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991.
Hussein Farah Susanne N. Wijesinghe Thomas Nicholson Fawzeyah Alnajjar Michelangelo Certo Abdullah Alghamdi Edward T. Davis Stephen P. Young Claudio Mauro Simon W. Jones 《International journal of molecular sciences》2022,23(6)
Changes in cellular metabolism have been implicated in mediating the activated fibroblast phenotype in a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim of this study was therefore to characterise the metabolic profile of synovial joint fluid and synovial fibroblasts under both basal and inflammatory conditions in a cohort of obese and normal-weight hip OA patients. Furthermore, we sought to ascertain whether modulation of a metabolic pathway in OA synovial fibroblasts could alter their inflammatory activity. Synovium and synovial fluid was obtained from hip OA patients, who were either of normal-weight or obese and were undergoing elective joint replacement surgery. The synovial fluid metabolome was determined by 1H NMR spectroscopy. The metabolic profile of isolated synovial fibroblasts in vitro was characterised by lactate secretion, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyser. The effects of a small molecule pharmacological inhibitor and siRNA targeted at glutaminase-1 (GLS1) were assessed to probe the role of glutamine metabolism in OA synovial fibroblast function. Obese OA patient synovial fluid (n = 5) exhibited a different metabotype, compared to normal-weight patient fluid (n = 6), with significantly increased levels of 1, 3-dimethylurate, N-Nitrosodimethylamine, succinate, tyrosine, pyruvate, glucose, glycine and lactate, and enrichment of the glutamine–glutamate metabolic pathway, which correlated with increasing adiposity. In vitro, isolated obese OA fibroblasts exhibited greater basal lactate secretion and aerobic glycolysis, and increased mitochondrial respiration when stimulated with pro-inflammatory cytokine TNFα, compared to fibroblasts from normal-weight patients. Inhibition of GLS1 attenuated the TNFα-induced expression and secretion of IL-6 in OA synovial fibroblasts. These findings suggest that altered cellular metabolism underpins the inflammatory phenotype of OA fibroblasts, and that targeted inhibition of glutamine–glutamate metabolism may provide a route to reducing the pathological effects of joint inflammation in OA patients who are obese. 相似文献
992.
Tingting Gu Jesper Just Katrine Tang Stenz Yan Yan Peter Sieljacks Jakob Wang Thomas Skjaerlund Groennebaek Jesper Emil Jakobsgaard Emil Rindom Jon Herskind Anders Gravholt Thomas Ravn Lassen Mathias Jrgensen Rikke Bk Eugenio Gutirrez-Jimnez Nina Kerting Iversen Peter Mondrup Rasmussen Jens Randel Nyengaard Malene Mller Jrgensen Frank de Paoli Hans Erik Btker Jrgen Kjems Kristian Vissing Kim Ryun Drasbek 《International journal of molecular sciences》2022,23(6)
Ischemic conditioning and exercise have been suggested for protecting against brain ischemia-reperfusion injury. However, the endogenous protective mechanisms stimulated by these interventions remain unclear. Here, in a comprehensive translational study, we investigated the protective role of extracellular vesicles (EVs) released after remote ischemic conditioning (RIC), blood flow restricted resistance exercise (BFRRE), or high-load resistance exercise (HLRE). Blood samples were collected from human participants before and at serial time points after intervention. RIC and BFRRE plasma EVs released early after stimulation improved viability of endothelial cells subjected to oxygen-glucose deprivation. Furthermore, post-RIC EVs accumulated in the ischemic area of a stroke mouse model, and a mean decrease in infarct volume was observed for post-RIC EVs, although not reaching statistical significance. Thus, circulating EVs induced by RIC and BFRRE can mediate protection, but the in vivo and translational effects of conditioned EVs require further experimental verification. 相似文献
993.
Daniela Grimm Herbert Schulz Marcus Krüger Jos Luis Corts-Snchez Marcel Egli Armin Kraus Jayashree Sahana Thomas J. Corydon Ruth Hemmersbach Petra M. Wise Manfred Infanger Markus Wehland 《International journal of molecular sciences》2022,23(6)
Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology. 相似文献
994.
995.
Hans Liew Stewart Mein Thomas Tessonnier Amir Abdollahi Jürgen Debus Ivana Dokic Andrea Mairani 《International journal of molecular sciences》2022,23(6)
The impact of the exact temporal pulse structure on the potential cell and tissue sparing of ultra-high dose-rate irradiation applied in FLASH studies has gained increasing attention. A previous version of our biophysical mechanistic model (UNIVERSE: UNIfied and VERSatile bio response Engine), based on the oxygen depletion hypothesis, has been extended in this work by considering oxygen-dependent damage fixation dynamics on the sub-milliseconds scale and introducing an explicit implementation of the temporal pulse structure. The model successfully reproduces in vitro experimental data on the fast kinetics of the oxygen effect in irradiated mammalian cells. The implemented changes result in a reduction in the assumed amount of oxygen depletion. Furthermore, its increase towards conventional dose-rates is parameterized based on experimental data from the literature. A recalculation of previous benchmarks shows that the model retains its predictive power, while the assumed amount of depleted oxygen approaches measured values. The updated UNIVERSE could be used to investigate the impact of different combinations of pulse structure parameters (e.g., dose per pulse, pulse frequency, number of pulses, etc.), thereby aiding the optimization of potential clinical application and the development of suitable accelerators. 相似文献
996.
T.Stegmaier V.von Amim M.Linke M.Milwich J.Sarsour A.Scherrieble P.Schneider H.Planck 戴自怡 《国际纺织导报》2007,35(6):10-12,14
纤维基技术的应用对仿生学的成功发展呈现出巨大的潜力,因为宇宙成物在生长过程、多毛结构和增强纤维方面具有许多相似性.约七年前,邓肯道夫纺织技术与工艺研究所协同众位生物学家一起开创了仿生学的研发,至今方兴未艾. 相似文献
997.
A robust adaptive estimation procedure for location estimation problems is developed. Classification in this procedure is done on the basis of skewness and tailweight, using two statistics that are ratios of linear functions of sample order statistics. The associated estimators are of the general type known as M-estimators, Following the development of the adaptive location estimation procedure, an application to the k population selection problem is given. Monte Carlo results show the superiority of the adaptive procedure to the sample means procedure, the rank sum procedure, and the previously developed adaptive procedure of Randles, Ramberg, and Hogg. 相似文献
998.
999.
Thomas J. Siller Alma Rosales John Haines Aaron Benally 《Canadian Metallurgical Quarterly》2009,135(3):102-108
The development of engineering students’ professional skills has gained considerable national attention from Accreditation Board for Engineering and Technology, the National Academy of Engineering, ASCE, and other constituents. There is little debate that these professional skills are necessary. Engineering programs have tried many approaches to develop these skills in the undergraduate programs. Colorado State University (CSU) has developed a new approach modeled on the type of professional development that occurs in the professional environment. This new Professional Learning Institute (PLI) provides students with a broad array of workshops, presentations, and experiential opportunities addressing the areas of cross cultural communication and teamwork, innovation, leadership, ethics, and public service. This program introduces students to the concept of professional development through required extracurricular activities, includes minimum requirements along with requirements to earn certificates in specialty areas for motivated students. The majority of offerings in the PLI are presented by leaders from the engineering profession who have teamed with CSU to provide high quality programs for our students. 相似文献
1000.
F.J. Berry I.S. Lyubutin E.A. Moore M.F. Thomas T.V. Dmitrieva 《Materials Chemistry and Physics》2009,113(2-3):714-716
The tin-doped sulphur-containing compound of composition Fe1.05Cr1.90Sn0.05S4, in which tin is located on the octahedral sites as Sn(IV) in the spinel-related structure, has been examined by 119Sn Mössbauer spectroscopy. The data complement results obtained by 57Fe Mössbauer spectroscopy and show that tin doping increases the magnetic ordering temperature of pure FeCr2S4. These results are compared with the data obtained on tin-doped CuCr2X4 compounds (X = O, S, Se). 相似文献