RESUMO
PURPOSE: As a well-known cardioprotective factor, the relevance of adiponectin (APN) to heart function following sepsis remains largely unknown. The present study evaluated the effects of plasma APN levels on heart function and 28-day mortality in sepsis patients. MATERIALS AND METHODS: This was a prospective study that was performed with 98 patients with sepsis and 32 controls. Left ventricular systolic dysfunction (LVSD) was defined as a left ventricular ejection fraction (LVEF) ≤ 45% based on echocardiography. The effects of APN on the development of sepsis-related LVSD and prediction of 28-day mortality were evaluated. RESULTS: Plasma APN levels significantly decreased in sepsis patients compared with controls, with rising severity of illness, and positively correlated with the LVEF and stroke volume index. Sepsis patients with LVSD had lower APN levels than patients without LVSD. According to the receiver operating characteristic curve, plasma APN levels had the comparable value in prediction of LVSD incidence than those conditional factors, including brain natriuretic peptide (BNP) and highly sensitive cardiac troponin T (hsTnT). Twenty-three of the 98 sepsis patients (23.47%) died at 28 days. Adiponectin levels were an independent predictive factor for 28-day mortality. CONCLUSIONS: Low APN levels were associated with the incidence of LVSD and 28-day mortality in sepsis patients. Adiponectin may be a novel factor that may be useful for the diagnosis of LVSD.
Assuntos
Adiponectina/sangue , Sepse/sangue , Sepse/epidemiologia , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pequim/epidemiologia , Biomarcadores/sangue , Comorbidade , Ecocardiografia/métodos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Escores de Disfunção Orgânica , Estudos Prospectivos , Curva ROC , Sepse/mortalidade , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/mortalidade , Adulto JovemRESUMO
Fine particulate matter (PM2.5) is the primary air pollutant that is able to induce airway injury. Compelling evidence has shown the involvement of IL-17A in lung injury, while its contribution to PM2.5-induced lung injury remains largely unknown. Here, we probed into the possible role of IL-17A in mouse models of PM2.5-induced lung injury. Mice were instilled with PM2.5 to construct a lung injury model. Flow cytometry was carried out to isolate γδT and Th17 cells. ELISA was adopted to detect the expression of inflammatory factors in the supernatant of lavage fluid. Primary bronchial epithelial cells (mBECs) were extracted, and the expression of TGF signalling pathway-, autophagy- and PI3K/Akt/mTOR signalling pathway-related proteins in mBECs was detected by immunofluorescence assay and Western blot analysis. The mitochondrial function was also evaluated. PM2.5 aggravated the inflammatory response through enhancing the secretion of IL-17A by γδT/Th17 cells. Meanwhile, PM2.5 activated the TGF signalling pathway and induced EMT progression in bronchial epithelial cells, thereby contributing to pulmonary fibrosis. Besides, PM2.5 suppressed autophagy of bronchial epithelial cells by up-regulating IL-17A, which in turn activated the PI3K/Akt/mTOR signalling pathway. Furthermore, IL-17A impaired the energy metabolism of airway epithelial cells in the PM2.5-induced models. This study suggested that PM2.5 could inhibit autophagy of bronchial epithelial cells and promote pulmonary inflammation and fibrosis by inducing the secretion of IL-17A in γδT and Th17 cells and regulating the PI3K/Akt/mTOR signalling pathway.
Assuntos
Interleucina-17/biossíntese , Material Particulado/efeitos adversos , Pneumonia/etiologia , Pneumonia/metabolismo , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Suscetibilidade a Doenças , Células Epiteliais , Humanos , Masculino , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Pneumonia/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fibrose Pulmonar/patologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Transdução de Sinais , Fator 1 de Transcrição de Linfócitos T/imunologia , Fator 1 de Transcrição de Linfócitos T/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
OBJECTIVE: To investigate the impact of death-associated protein kinase 1 (Dapk1) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) via p38MAPK/NF-κB pathway. METHODS: Dapk1+/+ and Dapk1-/- mice were randomized into Control, LPS, SB203580 (a p38MAPK pathway inhibitor) + LPS, and PDTC (a NF-κB pathway inhibitor) + LPS groups. Cell counts, lung wet to dry weight ratio (W/D weight ratio), as well as indicators of oxidative stress were determined followed by the detection with HE staining, ELISA, qRT-PCR, Western blotting and Immunofluorescence. Besides, to explore whether the effect of Dapk1 on ALI directly mediated via p38MAPK/NF-κB pathway, mice were injected with TC-DAPK 6 (a Dapk1 inhibitor) with or without SB203580/PDTC before LPS administration. RESULTS: LPS induced lung injury with increased lung W/D weight ratio, which could be partly reversed by SB203580 and PDTC in LPS-induced mice with activated p38MAPK/NF-κB pathway in lung tissues, especially in Dapk1-/- mice. SB203580 and PDTC reduced total cells and neutrophils in BALF in LPS-induced mice, accompanying with decreased levels of TNF-α, IL-6, MPO, LPO and MDA and the expressions of beclin-1, Atg5 and LC3II, but with the up-regulated activities of SOD and GSH-Px, as well as p62 protein expression. Besides, TC-DAPK 6 aggravated the pathologic injury in LPS-induced ALI with more serious inflammatory response, oxidative stress and autophagy as well as the activated p38MAPK/NF-κB pathway, which were reversed by SB203580 or PDTC. CONCLUSION: Dapk1 improved oxidative stress, inhibited autophagy, and reduce inflammatory response of LPS-induced ALI mice by inhibiting p38MAPK/NF-κB pathway.
Assuntos
Lesão Pulmonar Aguda/metabolismo , Proteínas Quinases Associadas com Morte Celular/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Autofagia , Proteínas Quinases Associadas com Morte Celular/deficiência , Proteínas Quinases Associadas com Morte Celular/genética , Imidazóis/farmacologia , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Estresse Oxidativo , Piridinas/farmacologia , Pirrolidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tiocarbamatos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: Whitmania pigra Whitman (W pigra), a traditional Chinese medicine, has functions of breaking stagnant and eliminating blood stasis. The aim of this study was to investigate the underlying mechanism of W pigra against deep vein thrombosis (DVT). METHODS: A rat model of DVT induced by inferior vena cava stenosis was successfully established. Rats were administered vehicle (saline solution, p.o.), three doses of W pigra aqueous extract (34.7, 104.2, or 312.5 mg crude W pigra/kg, p.o.), heparin (200 U/kg, i.v.), or clopidogrel (25 mg/kg, p.o.) once daily for 2 d. Thrombus weight and histopathological changes were examined. Blood samples were collected to determine blood cell counts, blood viscosity, blood coagulation, blood fibrinolysis, serum levels of interleukin-1ß, and tumor necrosis factor-α. Protein expressions of Sirtuin1 (SIRT1), acetylated p65 (Ace-p65), and phosphorylated p65 (p-p65) were determined by Western blot. Furthermore, SIRT1-specific inhibitor EX527 was applied to confirm the role of SIRT1 in the antithrombotic effect of W pigra. RESULTS: W pigra significantly decreased thrombus weight. W pigra had no effects on blood cell counts, whole blood viscosity, blood coagulation, blood fibrinolysis. However, it reduced tissue factor protein expression in the vein wall and thrombus. Moreover, it sharply increased SIRT1 protein expression and decreased leukocytes recruitment in the thrombus and vein wall, serum levels of interleukin-1ß and tumor necrosis factor-α, and protein expressions of Ace-p65 and p-p65. Furthermore, the antithrombotic effect of W pigra was significantly abolished by EX527. CONCLUSIONS: Aqueous extract of W pigra effectively reduced DVT burden by inhibiting inflammation via SIRT1/nuclear factor-kappa B signaling pathway.
Assuntos
Produtos Biológicos/uso terapêutico , Sanguessugas , NF-kappa B/metabolismo , Sirtuína 1/metabolismo , Trombose Venosa/tratamento farmacológico , Animais , Produtos Biológicos/farmacologia , Carbazóis , Citocinas/sangue , Avaliação Pré-Clínica de Medicamentos , Feminino , Inflamação/tratamento farmacológico , Masculino , Medicina Tradicional Chinesa , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/antagonistas & inibidores , Tromboplastina/metabolismo , Trombose Venosa/metabolismoRESUMO
We evaluated the effects of Klotho on pulmonary vascular remodeling and cell proliferation and apoptosis in rat models with PM2.5-induced pulmonary arterial hypertension (PAH) via the Wnt signaling pathway. After establishing rat models of PM2.5-induced PAH, these Sprague-Dawley male rats were randomized into control and model groups. Cells extracted from the model rats were sub-categorized into different groups. Activation of Wnt/ß-catenin signaling transcription factor was detected by a TOPFlash/FOPFlash assay. A serial of experiment was conducted to identify the mechanism of Klotho on PHA via the Wnt signaling pathway. VEGF levels and PaCO2 content were higher in the model group, while PaO2, NO2- /NO3- content and Klotho level was lower compared to the control group. In comparison to the control group, the model group had decreased Klotho and Bax levels, and elevated Wnt-1, ß-catenin, bcl-2, survivin, and PCNA expression, VEGF, IL-6, TNF-α, TNF-ß1, and bFGF levels, as well as the percentage of pulmonary artery ring contraction. The Klotho vector, DKK-1 and DKK-1 + Klotho vector groups exhibited reduced cell proliferation, luciferase activity, and the expression of Wnt-1, ß-catenin, bcl-2, survivin, and PCNA, as well as shortened S phase compared with the blank and NC groups. Compared with the Klotho vector and DKK-1 groups, the DKK-1 + Klotho vector groups had reduced cell proliferation, luciferase activity, and the expression of Wnt-1, ß-catenin, bcl-2, survivin, and PCNA, as well as a shortened S phase. Conclusively, Klotho inhibits pulmonary vascular remodeling by inactivation of Wnt signaling pathway.
Assuntos
Glucuronidase/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Material Particulado/toxicidade , Artéria Pulmonar/efeitos dos fármacos , Remodelação Vascular/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Apoptose , Ciclo Celular , Proliferação de Células , Células Cultivadas , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Proteínas Klotho , Masculino , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Ratos , Ratos Sprague-Dawley , Regulação para CimaRESUMO
OBJECTIVE: This report aimed to review the angiographic characteristics and evaluate the safety and feasibility of endovascular treatment of A1 aneurysms. METHODS: Nineteen ruptured and 13 unruptured A1 aneurysms treated endovascularly were evaluated in this study. The angiographic and clinical records were retrospectively reviewed. RESULTS: Endovascular treatments were successfully applied in all 32 aneurysms. Conventional coiling was performed in 24 aneurysms, stent-assisted coiling in 7, and solo stenting in 1. The immediate angiographic result was 1 aneurysm in 15, two aneurysms in 10, and 3 in 7 aneurysms according to the Raymond grade. Intraoperative rupture was detected in 1 case without clinical consequence, and no other procedure-related complication occurred. Angiographic follow-up (mean, 12 months; range, 2-42 months) of 25 aneurysms showed total occlusion in 20, improvement in 1, stability in 3, and recurrence in 1. The only recurrence was detected in a case treated using conventional coiling, and it was retreated with stent-assisted coiling. Clinical follow-up (mean, 25 months; range, 6-93 months) was available in 24 of 30 patients, and the modified Rankin Scale score was 0-1 in 22 patients. CONCLUSIONS: Endovascular treatment is technically feasible and safe for A1 aneurysms.
Assuntos
Angiografia Cerebral , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Stents , Adulto , Idoso , Procedimentos Endovasculares/instrumentação , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Context The roots of Ilex asprella (Hook. et Arn.) Champ. ex Benth. (Aquifoliaceae) are widely used in Chinese medicine to treat influenza, amygdalitis, pertussis, etc. Their mechanism of action is still unknown, which raises the need to identify new bioactive compounds in this plant. Objective In this study, we isolated a novel saponin containing sulphonic groups, namely, asprellcoside A (1) and a known phenolic glycoside compound (2) from the roots of Ilex asprella and evaluated their bioactivities. Materials and methods Molecular structures were elucidated by analysing their spectral and chemical properties. The viability of A549 cells was tested using a MTT assay. Ability of the compounds to inhibit viruses was determined using the neuraminidase activity assay. Their anti-inflammatory effects were tested using the IP-10 activity assay using various concentrations (compound 1: 0.6, 0.2, 0.6, 1.70, 5.00 and 15.00 µM; compound 2: 0.4, 1.2, 3.6, 11.0, 33.0 and 100 µM). Their inhibitory effect on platelet aggregation induced by adenosine diphosphate (ADP) in rabbit plasma was determined at 60 and 80 µM. Results Both compounds inhibit influenza virus strain A/PuertoRico/8/1934 (H1N1) strongly with EC50 values of 4.1 and 1.7 µM, respectively. Both compounds inhibit the secretion of IP-10 with EC50 values of 6.6 and 2.5 µM, respectively. Compound 1 alone inhibited platelet aggregation significantly, with the rate of suppression being 47 ± 8 and 38 ± 3%, at 60 and 80 µM, respectively. Conclusions The results suggest that both compounds may be valid therapeutics against influenza virus infection and that compound 1 may be a novel agent for treating thrombosis.
Assuntos
Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Glicosídeos/farmacologia , Extratos Vegetais/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antivirais/química , Antivirais/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Cães , Relação Dose-Resposta a Droga , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Ilex/química , Mediadores da Inflamação/metabolismo , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/enzimologia , Células Madin Darby de Rim Canino , Estrutura Molecular , Neuraminidase/antagonistas & inibidores , Neuraminidase/metabolismo , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas , Plantas Medicinais , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/isolamento & purificação , Coelhos , Relação Estrutura-AtividadeRESUMO
Fenestrated vertebrobasilar junction-related aneurysms (fVBJ-AN) are uncommon and endovascular management strategies have become the first options for the treatment of these lesions. This clinical study aimed to report our experience in the endovascular management of these lesions and to review the literature. We retrospectively reviewed 10 consecutive patients harboring 12 fVBJ-AN between January 2007 and December 2014. The demographic, angiographic and clinical data were reviewed. Additionally, a literature review was performed. Endovascular management strategies were successfully applied in all 10 patients. Post-procedural angiograms indicated total occlusion in eight (66.7%) aneurysms, a residual neck in one (8.3%) aneurysm, and three residual aneurysms (25%). No procedure-related complications were observed. Follow-up angiograms were obtained in eight patients and revealed nine occluded aneurysms and one improved aneurysm; two patients were lost to angiographic follow-up. Clinical follow-ups were obtained in all patients (until July 2015), and the modified Rankin Scale scores at 69.5months (range 17-101months) of follow-up were 0 in eight patients and 1 in two patients. Endovascular management strategies provided a high occlusion rate and an acceptable complication rate and are thus efficacious in the treatment of fVBJ-AN. Further studies are necessary to validate the utility of these treatments due to the low incidence of fVBJ-AN.
Assuntos
Embolização Terapêutica/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Aneurisma Intracraniano/terapia , Adulto , Idoso , Angiografia Cerebral , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , StentsRESUMO
PURPOSE: To report the feasibility of parametric color-coded digital subtraction angiography (DSA) in complementing the traditional, subjective way of leptomeningeal collateral assessment in acute middle cerebral artery (MCA) occlusions. METHODS: Thirty-three consecutive patients with acute MCA occlusion who received endovascular treatment were recruited for investigation. Eighteen of 33 consecutive patients were included. The target downstream territory (TDT) of MCA and reference point at terminal internal carotid artery of each patient was contoured by 5 raters independently on the basis of anteroposterior 2-dimensional DSA. Two parameters of relative maximum density of TDT (rDensitymax) and peak time interval (ΔPT) between reference and TDT were extracted by the use of parametric DSA analysis software. Interrater reliability was tested with intraclass correlation coefficients. Parameters with sufficient interrater reliability entered validity evaluation. Then, the correlation test with the American Society of Interventional and Therapeutic Neuroradiology collateral grading system and efficacy in predicting favorable clinical outcome was evaluated. RESULTS: The intraclass correlation coefficient of rDensitymax and ΔPT were 0.983, 95% confidence interval 0.968-0.993 and 0.831, 95% confidence interval 0.705-0.923, respectively. The parameter rDensitymax showed a strong correlation with the American Society of Interventional and Therapeutic Neuroradiology collateral grading system score (r of Spearman correlation test = 0.869, P < 0.001) and mRS at 3 months (partial correlation coefficient = 0.616, P = 0.009), whereas ΔPT_average did not. A cut-off point of 0.224 in rDensitymax predicted a favorable clinical outcome with high sensitivity and specificity. CONCLUSIONS: The relative maximum contrast density of MCA territory on 2-dimensional DSA measured by parametric imaging technique appears to be a simple and reliable metric for the assessment of leptomeningeal collaterals in cases of acute MCA occlusion.
Assuntos
Angiografia Digital/métodos , Angiografia Cerebral/métodos , Circulação Cerebrovascular , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/terapia , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo , Circulação Colateral , Procedimentos Endovasculares , Feminino , Humanos , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Método Simples-Cego , Resultado do TratamentoRESUMO
PURPOSE: The treatment of ruptured vertebral artery dissecting aneurysms (VADAs) continues to be controversial. Our goal was to evaluate the safety, efficacy, and long-term outcomes of internal trapping and stent-assisted coiling (SAC) for ruptured VADAs distal to the posterior inferior cerebellar artery (supra-PICA VADAs), which is the most common subset. METHODS: A retrospective review was conducted of 39 consecutive ruptured supra-PICA VADAs treated with internal trapping (n = 20) or with SAC (n = 19) at our institution. The clinical and angiographic data were retrospectively compared. RESULTS: The immediate total occlusion rate of the VADAs was 80 % in the trapping group, which improved to 88.9 % at the follow-ups (45 months on average). Unwanted occlusions of the posterior inferior cerebellar artery (PICA) were detected in three trapped cases. Incomplete obliteration of the VADA or unwanted occlusions of the PICA were detected primarily in the VADAs closest to the PICA. In the stenting group, the immediate total occlusion rate was 47.4 %, which improved to 100 % at the follow-ups (39 months on average). The immediate total occlusion rate of the VADAs was higher in the trapping group (p < 0.05), but the later total occlusion was slightly higher in the stenting group (p > 0.05). CONCLUSIONS: Our preliminary results showed that internal trapping and stent-assisted coiling are both technically feasible for treating ruptured supra-PICA VADAs. Although not statistically significant, procedural related complications occurred more frequently in the trapping group. When the VADAs are close to the PICA, we suggest that the lesions should be treated using SAC.
Assuntos
Aneurisma Roto/terapia , Embolização Terapêutica , Aneurisma Intracraniano/terapia , Stents , Dissecação da Artéria Vertebral/terapia , Adulto , Aneurisma Roto/diagnóstico por imagem , Angiografia Cerebral , Artérias Cerebrais/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ruptura Espontânea , Resultado do Tratamento , Artéria Vertebral/diagnóstico por imagem , Dissecação da Artéria Vertebral/diagnóstico por imagemRESUMO
OBJECTIVE: To investigate the effects of superfine comminution extraction technology of ginseng total saponins from Panax ginseng fibrous root, and to make sure the optimal extraction condition. METHODS: Optimal condition of ginseng total saponins from Panax ginseng fibrous root was based on single factor experiment to study the effects of crushing degree, extraction time, alcohol concentration and extraction temperature on extraction rate. Response surface method was used to investigate three main factors such as superfine comminution time, extraction time and alcohol concentration. RESULTS: The relationship between content of ginseng total saponins in Panax ginseng fibrous root and three factors fitted second degree polynomial models. The optimal extraction condition was 9 min of superfine comminution time, 70% of alcohol, 50 degrees C of extraction temperature and 70 min of extraction time. Under the optimal condition, ginseng total saponins from Panax ginseng fibrous root was average 94. 81%, which was consistent with the predicted value. CONCLUSION: The optimization of technology is rapid, efficient, simple and stable.
Assuntos
Panax/química , Raízes de Plantas/química , Plantas Medicinais/química , Saponinas/química , Tecnologia Farmacêutica/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Etanol/química , Tamanho da Partícula , Saponinas/isolamento & purificação , Solubilidade , Temperatura , Fatores de TempoRESUMO
OBJECTIVE: Interleukin (IL)-1ß and IL-18 are key proinflammatory cytokines that play important roles in the pathophysiology of vein graft remodeling. However, the mechanism of IL-1ß/IL-18 production and its role in the development of graft remodeling remain unclear. APPROACH AND RESULTS: IL-1ß/IL-18 were rapidly expressed in venous interposition grafts. Vascular smooth muscle cell (VSMC) death and monocytic inflammasome activation occurred in grafted veins. Necrotic VSMCs induced the expression of IL-1ß, IL-18, and other inflammasome-associated proteins in monocytes, which was partially inhibited by their antagonist, recombinant IL-1ra-Fc-IL-18bp. Activated monocytes stimulated proliferation of VSMCs by activating cell growth-related signaling molecules (AKT, STAT3, ERK1/2, and mTOR [AKT/protein kinase B, signal transducer and activator of transcription 3, extracellular signal-regulated kinase 1/2, mammalian target of rapamycin]) and increasing production of platelet-derived growth factor-bb; these effects were suppressed by IL-1ra-Fc-IL-18bp. Activated monocytes also promoted migration of VSMCs, which was independent of IL-1ß/IL-18 signaling. Importantly, administration of IL-1ra-Fc-IL-18bp inhibited activation of cell growth-related signaling molecules, VSMC proliferation, and vein graft thickening in vivo. CONCLUSIONS: Our work identified an interaction among necrotic VSMCs, monocytes, and viable VSMCs through IL-1ß/IL-18 signaling, which might be exploited as a therapeutic target in vein graft remodeling.
Assuntos
Implante de Prótese Vascular , Artérias Carótidas/cirurgia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Interleucina-18/fisiologia , Interleucina-1beta/fisiologia , Monócitos/citologia , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/citologia , Neointima , Proteínas Recombinantes de Fusão/farmacologia , Transdução de Sinais/fisiologia , Veia Cava Superior/transplante , Animais , Apoptose , Linhagem Celular Tumoral , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Humanos , Inflamassomos/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Interleucina-18/biossíntese , Interleucina-18/genética , Interleucina-1beta/biossíntese , Interleucina-1beta/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/metabolismo , Miócitos de Músculo Liso/metabolismo , Necrose , RNA Mensageiro/biossíntese , Proteínas Recombinantes de Fusão/uso terapêutico , Veia Safena/citologia , Organismos Livres de Patógenos Específicos , Veia Cava Superior/metabolismoRESUMO
OBJECTIVE: Blood blister-like aneurysms (BBAs) are unique due to their high risk of recurrent bleeding associated with their fragile neck. The best treatment for BBAs is still controversial. This paper sought to evaluate the safety and efficacy of stent-assisted coiling and subsequent overlapping stents (SAC+OS) in the treatment of BBAs. METHODS: Fifteen consecutive patients with ruptured BBAs managed with SAC+OS were enrolled in this study. The clinical characteristics, procedural data, angiographic outcome, and follow-up results were reviewed. RESULTS: SAC+OS were successfully performed in all 15 cases. The instant angiographic result was total occlusion in 6 cases, residual neck in 7 cases, and residual aneurysm in 2 cases. Angiographic follow-ups revealed total occlusion in all 6 cases treated by triple or quadruple stents, and 6 of 9 cases treated by double stents. Major recanalization was detected in 3 cases treated by double stents. The modified Rankin Scale score at 4-52 months follow-up (23.8 months on average) was 0 in 6 cases, 1 in 8 cases, and 3 in one case. CONCLUSION: Stent-assisted coiling and subsequent overlapping stents are feasible and safe for BBAs. It can be helpful to further decrease the risk of recanalization with more stents. Early angiographic follow-up within 2 weeks is recommended.
Assuntos
Aneurisma Roto/cirurgia , Vesícula/cirurgia , Artéria Carótida Interna/cirurgia , Aneurisma Intracraniano/cirurgia , Stents , Adulto , Aneurisma Roto/complicações , Vesícula/diagnóstico , Angiografia Cerebral/métodos , Embolização Terapêutica/métodos , Feminino , Humanos , Aneurisma Intracraniano/complicações , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Small anterior communicating artery aneurysms with recurrent bleeding and adjacent hematoma may have a high risk of post-operative rebleeding. This clinical study summarizes our preliminary experience with this subset of aneurysms, which were treated with endovascular coiling and subsequent Onyx 34 embolization. METHODS: We retrospectively reviewed the data of 9 patients suffering from small anterior communicating artery aneurysms treated with the combination of coils and Onyx. The clinical characteristics, angiographic outcomes, and follow-up results are reviewed. RESULTS: Endovascular coiling and Onyx embolization were successfully accomplished in all 9 cases. The Raymond scale ratings of the treatments are all class I with the parent arteries kept patent. One patient died of severe brain edema on the 5th post-operative day. The modified Rankin scale (mRS) score for the other 8 patients at follow-ups (6m to 26m, 15.8m on average) was 0 in 5 cases, 1 in 2 cases, and 3 in 1 case. Seven of 8 patients (87.5%) underwent angiographic follow-up that demonstrated persistent durable occlusion with no recanalization. CONCLUSIONS: Endovascular coiling and subsequent Onyx 34 embolization may be effective in treating anterior communicating artery aneurysms with adjacent hematoma. Further studies with larger sample size and adequate follow-up are required to verify its safety and efficacy as well as to evaluate the long-term outcome.
Assuntos
Aneurisma Roto/cirurgia , Dimetil Sulfóxido/uso terapêutico , Embolização Terapêutica , Procedimentos Endovasculares , Hematoma/cirurgia , Aneurisma Intracraniano/cirurgia , Polivinil/uso terapêutico , Tantálio/uso terapêutico , Adulto , Aneurisma Roto/complicações , Embolização Terapêutica/métodos , Feminino , Seguimentos , Hematoma/complicações , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The proliferation of cardiac fibroblasts (CFs) is a key pathological process in the cardiac remodeling. To establish an objective, quantitative method for the analysis of cell proliferation and cell cycle, we applied the high-content screening (HCS) and flow cytometry (FCM) techniques. CFs, isolated by enzyme digestion from newborn C57BL/6J mice, were serum starved for 12 h and then given 10% fetal bovine serum (FBS) for 24 h. Followed by BrdU and DAPI (or 7-AAD) staining, CFs proliferation and cell cycle were analyzed by HCS and FCM, respectively. Discoidin domain receptor 2 (DDR2) staining indicated that the purity of isolated CFs was over 95%. (1) HCS analysis showed that the ratio of BrdU-positive cells was significantly increased in 10% FBS treated group compared with that in serum-free control group [(12.96 ± 0.67)% vs (2.77 ± 0.33)%; P < 0.05]. Cell cycle analysis showed that CFs in G0/G1 phase were diploid, and CFs in S phase were companied with proliferation, DNA replication and enlarged nuclei; CFs in G2 phase were tetraploid, and CFs in M phase produced two identical cells (2N). (2) FCM analysis showed that the ratio of BrdU-positive cells was increased in 10% FBS treated group compared with that in the control group [(11.10 ± 0.42)% vs (2.22 ± 0.31)%; P < 0.05]; DNA content histogram of cell cycle analysis indicated that the platform of S phase elevated in 10% FBS group compared with control group. (3) There were no differences between the two methods in the results of proliferation and cell cycle analysis. In conclusion, HCS and FCM methods are reliable, stable and consistent in assessment of the proliferation and cell cycle in CFs.
Assuntos
Proliferação de Células , Fibroblastos/citologia , Citometria de Fluxo , Miocárdio/citologia , Animais , Ciclo Celular , Camundongos , Camundongos Endogâmicos C57BL , MitoseRESUMO
OBJECTIVE: Delayed or impaired reendothelialization is a major cause of stent thrombosis in the interventional treatment of coronary heart disease. T cells are involved in neointima formation of injured arteries. However, the regulated mechanism of reendothelialization and the role of CD8 T cell in reendothelialization are unclear. METHODS AND RESULTS: Immunofluorescence staining showed that CD8 positive cells were increased in wire injured femoral artery of mice. On day 21 after injury, elastin staining showed that knockout of CD8 (CD8(-/-)) significantly increased intimal thickness and a ratio of intima to media by 1.8 folds and 1.9 folds respectively in injured arteries. Evans blue staining showed that knockout of CD8 delayed the reendothelialization area on day 7 after injury (18.8±0.5% versus 42.1±5.6%, p<0.05). In vitro, a migration assay revealed that CD8(-/-) T cells co-cultured with WT macrophages significantly inhibited the migration of the endothelial cells (ECs); compared to CD4(+) T cells, and CD8(+) T cells could promote the ECs migration. Furthermore, real-time PCR analysis showed that knockout of CD8 increased the level of tumor necrosis factor α (TNF-α) in injured arteries and cytometric bead cytokine array showed that TNF-α was elevated in cultured CD8(-/-) T cells. Finally, a wound-healing assay showed that recombinant TNF-α significantly inhibited the migration of ECs. CONCLUSION: Our study suggested that CD8(+) T cells could promote the reendothelialization and inhibit the neointima formation after the artery wire injury, and this effect is at least partly dependent on decreasing TNF-α production promoting ECs migration.
Assuntos
Antígenos CD8/genética , Movimento Celular/efeitos dos fármacos , Células Endoteliais/patologia , Artéria Femoral/lesões , Técnicas de Inativação de Genes , Neointima/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Animais , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Células Endoteliais/efeitos dos fármacos , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/metabolismo , Artéria Femoral/patologia , Deleção de Genes , Humanos , Masculino , Camundongos , Neointima/patologia , Proteínas Recombinantes/farmacologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Novel NH(2)-functionalized cellulose acetate (CA)/silica composite nanofibrous membranes were successfully prepared by sol-gel combined with electrospinning technology. Tetraethoxysilane (TEOS) as a silica source, CA as precursor and 3-ureidopropyltriethoxysilane as a coupling agent were used in membrane preparation. The membrane's chemical and morphological structures were investigated by scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM) images, X-ray diffraction (XRD), element analyzer, Fourier-transform infrared spectroscopy (FTIR) and N(2) adsorption-desorption isotherms. The composite nanofibrous membranes exhibited high surface area and porosity. The membranes were used for Cr(VI) ion removal from aqueous solution through static and dynamic experiments. The adsorption behavior of Cr(VI) can be well described by the Langmuir adsorption model, and the maximum adsorption capacity for Cr(VI) is estimated to be 19.46 mg/g. The membrane can be conveniently regenerated by alkalization. Thus the composite membrane prepared from biodegradable raw material has potential applications in the field of water treatment.