 0.05) and increased crossing-target number (1.93 ± 0.22 versus 3.08 ± 0.17; p < 0.01) in the probe test of LPS-treated mice. Geraniin also ameliorated LPS-elicited neural/synaptic impairments and decreased levels of LPS-induced Aß generation (p < 0.05), amyloid precursor protein (APP) (p < 0.05) and ß-site amyloid precursor protein cleavage enzyme 1 (BACE1) (p < 0.05). Furthermore, geraniin suppressed the production of pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) (9.85 ± 0.58 versus 5.20 ± 0.52 pg/mg of protein; p < 0.01), interleukin (IL)-1ß (16.31 ± 0.67 versus 8.62 ± 0.46 pg/mg of protein; p < 0.01), and IL-6 (12.12 ± 0.45 versus 7.43 ± 0.32 pg/mg of protein; p < 0.05), and inhibited glial cell activation. Moreover, geraniin effectively polarized the microglia toward an anti-inflammatory M2 phenotype. Further study revealed that geraniin targeted toll-like receptor 4 (TLR4)-mediated signaling and decreased the production of pro-inflammatory cytokines in BV-2 microglial cells. These results indicate that geraniin mitigates LPS-elicited neural/synaptic neurodegeneration, amyloidogenesis, neuroinflammation, and cognitive impairment and suggest geraniin as a therapeutic option for neuroinflammation-associated neurological disorders, such as Alzheimer's disease.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Glucosídeos/administração & dosagem , Taninos Hidrolisáveis/administração & dosagem , Receptor 4 Toll-Like/imunologia , Secretases da Proteína Precursora do Amiloide , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/imunologia , Animais , Ácido Aspártico Endopeptidases , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/genética , Disfunção Cognitiva/imunologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/imunologia , NF-kappa B/genética , NF-kappa B/imunologia , Neuroglia/efeitos dos fármacos , Neuroglia/imunologia , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
6.
Anticancer Res ; 39(8): 4475-4478, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366547

RESUMO

Chronic inflammation is involved in the development of cancer, lifestyle-related diseases, and autoimmune diseases. It also influences the severity of these diseases. Macrophages that accumulate in tumor tissues and adipose tissues of obesity have been shown to increase expression of inflammatory cytokines, thereby inducing inflammatory changes in these tissues. The macrophage phenotype is believed to be important in mediating inflammatory changes in tissues. Recently, monocytes/macrophages activated with low-dose lipopolysaccharide (LPS) were demonstrated to suppress increased expression of monocyte chemotactic protein (MCP)-1 and inflammatory cytokines (interleukin (IL)-1 ß, IL-8, and tumor necrosis factor (TNF)-α). By suppressing the increased expression of chemotaxis-related and inflammation-related factors, monocytes/macrophages activated with low-dose LPS are considered to suppress the migration of macrophages into tissues and to regulate inflammatory changes in these tissues, respectively. The effects of macrophages activated with low-dose LPS were different from those of macrophages activated with high-dose LPS. In this review, we discuss the usefulness of monocytes/macrophages activation by low-dose LPS.


Assuntos
Inflamação/tratamento farmacológico , Lipopolissacarídeos/uso terapêutico , Neoplasias/tratamento farmacológico , Obesidade/genética , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Quimiocina CCL2/genética , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Interleucina-1beta/genética , Interleucina-8/genética , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Neoplasias/genética , Obesidade/patologia , Fator de Necrose Tumoral alfa/genética
7.
Yi Chuan ; 41(7): 625-633, 2019 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-31307971

RESUMO

Normal tissues adjacent to the tumour (NAT) are widely used as controls in comparative studies to search for cancer-associated genes. However, the gene expression profiles between NAT and non-tumour-bearing tissues are different. The presence of NAT-specific expressed genes often hinders traditional transcriptional profiles studies. Further, studies on the differences in gene expression profiles between NAT and tumour-free tissues are infrequently performed. In this study, we sequenced and analysed the transcriptomes of tumour tissues (T), matched NAT and contralateral breast normal tissues (CBN) of 14 breast cancer patients, and identified 102 differentially expressed genes (DEGs) between CBN and NAT. Gene enrichment and protein-protein interaction (PPI) analyses revealed that these DEGs are significantly enriched in TNF (tumour necrosis factor) signalling and EMT (epithelial-mesenchymal transition) gene sets closely associated with oncogenesis. Comparative analyses of the transcriptomic profiles between NAT and CBN, NAT and T identified 23 NAT-specific highly-expressed genes, namely tumour-adjacent speci?cally activated (TASA) genes. These genes were significantly enriched in TNF signalling gene set, and 15 of which have not been previously reported. The results indicate that TASA genes are common in adjacent tissues and are related to the TNF signalling in the immune system. The tumour-adjacent tissues harbour tumour-like expressed genes that could contribute to tumour initiation but are often missed in NAT-T pair-wise studies.


Assuntos
Neoplasias da Mama/genética , Transcriptoma , Mama , Transformação Celular Neoplásica , Transição Epitelial-Mesenquimal , Feminino , Humanos , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética
8.
J Dairy Sci ; 102(9): 7707-7716, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31326176

RESUMO

Maillard reaction products formed from whey protein isolate (WPI) and sugar have been shown to have an anti-inflammatory effect in vitro. Here, we incubated WPI and galactose (GWA) in an aqueous solution at 65°C for 24 h to produce a glycated conjugate, which was then fermented using Lactobacillus gasseri 4M13 to obtain the fermented product (F-GWA). We demonstrated that F-GWA had an anti-inflammatory effect on lipopolysaccharide (LPS)-stimulated RAW264.7 cells. It reduced both LPS-stimulated nitric oxide production and LPS-stimulated increases in the gene expression levels of tumor necrosis factor-α and cyclooxygenase-2 in a dose-dependent manner. Furthermore, F-GWA inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase, members of the mitogen-activated protein kinase family. The glycation process was evaluated by measuring fluorescence intensity and the furosine concentration during the Maillard reaction to form GWA. The protein modifications of WPI were analyzed using MALDI-TOF tandem mass spectrometry. We found that the combination of the Maillard reaction and L. gasseri 4M13 fermentation increased the prebiotic properties of GWA as well as organic acid production, compared with the nonreacted WPI and galactose.


Assuntos
Anti-Inflamatórios/farmacologia , Fermentação , Lactobacillus gasseri/metabolismo , Macrófagos/fisiologia , Reação de Maillard , Proteínas do Soro do Leite/química , Animais , Ciclo-Oxigenase 2/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Galactose/metabolismo , Expressão Gênica/efeitos dos fármacos , Produtos Finais de Glicação Avançada , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Óxido Nítrico/metabolismo , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Proteínas do Soro do Leite/metabolismo
9.
J Agric Food Chem ; 67(30): 8361-8369, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31339708

RESUMO

The calcium-sensing receptor (CaSR), a G-protein receptor, is well recognized for its role in the regulation of adipocyte proliferation, in modulating adipose tissue dysfunction, and as a potential target for therapeutic intervention. In the present study, we investigate the anti-inflammatory effect of γ-glutamylvaline (γ-EV) on mouse adipocytes and explore the role of γ-EV-activated CaSR in the regulation of cellular homeostasis using the mouse 3T3-L1 cell line in vitro model. Our results indicate that the 3T3-L1 adipocyte-like cells accumulated lipids and expressed CaSR after 2 days of differentiation and 7 days of maturation period. The pretreatment with γ-EV (10 µM) suppressed the production of TNF-α-induced pro-inflammatory cytokines, i.e., IL-6 (23.92 ± 5.45 ng/mL, p < 0.05)) and MCP-1 (101.17 ± 39.93 ng/mL, p < 0.05), while enhancing the expression of PPARγ (1.249 ± 0.109, p < 0.001) and adiponectin (7.37 ± 0.59 ng/mL, p < 0.05). Elevated expression of Wnt5a was detected in γ-EV-treated cells (115.90 ± 45.50, p < 0.001), suggesting the involvement of the Wnt/ß-catenin pathway. Also, phosphorylation of ß-catenin was shown to be significantly inhibited (0.442 ± 0.034) by TNF-α but restored when cells were pretreated with γ-EV (0.765 ± 0.048, p < 0.05). These findings suggest that γ-EV-induced CaSR activation not only prevents TNF-α-induced inflammation in adipocytes but also modulates the cross-talk between Wnt and PPARγ pathways. Concentrations of serine phosphorylated IRS-1 were shown to be lower in γ-EV-treated cells, indicating γ-EV may also prevent inflammation in the context of insulin resistance. Thus, γ-EV-activated CaSR plays a significant role in the cross-talk between adipocyte inflammatory and metabolic pathways through the regulation of extracellular sensing.


Assuntos
Adipócitos/efeitos dos fármacos , Dipeptídeos/farmacologia , Receptores de Detecção de Cálcio/imunologia , Células 3T3-L1 , Adipócitos/imunologia , Animais , Interleucina-6/genética , Interleucina-6/imunologia , Camundongos , PPAR gama/genética , PPAR gama/imunologia , Fosforilação , Receptores de Detecção de Cálcio/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
10.
J Agric Food Chem ; 67(28): 7869-7879, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31287296

RESUMO

Carnitine, a dietary quaternary amine mainly from red meat, is metabolized to trimethylamine (TMA) by gut microbiota and subsequently oxidized to trimethylamine-N-oxide (TMAO) by host hepatic enzymes, flavin monooxygenases (FMOs). The objective of this study aims to investigate the effects of flavonoids from oolong tea and citrus peels on reducing TMAO formation and protecting vascular inflammation in carnitine-feeding mice. The results showed that mice treated with 1.3% carnitine in drinking water significantly (p < 0.05) increased the plasma levels of TMAO compared to control group, whereas the plasma TMAO was remarkedly reduced by flavonoids used. Meanwhile, these dietary phenolic compounds significantly (p < 0.05) decreased hepatic FMO3 mRNA levels compared to carnitine only group. Additionally, oolong tea extract decreased mRNA levels of vascular inflammatory markers such as tissue necrosis factor-alpha (TNF-α), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Polymethoxyflavones significantly lowered the expression of VCAM-1 and showed a decreasing trend in TNF-α and E-selectin mRNA expression compared to the carnitine group. Genus-level analysis of the gut microbiota in the cecum showed that these dietary phenolic compounds induced an increase in the relative abundances of Bacteroides. Oolong tea extract-treated group up-regulated Lactobacillus genus, compared to the carnitine only group. Administration of polymethoxyflavones increased Akkermansia in mice.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Camellia sinensis/química , Carnitina/metabolismo , Citrus/química , Flavonas/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Aterosclerose/genética , Aterosclerose/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Biotransformação/efeitos dos fármacos , Feminino , Flavonas/análise , Microbioma Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Humanos , Metilaminas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/análise , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
11.
J Agric Food Chem ; 67(32): 8810-8818, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31318199

RESUMO

Citrus grandis (L.) Osbeck is a popular fruit cultivated around the world, and its peels are sometimes used for the treatment of cough, abdominal pain, and indigestion in China. However, the peel is discarded after fruit consumption in most cases, and its chemical constituents and biological activities have not been validated before. The present study focused on evaluation of the chemical and pharmacological profile of coumarins from peels of C. grandis against inflammation. The extracts and phytochemicals from peels of C. grandis were prepared, and anti-inflammatory activities were carried out in vivo and in vitro, including inhibiting xylene-induced ear edema and carrageenan-induced paw edema in mice and the production of inflammatory cytokines (interleukin 1ß, prostaglandin 2, and tumor-necrosis factor α) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results indicated that methanolic extract, ethyl acetate fraction, and four major coumarins (compounds 7, 8, 13, and 16) inhibited swelling induced by xylene and carrageenan, separately, in vivo. Furthermore, 18 coumarins inhibited inflammatory factor secretion in macrophages primed by LPS, in which compounds 4, 6, 7, 10, 17 showed the most pronounced change, which were comparable to dexamethasone. In summary, peel of C. grandis showed an anti-inflammatory effect and coumarin compounds were responsible for regulating inflammatory mediators and cytokines, which might provide a novel nutritional strategy for inflammatory diseases.


Assuntos
Anti-Inflamatórios/administração & dosagem , Citrus/química , Cumarínicos/administração & dosagem , Edema/tratamento farmacológico , Frutas/química , Extratos Vegetais/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Cumarínicos/química , Cumarínicos/isolamento & purificação , Dinoprostona/imunologia , Edema/genética , Edema/imunologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Resíduos/análise
12.
Medicine (Baltimore) ; 98(26): e15963, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261503

RESUMO

BACKGROUND: Genetic factors in the pathogenesis of Kawasaki disease (KD) have received a lot of attention during the past decade. Some studies have reported that tumor necrosis factor (TNF)-α-308 polymorphism has been associated with KD. However, there have been inconsonant results among different studies. To increase the power for clarifying the influence of TNF on KD, a meta-analysis of case-control studies were performed. METHODS: The following databases were searched to identify related studies: PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP databases according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Search terms included "Kawasaki disease" or "KD," "tumor necrosis factor-alpha" or "TNF-α," and "polymorphism" or "mutation." Two reviewers independently extracted data and assessed study quality using Newcastle-Ottawa Scale. Odds ratios (ORs) with corresponding 95% confidence intervals (CI) were used to assess the strength of the association. Accounting for heterogeneity, a fixed or random effects model was respectively adopted. Heterogeneity was checked using the Q test and the I statistic. A cumulative meta-analysis was conducted to estimate the tendency of pooled OR. Funnel plots and Egger tests were performed to test for possible publication bias and sensitivity analyses were done to ensure authenticity of the outcome. RESULTS: Eleven separate studies were suitable for the inclusion criterion. The selected studies contained 2582 participants, including 841 in KD group and 1741controls. The pooled odds ratio of G versus A with the random effect model was 1.09 (95% CI = 0.69-1.70, P = .72) and the genotype effects for GG versus GA+AA was 1.14 (95% CI = 0.68-1.90, P = .62) in the whole population separately. Unfortunately, no significant association was detected between the TNF-α-308 polymorphism and KD risk under allele and genotype model. CONCLUSION: No association between the TNF-α-308 polymorphism and KD was found in our meta-analysis and further studies with larger sample size and more ethnicities are expected to be conducted in the future to validate the results.


Assuntos
Predisposição Genética para Doença , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética , Humanos
13.
Medicine (Baltimore) ; 98(26): e16029, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261506

RESUMO

BACKGROUND: To study the occurrence and prognosis of acute respiratory distress syndrome (ARDS) using single nucleotide polymorphisms (SNPs) of TNF-α rs1800629, IL-6 rs1800796, and MyD88 rs7744 loci in the TLR4/NF-κB pathway. METHODS: Genotypes were analyzed for TNF-α rs1800629, IL-6 rs1800796, and MyD88 rs7744 loci. Plasma TNF-α and IL-6 levels and MyD88 mRNA expression in peripheral blood mononuclear cells (PBMCs) of 300 ARDS patients and 300 non-ARDS patients (control group) were examined. The patients were followed up for 60 days, and the prognosis outcome was recorded. RESULTS: The TNF-α rs1800629 locus A allele and the IL-6 rs1800796 locus G allele were found to be risk factors for ARDS (adjusted OR = 1.452, 95% CI: 1.211-1.689, P < .001 and adjusted OR = 1.205, 95% CI: 1.058-1.358, P = .005, respectively). The G allele at MyD88 rs7744 locus was a protective factor against ARDS (adjusted OR = 0.748, 95% CI: 0.631-0.876, P < .001). Compared with the other groups, homozygotes for TNF-α rs1800629, IL-6 rs1800796, and MyD88 rs7744 loci had higher expression levels, of which homozygotes for TNF-α rs1800629 and IL-6 rs1800796 loci had lower 60-day survival rates, while MyD88 rs7744 locus homozygotes had a higher 60-day survival rate. CONCLUSION: The effect of TNF-α rs1800629, IL-6 rs1800796, and MyD88 rs7744 SNPs on gene expression level is a likely cause of ARDS occurrence and poor prognosis.


Assuntos
NF-kappa B/genética , Polimorfismo de Nucleotídeo Único , Síndrome do Desconforto Respiratório do Adulto/genética , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Biomarcadores/sangue , Feminino , Expressão Gênica/genética , Humanos , Interleucina-6/sangue , Interleucina-6/genética , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/sangue , Fator 88 de Diferenciação Mieloide/genética , NF-kappa B/sangue , Prognóstico , RNA Mensageiro/sangue , Síndrome do Desconforto Respiratório do Adulto/sangue , Síndrome do Desconforto Respiratório do Adulto/diagnóstico , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Transdução de Sinais , Análise de Sobrevida , Receptor 4 Toll-Like/sangue , Fator de Necrose Tumoral alfa/sangue
14.
DNA Cell Biol ; 38(8): 874-879, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31215797

RESUMO

Microglia-mediated neuroinflammation plays an important role in Alzheimer's disease development. Resveratrol, a natural polyphenol from the Japanese knotweed (Polygonum cuspidatumand), is known to protect against neuroinflammation, but the mechanism remains unclear. To begin to explore potential mechanisms, we created a model of inflammatory injury in BV-2 murine microglial cells based on the induction of amyloid-ß. We found that resveratrol (10 and 50 nM) significantly inhibited Aß-induced proliferation and activation of BV-2 cells, as well as their release of the proinflammatory cytokines, IL-6 and TNF-α. Resveratrol also suppressed the overexpression of cleaved caspase-1 and IL-1ß, and decreased Aß-stimulated degradation of IkBα and phosphorylation of NF-κB phosphorylation. Western blot analysis showed that Aß upregulated the TXNIP/TRX/NLRP3 pathway, while resveratrol treatment inhibited it. We conclude that resveratrol protects microglia from Aß-stimulated inflammation by suppressing the inflammatory response, at least in part by inhibiting the TXNIP/TRX/NLRP3 signaling pathway.


Assuntos
Proteínas de Transporte/metabolismo , Microglia/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Resveratrol/farmacologia , Tiorredoxinas/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Caspase 1/metabolismo , Linhagem Celular , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Microglia/fisiologia , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/toxicidade , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
15.
Gene ; 711: 143924, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31212050

RESUMO

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to inflammatory pathways and many metabolic disorders, such as obesity and dyslipidemia. Metabolic syndrome (MetS) is an emergent problem among patients with epilepsy. However, little is known about interaction between MnSOD Ala16Val SNP and metabolic comorbities in epilepsy. Thus, we investigated the relationship between MnSOD Ala16Val SNP with epilepsy and its influence on MetS, inflammation, apoptosis and DNA damage parameters. Ninety subjects were evaluated (47 epilepsy patients and 43 healthy controls) by questionnaires and laboratorial exams. Levels of inflammatory, apoptotic and DNA damage markers, as well as MnSOD polymorphism were assessed. An increased proportion of VV genotype in epilepsy group when compared to control group was observed. Tumor Necrosis Factor-α (TNF-α), Acetylcholinesterase, caspase-8, and Picogreen levels were increased in VV epilepsy group. An important correlation between TNF-α vs caspase-8, and Cholesterol vs. Triglycerides was observed in the epilepsy group with VV genotype. Our findings suggest that the MnSOD Ala16Val SNP might have an important role in epilepsy, mainly in patients with generalized seizures and particularly with VV genotype. The metabolic parameters also presented significant results in epilepsy group with VV genotype, which applying attention in view of further consequences and disorders that could be developed.


Assuntos
Substituição de Aminoácidos , Colesterol/metabolismo , Convulsões/genética , Superóxido Dismutase/genética , Triglicerídeos/metabolismo , Acetilcolinesterase/genética , Adulto , Estudos de Casos e Controles , Caspase 8/genética , Dano ao DNA , Feminino , Proteínas Ligadas por GPI/genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Estresse Oxidativo , Fator de Necrose Tumoral alfa/genética
16.
J Sci Food Agric ; 99(13): 5870-5880, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31206687

RESUMO

BACKGROUND: Sepsis is a set of serious organic manifestations caused by an infection, whose progression culminates in exacerbated inflammation and oxidative stress, poor prognosis, and high hospital costs. Antioxidants used against sepsis have been evaluated, including essential oils such as ß-caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The aim of this study was to evaluate the anti-inflammatory activity of the association of these two compounds. RESULTS: Treatment with BCP-DHA, at a dose of 200 µL/animal, significantly inhibited the migration of neutrophils in a Cg-induced peritonitis model. After Staphylococcus aureus infection, in the groups treated with BCP-DHA there was a significant decrease in the total and differential count of leukocytes, increased expression of cytokines TNF-α and IFN-γ in treated groups, an increase of IL-4 and IL-5 in B/D and B/D + SA groups, and an augmentation of IL-6 and IL-12 groups in B/D + SA groups. Histological and bacterial analysis revealed lower neutrophil migration and lower bacterial load in the infected and treated groups. CONCLUSION: In general, the BCP-DHA association presented anti-inflammatory activity against two different models of acute inflammation and infection, showing promising potential as a therapeutic adjuvant in sepsis. © 2019 Society of Chemical Industry.


Assuntos
Anti-Inflamatórios/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Peritonite/tratamento farmacológico , Sepse/tratamento farmacológico , Sesquiterpenos/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Quimioterapia Combinada , Humanos , Interleucina-12/genética , Interleucina-12/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Peritonite/genética , Peritonite/imunologia , Peritonite/microbiologia , Sepse/genética , Sepse/imunologia , Sepse/microbiologia , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
17.
J Sci Food Agric ; 99(13): 6076-6083, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31233219

RESUMO

BACKGROUND: This study was conducted to evaluate the health benefits to weaning pigs, raised under low sanitary conditions, of dietary supplementation with a multi-strain yeast fraction product (Cyberlindnera jadinii and Saccharomyces cerevisiae). In total, 160 weaning pigs (7.21 ± 1.05 kg) were randomly allotted to two dietary treatments in a 6-week feeding trial. The dietary treatments included a corn-soybean meal-based basal diet (CON) and CON + 2 g kg-1 multi-strain yeast fraction product (MsYF) during weeks 1-2 and 0.4 g kg-1 MsYF during weeks 3-6. RESULTS: The MsYF supplementation increased (P < 0.05) body weight (BW) at day 42 and average daily gain (ADG) during days 1-14 and days 1-42 (P < 0.05) compared to CON. The total tract digestibility of dry matter (DM), fecal Lactobacillus counts, and serum immunoglobulin G (IgG) concentration at day 42 were higher (P < 0.05) in pigs fed a MsYF supplemented diet. The concentration of serum haptoglobin in pigs receiving a MsYF-supplemented diet was higher (P < 0.05) at days 7, 14, and 42 than those receiving CON. The mRNA expression for INF-γ and TNF-α genes were lower (P < 0.05) at days 14 and 7 respectively and the expression of IL-6 and TLR-2 genes was lower (P < 0.01) at days 7 and 14 in pigs fed an MsFY supplemented diet than those fed CON. CONCLUSION: Supplementation with a multi-strain yeast fraction product had a positive effect on ADG during the early post-weaning period and led to better health in weaning pigs. © 2019 Society of Chemical Industry.


Assuntos
Saccharomyces cerevisiae/química , Suínos/crescimento & desenvolvimento , Leveduras/química , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Suplementos Nutricionais/análise , Fezes/microbiologia , Microbioma Gastrointestinal , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Higiene , Interferon-alfa/genética , Interferon-alfa/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Suínos/genética , Suínos/imunologia , Suínos/microbiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Desmame
18.
Genet Test Mol Biomarkers ; 23(6): 363-372, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31161819

RESUMO

Background and Aims: The relationship between the promoter polymorphism (-308G/A) of the tumor necrosis factor-alpha (TNF-α) gene and the susceptibility to asthma has been tested in several studies. However, the results have been inconsistent. Therefore, we performed an updated meta-analysis to evaluate the relationship between this promoter polymorphism of the TNF-α gene and the risk of asthma. Methods: Fifty case-control studies were included in this meta-analysis which provided 17,937 controls and 9961 asthma patients. The pooled p-value, odds ratio (OR), and 95% confidence interval (95% CI) were used to investigate the strength of the association of this polymorphism of the TNF-α gene with the risk of asthma. The meta-analysis was carried out by Comprehensive Meta-Analysis software. Results: The results of our meta-analysis revealed that the TNF-α polymorphism (-308, G/A) was strongly associated with the risk of asthma (p < 0.05 in the allelic, dominant, and recessive models, respectively). In further analyses, based on age group and ethnicity, we observed this association for all subpopulations examined (p < 0.05 in allelic, dominant, and recessive models, respectively). Conclusion: This large-scale meta-analysis supports a strong association between the TNF-α gene promoter polymorphism (-308G/A) and the development to asthma in both children and adults.


Assuntos
Asma/genética , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Fatores de Risco , Fator de Necrose Tumoral alfa/metabolismo
19.
Vet Microbiol ; 234: 25-33, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31213269

RESUMO

Porcine productive and respiratory syndrome virus (PRRSV) and classical swine fever virus (CSFV) both are major pathogens of swine that pose a great threat to the Chinese pig industry. It has been found that PRRSV infection can lead to vaccination failure of CSFV C strain-derived modified live vaccine (CSFV-C) by interfering with the immune responses to the latter. To investigate whether PRRSV can suppress CSFV-C replication, we created a 3D4/21-based cell line PAM39 that is susceptible to both viruses by expressing PRRSV receptors CD163 and CD169, and then investigated their interplay under the condition of either sequential or simultaneous co-infection. The most significant suppressive effect came from the sequential infection when the cells were first infected by PRRSV and then followed by CSFV-C at an interval of 6 h. In addition, this effect was independent of PRRSV strains. Mechanistically, PRRSV induced an elevated level of a subset of pro-inflammatory cytokines, especially tumor necrosis factor (TNF-α), through the nuclear factor κB (NF-κB) signaling pathway to inhibit the replication of CSFV-C in vitro. Thus, our studies provide an alternative explanation on PRRSV-induced CSFV vaccination failure, and this has an important implication in CSF vaccination and control.


Assuntos
Vírus da Febre Suína Clássica/fisiologia , Vírus da Síndrome Respiratória e Reprodutiva Suína , Fator de Necrose Tumoral alfa/imunologia , Replicação Viral , Animais , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Linhagem Celular , Imunofluorescência , NF-kappa B/metabolismo , RNA Interferente Pequeno , Receptores de Superfície Celular/genética , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Transdução de Sinais , Suínos , Fator de Necrose Tumoral alfa/genética
20.
J Dairy Sci ; 102(8): 7556-7569, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31229286

RESUMO

The aim of this study was to investigate whether the ruminal epithelium activates a local inflammatory response following a short-term subacute ruminal acidosis (SARA) challenge. Seven ruminally cannulated, nonpregnant, nonlactating beef heifers, fed a baseline total mixed ration (TMR) with 50:50 forage-to-concentrate ratio, were used in a crossover design with 2 periods and 2 treatments: SARA and control (CON). Induction of SARA included feed restriction (25% of dry matter intake [DMI] for 24 h) followed by a grain overload (30% of baseline DMI) and provision of the full TMR; whereas, the CON group received the TMR ad libitum. Ruminal pH was recorded using indwelling probes, and ruminal lipopolysaccharide (LPS) concentration was measured daily following the challenge until d 6. Biopsies of ruminal papillae from the ventral sac were collected on d 2 and 6 after the grain overload. Transcript abundance of genes associated with acute inflammation was measured by quantitative real-time PCR, normalized to the geometric mean of 3 stable housekeeping genes. Target genes included toll-like receptor-2 (TLR2), TLR4, TLR9, tumor necrosis factor-α (TNFA), prostaglandin endoperoxide synthase-1 (PTGS1), PTGS2 transforming growth factor ß-1 (TGFB1), and 4 intermediate enzymes of leukotriene synthesis (ALOX5, ALOX5AP, LTA4H, and LTC4S). Protein localization and expression of TLR4 were quantified by image analysis of fluorescence intensity. Statistical analysis was performed using as a crossover design with fixed effects of treatment, day, and the treatment × day interaction with the random effect of day within period. Ruminal pH was below 5.6 for 4.5 h/d and below 5.8 for 6.9 h/d in the SARA group compared with 22 and 72 min/d, respectively, for CON. Ruminal LPS concentration peaked on d 2 in SARA heifers at 51,481 endotoxin units (EU)/mL compared with 13,331 EU/mL in CON. Following grain overload, small but statistically significant decreases in the transcriptional abundance of TLR2, TLR4, TNF, PTGS2, ALOX5, and ALOX5AP were seen in SARA versus CON heifers. A functionally relevant decrease in TLR4 expression in SARA heifers compared with CON was confirmed by a decrease in fluorescence intensity of the corresponding protein following immunohistofluorescent staining of papillae. The study results indicate a suppression of the inflammatory response in the ruminal epithelium and suggest that the response is tightly regulated, allowing for tissue recovery and return to homeostasis following SARA.


Assuntos
Acidose/veterinária , Doenças dos Bovinos/imunologia , Epitélio/imunologia , Rúmen/imunologia , Acidose/induzido quimicamente , Acidose/genética , Acidose/imunologia , Animais , Bovinos , Doenças dos Bovinos/induzido quimicamente , Doenças dos Bovinos/genética , Dieta/veterinária , Feminino , Concentração de Íons de Hidrogênio , Lipopolissacarídeos/efeitos adversos , Lipopolissacarídeos/imunologia , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandina-Endoperóxido Sintases/imunologia , Rúmen/química , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
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