Репозиторий Университета

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. We studied the expression of Hif-1α, Nf-κb, and Vegf genes in the liver and serum levels of HIF-1α, erythropoietin, VEGF, TGF-β, 8-isoprostane, and corticosterone in Wistar rats with different resistance to hypoxia in 5 and 90 min after acute exposure to hypobaric hypoxia. In 5 min after hypoxic exposure, Hif-1α expression in the liver and serum levels of erythropoietin, VEGF, and TGF-β in high-resistant rats were higher than in low-resistant animals. In highresistant rats, the increment in expression of Nf-κb gene responsible for the control over the inflammatory processes was more pronounced than in low-resistant animals. In 90 min after hypoxic exposure, the serum levels of HIF-1α, erythropoietin, VEGF, and TGF-β returned to normal in high-resistant rats, while in low-resistant animals, an increase in 8-isoprostane and TGF-β concentrations was observed. The rats with different resistance to hypoxia were characterized by different changes in biomolecular parameters determining predilection to inflammatory diseases.

© 2018 Medknow Publications. All rights reserved. 2-Amino-4H-chromene derivatives possess anticancer property proved on different in vivo and in vitro models of malignancies such breast, nasopharyngeal, bladder, ovary carcinomas, astrocytoma, and osteosarcoma. We assumed it might be effective to apply one of the derivatives as promising approach to lung carcinoma treatment.To evaluate how novel 4-Aryl substituted 2-Amino-4H-chromene derivative AX-554 impacts tumor growth and progression, as well as possible mechanisms for anticancer effect development on in vivo patient-derived heterotopic xenograft model of lung carcinoma in mice. This was an experimental in vivo study. 40 nu/nu BALB/c female mice were randomly allocated into four equal groups: Intact, control, reference, and main group. Animals of three latter groups were ingrafted with human-derived lung adenocarcinoma. Antitumor and antimetastatic action of AX-554 novel aminochromone derivative as a substance were studied. Mice survival was registered. Kinase of anaplastic lymphoma (ALK), tubulin Beta-3 (TUBB3), and c-mesenchymal-epithelial transition (MET) concentrations in the prime tumor nodes homogenates were determined by quantitative enzyme-linked immunosorbent assay. Dannet's parametric criterion and the nonparametric exact Fisher test were used. The normality of the distribution was determined using ANOVA. The survival curve was analyzed using Gehan's criterion with the Yates's correction. Aminochromone derivative possesses an inhibitory effect on human lung adenocarcinoma transplanted into nu/nu BALB/c female mice, as well as significant antimetastatic activity. About 50 mg/kg/day AX-554 intragastric course increases animals' life expectancy of more than 3.3 times when compared with the control and induces remission in 60% of cases. The anticancer effect of the derivative is due to anti-ALK-mediated activation of tumor cells apoptosis and suppression TUBB3-dependent cell proliferation.

© 2018, Pleiades Publishing, Inc. Abstract: The paper reports the first study of genetic diversity of the domestic yak in the Sayan-Altai region of Russia (Altai and Tuva) and Mongolia (Khuvsgul and Gobi) on the basis of the polymorphism analysis of the mtDNA D-loop hypervariable region. It has been demonstrated that, among all the studied populations, Tuva yaks are characterized by the highest haplotype diversity. Four new haplotypes, A4, A13, D9, and E3, have been described for the first time. The analysis of the contribution of maternal genetic component to the yak intrabreed and interbreed mtDNA diversity revealed two large clades. For the first time, comparative analysis of genetic structure of the Russian yak populations was carried out using 15 microsatellite loci. Low genetic difference between the populations was revealed, which may apparently be accounted for by the specific features of farm breeding, in particular, by animal exchange between the adjacent territories of the Sayan-Altai region.

© 2018, Mary Ann Liebert, Inc. Background: Laparoscopic D3 anterior posterior extended mesenterectomy (D3APEM) in right colectomy has received increased attention. The aim of this study is to prove feasibility, systemize technical accomplishment, and provide short-term outcomes data. Methods: From July 2013 to February 2017, 18 patients with adenocarcinoma in the right colon underwent right colectomy with laparoscopic D3APEM, including lymph nodes anterior and posterior to the superior mesenteric vessels. A reconstructed three-dimensional anatomy map derived from the staging computed tomography was used as a road map at surgery. The procedure was systematized into seven operative steps: Step 1, trocar placement and inspection; Step 2, release of the transverse colon; Step 3, identification of the terminal mesenteric vessels; Step 4, release of the anterior flap; Step 5, division of the transverse mesocolon; Step 6, release of the posterior flap; and Step 7, anastomosis and specimen removal. Patient disposition and variations regarding vascular anatomy and ability to expose consequentially may necessitate a variation in the sequence of the steps. Results: A total of 7 (39%) cases were converted, 3 due to bleeding and 4 due to challenging dissection. Median operative time and blood loss were 276 minutes (168-439 minutes) and 200 mL (< 50-1300 mL), respectively. Postoperative complications occurred in 6 (33%), including 2 (11%) major complication requiring reoperation. Median hospital stay was 5 days (3-13 days). R0 resection was achieved in all cases. Median number of the lymph nodes harvested was 40 (25-86), including 11.5 (4-35) in the D3 volume. Six patients (33%) had positive nodes, 3 of them affecting the D3 zone, including 1 case of a skip metastasis. There was no mortality, and at present all the patients are alive. One patient developed distant lymph node metastases. Conclusion: Laparoscopic right colectomy with D3APEM is feasible, associated with acceptable morbidity and fast recovery; now in readiness for introduction in specialized colorectal institutions.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Sequential courses of anticancer target therapy lead to selection of drug-resistant cells, which results in continuous decrease of clinical response. Here we present a new approach for predicting effective combinations of target drugs, which act in a synergistic manner. Synergistic combinations of drugs may prevent or postpone acquired resistance, thus increasing treatment efficiency. We cultured human ovarian carcinoma SKOV-3 and neuroblastoma NGP-127 cancer cell lines in the presence of Tyrosine Kinase Inhibitors (Pazopanib, Sorafenib, and Sunitinib) and Rapalogues (Temsirolimus and Everolimus) for four months and obtained cell lines demonstrating increased drug resistance. We investigated gene expression profiles of intact and resistant cells by microarrays and analyzed alterations in 378 cancer-related signaling pathways using the bioinformatical platform Oncobox. This revealed numerous pathways linked with development of drug resistant phenotypes. Our approach is based on targeting proteins involved in as many as possible signaling pathways upregulated in resistant cells. We tested 13 combinations of drugs and/or selective inhibitors predicted by Oncobox and 10 random combinations. Synergy scores for Oncobox predictions were significantly higher than for randomly selected drug combinations. Thus, the proposed approach significantly outperforms random selection of drugs and can be adopted to enhance discovery of new synergistic combinations of anticancer target drugs.

© 2018; Pediatria Ltd. All rights reserved. Congenital uropathies (CU) are anomalies associated with impaired patency of the upper and lower urinary tract and include congenital hydronephrosis, megaureter, primary vesicoureteral reflux (VUR), infravesical obstruction with prevalence in the pediatric population up to 1,4-2,8%. The most dangerous complication of CU is the development of kidney fibrosis in 30-60% of children combined with a persistent urinary system infection (USI). The lack of effective methods for early diagnosis and evaluation of renal parenchyma fibrosis treatment efficacy dictates the need for further search for molecular indicators of kidney injury. The article describes the study of inflammation biomarkers (interleukin 6 (IL6), inertleukin 8 (IL8), interleukin 10 (IL10)) and fibrosis (monocyte chemoattractant protein 1 (MCP1), transforming growth factor Β1 (TGFΒ1), vasculoendothelial growth factor (VEGF)) in urine in children with CU for diagnosis, monitoring and predicting the course of pathology. The study included 255 patients with various variants of CU (congenital hydronephrosis - 75, VUR - 169, infravesical obstruction - 11). The mean age of the patients was 4,3±3,2 years. The comparison group included 20 almost healthy children stratified by sex and age without USI. Biomarkers were determined by the method of enzyme immunoassay (ELISA) in the dynamics of pathology. All patients had an increase in urinary levels of proinflammatory cytokines (IL6, 8), even without clinical picture of USI. The increase in the concentration of MCP1 and TGFΒ1 in the urine is proportional to the degree and duration of VUR before its treatment, their content increased after 6 months after the correction of VUR and indicated the persistence of latent pyelonephritis and fibrosis progression. Molecular diagnosis of inflammation and fibrosis markers n the urine is a promising noninvasive method for assessing the pathological process in kidneys, the effectiveness and adequacy of the treatment.

The atherosclerosis is considered among the most prevalent diseases. In Russia, N. N. Anitchkov and A. L. Miasnikov are founders of atherosclerosis studies. Valentina Iosifovna Miasnikova, doctor of medical sciences, professor of the Chair of Faculty Therapy #2 of the Sechenov University is one the numerous followers of A. L. Miasnikov. From the early 1960s, Valentina Iosifovna, proceeding with ideas of N. N. Anitchkov and A. L. Miasnikov, actively investigated pathogenesis of atherosclerosis. The professor V. I. Kalmykova, one of the first in Russia presented pathogenesis of atherosclerosis as a multi-factorial process and, combining theories existed at that moment, described effect of peroxidation of lipids on all stages of development of atherosclerotic plaque. She carried out a unique scientific investigation concerning studying intensity of peroxidation of lipids and antioxidant activity of lipids in patients with various degree of expression of ischemic heart disease. The gender characteristics of content of peroxides and antioxidant activity of lipids of blood serum were established. The research works of professor V. I. Kalmykova made an invaluable contribution into comprehension of pathogenesis of atherosclerosis and obtained an international approval. The scientific data obtained by V. I. Kalmykova were confirmed by studies of national and international researchers. Nowadays, the role of oxidation process in pathogenesis of atherosclerosis and ischemic heart disease is generally acknowledged.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature.  Introduction: Nitroproston® is a novel multi-target drug bearing natural prostaglandin E 2 (PGE 2 ) and nitric oxide (NO)-donating fragments for treatment of inflammatory and obstructive diseases (i.e., asthma and obstructive bronchitis). Objectives: To investigate the effects of Nitroproston® administration on plasma metabolomics in vivo. Methods: Experimental in vivo study randomly assigning the target drug (treatment group) or a saline solution without the drug (vehicle control group) to 12 rabbits (n = 6 in each group). Untargeted (5880 initial features; 1869 negative–4011 positive ion peaks; UPLC–IT–TOF/MS) and 84 targeted moieties (Nitroproston® related metabolites, prostaglandins, steroids, purines, pyrimidines and amino acids; HPLC–QQQ–MS/MS) were measured from plasma at 0, 2, 4, 6, 8, 12, 18, 24, 32 and 60 min after administration. Results: PGE 2 , 13,14-dihydro-15-keto-PGE 2 , PGB 2 , 1,3-GDN and 15-keto-PGE 2 increased in the treatment group. Steroids (i.e., cortisone, progesterone), organic acids, 3-oxododecanoic acid, nicotinate d-ribonucleoside, thymidine, the amino acids serine and aspartate, and derivatives pyridinoline, aminoadipic acid and uric acid increased (p < 0.05 AUCROC curve > 0.75) after treatment. Purines (i.e., xanthine, guanine, guanosine), bile acids, acylcarnitines and the amino acids l-tryptophan and l-phenylalanine were decreased. Nitroproston® impacted steroidogenesis, purine metabolism and ammonia recycling pathways, among others. Conclusion: Nitroproston®, a multi action novel drug based on natural prostaglandins, altered metabolites (i.e., guanine, adenine, cortisol, cortisone and aspartate) involved in purine metabolism, urea and ammonia biological cycles, steroidogenesis, among other pathways. Suggested mechanisms of action, metabolic pathway interconnections and useful information to further understand the metabolic effects of prostaglandin administration are presented.

© 2018 IEEE. We study both theoretically and experimentally an ability for shaping the spectra of the terahertz (THz) pulses, emitted by a photoconductive antennas (PCAs) with the logspiral configuration of electrodes, by impedance matching. We select and fabricate 2 configurations of the LT-GaAs PCAs possessing different frequency-dependent impedances and THz spectra. By comparing the results of our studies, we firstly demonstrate high-to-moderate correlation between the frequency-dependent impedance matching efficiency and the THz spectra. The proposed approach makes possible optimizing the PCA performance for accommodating the needs of the THz technology use in various branches, especially in condensed matter and biomedicine.

© 2018 IEEE. Technique of laser microsurgery of cell spheroids with nanosecond laser pulses was used to develop a new simple reproducible model for studying regeneration in vitro. Wound restoration accompanying the reparative processes occurred gradually over seven days due to rearrangement of surviving non-proliferating cells. Skin anti-ageing drugs can be tested on the developed model of cell spheroid's regeneration.

© 2018 IEEE. In our work, we have performed in vitro terahertz (THz) measurements of gelatin-embedded malignant human brain gliomas using the THz pulsed spectroscopy. The gelatin embedding yields sustain the THz response of tissues close to that of the freshly-excised ones for a long time after the resection. We have observed significant differences between the THz responses of normal and pathological tissues of the brain, which highlights a potential of the THz technology in label-free intraoperative neurodiagnosis of tumors.

© 2018 IEEE. We have proposed a method of THz solid immersion microscopy, which yields imaging soft biological tissues with the sub-wavelength resolution up to 0.2-wavelengths. To achieve this advanced resolution, it employs a solid immersion phenomenon - i.e. a reduction in the dimensions of the THz beam caustic by its formation on a small distance behind the medium featuring high refractive index. We have assembled an experimental setup, which realizes the principles of the THz solid immersion microscopy, and proposed an approach for handling the soft tissue at the object plane. This setup uses a backward-wave oscillator, as a source of continuous-wave THz radiation, and a Golay cell, as a detector of the THz field intensity. We have examined the resolution of the THz solid immersion microscopy using both numerical simulations and experimental studies. Finally, in order to highlight the prospective of the proposed THz imaging modality, we have applied the experimental setup for imaging of representative examples of biological tissues.

© 2018 IEEE. Modern progress in terahertz (THz) diagnostics of malignancies, including non-invasive, least-invasive and intraoperative techniques is briefly discussed. Special attention is paid to intraoperative diagnosis of brain tumors, which is a rapidly developing field nowadays. We discuss our recent results in this research field, which are associated with (i) in vitro studies the THz dielectric response of gelatin-embedded human brain tumors (including gliomas and meningiomas featuring different grades), (ii) analysis an ability for differentiation between normal and pathological tissues of the brain relying on the methods of THz spectroscopy and imaging, and, finally, (iii) development of novel THz instrumentation for the intraoperative detection of margins of tumors in order to guarantee its gross total resection.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Neonatal sepsis is one of the major causes of mortality and morbidity in newborns, greatly associated with severe acute kidney injury (AKI) and failure. Handling of newborns with kidney damage can be significantly different compared to adults, and it is necessary to consider the individuality of an organism’s response to systemic inflammation. In this study, we used lipopolysaccharide (LPS)-mediated acute kidney injury model to study mechanisms of kidney cells damage in neonatal and adult rats. We found LPS-associated oxidative stress was more severe in adults compared to neonates, as judged by levels of carbonylated proteins and products of lipids peroxidation. In both models, LPS-mediated septic simulation caused apoptosis of kidney cells, albeit to a different degree. Elevated levels of proliferating cell nuclear antigen (PCNA) in the kidney dropped after LPS administration in neonates but increased in adults. Renal fibrosis, as estimated by smooth muscle actin levels, was significantly higher in adult kidneys, whereas these changes were less profound in LPS-treated neonatal kidneys. We concluded that in LPS-mediated AKI model, renal cells of neonatal rats were more tolerant to oxidative stress and suffered less from long-term pathological consequences, such as fibrosis. In addition, we assume that by some features LPS administration simulates the conditions of accelerated aging.

© 2018 2018 S. Karger AG, Basel. Background: Transurethral resection of the prostate (TURP) is considered to be the standard treatment for patients with benign prostatic obstruction (BPO) ≤80 mL. However, up to 14.7% of the patients require secondary TURP due to recurrent BPO. The aim of our study was to describe specific features of holmium laser enucleation of the prostate (HoLEP) and thulium laser enucleation of the prostate (ThuLEP) in patients with recurrent BPO after previous prostate surgery. Materials and Methods: A total of 768 consecutive patients from our prospective collected database were retrospectively reviewed and divided into 4 groups: group A (489 patients) and group C (253 patients) underwent primary HoLEP and ThuLEP treatment, while group B (17 patients) and D (9 patients) included patients with recurrent BPO who were treated with HoLEP and ThuLEP, respectively. Results: There were no significant differences in preoperative parameters between the groups at primary (A and C) and secondary (B and D) treatment except their age. At 6-month follow-up, voiding parameters and symptom scores showed statistically significant improvements compared to baseline without differences between the groups. The mean operative time was comparable between the groups and did not differ significantly (p > 0.05). Conclusions: Laser enucleation for the treatment of recurrent BPO is feasible and seems to be a safe and effective procedure.

© 2018, Springer International Publishing AG, part of Springer Nature.  Molecular oxygen (O 2 ) is a key player in cell mitochondrial function, redox balance and oxidative stress, normal tissue function and many common disease states. Various chemical, physical and biological methods have been proposed for measurement, real-time monitoring and imaging of O 2 concentration, state of decreased O 2 (hypoxia) and related parameters in cells and tissue. Here, we review the established and emerging optical microscopy techniques allowing to visualize O 2 levels in cells and tissue samples, mostly under in vitro and ex vivo, but also under in vivo settings. Particular examples include fluorescent hypoxia stains, fluorescent protein reporter systems, phosphorescent probes and nanosensors of different types. These techniques allow high-resolution mapping of O 2 gradients in live or post-mortem tissue, in 2D or 3D, qualitatively or quantitatively. They enable control and monitoring of oxygenation conditions and their correlation with other biomarkers of cell and tissue function. Comparison of these techniques and corresponding imaging setups, their analytical capabilities and typical applications are given.

© 2018 The Association of Coloproctology of Great Britain and Ireland.  Aim To describe the technique of a modified extraperitoneal retrotransversalis end colostomy as part of a laparoscopic abdominoperineal excision (APR). Method The colostomy site is preoperatively chosen and used intra-operatively for a trocar. After the rectum has been mobilized the descending colon is freed. The peritoneal margin is gently grasped and the parietal peritoneum and extraperitoneal together with the transversalis fascia are separated from the transverse abdominal muscle fibres upwards for 3–4 cm aiming at the trocar site to form the extraperitoneal retrotransversalis canal. The stoma site trocar is partially withdrawn and its head is turned laterally until its tip is positioned in the layer between the abdominal wall muscles and underlying transversalis and extraperitoneal fascia together with the parietal peritoneum. The CO 2 source can be attached so that the gas helps to separate the layers, after which the colostomy trephine is formed at the site of the trocar, the grasper is inserted to gently deliver the blunt end of the descending colon through the canal and the end colostomy is formed in a usual way. Results No procedure-specific complications were noted in 39 patients who had laparoscopic APR with extraperitoneal retrotransversalis end colostomy from 2009 to 2016. In 23 patients who survived for 3.7 ± 1.7 years after surgery there were no clinical or CT signs of parastomal hernia or prolapse. Conclusion This single-institution retrospective case series demonstrates that laparoscopic extraperitoneal retrotransversalis end colostomy is feasible, safe and effective in preventing parastomal hernias and stomal prolapse.

© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Experimental Biology. Potato is the most economically important non-cereal food crop. Tuber formation in potato is regulated by phytohormones, cytokinins (CKs) in particular. The present work studied CK signal perception in potato. The sequenced potato genome of doubled monoploid Phureja was used for bioinformatic analysis and as a tool for identification of putative CK receptors from autotetraploid potato cv. Désirée. All basic elements of multistep phosphorelay required for CK signal transduction were identified in the Phureja genome, including three genes orthologous to three CK receptor genes (AHK 2-4) of Arabidopsis. As distinct from Phureja, autotetraploid potato contains at least two allelic isoforms of each receptor type. Putative receptor genes from Désirée plants were cloned, sequenced and expressed, and the main characteristics of encoded proteins were determined, in particular their consensus motifs, modelled structure, ligand-binding properties, and ability to transmit CK signals. In all studied aspects the predicted sensor histidine kinases met the requirements for genuine CK receptors. Expression of potato CK receptors was found to be organ-specific and sensitive to growth conditions, particularly to sucrose content. Our results provide a solid basis for further in-depth study of CK signaling system and biotechnological improvement of potato.

© 2018 by Turkish Association of Urology. Objective: Surgical site infection (SSI) is defined as infection at or near surgical incisions within 30 days of an operative procedure and classified either incisional superficial and deep or organ/space. The aim of the study is to report and compare the incidence and management of SSIs after robot-assisted laparoscopic radical prostatectomy (RALP) and retropubic radical prostatectomy (RRP). Material and methods: Within the last 4 years, we identified 285 patients that underwent RRP, n=187 (66%) or RALP, n=98 (34%). We reviewed the frequency, types and way of management of SSI complications. Results: A significant difference was found between RALP and RRP (2/98, 2% vs. 27/187, 14.4%; p<0.0001) as for SSIs. The time interval between the time of surgery and diagnosis of SSIs was longer in RALP relative to RRP (median 13.5 vs. 12.9 days, p=0.761). Conclusion: All types of SSIs could be developed after RP, however RALP patients only experienced organ or space SSIs and have a lower rate of SSIs and shorter treatment time.

© 2018 John Wiley  &  Sons Australia, Ltd This research is designed to test the hypothesis that elevated homocysteine (Hcy) levels in vivo, caused by a deficit in vitamin B complex, promote changes in cardiac function and redox status that lead to heart failure. In order to conduct the study, we used adult male Wistar albino rats (n = 30; 4 weeks old; 100 ± 15 g body weight). Hyperhomocysteinaemia (HHcy) in these animals was achieved by dietary manipulation. For 4 weeks, the animals were fed with a standard rodent chow (control, CF), a diet enriched in methionine with no deficiency in B vitamins (i.e., folic acid, B6 and B12) (HMNV) or a diet enriched in methionine and deficient in B vitamins (HMLV). After 28 days of dietary manipulation, all animals were killed. The rat hearts were isolated and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure. We found a negative correlation between elevated serum Hcy and total body and heart weight. The maximum rate of left ventricular pressure development was significantly increased in the HMNV group compared with in the other groups. Systolic left ventricular pressure was significantly changed in all groups. HHcy induces remodelling of the cardiac tissues, as moderate HHcy is associated with more prominent interstitial and perivascular fibrosis. Our results suggest that a high methionine diet without vitamin B complex causes profound negative effects associated with HHcy.