Acute myeloid leukemia (AML) is a heterogeneous group of hematological malignancies characterized by differentiation arrest, high relapse rates, and poor survival. The bone marrow (BM) microenvironment is recognized as a critical mediator of drug resistance and a primary site responsible for AML relapse. Our previous study reported that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr) induces AML cell differentiation by inhibiting pyrimidine synthesis and activating Checkpoint kinase 1.
View Article and Find Full Text PDF: Rehabilitation is a part of the comprehensive treatment of multiple sclerosis (MS). If present, psychological reactive states limit the results of the rehabilitation. The objectives were to determine the impact of psychological reactive states in these patients on the functionality obtained by rehabilitation and QoL, and to determine the connection between the objective and subjective evaluation.
View Article and Find Full Text PDFChanges in the hemostatic system during COVID infection lead to hypercoagulability. Numerous studies have evaluated hemostatic abnormalities in COVID patients during acute infection, in the period of hospitalization. However, the hemostatic status following hospital discharge has not been sufficiently assessed.
View Article and Find Full Text PDFLow-dose cytarabine (LDAC) is a standard therapy for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. While high doses of cytarabine induce cytotoxicity, the precise mechanism of action of LDAC in AML remains elusive. studies have demonstrated LDAC-induced differentiation; however, such differentiation is seldom observed .
View Article and Find Full Text PDFIntroduction: Prothrombin Belgrade mutation is the result of the c.1787G>A substitution in the prothrombin gene. It is located in the antithrombin and sodium binding site and leads to impaired inactivation of thrombin by antithrombin, resulting in antithrombin resistance and thrombotic disorders.
View Article and Find Full Text PDFBiofilm production facilitates microbial colonization of wounds and catheters. produces high levels of biofilm and causes difficult-to-treat nosocomial infections. is another strong biofilm producer which may facilitate adhesion by providing hyphae-mediated OmpA-binding sites.
View Article and Find Full Text PDFAntithrombin resistance is a rare subtype of hereditary thrombophilia caused by prothrombin gene variants, leading to thrombotic disorders. Recently, the Prothrombin Belgrade variant has been reported as a specific variant that leads to antithrombin resistance in two Serbian families with thrombosis. However, due to clinical data scarcity and the inapplicability of traditional genome-wide association studies (GWAS), a broader perspective on molecular and phenotypic mechanisms associated with the Prothrombin Belgrade variant is yet to be uncovered.
View Article and Find Full Text PDFBackground: Coagulation dysfunction represents a serious complication in patients during the COVID-19 infection, while fulminant thrombotic complications emerge as critical issues in individuals with severe COVID-19. In addition to a severe clinical presentation, comorbidities and age significantly contribute to the development of thrombotic complications in this disease. However, there is very little data on association of congenital thrombophilia and thrombotic events in the setting of COVID-19.
View Article and Find Full Text PDFAcute myeloid leukemia (AML) is characterized by arrested differentiation making differentiation therapy a promising treatment strategy. Recent success of inhibitors of mutated isocitrate dehydrogenase (IDH) invigorated interest in differentiation therapy of AML so that several new drugs have been proposed, including inhibitors of dihydroorotate dehydrogenase (DHODH), an enzyme in pyrimidine synthesis. Cytarabine, a backbone of standard AML therapy, is known to induce differentiation at low doses, but the mechanism is not completely elucidated.
View Article and Find Full Text PDFThe complexity in the styles of 1200 Byzantine icons painted between 13th and 16th from Greece, Russia and Romania was investigated through the Kolmogorov algorithmic information theory. The aim was to identify specific quantitative patterns which define the key characteristics of the three different painting schools. Our novel approach using the artificial surface images generated with Inverse FFT and the Midpoint Displacement (MD) algorithms, was validated by comparison of results with eight fractal and non-fractal indices.
View Article and Find Full Text PDFIn this paper, we present a hardware and software platform for signal processing (SPP) in long-range, multi-spectral, electro-optical systems (MSEOS). Such systems integrate various cameras such as lowlight color, medium or long-wave-infrared thermal and short-wave-infrared cameras together with other sensors such as laser range finders, radars, GPS receivers, etc. on rotational pan-tilt positioner platforms.
View Article and Find Full Text PDFAll-trans retinoic acid (ATRA)-based therapy for acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML), is the most successful example of differentiation therapy. Although ATRA can induce differentiation in some non-APL AML cell lines and primary blasts, clinical results of adding ATRA to standard therapy in non-APL AML patients have been inconsistent, probably due to use of different regimens and lack of diagnostic tools for identifying which patients may be sensitive to ATRA. In this study, we exposed primary blasts obtained from non-APL AML patients to ATRA to test for differentiation potential in vitro.
View Article and Find Full Text PDF5-Aminoimidazole-4-carboxamide ribonucleoside (AICAr) has been one of the most commonly used pharmacological modulators of AMPK activity. The majority of early studies on the role of AMPK, both in the physiological regulation of metabolism and in cancer pathogenesis, were based solely on the use of AICAr as an AMPK-activator. Even with more complex models of AMPK downregulation and knockout being introduced, AICAr remained a regular starting point for many studies focusing on AMPK biology.
View Article and Find Full Text PDFAcute respiratory distress syndrome is an acute inflammatory lung process, which leads to protein-rich nonhydrostatic pulmonary edema, refractory hypoxemia, and lung "stiffness". There are a number of therapies that are currently being investigated in the treatment of sepsis; one of the most promising treatment options at this moment is cytokine removal by hemoperfusion (CytoSorb). We present the case of a 29-year-old male patient who was admitted to the Medical Intensive Care Unit in a state of multiple organ dysfunction and massive bilateral pneumonia caused by influenza type A.
View Article and Find Full Text PDFBackground: All-trans retinoic acid (ATRA)-based treatment of acute promyelocytic leukemia (APL) is the most successful pharmacological treatment of acute myeloid leukemia (AML). Recent development of inhibitors of mutated isocitrate dehydrogenase and dihydroorotate dehydrogenase (DHODH) has revived interest in differentiation therapy of non-APL AML. Our previous studies demonstrated that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr) induced differentiation of monocytic cell lines by activating the ATR/Chk1 via pyrimidine depletion.
View Article and Find Full Text PDFAccess to information is key for improving the position of persons with disabilities in society. Familiarity with state regulations regarding access to information could be influenced by communication with state authorities concerning the rights of persons with disabilities, especially access to information. Familiarity with these regulations and the specified communication with state authorities might be affected by a number of background variables, such as age and education completed.
View Article and Find Full Text PDFBackground: Thrombosis is a major global disease burden with almost 60% of cases related to underlying heredity and most cases still idiopathic. Synonymous single nucleotide polymorphisms (sSNPs) are considered silent and phenotypically neutral. Our previous study revealed a novel synonymous FII c.
View Article and Find Full Text PDFBackground/aim: Thrombin plays significant roles in various types of cancer. However, the expression levels of prothrombin, the thrombin precursor, in cancer remain unclear. Variants of the 3'end of the prothrombin gene lead to increased prothrombin expression.
View Article and Find Full Text PDFInteractions between fullerene C and a frequently used supplement for sport activities, ephedrine (EPH), have been studied in detail by a combination of density functional theory (DFT), time dependent DFT (TD-DFT) calculations, the symmetry-adapted perturbation theory (SAPT) approach and molecular dynamics (MD) simulations. Information about interaction energies and non-covalent interactions formed between C and EPH have been obtained by DFT calculations. TD-DFT calculations have been used in order to obtain UV/vis spectra and to check whether the presence of the EPH molecule produces significant changes in the spectrum.
View Article and Find Full Text PDFMetabolic pathways play important roles in proliferation and differentiation of malignant cells. 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAr), a precursor in purine biosynthesis and a well-established activator of AMP-activated protein kinase (AMPK), induces widespread metabolic alterations and is commonly used for dissecting the role of metabolism in cancer. We have previously reported that AICAr promotes differentiation and inhibits proliferation of myeloid leukemia cells.
View Article and Find Full Text PDFInherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the AT gene (SERPINC1). Considering that the genotype phenotype relationship in AT deficiency patients remains unclear, especially in pediatric patients, the aim of our study was to evaluate genotype phenotype correlation in a Serbian pediatric population. A retrospective cohort study included 19 children younger than 18 years, from 15 Serbian families, with newly diagnosed AT deficiency.
View Article and Find Full Text PDFBackground: Hypophosphatemia can complicate and prolong the treatment of critically ill patients, and it is even thought to be related to mortality rate.
Objectives: The aim of this study is to determine whether using extemporary prepared phosphate buffer in pharmacy would help correct serum phosphate in critically ill patients.
Methods: A prospective study was conducted at the medical intensive care unit over a period of 1 year and included 50 patients who were diagnosed with hypophosphatemia.