Репозиторий Университета

© 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. Shown the efficiency of the LAS method in creating mechanically induced scaffolds with a multilayer biointerface.

© 2018 IEEE. In this work, we present the first histological ex vivo (porcine gum) and in vivo (human) study of effects of fractional Er fiber laser (wavelength 1550 nm, peak power 25 W) on keratinized gum and alveolar mucosa in oral cavity.

© 2018 IEEE. We demonstrate a wavelet-domain denoising technique for imaging of human brain malignant tissues by optical coherence tomography. It allows for reducing the scattering noise and retaining signal artifacts for each tissue type, including malignant glioma and meningioma.

© 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. We have proposed novel medical instruments based on sapphire shaped crystals fabricated using the edge-defined film-fed growth (EFG) or related techniques. Due to the favorable combination of the unique properties of sapphire (high thermal strength and mechanical hardness, impressive melting point and chemical resistance, transparency in a wide spectral range) the developed instruments could help to solve numerous important problems of medical diagnosis, therapy, and surgery.

© 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. Articular hyaline cartilage is extensively hydrated, but it is neither innervated nor vascularized, and its low cell density allows only extremely limited self-renewal. Most clinical and research efforts currently focus on the restoration of cartilage damaged in connection with osteoarthritis or trauma. Here, we discuss current clinical approaches for repairing cartilage, as well as research approaches which are currently developing, and those under translation into clinical practice. We also describe potential future directions in this area, including tissue engineering based on scaffolding and/or stem cells as well as a combination of gene and cell therapy. Particular focus is placed on cell-based approaches and the potential of recently characterized chondro-progenitors; progress with induced pluripotent stem cells is also discussed. In this context, we also consider the ability of different types of stem cell to restore hyaline cartilage and the importance of mimicking the environment in vivo during cell expansion and differentiation into mature chondrocytes.

© 2018 by the authors. There is growing awareness for the need of early diagnostic tools to aid in point-of-care testing in cancer. Tumor biopsy remains the conventional means in which to sample a tumor and often presents with challenges and associated risks. Therefore, alternative sources of tumor biomarkers is needed. Liquid biopsy has gained attention due to its non-invasive sampling of tumor tissue and ability to serially assess disease via a simple blood draw over the course of treatment. Among the leading technologies developing liquid biopsy solutions, microfluidics has recently come to the fore. Microfluidic platforms offer cellular separation and analysis platforms that allow for high throughout, high sensitivity and specificity, low sample volumes and reagent costs and precise liquid controlling capabilities. These characteristics make microfluidic technology a promising tool in separating and analyzing circulating tumor biomarkers for diagnosis, prognosis and monitoring. In this review, the characteristics of three kinds of circulating tumor markers will be described in the context of cancer, circulating tumor cells (CTCs), exosomes, and circulating tumor DNA (ctDNA). The review will focus on how the introduction of microfluidic technologies has improved the separation and analysis of these circulating tumor markers.

© 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 Zlobin, Mokrushina, Terekhov, Zalevsky, Bobik, Stepanova, Aliseychik, Kartseva, Panteleev, Golovin, Belogurov, Gabibov and Smirnov. Butyrylcholinesterase (BChE) is considered as an efficient stoichiometric antidote against organophosphorus (OP) poisons. Recently we utilized combination of calculations and ultrahigh-throughput screening (uHTS) to select BChE variants capable of catalytic destruction of OP pesticide paraoxon. The purpose of this study was to elucidate the molecular mechanism underlying enzymatic hydrolysis of paraoxon by BChE variants using hybrid quantum mechanical/molecular mechanical (QM/MM) calculations. Detailed analysis of accomplished QM/MM runs revealed that histidine residues introduced into the acyl-binding loop are always located in close proximity with aspartate residue at position 70. Histidine residue acts as general base thus leading to attacking water molecule activation and subsequent SN2 inline hydrolysis resulting in BChE reactivation. This combination resembles canonical catalytic triad found in active centers of various proteases. Carboxyl group activates histidine residue by altering its pKa, which in turn promotes the activation of water molecule in terms of its nucleophilicity. Observed re-protonation of catalytic serine residue at position 198 from histidine residue at position 438 recovers initial configuration of the enzyme's active center, facilitating next catalytic cycle. We therefore suggest that utilization of uHTS platform in combination with deciphering of molecular mechanisms by QM/MM calculations may significantly improve our knowledge of enzyme function, propose new strategies for enzyme design and open new horizons in generation of catalytic bioscavengers against OP poisons.

© 2018 The Author(s). Background: Amphibian trypanosomes were the first ever described trypanosomatids. Nevertheless, their taxonomy remains entangled because of pleomorphism and high prevalence of mixed infections. Despite the fact that the first species in this group were described in Europe, virtually none of the trypanosomes from European anurans was analyzed using modern molecular methods. Methods: In this study, we explored the diversity and phylogeny of trypanosomes in true frogs from Europe using light microscopy and molecular methods. Results: A comparison of observed morphotypes with previous descriptions allowed us to reliably identify three Trypanosoma spp., whereas the remaining two strains were considered to represent novel taxa. In all cases, more than one morphotype per blood sample was observed, indicating mixed infections. One hundred and thirty obtained 18S rRNA gene sequences were unambiguously subdivided into five groups, correspondent to the previously recognized or novel taxa of anuran trypanosomes. Conclusions: In this work we studied European frog trypanosomes. Even with a relatively moderate number of isolates, we were able to find not only three well-known species, but also two apparently new ones. We revealed that previous assignments of multiple isolates from distant geographical localities to one species based on superficial resemblance were unjustified. Our work also demonstrated a high prevalence of mixed trypanosome infections in frogs and proposed a plausible scenario of evolution of the genus Trypanosoma.

AIM: To evaluate the effectiveness of three-dimensional printing application in urology for localized renal cancer treatment using three-dimensional printed soft models. MATERIALS AND METHODS: The study included five patients with kidney tumors. The patients were treated in the Urology Clinic of I.M. Sechenov First Moscow State Medical University from February 2016 to June 2017. Personalized three-dimensional printed models based on computed tomographic images were created. Five surgeons took part in a survey in which the utility of computed tomographic images versus three-dimensional printed models for presurgical planning was compared. A laparoscopic partial nephrectomy training using the developed three-dimensional printed models was performed by the same surgeons in a surgical training box. RESULTS: The patients underwent endoscopic surgery using laparoscopic access. The average time of surgery was 187 min. All the operations were performed with complete renal artery clamping. The average warm ischemia time was 19.5 min and the average blood loss was 170 mL. No conversions to open surgery or radical nephrectomy, and no postoperative complications and deaths were observed. All the surgical margins were negative. The tumors were morphologically identified as renal cell carcinoma in four cases and as oncocytoma in one case. CONCLUSION: The developed three-dimensional printed models allow one to evaluate the pathological anatomy of tumors more effectively. High similarity between three-dimensional models and native kidneys contribute to improvement of surgical skills necessary for partial nephrectomy. Training on the three-dimensional models also allows surgeons to facilitate selection of an optimal surgical tactics for each patient.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. We analyzed diurnal hemodynamic parameters (HR, systolic BP, and diastolic BP) recorded from two groups of edematous and preeclamptic pregnant women. The unidirectional character of changes in the control over the functional state of cardiovascular system was revealed except for the indices, which mark a pathological process: elevated diurnal BP in preeclampsia and diminished percentage of oscillation power in edematous patients. Uniformity of the regulatory changes in patients with and without arterial hypertension can be viewed as manifestation of allostasis developed by the cardiovascular system during pregnancy. In preeclampsia, the greater allostatic load was reflected by the changes in diurnal, daytime, and nighttime BP and in the circadian index calculated for HR, systolic BP, and diastolic BP. In edematous patients, elevation of allostatic load was indicated by the percentage of ultradian rhythms.

© 2018 by the authors. Neonatal hypoxia–ischemia is one of the main causes of mortality and disability of newborns. To study the mechanisms of neonatal brain cell damage, we used a model of neonatal hypoxia–ischemia in seven-day-old rats, by annealing of the common carotid artery with subsequent hypoxia of 8% oxygen. We demonstrate that neonatal hypoxia–ischemia causes mitochondrial dysfunction associated with high production of reactive oxygen species, which leads to oxidative stress. Targeted delivery of antioxidants to the mitochondria can be an effective therapeutic approach to treat the deleterious effects of brain hypoxia–ischemia. We explored the neuroprotective properties of the mitochondria-targeted antioxidant SkQR1, which is the conjugate of a plant plastoquinone and a penetrating cation, rhodamine 19. Being introduced before or immediately after hypoxia–ischemia, SkQR1 affords neuroprotection as judged by the diminished brain damage and recovery of long-term neurological functions. Using vital sections of the brain, SkQR1 has been shown to reduce the development of oxidative stress. Thus, the mitochondrial-targeted antioxidant derived from plant plastoquinone can effectively protect the brain of newborns both in pre-ischemic and post-stroke conditions, making it a promising candidate for further clinical studies.

© 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 Wolters Kluwer Health, Inc. All rights reserved. This work presents the results of in-vitro biological activity studies of three novel anticancer agents, phosphonium salts based on the 3-hydroxypyridine scaffold, including one derivative of 4-deoxypyridoxine. Proliferation and viability of cells treated with these compounds was assessed by the colony formation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Effects of the compounds on apoptosis and cell cycle were studied by flow cytometry using annexin V-FITC/propidium iodide and propidium iodide staining, respectively. The influence of the compounds on mitochondrial membrane potential and intracellular reactive oxygen species was evaluated using tetramethyl rhodamine ethyl and DCFHA staining. Western blot analysis was used to study the changes in the expression of Bcl-xL, Bax, and caspase-3 apoptotic proteins. The treatment of ovarian adenocarcinoma cells OVCAR-4 with the tested compounds inhibited the growth and induced cell cycle arrest in the G1 phase. 3-Hydroxypyridine derivatives induced apoptosis by hyperexpression of Bax and caspase-3, whereas 4-deoxypyridoxine derivative induced cell death partly by reactive oxygen species generation and caspase-3 hyperexpression. These results indicate that the quaternary phosphonium salts studied represent potential therapeutic agents for the treatment of ovarian cancer.