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1.
Life Sci ; 237: 116978, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31644893

RESUMO

AIMS: The activation of NLRP3 inflammasome, which initiates an inflammatory cascade and triggers inflammatory death, plays a crucial role in the pathogenesis of spinal cord injury (SCI). Echinacoside (ECH) is a phenylethanoid glycoside possessing prominent anti-inflammatory effects and various neuroprotective properties in the central nervous system, but the effect of ECH on SCI was rarely studied. Therefore, the purpose of this experiment was to look into the therapeutic effects of ECH on SCI and the underlying mechanisms. MAIN METHODS: Basso-Beattie-Bresnahan (BBB) locomotion scale, Nissl staining, and hematoxylin-eosin (HE) staining was employed to examine the therapeutic effects of ECH on SCI. In addition, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) in BV-2 cells stimulated with lipopolysaccharides and adenosine 5'-triphosphate were examined. The expression levels of proteins involving NLRP3 inflammasome-related pathway were measured. KEY FINDINGS: The in vivo experiment indicated that administration of ECH significantly enhanced the BBB scores, reduced the neuron loss, and ameliorated the tissue architecture after SCI. Additionally, ECH dramatically inhibited NLRP3 inflammasome activation in the rat SCI model. In vitro study indicated that ECH significantly reduced ROS level, improved the MMP, blocked activation of NF-κB, and inhibited the NLRP3 inflammasome signaling pathway. The effect of ECH on inhibition of NLRP3 inflammasome signaling pathway was partially governed by suppression of the generation of ROS and activation of NF-κB. SIGNIFICANCE: ECH can accelerate motor function recovery in rats following SCI by inhibiting NLRP3 inflammasome-related signaling pathway, suggesting that ECH may serve as a potential therapeutic agent for treating SCI.


Assuntos
Glicosídeos/farmacologia , Inflamassomos/antagonistas & inibidores , Inflamação/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Traumatismos da Medula Espinal/prevenção & controle , Animais , Inflamação/complicações , Locomoção , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/patologia
2.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(7): 434-442, ago.-sept. 2019. ilus, graf, tab
Artigo em Inglês | IBECS | ID: ibc-182863

RESUMO

Background: Non-alcoholic fatty liver disease (NAFLD), a condition that leads to fibrosis, is caused by intake of very high-fat diets (HFDs). However, while the negative impact on the liver of these diets has been an issue of interest, systematic research on the effect of HFDs are lacking. Objective: To characterize the overall impact of HFDs on both molecular and morphological signs of liver remodeling. Methods: A study was conducted on male C57BL/6J mice to assess the effect of 4- and 8-week HFDs (60% kcal from fat) on (I) liver steatosis and fibrosis, and (II) expression of factors involved in inflammation and angiogenesis. Results: After an 8-week HFD, vascular endothelial growth factor type-2 receptor (VEGF-R2) and fatty acid translocase/trombospondin-1 receptor (CD36) were overexpressed in liver tissue of mice given HFDs. These changes suggest impaired liver angiogenesis and occurred together with (I) increased GPR78-BiP and EIF2alpha phosphorylation, suggesting endoplasmic reticulum stress, (II) induction of Col1a1 gene expression, a marker of fibrosis, and (III) increased CD31 immunolabeling, consistent with active angiogenesis and fibrosis. Conclusion: Our data show that very HFDs promote a rapid inflammatory response, as well as deregulation of angiogenesis, both consistent with development of liver fibrosis


Antecedentes: El hígado graso no alcohólico (HGNA) es una enfermedad hepática que ocasiona fibrosis y se genera por la ingesta de dietas ricas en grasa. Aunque los efectos nocivos de este tipo de dietas son de gran interés, no son muy abundantes los estudios sistemáticos sobre las consecuencias que su consumo puede tener en el hígado. Objetivo: Evaluar los efectos de una dieta rica en grasa sobre el remodelado hepático, tanto a nivel morfológico como molecular. Métodos: Se utilizaron ratones macho C57BL/6J tratados durante 4/8 semanas con una dieta que contenía un 60% de las kilocalorías procedentes de grasa sobre: 1) la aparición de esteatosis y/o fibrosis hepática y 2) la expresión de factores implicados en procesos de inflamación y angiogénesis. Resultados: Tras 8 semanas de dieta se observó un incremento en el receptor del factor de crecimiento vascular endotelial tipo 2 (R2-FCVE) y en la translocasa de ácidos grasos (CD36). Estos cambios, que sugieren que los procesos angiogénicos del hígado están alterados, fueron simultáneos a: 1) un aumento del GPR78-BiP y de la fosforilación de EIF2alpha, marcadores de estrés del retículo endoplásmico, 2) la inducción en la expresión del gen de colágeno Col1a1, indicador de fibrosis y 3) un incremento de células inmunofluorescentes para CD31 compatible con procesos de angiogénesis y de fibrosis. Conclusiones: Nuestros resultados muestran que las dietas con alto contenido en grasa inducen la rápida activación de respuestas inflamatorias, así como alteraciones en la angiogénesis, siendo ambos procesos compatibles con el desarrollo de fibrosis hepática


Assuntos
Animais , Camundongos , Gorduras na Dieta/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Inibidores da Angiogênese , Fígado Gorduroso/complicações , Fígado Gorduroso/veterinária , Inflamação/complicações , Fatores de Crescimento Endotelial/administração & dosagem , Antígenos CD36 , Fibrose , Projetos de Pesquisa , Western Blotting
3.
Chem Biol Interact ; 313: 108824, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31542397

RESUMO

Insect-based bioactive components are emerging as novel sources of drugs, effective against various diseases. Inflammation is considered to be an innate immune response developed by different organisms against foreign pathogens and cellular stress. However, repetitive elevated inflammation is considered to be responsible for development of many other diseases including colitis and arthritis. Due to the limited activities and side effects of non-steroidal anti-inflammatory drugs, researchers are continuously looking for alternative sources of drug molecules to alleviate the inflammatory related complications. Recently, insect-based bioactive components, such as venoms, haemocytes, cecropin A, papiliocin, N-acetyldopamine dimers, cecropin-TY1 peptide, cop A3 peptide, glycosaminoglycan, coprisin peptide, silk fibroin microparticles, and silk fibroin nanoparticles have been found to be active against different inflammatory mechanisms and associated diseases. Cancers, are some of the deadliest diseases, which are mainly treated by chemotherapy, radiation therapy and surgery. However, such treatments, mainly chemotherapy, is associated with enormous side effects. Therefore, as an alternative, less hazardous option, compounds from insects with anti-cancerous activity are being explored. Insect-derived compounds, such as cantharidin, norcantharidin, isocoumarin, plancyols A, plancypyrazine A, pancratistatin, narciclasine, and ungeremine, show potential anti-cancerous activity. In this review, we will be discussing the role of different potential drug molecules of insect origin with special emphasis on anti-inflammation and their association with health disorders and cancer.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Inflamação/complicações , Insetos/química , Animais , Artrite/tratamento farmacológico , Artrite/etiologia , Produtos Biológicos/farmacologia , Colite/tratamento farmacológico , Colite/etiologia , Humanos , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/etiologia
5.
J Cancer Res Clin Oncol ; 145(10): 2583-2593, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401675

RESUMO

OBJECTIVE: Exercise training is recently considered as a trend in adjuvant therapies for cancer patients, but its mechanisms need to be scrutinized further. This study is aimed to test the hypothesis that the patients who perform the high-intensity interval exercise training (HIIT) during hormone therapy would show improvements in low-grade inflammation and HSP70 compared to the controls receiving standard care. METHODS: Fifty two non-metastatic and hormone-responsive breast cancer patients were randomly assigned to high-intensity interval exercise (HIIT) (n = 26) and usual care (n = 26) groups. The HIIT groups participated in a high-intensity interval training protocol on a treadmill 3 days/week for 12 weeks. The training intensity was determined according to the predicted maximal heart rate. Demographic characteristics and medical history were collected via an interviewer-administered questionnaire at the baseline visit. Body fat was estimated based on skinfold thickness measured with calipers on the participant's nonsurgery side at the triceps, suprailiac crest. [Formula: see text] was estimated by 1-Mile Rockport Walk Test. Blood samples were collected 48 h before starting the exercise protocol and 48 h after the last exercise session. TNF-α, IL-6, IL-1ß, IL-10, and HSP70 levels in serum were measured using the enzyme-linked immunosorbent assay (ELISA) method according to the manufacture's instruction. Supernatant cytokine concentrations were determined by ELISA for IL-4 and IFN-γ. The data were analyzed by ANCOVA test that the pretest values were considered as covariate at P ≤ 0.05. RESULTS: HIIT improved [Formula: see text] in the HIIT group compared to the usual care group (P = 0.002). The serum levels of TNF-α (P = 0.001), IL-6 (P = 0.007), and IL-10 (P = 0.001) were lower in the HIIT group. The level of IL-4 (P = 0.050) in the stimulated peripheral blood mononuclear cells significantly increased in the HIIT group compared to the usual care group. Furthermore, the serum level of the HSP70 was significantly higher in the HIIT group in comparison to the usual care group (P = 0.050). The TNF-α/IL-10 (P = 0.050) and IL-6/IL-10 (P = 0.042) ratios were lower in the HIIT group. CONCLUSION: The results of this study indicated that HIIT has positive impacts on the cardiorespiratory fitness and inflammatory cytokines in the breast cancer patients undergoing hormone therapy.


Assuntos
Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Treinamento Intervalado de Alta Intensidade , Inflamação/complicações , Inflamação/metabolismo , Biomarcadores , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Citocinas/metabolismo , Feminino , Proteínas de Choque Térmico HSP70/genética , Treinamento Intervalado de Alta Intensidade/métodos , Humanos , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo
6.
Life Sci ; 233: 116727, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31381895

RESUMO

AIMS: Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in elderly people. The pathogenesis of neovascular AMD is known but is closely related to inflammation and choroidal neovascularization (CNV). The aim of this study was to investigate the anti-inflammatory and anti-angiogenic effects of calcium on neovascular AMD. MAIN METHODS: Human retinal pigment epithelial cells (ARPE-19) were used to identify protein markers of inflammation induced by differentiated macrophages. Choroidal neovascularization (CNV) mouse model was established by rupturing the Bruch's membrane using laser photocoagulation in C57BL/6 mice. Mice were divided into the following groups: untreated control and calcium supplemented. The expression levels of toll-like receptor isotype (TLR) 4, nuclear factor kappa B (NF-κB), hypoxia-inducible factor-1α (Hif-1α), and vascular endothelial growth factor (VEGF) were investigated to check whether calcium supplementation results in suppression of inflammation and has an anti-angiogenic effect. CNV was evaluated by immunofluorescence staining on choroidal flat mounts. KEY FINDING: The inflammation-induced expression of TLR4, NF-κB, and Hif-1α was decreased in ARPE-19 cells after calcium supplementation. Inhibition of the transcriptional activation of ARPE-19 cells by Hif-1α suppression resulted in decreased VEGF expression. In the laser-induced CNV mouse model, calcium supplementation inhibited inflammatory mediators and neovascularization in the retinal tissue. SIGNIFICANCE: Supplementation with calcium seems to constrain inveterate symptoms of neovascular AMD by inhibiting inflammation and angiogenesis in the laser-induced CNV mouse model.


Assuntos
Inibidores da Angiogênese/farmacologia , Cálcio/farmacologia , Neovascularização de Coroide/prevenção & controle , Mediadores da Inflamação/metabolismo , Inflamação/complicações , Epitélio Pigmentado da Retina/efeitos dos fármacos , Animais , Células Cultivadas , Neovascularização de Coroide/etiologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/metabolismo
7.
Life Sci ; 233: 116741, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31398419

RESUMO

AIMS: Carbon black nanoparticles (CBNPs) are widely used in industrial field. Sensitive stages such as pregnancy are assumed to be more susceptible to stimulus, however whether pregnancy exposure to CBNPs (PrE-to-CBNPs) would cause long-term toxic effects in dams and the underlying mechanisms remain poorly addressed. The present study is aimed to determine the long-term toxic effects of PrE-to-CBNPs in dams. MATERIALS AND METHODS: The pregnant mice were randomly divided into control group, low (21 µg/animal), medium (103 µg/animal) and high (515 µg/animal) CBNPs-treated groups. From gestational day (GD) 9 to GD18, the pregnant mice were intranasal exposed. At 49 days after parturition, lung tissues and bronchoalveolar lavage fluid (BALF) were obtained. Weight change, lung histopathology, lung ultrastructural pathology, cell count in BALF, oxidative stress/inflammatory maker and autophagy/lysosome-related protein expression were determined. KEY FINDINGS: PrE-to-CBNPs caused a dose-dependent persistent lung injury in mice even 49 days after parturition, including the deteriorative lung histopathological changes, elevation of oxidative stress marker Nrf-2, HO-1 and CHOP, infiltration of macrophage and increased mRNA expression of inflammatory cytokines in the lung tissues and elevation of cells in BALF. However, PrE-to-CBNPs did not induce significant neutrophil infiltration and fibrosis. Moreover, we found that CBNPs could deposit in the lysosomes and decrease cathepsin D (an important hydrolase in lysosome), which might be associated with the dysfunction of lysosome and autophagy. SIGNIFICANCE: Our study demonstrated that PrE-to-CBNPs could result in long-term lung injury in dams, and lysosomal dysfunction was probably linked to this process.


Assuntos
Inflamação/complicações , Lesão Pulmonar/etiologia , Lisossomos/patologia , Nanopartículas/efeitos adversos , Estresse Oxidativo , Efeitos Tardios da Exposição Pré-Natal/etiologia , Fuligem/efeitos adversos , Animais , Autofagia , Citocinas/metabolismo , Feminino , Lesão Pulmonar/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia
8.
BMC Neurol ; 19(1): 148, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269910

RESUMO

BACKGROUND: Almost 40% of stroke patients have a poor outcome at 3 months after the index event. Predictors for stroke outcome in the early acute phase may help to tailor stroke treatment. Infection and inflammation are considered to influence stroke outcome. METHODS: In a prospective multicenter study in Germany and Spain, including 486 patients with acute ischemic stroke, we used multivariable regression analysis to investigate the association of poor outcome with monocytic HLA-DR (mHLA-DR) expression, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide-binding protein (LBP) as markers for immunodepression, inflammation and infection. Outcome was assessed at 3 months after stroke via a structured telephone interview using the modified Rankin Scale (mRS). Poor outcome was defined as a mRS score of 3 or higher which included death. Furthermore, a time-to-event analysis for death within 3 months was performed. RESULTS: Three-month outcome data was available for 391 patients. Female sex, older age, diabetes mellitus, atrial fibrillation, stroke-associated pneumonia (SAP) and higher National Institute of Health Stroke Scale (NIHSS) score as well as lower mHLA-DR levels, higher IL-6 and LBP-levels at day 1 were associated with poor outcome at 3 months in bivariate analysis. Furthermore, multivariable analysis revealed that lower mHLA-DR expression was associated with poor outcome. Female sex, older age, atrial fibrillation, SAP, higher NIHSS score, lower mHLA-DR expression and higher IL-6 levels were associated with shorter survival time in bivariate analysis. In multivariable analysis, SAP and higher IL-6 levels on day 1 were associated with shorter survival time. CONCLUSIONS: SAP, lower mHLA-DR-expression and higher IL-6 levels on day one are associated with poor outcome and shorter survival time at 3 months after stroke onset. TRIAL REGISTRATION: www.clinicaltrials.gov, NCT01079728 , March 3, 2010.


Assuntos
Isquemia Encefálica/imunologia , Antígenos HLA-DR/sangue , Interleucina-6/sangue , Pneumonia/etiologia , Acidente Vascular Cerebral/imunologia , Proteínas da Fase Aguda , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Isquemia Encefálica/mortalidade , Proteínas de Transporte/sangue , Diabetes Mellitus , Feminino , Alemanha , Humanos , Tolerância Imunológica , Inflamação/complicações , Interleucina-10/sangue , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Pneumonia/mortalidade , Estudos Prospectivos , Espanha , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue
9.
Clin Interv Aging ; 14: 1199-1206, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308643

RESUMO

Objective: Emerging evidence suggests that systemic inflammation is a predictor of poor prognosis in acute myocardial infarction (AMI). In this study, we sought to assess whether inflammation-based prognostic scores are associated with in-hospital outcomes in elderly patients with AMI. Methods: In this retrospective study, patients who were over 75-years-old and met the diagnostic criteria for AMI were consecutively recruited from January 1, 2016, to March 31, 2019. Logistic regression and receiver-operating characteristic (ROC) analyses were performed to evaluate the predictive value of the inflammation-based Glasgow Prognostic Score (GPS), Prognostic Index (PI) and Prognostic Nutritional Index (PNI). Results: A total of 273 patients were enrolled. The incidence of major cardiovascular adverse events (MACEs) and mortality during hospitalization increased significantly with increasing GPS and PI scores. Multiple logistic regression showed that the GPS was independently associated with MACEs (score 1, RR: 6.711, 95% CI: 1.409-31.968; score 2, RR: 14.063, 95% CI: 3.018-65.535) and mortality (score 1, RR: 8.656, 95% CI: 1.068-70.126; score 2, RR: 10.549, 95% CI: 1.317-84.465). The PI was also independently predictive of MACEs (score 2, RR: 5.132, 95% CI: 1.451-18.148). No significant difference was observed in the PNI between patients with different in-hospital outcomes. When in-hospital MACEs were used as an endpoint, the area under the curve (AUC) of the GPS was 0.740 (95% CI 0.678-0.802), and the AUC of the PI was 0.703 (95% CI 0.634-0.773). When mortality was used as an endpoint, the AUC of the GPS was 0.677 (95% CI 0.602-0.753), and the AUC of the PI was 0.667 (95% CI 0.577-0.757). Conclusion: The severity of systemic inflammation is a strong predictor of poor prognosis in elderly patients with AMI. Among these three inflammation-based prognostic scores, the GPS has a better predictive value than the PI and PNI for in-hospital MACEs and mortality.


Assuntos
Inflamação/complicações , Inflamação/mortalidade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Idoso , Área Sob a Curva , Biomarcadores/sangue , Feminino , Humanos , Inflamação/sangue , Masculino , Análise Multivariada , Infarto do Miocárdio/sangue , Avaliação Nutricional , Prognóstico , Curva ROC , Estudos Retrospectivos
10.
Dtsch Med Wochenschr ; 144(14): 969-977, 2019 07.
Artigo em Alemão | MEDLINE | ID: mdl-31311047

RESUMO

In recent years, considerable progress has been made in the detection and treatment of iron deficiency. The results are also relevant for many specialist areas and, in particular, for patients with chronic inflammatory diseases. In daily practice, iron deficiency is often neither identified nor consistently treated.An iron deficiency can - even before anaemia occurs - reduce the quality of life and influence the course of the underlying disease. In patients with chronic diseases , the iron status should be monitored regularly. Especially, the currently available oral iron preparations for these patients are inefficient, because of the limitated tolerability and, furthermore, because of restricted enteral iron uptake due to inflammation. For this reason, various guidelines recommend intravenous iron substitution.


Assuntos
Anemia Ferropriva , Doença Crônica , Inflamação , Ferro , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/etiologia , Anemia Ferropriva/prevenção & controle , Humanos , Inflamação/complicações , Inflamação/fisiopatologia , Ferro/administração & dosagem , Ferro/uso terapêutico , Qualidade de Vida
11.
Nat Med ; 25(8): 1225-1233, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31332392

RESUMO

Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries1, and is often accompanied by insulin resistance2. The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity3,4. This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels. Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility. Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype. This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.


Assuntos
Ácidos e Sais Biliares/metabolismo , Fator de Transcrição GATA3/fisiologia , Microbioma Gastrointestinal , Interleucinas/fisiologia , Síndrome do Ovário Policístico/etiologia , Animais , Feminino , Humanos , Inflamação/complicações , Resistência à Insulina , Camundongos , Camundongos Endogâmicos C57BL , Ovário/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia
12.
Molecules ; 24(11)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31195760

RESUMO

Hispidulin (4',5,7-trihydroxy-6-methoxyflavone) is a natural compound derived from traditional Chinese medicinal herbs, and it is known to have an anti-inflammatory effect. Here, we investigated the effect of hispidulin on the immunoglobulin E (IgE)-mediated allergic responses in rat basophilic leukemia (RBL)-2H3 mast cells. When RBL-2H3 cells were sensitized with anti-dinitrophenyl (anti-DNP) IgE and subsequently stimulated with DNP-human serum albumin (HSA), histamine and ß-hexosaminidase were released from the cells by degranulation of activated mast cells. However, pretreatment with hispidulin before the stimulation of DNP-HSA markedly attenuated release of both in anti-DNP IgE-sensitized cells. Furthermore, we investigated whether hispidulin inhibits anti-DNP IgE and DNP-HSA-induced passive cutaneous anaphylaxis (PCA), as an animal model for Type I allergies. Hispidulin markedly decreased the PCA reaction and allergic edema of ears in mice. In addition, activated RBL-2H3 cells induced the expression of inflammatory cytokines (tumor necrosis factor-α and interleukin-4), which are critical for the pathogenesis of allergic disease, through the activation of c-Jun N-terminal kinase (JNK). Inhibition of JNK activation by hispidulin treatment reduced the induction of cytokine expression in the activated mast cells. Our results indicate that hispidulin might be a possible therapeutic candidate for allergic inflammatory diseases through the suppression of degranulation and inflammatory cytokines expression.


Assuntos
Citocinas/metabolismo , Regulação para Baixo , Flavonas/uso terapêutico , Liberação de Histamina , Hipersensibilidade/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Inflamação/tratamento farmacológico , Mastócitos/patologia , Animais , Degranulação Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Flavonas/química , Flavonas/farmacologia , Liberação de Histamina/efeitos dos fármacos , Hipersensibilidade/complicações , Imunoglobulina E/metabolismo , Inflamação/complicações , Inflamação/patologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Mastócitos/efeitos dos fármacos , Camundongos Endogâmicos ICR , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Fosforilação/efeitos dos fármacos
13.
Nat Commun ; 10(1): 2769, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31235690

RESUMO

Loss of appetite or anorexia associated with inflammation impairs quality of life and increases morbidity in many diseases. However, the exact neural mechanism that mediates inflammation-associated anorexia is still poorly understood. Here we identified a population of neurons, marked by the expression of protein kinase C-delta, in the oval region of the bed nucleus of the stria terminalis (BNST), which are activated by various inflammatory signals. Silencing of these neurons attenuates the anorexia caused by these inflammatory signals. Our results demonstrate that these neurons mediate bidirectional control of general feeding behaviors. These neurons inhibit the lateral hypothalamus-projecting neurons in the ventrolateral part of BNST to regulate feeding, receive inputs from the canonical feeding regions of arcuate nucleus and parabrachial nucleus. Our data therefore define a BNST microcircuit that might coordinate canonical feeding centers to regulate food intake, which could offer therapeutic targets for feeding-related diseases such as anorexia and obesity.


Assuntos
Anorexia/fisiopatologia , Comportamento Alimentar/fisiologia , Inflamação/fisiopatologia , Neurônios/fisiologia , Núcleos Septais/fisiologia , Animais , Anorexia/etiologia , Anorexia/prevenção & controle , Núcleo Arqueado do Hipotálamo/fisiologia , Modelos Animais de Doenças , Ingestão de Alimentos/fisiologia , Feminino , Humanos , Inflamação/complicações , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Vias Neurais/fisiologia , Obesidade/etiologia , Obesidade/fisiopatologia , Núcleos Parabraquiais/fisiologia , Proteína Quinase C-delta/genética , Proteína Quinase C-delta/metabolismo , Núcleos Septais/citologia , Técnicas Estereotáxicas
14.
Biomed Res Int ; 2019: 6769789, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31139644

RESUMO

Objective: Observe the protective effect of chlorogenic acid on dextran sulfate-induced ulcerative colitis in mice and explore the regulation of MAPK/ERK/JNK signaling pathway. Methods: Seventy C57BL/6 mice (half males and half females) were randomly divided into 7 groups, 10 in each group: control group (CON group), UC model group (UC group), and sulfasalazine-positive control group (SASP group), chlorogenic acid low dose group (CGA-L group), chlorogenic acid medium dose group (CGA-M group), chlorogenic acid high dose group (CGA-H group), and ERK inhibitor + chlorogenic acid group (E+CGA group). The effects of chlorogenic acid on UC were evaluated by colon mucosa damage index (CMDI), HE staining, immunohistochemistry, ELISA, and Western blot. The relationship between chlorogenic acid and MAPK/ERK/JNK signaling pathway was explored by adding ERK inhibitor. Results: The UC models were established successfully by drinking DSS water. Chlorogenic acid reduces DSS-induced colonic mucosal damage, inhibits DSS-induced inflammation, oxidative stress, and apoptosis in colon, and reduces ERK1/2, p -ERK, p38, p-p38, JNK, and p-JNK protein expression. ERK inhibitor U0126 reversed the protective effect of chlorogenic acid on colon tissue. Conclusion: Chlorogenic acid can alleviate DSS-induced ulcerative colitis in mice, which can significantly reduce tissue inflammation and apoptosis, and its mechanism is related to the MAPK/ERK/JNK signaling pathway.


Assuntos
Ácido Clorogênico/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/enzimologia , Sistema de Sinalização das MAP Quinases , Animais , Apoptose , Ácido Clorogênico/química , Ácido Clorogênico/farmacologia , Colite Ulcerativa/induzido quimicamente , Colo/patologia , Sulfato de Dextrana , Feminino , Inflamação/complicações , Inflamação/patologia , Mucosa Intestinal/patologia , Masculino , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos
15.
MBio ; 10(3)2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064831

RESUMO

The microbiota-gut-brain axis is a bidirectional communication system that is poorly understood. Alzheimer's disease (AD), the most common cause of dementia, has long been associated with bacterial infections and inflammation-causing immunosenescence. Recent studies examining the intestinal microbiota of AD patients revealed that their microbiome differs from that of subjects without dementia. In this work, we prospectively enrolled 108 nursing home elders and followed each for up to 5 months, collecting longitudinal stool samples from which we performed metagenomic sequencing and in vitro T84 intestinal epithelial cell functional assays for P-glycoprotein (P-gp) expression, a critical mediator of intestinal homeostasis. Our analysis identified clinical parameters as well as numerous microbial taxa and functional genes that act as predictors of AD dementia in comparison to elders without dementia or with other dementia types. We further demonstrate that stool samples from elders with AD can induce lower P-gp expression levels in vitro those samples from elders without dementia or with other dementia types. We also paired functional studies with machine learning approaches to identify bacterial species differentiating the microbiome of AD elders from that of elders without dementia, which in turn are accurate predictors of the loss of dysregulation of the P-gp pathway. We observed that the microbiome of AD elders shows a lower proportion and prevalence of bacteria with the potential to synthesize butyrate, as well as higher abundances of taxa that are known to cause proinflammatory states. Therefore, a potential nexus between the intestinal microbiome and AD is the modulation of intestinal homeostasis by increases in inflammatory, and decreases in anti-inflammatory, microbial metabolism.IMPORTANCE Studies of the intestinal microbiome and AD have demonstrated associations with microbiome composition at the genus level among matched cohorts. We move this body of literature forward by more deeply investigating microbiome composition via metagenomics and by comparing AD patients against those without dementia and with other dementia types. We also exploit machine learning approaches that combine both metagenomic and clinical data. Finally, our functional studies using stool samples from elders demonstrate how the c microbiome of AD elders can affect intestinal health via dysregulation of the P-glycoprotein pathway. P-glycoprotein dysregulation contributes directly to inflammatory disorders of the intestine. Since AD has been long thought to be linked to chronic bacterial infections as a possible etiology, our findings therefore fill a gap in knowledge in the field of AD research by identifying a nexus between the microbiome, loss of intestinal homeostasis, and inflammation that may underlie this neurodegenerative disorder.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Doença de Alzheimer/microbiologia , Disbiose , Microbioma Gastrointestinal , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Bactérias/classificação , Bactérias/isolamento & purificação , Demência/microbiologia , Células Epiteliais/metabolismo , Fezes/microbiologia , Feminino , Homeostase , Humanos , Inflamação/complicações , Intestinos/microbiologia , Aprendizado de Máquina , Masculino , Redes e Vias Metabólicas/imunologia , Metagenômica , Estudos Prospectivos , RNA Ribossômico 16S/genética
16.
Environ Sci Pollut Res Int ; 26(18): 18200-18207, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31041709

RESUMO

Previous studies have shown that exposure to particulate matter (PM) increased variety of health problems, particularly cardiovascular diseases leading to premature mortality. The cardiac effects of particulate matter containing PM10 include increased infarct size, decreased heart function, and increased arrhythmias in experimental ischemia-reperfusion models in rats. The aim of this study was to evaluate the effects of particles with an aerodynamic diameter smaller than 10 µm (PM10) on isolated-rat heart and also to determine the efficacy of gallic acid (GA) as a preventive agent in oxidative damage. The healthy rats were divided into 8 equal groups which served as, control, GA, PM10 (0.5, 2.5, and 5 mg/kg), and PM10+GA groups. PM10 administered into the lungs via the trachea in two stages with 48-h interval. After all experiments, the electrocardiogram was recorded. Then, the hemodynamic parameters and ventricular arrhythmias in rat isolated-hearts were assessed using Langendorff apparatus and according to the Lambeth conventions. In addition, the inflammation and oxidative stress factors in cardiac tissues were evaluated in all groups. The obtained results showed that the exposure to PM caused to decrease in cardiac hemodynamic and electrocardiogram parameters. Also, in PM10 rat groups, the IL-6, TNF-α, and oxidative stress parameters were increased. Gallic acid preserved the value of cardiac parameters and inflammation in rat hearts. In summary, we added a novel therapeutic effect of gallic acid for cardiac dysfunction induced by particulate matter. These findings could be related to antioxidant and antiinflammation properties and the obtained results suggest that natural antioxidant like gallic acid could be a therapeutic agent in prevention and management of health issues in the polluted areas of the world.


Assuntos
Poluentes Atmosféricos/toxicidade , Ácido Gálico/farmacologia , Coração/efeitos dos fármacos , Material Particulado/toxicidade , Substâncias Protetoras/farmacologia , Animais , Arritmias Cardíacas/induzido quimicamente , Eletrocardiografia , Inflamação/induzido quimicamente , Inflamação/complicações , Masculino , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley
17.
Int J Infect Dis ; 84: 121-126, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31085316

RESUMO

OBJECTIVES: Myelopathy is a well-established long-term clinical manifestation of HTLV-1 infection. Besides motor dysfunction, cognitive impairment may be another consequence of HTLV-1 infection. Moreover, inflammatory markers may be associated with cognitive impairment in these patients. The present study compared the cognitive performance of HAM/TSP patients with healthy controls and investigated the associations between cognitive performance, proviral load and blood inflammatory markers. METHODS: Eighty-three patients fulfilling diagnostic criteria for HAM/TSP were submitted to a comprehensive clinical, cognitive and functional evaluation, brain magnetic resonance imaging and determination of levels of IL-1ß, IL-6, TNF-α, immunoglobulins and HTLV-1 proviral load in blood and cerebrospinal fluid. The control group was composed of 88 cognitively healthy subjects, matched for age, sex and educational level. RESULTS: Compared to healthy subjects, HAM/TSP patients displayed significant global cognitive impairment and executive function deficits. HAM/TSP cognitive impairment was significantly associated with altered levels of IgM, IgG, IL-6 and TNF-α in blood. There was no association between HAM/TSP cognitive impairment and HTLV-1 proviral load. CONCLUSIONS: This study suggests cognitive impairment may be a long-term clinical manifestation of HTLV-1 infection, which seems to be linked to the persistent inflammatory activity that is found in the disease.


Assuntos
Disfunção Cognitiva/etiologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Inflamação/complicações , Paraparesia Espástica Tropical/complicações , Provírus/isolamento & purificação , Carga Viral , Adulto , Idoso , Citocinas/sangue , Feminino , Humanos , Imunoglobulinas/sangue , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/imunologia
18.
Chin Clin Oncol ; 8(2): 19, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31070039

RESUMO

Inflammation plays pivotal roles in the development of pancreatic cancer, from initiation, progression to metastasis. In humans, many known risk factors for pancreatic cancer, including alcohol consumption, cigarette smoking, diabetes and chronic pancreatitis, are often characterized by the induction of chronic inflammation. In mice, while oncogenic Kras itself causes spontaneous infiltration of immune cells, the additional chronic inflammatory damage further accelerates the progression of pancreatic cancer. Infiltrated immune cells in pancreatic cancer are essential for the initiation and development of pancreatic cancer, and produce immune-suppressive signals to dampen antitumor T-cell responses in tumor. Investigation into the mechanisms by which leukocytes contribute to the development of pancreatic cancer will help to find new approaches to improve therapy for this disease.


Assuntos
Carcinoma Ductal Pancreático/etiologia , Inflamação/complicações , Neoplasias Pancreáticas/etiologia , Animais , Carcinoma Ductal Pancreático/patologia , Progressão da Doença , Humanos , Inflamação/fisiopatologia , Neoplasias Pancreáticas/patologia , Transdução de Sinais
19.
Int J Mol Sci ; 20(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075962

RESUMO

This study focuses on the effect of honokiol (HON) on glucose homeostasis, insulin resistance, dyslipidemia, hepatic steatosis, and inflammation in type 2 diabetic db/db mice. Male C57BL/KsJ-db/db mice were fed a normal diet with or without HON (0.02%, w/w) or pioglitazone (PIO, anti-diabetic agent, 0.01%, w/w) for 5 weeks. Blood biomarker, tissue morphology and enzymatic and genetic parameters were determined. PIO significantly decreased food intake, fasting blood glucose, and glycosylated hemoglobin (HbA1c) levels, but markedly increased body weight, adipose tissue weight, and plasma leptin levels. HON did not significantly affect food intake, body weight, or levels of plasma leptin and blood glucose. However, HON led to significant decreases in adipose tissue weight, plasma insulin, blood HbA1c and HOMA-IR levels and improved glucose tolerance. The anti-diabetic and anti-adiposity effects of HON were partially related to the inhibition of gluconeogenic enzymes and their mRNA expression in the liver; and the inhibition of lipogenic enzymes in adipose tissue, respectively. Unlike PIO, HON did not affect dyslipidemia, but ameliorated hepatic steatosis by inhibiting hepatic lipogenic enzymes activity. Moreover, HON exhibited anti-inflammatory effects similar to PIO. These results suggest that HON can protect against type 2 diabetes by improving insulin resistance, glucose and lipid metabolism, and inflammation.


Assuntos
Compostos de Bifenilo/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fígado Gorduroso/tratamento farmacológico , Inflamação/tratamento farmacológico , Resistência à Insulina , Lignanas/uso terapêutico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Compostos de Bifenilo/farmacologia , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Dislipidemias/sangue , Dislipidemias/complicações , Fígado Gorduroso/sangue , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia , Comportamento Alimentar/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Inflamação/sangue , Inflamação/complicações , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Leptina/sangue , Lignanas/farmacologia , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos
20.
Int J Mol Sci ; 20(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075981

RESUMO

Decreased inflammatory status has been reported in subjects with mild unconjugated hyperbilirubinemia. However, mechanisms of the anti-inflammatory actions of bilirubin (BR) are not fully understood. The aim of this study is to assess the role of BR in systemic inflammation using hyperbilirubinemic Gunn rats as well as their normobilirubinemic littermates and further in primary hepatocytes. The rats were treated with lipopolysaccharide (LPS, 6 mg/kg intraperitoneally) for 12 h, their blood and liver were collected for analyses of inflammatory and hepatic injury markers. Primary hepatocytes were treated with BR and TNF-α. LPS-treated Gunn rats had a significantly decreased inflammatory response, as evidenced by the anti-inflammatory profile of white blood cell subsets, and lower hepatic and systemic expressions of IL-6, TNF-α, IL-1ß, and IL-10. Hepatic mRNA expression of LPS-binding protein was upregulated in Gunn rats before and after LPS treatment. In addition, liver injury markers were lower in Gunn rats as compared to in LPS-treated controls. The exposure of primary hepatocytes to TNF-α with BR led to a milder decrease in phosphorylation of the NF-κB p65 subunit compared to in cells without BR. In conclusion, hyperbilirubinemia in Gunn rats is associated with an attenuated systemic inflammatory response and decreased liver damage upon exposure to LPS.


Assuntos
Hiperbilirrubinemia/complicações , Inflamação/complicações , Animais , Apoptose/efeitos dos fármacos , Bilirrubina/farmacologia , Biomarcadores/sangue , Células Cultivadas , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Citoproteção/efeitos dos fármacos , Feminino , Hepatócitos/metabolismo , Hiperbilirrubinemia/sangue , Leucócitos/metabolismo , Lipopolissacarídeos , Fígado/metabolismo , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Gunn , Transdução de Sinais
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