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Hematopoietic stem cells (HSCs) remain mostly quiescent under steady-state conditions but switch to a proliferative state following hematopoietic stress, e.g., bone marrow (BM) injury, transplantation, or systemic infection and inflammation. The homeostatic balance between quiescence, self-renewal, and differentiation of HSCs is strongly dependent on their interactions with cells that constitute a specialized microanatomical environment in the BM known as the HSC niche. Here, we identified the secreted extracellular matrix protein Del-1 as a component and regulator of the HSC niche. Specifically, we found that Del-1 was expressed by several cellular components of the HSC niche, including arteriolar endothelial cells, CXCL12-abundant reticular (CAR) cells, and cells of the osteoblastic lineage. Del-1 promoted critical functions of the HSC niche, as it regulated long-term HSC (LT-HSC) proliferation and differentiation toward the myeloid lineage. Del-1 deficiency in mice resulted in reduced LT-HSC proliferation and infringed preferentially upon myelopoiesis under both steady-state and stressful conditions, such as hematopoietic cell transplantation and G-CSF- or inflammation-induced stress myelopoiesis. Del-1-induced HSC proliferation and myeloid lineage commitment were mediated by [beta] integrin on hematopoietic progenitors. This hitherto unknown Del-1 function in the HSC niche represents a juxtacrine homeostatic adaptation of the hematopoietic system in stress myelopoiesis., Introduction Hematopoietic stem cells (HSC) lie at the core of the hematopoietic and immune systems and have a unique capacity for self-renewal and differentiation to multipotent and lineage-committed hematopoietic progenitors, [...]

Trained immunity is a long-term increase in responsiveness of innate immune cells, induced by certain infections and vaccines. During the last 3 years of the COVID-19 pandemic, vaccines that induce trained immunity, such as BCG, MMR, OPV, and others, have been investigated for their capacity to protect against COVID-19. Further, trained immunity-inducing vaccines have been shown to improve B and T cell responsiveness to both mRNA- and adenovirus-based anti-COVID-19 vaccines. Moreover, SARS-CoV-2 infection itself induces inappropriately strong programs of trained immunity in some individuals, which may contribute to the long-term inflammatory sequelae. In this review, we detail these and other aspects of the role of trained immunity in SARS-CoV-2 infection and COVID-19. We also examine the learnings from the trained immunity studies conducted in the context of this pandemic and discuss how they may help us in preparing for future infectious outbreaks. Trained immunity-inducing vaccines have been suggested to protect against heterologous infections, including COVID-19. This review presents the studies performed during the pandemic that have investigated the effects of vaccines such as BCG, OPV, MMR, and others against COVID-19. In addition, data are reviewed that suggest that COVID-19 itself and the novel COVID-19 vaccines can also induce trained immunity programs. [ABSTRACT FROM AUTHOR]

Abstract Background The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis. Methods Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography. Results Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and DLCO were independent predictors of systolic pulmonary artery pressure. Conclusion Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis.

Abstract Background Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been of diagnostic value in Northern European Caucasian patients with rheumatoid arthritis (RA). In these populations, anti-CCP antibodies are associated with the HLA-DRB1 shared epitope. We assessed the diagnostic value of anti-CCP antibodies in Greek patients with RA where the HLA shared epitope was reported in a minority of patients. Methods Using an enzyme-linked immunosorbent assay (ELISA) (CCP2) kit, we tested anti-CCP antibodies in serum samples from 155 Greek patients with RA, 178 patients with other rheumatic diseases, and 100 blood donors. We also determined rheumatoid factor (RF) and compared it to anti-CCP antibodies for area under the curve (AUC), sensitivity, specificity and likelihood ratios. Results Sensitivity of anti-CCP2 antibodies and RF for RA was 63.2% and 59.1%, and specificity was 95.0% and 91.2%, respectively. When considered simultaneously, the AUC for anti-CCP antibodies was 0.90 with 95% CI of 0.87 to 0.93 and the AUC for RF was 0.71 with 95% CI of 0.64 to 0.77. The presence of both antibodies increased specificity to 98.2%. Anti-CCP antibodies were positive in 34.9% of RF-negative RA patients. Anti-CCP antibodies showed a correlation with the radiographic joint damage. Anti-CCP-positive RA patients had increased the swollen joint count and serum CRP concentration compared to anti-CCP-negative RA patients (Mann-Whitney U test, p = 0.01, and p < 0.001, respectively). However, no correlation was found between anti-CCP antibodies and DAS28 score (r = 0.13, p = 0.12). Conclusion In Greek patients with RA, anti-CCP2 antibodies exhibit a better diagnostic value than RF and a correlation with radiological joint damage and therefore are useful in everyday rheumatology practice.

This study introduces a novel magnetic nanohybrid material consisting of ferromagnetic (FM) bcc Fe–Co nanoparticles (NPs) grown on nanodiamond (ND) nanotemplates. A combination of wet chemistry, which produces chemical precursors and their subsequent thermal treatment under vacuum, was utilized for its development. The characterization and study of the prepared samples performed with a range of specialized experimental techniques reveal that thermal treatment of the as-prepared hybrid precursors under a range of annealing conditions leads to the development of Co-rich Fe–Co alloy NPs, with average sizes in the range of 6–10 nm, that exhibit uniform distribution on the surfaces of the ND nanotemplates and demonstrate FM behavior throughout a temperature range from 2 K to 400 K, with maximum magnetization values ranging between 18.9 and 21.1 emu/g and coercivities ranging between 112 and 881 Oe. Moreover, 57Fe Mössbauer spectroscopy reveals that apart from the predominant bcc FM Fe–Co phase, iron atoms also participate in the formation of a secondary martensitic-type Fe–Co phase. The emergence of this distinctive phase is attributed to the diffusion of carbon atoms within the Fe–Co lattices during their formation at elevated temperatures. The source of these carbon atoms is related to the unique morphological properties of the ND growth matrices, which facilitate surface sp2 formations. Apart from their diffusion within the Fe–Co NP lattice, the carbon atoms also reconstruct layered graphitic-type nanostructures enveloping the metallic alloy NPs. These non-typical nanohybrid materials, reported here for the first time in the literature, hold significant potential for use in applications related, but not limited to, biomedicine, biopharmaceutics, catalysis, and other various contemporary technological fields. [ABSTRACT FROM AUTHOR]

A novel endeavor based on the synthesis, characterization and study of a hybrid crystalline magnetic nanostructured material composed of bimetallic iron–rhodium nanoalloys, grown on nanodiamond nanotemplates, is reported in this study. The development of this hybrid magnetic nanomaterial is grounded in the combination of wet chemistry and thermal annealing under vacuum. In order to assess, evaluate and interpret the role and special properties of the nanodiamond supporting nanotemplates on the growth and properties of the bimetallic ferromagnetic Fe–Rh nanoparticles on their surfaces, unsupported free FeRh nanoparticles of the same nominal stoichiometry as for the hybrid sample were also synthesized. The characterization and study of the prepared samples with a range of specialized experimental techniques, including X-ray diffraction, transmission and scanning transmission electron microscopy with energy dispersive X-ray analysis, magnetization and magnetic susceptibility measurements and 57Fe Mössbauer spectroscopy, reveal that thermal annealing of the hybrid sample under specific conditions (vacuum, 700 °C, 30 min) leads to the formation of a rhodium-rich FeRh alloy nanostructured phase, with an average particle size of 4 nm and good dispersion on the surfaces of the nanodiamond nanotemplates and hard ferromagnetic characteristics at room temperature (coercivity of ~500 Oe). In contrast, thermal annealing of the unsupported free nanoparticle sample under the same conditions fails to deliver ferromagnetic characteristics to the FeRh nanostructured alloy phase, which shows only paramagnetic characteristics at room temperature and spin glass ordering at low temperatures. The ferromagnetic nanohybrids are proposed to be exploited in a variety of important technological applications, such as magnetic recording, magnetic resonance imaging contrast and magnetic hyperthermia agents. [ABSTRACT FROM AUTHOR]

The article presents abstracts of papers presented at the 12th Annual Meeting of the German Society for Clinical Chemistry and Laboratory Medicine on topics including individualized immunotherapies, cystic fibrosis screening for newborns and atherogenic lipoprotein.

The article presents abstracts on laboratory medicine which include the use of flow cytometry in the diagnosis of myelodysplastic syndrome (MDS), the significance of DNA methylation in colorectal cancer and the association between skin aging and epigenetic modifications.