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1.
Mol Biol (Mosk) ; 53(5): 755-773, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31661476

RESUMO

Dysregulated proinflammatory cytokine expression may result in the development of severe pathologies, such as rheumatoid arthritis, psoriasis, and neurodegenerative diseases. Transgenic mice and, in particular, those with controllable systemic overexpression of proinflammatory cytokines have recently become an essential instrument to study the molecular mechanisms underlying disease development. Importantly, many of the models are humanized by introducing a human cytokine gene, while leaving or removing the respective endogenous mouse gene. Humanized mice are especially valuable for biomedical research as they provide a relevant model to develop therapies based on blocking the pathogenic activity of a cytokine or to establish the functional significance of genome polymorphisms. The review discusses the available humanized mouse models with overexpression of key proinflammatory cytokines (TNF, IL-ip, and IL-6) and inflammatory cytokines with more specific functions (IL-8, IL-17, and IL-32) and their significance for basic and clinical research.


Assuntos
Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Regulação para Cima , Animais , Artrite Reumatoide/genética , Citocinas/biossíntese , Humanos , Camundongos , Camundongos Transgênicos , Doenças Neurodegenerativas/genética , Psoríase/genética
2.
Medicine (Baltimore) ; 98(40): e17233, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577714

RESUMO

RATIONALE: The pathology of gouty arthritis and reactive arthritis (ReA) partially overlaps, and both diseases are characterized by the production of inflammatory cytokines associated with the activation of monocytes and macrophages. However, the precise cytokine profile of cases with a coexistence of both diseases is unknown, and there are few reports on the course of treatment in patients with both gouty arthritis and ReA. PATIENT CONCERNS: A 39-year-old man with a recurrent episode of gouty arthritis presented prednisolone-resistant polyarthritis with high level of C-reactive protein (CRP). He had the features of gouty arthritis such as active synovitis of the first manifestation of metatarsophalangeal (MTP) joints and the presence of monosodium urate (MSU) crystals from synovial fluid. But he also had the features of ReA such as the presence of tenosynovitis in the upper limb, the positivity of human leukocyte antigen (HLA)-B27, a history of sexual contact and positive findings of anti-Chlamydia trachomatis-specific IgA and IgG serum antibodies. DIAGNOSES: He was diagnosed with HLA-B27 associated Chlamydia-induced ReA accompanied by gout flares. INTERVENTIONS: He was treated with 180 mg/day of loxoprofen, 1 mg/day of colchicine, and 10 mg/day of prednisolone for gout flares. However, his polyarthritis worsened with an increased level of CRP (23.16 mg/dL). Accordingly, we added 500 mg/day of salazosulfapyridine followed by adalimumab (ADA) 40 mg once every 2 weeks. OUTCOMES: After starting ADA, the patient's symptoms and laboratory findings showed rapid improvement and he achieved clinical remission 1 month after initiation of ADA treatment. As of this writing, the patient's clinical remission has been maintained for >1 year. LESSONS: This case suggests that with exacerbation of arthritis during gouty arthritis, coexistence with other pathologies such as peripheral spondyloarthritis should be considered, and early intensive treatment including tumor necrosis factor inhibitors may be necessary.


Assuntos
Artrite Reativa/etiologia , Infecções por Chlamydia/complicações , Gota/complicações , Adulto , Artrite Reativa/tratamento farmacológico , Proteína C-Reativa/análise , Infecções por Chlamydia/tratamento farmacológico , Chlamydia trachomatis , Citocinas/metabolismo , Gota/tratamento farmacológico , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Fator de Necrose Tumoral alfa/antagonistas & inibidores
3.
Toxicol Lett ; 316: 10-19, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31476341

RESUMO

Rapid risk assessment models for different types of cigarette smoke extract (CSE) exposure are critical to understanding the etiology of chronic obstructive pulmonary disease. The present study investigated inflammation of cultured tracheal tissues with CSE exposure. Rat trachea rings were isolated, cultured, then exposed to various concentrations of CSE from 3R4 F reference cigarettes for 4 h. Tissue/cellular morphology, ultrastructure, viability and damage, inflammatory cell infiltration, and inflammatory protein levels were measured and compared to untreated controls. Human bronchial epithelial cells (BEAS-2B) exposed to 0 or 300 µg/mL CSE were cocultured with macrophages to assess extent of mobilization and phagocytosis. Endotracheal epithelium cilia densities were significantly reduced with increasing CSE concentrations, while mucous membranes became increasingly disordered; both eventually disappeared. Macrophages became larger as the CSE concentration increased, with microvilli and extended pseudopodium covering their surface, and many primary and secondary lysosomes present in the cytoplasm. Inflammatory cell infiltration also increased with increasing CSE dose, as did intracellular adhesion molecule-1(ICAM-1), interleukin-6(IL-6). The method described here may be useful to qualitatively characterized the effects of the compound under study. Then, we use BEAS-2B cell line system to strength the observation made in the cultured tissues. Probably, an approach to integrate results from both experiments will facilitate its application. These results demonstrate that cultured rat tracheal rings have a whole-tissue structure that undergoes inflammatory processes similar to in vivo tissues upon CSE exposure.


Assuntos
Células Epiteliais/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/etiologia , Fumaça/efeitos adversos , Fumar/efeitos adversos , Tabaco/efeitos adversos , Traqueia/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Humanos , Mediadores da Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Macrófagos/ultraestrutura , Masculino , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Ratos Sprague-Dawley , Medição de Risco , Fatores de Tempo , Técnicas de Cultura de Tecidos , Traqueia/metabolismo , Traqueia/ultraestrutura
4.
Adv Exp Med Biol ; 1161: 27-35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562619

RESUMO

Surgery can be a life-saving procedure; however, significant complications may occur after routine procedures especially in older and more frail patients. Perioperative neurocognitive disorders (PNDs), including delirium and postoperative cognitive dysfunction, are the most common complications in older adults following common procedures such as orthopedic or cardiac surgery. The consequences of PNDs can be devastating, with longer in-hospital stay, poorer prognosis, and higher mortality rates. Inflammation is gaining considerable interest as a critical driver of cognitive deficits. In this regard, resolution of inflammation, once thought to be a passive process, may provide novel approaches to treat neuroinflammation and PNDs. Herein we review the role for impaired resolution after surgery and the growing role of specialized pro-resolving mediators (SPMs) in regulating postoperative neuroinflammation and neurological complications after surgery.


Assuntos
Mediadores da Inflamação , Transtornos Neurocognitivos , Complicações Pós-Operatórias , Humanos , Inflamação/fisiopatologia , Mediadores da Inflamação/metabolismo , Transtornos Neurocognitivos/fisiopatologia , Período Perioperatório , Complicações Pós-Operatórias/fisiopatologia
5.
Anticancer Res ; 39(9): 5039-5045, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519612

RESUMO

BACKGROUND/AIM: Although complete resection of liver metastases colorectal cancer (CLM) is the only potentially curative treatment, surgery alone is not enough, as the recurrence rate after resection is high. Therefore, in clinical practice, adjuvant chemotherapy is performed after resection of CLM. However, the evidence supporting the efficacy of such adjuvant chemotherapy is not sufficient. Previous reports have noted that adjuvant chemotherapy after resection of CLM is effective only in patients with a high risk of recurrence. The purpose of this study was to classify the risk of recurrence using systemic inflammatory markers reportedly associated with clinical outcomes in patients with various types of malignancies, and evaluate the efficacy of adjuvant chemotherapy according to the risk of recurrence. PATIENTS AND METHODS: The medical records of 119 patients with CLM who underwent potentially curative surgery between 1996 and 2017 were retrospectively reviewed. Preoperative blood samples were obtained within 2 weeks before resection of CLM. was calculated from the blood samples Dividing the serum C-reactive protein level by the serum albumin level derived the C-reactive protein-to-albumin ratio (CAR), reflecting the risk of recurrence. The optimal cut-off value of the CAR was determined according to receiver operating characteristic curve analysis, and then the patients were classified into the high-CAR (high recurrence risk) or low-CAR (low recurrence risk) group. The relationship between the CAR and relapse-free survival after resection of CLM was examined and the efficacy of adjuvant chemotherapy according to the risk of recurrence was evaluated. RESULTS: The cut-off value of the CAR was set at 0.0471. The relapse-free survival rate was significantly better in the low-CAR group than in the high-CAR group. Efficacy of adjuvant chemotherapy after resection of CLM was not recognized in the low-CAR group, whereas the relapse-free survival rates were significantly better for patients who were treated with adjuvant chemotherapy after resection of CLM in the high-CAR group. CONCLUSION: The preoperative CAR, as a systemic inflammatory marker, was found to be useful as a prognostic marker in patients with CLM who were treated with potentially curative resection. Furthermore, it was suggested that adjuvant chemotherapy after resection of CLM may be effective for preventing recurrence in patients with high levels of inflammatory markers who have a high risk of recurrence.


Assuntos
Biomarcadores , Neoplasias Colorretais/patologia , Mediadores da Inflamação/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Recidiva , Estudos Retrospectivos , Adulto Jovem
6.
Adv Exp Med Biol ; 1161: 45-64, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562621

RESUMO

After myocardial infarction, splenic leukocytes direct biosynthesis of specialized pro-resolving mediators (SPMs) that are essential for the resolution of inflammation and tissue repair. In a laboratory environment, after coronary ligation of healthy risk free rodents (young adult mice) leukocytes biosynthesize SPMs with induced activity of lipoxygenases and cyclooxygenases, which facilitate cardiac repair. Activated monocytes/macrophages drive the biosynthesis of SPMs following experimental myocardial infarction in mice during the acute heart failure. In the presented review, we provided the recent updates on SPMs (resolvins, lipoxins and maresins) in cardiac repair that may serve as novel therapeutics for future heart failure therapy/management. We incorporated the underlying causes of non-resolving inflammation following cardiac injury if superimposed with obesity, hypertension, diabetes, disrupted circadian rhythm, co-medication (painkillers or oncological therapeutics), and/or aging that may delay or impair the biosynthesis of SPMs, intensifying pathological remodeling in heart failure.


Assuntos
Insuficiência Cardíaca , Mediadores da Inflamação , Animais , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Inflamação/fisiopatologia , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/uso terapêutico , Leucócitos , Infarto do Miocárdio
7.
Adv Exp Med Biol ; 1161: 65-75, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562622

RESUMO

Inflammation is a fundamentally protective process that guards the host from invading pathogens and is central in the repair and regeneration of damaged tissue. However, when uncontrolled, the overzealous response leads to tissue damage and malaise. Indeed, this process is now appreciated to be at the center of many chronic inflammatory diseases including vascular disease and arthritis. Studies investigating the mechanisms through which acute inflammation is actively turned off allowing tissues to regain function demonstrated that the essential fatty acids, arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are enzymatically converted to bioactive mediators. These autacoids carry distinct structures and biological actions, actively reprogramming the inflammatory reaction to promote its termination by counter-regulating the production of pro-inflammatory mediators and regulate leukocyte trafficking as well as phenotype. Recently we found that n-3 docosapentaenoic acid (DPA), which was until then only regarded as a biosynthetic intermediate in the formation of DHA from EPA, is also converted to structurally distinct bioactive mediators that reprogram the host immune response. In the present review we will discuss the evidence underpinning the biological actions of these novel n-3 DPA-derived autacoids in particular as they pertain to the vascular system.


Assuntos
Vasos Sanguíneos , Inibidores de Hidroximetilglutaril-CoA Redutases , Mediadores da Inflamação , Inflamação , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/fisiologia , Ácidos Docosa-Hexaenoicos/química , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Mediadores da Inflamação/química , Mediadores da Inflamação/metabolismo , Leucócitos/efeitos dos fármacos
8.
Int J Nanomedicine ; 14: 5215-5228, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371957

RESUMO

Background: Resveratrol (RSV) has attracted interest as an alternative drug for the treatment of acute lung injury (ALI) and other pulmonary diseases, but its poor oral bioavailability is a limitation. In this study, we employed drug delivery nanotechnology to improve the stability, lung localization and efficacy of orally administered resveratrol to control lung damage leading to ALI. Methods and materials: RSV-loaded lipid-core nanocapsules (RSV-LNCs), prepared by interfacial deposition of biodegradable polymers, were given orally to A/J mice prior to lipopolysaccharide (LPS) intranasal instillation. Inflammatory changes, oxidative stress and lung tissue elastance were assessed 24 h after LPS challenge. Results: RSV-LNCs (5 mg/kg), given 1, 4, 6 or 12 h but not 24 h before provocation, inhibited LPS-induced leukocyte accumulation in the bronchoalveolar fluid (BALF), whereas unloaded nanocapsules (ULNCs) or free RSV (5 mg/kg) were ineffective. RSV-LNCs (2.5-10 mg/kg) but not ULNCs or RSV improved lung function and prevented total leukocyte and neutrophil accumulation equally in both BALF and lung tissue when given 4 h before LPS challenge. Similar findings were seen concerning the generation of a range of pro-inflammatory cytokines such as IL-6, KC, MIP-1α, MIP-2, MCP-1 and RANTES in lung tissue. In addition, only RSV-LNCs inhibited MDA levels and SOD activity in parallel with blockade of the ERK and PI3K/Akt pathways following LPS provocation. Conclusion: Nanoformulation of RSV in biodegradable oil-core polymers is an effective strategy to improve the anti-ALI activity of RSV, suggesting that the modified-release formulation of this plant polyphenol may be of great value in clinical conditions associated with ALI and respiratory failure.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/enzimologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Nanocápsulas/química , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resveratrol/administração & dosagem , Resveratrol/uso terapêutico , Transdução de Sinais , Lesão Pulmonar Aguda/complicações , Administração Oral , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Masculino , Camundongos Endogâmicos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Hipersensibilidade Respiratória/complicações , Hipersensibilidade Respiratória/patologia , Resveratrol/farmacologia
9.
Life Sci ; 233: 116727, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31381895

RESUMO

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


Assuntos
Inibidores da Angiogênese/farmacologia , Cálcio/farmacologia , Neovascularização de Coroide/prevenção & controle , Mediadores da Inflamação/metabolismo , Inflamação/complicações , Epitélio Pigmentado da Retina/efeitos dos fármacos , Animais , Células Cultivadas , Neovascularização de Coroide/etiologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/metabolismo
10.
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
11.
Medicine (Baltimore) ; 98(34): e15852, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441836

RESUMO

BACKGROUND: The purpose of this study was to investigate the benefits and harm of combined administration of tranexamic acid (TXA) and dexamethasone (Dexa) in total knee arthroplasty (TKA). METHODS: A total of 88 consecutive patients undergoing TKA for knee osteoarthritis were stratified in 2 groups. All surgeries were performed under general anesthesia. Brief, patients in the TXA + Dexa group (n = 45) received 10 mg Dexa just after the anesthesia, and repeated at 24 hours after the surgery; and patients in the TXA group (n = 43) received 2 ml of normal saline solution at the same time. The measured outcomes were the C-reactive protein (CRP) and interleukin-6 (IL-6) from preoperatively to postoperatively, and postoperative nausea and vomiting (PONV), fatigue, range of motion (ROM), length of stay (LOS), and the analgesic and antiemetic rescue consumption RESULTS:: The level of CRP and IL-6 in the TXA + Dexa group were lower than that in the TXA group at 24 hours (P < .001, P < .001), 48 hours (P < .001, P < .001), and 72 hours (P < .001, P < .001) after the surgery. The pain scores in the TXA + Dexa group were lower during walking at 24 hours (P < .001), 48 hours (P < .001), and 72 hours (P < .001) and at rest at 24 hours (P = .022) after the surgery. Patients in the TXA + Dexa group had a lower nausea score, the incidence of PONV, fatigue, and the analgesic and antiemetic rescue consumption, and had a greater ROM than that in the TXA group. No significant differences were found in LOS and complications. CONCLUSION: The combined administration of TXA + Dexa significantly reduced the level of postoperative CRP and IL-6, relieve postoperative pain, ameliorate the incidence of POVN, provide additional analgesic and antiemetic effects, reduce postoperative fatigue, and improve ROM, without increasing the risk of complications in primary TKA.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antifibrinolíticos/uso terapêutico , Artroplastia do Joelho/métodos , Dexametasona/uso terapêutico , Ácido Tranexâmico/uso terapêutico , Idoso , Analgésicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Antieméticos/administração & dosagem , Perda Sanguínea Cirúrgica/prevenção & controle , Proteína C-Reativa/efeitos dos fármacos , Dexametasona/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/biossíntese , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/prevenção & controle , Náusea e Vômito Pós-Operatórios/prevenção & controle , Amplitude de Movimento Articular , Ácido Tranexâmico/administração & dosagem
12.
Medicine (Baltimore) ; 98(34): e16793, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441851

RESUMO

Osteoporosis is a chronic, progressive disease in which early diagnosis is very important. The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have been reported as new predictors in inflammatory and immune diseases including osteoporosis. No studies have reported the relationship between monocyte-to-lymphocyte ratio (MLR) and osteoporosis patients.To investigated the ability of MLR to predict osteoporosis.Three hundred sixteen osteoporosis patients and 111 healthy control subjects were enrolled. Patients' laboratory and clinical characteristics were recorded. MLR, NLR, and PLR levels were calculated. The differences were compared and the diagnostic values of MLR were analyzed.There were 76 male and 105 female patients included, with a mean age of 56.57 ±â€Š9.95 years. The levels of MLR, NLR, and PLR in osteoporosis patients were all higher than those in healthy control subjects. The area under the curve of MLR was higher than those of NLR and PLR. Multivariate linear regression analysis showed that T-score was affected by age and MLR. MLR was positively correlated with C-reactive protein, erythrocyte sedimentation rate, red blood cell distribution width, age, sex, and inversely with hemoglobin. MLR and PLR levels were significantly higher in osteoporosis patients than in osteopenia patients (P < .05).The present study shows that MLR had a higher diagnostic value for osteoporosis. MLR may be a reliable, inexpensive, and novel potential predictor of osteoporosis.


Assuntos
Linfócitos/metabolismo , Monócitos/metabolismo , Osteoporose/sangue , Adulto , Fatores Etários , Idoso , Plaquetas/metabolismo , Sedimentação Sanguínea , Proteína C-Reativa/biossíntese , Estudos Transversais , Feminino , Hemoglobinas/análise , Humanos , Mediadores da Inflamação/metabolismo , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
13.
Medicine (Baltimore) ; 98(32): e16737, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393385

RESUMO

RATIONALE: Giant cell arteritis (GCA) is known to present with typical manifestations like temporal headache and visual abnormalities. However, several cases with atypical manifestations were reported. Stroke occurs in 3% to 7% of patients with GCA. PATIENT CONCERNS: A 67-year-old male patient with known hypertension presented with somnolence, disorientation and mild bilateral limb ataxia. The magnetic resonance imaging showed multiple acute infarctions in the territory of the vertebrobasilar system with occlusion of the left vertebral artery. DIAGNOSIS: Ten months later, during a routine neurovascular follow-up, recanalization of the left vertebral artery was observed and a hypoechoic concentric "halo" sign around both vertebral arteries, mainly on the left side was evident. On further examination of the superficial temporal artery, a hypoechoic concentric "halo" sign was also found, which-along with increased inflammatory markers-raised suspicion about GCA. Classical GCA features like headache, temporal tenderness or amaurosis fugax were not present. Repeated in-depth diagnostic work-up including 48 hours Holter-ECG did not reveal another stroke etiology. INTERVENTIONS: Intravenous Methylprednisolone 250 mg/d was immediately started and after 6 days the dose was tapered to 80 mg/d. The patient was discharged on a tapering scheme with the recommendation to start azathioprine. Additionally, we placed the patient on acetylsalicylic acid 100 mg/d and clopidogrel 75 mg/d. However, the patient was not compliant to treatment; he stopped prednisolone early and did not start azathioprine. OUTCOMES: The inflammatory markers were markedly reduced at the beginning of the treatment. After stopping the immunosuppressive medications, the inflammatory markers were once again increased. Three months later, the patient developed bilateral middle cerebral artery and right occipital lobe infarctions. LESSONS: In patients with cryptogenic vertebrobasilar strokes, GCA may be considered in the differential diagnosis, especially if the inflammatory markers are increased.


Assuntos
Arterite de Células Gigantes/complicações , Acidente Vascular Cerebral/complicações , Artéria Vertebral/patologia , Idoso , Biomarcadores , Arterite de Células Gigantes/tratamento farmacológico , Humanos , Mediadores da Inflamação/metabolismo , Imagem por Ressonância Magnética , Masculino , Metilprednisolona/uso terapêutico
14.
Medicine (Baltimore) ; 98(32): e16470, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393351

RESUMO

We aimed to investigate the correlation of long noncoding RNA nuclear enriched abundant transcript 1 (lnc-NEAT1), microRNA-124 (miR-124) and lnc-NEAT1/miR-124 axis with disease risk, severity, inflammatory cytokines, and survival of sepsis.Eighty-two patients with sepsis and 82 healthy controls (HCs) were consecutively enrolled. Blood samples were collected for detection of lnc-NEAT1 and miR-124 expressions (using RT-qPCR) and measurement of inflammatory cytokines expressions (by ELISA). Severity and organ failure were assessed by acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score, and survival was assessed.Lnc-NEAT1 expression was increased while miR-124 expression was decreased in patients with sepsis compared to HCs, and both of them were able to distinguish patients with sepsis from HCs. For disease condition, lnc-NEAT1 positively associated with APACHE II score, SOFA score, and expressions of C-reactive protein (CRP), procalcitonin, tumor necrosis factor α (TNF-α), and interleukin-1ß (IL-1ß), whereas miR-124 negatively correlated with APACHE II score, SOFA score and levels of serum creatinine (Scr), CRP, TNF-α, IL-1ß, interleukin-6 (IL-6) and interleukin-17 (IL-17). Regarding prognosis, lnc-NEAT1 was upregulated but miR-124 was downregulated in nonsurvivors compared to survivors. Additionally, lnc-NEAT1 negatively correlated with miR-124. Besides, lnc-NEAT1/miR-124 axis was increased in patients with sepsis compared to HCs, and positively associated with APACHE II score, SOFA score, and levels of Scr, CRP, TNF-α, IL-1ß, IL-6, and IL-17, while negatively correlated with survival. Most importantly, lnc-NEAT1/miR-124 axis presented numerically increased predictive value for sepsis risk and survival compared to each index alone.Lnc-NEAT1/miR-124 axis correlates with increased sepsis risk, and associates with higher inflammation, deteriorative disease condition, and decreased survival in patients with sepsis.


Assuntos
Mediadores da Inflamação/metabolismo , RNA Longo não Codificante/biossíntese , Sepse/mortalidade , Sepse/fisiopatologia , APACHE , Adulto , Idoso , Deterioração Clínica , Citocinas/metabolismo , Feminino , Humanos , Masculino , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Índice de Gravidade de Doença
15.
Physiol Rev ; 99(4): 1701-1763, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31339053

RESUMO

Obesity is increasingly prevalent and is associated with substantial cardiovascular risk. Adipose tissue distribution and morphology play a key role in determining the degree of adverse effects, and a key factor in the disease process appears to be the inflammatory cell population in adipose tissue. Healthy adipose tissue secretes a number of vasoactive adipokines and anti-inflammatory cytokines, and changes to this secretory profile will contribute to pathogenesis in obesity. In this review, we discuss the links between adipokine dysregulation and the development of hypertension and diabetes and explore the potential for manipulating adipose tissue morphology and its immune cell population to improve cardiovascular health in obesity.


Assuntos
Tecido Adiposo/fisiopatologia , Pressão Sanguínea , Diabetes Mellitus/fisiopatologia , Hipertensão/fisiopatologia , Obesidade/fisiopatologia , Adipocinas/metabolismo , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Adiposidade , Animais , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/imunologia , Diabetes Mellitus/metabolismo , Humanos , Hipertensão/epidemiologia , Hipertensão/imunologia , Hipertensão/metabolismo , Mediadores da Inflamação/metabolismo , Obesidade/epidemiologia , Obesidade/imunologia , Obesidade/metabolismo , Fenótipo , Medição de Risco , Fatores de Risco , Transdução de Sinais , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia
16.
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
17.
Biosci Biotechnol Biochem ; 83(9): 1655-1662, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31272285

RESUMO

Diabetic retinopathy (DR) is a leading cause of new-onset blindness. Recent studies showed that protecting retinal ganglion cells (RGCs) from high glucose-induced injury is a promising strategy for delaying DR. This study is to investigate the role of miR-145-5p in high glucose-induced RGC injury. Here, RGCs were randomly divided into low glucose and high glucose groups. PCR assay showed miR-145-5p was significantly upregulated in high glucose group. Transfection of miR-145-5p inhibitor decreased pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) levels, elevated cell viability and proliferation, as well as suppressed cell apoptosis by ELISA, MTT, EdU proliferation, colony formation and flow cytometry assays, respectively. Moreover, dual-luciferase reporter assay confirmed FGF5 as a target gene of miR-145-5p. FGF5 knockdown could partially reverse the protective effects of miR-145-5p on RGC-5 cells. In conclusion, our results demonstrated that inhibition of miR-145-5p might be a neuroprotective target for diabetes mellitus-related DR. Abbreviations: DR: diabetic retinopathy; RGCs: retinal ganglion cells; miR-145-5p: microRNA-145-5p; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6; FGF: fibroblast growth factor; ATCC: American Type Culture Collection; WT: wild type; MUT: mutant type.


Assuntos
Sobrevivência Celular , Retinopatia Diabética/patologia , Regulação para Baixo , Fator 5 de Crescimento de Fibroblastos/metabolismo , MicroRNAs/metabolismo , Células Ganglionares da Retina/metabolismo , Apoptose , Linhagem Celular , Citocinas/metabolismo , Retinopatia Diabética/metabolismo , Fator 5 de Crescimento de Fibroblastos/genética , Glucose/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Células Ganglionares da Retina/citologia
18.
Life Sci ; 232: 116677, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31340166

RESUMO

AIMS: Senescence is a state ensuing aging to eliminate age-associated damage with an irreversible cell-cycle arrest mechanism, which is historically believed to be one of the tumor responses to therapy. Doxorubicin as an anti-cancer drug has been used in cancer treatment for a long time. Liposomal doxorubicin (Ldox) is a liposomal formulation of doxorubicin, which increases the doxorubicin permanency. The aim of this study was to examine the toxicity of these two formulations by comparing them in terms of their ability to induce cellular senescence. MAIN METHODS: The study groups included a control group, three DOX (0.75, 0.5, 0.1 mg/kg/BW) and three Ldox groups (0.1, 0.05, 0.025 mg/kg/BW). Heart tissues were studied regarding oxidative stress assessment, mitochondrial function, inflammatory markers and biochemical and histopathological evaluation. Real-Time PCR was used for P53 and SA ß-gal expression. KEY FINDINGS: Based on the results, the highest doses of Dox and Ldox (0.75 and 0.1 mg/kg/BW respectively) significantly increased the level of inflammatory markers and according to other factors especially p53 and SA ß-gal expression, both were able to induce senescence but the changes in Ldox were less tangible than the Dox.


Assuntos
Senescência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , NF-kappa B/metabolismo , Animais , Biomarcadores/metabolismo , Doxorrubicina/análogos & derivados , Glutationa Peroxidase/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53/metabolismo
19.
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
20.
Toxicol Lett ; 314: 89-97, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31325635

RESUMO

Ethanol is a key factor in the pathogenesis of alcoholic liver disease (ALD), commonly characterized as liver inflammation. Recently, circular (circ)RNAs have emerged as important targets to cure liver diseases. However, there are no studies investigating the role of circ_1639 in reducing inflammatory responses in ALD. In this study, we found that circ_1639 was upregulated in Kupffer cells from the livers of alcohol fed mice. We hypothesized that circ_1639 inhibition is a potential novel therapy for treating ALD. To test this hypothesis, RAW 264.7 cells were treated with ethanol and transfected with circ_1639 overexpression or knockdown plasmids. We present western blotting, qRT-PCR, and ELISA data that suggest that circ_1639 is a proinflammatory factor in the liver and is involved in the activation of the NF-κB signaling pathway. Using luciferase reporter assay, we confirmed that microRNA (miR)-122 is a target gene of circ_1639. We also show that TNFRSF13C is a key regulator of RAW 264.7 cell activation, and acts as a downstream target for miR-122. In summary, our results suggest that inhibition of circ_1639 expression may reduce inflammatory responses in ALD.


Assuntos
Mediadores da Inflamação/metabolismo , Hepatopatias Alcoólicas/metabolismo , Fígado/metabolismo , MicroRNAs/metabolismo , RNA/metabolismo , Animais , Receptor do Fator Ativador de Células B/genética , Receptor do Fator Ativador de Células B/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Macrófagos do Fígado/metabolismo , Fígado/patologia , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/prevenção & controle , Ativação de Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Células RAW 264.7 , RNA/genética , Transdução de Sinais
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