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1.
Acta Cir Bras ; 34(7): e201900703, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531538

RESUMO

PURPOSE: To compare four types of mesh regarding visceral adhesions, inflammatory response and incorporation. METHODS: Sixty Wistar rats were divided into four groups, with different meshes implanted intraperitoneally: polytetrafluoroethylene (ePTFE group); polypropylene with polydioxanone and oxidized cellulose (PCD); polypropylene (PM) and polypropylene with silicone (PMS). The variables analyzed were: area covered by adhesions, incorporation of the mesh and inflammatory reaction (evaluated histologically and by COX2 immunochemistry). RESULTS: The PMS group had the lowest adhesion area (63.1%) and grade 1 adhesions. The ePTFE and PM groups presented almost the total area of their surface covered by adherences (99.8% and 97.7% respectively) The group ePTFE had the highest percentage of area without incorporation (42%; p <0.001) with no difference between the other meshes. The PMS group had the best incorporation rate. And the histological analysis revealed that the inflammation scores were significantly different. CONCLUSIONS: The PM mesh had higher density of adherences, larger area of adherences, adherences to organs and percentage of incorporation. ePTFE had the higher area of adherences and lower incorporation. The PMS mesh performed best in the inflammation score, had a higher incorporation and lower area of adherences, and it was considered the best type of mesh.


Assuntos
Hérnia Incisional/cirurgia , Inflamação/patologia , Próteses e Implantes , Telas Cirúrgicas/normas , Aderências Teciduais/patologia , Parede Abdominal/patologia , Animais , Celulose Oxidada/efeitos adversos , Masculino , Teste de Materiais , Polipropilenos/efeitos adversos , Politetrafluoretileno/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Próteses e Implantes/efeitos adversos , Ratos , Ratos Wistar , Silicones/efeitos adversos , Estatísticas não Paramétricas , Telas Cirúrgicas/efeitos adversos , Aderências Teciduais/prevenção & controle , Vísceras/fisiologia
2.
Isr Med Assoc J ; 21(7): 454-459, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507120

RESUMO

BACKGROUND: Platelets have the ability to influence the immune system and the inflammatory process and may be strongly involved in the whole pathogenic process of chronic inflammatory joint diseases, such as rheumatoid arthritis. They may play a significant role even before the clinical onset of the disease, contributing to the loss of tolerance of the immune system and the induction of autoimmunity. Subsequently, they can interact with the most important cellular players involved in autoimmunity and inflammation, namely innate immunity cells and T cells and eventually contribute to the building of inflammation in the synovium, thus inducing the activation, migration, and proliferation of fibroblasts that eventually lead to joint damage. Due to their peculiar features, studying the behavior of platelets is a challenging task; however, platelets may prove to be valuable therapeutic targets in the future.


Assuntos
Artrite Reumatoide/imunologia , Plaquetas/imunologia , Sinovite/imunologia , Artrite Reumatoide/patologia , Autoimunidade/imunologia , Fibroblastos/imunologia , Humanos , Imunidade Inata/imunologia , Inflamação/imunologia , Inflamação/patologia , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Sinovite/patologia , Linfócitos T/imunologia
3.
Braz Oral Res ; 33: e085, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31483051

RESUMO

The aim of this study was to evaluate the immunoexpression of human leukocyte antigen-DR (HLA-DR) in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC), and to correlate the findings with clinical (tumor size/extent, regional lymph node metastasis, and clinical stage) and histopathological (grade of epithelial dysplasia and inflammatory infiltrate for AC and histopathological grade of malignancy for LLSCC) parameters. Twenty-four AC and 48 LLSCC cases (24 with regional nodal metastasis and 24 without regional nodal metastasis) were selected. The scores of immunopositive cells for HLA-DR in the epithelial component of the lesions were assessed and the results were analyzed statistically using the nonparametric Mann-Whitney test. Epithelial expression of HLA-DR was observed in only five (20.8%) cases of AC (two low-grade and three high-grade lesions), with a very low median score of immunopositivity. By contrast, expression of HLA-DR was found in most LLSCC (97.9%), with a relatively high median score of positive cells. The score of HLA-DR-positive cells tended to be higher in tumors with regional lymph node metastasis, tumors in advanced clinical stages, and low-grade tumors, but the difference was not statistically significant (p > 0.05). In addition, there was a tendency towards higher expression of HLA-DR in highly/moderately keratinized tumors, and tumors with little/moderate nuclear pleomorphism (p > 0.05). The results suggest a potential role of HLA-DR in lip carcinogenesis, particularly in the development and progression of LLSCC. The expression of this protein can be related to the degree of cell differentiation in these tumors.


Assuntos
Queilite/imunologia , Antígenos HLA-DR/imunologia , Neoplasias Labiais/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/imunologia , Queilite/patologia , Feminino , Humanos , Inflamação/patologia , Neoplasias Labiais/patologia , Neoplasias Labiais/secundário , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário
4.
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
5.
Life Sci ; 234: 116773, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31422095

RESUMO

AIMS: NLRP3 inflammasome activation is essential for the development and prognosis of diabetic cardiomyopathy (DCM). The anti-aging protein Klotho is suggested to modulate tissue inflammatory responses. The aim of the present study was to examine the protective effects of Klotho on DCM. MAIN METHODS: A streptozotocin-induced diabetes mouse model was established to assess the effects of Klotho in vivo, which was administered for 12 weeks. The characteristics of type 1 DCM were evaluated by general status, echocardiography, and histopathology. The expression of associated factors was determined by RT-qPCR and western blotting. Parallel experiments to determine the molecular mechanism through which Klotho prevents DCM were performed using H9C2 cells exposed to high glucose (35 mM). KEY FINDINGS: Diabetes-induced increases in serum creatine kinase-muscle/brain and lactate dehydrogenase levels, cardiac fibrosis, cardiomyocyte apoptosis, and cardiac dysfunction were ameliorated by Klotho. Additionally, Klotho suppressed TXNIP expression, NLRP3 inflammasome activation, and expression of the inflammatory cytokines tumor necrosis factor ɑ, interleukin-1ß, and interleukin-18 in vivo. In high glucose-cultured cardiomyocytes, Klotho and N-acetylcysteine significantly downregulated intracellular reactive oxygen species generation and TXNIP/NLRP3 inflammasome activation. Pretreatment of H9C2 cells with NLRP3 siRNA or Klotho prevented high glucose-induced inflammation and apoptosis in H9C2 cells. SIGNIFICANCE: Our results demonstrate that the protective effect of Klotho on diabetes-induced cardiac injury is associated with inhibition of the NLRP3 inflammasome pathway, suggesting its therapeutic potential for DCM.


Assuntos
Diabetes Mellitus Experimental/imunologia , Cardiomiopatias Diabéticas/imunologia , Glucuronidase/imunologia , Inflamassomos/imunologia , Inflamação/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Animais , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/uso terapêutico , Cardiotônicos/imunologia , Cardiotônicos/uso terapêutico , Linhagem Celular , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/patologia , Glucuronidase/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/patologia , Masculino , Camundongos Endogâmicos C57BL , Ratos , Espécies Reativas de Oxigênio/imunologia
6.
Medicine (Baltimore) ; 98(33): e16875, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415428

RESUMO

EGFR-TKIs have been widely used in the first-line treatment of NSCLC patients harboring EGFR mutations. However, the prognosis indicators are limited. In the present study, the prognostic value of systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) were assessed in EGFR-Mutant lung adenocarcinoma patients treated with first-generation EGFR-TKIs. Two hundred three patients were included in this retrospective analysis. SII was calculated as platelet counts × neutrophil counts / lymphocyte counts. Receiver operating characteristic (ROC) curve was used to evaluate the optimal cut-off value for SII, NLR, and PLR. Univariate and multivariate survival analysis were performed to identify factors correlated with PFS and OS. Applying cut-offs of ≥1066.935 (SII), ≥4.40 (NLR), and ≥182.595 (PLR), higher NLR was associated with worse Eastern Cooperative Oncology Group performance status (ECOG PS) (P = .006), and higher brain metastasis rate (P = .03), higher PLR was associated with smoking history (P = .037), and worse ECOG PS (P = .001), and higher SII groups were associated with worse ECOG PS (P = .002). In univariate analysis, higher NLR (P < .001), higher PLR (P = .002), and higher SII (P < .001) were associated with worse PFS. Higher NLR (P < .001), and higher SII (P < .001) were associated with worse OS. In multivariate analysis, NLR (HR 1.736;95%CI:1.020-2.954; P = .03), PLR (HR 1.823; 95%CI:1.059-3.137; P = .04), and SII (HR2.577; 95%CI:1.677-3.958; P < .001) were independently correlated with PFS. While only SII (HR 2.802; 95%CI:1.659-4.733; P < .001) was independently correlated with OS. The present study demonstrated that SII is an independent prognostic factor for poor survival of advanced EGFR-Mutant lung adenocarcinoma patients treated with first-generation TKIs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Receptores ErbB/uso terapêutico , Feminino , Humanos , Inflamação/patologia , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sensibilidade e Especificidade
7.
Cell Physiol Biochem ; 53(2): 355-365, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31385664

RESUMO

BACKGROUND/AIMS: NLRP3 inflammasome activation has been reported to be an early mechanism responsible for glomerular inflammation and injury in obese mice. However, the precise mechanism of obesity-induced NLRP3 inflammasome activation remains unknown. The present study explored whether adipokine visfatin mediates obesity-induced NLRP3 inflammasome activation and consequent podocyte injury. METHODS: Inflammasome formation and immunofluorescence expressions were quantified by confocal microscopy. Caspase-activity, IL-1ß production and VEGF concentrations were measured by ELISA. RESULTS: Confocal microscopic analysis showed that visfatin treatment increased the colocalization of Nlrp3 with Asc or Nlrp3 with caspase-1 in podocytes indicating the formation of NLRP3 inflammasomes. This visfatin-induced NLRP3 inflammasome formation was abolished by pretreatment of podocytes with Asc siRNA. Correspondingly, visfatin treatment significantly increased the caspase-1 activity and IL-1ß production in podocytes, which was significantly attenuated by Asc siRNA transfection. Further RT-PCR and confocal microscopic analysis demonstrated that visfatin treatment significantly decreased the podocin expression (podocyte damage). Podocytes pretreatment with Asc siRNA or caspase-1 inhibitor, WEHD attenuated this visfatin-induced podocin reduction. Furthermore, Asc siRNA transfection was found to preserve podocyte morphology by maintaining the distinct arrangement of F-actin fibers normally lost in response to visfatin. It also prevented podocyte dysfunction by restoring visfatin-induced suppression of VEGF production and secretion. CONCLUSION: Visfatin induces NLRP3 inflammasome activation in podocytes and thereby resulting in podocyte injury.


Assuntos
Adipocinas/imunologia , Inflamassomos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Nicotinamida Fosforribosiltransferase/imunologia , Podócitos/imunologia , Animais , Linhagem Celular , Inflamação/imunologia , Inflamação/patologia , Interleucina-1beta/imunologia , Camundongos , Obesidade/imunologia , Obesidade/patologia , Podócitos/citologia , Podócitos/patologia , Fator A de Crescimento do Endotélio Vascular/imunologia
8.
Braz Oral Res ; 33: e060, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365705

RESUMO

This study evaluated the effect of hypertension on tissue response and biomineralization capacity of white Mineral Trioxide Aggregate (MTA), High-plasticity MTA (MTA HP), and Biodentine® (BDT) in rats. Polyethylene tubes filled with MTA, MTA HP, BDT, and the control group (empty tubes) were placed into the dorsal subcutaneous tissue of 32 male rats (16 normotensive (NT) and 16 hypertensive rats - 8 per group). After 7 and 30 days, the polyethylene tubes surrounded by connective tissue were removed, fixed, and embedded in histological resin. The mean number of inflammatory cells was estimated in HE-stained sections, biomineralization was quantified as area (µm2) by Kossa (VK) staining, and examination by polarized light (LP) microscopy was performed. The differences amongst the groups were analyzed statistically by the Mann-Whitney or Student's t test, according to Shapiro-Wilk test of normality (p < 0.05). The inflammatory responses to all materials were greater in hypertensive rats than in NT rats (p < 0.05). Positive VK staining in MTA and BDT were more pronounced in NT rats at 7 and 30 days (p < 0.05). Birefringent structures in LP for MTA, MTA HP, and BDT were more pronounced in NT rats at 7 days (p<0.05). In rats, hypertension was able to increase inflammatory infiltrate and decrease biomineralization of the tested materials.


Assuntos
Compostos de Alumínio/farmacologia , Materiais Biocompatíveis/farmacologia , Biomineralização/fisiologia , Compostos de Cálcio/farmacologia , Hipertensão/fisiopatologia , Óxidos/farmacologia , Silicatos/farmacologia , Tela Subcutânea/efeitos dos fármacos , Tela Subcutânea/fisiopatologia , Animais , Combinação de Medicamentos , Hipertensão/complicações , Inflamação/patologia , Inflamação/fisiopatologia , Masculino , Teste de Materiais , Microscopia de Polarização , Ratos Wistar , Reprodutibilidade dos Testes , Tela Subcutânea/patologia , Fatores de Tempo
9.
Anticancer Res ; 39(8): 4491-4494, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366550

RESUMO

BACKGROUND/AIM: High-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein that exerts a range of proinflammatory actions when it is secreted extracellularly. We hypothesized that HMGB1 released from damaged cells in pituitary apoplexy would exacerbate the neurological symptoms due to acute inflammation. PATIENTS AND METHODS: All the patients included in this study suffered from non-functioning pituitary adenoma. Four patients with apoplexy and three patients without apoplexy were included in this study. They underwent endonasal transsphenoidal endoscopic surgery to resect the tumors. We conducted enzyme-linked immunosorbent assay (ELISA) to measure HMGB1 in the surgical specimens. RESULTS: Patients with apoplexy expressed HMGB1 at significantly higher levels than those in the non-apoplexy group (p=0.0478). CONCLUSION: HMGB1 may be involved in subacute inflammation of pituitary apoplexy. Further work is needed to elucidate the detailed biological significance of HMGB1 in this disease.


Assuntos
Proteína HMGB1/genética , Inflamação/genética , Apoplexia Hipofisária/genética , Neoplasias Hipofisárias/genética , Adenoma/genética , Adenoma/patologia , Adenoma/cirurgia , Adulto , Endoscopia , Ensaio de Imunoadsorção Enzimática , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Inflamação/diagnóstico por imagem , Inflamação/patologia , Inflamação/cirurgia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Apoplexia Hipofisária/diagnóstico por imagem , Apoplexia Hipofisária/patologia , Apoplexia Hipofisária/cirurgia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia
10.
Klin Lab Diagn ; 64(7): 417-423, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31408594

RESUMO

Recently, they increasingly began to pay attention to the role of a nonspecific immune-inflammatory vascular response as a link in general pathogenetic mechanisms with a change in the elastic properties of arteries and phenomena of destructive bone changes, which at the subclinical level is of great importance for the prevention of the development of socially significant diseases. A total of 104 patients were examined (mean age 57.45 years), which were divided into three groups. The first group included 39 healthy women, the second group included 30 patients with hypertension and osteopenia, and the third group included 35 women with hypertension and osteoporosis. The analysis of markers of the immune inflammatory response, endothelial dysfunction, hormonal and mineral-vitamin status parameters was conducted against the background of the study of parameters of daily monitoring of arterial pressure, study of parameters of vascular wall stiffness and densitometry to clarify the predictors of cardiovascular and degenerative bone changes in postmenopausal women. A significant increase in the concentration of HF-CRP, the level of homocystemine, IL-8, parathyroid hormone, against the background of a significant decrease in the level of estrogen, progesterone, testosterone, with a persistent tendency to increase in total cholesterol, atherogenic lipid fractions, myeloperoxidase, endothelin-1 and decrease was recorded calcitonin, total and ionized calcium, with a significantly minimal value of vitamin D in the 3rd group of patients. The risks of development and progression of bone destructive changes were calculated using the logistic regression method for the group of AH with osteopenia and osteoporosis. Thus, for patients with hypertension and osteopenia, a significantly significant parameter associated with the risk of developing osteoporosis was an indicator of the velocity of the pulse wave, an increase in the level of which exceeds 12.05 m/s is associated with an increased risk of developing osteoporosis by 3.8 times. Increased levels of pro-inflammatory parameters, IL-6 and 8, TNF-α, HB-SRB, parathyroid hormone and reduced levels of progesterone and IL10, took the most active part in aggravating the degree of available bone tissue destruction. Timely specialized multidirectional study of biochemical and instrumental parameters (in particular, the study of the speed of the pulse wave and densitometry) can be the basis for the development of personalized prevention and treatment tactics for women in order to prevent socially dangerous cardiovascular and bone complications.


Assuntos
Hipertensão/patologia , Inflamação/patologia , Osteoporose/patologia , Densidade Óssea , Doenças Ósseas Metabólicas/imunologia , Doenças Ósseas Metabólicas/patologia , Osso e Ossos , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Hormônios/sangue , Humanos , Hipertensão/imunologia , Pessoa de Meia-Idade , Osteoporose/imunologia , Pós-Menopausa
11.
Life Sci ; 232: 116653, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302194

RESUMO

Huntington's disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion in the gene encoding the huntingtin protein (HTT). This expansion leads to the formation of mutant huntingtin protein (mHTT) that is expressed in many body tissue cells. The mHTT interacts with several molecular pathways within different cell types, affecting the regulation of the immune system cells. It is still very limited the understanding of the immune changes in peripheral tissues in HD. Herein, we investigated the levels of inflammatory and regulatory cytokines in peripheral organs (i.e. kidney, heart, liver and spleen) of the 12-month-old BACHD model of HD. This robust murine model closely resembles the human disease. We found significant changes in cytokine levels in all organs analyzed. Increased levels of IL-6 were found in the kidney, while levels of IL-6 and IL-12p70 were increased in the heart of BACHD mice in comparison with wild-type (WT) animals. In the liver, we observed enhanced IL-12p70 and TNF-α levels. In the spleen, there was an increase in the levels of IL-4 and a decrease in the levels of IL-5 and IL-6 in BACHD compared to WT. Our findings provide the first evidence that the BACHD model also exhibits immune changes in peripheral organs, opening an avenue for the investigation of the potential role played by peripheral inflammatory response in HD. Further studies are needed to systematically address the mechanisms and pathways underlying immune signaling in peripheral organs in HD.


Assuntos
Doença de Huntington/patologia , Inflamação/patologia , Animais , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Doença de Huntington/metabolismo , Inflamação/metabolismo , Fígado/metabolismo , Masculino , Camundongos
12.
Zhonghua Shao Shang Za Zhi ; 35(7): 548-551, 2019 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-31357829

RESUMO

Persistent inflammation-immunosuppression-catabolism syndrome (PICS) is a clinical syndrome in patients surviving from severe trauma or sepsis, which is characterized by prolonged stays in intensive care unit, persistent inflammation response, immune suppression, high protein catabolism, and high mortality. This article aims to review the proposed process of the concept, the mechanism, the clinical features, and the diagnosis and treatment progress of PICS, which is helpful for further understanding pathogenesis and pathophysiological mechanism of PICS in patients with severe burns and improving clinical curative efficacy and prognosis of patients with severe burns.


Assuntos
Queimaduras/patologia , Queimaduras/terapia , Tolerância Imunológica , Inflamação/patologia , Estado Terminal , Humanos , Síndrome
13.
Life Sci ; 232: 116623, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31279781

RESUMO

AIMS: Doxorubicin, an antibiotic belonging to anthracycline family, has been used for treatment of malignancies. Cardiotoxicity is the main adverse effect of doxorubicin. Apigenin, as a flavonoid, has antioxidant, anti-inflammatory and anti-tumoral properties. The aim of this study was the assessment of any protective effect of apigenin on cardiotoxicity induced by doxorubicin. MAIN METHODS: 40 male Wistar rats were randomly divided into 4 groups: control, cardiotoxicity (DOX), apigenin treated group (DOX + Api 25) and apigenin group (Api 25). At the end of the experiment, the markers of cardiac function (%EF, %FS, LVIDs, LVIDd), cardiac and liver injury (LDH, CK-MB, cTn-I, ALT, and AST), cardiac apoptosis (Bax, Bcl-2 and Caspase3), cardiac oxidative stress (SOD, GSH, MDA) and cardiac fibrosis were measured. KEY FINDINGS: Apigenin improved cardiac functional parameters. The levels of cardiac and liver injury markers were significantly decreased in DOX + Api 25 compared to DOX. Treatment with apigenin caused significant decrease in percentage of cardiac fibrosis in comparison with DOX. Apigenin in DOX + Api 25 group led to significant decrease in apoptotic proteins (Casp3, Bax) and a significant increase in anti-apoptotic proteins (Bcl2). In apigenin treatment groups, SOD levels significantly increased while a significant decrease was observed in MDA. The amount of GSH in DOX + Api 25 had no significant change in comparison to control and Api 25 groups. SIGNIFICANCE: Apigenin reduced cardiac injuries induced by DOX through anti-fibrotic, antioxidant and anti-apoptotic properties. It seems that apigenin prevents cardiac injuries and improves cardiac function.


Assuntos
Apigenina/farmacologia , Cardiotoxicidade/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Apigenina/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Doxorrubicina/efeitos adversos , Doxorrubicina/metabolismo , Flavonoides/farmacologia , Testes de Função Cardíaca , Inflamação/patologia , Masculino , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
14.
Life Sci ; 233: 116696, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31351969

RESUMO

AIMS: To explore the mechanism of how LSD1 regulates autophagy and the correlation between LSD1 and Ox-LDL-induced inflammation. MAIN METHODS: RAW264.7 cells were used during the whole study. Firstly, the effect of Ox-LDL-stimulation on LSD1 expression was detected. Through loss-of-function assay, the associations between LSD1 interference and SESN2 expression, autophagy, NLRP3 inflammasome and inflammatory cytokines were explored. Finally, the function of LSD1 exerted on activation of PI3K/Akt/mTOR signal pathway was detected using western blotting assay. KEY FINDINGS: The expression of LSD1 was significantly elevated in Ox-LDL-treated RAW264.7 cells. Inhibition of LSD1 promoted autophagy, inhibited inflammation and activated NLRP3 inflammasome. SESN2 was elevated by LSD1 inhibition, and thus activate the PI3K/Akt/mTOR signal pathway. What' more, Knockdown of SESN2 or deactivate the PI3K/Akt/mTOR signal pathway partly reversed the effect of LSD1 inhibition on autophagy. SIGNIFICANCE: Our present study drew the finding that the knockdown of LSD1 meliorated Ox-LDL-stimulated NLRP3 activation and inflammation through promoting autophagy via SESN2-mediated PI3K/Akt/mTOR pathway.


Assuntos
Autofagia , Regulação da Expressão Gênica/efeitos dos fármacos , Histona Desmetilases/metabolismo , Inflamação/patologia , Lipoproteínas LDL/efeitos adversos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas Nucleares/metabolismo , Animais , Células Cultivadas , Histona Desmetilases/antagonistas & inibidores , Histona Desmetilases/genética , Inflamação/etiologia , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas Nucleares/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
15.
High Blood Press Cardiovasc Prev ; 26(4): 321-329, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31325087

RESUMO

Cardiovascular disease (CVD) remains the leading cause of morbility and mortality worldwide. The identification of common cardiovascular risk factors has led to the development of effective treatments that enabled a significant reduction of the global cardiovascular disease burden. However, a significant proportion of cardiovascular risk remains unexplained by these risk factors leaving many individuals at risk of cardiovascular events despite good control of the risk factors. Recent randomized clinical trials and Mendelian randomization studies have suggested that inflammation explains a significant proportion of the residual cardiovascular risk in subjects with good control of risk factors. An accelerated process of vascular ageing is increasingly recognized as a potential mechanism by which inflammation might increase the risk of CVD. In turn, cellular ageing represents an important source of inflammation within the vascular wall, potentially creating a vicious cycle that might promote progression of atherosclerosis, independently from the individual cardiovascular risk factor burden. In this review, we summarise current evidence suggesting a role for biological ageing in CVD and how inflammation might act as a key mediator of this association.


Assuntos
Envelhecimento/metabolismo , Doenças Cardiovasculares/metabolismo , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Telômero/metabolismo , Fatores Etários , Envelhecimento/genética , Envelhecimento/patologia , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Senescência Celular , Humanos , Inflamação/genética , Inflamação/patologia , Inflamação/fisiopatologia , Medição de Risco , Fatores de Risco , Transdução de Sinais , Telômero/genética , Telômero/patologia , Homeostase do Telômero , Encurtamento do Telômero , Fatores de Tempo
16.
Expert Opin Investig Drugs ; 28(8): 733-740, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31347405

RESUMO

Introduction: Cachexia is frequent in chronic diseases and especially during cancer development. Multiple definitions of cachexia have been proposed; it may be considered a multifactorial complex syndrome that presents with progressive unintentional weight loss and wasting of muscle mass and adipose tissue. Area covered: This article covers phase-I and phase-II clinical trials of investigational drugs for cancer cachexia. We performed a search on PubMed with keywords as cancer cachexia, phase-I/phase-II trial, drug, identifying articles relevant to this review. Studies were conducted using compounds, including anabolic agents such as ghrelin analogs, selective androgen receptor modulators, as well as anti-inflammatory drugs such as thalidomide, OHR, anti-interleukin antibody, cannabinoids, and omega-3 supplements. We also describe the mechanisms of action of these molecules and their phase-I and phase-II study design. The major outcomes were appetite stimulation, weight gain, improvement of muscle mass and function, modulation of inflammation, and quality of life. Expert opinion: The molecules discussed act on molecular pathways involved in cancer cachexia; they modulate appetite, anabolic effects, inflammation and direct interaction with muscle. Considering the multifactorial aspects of the cachexia syndrome, the combination of these drugs with metabolic and nutritional interventions may represent the most promising therapeutic approach to cancer cachexia.


Assuntos
Caquexia/tratamento farmacológico , Drogas em Investigação/uso terapêutico , Neoplasias/complicações , Apetite/efeitos dos fármacos , Caquexia/etiologia , Caquexia/fisiopatologia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Drogas em Investigação/farmacologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Apoio Nutricional/métodos , Qualidade de Vida , Projetos de Pesquisa
17.
Nat Commun ; 10(1): 2955, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273203

RESUMO

Dendritic cells (DCs), a vital component of the innate immune system, are considered to lack antigen specificity and be devoid of immunological memory. Strategies that can induce memory-like responses from innate cells can be utilized to elicit protective immunity in immune deficient persons. Here we utilize an experimental immunization strategy to modulate DC inflammatory and memory-like responses against an opportunistic fungal pathogen that causes significant disease in immunocompromised individuals. Our results show that DCs isolated from protectively immunized mice exhibit enhanced transcriptional activation of interferon and immune signaling pathways. We also show long-term memory-like cytokine responses upon subsequent challenge with the fungal pathogen that are abrogated with inhibitors of specific histone modifications. Altogether, our study demonstrates that immunization strategies can be designed to elicit memory-like DC responses against infectious disease.


Assuntos
Células Dendríticas/imunologia , Memória Imunológica , Animais , Criptococose/imunologia , Criptococose/microbiologia , Cryptococcus/fisiologia , Células Dendríticas/microbiologia , Feminino , Histonas/metabolismo , Imunidade Inata , Inflamação/genética , Inflamação/patologia , Interferon gama/metabolismo , Pulmão/imunologia , Pulmão/microbiologia , Camundongos Endogâmicos BALB C , Fenótipo , Processamento de Proteína Pós-Traducional , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Vacinação
18.
Nat Commun ; 10(1): 2961, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273197

RESUMO

Persistent inflammation is a hallmark of many human diseases, including anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and atherosclerosis. Here, we describe a dominant trigger of inflammation: human serum factor H-related protein FHR1. In vitro, this protein selectively binds to necrotic cells via its N-terminus; in addition, it binds near necrotic glomerular sites of AAV patients and necrotic areas in atherosclerotic plaques. FHR1, but not factor H, FHR2 or FHR3 strongly induces inflammasome NLRP3 in blood-derived human monocytes, which subsequently secrete IL-1ß, TNFα, IL-18 and IL-6. FHR1 triggers the phospholipase C-pathway via the G-protein coupled receptor EMR2 independent of complement. Moreover, FHR1 concentrations of AAV patients negatively correlate with glomerular filtration rates and associate with the levels of inflammation and progressive disease. These data highlight an unexpected role for FHR1 during sterile inflammation, may explain why FHR1-deficiency protects against certain diseases, and identifies potential targets for treatment of auto-inflammatory diseases.


Assuntos
Proteínas Inativadoras do Complemento C3b/metabolismo , Inflamassomos/metabolismo , Monócitos/metabolismo , Monócitos/patologia , Doenças Vasculares/metabolismo , Doenças Vasculares/patologia , Proteína C-Reativa/metabolismo , Proteínas do Sistema Complemento/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Proteínas Imobilizadas/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Lipoproteínas LDL/metabolismo , Malondialdeído/metabolismo , Modelos Biológicos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Necrose , Ligação Proteica , Receptores Acoplados a Proteínas-G/metabolismo , Soro/metabolismo , Fosfolipases Tipo C/metabolismo
19.
Medicine (Baltimore) ; 98(26): e16188, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261556

RESUMO

Neutrophil to lymphocyte ratio (NLR) is a simple, noninvasive, inexpensive inflammatory marker that can useful in the assessment of inflammatory activity, especially in pediatric ages. The aim of our study was to establish correlations between the presence of Helicobacter pylori (HP) proved histologically and NLR in children.A prospective, case-control study was performed on 137 pediatric patients aged between 1 and 18 years, admitted in a Pediatric Tertiary Hospital from Romania, between April 2016 and January 2018. According to the histologic examination, the children were divided into 2 groups: group 1: 50 children with HP infection, and group 2: 87 children without any pathologic findings.The mean age for the study group was 12.86 ±â€Š3.796 years, whereas for control group, it was 12.10 ±â€Š3.879 years (P = .3001). HP infection was significantly more frequent among children from rural area (P = .0089). Epigastric pain and loss of appetite were significantly associated with HP infection (P = .0350 /P = .0281). We noticed that the leukocyte and neutrophil counts were significantly higher in group 1 (P = .0076/P = .0306). We did not find any significant statistical differences between the 2 groups in terms of lymphocytes, erythrocyte sedimentation rate, and NLR or other assessed laboratory parameters. Regarding the IgA antibodies anti-HP and rapid urease test, they were both significantly associated with histologically confirmed HP infection (P < .0001).Even though, we did not identify significant differences in term of NLR between HP-induced gastritis children and healthy controls, the mean NLR values were higher HP-positive patients.


Assuntos
Gastrite/sangue , Gastrite/imunologia , Adolescente , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Feminino , Gastrite/patologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/patologia , Helicobacter pylori , Humanos , Inflamação/sangue , Inflamação/imunologia , Inflamação/patologia , Masculino , Estudos Prospectivos
20.
Rom J Ophthalmol ; 63(2): 161-165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31334395

RESUMO

Objective: To establish the magnitude of endothelial cells alterations in acute anterior uveitis (AAU) and the clinical impact of local anti-inflammatory treatment. Methods: 27 patients at first episode of unilateral AAU were included. According to the moment of presentation in our departments, two different groups were created, early treatment uveitis group (ETUG) and delayed treatment uveitis group (DTUG). Each patient underwent a corneal endothelial specular microscopy, in both eyes, two weeks after we begun the topical treatment. Results: A statistically significant endothelial cells loss in the uveitis eye was identified in both groups, more important in DTUG. Also, in this group, the pleomorfism, polimegathism and central corneal thickness (CCT) were statistically significant increased. Conclusions: The patients with unilateral AAU and delayed presentation showed more important alterations, first structural and then functional, due to a prolonged inflammatory response. This, in association with other favorable ocular conditions can progress to a permanent corneal endothelial decompensation. The sooner the anti-inflammatory treatment was initiated, the more limited were the destructive processes. Abbreviations: AAU = Acute Anterior Uveitis, ETUG = Early Treatment Uveitis Group, DTUG = Delayed Treatment Uveitis Group, CCT = Central Corneal Thickness, CV = Coefficient of Variation, ECD = Endothelial Cells Density, HEX = Percentage of Hexagonal Cells.


Assuntos
Anti-Inflamatórios/administração & dosagem , Epitélio Posterior/patologia , Inflamação/tratamento farmacológico , Uveíte Anterior/tratamento farmacológico , Doença Aguda , Administração Tópica , Adulto , Contagem de Células , Epitélio Posterior/efeitos dos fármacos , Feminino , Humanos , Inflamação/patologia , Masculino , Soluções Oftálmicas , Uveíte Anterior/diagnóstico
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