| 11. |
- Corciulo, Carmen, et al.
(author)
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Physiological levels of estradiol limit murine osteoarthritis progression
- 2022
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In: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 255:2, s. 39-51
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Journal article (peer-reviewed)abstract
- Among patients with knee osteoarthritis (OA), postmenopausal women are over-represented. The purpose of this study was to determine whether deficiency of female sex steroids affects OA progression and to evaluate the protective effect of treatment with a physiological dose of 17 beta-estradiol (E2) on OA progression using a murine model. Ovariectomy (OVX) of female mice was used to mimic a postmenopausal state. OVX or sham-operated mice underwent surgery for destabilization of the medial meniscus (DMM) to induce OA. E2 was administered in a pulsed manner for 2 and 8 weeks. OVX of OA mice did not influence the cartilage phenotype or synovial thickness, while both cortical and trabecular subchondral bone mineral density (BMD) decreased after OVX compared with sham-operated mice at 8 weeks post-DMM surgery. Additionally, OVX mice displayed decreased motor activity, reduced threshold of pain sensitivity, and increased number of T cells in the inguinal lymph nodes compared to sham-operated mice 2 weeks after OA induction. Eight weeks of treatment with E2 prevented cartilage damage and thickening of the synovium in OVX OA mice. The motor activity was improved after E2 replacement at the 2 weeks time point, which was also associated with lower pain sensitivity in the OA paw. E2 treatment protected against OVX-induced loss of subchondral trabecular bone. The number of T cells in the inguinal lymph nodes was reduced by E2 treatment after 8 weeks. This study demonstrates that treatment with a physiological dose of E2 exerts a protective role by reducing OA symptoms.
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| 12. |
- Corciulo, Carmen, et al.
(author)
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Pulsed administration for physiological estrogen replacement in mice
- 2021
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In: F1000Research. - : F1000 Research Ltd. - 2046-1402 .- 1759-796X. ; 10
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Journal article (peer-reviewed)abstract
- Estrogens are important regulators of body physiology and have major effects on metabolism, bone, the immune- and central nervous systems. The specific mechanisms underlying the effects of estrogens on various cells, tissues and organs are unclear and mouse models constitute a powerful experimental tool to define the physiological and pathological properties of estrogens. Menopause can be mimicked in animal models by surgical removal of the ovaries and replacement therapy with 17β-estradiol in ovariectomized (OVX) mice is a common technique used to determine specific effects of the hormone. However, these studies are complicated by the non-monotonic dose-response of estradiol, when given as therapy. Increased knowledge of how to distribute estradiol in terms of solvent, dose, and administration frequency, is required in order to accurately mimic physiological conditions in studies where estradiol treatment is performed. In this study, mice were OVX and treated with physiological doses of 17β-estradiol-3-benzoate (E2) dissolved in miglyol or PBS. Subcutaneous injections were performed every 4 days to resemble the estrus cycle in mice. Results show that OVX induces an osteoporotic phenotype, fat accumulation and impairment of the locomotor ability, as expected. Pulsed administration of physiological doses of E2 dissolved in miglyol rescues the phenotypes induced by OVX. However, when E2 is dissolved in PBS the effects are less pronounced, possibly due to rapid wash out of the steroid.
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| 13. |
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| 14. |
- Humeniuk, Piotr, et al.
(author)
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Profiling of innate and adaptive immune cells during influenza virus infection reveals sex bias in invariant natural killer T (iNKT) cells
- 2023
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In: Immunity, Inflammation and Disease. - 2050-4527. ; 11:4
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Journal article (peer-reviewed)abstract
- Background: Influenza A virus (IAV) infection leads to significant morbidity and mortality. Biological sex influences the immune responses to IAV infection, resulting in higher mortality in women of reproductive age. Previous studies revealed increased activation of T and B cells in female mice after IAV infection, but extensive analysis of sex differences in both innate and adaptive immune cells over time is lacking. Invariant natural killer T (iNKT) cells are fast-reacting forces and modulators of immune responses that are important to IAV immunity, but it is not known if the presence and function of iNKT cells differ between females and males. The aim of this study was to determine immunological mechanisms that contribute to the increased disease severity in female mice during IAV infection. Methods: Female and male mice were infected with mouse-adapted IAV and monitored for weight loss and survival. Immune cell populations and cytokine expression in bronchoalveolar lavage fluid, lung, and mediastinal lymph node were determined at three time points after infection using flow cytometry and ELISA. Results: The results reveal increased severity and mortality in adult female mice compared to age- matched males. Female mice show larger increases in innate and adaptive immune cell populations and cytokine production in lung compared to mock on Day 6 postinfection. On Day 9 postinfection, female mice express higher numbers of iNKT cells in lung and liver compared to males. Conclusions: This comprehensive analysis of immune cells and cytokines over time following IAV infection reveals increased leukocyte expansion and stronger proinflammatory cytokine responses in female mice during disease initiation. Furthermore, this is the first study to report a sex bias in iNKT cell populations after IAV infection. The data suggests that the process of recovery from IAV-induced airway inflammation is associated with increased expansion of several different iNKT cell subpopulations in female mice.
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| 15. |
- Lawenius, Lina, et al.
(author)
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Pasteurized Akkermansia muciniphila protects from fat mass gain but not from bone loss
- 2020
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In: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 318:4
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Journal article (peer-reviewed)abstract
- Probiotic bacteria can protect from ovariectomy (ovx)-induced bone loss in mice. Akkermansia muciniphila is considered to have probiotic potential due to its beneficial effect on obesity and insulin resistance. The purpose of the present study was to determine if treatment with pasteurized Akkermansia muciniphila (pAkk) could prevent ovx-induced bone loss. Mice were treated with vehicle or pAkk for 4 wk, starting 3 days before ovx or sham surgery. Treatment with pAkk reduced fat mass accumulation confirming earlier findings. However, treatment with pAkk decreased trabecular and cortical bone mass in femur and vertebra of gonadal intact mice and did not protect from ovx-induced bone loss. Treatment with pAkk increased serum parathyroid hormone (PTH) levels and increased expression of the calcium transporter Trpv5 in kidney suggesting increased reabsorption of calcium in the kidneys. Serum amyloid A 3 (SAA3) can suppress bone formation and mediate the effects of PTH on bone resorption and bone loss in mice and treatment with pAkk increased serum levels of SAA3 and gene expression of Saa3 in colon. Moreover, regulatory T cells can be protective of bone and pAkk-treated mice had decreased number of regulatory T cells in mesenteric lymph nodes and bone marrow. In conclusion, treatment with pAkk protected from ovx-induced fat mass gain but not from bone loss and reduced bone mass in gonadal intact mice. Our findings with pAkk differ from some probiotics that have been shown to protect bone mass, demonstrating that not all prebiotic and probiotic factors have the same effect on bone.
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| 16. |
- Lejaeghere, Kurt, et al.
(author)
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Reproducibility in density functional theory calculations of solids.
- 2016
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 351:6280, s. 1415-1422
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Journal article (peer-reviewed)abstract
- The widespread popularity of density functional theory has given rise to an extensive range of dedicated codes for predicting molecular and crystalline properties. However, each code implements the formalism in a different way, raising questions about the reproducibility of such predictions. We report the results of a community-wide effort that compared 15 solid-state codes, using 40 different potentials or basis set types, to assess the quality of the Perdew-Burke-Ernzerhof equations of state for 71 elemental crystals. We conclude that predictions from recent codes and pseudopotentials agree very well, with pairwise differences that are comparable to those between different high-precision experiments. Older methods, however, have less precise agreement. Our benchmark provides a framework for users and developers to document the precision of new applications and methodological improvements.
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| 17. |
- Lundgren, Edvin, et al.
(author)
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Kinetic hindrance during the initial oxidation of Pd(100) at ambient pressures
- 2004
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In: Physical Review Letters. - 1079-7114. ; 92:4
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Journal article (peer-reviewed)abstract
- The oxidation of the Pd(100) surface at oxygen pressures in the 10(-6) to 10(3) mbar range and temperatures up to 1000 K has been studied in situ by surface x-ray diffraction (SXRD). The results provide direct structural information on the phases present in the surface region and on the kinetics of the oxide formation. Depending on the (T,p) environmental conditions, we observe either a thin (root5 x root5)R27degrees surface oxide or the growth of a rough, poorly ordered bulk oxide film of PdO predominantly with (001) orientation. By either comparison to the surface phase diagram from first-principles atomistic thermodynamics or by explicit time-resolved measurements we identify a strong kinetic hindrance to the bulk oxide formation even at temperatures as high as 675 K.
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| 18. |
- Lundgren, Edvin, et al.
(author)
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The intermetallic oxidation of Pd(100)
- 2002
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In: 7th International Conference on Nanometer-Scale Science and Technology and 21st European Conference on Surface Science.
-
Conference paper (peer-reviewed)abstract
- We have studied the Pd(100)-(√5×√5)-O structure formed by adsorption of 0.8 ML of oxygen by Scanning Tunneling Microscopy (STM), High Resolution Core Level Spectroscopy (HRCLS) and Density Functional Theory (DFT). We show that a recent tensor Low Energy Electron Diffraction (LEED) analysis of the Pd(100)-(√5×√5)-O structure is incompatible with our results from this structure. A new model that is consistent with our results is suggested. We also demonstrate the existence of dislocations observed by STM in the Pd(100)-(√5×√5)-O structure and explain their geometrical arrangement
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| 19. |
- Nash, Gerard, et al.
(author)
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Haemorheological result in a large multicentre study of claudicants treated with ketanserin
- 1990
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In: Clinical Hemorheology. - New York, USA : Pergamon Press. - 0271-5198. ; 10, s. 321-327
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Journal article (peer-reviewed)abstract
- Abstract An international, multi-centre trial was carried out to test the haemorheological effects of ketanserin, a serotonin antagonist, after treatment of intermittent claudicants for 1 year. Haematological indices, whole blood viscosity, plasma viscosity and red cell and white cell filterabi1ity were measured using standardised techniques. Even so, inter-laboratory variability, and intra-laboratory changes in control values in some centres over the 1 year period proved to be major obstacles. The pooled data showed no evidence of haemorheological changes, although data from the single largest centre indicated slightly lowered haematocrit and blood and plasma viscosity. Any rheological effects of serotonin antagonists in intermittent claudicants are probably small and unlikely to be the main source of any clinical efficacy. In general, it would appear that standardisation and monitoring of laboratory techniques must be strictly carried out if there is to be any hope of successfully carrying out multi-centre haemorheological trials. . Key words: Blood Rheology; Claudication; Serotonin Antagonists;
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| 20. |
- Scheffler, Julia M., et al.
(author)
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ER alpha Signaling in a Subset of CXCL12-Abundant Reticular Cells Regulates Trabecular Bone in Mice
- 2022
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In: JBMR Plus. - : Wiley. - 2473-4039. ; 6:8
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Journal article (peer-reviewed)abstract
- Estrogen has pronounced effects on the immune system, which also influences bone homeostasis. In recent years, stromal cells in lymphoid organs have gained increasing attention as they not only support the regulation of immune responses but also affect bone remodeling. A conditional knockout mouse model where estrogen receptor alpha (ER alpha) is deleted in CCL19-expressing stromal cells (Ccl19-Cre ER alpha(fl/fl) mice) was generated and bone densitometry was performed to analyze the importance of stromal cell-specific ER alpha signaling on the skeleton. Results showed that female Ccl19-Cre ER alpha(fl/fl) mice display reduced total bone mineral density and detailed X-ray analyses revealed that ER alpha expression in CCL19-expressing stromal cells is important for trabecular but not cortical bone homeostasis. Further analysis showed that the trabecular bone loss is caused by increased osteoclastogenesis. Additionally, the bone formation rate was reduced; however, the expression of osteoprogenitor genes was not altered. Analysis of the bone marrow stromal cell compartment revealed a deletion of ER alpha in a subgroup of CXCL12-abundant reticular (CAR) cells resulting in increased secretion of the pro-osteoclastogenic chemokine CXCL12. In conclusion, this study reveals the importance of ER alpha signaling in CAR cells for bone health. (c) 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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