| 1. |
- Bailey, D. L., et al.
(författare)
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Combined PET/MRI : Global Warming-Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tubingen, Germany
- 2018
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Ingår i: Molecular Imaging and Biology. - : SPRINGER. - 1536-1632 .- 1860-2002. ; 20:1, s. 4-20
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Forskningsöversikt (refereegranskat)abstract
- The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tubingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we are in a position to describe the in vivo nature of disease processes, metabolism, evolution of cancer and the monitoring of response to pharmacological interventions and therapies. As such, PET/MRI is a key to advancing medicine and patient care.
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| 2. |
- Liu, P., et al.
(författare)
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Loss of menin in osteoblast lineage affects osteocyte-osteoclast crosstalk causing osteoporosis
- 2017
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Ingår i: Cell Death and Differentiation. - : Springer Science and Business Media LLC. - 1350-9047 .- 1476-5403. ; 24:4, s. 672-682
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Tidskriftsartikel (refereegranskat)abstract
- During osteoporosis bone formation by osteoblasts is reduced and/or bone resorption by osteoclasts is enhanced. Currently, only a few factors have been identified in the regulation of bone integrity by osteoblast-derived osteocytes. In this study, we show that specific disruption of menin, encoded by multiple endocrine neoplasia type 1 (Men1), in osteoblasts and osteocytes caused osteoporosis despite the preservation of osteoblast differentiation and the bone formation rate. Instead, an increase in osteoclast numbers and bone resorption was detected that persisted even when the deletion of Men1 was restricted to osteocytes. We demonstrate that isolated Men1-deficient osteocytes expressed numerous soluble mediators, such as C-X-C motif chemokine 10 (CXCL10), and that CXCL10-mediated osteoclastogenesis was reduced by CXCL10-neutralizing antibodies. Collectively, our data reveal a novel role for Men1 in osteocyte-osteoclast crosstalk by controlling osteoclastogenesis through the action of soluble factors. A role for Men1 in maintaining bone integrity and thereby preventing osteoporosis is proposed.
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| 3. |
- Friscic, J., et al.
(författare)
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Dietary Derived Propionate Regulates Pathogenic Fibroblast Function and Ameliorates Experimental Arthritis and Inflammatory Tissue Priming
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Short-chain fatty acids are gut-bacteria-derived metabolites that execute important regulatory functions on adaptive immune responses, yet their influence on inflammation driven by innate immunity remains understudied. Here, we show that propionate treatment in drinking water or upon local application into the joint reduced experimental arthritis and lowered inflammatory tissue priming mediated by synovial fibroblasts. On a cellular level, incubation of synovial fibroblasts with propionate or a physiological mixture of short-chain fatty acids interfered with production of inflammatory mediators and migration and induced immune-regulatory fibroblast senescence. Our study suggests that propionate mediates its alleviating effect on arthritis by direct abrogation of local arthritogenic fibroblast function.
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| 4. |
- Rauch, Alexander, et al.
(författare)
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Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor.
- 2010
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Ingår i: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 11:6, s. 517-31
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Tidskriftsartikel (refereegranskat)abstract
- Development of osteoporosis severely complicates long-term glucocorticoid (GC) therapy. Using a Cre-transgenic mouse line, we now demonstrate that GCs are unable to repress bone formation in the absence of glucocorticoid receptor (GR) expression in osteoblasts as they become refractory to hormone-induced apoptosis, inhibition of proliferation, and differentiation. In contrast, GC treatment still reduces bone formation in mice carrying a mutation that only disrupts GR dimerization, resulting in bone loss in vivo, enhanced apoptosis, and suppressed differentiation in vitro. The inhibitory GC effects on osteoblasts can be explained by a mechanism involving suppression of cytokines, such as interleukin 11, via interaction of the monomeric GR with AP-1, but not NF-kappaB. Thus, GCs inhibit cytokines independent of GR dimerization and thereby attenuate osteoblast differentiation, which accounts, in part, for bone loss during GC therapy.
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| 5. |
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| 6. |
- Cao, Shan, et al.
(författare)
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L-arginine metabolism inhibits arthritis and inflammatory bone loss
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ PUBLISHING GROUP. - 0003-4967 .- 1468-2060. ; 83, s. 72-87
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss.MethodsL-arginine was applied to three arthritis models (collagen-induced arthritis, serum-induced arthritis and human TNF transgenic mice). Inflammation was assessed clinically and histologically, while bone changes were quantified by mu CT and histomorphometry. In vitro, effects of L-arginine on osteoclast differentiation were analysed by RNA-seq and mass spectrometry (MS). Seahorse, Single Cell ENergetIc metabolism by profilIng Translation inHibition and transmission electron microscopy were used for detecting metabolic changes in osteoclasts. Moreover, arginine-associated metabolites were measured in the serum of rheumatoid arthritis (RA) and pre-RA patients.ResultsL-arginine inhibited arthritis and bone loss in all three models and directly blocked TNF alpha-induced murine and human osteoclastogenesis. RNA-seq and MS analyses indicated that L-arginine switched glycolysis to oxidative phosphorylation in inflammatory osteoclasts leading to increased ATP production, purine metabolism and elevated inosine and hypoxanthine levels. Adenosine deaminase inhibitors blocking inosine and hypoxanthine production abolished the inhibition of L-arginine on osteoclastogenesis in vitro and in vivo. Altered arginine levels were also found in RA and pre-RA patients.ConclusionOur study demonstrated that L-arginine ameliorates arthritis and bone erosion through metabolic reprogramming and perturbation of purine metabolism in osteoclasts.
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| 7. |
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| 8. |
- Zaiss, J., et al.
(författare)
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Impact of Lagrangian Sea Surface Temperature Variability on Southern Ocean Phytoplankton Community Growth Rates
- 2021
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Ingår i: Global Biogeochemical Cycles. - : American Geophysical Union (AGU). - 0886-6236 .- 1944-9224. ; 35:8
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Tidskriftsartikel (refereegranskat)abstract
- Ocean phytoplankton play a critical role in the global carbon cycle, contributing similar to 50% of global photosynthesis. As planktonic organisms, phytoplankton encounter significant environmental variability as they are advected throughout the ocean. How this variability impacts phytoplankton growth rates and population dynamics remains unclear. Here, we systematically investigated the impact of different rates and magnitudes of sea surface temperature (SST) variability on phytoplankton community growth rates using surface drifter observations from the Southern Ocean (>30 degrees S) and a phenotype-based ecosystem model. Short-term SST variability (<7 days) had a minimal impact on phytoplankton community growth rates. Moderate SST changes of 3-4 degrees C over 7-45 days produced a large time lag between the temperature change and the biological response. The impact of SST variability on community growth rates was nonlinear and a function of the rate and magnitude of change. Additionally, the nature of variability generated in a Lagrangian reference frame (following trajectories of surface water parcels) was larger than that within an Eulerian reference frame (fixed point), which initiated different phytoplankton responses between the two reference frames. Finally, we found that these dynamics were not captured by the Eppley growth model commonly used in global biogeochemical models and resulted in an overestimation of community growth rates, particularly in dynamic, strong frontal regions of the Southern Ocean. This work demonstrates that the timescale for environmental selection (community replacement) is a critical factor in determining community composition and takes a first step towards including the impact of variability and biological response times into biogeochemical models.
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| 9. |
- Zhou, Jinyuan, et al.
(författare)
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Review and consensus recommendations on clinical APT-weighted imaging approaches at 3T : Application to brain tumors
- 2022
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 88:2, s. 546-574
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Tidskriftsartikel (refereegranskat)abstract
- Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi-center trials in larger patient cohorts and, ultimately, routine clinical use.
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