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1.
Regen Med ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829095

RESUMO

Aim: To determine the efficacy and safety of intracoronary infusion of autologous bone marrow mesenchymal stem cells (MSCINJ) in combination with intensive atorvastatin (ATV) treatment for patients with anterior ST-segment elevation myocardial infarction-elevation myocardial infarction. Patients & methods: The trial enrolls a total of 100 patients with anterior ST-elevation myocardial infarction. The subjects are randomly assigned (1:1:1:1) to receive routine ATV (20 mg/d) with placebo or MSCsINJ and intensive ATV (80 mg/d) with placebo or MSCsINJ. The primary end point is the absolute change of left ventricular ejection fraction within 12 months. The secondary end points include parameters in cardiac function, remodeling and regeneration, quality of life, biomarkers and clinical outcomes. Results & conclusion: The trial will implicate the essential of cardiac micro-environment improvement ('fertilizing') for cell-based therapy. Clinical Trial Registration: NCT03047772.

2.
Stem Cells Transl Med ; 8(10): 1068-1083, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31245934

RESUMO

Our previous studies showed that the combination of atorvastatin (ATV) and single injection of ATV-pretreated mesenchymal stem cells (MSCs) (ATV -MSCs) at 1 week post-acute myocardial infarction (AMI) promoted MSC recruitment and survival. This study aimed to investigate whether the combinatorial therapy of intensive ATV with multiple injections of ATV -MSCs has greater efficacy at different stages to better define the optimal strategy for MSC therapy in AMI. In order to determine the optimal time window for MSC treatment, we first assessed stromal cell-derived factor-1 (SDF-1) dynamic expression and inflammation. Next, we compared MSC recruitment and differentiation, cardiac function, infarct size, and angiogenesis among animal groups with single, dual, and triple injections of ATV -MSCs at early (Early1, Early2, Early3), mid-term (Mid1, Mid2, Mid3), and late (Late1, Late2, Late3) stages. Compared with AMI control, intensive ATV significantly augmented SDF-1 expression 1.5∼2.6-fold in peri-infarcted region with inhibited inflammation. ATV -MSCs implantation with ATV administration further enhanced MSC recruitment rate by 3.9%∼24.0%, improved left ventricular ejection fraction (LVEF) by 2.0%∼16.2%, and reduced infarct size in all groups 6 weeks post-AMI with most prominent improvement in mid groups and still effective in late groups. Mechanistically, ATV -MSCs remarkably suppressed inflammation and apoptosis while increasing angiogenesis. Furthermore, triple injections of ATV -MSCs were much more effective than single administration during early and mid-term stages of AMI with the best effects in Mid3 group. We conclude that the optimal strategy is multiple injections of ATV -MSCs combined with intensive ATV administration at mid-term stage of AMI. The translational potential of this strategy is clinically promising. Stem Cells Translational Medicine 2019;8:1068-1083.

3.
Front Immunol ; 10: 62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30761134

RESUMO

Type 2 immunity participates in the pathogeneses of helminth infection and allergic diseases. Emerging evidence indicates that the components of type 2 immunity are also involved in maintaining metabolic hemostasis and facilitating the healing process after tissue injury. Numerous preclinical studies have suggested regulation of type 2 immunity-related cytokines, such as interleukin-4, -13, and -33, and cell types, such as M2 macrophages, mast cells, and eosinophils, affects cardiac functions after myocardial infarction (MI), providing new insights into the importance of immune modulation in the infarcted heart. This review provides an overview of the functions of these cytokines and cells in the setting of MI as well as their potential to predict the severity and prognosis of MI.


Assuntos
Imunidade Inata , Infarto do Miocárdio/imunologia , Animais , Polaridade Celular , Colágeno/metabolismo , Modelos Animais de Doenças , Eosinófilos/imunologia , Humanos , Inflamação/imunologia , Interleucinas/biossíntese , Macrófagos/imunologia , Mastócitos/imunologia , Camundongos , Infarto do Miocárdio/patologia , Neovascularização Fisiológica/imunologia , Ratos
4.
Front Pharmacol ; 8: 775, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29163161

RESUMO

Background and Aims: Tongxinluo (TXL) is a multifunctional traditional Chinese medicine that has been widely used to treat cardiovascular and cerebrovascular diseases. However, no studies have explored whether TXL can protect human cardiomyocytes (HCMs) from ischemia/reperfusion (I/R) injury. Reperfusion Injury Salvage Kinase (RISK) pathway activation was previously demonstrated to protect the hearts against I/R injury and it is generally activated via Akt or (and) Erk 1/2, and their common downstream protein, ribosomal protein S6 kinase (p70s6k). In addition, prior studies proved that TXL treatment of cells promoted secretion of VEGF, which could be stimulated by the increased phosphorylation of one p70s6k subtype, p70s6k1. Consequently, we hypothesized TXL could protect HCMs from I/R injury by activating p70s6k1 and investigated the underlying mechanism. Methods and Results: HCMs were exposed to hypoxia (18 h) and reoxygenation (2 h) (H/R), with or without TXL pretreatment. H/R reduced mitochondrial membrane potential, increased bax/bcl-2 ratios and cytochrome C levels and induced HCM apoptosis. TXL preconditioning reversed these H/R-induced changes in a dose-dependent manner and was most effective at 400 µg/mL. The anti-apoptotic effect of TXL was abrogated by rapamycin, an inhibitor of p70s6k. However, inhibitors of Erk1/2 (U0126) or Akt (LY294002) failed to inhibit the protective effect of TXL. TXL increased p70s6k1 expression and, thus, enhanced its phosphorylation. Furthermore, transfection of cardiomyocytes with siRNA to p70s6k1 abolished the protective effects of TXL. Among the micro-RNAs (miR-145-5p, miR-128-3p and miR-497-5p) previously reported to target p70s6k1, TXL downregulated miR-128-3p in HCMs during H/R, but had no effects on miR-145-5p and miR-497-5p. An in vivo study confirmed the role of the p70s6k1 pathway in the infarct-sparing effect of TXL, demonstrating that TXL decreased miR-128-3p levels in the rat myocardium during I/R. Transfection of HCMs with a hsa-miR-128-3p mimic eliminated the protective effects of TXL. Conclusions: The miR-128-3p/p70s6k1 signaling pathway is involved in protection by TXL against HCM apoptosis during H/R. Overexpression of p70s6k1 is, therefore, a potential new strategy for alleviating myocardial reperfusion injury.

5.
Front Physiol ; 8: 494, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28751864

RESUMO

Although exosomes were previously recognized as a mechanism for discharging useless cellular components, growing evidence has elucidated their roles in conveying information between cells. They contribute to cell-cell communication by carrying nucleic acids, proteins and lipids that can, in turn, regulate behavior of the target cells. Recent research suggested that exosomes extensively participate in progression of diverse cardiovascular diseases (CVDs), such as myocardial infarction, cardiomyopathy, pulmonary arterial hypertension and others. Here, we summarize effects of exosome-derived molecules (mainly microRNAs and proteins) on cardiac function, to examine their potential applications as biomarkers or therapeutics in CVDs.

6.
Appl Radiat Isot ; 70(1): 332-5, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22019094

RESUMO

We estimated the dosimetry of [(18)F]fluoroacetate (FAC) with the method established by MIRD based on biodistribution data of rats. We selected some important organs and computed their residence time, their absorbed doses and effective dose with the (%ID(Organ)) (human) data using OLINDA/EXM 1.1 program. We observed the highest absorbed doses in the heart wall (0.025mGy/MBq) and the lowest in skin (0.0079mGy/MBq). The total mean absorbed doses and the effective doses were 0.011mGy/MBq and 0.014mSv/MBq, respectively. A 370-MBq injection of FAC leads to an estimated effective dose of 5.2mSv. The potential radiation risk associated with FAC/PET imaging is well within the accepted limits.


Assuntos
Fluoracetatos/farmacocinética , Modelos Biológicos , Contagem Corporal Total/métodos , Animais , Carga Corporal (Radioterapia) , Simulação por Computador , Humanos , Masculino , Taxa de Depuração Metabólica , Especificidade de Órgãos , Doses de Radiação , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Especificidade da Espécie , Distribuição Tecidual
7.
Nucl Med Commun ; 32(11): 1018-25, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21956489

RESUMO

OBJECTIVE: To evaluate the clinical value of F-fluorodeoxyglucose positron emission tomography and computed tomography (¹8F-FDG PET/CT) in postoperative patients with gastrointestinal mucinous adenocarcinoma. METHODS: From July 2007 to March 2009, 30 patients who had previous surgical resection of histopathologically diagnosed gastrointestinal mucinous adenocarcinoma underwent ¹8F-FDG PET/CT scans in our center. The standard of reference for tumor recurrence, regional lymph node (LN) metastasis, peritoneal and distant metastasis consisted of histopathologic confirmation or clinical follow-up information for at least 6 months after PET/CT examinations. RESULTS: With final diagnosis, tumor recurrences were confirmed in eight of the 30 patients (26.7%). If a maximum standardized uptake value (SUVmax) of 2.5 or more was used as a cut-off point, the sensitivity, specificity, and accuracy of PET/CT were 87.5, 77.3, and 80.0%, respectively. However, if an SUVmax of 4.0 or more was the criterion, the sensitivity, specificity, and accuracy were 25.0, 86.4, and 70.0%, respectively. A cut-off point of 2.5 showed a higher sensitivity (P=0.041), and there was no statistical difference in the specificity and the accuracy of these two criteria. For the diagnosis of metastasis in regional LNs and peritoneum, the detection rate was 95.2 and 86.4%, respectively. In addition, we followed up 20 patients with 26 suspicious distant lesions. The sensitivity, specificity, and accuracy were 58.3, 92.9, and 76.9%, respectively. CONCLUSION: ¹8F-FDG PET/CT may be effective to discriminate tumor recurrence, and to detect regional LNs, peritoneal and distant metastasis in postoperative patients with gastrointestinal mucinous adenocarcinoma.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico por imagem , Neoplasias Gastrointestinais/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma Mucinoso/secundário , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Feminino , Fluordesoxiglucose F18 , Seguimentos , Neoplasias Gastrointestinais/cirurgia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Linfonodos/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Peritônio/diagnóstico por imagem , Peritônio/patologia , Período Pós-Operatório , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade
8.
Parasit Vectors ; 4: 47, 2011 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21457538

RESUMO

BACKGROUND: Toxoplasma gondii is an important zoonotic pathogen causing significant human and animal health problems. Infection in dairy goats not only results in significant reproductive losses, but also represents an important source of human infection due to consumption of infected meat and milk. In the present study we report for the first time seroprevalence of T. gondii infection in Guanzhong and Saanen dairy goats in Shaanxi province, Northwestern China. RESULTS: Sera from 751 dairy goats from 9 farms in 6 counties were examined for T. gondii antibodies with an indirect haemagglutination (IHA) test. Antibodies to T. gondii were detected in 106 (14.1%) serum samples, with antibody titres ranging from 1:64 to 1:1024. Seropositive goats were found in all 9 farms and seroprevalences in Guanzhong (16.3%, 75/461) and Saanen (10.7%, 31/290) dairy goats were not statistically significantly different. All the factors (sex, age and location) reported in the present study affected prevalence of infection, and seroprevalence increased with age, suggesting postnatal acquisition of T. gondii infection. CONCLUSIONS: The results of the present survey indicate that infection by T. gondii is widely prevalent in dairy goats in Shaanxi province, Northwestern China, and this has implications for prevention and control of toxoplasmosis in this province.


Assuntos
Doenças das Cabras/epidemiologia , Toxoplasma/imunologia , Toxoplasmose Animal/epidemiologia , Animais , Anticorpos Antiprotozoários/sangue , China/epidemiologia , Feminino , Doenças das Cabras/parasitologia , Cabras , Testes de Hemaglutinação , Masculino , Estudos Soroepidemiológicos , Soro/imunologia , Toxoplasmose Animal/parasitologia
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