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排序方式: 共有740条查询结果,搜索用时 15 毫秒
1.
Takeshi Sakata Yongmei Wang Bernard P Halloran Hashem Z Elalieh Jay Cao Daniel D Bikle 《Journal of bone and mineral research》2004,19(3):436-446
We showed that unloading markedly diminished the effects of IGF-I to activate its signaling pathways, and the disintegrin echistatin showed a similar block in osteoprogenitor cells. Furthermore, unloading decreased alphaVbeta3 integrin expression. These results show that skeletal unloading induces resistance to IGF-I by inhibiting activation of the IGF-I signaling pathways at least in part through downregulation of integrin signaling. INTRODUCTION: We have previously reported that skeletal unloading induces resistance to insulin-like growth factor-I (IGF-I) with respect to bone formation. However, the underlying mechanism remains unclear. The aim of this study was to clarify how skeletal unloading induces resistance to the effects of IGF-I administration in vivo and in vitro with respect to bone formation. MATERIALS AND METHODS: We first determined the response of bone to IGF-I administration in vivo during skeletal unloading. We then evaluated the response of osteoprogenitor cells isolated from unloaded bones to IGF-I treatment in vitro with respect to activation of the IGF-I signaling pathways. Finally we examined the potential role of integrins in mediating the responsiveness of osteoprogenitor cells to IGF-I. RESULTS: IGF-I administration in vivo significantly increased proliferation of osteoblasts. Unloading markedly decreased proliferation and blocked the ability of IGF-I to increase proliferation. On a cellular level, IGF-I treatment in vitro stimulated the activation of its receptor, Ras, ERK1/2 (p44/42 MAPK), and Akt in cultured osteoprogenitor cells from normally loaded bones, but these effects were markedly diminished in cells from unloaded bones. These results were not caused by altered phosphatase activity or changes in receptor binding to IGF-I. Inhibition of the Ras/MAPK pathway was more impacted by unloading than that of Akt. The disintegrin echistatin (an antagonist of the alphaVbeta3 integrin) blocked the ability of IGF-I to stimulate its receptor phosphorylation and osteoblast proliferation, similar to that seen in cells from unloaded bone. Furthermore, unloading significantly decreased the mRNA levels both of alphaV and beta3 integrin subunits in osteoprogenitor cells. CONCLUSION: These results indicate that skeletal unloading induces resistance to IGF-I by inhibiting the activation of IGF-I signaling pathways, at least in part, through downregulation of integrin signaling, resulting in decreased proliferation of osteoblasts and their precursors. 相似文献
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Ruichong Ma Margarida Rei Isaac Woodhouse Katherine Ferris Sophie Kirschner Anandhakumar Chandran Uzi Gileadi Ji-Li Chen Mariana Pereira Pinho Yoanna Ariosa-Morejon Skirmantas Kriaucionis Nicola Ternette Hashem Koohy Olaf Ansorge Graham Ogg Puneet Plaha Vincenzo Cerundolo 《Neuro-oncology》2022,24(12):2093
4.
Shohreh Alipour Hashem Montaseri Azadeh Khalili 《Journal of chemotherapy (Florence, Italy)》2016,28(5):411-416
Aerosolized chemotherapeutics leads to higher, localized and continuous concentrations of active agents in lung tissue with lower side effects for other organs. The present study was performed on jugular vein cannulated rats which endothracheally received 4 mg/kg of free paclitaxel powder (Free-PTX), paclitaxel-loaded alginate microparticles (PTX-ALG-MPs) and i.v. paclitaxel (Anzatax®). Pharmacokinetic parameters for Free-PTX and PTX-ALG-MPs contain higher AUC, mean residence time (MRT),half-life and bioavailability, with lower elimination constant (ke). Statistical analysis showed that the amount of paclitaxel per gram of lung tissue after 0.5, 6 and 24 h after administration of Free-PTX was lower than PTX-ALG-MPs. Lung tissue AUC for Free-PTX was lower than PTX-ALG-MPs. According to the obvious advantages obtained, such as dose lowering and increasing paclitaxel residence time and half-life. It should be noted that cell cytotoxicity test on normal airway cell lines was not examined in this study but due to previous reports on safety of inhaled paclitaxel, it can be suggested that pulmonary delivery of paclitaxel can be a useful non-invasive route of administration compared with i.v administration. 相似文献
5.
Hashem T. Al-Salman Abdulmonem A. Al-Hussien Ibrahim H. Al-Ahmed 《Neurosciences (Riyadh, Saudi Arabia)》2021,26(1):89
Sprengel deformity is a congenital anomaly arising mainly in the shoulder girdle, associated with elevation of dysplastic scapula. skeletal anomalies, mainly Klippel-Feil syndrome, hemivertebrae, and omovertebral bone may be present along Sprengel anomaly. The omovertebral bone is an abnormal bone that originates from the superomedial edge of the scapula with different insertion points along the posterior cervical spine, seen in about third of the patients with Sprengel anomaly. While cosmetic to functional impairment is a common presentation to the omovertebral bone, cervical myelopathy is a rare presentation. Here, we described our experience, management and follow up of 13-year-old boy presented with cervical myelopathy secondary to the omovertebral bone.Sprengel deformity is a complex anomaly of the shoulder girdle, associated with elevation of dysplastic scapula.1-4 Clinically, it is associated with disfigurement and limitation of shoulder movement. Other skeletal anomalies – mainly, Klippel–Feil syndrome, hemivertebrae, and omovertebral bone may be present.4 The omovertebral bone is an abnormal bone that originates from the superomedial edge of the scapula with different insertion points along the posterior cervical spine, seen in about a third of patients with Sprengel anomaly.2,5 The clinical presentation ranges from cosmetic to functional impairment, while cervical myelopathy is a rare presentation related to omovertebral bone. The management and follow up is less described in the literature contributed to its rare occurance.6 Here, the author described a 13-year- old boy diagnosed with Sprengel deformity presented with myelopathic manifestation, where cervical magnetic resonance imaging (MRI) showed signal cord changes secondary to compression by intraspinal extension of the omovertebral bone. The patient underwent uneventful resection of the abnormal bone, and spinal cord decompression. 相似文献
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MH Esmaeili M Movahedi A Faraji H Haghdoost-Yazdi 《Neurotoxicology and teratology》2012,34(5):489-494
β-Carbolines (BCs) are considered to be endogenous toxins and have been proposed as possible causative candidates inducing Parkinson's disease (PD). However, there is controversy about the effect and also effective dose of these compounds in the etiology of PD. This study was designed to further examine the effect of norharman (NH), a BC which in mammalian brain occurs at high levels in the substantia nigra, on the development of Parkinsonism-like behaviors in rats. A small amount (4μl) of NH solution at 2 or 200ng/ml was unilaterally injected into either striatum or substantia nigra (SN) by stereotaxic surgery. The development of Parkinsonism was assessed by three conventional behavioral tests, compared to the effects of unilateral 6-hydroxydopamine (6-OHDA) - induced lesions in the nigrostriatal pathway. An apomorphine-induced rotational test revealed no Parkinsonism-like behavior in the NH treated groups. However, rats that received the high concentration of NH into their SN showed significant biased swings in the elevated body swing test. In a rotarod test, NH treated groups showed relatively weak motor performance and their learning patterns were close to that of the 6-OHDA treated rats. Considering that the rotational test is only valid in animals with severe Parkinsonism, but time spent on the rotating rod correlates inversely with severity of Parkinsonism, our results indicate that a single exposure to low amounts of NH is effective in producing moderate Parkinsonism-like behavioral symptoms, possibly through a neurotoxic effect of this agent on the SN dopaminergic neurons. 相似文献
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9.
Fatemeh?Ramezani Mostafa?Habibi Hashem?Rafii-Tabar Massoud?AmanlouEmail author 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2015,23(1):9
Background
Gold nanoparticles now command a great deal of attention for medical applications. Despite the importance of nano-bio interfaces, interaction between peptides and proteins with gold surfaces is not still fully understood, especially in a molecular level.Methods
In the present study computational simulation of adsorption of 20 amino acids, in three forms of mono-amino acid, homo di-peptide and homo tri-peptide, on the gold nanoparticles was performed by Gromacs using OPLSAA force field. The flexibility, stability, and size effect of the peptides on the gold nanoparticles were studied as well as the molecular structure of them.Results
According to our results, adsorbed homo tri-peptides on the gold surface had more flexibility, more gyration, and the farthest distance from the GNP in comparison with homo di-peptides and mono-amino acids.Conclusion
Our findings provide new insights into the precise control of interactions between amino acids anchored on the GNPs.10.
Parisa Akhlaghi Hashem Miri-Hakimabad Laleh Rafat-Motavalli 《Journal of radiation research》2015,56(4):646-655
In order to establish an organ and effective dose database for Iranian children undergoing computed tomography (CT) examinations, in the first step, two Iranian 11-year-old phantoms were constructed from image series obtained from CT and magnetic resonance imaging (MRI). Organ and effective doses for these phantoms were calculated for head, chest, abdomen–pelvis and chest–abdomen–pelvis (CAP) scans at tube voltages of 80, 100 and 120 kVp, and then they were compared with those of the University of Florida (UF) 11-year-old male phantom. Depth distributions of the organs and the mass of the surrounding tissues located in the beam path, which shield the internal organs, were determined for all phantoms. From the results, it was determined that the main organs of the UF phantom receive smaller doses than the two Iranian phantoms, except for the urinary bladder of the Iranian girl phantom. In addition, the relationship between the anatomical differences and the size of the dose delivered was also investigated and the discrepancies between the results were examined and justified. 相似文献