Zobrazení zdroje stránky Irwinserup7242

Numerous studies confirmed that aberrant microRNA (miRNA) expression contributes to cancer development and progression. We carried out this study to explore the expression profile of miRNAs in intermediate risk acute myeloid leukemia (AML) and locate certain miRNAs as biomarkers. We profiled differentially expressed miRNAs by performing miRNA sequencing analysis in the patients' samples. Bioinformatic analysis showed the most significantly expressed genes mostly involved in cellular component organization, cell differentiation, and cell development. Reverse-transcription polymerase chain reaction validated the expression of miR-582-5p in different groups of AML samples. It was confirmed that miR-582-5p was downregulated in newly diagnosed AML and relapse/refractory AML compared with CR AML or controls. Among intermediate risk AML patients with normal cytogenetics, a lower level of miR-582-5p is correlated with an unfavorable outcome, and a shorter overall survival. [https://www.selleckchem.com/products/sovleplenib-hmpl-523.html Sovleplenib] Gain- and loss-of-function experiments revealed that miR-582-5p could inhibit proliferation, suppress migration, and invasion ability and induce apoptosis of leukemia cells. Furthermore, overexpression of miR-582-5p can increase sensitivity of cells to Ara-C. In conclusion, miR-582-5p can serve as an antioncogenic biomarker in intermediate risk AML with normal cytogenetics for risk classification and outcome prediction. These results showed a novel role for miR-582-5p in predicting the prognosis and promoting the tumor growth of AML.Chondral lesions lead to degenerative changes in the surrounding cartilage tissue, increasing the risk of developing post-traumatic osteoarthritis (PTOA). This study aimed to investigate the feasibility of quantitative magnetic resonance imaging (qMRI) for evaluation of articular cartilage in PTOA. Articular explants containing surgically induced and repaired chondral lesions were obtained from the stifle joints of seven Shetland ponies (14 samples). Three age-matched nonoperated ponies served as controls (six samples). The samples were imaged at 9.4 T. The measured qMRI parameters included T1 , T2 , continuous-wave T1ρ (CWT1ρ ), adiabatic T1ρ (AdT1ρ ), and T2ρ (AdT2ρ ) and relaxation along a fictitious field (TRAFF ). For reference, cartilage equilibrium and dynamic moduli, proteoglycan content and collagen fiber orientation were determined. Mean values and profiles from full-thickness cartilage regions of interest, at increasing distances from the lesions, were used to compare experimental against control and to correlate qMRI with the references. Significant alterations were detected by qMRI parameters, including prolonged T1 , CWT1ρ , and AdT1ρ in the regions adjacent to the lesions. The changes were confirmed by the reference methods. CWT1ρ was more strongly associated with the reference measurements and prolonged in the affected regions at lower spin-locking amplitudes. Moderate to strong correlations were found between all qMRI parameters and the reference parameters (ρ = -0.531 to -0.757). T1 , low spin-lock amplitude CWT1ρ , and AdT1ρ were most responsive to changes in visually intact cartilage adjacent to the lesions. In the context of PTOA, these findings highlight the potential of T1 , CWT1ρ , and AdT1ρ in evaluation of compositional and structural changes in cartilage.Myocarditis is an inflammation of the myocardium that can progress to a more severe phenotype of dilated cardiomyopathy (DCM). Three main harmful factors determine this progression inflammation, cell death, and oxidative stress. Lipoxins and their derivatives are endogenous proresolving mediators that induce the resolution of the inflammatory process. This study aims to determine whether these mediators play a protective role in a murine model of experimental autoimmune myocarditis (EAM) by treating with the lipoxin A4 analog BML-111. We observed that EAM mice presented extensive infiltration areas that correlated with higher levels of inflammatory and cardiac damage markers. Both parameters were significantly reduced in BML-treated EAM mice. Consistently, cardiac dysfunction, hypertrophy, and emerging fibrosis detected in EAM mice was prevented by BML-111 treatment. At the molecular level, we demonstrated that treatment with BML-111 hampered apoptosis and oxidative stress induction by EAM. Moreover, both in vivo and in vitro studies revealed that these beneficial effects were mediated by activation of Nrf2 pathway through CaMKK2-AMPKα kinase pathway. Altogether, our data indicate that treatment with the lipoxin derivative BML-111 effectively alleviates EAM outcome and prevents cardiac dysfunction, thus, underscoring the therapeutic potential of lipoxins and their derivatives to treat myocarditis and other inflammatory cardiovascular diseases.Extracellular vesicles (EVs) are abundant, lipid-enclosed vectors that contain nucleic acids and proteins, they can be secreted from donor cells and freely circulate, and they can be engulfed by recipient cells thus enabling systemic communication between heterotypic cell types. However, genetic tools for labeling, isolating, and auditing cell type-specific EVs in vivo, without prior in vitro manipulation, are lacking. We have used CRISPR-Cas9-mediated genome editing to generate mice bearing a CD63-emGFPloxP/stop/loxP knock-in cassette that enables the specific labeling of circulating CD63+ vesicles from any cell type when crossed with lineage-specific Cre recombinase driver mice. As proof-of-principle, we have crossed these mice with Cdh5-CreERT2 mice to generate CD63emGFP+ vasculature. Using these mice, we show that developing vasculature is marked with emerald GFP (emGFP) following tamoxifen administration to pregnant females. In adult mice, quiescent vasculature and angiogenic vasculature (in tumors) is also marked with emGFP. Moreover, whole plasma-purified EVs contain a subpopulation of emGFP+ vesicles that are derived from the endothelium, co-express additional EV (e.g., CD9 and CD81) and endothelial cell (e.g., CD105) markers, and they harbor specific miRNAs (e.g., miR-126, miR-30c, and miR-125b). This new mouse strain should be a useful genetic tool for generating cell type-specific, CD63+ EVs that freely circulate in serum and can subsequently be isolated and characterized using standard methodologies.