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排序方式: 共有3477条查询结果,搜索用时 46 毫秒
1.
Qian Zhang Larry D. Mesner Gina M. Calabrese Naomi Dirckx Zhu Li Angela Verardo Qian Yang Robert J. Tower Marie-Claude Faugere Charles R. Farber Thomas L. Clemens 《The Journal of clinical investigation》2021,131(7)
Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass. 相似文献
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Renaud Snanoudj Nassim Kamar Elisabeth Cassuto Sophie Caillard Marie Metzger Pierre Merville Antoine Thierry Isabelle Jollet Philippe Grimbert Dany Anglicheau Marc Hazzan Gabriel Choukroun Bruno Hurault De Ligny Bénedicte Janbon Vincent Vuiblet Anne Devys Yann Le Meur Michel Delahousse Jean-Luc Taupin 《Kidney international》2019,95(6):1471-1485
6.
Jér?me Dumortier Marie-Claude Gagnieu Janine Salandre Olivier Guillaud Philipe Guillem Mustapha Adham Olivier Boillot 《Liver transplantation》2006,12(9):1342-1346
Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of this prospective study was to evaluate the effect of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in liver transplant patients presenting GI side-effects Since January 2003, stable liver transplant patients receiving MMF and presenting GI disorders, without evidence of other origin than MMF were enrolled. Conversion was performed without a washout period at an equimolar daily dosage. Thirty-six patients were included after a median delay of 45 months after liver transplantation (LT) (16 women and 20 men, median age of 47 years). Diarrhoea was the main clinical symptom (n = 28, 77.7%). At the time of inclusion, patients were treated with MMF since 18 months (range 3-28) and GI disorders were known for 9 months (range 3-12). After a median follow-up of 12 months after conversion, GI disorders were resolved in 20 patients (55%), improved in 6 patients (17%) and not modified or worsened in 10 patients (28%). Our results strongly suggest that conversion from MMF to EC-MPS in liver transplant patients can improve gastrointestinal disorders in a majority of the patients, and therefore might be considered as the best therapeutic option. 相似文献
7.
In brain regions containing noradrenergic (NA) cell bodies or terminals, DSP-4 induces changes in the activity of catecholamine-synthesizing enzymes which suggest that central NA neurons are lesioned by this neurotoxin. In contrast, the lack of change in the same enzymatic activities in an area containing mostly adrenergic (A) neurons (C2 region), favors the hypothesis of a resistance of the A neurons to DSP-4. Furthermore, the enzymatic changes observed in peripheral organs suggest a peripheral activation of the NA cell bodies in response to lesioning of the sympathetic terminals by DSP-4. 相似文献
8.
Nicolas Borenstein Valérie Chetboul Patrick Bruneval Mehrak Hekmati Renaud Tissier Luc Behr Geneviève Derumeaux Didier Montarras 《European journal of cardio-thoracic surgery》2007,31(3):444-451
OBJECTIVE: Cell therapy may be a promising alternative or adjunct to current treatment modalities for ischemic heart failure. But little is known on the impact of myogenic cell transplantation in large animal models of non-ischemic cardiomyopathy. The aim of the present study was to explore whether an ovine model of toxin-induced heart disease could benefit from non-cultured skeletal muscle cell transplantation. METHODS: Sequential intracoronary injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until echocardiographic detection of myocardial dysfunction. Sheep were then randomly assigned to either non-cultured cell transplantation (n=8) or placebo injection (n=5). For the cell therapy group, a skeletal muscle biopsy (about 10 g) was explanted from each animal approximately 3h before grafting. After thoracotomy, 20 epicardial injections were carried out. The animals were assessed one last time before sacrifice, 2 months after the thoracotomy. Cells were tracked with cmDiI (red fluorescence) and characterized with immunohistochemistry with monoclonal antibodies to a fast skeletal isoform of myosin heavy chain. RESULTS: Two months after intramyocardial grafting, tissue Doppler imaging and conventional echocardiographic assessment of the groups showed a marked improvement in the non-cultured cell therapy group. Ejection fraction (EF) (p<0.05) as well as systolic endocardial velocities (p<0.01) improved versus the placebo group. CmDiI and skeletal myosin heavy chain expression was detected in all animals at 2 months after implantation confirming engraftment of skeletal muscle cells. CONCLUSIONS: In conclusion, our data indicate that non-cultured muscle cell transplantation is feasible and may translate into a functional benefit in an ovine model of dilated heart failure. 相似文献
9.
M Ovize M de Lorgeril D Cathignol J Delaye S Renaud 《Journal of cardiovascular pharmacology》1990,16(4):641-645
Molsidomine and its metabolite, SIN-1, a donor of nitric oxide, are potent coronary vasodilator and anti-ischemic agents. Recently, SIN-1 and nitric oxide have also been shown to inhibit platelet adhesion and aggregation in vitro. The present study in dogs was designed to evaluate the in vivo antithrombotic properties of SIN-1. Coronary intimal damage and stenosis are known to induce coronary cyclic flow variations that reflect platelet thrombus formation followed by disaggregation and embolization (Folts preparation). This model of coronary artery thrombosis appears to simulate the combination of some of the factors contributing to unstable angina and myocardial infarction in human. SIN-1 infusion (10 micrograms/kg/min) significantly reduced the frequency of cyclic flow variations: 4.9 +/- 6.2/h vs. 14 +/- 4.6/h (before treatment, p less than 0.03, n = 6). Results were similar to those obtained with aspirin (5 mg/kg, bolus i.v.: 1.5 +/- 0.6/h vs. 11.7 +/- 3/h, p less than 0.03, n = 5) whereas saline had no effect (17.8 +/- 2.2/h vs. 19.3 +/- 2.4/h, n = 5). As expected, blood pressure was decreased only in the SIN-1 group: 56.2 +/- 7.8 vs. 87.3 +/- 9.3 mm Hg (p less than 0.02) (mean arterial blood pressure). The present results suggest that the well-documented anti-ischemic properties of SIN-1 could be partly due to its antithrombotic activity, clearly demonstrated with the model of coronary thrombosis used here in the dog. 相似文献
10.
D Kurtak H Jamnback R Meyer M Ocran P Renaud 《Journal of the American Mosquito Control Association》1987,3(2):201-210
The Onchocerciasis Control Program of the World Health Organization is carrying out an extensive screening program in a search for new larvicides to be used for control of Simulium damnosum s.l. Emphasis has been given to finding a pyrethroid and a carbamate to supplement the organophosphates currently in use. These chemicals with differing modes of action, together with Bacillus thuringiensis H-14, are being used in an attempt to cope with the development and spread of resistance to the organophosphates temephos and chlorphoxim. 相似文献