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Cellular models and tissue equivalent systems for evaluating the structures and significance of age-modified proteins 总被引:1,自引:0,他引:1
R W Gracy K U Yüksel T M Jacobson M L Chapman J C Hevelone G E Wise S D Dimitrijevich 《Gerontology》1991,37(1-3):113-127
The accumulation of modified proteins in aging is well documented in many aging models. For example, the deamidated isoforms of triosephosphate isomerase accumulate in: (a) old erythrocytes, (b) fibroblasts from old donors, (c) fibroblasts aged in vitro, (d) premature-aging syndromes and (e) old cells in the eye lens. However, a fundamental remaining question is: 'Do such modified proteins interfere with cellular function?' It has been difficult to assess this question at the molecular level using whole-organism models and equally frustrating to evaluate the physiological significance of such changes using classical cellular models. Tissue equivalent systems (TES) provide an opportunity for examining the molecular basis and physiological consequences of modified proteins during aging. TES are composed of differentiating and proliferating heterogeneous cell types with symbiotic cell-cell and cell-matrix interactions. They closely resemble, both morphologically and functionally, the tissues from which they were derived. Aging studies utilizing TES can provide information on modifications of protein structures, isozyme patterns, enzymes of the cellular environmental protection system and metabolic parameters which may regulate protein synthesis and degradation. 相似文献
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Thom E. Snijders Tom P.C. Schlösser Nathanael D. Heckmann Taro Tezuka Rene M. Castelein Rob P. Stevenson Harry Weinans Arthur de Gast Lawrence D. Dorr 《The Journal of arthroplasty》2021,36(6):2184-2188.e1
BackgroundAnterior and posterior pelvic tilt appears to play a role in total hip arthroplasty (THA) stability. When changing from the standing to the sitting position, the pelvis typically rotates posteriorly while the hips flex and this affects the femoro-acetabular positions. This case-control study compares changes in 3-D acetabular cup orientation during functional pelvic tilt between posterior THA dislocations vs stable THAs.MethodsStanding and sitting 3-D cup orientation was compared between fifteen posterior dislocations vs 233 prospectively followed stable THAs. 3-D cup orientation was calculated using previously validated trigonometric algorithms on biplanar radiographs. Those algorithms combine the angles in the three anatomical planes (coronal inclination, transverse version, and sagittal ante-inclination) in the standing position with the change in sagittal pelvic tilt from standing to sitting to calculate the 3-D orientation in the sitting position.ResultsThe standing cup orientation of the dislocated THAs was only characterized by a lower coronal inclination (P = .039). Compared with the controls, from standing to sitting, they showed less posterior pelvic tilt (P < .001). This led to a significant lower coronal inclination (P < .001) and sagittal ante-inclination (P < .001) in the sitting position but similar transverse version (P = .366).ConclusionsComparing posterior THA dislocations to stable THAs, there is a lower increase of all three orientation angles from standing to sitting. This leads to a decreased sitting coronal inclination and sagittal ante-inclination which may lead to an increased risk of impingement ensued by THA instability. By contrast, the transverse version was not significantly different in both positions. This confirms the importance of biplanar data on functional cup orientation.Level of EvidenceDiagnostic, Level III. 相似文献
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RuthMabel Boytz Mikołaj Słabicki Sita Ramaswamy J. J. Patten Charles Zou Chengcheng Meng Brett L. Hurst Jinhua Wang Radosław P. Nowak Priscilla L. Yang Martin Sattler Richard M. Stone James D. Griffin Nathanael S. Gray Suryaram Gummuluru Robert A. Davey Ellen Weisberg 《Journal of medical virology》2023,95(1):e28157
Coronavirus disease 2019 (COVID-19) remains a major public health concern, and vaccine unavailability, hesitancy, or failure underscore the need for discovery of efficacious antiviral drug therapies. Numerous approved drugs target protein kinases associated with viral life cycle and symptoms of infection. Repurposing of kinase inhibitors is appealing as they have been vetted for safety and are more accessible for COVID-19 treatment. However, an understanding of drug mechanism is needed to improve our understanding of the factors involved in pathogenesis. We tested the in vitro activity of three kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including inhibitors of AXL kinase, a host cell factor that contributes to successful SARS-CoV-2 infection. Using multiple cell-based assays and approaches, gilteritinib, nintedanib, and imatinib were thoroughly evaluated for activity against SARS-CoV-2 variants. Each drug exhibited antiviral activity, but with stark differences in potency, suggesting differences in host dependency for kinase targets. Importantly, for gilteritinib, the amount of compound needed to achieve 90% infection inhibition, at least in part involving blockade of spike protein-mediated viral entry and at concentrations not inducing phospholipidosis (PLD), approached a clinically achievable concentration. Knockout of AXL, a target of gilteritinib and nintedanib, impaired SARS-CoV-2 variant infectivity, supporting a role for AXL in SARS-CoV-2 infection and supporting further investigation of drug-mediated AXL inhibition as a COVID-19 treatment. This study supports further evaluation of AXL-targeting kinase inhibitors as potential antiviral agents and treatments for COVID-19. Additional mechanistic studies are needed to determine underlying differences in virus response. 相似文献
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Xiang Li Chun-Hao Huang Francisco J. Snchez-Rivera Margaret C. Kennedy Darjus F. Tschaharganeh John P. Morris IV Antonella Montinaro Kevin P. O'Rourke Ana Banito John E. Wilkinson Chi-Chao Chen Yu-Jui Ho Lukas E. Dow Sha Tian Wei Luan Elisa de Stanchina Tinghu Zhang Nathanael S. Gray Henning Walczak Scott W. Lowe 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(17)
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Ceramic on ceramic hip prostheses are an increasingly popular choice for hip replacement. Modern manufacturing techniques and developments have increased the strength and reliability of ceramic materials. The alternative bearing couples such as metal-on-polyethylene and metal-on-metal are more inclined to wear and produce particulate debris. Despite reports of fractures and stripe wear, harder, more inert and more wear resistant, modern ceramic–ceramic hip replacements provide a strong alternative to traditional bearings. 相似文献
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Richard Camara Nathanael Matei John H Zhang 《Journal of cerebral blood flow and metabolism》2021,41(5):945
While the time window for reperfusion after ischemic stroke continues to increase, many patients are not candidates for reperfusion under current guidelines that allow for reperfusion within 24 h after last known well time; however, many case studies report favorable outcomes beyond 24 h after symptom onset for both spontaneous and medically induced recanalization. Furthermore, modern imaging allows for identification of penumbra at extended time points, and reperfusion risk factors and complications are becoming better understood. Taken together, continued urgency exists to better understand the pathophysiologic mechanisms and ideal setting of delayed recanalization beyond 24 h after onset of ischemia. 相似文献