Starting from benzyl 30-oxobetulinate and 30-oxobetulin diacetate, substituted dienes were synthesized and subjected to Diels-Alder reaction, yielding a variety of triterpenoid phthalates, phthalimides, and related derivatives. A total of 55 new compounds were prepared and tested for in vitro cytotoxic activity against eight cancer cell lines and two non-cancerous cell lines. Four compounds with IC values of 5 μM or lower were selected for further investigation.
View Article and Find Full Text PDFPediatric low-hypodiploidy B-cell acute lymphoblastic leukemia (LH-ALL) with variants has been proposed to be considered a manifestation of Li-Fraumeni syndrome (LFS). However, our study demonstrates that of the majority the pathogenic variants in the TP53 gene are somatic (70.5%), and only 12.
View Article and Find Full Text PDFOvarian cancer (OC) is the most lethal gynecologic malignancy worldwide. The major clinical challenge includes the asymptomatic state of the disease, making diagnosis possible only at advanced stages. Another OC complication is the high relapse rate and poor prognosis following the standard first-line treatment with platinum-based chemotherapy.
View Article and Find Full Text PDFA series of triterpenoid pyrones was synthesized and subsequently modified to introduce phthalimide or phthalate moieties into the triterpenoid skeleton. These compounds underwent in vitro cytotoxicity screening, revealing that a subset of six compounds exhibited potent activity, with IC values in the low micromolar range. Further biological evaluations, including Annexin V and propidium iodide staining experiment revealed, that all compounds induce selective apoptosis in cancer cells.
View Article and Find Full Text PDFIntroduction: Immunometabolism is essential factor of tumor progression, and tumor-associated macrophages are characterized by substantial changes in their metabolic status. In this study for the first time, we applied targeted amino acid LC-MS/MS analysis to compare amino acid metabolism of circulating monocytes isolated from patients with breast, ovarian, lung, and colorectal cancer.
Methods: Monocyte metabolomics was analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/ MS) analysis of amino acid extracts.
Simultaneous multilineage hematologic malignancies are uncommon and associated with poorer prognosis than single-lineage leukemia or lymphoma. Here, we describe a concomitant malignant neoplasm in a 4-year-old boy. The child presented with massive lymphoproliferative syndrome, nasal breathing difficulties, and snoring.
View Article and Find Full Text PDFUnderstanding the immunological mechanisms of protection and the viral proteins involved in the induction of a protective immune response to the African swine fever virus (ASFV) is still limited. In the last years, the CD2v protein (gp110-140) of the ASFV has been proven to be a serotype-specific protein. Current work is devoted to the investigation of the possibility of creating protection against virulent ASFV strain Mozambique-78 (seroimmunotype III) in pigs previously vaccinated with vaccine strain FK-32/135 (seroimmunotype IV) and then immunized with the pUBB76A_CD2v plasmid, containing a chimeric nucleotide sequence from the CD2v protein gene (EP402R, nucleotides from 49 to 651) from the MK-200 strain (seroimmunotype III).
View Article and Find Full Text PDFIntroduction: In this study, we aimed to compare the immunophenotype of tumor cells in children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) harboring rearrangements of the CRLF2 gene with that in children without such aberrations with a specific focus on the surface expression of the related protein thymic stromal lymphopoietin receptor (TSLPR).
Methods: We examined bone marrow samples from 46 patients with primary BCP-ALL who had CRLF2 rearrangements detected by FISH (CRLF2(+) cohort). A total of 140 consecutive patients with intact CRLF2 were included in a control CRLF2(-) cohort.
Introduction: Circulating monocytes are main source for tumor-associated macrophages (TAMs) that control tumor growth, angiogenesis, metastasis and therapy resistance. We raised the questions how monocyte programming is affected by growing tumors localized in colon and rectal sections, and how treatment onsets affect monocyte programming in the circulation.
Methods: Patients with rectal cancer and colon cancer were enrolled in the study.
Tumor‑associated macrophages (TAMs) are crucial cells of the tumor microenvironment (TME), which belong to the innate immune system and regulate primary tumor growth, immunosuppression, angiogenesis, extracellular matrix remodeling and metastasis. The review discusses current knowledge of essential cell‑cell interactions of TAMs within the TME of solid tumors. It summarizes the mechanisms of stromal cell (including cancer‑associated fibroblasts and endothelial cells)‑mediated monocyte recruitment and regulation of differentiation, as well as pro‑tumor and antitumor polarization of TAMs.
View Article and Find Full Text PDFThe cationic complexes of Mn(III) with the 5-Hal-sal323 (Hal = Cl, Br) ligands and a paramagnetic doubly charged counterion [ReCl] have been synthesized: [Mn(5-Cl-sal323)][ReCl] () and [Mn(5-Br-sal323)][ReCl] (). Their crystal structures and magnetic properties have been studied. These isostructural two-component ionic compounds show a thermally induced spin transition at high temperature associated with the cationic subsystem and a field-induced slow magnetic relaxation of magnetization at cryogenic temperature, associated with the anionic subsystem.
View Article and Find Full Text PDFAfrican swine fever (ASF) is an infectious disease of domestic and wild pigs of all breeds and ages, with the acute form of the disease being characterized by high fever, hemorrhages in the reticuloendothelial system and a high mortality rate. Registered safe and efficacious ASF vaccines are not available. The development of experimental ASF vaccines, particularly live attenuated, have considerably intensified in the last years.
View Article and Find Full Text PDFOvarian cancer (OC) is one of the most common gynecological cancers, with the worst prognosis and the highest mortality rate. Peritoneal dissemination (or carcinomatosis) accompanied by ascites formation is the most unfavorable factor in the progression and recurrence of OC. Tumor cells in ascites are present as either separate cells or, more often, as cell aggregates, i.
View Article and Find Full Text PDFThe spread of African swine fever (ASF) in Eurasia has forced a return to the development of live vaccines based on naturally or experimentally attenuated strains of the virus including those resulting from genetic manipulations. This process includes evaluation of the immunomodulating properties of the vaccines. In this report we provide our assessment of two tests for immunobiological evaluation of a candidate live vaccine against ASF from the attenuated ASF virus (ASFV) strain KK-202: (i) investigation of the effect of the attenuated ASFV strain KK-202 on the protectiveness of the vaccine ASFV strain FK-32/135 and a vaccine against classical swine fever (CSF) from the strain LK-VNIIVViM; (ii) determination of the phagocytic activity of blood neutrophils in pigs inoculated with ASFV strains differing in virulence.
View Article and Find Full Text PDFThree tetraphenylborates of mononuclear Mn(III) cation complexes with hexadentate ligands, the products of the reaction between a N,N'-bis(3-aminopropyl)ethylenediamine and salicylaldehydes with the different haloid substitutions at the 5 or 3,5 positions, have been synthesized: [Mn(5-F-sal-N-1,5,8,12)]BPh (1), [Mn(3,5-diCl-sal-N-1,5,8,12)]BPh (2) and [Mn(3,5-Br,Cl-sal-N-1,5,8,12)]BPh (3). Their crystal structure, dielectric constant (ϵ) and magnetic properties have been studied. Ligand substituents have a dramatic effect on the structure and magnetic properties of the complexes.
View Article and Find Full Text PDFNovel triterpene derivatives were prepared and evaluated in salsolinol (SAL)- and glutamate (Glu)-induced models of neurodegeneration in neuron-like SH-SY5Y cells. Among the tested compounds, betulin triazole 4 bearing a tetraacetyl-β-d-glucose substituent showed a highly potent neuroprotective effect. Further studies revealed that removal of tetraacetyl-β-d-glucose part (free triazole derivative 10) resulted in strong neuroprotection in the SAL model at 1 μM, but this derivative suffered from cytotoxicity at higher concentrations.
View Article and Find Full Text PDFIntroduction: Accurate detection of GATA1 mutation is highly significant in patients with acute myeloid leukemia (AML) and trisomy 21 as it allows optimization of clinical protocol. This study was aimed at (a) enhanced search for GATA1 mutations; and (b) characterization of molecular landscapes for such conditions.
Methods: The DNA samples from 44 patients with newly diagnosed de novo AML with trisomy 21 were examined by fragment analysis and Sanger sequencing of the GATA1 exon 2, complemented by targeted high-throughput sequencing (HTS).
This article summarizes the study results on the generation of attenuated strains of African swine fever virus (ASFV) of seroimmunotypes I-VIII and the creation of live vaccines for temporary protection of pigs during a period of epizootics in the surveillance zone (a zone adjacent to the area of outbreak). These studies were initiated at the Federal Research Center for Virology and Microbiology (FRCVM, formerly VNIIVViM) at the time of introduction of the pathogen to the Iberian Peninsula in the middle of the 20th century. The developed experimental vaccines against ASFV seroimmunotypes I-V provided protection against virulent strains of homologous seroimmunotypes by day 14 after vaccination, lasting at least four months.
View Article and Find Full Text PDFBackground: Inflammatory myofibroblastic tumors (IMTs) are exceptionally rare neoplasms, which are often driven by rearranged tyrosine kinases.
Methods: This study considered 33 consecutive patients with IMT (median age, 6.6; age range, 0.
Influenza A viruses continue to circulate throughout the world as yearly epidemics or occasional pandemics. Influenza infections can be prevented by seasonal multivalent or monovalent pandemic vaccines. In the present study, we describe a novel multiplex microarray immunoassay (MAIA) for simultaneous measurement of virus-specific IgG and IgM antibodies using Pandemrix-vaccinated adult sera collected at day 0 and 28 and 180 days after vaccination as the study material.
View Article and Find Full Text PDFSerological assays are used to diagnose and characterize host immune responses against microbial pathogens. Microarray technologies facilitate high-throughput immunoassays of antibody detection against multiple pathogens simultaneously. To improve survey of influenza A virus (IAV), influenza B virus (IBV), respiratory syncytial virus (RSV), and adenovirus (AdV) antibody levels, we developed a microarray consisting of IAV H1N1, IAV H1N1pdm09 (vaccine), IAV H3N2, IBV Victoria, IBV Yamagata, RSV, AdV type 5 hexon protein, and control antigens printed on the bottom of a microtiter plate well.
View Article and Find Full Text PDFTriterpenoids are natural products from plants and many other organisms that have various biological activities, such as antitumor, antiviral, antimicrobial, and protective activities. This review covers the synthesis and biological evaluation of pentacyclic triterpene (PT) conjugates with other molecules that have been found to increase the IC or improve the pharmacological profile of the parent PT. Some of these molecules are designed to target specific proteins or cellular organelles, which has resulted in highly selective lead structures for drug development.
View Article and Find Full Text PDFBackground: Flow cytometry (FCM) plays a crucial role in the differential diagnosis of Burkitt lymphoma/leukemia (BL) and B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The presence of surface IgM (sIgM) alone or with light chain restriction indicates a mature blast phenotype (BIV by EGIL) and is usually observed in BL. However, sIgM expression could also be detected in transitional BCP-ALL cases.
View Article and Find Full Text PDFWe present herein the synthesis, crystal structure, and electric and magnetic properties of the spin-crossover salt [Mn(5-Cl-sal-N-1,5,8,12)]TCNQ ⋅2 CH CN (I), where 5-Cl-sal-N-1,5,8,12=N,N'-bis(3-(2-oxy-5-chlorobenzylideneamino)propyl)-ethylenediamine, containing distinct conductive and magnetic blocks along with acetonitrile solvent molecules. The Mn complex with a Schiff-base ligand, [Mn(5-Cl-sal-N-1,5,8,12)] , acts as the magnetic unit, and the π-electron acceptor 7,7,8,8-tetracyanoquinodimethane (TCNQ ) is the conducting unit. The title compound (I) exhibits semiconducting behavior with room temperature conductivity σ ≈1×10 ohm cm and activation energy Δ ≈0.
View Article and Find Full Text PDF