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排序方式: 共有2610条查询结果,搜索用时 46 毫秒
81.
Greco E Quintiliani G Santucci MB Serafino A Ciccaglione AR Marcantonio C Papi M Maulucci G Delogu G Martino A Goletti D Sarmati L Andreoni M Altieri A Alma M Caccamo N Di Liberto D De Spirito M Savage ND Nisini R Dieli F Ottenhoff TH Fraziano M 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(21):E1360-E1368
We have generated unique asymmetric liposomes with phosphatidylserine (PS) distributed at the outer membrane surface to resemble apoptotic bodies and phosphatidic acid (PA) at the inner layer as a strategy to enhance innate antimycobacterial activity in phagocytes while limiting the inflammatory response. Results show that these apoptotic body-like liposomes carrying PA (ABL/PA) (i) are more efficiently internalized by human macrophages than by nonprofessional phagocytes, (ii) induce cytosolic Ca(2+) influx, (iii) promote Ca(2+)-dependent maturation of phagolysosomes containing Mycobacterium tuberculosis (MTB), (iv) induce Ca(2+)-dependent reactive oxygen species (ROS) production, (v) inhibit intracellular mycobacterial growth in differentiated THP-1 cells as well as in type-1 and -2 human macrophages, and (vi) down-regulate tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-1β, IL-18, and IL-23 and up-regulate transforming growth factor (TGF)-β without altering IL-10, IL-27, and IL-6 mRNA expression. Also, ABL/PA promoted intracellular killing of M. tuberculosis in bronchoalveolar lavage cells from patients with active pulmonary tuberculosis. Furthermore, the treatment of MTB-infected mice with ABL/PA, in combination or not with isoniazid (INH), dramatically reduced lung and, to a lesser extent, liver and spleen mycobacterial loads, with a concomitant 10-fold reduction of serum TNF-α, IL-1β, and IFN-γ compared with that in untreated mice. Altogether, these results suggest that apoptotic body-like liposomes may be used as a Janus-faced immunotherapeutic platform to deliver polar secondary lipid messengers, such as PA, into phagocytes to improve and recover phagolysosome biogenesis and pathogen killing while limiting the inflammatory response. 相似文献
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Scheppke L Murphy EA Zarpellon A Hofmann JJ Merkulova A Shields DJ Weis SM Byzova TV Ruggeri ZM Iruela-Arispe ML Cheresh DA 《Blood》2012,119(9):2149-2158
Vascular development and angiogenesis initially depend on endothelial tip cell invasion, which is followed by a series of maturation steps, including lumen formation and recruitment of perivascular cells. Notch ligands expressed on the endothelium and their cognate receptors expressed on perivascular cells are involved in blood vessel maturation, though little is known regarding the Notch-dependent effectors that facilitate perivascular coverage of nascent vessels. Here, we report that vascular smooth muscle cell (VSMC) recognition of the Notch ligand Jagged1 on endothelial cells leads to expression of integrin αvβ3 on VSMCs. Once expressed, integrin αvβ3 facilitates VSMC adhesion to VWF in the endothelial basement membrane of developing retinal arteries, leading to vessel maturation. Genetic or pharmacologic disruption of Jagged1, Notch, αvβ3, or VWF suppresses VSMC coverage of nascent vessels and arterial maturation during vascular development. Therefore, we define a Notch-mediated interaction between the developing endothelium and VSMCs leading to adhesion of VSMCs to the endothelial basement membrane and arterial maturation. 相似文献
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Antonino Cannas Giuseppe Borghero Gian Luca Floris Paolo Solla Adriano Chiò Bryan J. Traynor Andrea Calvo Gabriella Restagno Elisa Majounie Emanuela Costantino Valeria Piras Loredana Lavra Carla Pani Gianni Orofino Francesca Di Stefano Paolo Tacconi Marcello Mario Mascia Antonella Muroni Maria Rita Murru Stefania Tranquilli Daniela Corongiu Marcella Rolesu Stefania Cuccu Francesco Marrosu Maria Giovanna Marrosu 《Neurogenetics》2013,14(2):161-166
Based on our previous finding of the p.A382T founder mutation in ALS patients with concomitant parkinsonism in the Sardinian population, we hypothesized that the same variant may underlie Parkinson's disease (PD) and/or other forms of degenerative parkinsonism on this Mediterranean island. We screened a cohort of 611 patients with PD (544 cases) and other forms of degenerative parkinsonism (67 cases) and 604 unrelated controls for the c.1144G > A (p.A382T) missense mutation of the TARDBP gene. The p.A382T mutation was identified in nine patients with parkinsonism. Of these, five (0.9 % of PD patients) presented a typical PD (two with familiar forms), while four patients (6.0 % of all other forms of parkinsonism) presented a peculiar clinical presentation quite different from classical atypical parkinsonism with an overlap of extrapyramidal–pyramidal–cognitive clinical signs. The mutation was found in eight Sardinian controls (1.3 %) consistent with a founder mutation in the island population. Our findings suggest that the clinical presentation of the p.A382T TARDBP gene mutation may include forms of parkinsonism in which the extrapyramidal signs are the crucial core of the disease at onset. These forms can present PSP or CBD-like clinical signs, with bulbar and/or extrabulbar pyramidal signs and cognitive impairment. No evidence of association has been found between TARDBP gene mutation and typical PD. 相似文献
87.
Heat stress (HS) induces adaptive responses that are responsible for alterations of carbohydrate and lipid metabolism. This study aimed to evaluate the effects of chronic heat treatment on the expression and secretion of leptin and adiponectin, important regulators of energy homeostasis, food intake and insulin action. C57BL/6 mice were subdivided into three groups (24 mice each). The first group was kept under control conditions (C: 22±2?°C). The second group was exposed to HS (35±1?°C). The third group was kept under control conditions and was food restricted (FR). The HS group had higher rectal temperature than the C and FR groups and lower food intake than the C group. Hspa1 (Hspa1a) gene expression in adipose tissue, muscle and liver was higher under HS than FR and C. Heat treatment resulted in decreased blood glucose and non-esterified fatty acids; increased leptin, adiponectin and insulin secretion; and greater glucose disposal. Leptin, adiponectin, leptin and adiponectin receptors, insulin receptor substrate-1 and glucose transporter mRNAs were up-regulated in HS mice. This study provides evidence that HS improves leptin and adiponectin signalling in adipose tissue, muscle and liver. Heat stress was responsible for improving insulin sensitivity and glucose uptake in peripheral tissues, probably mediated by adipokines. Changes in the adipokine levels and sensitivity to them may be considered as an adaptive response to heat. 相似文献
88.
Rosso R Di Biagio A Maggiolo F Nulvesu L Callegaro AP Taramasso L Bruzzone B Viscoli C 《AIDS care》2012,24(1):54-58
The choice of an antiretroviral regimen can often impact on adherence, treatment satisfaction and therefore influence on clinical outcome. These concerns are particularly true in adolescents. In this setting, adherence is usually affected by multifactor events and biopsychosocial factors, which connect and changeover time. We evaluated the effect of a switch to a single-pill fixed-dose regimen on patient-reported outcomes, virologic and immunologic outcomes, and safety in a cohort of adolescents with perinatal HIV-1 infection. In addition, we evaluated the effect on low-level residual HIV-RNA. An open-label, non-randomised study was performed: 12 adolescents with a confirmed viremia <50 copies/mL treated with lamivudine or emtricitabine, tenofovir and efavirenz were switched to one-pill fixed-dose regimen of emtricitabine/tenofovir/efavirenz. At the end of follow-up, the new regimen was associated with improvements in treatment satisfaction, HIV-symptoms, whereas adherence remained high. No immunological or virological significative changes were observed. No side-effects were registered. Moreover, the low-level residual HIV-RNA was <3 copie/mL in all patients. One-pill fixed-dose regimen is an added value that favours adherence, reduces HIV-symptoms, improves patients' satisfaction and could better control of HIV-RNA in adolescents, too. 相似文献
89.
Renato Pietro Ricci Carlo Pignalberi Barbara Magris Stefano Aquilani Vito Altamura Loredana Morichelli Antonio Porfili Laura Quarta Fabio Saputo Massimo Santini 《Journal of interventional cardiac electrophysiology》2012,33(1):113-121
Background
In 2007, great concern arose regarding failure of implantable cardioverter defibrillator (ICD) leads from several manufacturers. 相似文献90.
Fattovich G Baroni GS Pasino M Pierantonelli I Covolo L Ieluzzi D Passigato N Tonon A Faraci MG Guido M Negro F 《Digestive and liver disease》2012,44(5):419-425
Background and aimThe role of insulin resistance in predicting virological response to therapy of chronic hepatitis C is debated. We assessed the association between basal (defined as homeostasis model assessment of insulin resistance (HOMA-IR) > 2) and post-load insulin resistance (as oral glucose insulin sensitivity index < 9.8 mg/kg/min) with the rapid and sustained virological responses in chronic hepatitis C.MethodsObservational prospective study of 124 treatment-naïve patients with chronic hepatitis C not fulfilling the metabolic syndrome criteria, adherent to a standard treatment with pegylated interferon alpha plus ribavirin.ResultsInsulin resistance was detected in 50% (by HOMA-IR) and 29% (by oral glucose insulin sensitivity index) of patients. Independent predictors of rapid virologic response were hepatitis C virus (HCV) genotype 2 (odds ratio 5.66; 95% confidence interval 1.88–17.01), HCV genotype 3 (odds ratio 5.23; 95% confidence interval 1.84–14.84) and lower basal ferritin levels (odds ratio 0.99; 95% confidence interval 0.993–0.998). Independent predictors of sustained virologic response were HCV genotype 2 (odds ratio 19.54; 95% confidence interval 2.29–166.41) and HCV genotype 3 (odds ratio 3.24; 95% confidence interval 1.10–9.58). Rapid virologic response was by itself predictive of sustained virologic response (odds ratio 40.90; 95% confidence interval 5.37–311.53).ConclusionsInsulin resistance, measured by both static and dynamic methods, does not predict rapid or sustained virologic response in chronic hepatitis C patients without the metabolic syndrome. 相似文献