Serum Beta-Defensin-2 is a biomarker for psoriasis but not subclinical atherosclerosis: Role of IL17a, PI-3 kinase and Rac1.

Background: Beta-defensins (BDs) are antimicrobial peptides secreted upon epithelial injury. Both chemotactic and antimicrobial properties of BDs function as initial steps in host defense and prime the adaptive immune system in the body. Psoriasis, a chronic immune-mediated inflammatory disease, has both visible cutaneous manifestations as well as known associations with higher incidence of cardiometabolic complications and vascular inflammation. Objectives: We aimed to investigate the circulating expression of beta-defensin-2 (BD2) in psoriasis at baseline compared to control subjects, along with changes in BD2 levels following biologic treatment at one-year. The contribution of BD2 to subclinical atherosclerosis is also assessed. In addition, we have sought to unravel signaling mechanisms linking inflammation with BD2 expression. Methods: Multimodality imaging as well inflammatory biomarker assays were performed in biologic naïve psoriasis (n=71) and non-psoriasis (n=53) subjects. A subset of psoriasis patients were followed for one-year after biological intervention (anti-Tumor Necrosis Factor-α (TNFα), n=30; anti-Interleukin17A (IL17A), n=21). Measurements of circulating BD2 were completed by Enzyme-Linked Immunosorbent Assay (ELISA). Using HaCaT transformed keratinocytes, expression of BD2 upon cytokine treatment was assessed by quantitative polymerase chain reaction (qPCR) and ELISA. Results: Herein, we confirm that human circulating BD2 levels associate with psoriasis, which attenuate upon biologic interventions (anti-TNFα, anti-IL-17A). A link between circulating BD2 and sub-clinical atherosclerosis markers was not observed. Furthermore, we demonstrate that IL-17A-driven BD2 expression occurs in a Phosphatidylinositol 3-kinase (PI3-kinase) and Rac1 GTPase-dependent manner. Conclusions: Our findings expand on the potential role of BD2 as a tractable biomarker in psoriasis patients and describes the role of an IL-17A-PI3-kinase/Rac signaling axis in regulating BD2 levels in keratinocytes.

Novel biocatalysts based on enzymes in complexes with nano- and micromaterials.

In today's world, there is a wide array of materials engineered at the nano- and microscale, with numerous applications attributed to these innovations. This review aims to provide a concise overview of how nano- and micromaterials are utilized for enzyme immobilization. Enzymes act as eco-friendly biocatalysts extensively used in various industries and medicine. However, their widespread adoption faces challenges due to factors such as enzyme instability under different conditions, resulting in reduced effectiveness, high costs, and limited reusability. To address these issues, researchers have explored immobilization techniques using nano- and microscale materials as a potential solution. Such techniques offer the promise of enhancing enzyme stability against varying temperatures, solvents, pH levels, pollutants, and impurities. Consequently, enzyme immobilization remains a subject of great interest within both the scientific community and the industrial sector. As of now, the primary goal of enzyme immobilization is not solely limited to enabling reusability and stability. It has been demonstrated as a powerful tool to enhance various enzyme properties and improve biocatalyst performance and characteristics. The integration of nano- and microscale materials into biomedical devices is seamless, given the similarity in size to most biological systems. Common materials employed in developing these nanotechnology products include synthetic polymers, carbon-based nanomaterials, magnetic micro- and nanoparticles, metal and metal oxide nanoparticles, metal-organic frameworks, nano-sized mesoporous hydrogen-bonded organic frameworks, protein-based nano-delivery systems, lipid-based nano- and micromaterials, and polysaccharide-based nanoparticles.

Update of ion-optical system of neutral beam of Tokamak à Configuration Variable.

An injector of fast deuterium atoms for plasma heating was designed and installed at the Tokamak à Configuration Variable (TCV). The neutral beam can deliver 1 MW power to the plasma in 2 s pulses. An ion beam of the injector is formed by a triode multislit ion-optical system with spherical electrodes which provide ballistic focusing. Tests at TCV revealed that the total angular divergence of the neutral beam across the slits exceeded the expected value more than twice. It was finally established that this increase in divergence was caused by the asymmetry of the chamfers at the slit edges of the plasma electrode. The redesigned shape of the slits of the plasma grid together with precise machining significantly improved the beam quality. Experimental testing proved that the neutral beam profile in the direction across the grid slits became very close to the expected value.

[The use of immunomodulators, antioxidants and hepatoprotectors for the correction of the liver, erythrocites and the immune system disorders in chronic ethanol intoxication]. / Ispol'zovanie immunomoduliatorov, antioksidantov i gepatoprotektorov dlia korrektsii narushenii v pecheni, éritrotsitakh i immunnoi sisteme pri khronicheskoi intoksikatsii étanolom.

The effectiveness of three various combinations of an immunomodulator with an antioxidant and a membrane protector in the correction of metabolic and immune disorders has been studied in the experiment under 60-days ethanol intoxication. The development of such biochemical syndromes of the liver damage as cytolysis, intrahepatic, intracellular cholestasis, toxic liver damage by necrotic type, insufficiency of synthetic processes and inflammatory has been revealed. Oxidative stress development and the activation of lipid peroxidation on the systemic (blood plasma) and local level (erythrocytes) have been established. Suppression of adaptive immunity formation and phagocytic capabilities of neutrophils under the increase in their oxygen-dependent activity has been determined, which indicates the presence and possible progression of the inflammatory process at the systemic level. A disorder of erythrocytes metabolic activity, a decrease in stable metabolites of nitric oxide detected in blood plasma been revealed, indicating its uncompensated consumption, causing vasoconstriction and thrombosis, which can additionally arise due to the established increase in the prothrombin index. Combined use of "Longidasa", "Mexicor", "Essentiale forte N" or "Glutoxim", "Mexidol", "Heptral" was more effective in the correction of immune-metabolic disorders in chronic alcohol intoxication than "Hepon", "Hypoxen" and "Phosphogliv".

Excimer Emission of Acridine Orange Adsorbed on Gadolinium-Yttrium Orthovanadate Nanoparticles.

Studying the complexes of inorganic nanoparticles - organic dye molecules is of great importance for their theranostics application. In this paper, we report gadolinium-yttrium orthovanadate nanoparticles (VNPs) - Acridine Orange (AO) complex formation in water solutions. To study the interactions between VNPs and AO, the methods of steady-state and time-resolved spectroscopy were used. It was shown that in aqueous solutions containing VNPs, AO aggregation takes place with a sandwich-like stacking of AO molecules in the near-surface layer of VNPs. The VNPs-AO complex formation causes significant changes in the AO fluorescence spectrum, namely, the appearance of a new broad, structureless band in the long-wavelength spectral edge, which was not observed in AO spectrum in a pure water solution. By analyzing of the absorption, fluorescence excitation spectra and fluorescence decay, the static excimer origin of the long-wavelength fluorescence band has been established.

Semiclassical bifurcations and topological phase transitions in a one-dimensional lattice of coupled Lipkin-Meshkov-Glick models.

In this work we study a one-dimensional lattice of Lipkin-Meshkov-Glick models with alternating couplings between nearest-neighbors sites, which resembles the Su-Schrieffer-Heeger model. Typical properties of the underlying models are present in our semiclassical-topological hybrid system, allowing us to investigate an interplay between semiclassical bifurcations at mean-field level and topological phases. Our results show that bifurcations of the energy landscape lead to diverse ordered quantum phases. Furthermore, the study of the quantum fluctuations around the mean-field solution reveals the existence of nontrivial topological phases. These are characterized by the emergence of localized states at the edges of a chain with free open-boundary conditions.

[Desadaptive Reaction and Development of Arterial Hypertension in Conditions of Professional Stress].

PURPOSE: to compare prevalence of maladaptive responses and risk of hypertension and cardiovascular remodeling. MATERIAL AND METHODS: We examined using clinical and instrumental methods 1321 workers of locomotive crews; 472 of those examined were followed-up for 12 years. RESULTS: Machinists with maladaptive responses compared with the group of individuals with normal tension of adaptation processes had greater left ventricular myocardial mass and carotid artery intima-media thickness regardless of blood pressure (BP) level. During follow up 380/472 persons maintained normal BP while 87 developed hypertension (5 patients with symptomatic hypertension were excluded from analysis). According to modified MMPI test persons with hypertension had higher scores on scales 2, 8, and 6. Personality profile was characterized by presence of mixed type of response with combination of high need for self-realization and tendency to curb behavioral reactions.

Quantum phase transitions in networks of Lipkin-Meshkov-Glick models.

We study the quantum critical behavior of networks consisting of Lipkin-Meshkov-Glick models with an anisotropic ferromagnetic coupling. We focus on the low-energy properties of the system within a mean-field approach and the quantum corrections around the mean-field solution. Our results show that the weak-coupling regime corresponds to the paramagnetic phase when the local field dominates the dynamics, but the local anisotropy leads to the existence of an exponentially degenerate ground state. In the strong-coupling regime, the ground state is twofold degenerate and possesses long-range magnetic ordering. Analytical results for a network with the ring topology are obtained.

Development of a negative ion-based neutral beam injector in Novosibirsk.

A 1000 keV, 5 MW, 1000 s neutral beam injector based on negative ions is being developed in the Budker Institute of Nuclear Physics, Novosibirsk in collaboration with Tri Alpha Energy, Inc. The innovative design of the injector features the spatially separated ion source and an electrostatic accelerator. Plasma or photon neutralizer and energy recuperation of the remaining ion species is employed in the injector to provide an overall energy efficiency of the system as high as 80%. A test stand for the beam acceleration is now under construction. A prototype of the negative ion beam source has been fabricated and installed at the test stand. The prototype ion source is designed to produce 120 keV, 1.5 A beam.

MEMO1, a new IRS1-interacting protein, induces epithelial-mesenchymal transition in mammary epithelial cells.

MEMO1 (mediator of ErbB2-driven cell motility 1) regulates HER2-dependent cell migration. Increased MEMO1 expression is associated with cancer aggressiveness. Here, we found that MEMO1 is also involved in breast carcinogenesis via regulating insulin-like growth factor-I receptor-dependent signaling events. We showed that MEMO1 binds to insulin receptor substrate 1, activates the downstream PI3K/Akt signaling pathway, leads to upregulation of Snail1 and thereby triggers the epithelial-mesenchymal transition (EMT) program. In addition, MEMO1 overexpression is accompanied by growth factor-independent proliferation, anchorage-independent growth in soft agar, and enhanced metastatic potential. Together, these findings suggest that MEMO1 acts as an oncogene and is a potential therapeutic target for cancer treatment.

Comparative study of dye-loaded liposome accumulation in sensitive and resistant human breast cancer cells.

UNLABELLED: The aim of this research is to study the dynamics and efficiency of liposome accumulation in sensitive and resistant human breast cancer cells. METHODS: Methods of fluorescence microscopy, fluorescence microspectroscopy and MTT-test have been used. RESULTS: The liposome-to-cell interaction and dye cellular uptake in sensitive, cisplatin-resistant and doxorubicin-resistant MCF-7 human breast cancer cells have been analyzed using time changes in both fluorescence resonance energy transfer signal from the donor probe DiO to the acceptor one DiI preloaded in liposomes and cell image brightness. CONCLUSION: Obtained results show that resistant cells accumulate dye-loaded liposomes more effectively and reveal more effective dye molecule cellular uptake.

Atrial fibrillation in endurance-trained athletes.

BACKGROUND: Endurance exercise training produces multiple cardiac adaptations including changes in electrophysiological function that may make endurance-trained athletes more vulnerable to atrial fibrillation (AF). This possible association is not recognised by many practising cardiologists and sports physicians. Consequently, we performed a literature review to examine the relationship between atrial fibrillation and endurance exercise training among athletes. PubMed was searched from January 1960 through December 2008 to identify articles examining the relationship between endurance exercise training and AF. RESULTS: Evidence suggests that athletes are at increased risk for development of AF. Possible factors increasing AF in this population include increased parasympathetic tone, reduced sympathetic tone, increased atrial size and increased inflammation. DISCUSSION: Suggested management of AF in athletes should follow similar principles to those used to manage AF in the general population.

[Studies of YB-1 protein in breast tumors].

The multifunctional mammalian protein YB-1 is involved in multiple DNA- and mRNA-dependent events in the cell and regulates gene expression at different levels. The intracellular localization and relative mRNA content of YB-1 in the breast tumors were studied. The presence of cells with nuclear YB-1 localization in the tumor cell population is a poor predictor that correlates with larger tumors (more than 5 cm). The high YB-1 mRNA content in the breast tumors promotes metastasis of small neoplasms and patients with breast cancer who have high tumor tissue YB-1 mRNA levels may referred to as an early distant metastasis risk group. The findings suggest that combined determination of YB-1 intercellular localization and mRNA levels can ensure a more reliable prognosis of breast cancer.

Proteasome system of protein degradation and processing.

In eukaryotic cells, degradation of most intracellular proteins is realized by proteasomes. The substrates for proteolysis are selected by the fact that the gate to the proteolytic chamber of the proteasome is usually closed, and only proteins carrying a special "label" can get into it. A polyubiquitin chain plays the role of the "label": degradation affects proteins conjugated with a ubiquitin (Ub) chain that consists at minimum of four molecules. Upon entering the proteasome channel, the polypeptide chain of the protein unfolds and stretches along it, being hydrolyzed to short peptides. Ubiquitin per se does not get into the proteasome, but, after destruction of the "labeled" molecule, it is released and labels another molecule. This process has been named "Ub-dependent protein degradation". In this review we systematize current data on the Ub-proteasome system, describe in detail proteasome structure, the ubiquitination system, and the classical ATP/Ub-dependent mechanism of protein degradation, as well as try to focus readers' attention on the existence of alternative mechanisms of proteasomal degradation and processing of proteins. Data on damages of the proteasome system that lead to the development of different diseases are given separately.

[The study of preimplantation development of mice embryos labelled with green fluorescent protein gene (EGFp)].

One of the crucial problems of developmental biology is the study of mechanisms of regulation of gene expression in early embryogenesis. Here we studied dynamics of mosaic appearance of a marker fluorescent protein in in vitro developing mice embryo derived from zygotes after microinjections to male pronuclei of cloned DNA fragment carrying EGFP under control of different promoters. Main attention was paid to initial stages of development, when structural rearrangements and reprogramming of both parental genomes, activation of zygotic genes, and control of development by embryo genome take place.

[Left ventricular hypertrophy and thickening of common carotid artery wall in men aged 40 - 54 years with I degree arterial hypertension].

We carried out clinical-instrumental examination of 456 men aged 40-54 years. First degree arterial hypertension was revealed in 165 men. Left ventricular hypertrophy was found in 48 (30%), increased intima-media thickness (IMT) - in 67 (41%) patients. There was significant medium power relationship between IMT and left ventricular myocardial mass (correlation coefficient 0.41). Formation of left ventricular hypertrophy was related to parameters of 24 hour blood pressure monitoring, arterial hypertension in brothers and sisters, body weight, and duration of obesity. Significant medium power relation was obtained between tension of endothelial system of hemostasis (protein C) and severity of left ventricular hypertrophy (correlation coefficient - 0,3). Age, heredity, low density lipoprotein, cholesterol, uric acid level mattered for IMT increase.

Beam formation by ion optical system with slit finite length apertures.

Ion beam formation by four-electrode ion optical system with slit finite length apertures is considered. Results of numerical simulations by two and three dimensional codes shown that accurate ion beam formation in slit aperture with semicircular ends can be provided. In experimental studies of beam formation in single slit ion optical system angular beam divergences of 0.53 degrees across the slit and 0.35 degrees along it were measured. Studied slit ion optical system will be used for ion beam formation in diagnostic neutral injector for large W-7X stellarator.

[The effect of prolonged repeated immobilisation on metabolism of biogenic amins in the lungs of rats with different prognostic resistance against emotional stress].

In chronic experiment on male albino rats divided into active and passive groups according to their behavior in "open field" test significant differences in character of lung metabolic activity upon biogenic amines were found out. In both groups the highest level of histamine in arterial and venous blood was registered on the 5th day, 5-hydroxytriptamine--on the 10-20 days and catecholamine--on the 20th day of the experiment. On the 5th day lungs pf passive rats uptaked catecholamines from blood whereas lungs of active ones put in into blood. Histamine and 5-hydroxytriptamine uptake took place on the 5th day only in active rats, but on the 10th only lungs of passive ones absorbed 5-hydroxytriptamine from blood. Intergroup differences of lung metabolic activity upon histamine and 5-hydroxytriptamine were removed on the 20th day. Lung monoamine oxydase activity was significantly increased in active rats and decreased in passive ones in all periods of experiment.

[Distribution of foreign mitochondrial DNA during the first splittings of the transmitochondrial mouse embryos].

Distribution of human mitochondrial DNA (mtDNA) among separate murine blastomeres was analyzed during the splitting of embryos in which the suspension of human mitochondria had been injected at the one- or two-cell stage. Human mtDNA was detected by PCR with species specific primers. The total amount of the two- and four-cell murine embryos analyzed in the study was 339. In all embryos examined the copies of human mitochondrial genome were revealed along with murine mtDNA, which indicated the phenomenon of an artificially modeled heteroplasmy. The foreign mtDNA was not ubiquitous among the blastomeres of transmitochondrial embryos. Mathematical analysis of the results showed that in the period between the injection of human mitochondria and the subsequent splitting no equal distribution of the human mtDNA occurred in the cytoplasm. These results also point at the presence of more than 2-3 segregation units of mtDNA in the entire pool of mitochondria (about 5 x 10(2)) introduced into an embryo by microinjection.

Specificity of cyanine dye L-21 aggregation in solutions with nucleic acids.

Optical spectroscopy experiments were used to study the features of cyanine dye 3,3'-dimethyl-9-(2-thienyl)-thiacarbocyanine iodide (L-21) aggregation in binary solutions DMF:Tris-HCl buffer (pH = 8) containing nucleic acids (DNA or RNA). The appearance of absorption and luminescence bands associated with J-aggregates and dimers that are formed within the minor groove of DNA has been observed. The model of L-21 J-aggregate structure is proposed. It has been found that dimers are the building blocks of L-21 J-aggregates. Disorientation in dimers caused by the minor groove curvature is reason of observation of Davydov splitting in absorption spectrum of L-21 J-aggregates. In the solution containing DNA the absorption and luminescence bands of L-21 J-aggregates exhibit the specific properties that allows the dye L-21 to be used as a fluorescent probe for DNA detection.