Unraveling the Mechanism of Platelet Aggregation Suppression by Thioterpenoids: Molecular Docking and In Vivo Antiaggregant Activity.

Natural monoterpenes and their derivatives are widely considered the effective ingredients for the design and production of novel biologically active compounds. In this study, by using the molecular docking technique, we examined the effects of two series of "sulfide-sulfoxide-sulfone" thioterpenoids containing different (e.g.

Establishment and Characterization of Multi-Drug Resistant p53-Negative Osteosarcoma SaOS-2 Subline.

Aim: To establish a p53-negative osteosarcoma (OS) SaOS-2 cellular subline exhibiting resistance to specific chemotherapeutic agents, including topoisomerase II inhibitors, taxanes, and vinca alkaloids.

Methods: The OS subline exhibiting resistance to the chemotherapeutic agents indicated above was generated by the stepwise treatment of the parental SaOS-2 cell line with increasing concentrations of doxorubicin (Dox) for 5 months. Half-inhibitory concentrations (IC) for Dox, vinblastine (Vin), and paclitaxel (PTX) were calculated by a colorimetric MTS-based assay.

Photon Drag Currents and Terahertz Generation in α-Sn/Ge Quantum Wells.

We have fabricated α-Sn/Ge quantum well heterostructures by sandwiching nano-films of α-Sn between Ge nanolayers. The samples were grown via e-beam deposition and characterized by Raman spectroscopy, atomic force microscopy, temperature dependence of electrical resistivity and THz time-resolved spectroscopy. We have established the presence of α-Sn phase in the polycrystalline layers together with a high electron mobility μ = 2500 ± 100 cm V s.

2-Amino-Pyrrole-Carboxylate Attenuates Homology-Mediated DNA Repair and Sensitizes Cancer Cells to Doxorubicin.

Despite a high efficacy of chemotherapy in cancer treatment, acquired resistance of tumors to certain chemotherapeutic agents and frequent side effects remain the major factors of unfavorable prognosis in most cancer patients with unresectable, metastatic and recurrent forms of the disease. The discovery of novel molecular targets in tumors and development of new therapeutic approaches to enhance the efficiency of chemotherapeutic agents remain the biggest challenges in current oncology. Here we examined the ability of pyrrole-based heterocyclic compound 2-APC to sensitize tumor cells to the topoisomerase II inhibitor doxorubicin.

Infigratinib (BGJ 398), a Pan-FGFR Inhibitor, Targets P-Glycoprotein and Increases Chemotherapeutic-Induced Mortality of Multidrug-Resistant Tumor Cells.

The microtubule-targeting agents (MTAs) are well-known chemotherapeutic agents commonly used for therapy of a broad spectrum of human malignancies, exhibiting epithelial origin, including breast, lung, and prostate cancer. Despite the impressive response rates shortly after initiation of MTA-based therapy, the vast majority of human malignancies develop resistance to MTAs due to the different mechanisms. Here, we report that infigratinib (BGJ 398), a potent FGFR1-4 inhibitor, restores sensitivity of a broad spectrum of ABCB1-overexpressing cancer cells to certain chemotherapeutic agents, including paclitaxel (PTX) and doxorubicin (Dox).

Terahertz spectroscopy of diabetic and non-diabetic human blood plasma pellets.

Significance: The creation of fundamentally new approaches to storing various biomaterial and estimation parameters, without irreversible loss of any biomaterial, is a pressing challenge in clinical practice. We present a technology for studying samples of diabetic and non-diabetic human blood plasma in the terahertz (THz) frequency range.

Aim: The main idea of our study is to propose a method for diagnosis and storing the samples of diabetic and non-diabetic human blood plasma and to study these samples in the THz frequency range.

Central Mini-plication of the Medial Rectus for Convergence Insufficiency.

Five cases with a mean (± SD) age of 61 (12.02) years are described to study the outcomes of treatment with central mini-plication of the medial rectus (MR) muscles in adult convergence insufficiency with diplopia and near exotropia: mean preoperative deviation: 18 (± 2) pd. Surgical outcome was considered to be favorable when diplopia and symptoms were resolved and final exotropia at near was ≤8 pd at the end of follow-up.

Inhibition of fibroblast growth factor receptor-signaling sensitizes imatinib-resistant gastrointestinal stromal tumors to low doses of topoisomerase II inhibitors.

The acquired resistance of gastrointestinal stromal tumors (GISTs) to the targeted-based therapy remains the driving force to identify the novel approaches that are capable of increasing the sensitivity of GISTs to the current therapeutic regimens. Our present data show that BGJ398, a selective fibroblast growth factor receptor (FGFR) inhibitor, sensitizes imatinib (IM)-resistant GIST cells with receptor tyrosine kinase (RTK) switch (loss of c-KIT/gain of pFGFR2a) to the low doses of topoisomerase II inhibitors - doxorubicin (Dox) and etoposide (Eto). Mechanistically, pretreatment of IM-resistant GIST cells with BGJ398 for 12 h markedly enhanced proapoptotic and growth-suppressive effects of Dox (or Eto).

The off-label use of drugs for parenteral nutrition as a solvent of substances slightly soluble in water in pharmacological research.

Because of the problem to evaluate biological activity in water-soluble substances in all phases of preclinical and clinical studies, the research work enabled to develop the original solvent for poorly soluble compounds based on substances for parenteral nutrition. The main aim is to examine the impact of the original solvent based on substances for parenteral nutrition on biological systems exemplified by the hemostatic system, characterized by sensitivity and variability of the effects in response to any impact, and its comparison with the solvents that are conventional in pharmacological research. Experimental work is performed according to the "guidance on preclinical research of new pharmacological substances" .

Cytokine Profile of Patients with Allergic Rhinitis Caused by Pollen, Mite, and Microbial Allergen Sensitization.

Allergic rhinitis (AR) is especially prevalent among the population of large cities. Immunologically, the airway epithelium is a region where the population of allergen-presenting cells concentrates. These cells actively express a group of receptors of the innate immune system.

Enhancing 4-propylheptane dissociation with nickel nanocluster based on molecular dynamics simulations.

In the present work, a 0.4nm nickel cluster has been theoretically studied. Its equilibrium structural parameters have been calculated by the DFT method based on the PBEH1PBE hybrid functional and split-valence basis set Lanl2DZ including effective core potentials.

[MICROBIAL COMPOSITION OF VARIOUS SURFACES OF SKIN DURING DEVELOP- MENT OF ATOPIC DERMATITIS BASED ON DATA FROM MALDI-TOF MASS-SPECTROMETRY IDENTIFICATION METHOD].

Aim: Study transformation of skin microflora during development of atopic dermatitis.

Materials And Methods: 45 patients with various forms of atopic dermatitis (AtD) were examined. Control group consisted of 26 healthy individuals.

Fibrosis biomarkers in workers exposed to MWCNTs.

Multi-walled carbon nanotubes (MWCNT) with their unique physico-chemical properties offer numerous technological advantages and are projected to drive the next generation of manufacturing growth. As MWCNT have already found utility in different industries including construction, engineering, energy production, space exploration and biomedicine, large quantities of MWCNT may reach the environment and inadvertently lead to human exposure. This necessitates the urgent assessment of their potential health effects in humans.

Circulating Microparticles Alter Formation, Structure, and Properties of Fibrin Clots.

Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure, and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel.

[THROMBIN-MEDIATED EFFECTS OF BLOOD MICROPARTICLES ON FORMATION, STRUCTURE, AND STABILITY OF FIBRIN CLOTS].

The effects of blood microparticles (MPs) on the dynamics of fibrin polymerization, clot structure and susceptibility to fibrinolysis were studied. Kinetics of fibrin polymerization, fibrinolysis, thrombin generation in platelet-free, microparticle-depleted and microparticle-depleted plasma replenished with cephalin, from healthy donors were analyzed in parallel. MPs have profound effects on all stages of fibrin formation, decrease its turbidity.

[3-Hydroxy-1,5-diaryl-4-pivaloyl-2,5-dihydro-2-pyrrolones induce the mitotic exit failure and cell death in tumor cells in vitro].

Some compound refering to the 3-hydroxy-1,5-diaryl-4-pivaloyl-2,5-dihydro-2-pyrrolones have been found to cause an increase in the number of mitotic cells and their subsequent death in vitro. This increased in the number of mitotic cells was not associated with increased cellular proliferative activity and was likely due to mitotic exit failure. Of note, the effect was more pronounced in the tumor cells when compared to human fibroblasts.

Effects of Staphylococcus aureus supernatants on human lymphocyte surface receptors.

The effects of Staphylococcus aureus proteolytic enzymes on surface receptors of human lymphocytes were studied. Proteolytic activity was detected in 35 supernatants of 45 S. aureus strains.

Lymph and blood cytokines in fever of different severity.

Experiments on rats showed that pyrogenal-induced fever is associated with elevation of IL-1β, IL-6, and IL-10 content in the thoracic duct lymph and blood plasma, whereas low-grade fever induced by administration of Freund's complete adjuvant is associated with elevation of only IL-6 concentration. The increase in IL-1β concentration during fever and IL-6 concentration in both processes was more pronounced in the central lymph than in blood plasma. Unchanged concentrations of IL-1β and IL-10 in low-grade fever apparently reflect differences in the mechanisms of these pathological processes.

Expression of P2X receptor subtypes on CD34+ cells and c-kit+ cells of human umbilical blood.

The presence of several subtypes of P2X receptors on early hemopoietic precursors (CD34+) from human umbilical blood was detected by flow cytometry. The expression of P2X receptors on umbilical blood lymphocytes was an order of magnitude higher than that on adult human blood cells. Our results attest to early involvement of P2X receptors in differentiation of human hemopoietic cells.

[Bacterial proteases and bacterial resistance against human innate immunity factors].

The molecular and cell-mediated mechanisms that are developed by certain opportunistic and pathogenic bacteria and were obtained over the course of evolution to preserve resistance against principal components of human body innate immunity are summarized.

Cell microvesicles during experimental endotoxemia.

The dynamics of microvesicle formation in arterial blood in generalized Schwartzman phenomenon was studied. Successive (with 24-h interval) intravenous injections of endotoxin to rabbits in a dose of 1 mg/kg and 3 mg/kg caused an increase in the content of microvesicles in the blood, some of them containing ecto-5'-nucleotidase. Biphasic changes in arterial blood clotting time and erythrocyte hemolysis were observed.

Key role of mitochondria in apoptosis of lymphocytes.

Changes in the mitochondrial potential, expression of phosphatidylserine, parameters of direct and lateral light scattering, and DNA fragmentation during spontaneous and induced apoptosis in peripheral blood lymphocytes were studied by flow cytofluorometry. Dexamethasone and Ca2+ ionophore A23187 served as inductors of apoptosis. A decrease in the mitochondrial potential is an early sign of spontaneous and induced apoptosis.