Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.892
Filtrar
1.
Nihon Yakurigaku Zasshi ; 154(3): 108-113, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31527359

RESUMO

Similar to calcium (Ca2+) and chloride (Cl-) ion channels/transporters, potassium (K+) channels have been recognized as a crucial cancer treatment target. Recent studies have provided convincing evidences of positive correlation between elevated expression levels of Ca2+-activated K+ (KCa) channels and cancer proliferation, metastasis, and poor patient prognosis. In cancer cells, KCa1.1 and KCa3.1 KCa channels are co-localized with Ca2+-permeable Orai/TRP channels to provide a positive-feedback loop for Ca2+ entry. They are responsible for the promotion of cell growth and metastasis in the different types of cancer, and are therefore potential therapeutic targets and biomarkers for cancer. We determined the epigenetic and post-transcriptional dysregulation of KCa3.1 by class I histone deacetylase inhibitors in breast and prostate cancer cells. We further determined the transcriptional repression and protein degradation of KCa1.1 by vitamin D receptor agonists and androgen receptor antagonists, which are expected as potential therapeutic drugs for triple-negative breast cancer. The anti-inflammatory cytokine, interleukin-10 (IL-10) is an immunosuppressive factor involved in tumorigenesis, and plays a crucial role in escape from tumor immune surveillance. We determined KCa3.1 activators are a possible therapeutic option to suppress the tumor-promoting activities of IL-10. These results may provide new insights into cancer treatment focused on Ca2+-activated K+ channels.


Assuntos
Neoplasias da Mama/patologia , Inibidores de Histona Desacetilases/farmacologia , Canais de Potássio Cálcio-Ativados/metabolismo , Neoplasias da Próstata/patologia , Antagonistas de Receptores de Andrógenos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Epigênese Genética , Feminino , Humanos , Vigilância Imunológica , Interleucina-10/metabolismo , Masculino , Proteólise , Processamento Pós-Transcricional do RNA , Receptores de Calcitriol/agonistas
2.
Braz Oral Res ; 33: e040, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508724

RESUMO

The study characterizes dental implant surfaces treated with phosphoric acid to assess the effects of acid treatment on blood cells and correlate them with cytokine levels. The implant surfaces examined were divided into untreated metal surface (US; n = 50), metal surface treated with phosphoric acid (ATS; n = 50) and cement surface (CS; n = 50) groups. The samples were characterized by scanning electron microscopy (SEM) and rheometry. The implants were incubated with human blood mononuclear cells for 24 h, with surface rinsing in the ATS treatment. Cell viability was determined by colorimetric methods and cytokines in the culture supernatant were quantified using flow cytometry. In the ATS group, the surface porosity and contact surface were increased and plaques were observed on the surface. The blood flow and viscosity curves were similar among the treatments, and the high cell viability rates indicate the biocompatibility of the materials used. An increase in the levels of IL-2, IL-4, IL-6, IL-10 and TNF-α was observed in the ATS and CS groups. There were positive correlations between IL-10 and IL-2 levels and between IL-10 and IL-4 levels in the culture supernatant of the ATS group. The results suggest that implant surface treatment with phosphoric acid activates the production of inflammatory cytokines. The increased cytokine levels can modulate the immune response, thereby improving biofunctional processes and promoting the success of dental implants.


Assuntos
Citocinas/análise , Implantes Dentários , Materiais Dentários/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Ácidos Fosfóricos/farmacologia , Anti-Inflamatórios , Sobrevivência Celular , Citocinas/metabolismo , Cimentos Dentários , Humanos , Interleucina-10/análise , Interleucina-10/metabolismo , Microscopia Eletrônica de Varredura , Reologia , Propriedades de Superfície
3.
Sheng Li Xue Bao ; 71(4): 575-580, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31440754

RESUMO

The aim of the present study was to investigate the effect of salidroside (Sal) on inflammatory activation induced by lipopolysaccharide (LPS) in the co-culture of rat alveolar macrophages (AM) NR 8383 and type II alveolar epithelial cells (AEC II) RLE-6TN. CCK-8 colorimetric method was used to detect cell proliferation percentage. The enzyme-linked immunosorbent assay (ELISA) was used to determine the content of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein-2 (MIP-2) and interleukin-10 (IL-10) in the supernatant. Western blot was used to examine the expression levels of phosphorylated AKT (p-AKT) and total AKT protein. The results showed that pretreatment of RLE-6TN cells or co-culture of RLE-6TN and NR 8383 cells with 32 and 128 µg/mL Sal for 1 h, followed by continuous culture for 24 h, significantly increased the cell proliferation (P < 0.05). Compared with control group, 32 and 128 µg/mL Sal pretreatment significantly increased the ratio of p-AKT/AKT in RLE-6TN cells (P < 0.05). Pretreatment of 32 µg/mL Sal not only inhibited the secretion of TNF-α and MIP-2 by NR 8383 cells induced by LPS (P < 0.05), but also enhanced the inhibitory effect of RLE-6TN and NR 8383 cells co-culture on the secretion of TNF-α and MIP-2 by NR 8383 cells induced by LPS (P < 0.05). In addition, 32 µg/mL Sal pretreatment promoted LPS-induced IL-10 secretion by NR 8383 cells (P < 0.05), and enhanced the promoting effect of co-culture of RLE-6TN and NR 8383 cells on the IL-10 secretion by LPS-induced NR 8383 cells (P < 0.05). In conclusion, Sal may directly inhibit LPS-induced inflammatory activation of AM (NR 8383), promote the proliferation of AEC II (RLE-6TN) through PI3K/AKT signaling pathway, and enhance the regulatory effect of AEC II on LPS-induced inflammatory activation of AM.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Glucosídeos/farmacologia , Macrófagos Alveolares/efeitos dos fármacos , Fenóis/farmacologia , Transdução de Sinais , Células Epiteliais Alveolares/metabolismo , Animais , Linhagem Celular , Quimiocina CXCL2/metabolismo , Técnicas de Cocultura , Interleucina-10/metabolismo , Lipopolissacarídeos , Macrófagos Alveolares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Fator de Necrose Tumoral alfa/metabolismo
4.
Vet Immunol Immunopathol ; 216: 109912, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31446208

RESUMO

Melanoma in humans and canines is an aggressive and highly metastatic cancer. The mucosal forms in both species share genetic and histopathologic features, making dogs a valuable spontaneous disease animal model. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells of myeloid origin with immunosuppressive capabilities, which are increased in many human cancers and contribute to tumor immune evasion. They are a possible target to improve immunotherapy outcomes. Current information regarding MDSCs in canines is minimal, limiting their use as translational model for the study of MDSCs. The objective of this study was to characterize major MDSCs subsets (monocytic and polymorphonuclear) and the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) in canines with malignant melanoma and to evaluate changes in MDSCs and the cytokines over time in response to a GD3-based active immunotherapy. Whole blood and serum collected from 30 healthy controls and 33 patients enrolled in the University of Florida melanoma vaccine trial were analyzed by flow cytometry with canine specific CD11b, MHCII and anti-human CD14 antibodies to assess ostensibly polymorphonuclear-MDSC (CD11b+ MHCII- CD14-) and monocytic-MDSC (CD11b+ MHCII- CD14+) subsets. IL-10, MCP-1 and both MDSCs subsets were significantly elevated in melanoma dogs versus controls. Both MDSCs subsets decreased significantly following GD3-based immunotherapy administration but no significant changes in cytokines were seen over time. To our knowledge, this is the first report documenting increased monocytic-MDSCs in canine melanoma. This is consistent with human malignant melanoma data, supporting dogs as a valuable model for therapeutic intervention studies.


Assuntos
Quimiocina CCL2/metabolismo , Doenças do Cão/terapia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Interleucina-10/metabolismo , Melanoma/veterinária , Células Supressoras Mieloides/fisiologia , Animais , Quimiocina CCL2/genética , Doenças do Cão/metabolismo , Cães , Feminino , Gangliosídeos/administração & dosagem , Gangliosídeos/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Imunoterapia , Interleucina-10/genética , Masculino , Melanoma/terapia
5.
Adv Clin Exp Med ; 28(9): 1243-1248, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31430072

RESUMO

BACKGROUND: FoxP3 is a marker of human T regulatory cells (Tregs), which are supposed to play an important role in the pathophysiology of atherosclerosis. Interleukin 10 (IL-10) is a cytokine with pleiotropic, immunoregulatory properties, produced mostly by Tregs and B regulatory cells. Due to their anti-inflammatory action, both Tregs and IL-10 are believed to inhibit plaque development and decrease atherosclerosis progression. The effect of hypolipidemic drugs - statins or ezetimibe - on FoxP3-positive Tregs and anti-inflammatory cytokines, such as IL-10, is still unclear. OBJECTIVES: The objective of the study was to investigate the effects of 3 different therapies of equivalent hypolipidemic activity: atorvastatin, rosuvastatin, and combination therapy of atorvastatin and ezetimibe on FoxP3-Tregs transcription factor and IL-10 mRNA expression in peripheral blood mononuclear cells (PBMCs) from patients with stable coronary artery disease (CAD). MATERIAL AND METHODS: Sixty-five patients with diagnosed CAD participated in the study. They were randomly assigned to 3 therapeutic groups: atorvastatin at a dose of 40 mg/day (A40 group); rosuvastatin 20 mg/day (R20 group); and atorvastatin 10 mg/day combined with ezetimibe 10 mg/day (A10+E10 group). After 1 month and 6 months of therapy, the mRNA expression for FoxP3 and IL-10 in PBMCs was evaluated using real-time polymerase chain reaction (RT-PCR) and lipid parameters. RESULTS: An improvement in lipid parameters was observed in each of the groups studied; however, hypolipidemic treatment did not induce any change in FoxP3 and IL-10 mRNA expression. After 6 months, an increase in FoxP3 mRNA expression was noted in A40 group as compared to R20 group. CONCLUSIONS: None of the therapies of equal hypolipidemic efficacy affected FoxP3 and IL-10 mRNA expression in patients with stable CAD.


Assuntos
Anticolesterolemiantes , Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Anticolesterolemiantes/uso terapêutico , Atorvastatina/uso terapêutico , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Ezetimiba/uso terapêutico , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Humanos , Interleucina-10/metabolismo , Leucócitos Mononucleares , RNA Mensageiro
6.
Chem Biol Interact ; 311: 108758, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31348919

RESUMO

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in children. It is diagnosed by two main behavioral phenotypes i.e. social-communication impairments and repetitive behavior. ASD is complex disorder with unsolved etiology due to multiple genes involvement, epigenetic mechanism and environmental factors. The clinical and preclinical studies have been indicating the association of propionic acid with autism spectrum disorder. Numerous studies suggest the potential therapeutic effects of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in different brain disorders. This research evaluates the utility of selective agonist of PPAR-γ, pioglitazone in postnatal propionic acid induced ASD related symptomatology in male Wistar rats. PPA (250 mg/kg, p.o.) was administered to male offspring for three consecutive days from postnatal 21st day to 23rd day. PPA induced social impairment, repetitive behavior, hyperlocomotion, anxiety and low exploratory activity in rats. Also, postnatal propionic acid-treated rats showed higher levels of oxidative stress (increased in thiobarbituric acid reactive species and decreased in reduced glutathione) as well as inflammation (increased in interleukin-6, tumor necrosis factor-alpha and decreased in interleukin-10) in the cerebellum, brainstem and prefrontal cortex. The rats were treated daily with pioglitazone (10 mg/kg and 20 mg/kg, p.o.) from postnatal 24th day to end of the study. Treatment with pioglitazone, significantly attenuated the postnatal propionic acid-induced social impairment, repetitive behavior, hyperactivity, anxiety and low exploratory activity. Furthermore, pioglitazone also reduced the postnatal propionic acid-induced oxidative stress and neuroinflammation in aforementioned brain regions. Hence, pioglitazone improved the propionic acid-induced neurobehavioral and biochemical impairments in rats.


Assuntos
Transtorno do Espectro Autista/patologia , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/agonistas , Pioglitazona/farmacologia , Animais , Ansiedade/prevenção & controle , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/metabolismo , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Glutationa/metabolismo , Inflamação/prevenção & controle , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Locomoção/efeitos dos fármacos , Masculino , PPAR gama/metabolismo , Fenótipo , Pioglitazona/uso terapêutico , Propionatos/toxicidade , Ratos , Ratos Wistar
7.
Pan Afr Med J ; 32: 148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303919

RESUMO

Introduction: inflammatory cytokines have been associated with various cancers, including cervical cancers. Interpreting cytokine expression in liquid based cervical samples is quite challenging. This study is aimed at evaluating the levels of interleukin 8 and 10 in liquid based cervical samples. Methods: this is a descriptive analytical study carried out on eighty five (85) subjects aged between 23 and 68 years. Cervical samples were collected in liquid based medium and smears later examined after staining with Papanicolaou technique. These were categorized into low grade intra-epithelial lesion/malignancy, high grade intraepithelial lesion/malignancy according to the degree of dyskaryosis. Concentrations of interleukin 8 and interleukin 10 in the samples were determined by enzyme linked immunosorbent assay. Results: the mean age, standard deviation (SD) of the study subjects were 40.6 (7.8) years. A total number of 79 females (92.9%) were negative for intra-epithelial lesion/malignancy (NILM), while 4 (4.71%) and 2 (2.35%) were positive for low grade intra-epithelial lesion/malignancy (LILM) and high grade intra-epithelial lesion (HILM) respectively. While mean levels of interleukin 8 increased with the degree of malignancy, (107.27 ± 11.88pg/ml) in LILM, (114.80 ± 2.12pg/ml) in HILM when compared with NILM (88.39 ± 18.06pg/ml), (f = 0.700, p = 0.018); the mean levels of interleukin 10 was comparable between these groups (p ≥ 0.05). Pearson correlation coefficient analysis showed a negative association between interleukin 8 and interleukin 10 (r = -1.999, p = 0.000) in LILM. Conclusion: interleukin 8 cytokines in cervical cancer is associated with the degree of malignancy. Possible anti-inflammatory effect of interleukin 10 was not observed.


Assuntos
Neoplasia Intraepitelial Cervical/patologia , Interleucina-10/metabolismo , Interleucina-8/metabolismo , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Neoplasia Intraepitelial Cervical/diagnóstico , Colo do Útero/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal , Adulto Jovem
8.
Egypt J Immunol ; 26(1): 15-29, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31332993

RESUMO

Cow's milk allergy (CMA) is known to be either IgE- or non-IgE mediated. Regulatory T (Treg) cell defect is involved in the pathogenesis of both types. Vitamin D has been suggested to improve the generation of allergen-specific Treg cell populations with the potential to provide safe and long-term alleviation of disease symptoms. This study aimed to assess Vitamin D status in children with physician-diagnosed CMA and to investigate the effect of in vitro cultivation with Vitamin D on the percentage of antigen-driven CD4+CD25highFoxp3+IL10+ Treg cells following in vitro stimulation of cells with cow's milk allergen in culture. This cross-sectional study included 20 children with CMA and 20 healthy age and sex-matched children as a control group. All patients were subjected to clinical evaluation, cow's milk skin prick test (SPT), cow's milk elimination and oral re-challenge test in patients with negative cow's milk SPT and in those with gastrointestinal presentation, measurement of serum Vitamin D level and assessment of the percentage of antigen-driven CD4+CD25highFoxp3+IL10+ Treg cells in response to stimulation with cow's milk allergen extract with and without Vitamin D in culture. Vitamin D deficiency was detected in 80% of children with CMA. Percentage of Foxp3+ and IL10+ co-expression on Treg cells was significantly increased after stimulation with cow's milk allergen extract in the presence of Vitamin D. A significant positive correlation was observed between serum Vitamin D level and percentage of antigen-driven CD4+CD25highFoxp3+IL10+ Treg cells as well as level of Foxp3+ and IL10+ co-expression on Treg cells at baseline (control cultures without stimulation) and after PBMCs stimulation with cow's milk allergen extract in the presence of Vitamin D. Re-stimulation with cow's milk allergen extract was performed in vitro in order to evaluate milk-induced immune stimulation and regulation. In conclusion, patients with CMA whether IgE- or non-IgE mediated had Vitamin D deficiency with a decreased number of CD4+CD25highFoxp3+IL10+ Treg cells which increased after in vitro addition of Vitamin D with increased Foxp3 and IL10 co-expression.


Assuntos
Interleucina-10/metabolismo , Hipersensibilidade a Leite/imunologia , Linfócitos T Reguladores/citologia , Vitamina D/farmacologia , Animais , Bovinos , Células Cultivadas , Criança , Estudos Transversais , Fatores de Transcrição Forkhead/metabolismo , Humanos , Lactente
9.
Mol Immunol ; 112: 387-393, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288148

RESUMO

Programmed cell death 4 (Pdcd4) was found to be related to apoptosis upon first discovery. It was later found to play the role of tumor suppressor gene in a variety of tumors by inhibiting transcription and translation. Recently, it has been proposed that it may play an important role in some inflammatory diseases and in the immune response. In our previous study, deficiency of Pdcd4 was found to attenuate the formation of atherosclerotic plaques. This might be because deficiency of Pdcd4 may increase IL-10 expression and lipoautophagy by macrophages and attenuate the formation of foam cells. However, the effect of Pdcd4 on the subsets of T cells in hyperlipidemic mice still remained unclear. In the present study, results showed that Pdcd4 deficiency decreased the percentage of CD8+ T cells and increased that of regulatory T cells (Tregs) under hyperlipidemic conditions both in vitro and in vivo, which may be due to the reduced expression of co-stimulatory molecules CD28 and CD137, and the enhancive expression of co-inhibitory molecules CTLA-4. These results indicated that endogenous Pdcd4 promotes immune response mediated by T cells through regulation of the co-stimulatory molecules expression, which may contribute to the development of advanced atherosclerotic plaques. The current work provides new data to understand the role of Pdcd4 in different T cell subsets under hyperlipidemic microenvironment.


Assuntos
Proteínas Reguladoras de Apoptose/deficiência , Proteínas Reguladoras de Apoptose/metabolismo , Hiperlipidemias/metabolismo , Proteínas de Ligação a RNA/metabolismo , Subpopulações de Linfócitos T/metabolismo , Animais , Apoptose/fisiologia , Antígenos CD28/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Células Espumosas/metabolismo , Interleucina-10/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Placa Aterosclerótica/metabolismo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
10.
Cancer Sci ; 110(9): 2700-2710, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31276257

RESUMO

As one of the most frequently diagnosed cancers, esophageal squamous cell carcinoma (ESCC) remains the leading cause of malignancy-related death worldwide. Many studies have focused on the potential role of cancer cells in educating B cells during cancer progression. Here, we aim to explore the role of circulating exosomes from ESCC in the generation of two main regulatory B (Breg) subsets, including interleukin-10+ Bregs (B10) and programmed cell death (PD)-1high Bregs. Firstly, we observed an elevated percentage of B10 cells in peripheral blood of ESCC patients compared with healthy controls. Then we isolated and characterized exosomes from the peripheral blood of ESCC patients and an ESCC cell line. Exosomes from ESCC patients and the ESCC cell line suppressed the proliferation of B cells and induced the augmentation of B10 and PD-1high Breg cells. By comparing the long non-coding RNA and mRNA expression profiles in exosomes from ESCC patients or healthy controls, we identified a series of differentially expressed genes. Finally, we undertook gene annotation and pathway enrichment analyses on differentially expressed genes to explore the potential mechanism underlying the modulatory role of cancer exosomes in B cells. Our findings contribute to the study on B cell-mediated ESCC immunosuppression and shed light on the possible application of exosomes in anticancer therapies.


Assuntos
Linfócitos B Reguladores/imunologia , Neoplasias Esofágicas/imunologia , Carcinoma de Células Escamosas do Esôfago/imunologia , Exossomos/imunologia , Linfócitos B Reguladores/metabolismo , Diferenciação Celular/imunologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/sangue , Carcinoma de Células Escamosas do Esôfago/terapia , Exossomos/transplante , Feminino , Humanos , Interleucina-10/metabolismo , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/metabolismo
11.
Food Chem Toxicol ; 131: 110594, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226431

RESUMO

The phytochemical composition and the antioxidant and anti-inflammatory activities of a mixture of 23 plants, named Horchata, traditionally consumed in Ecuador, have been evaluated. The study was carried out using the hydroalcoholic extract (HHext) and infusion (IHext) of the horchata plant mixture. It was verified that thermal treatment affected the contents of vitamin C and carotenoids, but hardly those of polyphenols, which would be the main bioactive compounds in the infusion, the common form of preparation of horchata for consumption. Among phenolic compounds, caffeoylquinic acids, flavones and flavonols (mostly quercetin glycosides) were prominent. Both HHext and IHext extracts managed to protect RAW 264.7 macrophages against LPS-induced cytotoxic damage, increasing the levels of endogenous antioxidant enzymes and modulating the production of pro-inflammatory and anti-inflammatory cytokines. Greater protective effects were obtained for HHext compared to IHext, which was in agreement with its higher content of phenolic compounds favoured by a more efficient extraction in the hydroalcoholic medium. Nonetheless, the infusion still maintained a significant antioxidant and anti-inflammatory activity, which would support the protective effects on health traditionally attributed to its consumption by the population.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Ácido Ascórbico/análise , Biomarcadores/metabolismo , Carotenoides/análise , Equador , Inflamação/induzido quimicamente , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Camundongos , Nitritos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/química , Polifenóis/análise , Células RAW 264.7 , Temperatura Ambiente , Fator de Necrose Tumoral alfa/metabolismo
12.
J Appl Microbiol ; 127(3): 856-866, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31161702

RESUMO

AIMS: We developed a strategy for localized delivery of the LFCA (lactoferricinlactoferrampin), which is actively synthesized in situ by Lactococcus lactis (pAMJ399-LFCA/LLMG1363), and explored the possibility of using pAMJ399-LFCA/LLMG1363 as an alternative additive diet to antibiotics. METHODS AND RESULTS: The antimicrobial activities of the LFCA derived from pAMJ399-LFCA/LLMG1363 were tested in vitro. The results showed that LFCA had an inhibitory effect on Staphylococcus aureus, Escherichia coli and Salmonella enteritidis. Then, the pAMJ399-LFCA/LLMG1363 was used as an additive diet for piglets. Our data demonstrated that oral administration of pAMJ399-LFCA/LLMG1363 significantly improved the average daily gain, feed-to-gain ratio, intestinal mucosal integrity and decreased the serum endotoxin and d-lactic acid levels. The mRNA expression levels of intestinal tight junction proteins (including occludin, Claudin-1 and ZO-1) were significantly upregulated by pAMJ399-LFCA/LLMG1363 administration. The serum immunoglobulin G (IgG) levels, intestinal secretory immunoglobulin A (sIgA) levels, IL-2, IL-10 and TGF-ß levels were significantly increased by pAMJ399-LFCA/LLMG1363. Furthermore, our data revealed that oral administration of pAMJ399-LFCA/LLMG1363 significantly increased the number of general Lactobacillus, and decreased the total viable E. coli counts in the ileum and cecum contents. CONCLUSIONS: We developed a novel pAMJ399-LFCA/LLMG1363 secreting LFCA, which had probiotic effects on the growth performance, intestinal morphology, intestinal barrier function and immunological indices of weaned piglets. SIGNIFICANCE AND IMPACT OF THE STUDY: pAMJ399-LFCA/LLMG1363, with probiotic effects on the health of weaned piglets, may be a promising feed additive for weaned piglets.


Assuntos
Antibacterianos/farmacologia , Lactococcus lactis/metabolismo , Lactoferrina/farmacologia , Fragmentos de Peptídeos/farmacologia , Suínos/imunologia , Animais , Bovinos , Escherichia coli/efeitos dos fármacos , Interleucina-10/metabolismo , Interleucina-2/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Probióticos/farmacologia , Salmonella enteritidis/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo
13.
Environ Pollut ; 252(Pt B): 1288-1300, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31252126

RESUMO

Glyphosate (GLY)-based herbicide, one of the most widely used herbicides, might cause a series of environmental problems and pose a toxicological risk to aquatic organisms. However, data on the potential hazard and toxicity mechanism of GLY to fish gills are relatively scarce. In this study, a subacute toxicity test of common carp (Cyprinus carpio L.) treated with commercial GLY at 52.08 and 104.15 mg L-1 for 7 d was conducted. The results revealed that GLY exposure significantly inhibited Na+/K+-ATPase and increased AST and ALT activities in the fish gills. The biochemical assays results revealed that GLY treatment remarkably altered the transcriptional levels of HSP70 and HSP90; inhibited the activities of SOD, CAT, GPx, GR, and T-AOC; reduced the contents of GSH, but remarkably promoted MDA and PC contents, suggesting that GLY exposure induced oxidative stress and lipids and proteins damage in the carp gills. Further research revealed that GLY exposure also promoted expression of NF-κB, iNOS, IL-1ß, IL-6, IL-8, and TNF-α; altered the levels of IL-10 and TGF-ß, indicating that GLY exposure induced inflammatory response in the fish gills. Additionally, we found that GLY exposure activated apaf-1 and bax and inhibited bcl-2, induced caspase-9 and caspase-3 expression and caused remarkable histological damage in the fish gills. These results may further enriches the toxicity mechanistic theory of GLY to fish gills, which may be useful for the risk assessment of GLY and aquatic organism protection.


Assuntos
Carpas/metabolismo , Brânquias/lesões , Glicina/análogos & derivados , Herbicidas/toxicidade , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Transcrição Genética/efeitos dos fármacos , Animais , Caspase 3/metabolismo , Caspase 9/metabolismo , Brânquias/efeitos dos fármacos , Glicina/toxicidade , Interleucina-10/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos
14.
PLoS Negl Trop Dis ; 13(6): e0007500, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31216268

RESUMO

BACKGROUND: Leishmania parasites are transmitted to vertebrate hosts by phlebotomine sandflies and, in humans, may cause tegumentary or visceral leishmaniasis. The role of PKR (dsRNA activated kinase) and Toll-like receptor 3 (TLR3) activation in the control of Leishmania infection highlights the importance of the engagement of RNA sensors, which are usually involved in the antiviral cell response, in the fate of parasitism by Leishmania. We tested the hypothesis that Phlebovirus, a subgroup of the Bunyaviridae, transmitted by sandflies, would interfere with Leishmania infection. METHODOLOGY/PRINCIPAL FINDINGS: We tested two Phlebovirus isolates, Icoaraci and Pacui, from the rodents Nectomys sp. and Oryzomys sp., respectively, both natural sylvatic reservoir of Leishmania (Leishmania) amazonensis from the Amazon region. Phlebovirus coinfection with L. (L.) amazonensis in murine macrophages led to increased intracellular growth of L. (L.) amazonensis. Further studies with Icoaraci coinfection revealed the requirement of the PKR/IFN1 axis on the exacerbation of the parasite infection. L. (L.) amazonensis and Phlebovirus coinfection potentiated PKR activation and synergistically induced the expression of IFNß and IL-10. Importantly, in vivo coinfection of C57BL/6 mice corroborated the in vitro data. The exacerbation effect of RNA virus on parasite infection may be specific because coinfection with dengue virus (DENV2) exerted the opposite effect on parasite load. CONCLUSIONS: Altogether, our data suggest that coinfections with specific RNA viruses shared by vectors or reservoirs of Leishmania may enhance and sustain the activation of host cellular RNA sensors, resulting in aggravation of the parasite infection. The present work highlights new perspectives for the investigation of antiviral pathways as important modulators of protozoan infections.


Assuntos
Infecções por Bunyaviridae/complicações , Coinfecção/imunologia , Suscetibilidade a Doenças , Interferon beta/metabolismo , Interleucina-10/metabolismo , Leishmaniose/imunologia , eIF-2 Quinase/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Leishmania/imunologia , Camundongos Endogâmicos C57BL , Modelos Teóricos , Phlebovirus/imunologia
15.
J Biosci ; 44(2)2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31180043

RESUMO

In this study, zinc oxide nanoparticles (ZnO-NPs) were synthesized using the extract of Hyssops officinalis L. via green method and confirmed by transmission electron microscopy, field emission scanning electron microscopy, X-ray powder diffraction and Fourier transforms infrared spectroscopy techniques. In the in vivo section, the anti-angiogenesis and antiinflammatory properties of the NPs were evaluated by the chorioallantoic membrane (CAM) assay and mouse paw edema test (induced by carrageenan), respectively. In the in vitro section, changes in the expression of angiogenesis genes (VEGF and VEGFR) and inflammatory genes (IL-1B and IL-10) were investigated by real-time quantitative polymerase chain reaction technique. In order to evaluate the cytotoxicity of ZnO-NPs, 3-5, 4-dimethylthiazol-2-yl) -5, 2-tetrazolium bromide (MTT) test was used on MDA-MB231 breast adenocarcinoma cell line. The results of the CAM assay showed that the ZnO-NPs significantly reduced the number and length of blood vessels, as well as the size and weight of the embryos. Evaluation of mouse paw edema showed that the NPs are able to decrease inflammation. Changes in the expression pattern of VEGF and VEGFR genes in MCF7 cells showed that the NPs have inhibitory effect on the expression of both genes. Expression levels of IL-10 and IL-1B genes also increased and decreased, respectively. The MTT test showed that the NP have the ability to decrease breast cancer cells. In conclusion, our results confirm that the ZnO-NPs synthesized by green method have promising anti-cancer properties.


Assuntos
Inibidores da Angiogênese/síntese química , Anti-Inflamatórios/síntese química , Citotoxinas/síntese química , Edema/tratamento farmacológico , Hyssopus/química , Nanopartículas/administração & dosagem , Óxido de Zinco/farmacologia , Inibidores da Angiogênese/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Carragenina/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/efeitos dos fármacos , Citotoxinas/farmacologia , Edema/induzido quimicamente , Edema/fisiopatologia , Regulação da Expressão Gênica/efeitos dos fármacos , Química Verde , Membro Posterior , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Células MCF-7 , Camundongos , Nanopartículas/química , Extratos Vegetais/química , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Óxido de Zinco/química
16.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(4): 296-301, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31167687

RESUMO

Objective To investigate the role of CD161+ regulatory T cells (Treg) in reducing valve injury in rheumatic heart disease rats and the underlying mechanism. Methods CD161- and CD161+ regulatory T cells (Tregs) were separated by flow cytometry and then cultured. The concentrations of interleukin 10 (IL-10) and transforming growth factor ß (TGF-ß) in the supernates were detected by ELISA. Rat models of rheumatic heart disease were established by mixing A type hemolytic streptococcus suspension with Freund's complete adjuvant. They were divided into control group, CD161-Treg group and CD161+Treg group. One week later, heart blood and mitral valve were taken from the model rats. The proportion of follicular helper T (Tfh) cells, B cells and plasma cells was detected by flow cytometry. Histopathological changes were detected by HE staining and the number of B cells and plasma cells by immunohistochemical staining. ELISA was used to detect the level of IL-21 in serum. Results The ability of CD161+Tregs to secrete IL-10 and TGF-ß was significantly higher than that of CD161-Tregs. Compared with the rats injected with CD161-Tregs, CD161+Tregs could significantly reduce the damage of valve tissue and the proportion of B cells and plasma cells in valve tissue. Moreover, CD161+Tregs injection could reduce the proportion of Tfh cells, B cells and plasma cells in rat blood and decrease the content of IL-21 in serum. Conclusion CD161+Tregs can reduce the valve injury of rheumatic heart disease by inhibiting the proliferation and differentiation of Tfh cells and B cells.


Assuntos
Valvas Cardíacas/patologia , Cardiopatia Reumática/imunologia , Linfócitos T Reguladores/citologia , Animais , Linfócitos B/citologia , Interleucina-10/metabolismo , Interleucinas/sangue , Subfamília B de Receptores Semelhantes a Lectina de Células NK , Plasmócitos/citologia , Ratos , Fator de Crescimento Transformador beta/metabolismo
17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(4): 302-306, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31167688

RESUMO

Objective To investigate the anti-inflammatory activity of Ageratina adenophora essential oil (AAEO-CP) and its effects on the expression of Toll-like receptor 4 (TLR4) protein in lipopolysaccharide (LPS)-induced RAW264.7 cells. Methods RAW264.7 cells were divided into control group, LPS group, and LPS combined with AAEO-CP group. The cytotoxicity of AAEO-CP was detected by CCK-8 assay. The mRNA and protein expression of interleukin-6 (IL-6) and IL-10 were detected by real-time PCR and ELISA, respectively, and the protein expression of TLR4 in RAW264.7 cells was measured by Western blotting. Results AAEO-CP below 20 mg/mL was not cytotoxic to RAW264.7 cells. LPS increased the protein expression of TLR4, also increased the protein and mRNA expression of IL-6, but decrease the protein and mRNA expression of IL-10 in RAW264.7 cells. And all of the above results were reversed by AAEO-CP. Conclusion AAEO-CP can play the anti-inflammatory effects by increasing the expression of IL-10 protein and decreasing the expression of IL-6 protein, and inhibiting TLR4 protein in LPS-induced RAW264.7 cells.


Assuntos
Ageratina/química , Inflamação/patologia , Óleos Voláteis/farmacologia , Animais , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Camundongos , Células RAW 264.7 , Receptor 4 Toll-Like/metabolismo
18.
Rev Assoc Med Bras (1992) ; 65(5): 637-646, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31166440

RESUMO

OBJECTIVE: Aplastic anemia (AA) is an immune-mediated disease that destroys hematopoietic cells through activated T lymphocytes. B lymphocyte-mediated humoral immunity also plays an important role in the pathogenesis of AA. Regulatory B cell (Breg) subpopulation, which is defined as "B10", secretes interleukin 10 (IL-10). The objective of our experiment was to investigate whether the scale-down proportion of B10 cells in AA patients may play a key role in the pathogenesis. METHODS: A total of 38 AA patients (14 SAA patients and 24 NSAA patients) and 20 healthy control subjects were included. All subjects did not suffer from autoimmune diseases or any other diseases affecting the immune system, such as infectious diseases. Bone marrow mononuclear cells (PBMCs) were isolated and analyzed by Flow cytometry (FCM) and Immunofluorescence double-labeling assay. The relationship between the relative proportions of B10 and ProB10 and their associations to AA, as well as disease severity, were assessed by common clinical indicators and then examined. RESULTS: Our analyses revealed AA patients had significantly lower proportions of peripheral B10 and B10pro compared to healthy controls. SAA patients had a substantially lower percentage of B10 cells and B10pro cells compared to NSAA patients. In addition, B10 cells and B10pro cells were negatively correlated with absolute neutrophil counts, hemoglobin levels and platelet, and absolute reticulocyte counts in AA patients. CONCLUSIONS: The present study attempted to elucidate the potential role of the scale-down proportion of B10 cells in the pathogenesis of AA.


Assuntos
Anemia Aplástica/patologia , Linfócitos B Reguladores/patologia , Adolescente , Adulto , Idoso , Anemia Aplástica/sangue , Antígenos CD19/análise , Antígenos CD19/metabolismo , Células da Medula Óssea/citologia , Estudos de Casos e Controles , Células Cultivadas , Feminino , Citometria de Fluxo , Imunofluorescência , Humanos , Interleucina-10/análise , Interleucina-10/metabolismo , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Valores de Referência , Contagem de Reticulócitos , Índice de Gravidade de Doença , Adulto Jovem
19.
Future Microbiol ; 14: 705-716, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31161794

RESUMO

Aim: Aspergillus fumigatus is one of the most common opportunistic fungi that can cause invasive infection. To profile the kinetic variation of immune cells and cytokines after exposure to A. fumigatus thoroughly, we established a pulmonary A. fumigatus infection model in temporarily immunosuppressed mice. Materials & methods: Systematic and kinetic studies of different immune cells and cytokines were performed. Results: We observed that the granulocytes and macrophages recruited to the site of infection played an important role in the infectious phase. There was a significant increase in the cytokines IFN-γ, IL-6, TNF-α as well as the chemokines CXCL1, MIP-1α, MIP-2 and CCL5 after infection. IL-10 was found to participate in balancing the anti-inflammatory response in the recovery phases. The immune response mediated by T cells was mainly presented by the Th1-type on day 7 after exposure with a high proportion of IFN-γ+ CD4+ T cells and CD4+CD44highCD62Llow effector T cells. Conclusion: These kinetic parameters of the immune response might provide diagnostic clues for A. fumigatus infection.


Assuntos
Aspergilose/imunologia , Aspergillus fumigatus/patogenicidade , Quimiocinas/metabolismo , Citocinas/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Animais , Linfócitos T CD4-Positivos , Quimiocina CCL3/metabolismo , Quimiocina CCL5/metabolismo , Quimiocina CXCL1/metabolismo , Quimiocina CXCL2/metabolismo , Quimiocinas/sangue , Citocinas/sangue , Modelos Animais de Doenças , Hospedeiro Imunocomprometido , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Cinética , Pulmão/microbiologia , Pulmão/patologia , Linfonodos/microbiologia , Linfonodos/patologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Linfócitos T/imunologia , Células Th1/imunologia , Fator de Necrose Tumoral alfa/metabolismo
20.
Medicine (Baltimore) ; 98(24): e15700, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192910

RESUMO

INTRODUCTION: Despite the benefits, cardiovascular rehabilitation programs (CRPs) have been related to the appearance of signals and symptoms. Risk stratification protocols are commonly used to identify risks during the physical exercise; however, studies that investigate their efficacy to previse signals and symptoms are inconclusive. Furthermore, clinical, physical, and biochemical parameters have been used as risk markers for the appearance of adverse events, and to investigate their efficacy to previse signals and symptoms during the CRP sessions that could better guide the strategies adopted on these programs. OBJECTIVES: The aim of this study was to evaluate the correlations between risk stratification protocols and clinical, physical, and biochemical parameters with the appearance of signals/symptoms during CRP, as well as to evaluate if modifications on clinical, physical, and biochemical parameters could influence in the appearance of signals/symptoms during CRP. MATERIALS AND METHODS: The study was prospectively registered at ClinicalTrials.gov (NCT03446742). Forty-four patient participants of a CRP will be evaluated. First, their risk stratification is going to be performed by 2 evaluators and their clinical, physical, and biochemical parameters are going to be measured. Then, the patients are going to be followed during 24 sessions during their CRP routines in order to identify appearance of their signals/symptoms. So, the patients are going to perform their cardiovascular rehabilitation routines for 6 months and then, their clinical, physical, and biochemical parameters are going to be measured again and they are going to be followed during 24 sessions during their CRP routines in order to identify the appearance of their signals/symptoms.


Assuntos
Biomarcadores/metabolismo , Reabilitação Cardíaca/métodos , Doenças Cardiovasculares/prevenção & controle , Aptidão Cardiorrespiratória , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Protocolos Clínicos , Feminino , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Estudos Longitudinais , Masculino , Recuperação de Função Fisiológica , Projetos de Pesquisa , Medição de Risco , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo , Teste de Caminhada
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA