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排序方式: 共有395条查询结果,搜索用时 15 毫秒
71.
Aline Bamia Maha Sinane Rima Naït-Saïdi Jamila Dhiab Marc Keruzor Phu Hai Nguyen Agathe Bertho Flavie Soubigou Sophie Halliez Marc Blondel Capucine Trollet Martine Simonelig Gaëlle Friocourt Vincent Bringue Frdric Bihel Ccile Voisset 《Neurotherapeutics》2021,18(2):1137
Prion diseases are caused by the propagation of PrPSc, the pathological conformation of the PrPC prion protein. The molecular mechanisms underlying PrPSc propagation are still unsolved and no therapeutic solution is currently available. We thus sought to identify new anti-prion molecules and found that flunarizine inhibited PrPSc propagation in cell culture and significantly prolonged survival of prion-infected mice. Using an in silico therapeutic repositioning approach based on similarities with flunarizine chemical structure, we tested azelastine, duloxetine, ebastine, loperamide and metixene and showed that they all have an anti-prion activity. Like flunarizine, these marketed drugs reduced PrPSc propagation in cell culture and in mouse cerebellum organotypic slice culture, and inhibited the protein folding activity of the ribosome (PFAR). Strikingly, some of these drugs were also able to alleviate phenotypes due to PABPN1 nuclear aggregation in cell and Drosophila models of oculopharyngeal muscular dystrophy (OPMD). These data emphasize the therapeutic potential of anti-PFAR drugs for neurodegenerative and neuromuscular proteinopathies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-020-00992-6.Key Words: Prions, PrPSc, drug repositioning, PFAR, OPMD, PABPN1 相似文献
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Labidi-Galy SI Sisirak V Meeus P Gobert M Treilleux I Bajard A Combes JD Faget J Mithieux F Cassignol A Tredan O Durand I Ménétrier-Caux C Caux C Blay JY Ray-Coquard I Bendriss-Vermare N 《Cancer research》2011,71(16):5423-5434
In ovarian cancer, the immune system fails to eradicate established tumors partly due to the induction of immune tolerance within tumor microenvironment. In this study, we investigated the contribution of plasmacytoid dendritic cells (pDC) in the establishment of immune tolerance in a cohort of 44 ovarian cancer patients. In the tumor and malignant ascites, CD4(+)CD123(+)BDCA2(+) pDC were the most abundant dendritic cell subset; however, they were profoundly depleted in peripheral blood. The presence of pDC in primary ovarian cancer, but not ascites, was an independent prognostic factor associated with early relapse. Following chemotherapy, we observed a partial restoration of blood pDC levels in patients in complete remission. These findings show preferential recruitment of pDC into tumors where they express a partially mature phenotype that may reflect an in situ activation. Importantly, compared with pDC found in ascites or blood, tumor-associated pDC (TApDC) produced less IFN-α, TNF-α, IL-6, macrophage inflammatory protein-1β, and RANTES in response to toll-like receptor stimulation, and alterations in pDC functions were mainly mediated through tumor-derived TNF-α and TGF-β. Unlike ascites-derived pDC, TApDC induced IL-10 production from allogeneic naive CD4(+) T lymphocytes, suggesting the existence of a paracrine immunosuppressive loop. Taken together, our findings indicate that both local and systemic dysfunction of pDC play a critical role in the progression of ovarian cancer via induction of immune tolerance. 相似文献
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Diaz A García F Mozos A Caballero M León A Martinez A Gil C Plana M Gallart T Gatell JM Alós L 《The Journal of infectious diseases》2011,203(6):810-813
We studied the lymphoid tissue biopsies of 20 patients with chronic human immunodeficiency virus (HIV) infection by analyzing collagen deposition, CD4+ cell number, and gene expression of metalloproteinases (MMPs; MMP-2, MMP-9) and tissue inhibitors of MMPs (TIMPs; TIMP-1, TIMP-2). HIV-infected patients had significantly increased collagen deposition (P = .001), fewer CD4+ T cells (P = .05), and decreased MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios (P = .01), compared with HIV-negative control patients. Moreover, we found a significant negative correlation between collagen deposition and the MMP-9/TIMP-1 ratio (ρ = -0.50; P = .047). To our knowledge, this is the first time that MMP/TIMP imbalance has been correlated with lymphoid tissue collagen deposition and incomplete immune recovery in HIV-infected patients, even after long-term antiretroviral treatment. 相似文献
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Epilepsy is a common finding in chromosomal imbalances, but only a few chromosome abnormalities have a characteristic electro-clinical pattern. Trisomy X is one of the most common sex chromosome abnormalities in females, and is associated with considerable phenotypic variability. This report describes four 47,XXX females with mental deficiency and epilepsy. Although a specific electro-clinical pattern could not be defined, the epileptic phenotypes of these patients share many features; we suggest that the association 47,XXX/epilepsy/mental retardation may not be coincidental. This report also enlarges the clinical spectrum of the 47,XXX phenotype. Moreover, these observations highlight the critical role of chromosome X in epilepsy and mental retardation. 相似文献
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Agathe Houzé de l’Aulnoit Samuel Boudet Michaël Génin Pierre-François Gautier Jessica Schiro Denis Houzé de l’Aulnoit Régis Beuscart 《Journal of medical systems》2018,42(5):83
The fetal heart rate (FHR) is a marker of fetal well-being in utero (when monitoring maternal and/or fetal pathologies) and during labor. Here, we developed a smart mobile data module for the remote acquisition and transmission (via a Wi-Fi or 4G connection) of FHR recordings, together with a web-based viewer for displaying the FHR datasets on a computer, smartphone or tablet. In order to define the features required by users, we modelled the fetal monitoring procedure (in home and hospital settings) via semi-structured interviews with midwives and obstetricians. Using this information, we developed a mobile data transfer module based on a Raspberry Pi. When connected to a standalone fetal monitor, the module acquires the FHR signal and sends it (via a Wi-Fi or a 3G/4G mobile internet connection) to a secure server within our hospital information system. The archived, digitized signal data are linked to the patient’s electronic medical records. An HTML5/JavaScript web viewer converts the digitized FHR data into easily readable and interpretable graphs for viewing on a computer (running Windows, Linux or MacOS) or a mobile device (running Android, iOS or Windows Phone OS). The data can be viewed in real time or offline. The application includes tools required for correct interpretation of the data (signal loss calculation, scale adjustment, and precise measurements of the signal’s characteristics). We performed a proof-of-concept case study of the transmission, reception and visualization of FHR data for a pregnant woman at 30 weeks of amenorrhea. She was hospitalized in the pregnancy assessment unit and FHR data were acquired three times a day with a Philips Avalon® FM30 fetal monitor. The prototype (Raspberry Pi) was connected to the fetal monitor’s RS232 port. The emission and reception of prerecorded signals were tested and the web server correctly received the signals, and the FHR recording was visualized in real time on a computer, a tablet and smartphones (running Android and iOS) via the web viewer. This process did not perturb the hospital’s computer network. There was no data delay or loss during a 60-min test. The web viewer was tested successfully in the various usage situations. The system was as user-friendly as expected, and enabled rapid, secure archiving. We have developed a system for the acquisition, transmission, recording and visualization of RCF data. Healthcare professionals can view the FHR data remotely on their computer, tablet or smartphone. Integration of FHR data into a hospital information system enables optimal, secure, long-term data archiving. 相似文献
80.
A candidate molecular signature associated with tamoxifen failure in primary breast cancer
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Vendrell JA Robertson KE Ravel P Bray SE Bajard A Purdie CA Nguyen C Hadad SM Bieche I Chabaud S Bachelot T Thompson AM Cohen PA 《Breast cancer research : BCR》2008,10(5):R88-17