Aminomethylmorpholino Nucleosides as Novel Inhibitors of PARP1 and PARP2: Experimental and Molecular Modeling Analyses of Their Selectivity and Mechanism of Action.

Poly(ADP-ribose) polymerases 1 and 2 (PARP1 and PARP2) play a key role in DNA repair. As major sensors of DNA damage, they are activated to produce poly(ADP-ribose). PARP1/PARP2 inhibitors have emerged as effective drugs for the treatment of cancers with BRCA deficiencies.

Impact of the Ceria Particle Oxidation State on the Collecting Properties of Sophorolipids and Benzohydroxamic Acid.

The search for environmentally friendly alternatives to petroleum-based reagents in mineral processing requires fundamental studies of novel chemicals in model mineral systems. In this study, we evaluate the potential of acidic (ASL) and lactonic sophorolipids (LSL) as collectors in the froth flotation of ultrafine ceria, which serves as a model rare earth mineral (REM). We compare these two biosurfactants to a conventional petroleum-based collector, benzohydroxamic acid (BHA), in the flotation of ceria against hematite and quartz particles.

Synthesis of furanotriterpenoids from betulin and evaluation of Tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitory properties of new semi-synthetic triterpenoids.

For the first time, a synthetic route for preparing lupane and oleanane derivatives with a hydrogenated furan ring as a cycle A of triterpene scaffold is described. Most of the synthesized compounds, furanoterpenoids and their synthetic intermediates, were non-toxic against the tested cancer and non-cancerous cell lines, and evinced significant inhibitory activity with IC 1.0-9.

Influence of Tyrosyl-DNA Phosphodiesterase 1 Inhibitor on the Proapoptotic and Genotoxic Effects of Anticancer Agent Topotecan.

To date, various strategies have been proposed to increase the efficiency of cancer therapy. It is known that the action of DNA repair system can determine the resistance of cancer cells to DNA-damaging chemotherapy and radiotherapy, and one of these ways to increase therapeutic efficiency is the search for inhibitors of enzymes of the DNA repair system. Inhibition of the DNA repair enzyme tyrosyl-DNA phosphodiesterase1 (Tdp1) leads to an increase in the effectiveness of the topoisomerase 1 (Top1) inhibitor, the anticancer drug topotecan.

The Lipophilic Purine Nucleoside-Tdp1 Inhibitor-Enhances DNA Damage Induced by Topotecan In Vitro and Potentiates the Antitumor Effect of Topotecan In Vivo.

The use of cancer chemotherapy sensitizers is a promising approach to induce the effect of clinically used anticancer treatments. One of the interesting targets is Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), a DNA-repair enzyme, that may prevent the action of clinical Topoisomerase 1 (Top1) inhibitors, such as topotecan (Tpc). Tdp1 eliminates covalent Top1-DNA (Top1c) complexes that appear under the action of topotecan and determines the cytotoxic effect of this drug.

In Vitro and In Silico Studies of Human Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) Inhibition by Stereoisomeric Forms of Lipophilic Nucleosides: The Role of Carbohydrate Stereochemistry in Ligand-Enzyme Interactions.

Inhibition of human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1) by different chiral lipophilic nucleoside derivatives was studied. New Tdp1 inhibitors were found in the series of the studied compounds with IC = 2.7-6.

New Hybrid Compounds Combining Fragments of Usnic Acid and Thioether Are Inhibitors of Human Enzymes TDP1, TDP2 and PARP1.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) catalyzes the cleavage of the phosphodiester bond between the tyrosine residue of topoisomerase 1 (TOP1) and the 3' phosphate of DNA in the single-strand break generated by TOP1. TDP1 promotes the cleavage of the stable DNA-TOP1 complexes with the TOP1 inhibitor topotecan, which is a clinically used anticancer drug. This article reports the synthesis and study of usnic acid thioether and sulfoxide derivatives that efficiently suppress TDP1 activity, with IC values in the 1.

Design, Synthesis, and Molecular Docking Study of New Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors Combining Resin Acids and Adamantane Moieties.

In this paper, a series of novel abietyl and dehydroabietyl ureas, thioureas, amides, and thioamides bearing adamantane moieties were designed, synthesized, and evaluated for their inhibitory activities against tyrosil-DNA-phosphodiesterase 1 (TDP1). The synthesized compounds were able to inhibit TDP1 at micromolar concentrations (0.19-2.

Toward green flotation: Interaction of a sophorolipid biosurfactant with a copper sulfide.

The United Nations' Sustainable Development Goals have sparked growing interest in biosurfactants from many surfactant-loaded industries including those utilizing froth flotation for mineral separation. However, the interaction of biosurfactants with mineral surfaces is currently poorly understood. We bridge this gap by studying adsorption of a yeast-derived bola acidic sophorolipid (ASL) biosurfactant on djurleite (CuS).

Inhibition of Tyrosyl-DNA Phosphodiesterase 1 by Lipophilic Pyrimidine Nucleosides.

Inhibition of DNA repair enzymes tyrosyl-DNA phosphodiesterase 1 and poly(ADP-ribose)polymerases 1 and 2 in the presence of pyrimidine nucleoside derivatives was studied here. New effective Tdp1 inhibitors were found in a series of nucleoside derivatives possessing 2',3',5'-tri--benzoyl-d-ribofuranose and 5-substituted uracil moieties and have half-maximal inhibitory concentrations (IC) in the lower micromolar and submicromolar range. 2',3',5'-Tri--benzoyl-5-iodouridine manifested the strongest inhibitory effect on Tdp1 (IC = 0.

FN3 protein fragment containing two type III fibronectin domains from B. longum GT15 binds to human tumor necrosis factor alpha in vitro.

Most species of the genus Bifidobacterium contain the gene cluster PFNA, which is presumably involved in the species-specific communication between bacteria and their hosts. The gene cluster PFNA consists of five genes including fn3, which codes for a protein containing two fibronectin type III domains. Each fibronectin domain contains sites similar to cytokine-binding sites of human receptors.

Antibacterial Activity of Hybrid Polymeric Scaffold for Reconstruction of Tubular Bone Defects.

We studied antibacterial activity of a hybrid polymeric construction consisting of continuous and porous layers of ultrahigh-molecular-weight polyethylene reinforced by titanium. Experimental samples were impregnated with amoxycillin in subcritical Freon R22. The contact of bacterial culture with hybrid polymeric constructions saturated with amoxycillin suppressed the growth of microorganisms and the formation of their colonies.

Activation of CO at the electrode-electrolyte interface by a co-adsorbed cation and an electric field.

Carboxylate *CO2- has recently been identified as the first intermediate of the CO2 electroreduction independent of the reaction pathway. However, on the fundamental level, the structural and electronic properties of *CO2- remain poorly understood especially under the electrocatalytic conditions, which limits our capacity to rationally control the transformation of this reaction intermediate to CO or formate. To close this gap, we model using density functional theory (DFT) the interactions of *CO2- with the copper Cu(111) surface and a co-adsorbed sodium cation in the electric double layer (EDL), as well as the effects of electrode potential on these interactions.

On the origin of the elusive first intermediate of CO electroreduction.

We resolve the long-standing controversy about the first step of the CO electroreduction to fuels in aqueous electrolytes by providing direct spectroscopic evidence that the first intermediate of the CO conversion to formate on copper is a carboxylate anion *CO coordinated to the surface through one of its C-O bonds. We identify this intermediate and gain insight into its formation, its chemical and electronic properties, as well as its dependence on the electrode potential by taking advantage of a cutting-edge methodology that includes operando surface-enhanced Raman scattering (SERS) empowered by isotope exchange and electrochemical Stark effects, reaction kinetics (Tafel) analysis, and density functional theory (DFT) simulations. The SERS spectra are measured on an operating Cu surface.

Multilayer porous UHMWPE scaffolds for bone defects replacement.

Reconstruction of the structural integrity of the damaged bone tissue is an urgent problem. UHMWPE may be potentially used for the manufacture of porous implants simulating as closely as possible the porous cancellous bone tissue. But the extremely high molecular weight of the polymer does not allow using traditional methods of foaming.

Nitrogen-containing polymers as a platform for CO electroreduction.

Heterogeneous electroreduction of CO has received considerable attention in the past decade. However, none of the earlier reviews has been dedicated to nitrogen-containing polymers (N-polymers) as an emerging platform for conversion of CO to industrially useful chemicals. The term 'platform' is used here to underscore that the role of N-polymers is not only to serve as direct catalysts (through loaded metals) but also as co-catalysts/promoters and stabilizing agents.

Beneficial effects of cerium oxide nanoparticles in development of chondrocyte-seeded hydrogel constructs and cellular response to interleukin insults.

The harsh inflammatory environment associated with injured and arthritic joints represents a major challenge to articular cartilage repair. In this study, we report the effect of cerium oxide nanoparticles, or nanoceria, in modulating development of engineered cartilage and in combating the deleterious effects of interleukin-1α. Nanoceria was found to be biocompatible with bovine chondrocytes up to a concentration of 1000 μg/mL (60,000 cells/μg of nanoceria), and its presence significantly improved compressive mechanical properties and biochemical composition (i.

Stabilization of Silicon Carbide (SiC) micro- and nanoparticle dispersions in the presence of concentrated electrolyte.

Achieving a stable and robust dispersion of ultrafine particles in concentrated electrolytes is challenging due to the shielding of electrostatic repulsion. Stable dispersion of ultrafine particles in concentrated electrolytes is critical for several applications, including electro-codeposition of ceramic particles in protective metal coatings. We achieved the steric stabilization of SiC micro- and nano-particles in highly concentrated electroplating Watts solutions using their controlled coating with linear and branched polyethyleneimines (PEI) as dispersants.

Linking interfacial chemistry of CO2 to surface structures of hydrated metal oxide nanoparticles: hematite.

A better understanding of interaction with dissolved CO2 is required to rationally design and model the (photo)catalytic and sorption processes on metal (hydr)oxide nanoparticles (NPs) in aqueous media. Using in situ FTIR spectroscopy, we address this problem for rhombohedral 38 nm hematite (α-Fe2O3) nanoparticles as a model. We not only resolve the structures of the adsorbed carbonate species, but also specify their adsorption sites and their location on the nanoparticle surface.

Rational design of interfacial properties of ferric (hydr)oxide nanoparticles by adsorption of fatty acids from aqueous solutions.

Notwithstanding the great practical importance, still open are the questions how, why, and to what extent the size, morphology, and surface charge of metal (hydr)oxide nanoparticles (NPs) affect the adsorption form, adsorption strength, surface density, and packing order of organic (bio)molecules containing carboxylic groups. In this article, we conclusively answer these questions for a model system of ferric (hydr)oxide NPs and demonstrate applicability of the established relationships to manipulating their hydrophobicity and dispersibility. Employing in situ Fourier transform infrared (FTIR) spectroscopy and adsorption isotherm measurements, we study the interaction of 150, 38, and 9 nm hematite (α-Fe(2)O(3)) and ∼4 nm 2-line ferrihydrite with sodium laurate (dodecanoate) in water.

[Painless course of chronic calcificated pancreatitis manifesting as hyperglycemia].

The clinical case of chronic calcifying pancreas (CCP) was described. It was reveal that obligate sign CCP as a painful syndrome can disappeared in some circumstances, in particular when the patient refused of smoking and alcohol intake.

Adsorption of fatty acids on iron (hydr)oxides from aqueous solutions.

The interaction of iron (hydr)oxides with fatty acids is related to many industrial and natural processes. To resolve current controversies about the adsorption configurations of fatty acids and the conditions of the maximum hydrophobicity of the minerals, we perform a detailed study of the adsorption of sodium laurate (dodecanoate) on 150 nm hematite (α-Fe(2)O(3)) particles as a model system. The methods used include in situ FTIR spectroscopy, ex situ X-ray photoelectron spectroscopy (XPS), measurements of the adsorption isotherm and contact angle, as well as the density functional theory (DFT) calculations.

[Disorder of bone mineral density in patients with the digestive system diseases].

This article studies the clinical features of the flow of the gastrointestinal tract and liver in the formation of osteopenia and osteoporosis. Were shown the incidence of disorders of bone mineral density in patients with chronic pancreatitis, liver cirrhosis, gallstone disease, inflammatory bowel diseases, and diseases accompanied by syndrome of malabsorption (gluten enteropathy, a syndrome of short small intestine). Were established population (age, sex, lower body mass index, menopause), clinical and laboratory factors indicating high risk of lower bone mineral density in these patients.

Tailoring (bio)chemical activity of semiconducting nanoparticles: critical role of deposition and aggregation.

The impact of deposition and aggregation on (bio)chemical properties of semiconducting nanoparticles (NPs) is perhaps among the least studied aspects of aquatic chemistry of solids. Employing a combination of in situ FTIR and ex situ X-ray photoelectron spectroscopy (XPS) and using the Mn(II) oxygenation on hematite (α-Fe(2)O(3)) and anatase (TiO(2)) NPs as a model catalytic reaction, we discovered that the catalytic and sorption performance of the semiconducting NPs in the dark can be manipulated by depositing them on different supports or mixing them with other NPs. We introduce the electrochemical concept of the catalytic redox activity to explain the findings and to predict the effects of (co)aggregation and deposition on the catalytic and corrosion properties of ferric (hydr)oxides.