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1.
Anticancer Res ; 39(10): 5675-5682, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570466

RESUMO

BACKGROUND/AIM: This study explored the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) and use of antibiotics in advanced esophageal squamous cell carcinoma (ESCC) patients receiving immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: Patients were enrolled from two referral centers in Taiwan. Clinical benefit was defined as complete response, partial response, or a stable disease for ≥6 months via Response Evaluation Criteria In Solid Tumors 1.1. Clinicopathological factors' impact on overall survival (OS) and progression-free survival (PFS) was analyzed via Cox proportional hazards model. RESULTS: Forty-nine patients were enrolled. The median PFS and OS were 1.8 and 6.1 months, respectively. The median NLR at baseline was 6.40, and 21 patients received antibiotics. Both high NLR and use of antibiotics were associated with inferior PFS (p=0.028 and p<0.001, respectively) and OS (p<0.001 and p<0.001, respectively) in multivariate analysis. CONCLUSION: High NLR and use of antibiotics were associated with inferior survival in advanced ESCC patients receiving ICIs.


Assuntos
Antibacterianos/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Linfócitos/patologia , Neutrófilos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Taiwan
2.
Adv Exp Med Biol ; 1155: 755-771, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468446

RESUMO

In the last decade thiotaurine, 2-aminoethane thiosulfonate, has been investigated as an inflammatory modulating agent as a result of its ability to release hydrogen sulfide (H2S) known to play regulatory roles in inflammation. Thiotaurine can be included in the "taurine family" due to structural similarity to taurine and hypotaurine, and is characterized by the presence of a sulfane sulfur moiety. Thiotaurine can be produced by different pathways, such as the spontaneous transsulfuration between thiocysteine - a persulfide analogue of cysteine - and hypotaurine as well as in vivo from cystine. Moreover, the enzymatic oxidation of cysteamine to hypotaurine and thiotaurine in the presence of inorganic sulfur can occur in animal tissues and last but not least thiotaurine can be generated by the transfer of sulfur from mercaptopyruvate to hypotaurine catalyzed by a sulfurtransferase. Thiotaurine is an effective antioxidant agent as demonstrated by its ability to counteract the damage caused by pro-oxidants in the rat. Recently, we observed the influence of thiotaurine on human neutrophils functional responses. In particular, thiotaurine has been found to prevent human neutrophil spontaneous apoptosis suggesting an alternative or additional role to its antioxidant activity. It is likely that the sulfane sulfur of thiotaurine may modulate neutrophil activation via persulfidation of target proteins. In conclusion, thiotaurine can represent a biologically relevant sulfur donor acting as a biological intermediate in the transport, storage and release of sulfide.


Assuntos
Sulfeto de Hidrogênio , Taurina/análogos & derivados , Animais , Antioxidantes/farmacologia , Apoptose , Humanos , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Ratos , Transdução de Sinais , Sulfetos , Taurina/fisiologia
3.
Adv Exp Med Biol ; 1155: 1033-1048, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468465

RESUMO

The stable N-bromotaurine analogs (N-dibromo-dimethyl taurine, N-monobromo-dimethyl taurine), and bromamine T (BAT) show anti-inflammatory and microbicidal properties. These bromamines are good candidates for a treatment of skin infectious/inflammatory diseases as local antiseptics. Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is commonly used in various infectious/inflammatory diseases due to its analgesic and antipyretic therapeutic effects. However, systemic administration of ibuprofen may also result in adverse side effects. It has been reported that ibuprofen enhances serum levels of TNF-α and worsens secondary skin infections caused by invasive streptococci (S. pyogenes). Recently we have demonstrated that bromamines inhibit the stimulatory effect of ibuprofen on the production of inflammatory cytokines (TNF-α, IL-6). The aim of this study was to examine the combined antibacterial actions of ibuprofen and bromamines against S. pyogenes and their joint effect on the generation of reactive oxygen species (ROS) by activated neutrophils and macrophages. We have shown that the microbicidal activity of bromamines against S. pyogenes was not altered by ibuprofen. On the other hand, co-administration of ibuprofen and bromamines markedly decreased the generation of ROS by activated neutrophils and macrophages. Finally, we discuss how the antioxidant combined effect of bromamines and ibuprofen may affect a local defense system.


Assuntos
Antibacterianos/farmacologia , Ibuprofeno/farmacologia , Macrófagos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Taurina/análogos & derivados , Antioxidantes/farmacologia , Células Cultivadas , Humanos , Espécies Reativas de Oxigênio/metabolismo , Taurina/farmacologia
4.
Chem Biodivers ; 16(8): e1900204, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31298500

RESUMO

The purpose of this work was to determine the chemical composition and evaluate the antichemotactic, antioxidant, and antifungal activities of the essential oil obtained from the species Cryptocarya aschersoniana Mez, Cinnamomum amoenum (Ness & Mart.) Kosterm., and Schinus terebinthifolia Raddi, as well as the combination of C. aschersoniana essential oil and terbinafine against isolates of dermatophytes. Allo-aromadendrene, bicyclogermacrene, and germacrene B were identified as major compounds in essential oils. The essential oil of C. aschersoniana shown 100 % inhibitory effect on leukocyte migration at the concentration of 10 µg/mL while S. terebinthifolia oil presented 80.1 % inhibitory effect at the same concentration. Only S. terebinthifolia oil possessed free-radical-scavenging activity which indicates its antioxidant capacity. The essential oils were also tested against fungal isolates of dermatophyte species (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis and Microsporum gypseum), resulting in MIC ranging from 125 µg/mL to over 500 µg/mL. C. aschersoniana oil combined with terbinafine resulted in an additive interaction effect. In this case, the essential oil may act as a complement to conventional therapy for the topical treatment of superficial fungal infections, mainly because it is associated with an anti-inflammatory effect.


Assuntos
Anacardiaceae/química , Antifúngicos/química , Cinnamomum/química , Cryptocarya/química , Óleos Voláteis/química , Anacardiaceae/metabolismo , Antifúngicos/farmacologia , Antioxidantes/química , Candida/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Cinnamomum/metabolismo , Cryptocarya/metabolismo , Testes de Sensibilidade Microbiana , Microsporum/efeitos dos fármacos , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Óleos Voláteis/farmacologia , Extratos Vegetais/química , Trichophyton/efeitos dos fármacos
5.
Cancer Invest ; 37(6): 265-274, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31304800

RESUMO

A meta-analysis of 14 studies (16 cohorts) incorporating 1751 participants was performed to evaluate the correlation between baseline neutrophil-to-lymphocyte ratio (NLR) and outcome of immune checkpoint inhibitors (ICI). The pooled hazard ratio (HR) suggested elevated pretreatment NLR was associated with poor OS (HR: 2.61, 95% confidence intervals (CI): 1.77-3.86, p < 0.00001) and PFS (HR: 1.74, 95% CI: 1.34-2.27, p < 0.0001). Stratified analyses on tumor types, ICI agents, the cutoff value of NLR and study regions exhibited the similar outcomes. This study demonstrated that elevated NLR was a predictor of poor OS and PFS for ICI.


Assuntos
Antineoplásicos/imunologia , Antineoplásicos/uso terapêutico , Linfócitos/imunologia , Neutrófilos/imunologia , Feminino , Humanos , Imunoterapia/métodos , Contagem de Linfócitos , Linfócitos/efeitos dos fármacos , Masculino , Neutrófilos/efeitos dos fármacos , Prognóstico
6.
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
7.
Nord J Psychiatry ; 73(4-5): 288-292, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31164025

RESUMO

Background: Neuroleptic malignant syndrome (NMS) is a life-threatening side effect of antipsychotic medication. In this study, we aimed to investigate the hypothesis of inflammation via neutrophil-lymphocyte ratio (NLR) in the etiology of NMS. Methods: In this retrospective case-control study, data were collected using digital database of Bakirköy Mental Health Research and Training State Hospital by screening NMS diagnosis according to 'International Classification of Diseases (ICD-10) code: G21.0' between the years of 2007 and 2017. We included 32 hospitalizations with the diagnosis of NMS and 31 other acute psychiatric hospitalizations without NMS of same patients. NLR was calculated as proportion of absolute neutrophil count to absolute lymphocyte count. Significance level was accepted as p < .05. Results: The mean NLR value of NMS group was 9.55 ± 5.13 and control group was 2.06 ± 0.71 (p < .001). According to ROC analysis in our study group, we found a mean NLR cutoff value ≥4 and lymphocyte percent cutoff of ≤18.4% have the probability of correctly identifying patients with NMS with the 100% sensitivity and 100% specificity. Conclusions: In this retrospective study, we considered that higher NLR value in NMS episode might be a resemblance of systemic inflammatory state. In addition, our results suggest that both NLR and lymphocyte percentage may be alternative minor criteria which are more sensitive and specific than leukocyte levels and CPK.


Assuntos
Antipsicóticos/efeitos adversos , Linfócitos/metabolismo , Síndrome Maligna Neuroléptica/sangue , Síndrome Maligna Neuroléptica/diagnóstico , Neutrófilos/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Contagem de Leucócitos/métodos , Contagem de Linfócitos/métodos , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Estudos Retrospectivos
8.
Food Chem Toxicol ; 131: 110596, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226429

RESUMO

This study investigated the effects of chlorpyrifos (CPF) on immune-cell populations and intestinal inflammation using a mouse model of inflammatory bowel disease induced by dextran sulfate sodium (DSS). C57BL/6 mice were randomly assigned to five groups with one normal control (NC) and four DSS-treated groups. Mice in the NC group were given distilled water, whereas the DSS-treated groups received distilled water containing 3% DSS for 6 days to induce colitis. The NC and disease control (DC) groups were fed a control semipurified diet, while the remaining groups were exposed to CPF in the AIN-93 diet at doses of 1, 2.5, or 5 mg/kg/day throughout the study. Results showed that dietary exposure to CPF in colitic mice significantly increased circulating classical monocytes and upregulated gene expressions of chemokines in the colon compared to the NC group. Meanwhile, CPF exposure groups had lower plasma cholinesterase activities and higher percentages of circulating neutrophils than those of the DC group. A shorten length, tissue edema, and lipid peroxidation of the colon were also observed in all CPF-exposed mice. These findings suggest that dietary exposure to CPF affected immune-cell populations and inflammatory responses, which led to more severe tissue injury in mice with DSS-induced colitis.


Assuntos
Clorpirifos/toxicidade , Colite/imunologia , Leucócitos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Colo/metabolismo , Colo/patologia , Sulfato de Dextrana , Exposição Dietética , Leucócitos/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Regulação para Cima/efeitos dos fármacos
9.
Molecules ; 24(9)2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083328

RESUMO

Organosulfur compounds are bioactive components of garlic essential oil (EO), mustard oil, Ferula EOs, asafoetida, and other plant and food extracts. Traditionally, garlic (Allium sativum) is used to boost the immune system; however, the mechanisms involved in the putative immunomodulatory effects of garlic are unknown. We investigated the effects of garlic EO and 22 organosulfur compounds on human neutrophil responses. Garlic EO, allyl propyl disulfide, dipropyl disulfide, diallyl disulfide, and allyl isothiocyanate (AITC) directly activated Ca2+ flux in neutrophils, with the most potent being AITC. Although 1,3-dithiane did not activate neutrophil Ca2+ flux, this minor constituent of garlic EO stimulated neutrophil reactive oxygen species (ROS) production. In contrast, a close analog (1,4-dithiane) was unable to activate neutrophil ROS production. Although 1,3-dithiane-1-oxide also stimulated neutrophil ROS production, only traces of this oxidation product were generated after a 5 h treatment of HL60 cells with 1,3-dithiane. Evaluation of several phosphatidylinositol-3 kinase (PI3K) inhibitors with different subtype specificities (A-66, TGX 221, AS605240, and PI 3065) showed that the PI3K p110δ inhibitor PI 3065 was the most potent inhibitor of 1,3-dithiane-induced neutrophil ROS production. Furthermore, 1,3-dithiane enhanced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase 3 α/ß (GSK-3α/ß), and cAMP response element binding (CREB) protein in differentiated neutrophil-like HL60 cells. Density functional theory (DFT) calculations confirmed the reactivity of 1,3-dithiane vs. 1,4-dithiane, based on the frontier molecular orbital analysis. Our results demonstrate that certain organosulfur compounds can activate neutrophil functional activity and may serve as biological response modifiers by augmenting phagocyte functions.


Assuntos
Fatores Imunológicos/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Compostos Orgânicos/farmacologia , Compostos de Enxofre/farmacologia , Compostos Alílicos/farmacologia , Antioxidantes/metabolismo , Dissulfetos/farmacologia , Alho/química , Células HL-60 , Compostos Heterocíclicos/farmacologia , Humanos , Proteínas Quinases Ativadas por Mitógeno , Neutrófilos/metabolismo , Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Quinoxalinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sulfetos/farmacologia , Tiazolidinedionas/farmacologia
10.
Chem Biol Interact ; 308: 45-50, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31095933

RESUMO

The flavonoid hesperidin is abundantly found in citrus fruits and is used to treat vascular diseases. Previous studies described its gastroprotective actions against stress or ethanol-induced ulcer in rodents; however, results from indomethacin-induced ulcer were controversy. Therefore, given its clinical use and contradictory findings in acute models, this study aims to evaluate the effect of hesperidin (1-10 mg/kg, p.o) on chronic gastric ulcer induced by acetic acid in rats, a model that resembles the ulcer in humans. Moreover, the effects of hesperidin on mucin levels and on inflammatory and oxidative parameters at ulcer site were also measured. The treatment with hesperidin at 3 and 10 mg/kg, once a day, by seven days, accelerated by 34 and 62%, respectively, the ulcer healing process when compared to vehicle-treated group (99.1 ±â€¯6.4 mm2). Histological and histochemistry analyses confirmed the healing effect with significant favoring of mucin production. Hesperidin also promoted the preservation of reduced glutathione levels in the gastric mucosa tissue, as well as the normalization of superoxide dismutase and catalase activities at similar levels to those found in the non-ulcerated group. In addition, flavonoid administration increased the enzymatic activity of glutathione-S-transferase by 35%. Tissue lipoperoxides and myeloperoxidase activity were reduced after hesperidin treatment. In conclusion, the flavonoid hesperidin revealed a gastric healing activity in the ulcerated mucosa, an effect that showed to be associated with the reduction of oxidative damage at ulcer site, due to the reduction of the neutrophil migration and the strengthening of the mucus barrier next to the mucosa.


Assuntos
Glicosídeos/uso terapêutico , Hesperidina/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Ácido Acético/toxicidade , Animais , Catalase/metabolismo , Esquema de Medicação , Flavanonas/química , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Glutationa/metabolismo , Glicosídeos/farmacologia , Hesperidina/farmacologia , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo , Cicatrização/efeitos dos fármacos
11.
Int J Mol Sci ; 20(9)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060326

RESUMO

The immunomodulatory effects of mesenchymal stem cells (MSCs) are established. However, the effects of MSCs on neutrophil survival in acute lung injury (ALI) remain unclear. The goal of this study was to investigate the effect of an MSC-conditioned medium (MSC-CM) on neutrophil apoptosis in endotoxin-induced ALI. In this study, an MSC-CM was delivered via tail vein injection to wild-type male C57BL/6 mice 4 h after an intratracheal injection of lipopolysaccharide (LPS). Twenty-four hours later, bronchoalveolar lavage fluid (BALF) and lung tissue were collected to perform histology, immunohistochemistry, apoptosis assay of neutrophil, enzyme-linked immunosorbent assays, and an electrophoretic mobility shift assay. Human neutrophils were also collected from patients with sepsis-induced acute respiratory distress syndrome (ARDS). Human neutrophils were treated in vitro with LPS, with or without subsequent MSC-CM co-treatment, and were then analyzed. Administration of the MSC-CM resulted in a significant attenuation of histopathological changes, the levels of interleukin-6 and macrophage inflammatory protein 2, and neutrophil accumulation in mouse lung tissues of LPS-induced ALI. Additionally, MSC-CM therapy enhanced the apoptosis of BALF neutrophils and reduced the expression of the anti-apoptotic molecules, Bcl-xL and Mcl-1, both in vivo and in vitro experiments. Furthermore, phosphorylated and total levels of nuclear factor (NF)-κB p65 were reduced in lung tissues from LPS + MSC-CM mice. Human MSC-CM also reduced the activity levels of NF-κB and matrix metalloproteinase-9 in the human neutrophils from ARDS patients. Thus, the results of this study suggest that the MSC-CM attenuated LPS-induced ALI by inducing neutrophil apoptosis, associated with inhibition of the NF-κB pathway.


Assuntos
Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Apoptose/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Células-Tronco Mesenquimais/metabolismo , NF-kappa B/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Lesão Pulmonar Aguda/patologia , Animais , Citocinas/metabolismo , Endotoxinas/efeitos adversos , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Neutrófilos/imunologia
12.
Phytomedicine ; 59: 152777, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31004880

RESUMO

BACKGROUND: Cigarette smoke (CS) is a major contributor to the high incidence of chronic obstructive pulmonary disease (COPD) featured as chronic inflammation and airway obstruction. Mahuang-Tang is a traditional polyherbal mixture composed of four different herbs. It is widely used in Asia as a remedy for allergic reaction and inflammation. PURPOSE: We investigated the effects of a modificated Mahuang-Tang water extract (MTWE) against airway inflammation caused by CS and lipopolysaccharide (LPS) in mice and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells. METHODS: CS exposed to animals for 1 h per day from day 1 to day 7 and treated with LPS intranasally on day 4. One hour before CS exposure, animals were received MTWE (50 or 100 mg/kg) by oral gavage. Inflammatory cell count and cytokines levels were measured in the bronchoalveolar lavage fluid. Expression levels of matrix metalloprotease-9 (MMP-9) and extracellular signal-regulated kinase (Erk) were analyzed by western blotting. RESULTS: MTWE markedly decreased the neutrophil and other inflammatory cell counts in the bronchoalveolar lavage fluid and reduced proinflammatory mediators as evidenced by the decreases in inflammatory cell recruitment in lung tissue. Furthermore, MTWE meaningfully declined MMP-9 expression and reduced the Erk phosphorylation, caused by the CS and LPS exposure. In in vitro experiments, MTWE suppressed the elevated expression of proinflammatory cytokines induced by CSC treatment. MTWE reduced Erk phosphorylation and MMP-9 expression in CSC-stimulated H292 cells. CONCLUSION: Overall, MTWE effectively inhibited the pulmonary inflammation and MMP-9 expression caused by the CS and LPS exposure, which was closely involved in suppression of Erk phosphorylation. These results suggest that MTWE possesses a potential for the treatment of COPD.


Assuntos
Fumar Cigarros/efeitos adversos , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Pulmão/efeitos dos fármacos , Animais , Líquido da Lavagem Broncoalveolar , Citocinas/genética , Medicamentos de Ervas Chinesas/química , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Lipopolissacarídeos/toxicidade , Pulmão/patologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Fosforilação/efeitos dos fármacos , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Pneumonia/patologia
13.
Bull Exp Biol Med ; 166(6): 754-758, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31028579

RESUMO

We studied immunocorrecting effects of Semax (Met-Glu-His-Phe-Pro-Gly-Pro) on the model of "social" stress caused by sensory contact and intermale confrontation. Functional activity of the immune system of laboratory animals was evaluated in standard immunopharmacological tests: delayed-type hypersensitivity reaction, direct agglutination test, latex test for studying phagocytic activity of peripheral blood neutrophils, changes in differential leukocyte count, and weight of immunocompetent organs. It was found that changes in the immune response caused by "social" stress are multidirectional, which confirms the theory of stress-induced "immune imbalance". Semax acted as effective immune corrector restoring cellular and humoral immunogenesis reactions and phagocytic activity of neutrophils. This attested to the presence of immunomodulating properties in Semax and necessitates further studies in this field.


Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Fatores Imunológicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Nootrópicos/farmacologia , Fragmentos de Peptídeos/farmacologia , Estresse Psicológico/tratamento farmacológico , Hormônio Adrenocorticotrópico/farmacologia , Agressão , Animais , Animais não Endogâmicos , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Tardia/imunologia , Imunidade Inata/efeitos dos fármacos , Testes de Fixação do Látex , Contagem de Leucócitos , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Fagocitose/efeitos dos fármacos , Estresse Psicológico/imunologia , Estresse Psicológico/fisiopatologia
14.
Molecules ; 24(8)2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31018502

RESUMO

Several Ajuga species are used in Romanian folk medicine for their antioxidant, antimicrobial and anti-inflammatory properties, to treat pain, fever or arthritis. Still, the active compounds responsible for these effects and their mechanism of action are scarcely known. This research was designed to investigate the phytochemical profile (e.g. iridoids, polyphenolic compounds, phytosterols), as well as the biological potential (antioxidant, antibacterial, antifungal, anti-inflammatory properties) of two selected Ajuga species collected from different regions of Romanian spontaneous flora. The main compounds identified in A. reptans aerial parts extracts were 8-O-acetylharpagide, isoquercitrin and ß-sitosterol, whilst in A. genevensis were 8-O-acetylharpagide, luteolin and campesterol. The extracts were screened for their antioxidant potential using different methods (DPPH, TEAC, EPR) and the results showed a good activity, in accordance with the polyphenol content (18-26 mg GAE/g dw). The antifungal activity on the tested strains was good. The determination of few parameters linked with the inflammatory mechanism allowed the assessment of in vivo anti-inflammatory potential. Ajuga reptans and A. genevensis ethanol extracts had anti-inflammatory activity through lowering the oxidative stress, phagocytosis, PMN and total leukocytes. The best anti-oxidative and anti-inflammatory activity was observed for the Ajuga reptans 100 mg dw/mL extract when compared with diclofenac, thus the dose could be correlated with the pharmacological effect. These findings provide substantial evidence that both selected Ajuga species have the potential to be valued as sources of phytochemicals in effective anti-inflammatory herbal preparations.


Assuntos
Ajuga/química , Iridoides/farmacologia , Fitosteróis/farmacologia , Fitoterapia/métodos , Polifenóis/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Fungos/efeitos dos fármacos , Fungos/crescimento & desenvolvimento , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Inflamação/tratamento farmacológico , Iridoides/química , Iridoides/isolamento & purificação , Testes de Sensibilidade Microbiana , Neutrófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Fitosteróis/química , Fitosteróis/isolamento & purificação , Picratos/antagonistas & inibidores , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Plantas Medicinais , Polifenóis/química , Polifenóis/isolamento & purificação , Ratos , Ratos Wistar , Romênia
15.
Mediators Inflamm ; 2019: 1208086, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944544

RESUMO

In acute pulmonary inflammation, polymorphonuclear cells (PMNs) pass a transendothelial barrier from the circulation into the lung interstitium followed by a transepithelial migration into the alveolar space. These migration steps are regulated differentially by a concept of adhesion molecules and remain-despite decades of research-incompletely understood. Current knowledge of changes in the expression pattern of adhesion molecules mainly derives from in vitro studies or from studies in extrapulmonary organ systems, where regulation of adhesion molecules differs significantly. In a murine model of lung inflammation, we determined the expression pattern of nine relevant neutrophilic adhesion molecules on their way through the different compartments of the lung. We used a flow cytometry-based technique that allowed describing spatial distribution of the adhesion molecules expressed on PMNs during their migration through the lung in detail. For example, the highest expression of CD29 was found in the intravascular compartment, highlighting its impact on the initial adhesion to the endothelium. CD47 showed its peak of expression on the later phase of transendothelial migration, whereas CD11b and CD54 expression peaked interstitial. A pivotal role for transepithelial migration was found for the adhesion molecule CD172a. Thereby, expression may correlate with functional impact for specific migration steps. In vitro studies further confirmed our in vivo findings. In conclusion, we are the first to determine the changes in expression patterns of relevant adhesion molecules on their migration through the different compartments of the lung. These findings may help to further understand the regulation of neutrophil trafficking in the lung.


Assuntos
Moléculas de Adesão Celular/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Neutrófilos/metabolismo , Pneumonia/metabolismo , Lesão Pulmonar Aguda/metabolismo , Animais , Antígeno CD11b/metabolismo , Antígeno CD47/metabolismo , Adesão Celular/efeitos dos fármacos , Citometria de Fluxo , Inflamação/imunologia , Inflamação/metabolismo , Integrina beta1/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Lipopolissacarídeos/toxicidade , Pulmão/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Receptores Imunológicos/metabolismo
16.
Molecules ; 24(7)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30965630

RESUMO

Seventy-three compounds were identified from the methanol extract of V. luteola, and among these, three new (1⁻3) were characterized by spectroscopic and mass spectrometric analyses. The isolated constituents were assessed for anti-inflammatory potential evaluation, and several purified principles exhibited significant superoxide anion and elastase inhibitory effects.


Assuntos
Anti-Inflamatórios/farmacologia , Compostos Fitoquímicos/farmacologia , Vigna/química , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Citocalasina B/efeitos adversos , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Elastase Pancreática/antagonistas & inibidores , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Superóxidos/antagonistas & inibidores
17.
Int J Mol Sci ; 20(7)2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30970662

RESUMO

Salicylate-rich plants are an attractive alternative to synthetic anti-inflammatory drugs due to a better safety profile and the advantage of complementary anti-inflammatory and antioxidant effects of the co-occurring non-salicylate phytochemicals. Here, the phytochemical value and biological effects in vitro and ex vivo of the stems of one of such plants, Gaultheria procumbens L., were evaluated. The best extrahent for effective recovery of the active stem molecules was established in comparative studies of five extracts. The UHPLC-PDA-ESI-MS³, HPLC-PDA, and UV-photometric assays revealed that the selected acetone extract (AE) accumulates a rich polyphenolic fraction (35 identified constituents; total content 427.2 mg/g dw), mainly flavanols (catechins and proanthocyanidins; 201.3 mg/g dw) and methyl salicylate glycosides (199.9 mg/g dw). The extract and its model components were effective cyclooxygenase-2, lipoxygenase, and hyaluronidase inhibitors; exhibited strong antioxidant capacity in six non-cellular in vitro models (AE and procyanidins); and also significantly and dose-dependently reduced the levels of reactive oxygen species (ROS), and the release of cytokines (IL-1ß, IL-8, TNF-α) and proteinases (elastase-2, metalloproteinase-9) in human neutrophils stimulated ex vivo by lipopolysaccharide (LPS) and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). The cellular safety of AE was demonstrated by flow cytometry. The results support the application of the plant in traditional medicine and encourage the use of AE for development of new therapeutic agents.


Assuntos
Anti-Inflamatórios/farmacologia , Biflavonoides/farmacologia , Catequina/farmacologia , Gaultheria/química , Neutrófilos/citologia , Proantocianidinas/farmacologia , Salicilatos/farmacologia , Adulto , Anti-Inflamatórios/química , Biflavonoides/química , Catequina/química , Sobrevivência Celular , Citocinas/metabolismo , Humanos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Proantocianidinas/química , Espécies Reativas de Oxigênio/metabolismo , Salicilatos/química , Adulto Jovem
18.
Molecules ; 24(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022860

RESUMO

Carpesium divaricatum Sieb. & Zucc. has a long history of use as both a medicinal and a food plant. However, except for terpenoids, its chemical constituents have remained poorly investigated. The composition of hydroalcoholic extract from aerial parts of C. divaricatum was analyzed by HPLC-DAD-MSn, revealing the presence of numerous caffeic acid derivatives that were formerly unknown constituents of the plant. In all, 17 compounds, including commonly found chlorogenic acids and rarely occurring butyryl and methylbutyryl tricaffeoylhexaric acids, were tentatively identified. Fractionation of lipophilic extract from cultivated shoots led to the isolation of 12-oxo-phytodienoic acid (12-OPDA), which is a newly identified constituent of the plant. The compound, at concentrations of 0.5, 1.0, and 2.5 µM, significantly reduced IL-8, IL-1ß, TNFα, and CCL2 excretion by lipopolysaccharide (LPS)-stimulated human neutrophils. Reactive oxygen species (ROS) production induced by f-MLP was also significantly diminished in the neutrophils pretreated by 12-OPDA. The newly identified constituents of the plant seem to be partly responsible for its pharmacological activity and elevate the value of C. divaricatum as a potential functional food.


Assuntos
Asteraceae/química , Ácidos Cafeicos/química , Ácido Clorogênico/química , Ácidos Graxos Insaturados/química , Ácidos Cafeicos/isolamento & purificação , Ácidos Cafeicos/farmacologia , Quimiocina CCL2/genética , Ácido Clorogênico/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Ácidos Graxos Insaturados/isolamento & purificação , Ácidos Graxos Insaturados/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-8/genética , Lipopolissacarídeos/farmacologia , Neutrófilos/efeitos dos fármacos , Componentes Aéreos da Planta/química , Brotos de Planta/química , Espécies Reativas de Oxigênio/química , Fator de Necrose Tumoral alfa/genética
19.
BMC Res Notes ; 12(1): 228, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30992057

RESUMO

OBJECTIVE: Intravenous immune globulin (IVIG), pooled from human blood, is a polyspecific antibody preparation that inhibits the super-antigenic proteins associated with streptococcal and staphylococcal toxic shock, and the Shiga toxin. In addition to this toxin-neutralising activity, IVIG contains other pathogen-reactive antibodies that may confer additional therapeutic benefits. We sought to determine if pathogen-reactive antibodies that promote opsonophagocytosis of different organisms can be sequentially affinity-purified from one IVIG preparation. RESULTS: Antibodies that recognise cell wall antigens of Streptococcus pyogenes, Staphylococcus aureus, and vancomycin-resistant enterococcus (VRE) were sequentially affinity-purified from a single preparation of commercial IVIG and opsonophagocytic activity was assessed using a flow cytometry assay of neutrophil uptake. Non-specific IgG-binding proteins were removed from the S. aureus preparations using an immobilised Fc fragment column, produced using IVIG cleaved with the Immunoglobulin G-degrading enzyme of S. pyogenes (IdeS). Affinity-purified anti-S. aureus and anti-VRE immunoglobulin promoted significantly higher levels of opsonophagocytic uptake by human neutrophils than IVIG when identical total antibody concentrations were compared, confirming activity previously shown for affinity-purified anti-S. pyogenes immunoglobulin. The opsonophagocytic activities of anti-S. pyogenes, anti-S. aureus, and anti-VRE antibodies that were sequentially purified from a single IVIG preparation were undiminished compared to antibodies purified from previously unused IVIG.


Assuntos
Anticorpos Antibacterianos/farmacologia , Imunoglobulinas Intravenosas/química , Neutrófilos/efeitos dos fármacos , Proteínas Opsonizantes/farmacologia , Fagocitose/efeitos dos fármacos , Anticorpos Antibacterianos/isolamento & purificação , Antígenos de Bactérias/química , Antígenos de Bactérias/imunologia , Parede Celular/química , Cromatografia de Afinidade/métodos , Humanos , Fragmentos Fc das Imunoglobulinas/química , Neutrófilos/citologia , Neutrófilos/imunologia , Proteínas Opsonizantes/isolamento & purificação , Cultura Primária de Células , Staphylococcus aureus/química , Staphylococcus aureus/imunologia , Staphylococcus aureus/patogenicidade , Streptococcus pyogenes/química , Streptococcus pyogenes/imunologia , Streptococcus pyogenes/patogenicidade , Enterococos Resistentes à Vancomicina/química , Enterococos Resistentes à Vancomicina/imunologia , Enterococos Resistentes à Vancomicina/patogenicidade
20.
J Immunol Res ; 2019: 3560180, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944832

RESUMO

Nanotechnology has become a novel subject with impact in many research and technology areas. Nanoparticles (NPs), as a key component in nanotechnology, are widely used in many areas such as optical, magnetic, electrical, and mechanical engineering. The biomedical and pharmaceutical industries have embraced NPs as a viable drug delivery modality. As such, the potential for NP-induced cytotoxicity has emerged as a major concern for NP drug delivery systems. Thus, it is important to understand how NPs affect the innate immune system. As the most abundant myeloid cell type in innate immune responses, neutrophils are critical for concerns about potentially toxic side effects of NPs. When activated by innate immune stimuli, neutrophils may initiate NETosis to release neutrophil extracellular traps (NETs). Herein, we have reviewed the relationship between NPs and the induction of NETosis and release of NETs.


Assuntos
Armadilhas Extracelulares/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Inflamação , Nanoestruturas/efeitos adversos , Neutrófilos/imunologia , Animais , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas Metálicas/efeitos adversos , Nanopartículas Metálicas/uso terapêutico , Camundongos , Neutrófilos/efeitos dos fármacos
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