Репозиторий Университета

© 2020 Elsevier Ltd Novel octabromo-substituted lanthanide(III) phthalocyanines were obtained via template method starting from corresponding 4,5-dibromophthalonitrile and identified by high-resolution mass-spectrometry, 1H nuclear magnetic resonanse and infra red spectroscopy. To achieve an initial 4,5-dibromophthalonitrile the reaction conditions of Pd(0) catalyzed cyanation were optimized. The peripheral bromine atoms impact on the optical properties of phthalocyanine complexes. The bathochromic shift of the main absorption band (Q band) was observed going from unsubstituted to octachloro- and then to octabromo-substituted phthalocyanines. All complexes demonstrated nonlinear optical responses in the DMF solution. Increasing the intensity of laser radiation leads to a nonlinear decrease in transmittance and further restoration of optical properties when switching back to linear mode. Nonlinear optical responses depend on the central ion nature. Europium phthalocyanine showed the enhanced nonlinear absorption coefficient compared to lutetium and terbium complexes. This was caused by an enhanced population of excited state and faster excitement for complexes with large central ions. The impact of peripheral bromine groups into nonlinear optical properties was determined through the comparison with unsubstituted analogues.

© 2020 Immunotherapy methods using potential tumor microenvironment modulators have elicited durable therapeutic responses in cancer treatment. Immune checkpoint molecule programmed cell death-ligand 1 (PD-L1) and oncogenic transcription factor STAT3 (signal transducer and activator of transcription-3) assigned as inhibitory targets of our study and particular delivery system designed to deliver small interfering RNAs (siRNAs) to silence the targeted genes. Generated trimethyl chitosan (TMC) and thiolated chitosan (TC) nanoparticles (NPs) conjugated with HIV-1-derived TAT peptide and HA (hyaluronic acid) exhibited eligible physicochemical characteristics, notable siRNA encapsulation, serum stability, non-toxicity, controlled siRNA release, and extensive cellular uptake by cancer cells. Dual inhibition with STAT3/PD-L1 siRNA-loaded HA-TAT-TMC-TC NPs led to promising results, including significant downregulation of PD-L1 and STAT3 genes, striking suppressive effects on proliferation, migration, and angiogenesis of breast and melanoma cancer cell lines, and restrained tumor growth in vivo. These findings infer the capability of HA-TAT-TMC-TC NPs containing STAT3/PD-L1 siRNAs as a novel tumor-suppressive candidate in cancer treatment.

© 2020 Elsevier B.V. Parkinson's disease (PD) is a common neurodegenerative disorder that leads to significant morbidity and decline in the quality of life. It develops due to loss of dopaminergic neurons in the substantia nigra pars compacta, and among its pathogenic factors oxidative stress plays a critical role in disease progression. Pesticides are a broad class of chemicals widely used in agriculture and households for the protection of crops from insects and fungi. Several of them have been incriminated as risk factors for PD, but the underlying mechanisms have yet to be fully understood. MicroRNAs (miRNAs) are small, non-coding RNA molecules that play an important role in regulating mRNA translation and protein synthesis. miRNA levels have been shown to be affected in several diseases as well. Since the studies on the association between pesticides and PD have yet to reach definitive conclusions, here we review recent evidence on deregulated microRNAs upon pesticide exposure, and attempt to find an overlap between miRNAs deregulated in PD and pesticides, as a missing link between the two, and enhance future research in this direction.

© 2020 Elsevier Inc. Chronic obstructive pulmonary disease (COPD) is a common term for alveolar septal wall destruction resulting in emphysema, and chronic bronchitis accompanied by conductive airway remodelling. In general, this disease is characterized by a disbalance of proteolytic/anti-proteolytic activity, augmented inflammatory response, increased oxidative/nitrosative stress, rise in number of apoptotic cells and decreased proliferation. As the first responder to the various environmental stimuli, epithelium occupies an important position in different lung pathologies, including COPD. Epithelium sequentially transitions from the upper airways in the direction of the gas exchange surface in the alveoli, and every cell type possesses a distinct role in the maintenance of the homeostasis. Basically, a thick ciliated structure of the airway epithelium has a major function in mucus secretion, whereas, alveolar epithelium which forms a thin barrier covered by surfactant has a function in gas exchange. Following this line, we will try to reveal whether or not the chronic bronchitis and emphysema, being two pathological phenotypes in COPD, could originate in two different types of epithelium. In addition, this review focuses on the role of lung epithelium in COPD pathology, and summarises underlying mechanisms and potential therapeutics.

© 2019 The Authors Executive function is defined as a set of cognitive skills that are necessary to plan, monitor, and execute a sequence of goal-directed complex actions. Executive function is influenced by a variety of factors, including habitual sleep duration and diabetes. In the present study, we investigated in 18,769 Swedish adults (mean age: 61 y) the association between executive function, diabetes, and self-reported sleep duration. We observed a significant interaction between diabetes and sleep duration for the Trail Making Test (TMT) ratio (P < 0.01). This ratio is a measure of executive function where higher values indicate worse performance. Among diabetic participants (n = 1,523), long (defined as ≥9 h per day) vs. normal sleep duration (defined as 7–8 hours per day) was associated with a higher TMT ratio (P < 0.05). Similar significant results were observed in diabetic individuals without pharmacological treatment for diabetes (n = 1,062). Among non-diabetic participants (n = 17,246), no association between long sleep duration and the TMT ratio was observed (P > 0.05). Instead, short (defined as <7 h per day) vs. normal sleep duration was linked to a higher TMT ratio (P < 0.05). These findings suggest that the association between sleep duration and executive function differs between diabetic and non-diabetic middle-aged and older adults. Based on the cross-sectional design of the study, no firm conclusions can be drawn on the causality of the relations.

© 2019 Elsevier B.V. Expression of programmed death-ligand 1 (PD-L1) in cancer cells plays an important role in cancer-immune cell interaction. The emerging evidence suggests regulation of PD-L1 expression by several tumor microenvironmental cues. However, the association of PD-L1 expression with chemical and mechanical features of the tumor microenvironment, specifically epidermal growth factor receptor (EGFR) signaling and matrix stiffness, remains elusive. Herein, we determine whether EGFR targeting and substrate stiffness affect the regulation of PD-L1 expression. Breast carcinoma cell lines, MCF7 and MDA-MB-231, were cultured under different conditions targeting EGFR and exposing cells to distinct substrate stiffness to evaluate PD-L1 expression. Furthermore, the ability to form aggregates in short-term culture of breast carcinoma cells and its effect on expression level of PD-L1 was probed. Our results indicated that PD-L1 expression was altered in response to both EGFR inhibition and substrate stiffness. Additionally, a positive association between the formation of multicellular aggregates and PD-L1 expression was observed. MDA-MB-231 cells expressed the highest PD-L1 level on a stiff substrate, while inhibition of EGFR reduced expression of PD-L1. The results suggested that both physical and chemical features of tumor microenvironment regulate PD-L1 expression through alteration of tumor aggregate formation potential. In line with these results, the in-silico study highlighted a positive correlation between PD-L1 expression, EGFR signaling, epithelial to mesenchymal transition related transcription factors (EMT-TFs) and stemness markers in metastatic breast cancer. These findings improve our understanding of regulation of PD-L1 expression by tumor microenvironment leading to evasion of tumor cells from the immune system.

© 2019, The Author(s). Abstract: In 2014 the International Endohernia Society (IEHS) published the first international “Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias”. Guidelines reflect the currently best available evidence in diagnostics and therapy and give recommendations to help surgeons to standardize their techniques and to improve their results. However, science is a dynamic field which is continuously developing. Therefore, guidelines require regular updates to keep pace with the evolving literature. Methods: For the development of the original guidelines all relevant literature published up to year 2012 was analyzed using the ranking of the Oxford Centre for Evidence-Based-Medicine. For the present update all of the previous authors were asked to evaluate the literature published during the recent years from 2012 to 2017 and revise their statements and recommendations given in the initial guidelines accordingly. In two Consensus Conferences (October 2017 Beijing, March 2018 Cologne) the updates were presented, discussed, and confirmed. To avoid redundancy, only new statements or recommendations are included in this paper. Therefore, for full understanding both of the guidelines, the original and the current, must be read. In addition, the new developments in repair of abdominal wall hernias like surgical techniques within the abdominal wall, release operations (transversus muscle release, component separation), Botox application, and robot-assisted repair methods were included. Results: Due to an increase of the number of patients and further development of surgical techniques, repair of primary and secondary abdominal wall hernias attracts increasing interests of many surgeons. Whereas up to three decades ago hernia-related publications did not exceed 20 per year, currently this number is about 10-fold higher. Recent years are characterized by the advent of new techniques—minimal invasive techniques using robotics and laparoscopy, totally extraperitoneal repairs, novel myofascial release techniques for optimal closure of large defects, and Botox for relaxing the abdominal wall. Furthermore, a concomitant rectus diastasis was recognized as a significant risk factor for recurrence. Despite still insufficient evidence with respect to these new techniques it seemed to us necessary to include them in the update to stimulate surgeons to do research in these fields. Conclusion: Guidelines are recommendations based on best available evidence intended to help the surgeon to improve the quality of his daily work. However, science is a continuously evolving process, and as such guidelines should be updated about every 3 years. For a comprehensive reference, however, it is suggested to read both the initially guidelines published in 2014 together with the update. Moreover, the presented update includes also techniques which were not known 3 years before.

© 2019, The Author(s). Abstract: In 2014, the International Endohernia Society (IEHS) published the first international “Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias.” Guidelines reflect the currently best available evidence in diagnostics and therapy and give recommendations to help surgeons to standardize their techniques and to improve their results. However, science is a dynamic field which is continuously developing. Therefore, guidelines require regular updates to keep pace with the evolving literature. Methods: For the development of the original guidelines, all relevant literature published up to year 2012 was analyzed using the ranking of the Oxford Centre for Evidence-Based Medicine. For the present update, all of the previous authors were asked to evaluate the literature published during the recent years from 2012 to 2017 and revise their statements and recommendations given in the initial guidelines accordingly. In two Consensus Conferences (October 2017 Beijing, March 2018 Cologne), the updates were presented, discussed, and confirmed. To avoid redundancy, only new statements or recommendations are included in this paper. Therefore, for full understanding both of the guidelines, the original and the current, must be read. In addition, the new developments in repair of abdominal wall hernias like surgical techniques within the abdominal wall, release operations (transversus muscle release, component separation), Botox application, and robot-assisted repair methods were included. Results: Due to an increase of the number of patients and further development of surgical techniques, repair of primary and secondary abdominal wall hernias attracts increasing interests of many surgeons. Whereas up to three decades ago hernia-related publications did not exceed 20 per year, currently this number is about 10-fold higher. Recent years are characterized by the advent of new techniques—minimal invasive techniques using robotics and laparoscopy, totally extraperitoneal repairs, novel myofascial release techniques for optimal closure of large defects, and Botox for relaxing the abdominal wall. Furthermore, a concomitant rectus diastasis was recognized as a significant risk factor for recurrence. Despite insufficient evidence with respect to these new techniques, it seemed to us necessary to include them in the update to stimulate surgeons to do research in these fields. Conclusion: Guidelines are recommendations based on best available evidence intended to help the surgeon to improve the quality of his daily work. However, science is a continuously evolving process, and as such guidelines should be updated about every 3 years. For a comprehensive reference, however, it is suggested to read both the initial guidelines published in 2014 together with the update. Moreover, the presented update includes also techniques which were not known 3 years before.

© 2019, Pleiades Publishing, Inc. Abstract: Angiomyolipoma (AML) is one of the most frequent and, at the same time, AML molecular genetics is one of the least studied among benign tumors. We performed deep sequencing of 409 genes involved in oncogenesis in tumor samples and peripheral blood of patients with sporadic AML of the kidney. We recorded mutations in the TSC2 gene in 65% of samples, which is consistent with international results. As a result of our work, we uncovered mutations in the SETD2, PDGFRA, STK36, SYNE1, PIK3CD, NF1, TOP1, and ITGB3 genes in sporadic renal AML for the first time. In two samples, we were able to clarify the clinical and morphological diagnosis by finding mutations in the genes in tumors lacking TSC2 gene lesions. Mutations in MET and CDC73 are also causative for other types of renal tumors: papillary renal cell carcinoma and CDC73-related disorders, respectively. The latter disease is accompanied by kidney cysts and hamartomas. The obtained results demonstrate a promising potential of mutational profiling of sporadic renal angiomyolipoma (sAML). Genotyping of sAML is particularly important for clarification of the clinical diagnosis in ambiguous cases, as well as for a more in-depth understanding of AML molecular genetics and etiopathogenesis, and for the identification of new molecular targets for personalized AML therapies.

© 2018 The Author(s). Presently, many malaria-endemic countries in the world are transitioning towards malaria elimination. Out of the 105 countries with ongoing malaria transmission, 10 countries are classified as being in the pre-elimination phase of malaria control, and 9 countries are in the malaria elimination stage, whereas 7 countries are classified as being in the prevention of introduction phase. Between 2000 and 2015, 17 countries eliminated malaria (i.e., attained zero indigenous cases for 3 years or more). Seven countries were certified by the WHO as having successfully eliminated malaria. The purpose of this review was to analyse the epidemiological characteristics of vivax malaria during the various stages of malaria eradication (elimination) programmes in different countries in the past and present. Experiences of the republics of the former USSR with malaria are interesting, particularly since the data overwhelmingly were published in Russian and might not be known to western readers. Among the most important characteristics of Plasmodium vivax epidemiology at present are changes in the ratio of the short-incubation P. vivax to long-incubation P. vivax, the incidence of severe P. vivax cases, the increased numbers of asymptomatic P. vivax cases, the reduced response to anti-malarials and a few others. Various factors contributing towards the peculiarities of P. vivax epidemiology are discussed.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Purpose of Review: Sleep-wake disorders (SWD) are common not only in the general population but also in stroke patients, in whom SWD may be pre-existent or appear “de novo” as a consequence of brain damage. Despite increasing evidence of a negative impact of SWD on cardiocerebrovascular risk, cognitive functions, and quality of life, SWD are insufficiently considered in the prevention and management of patients with stroke. This narrative review aims at summarizing the current data on the bidirectional link between SWD and stroke. Recent Findings: Several studies have demonstrated that sleep-disordered breathing (SDB) is an independent risk factor for stroke and has a detrimental effect on stroke recovery. Short and long sleep duration and possibly other SWD (e.g., insomnia, circadian rhythm disorders) may also increase the risk of stroke and influence its outcome. Data on SDB treatment increasingly indicate a benefit on stroke risk and evolution while treatment of other SWD is still limited. Summary: A systematic search for SWD in stroke patients is justified due to their high frequency and their negative impact on stroke outcomes. Clinicians should actively consider available treatment options.

© 2018 Brzecka, Leszek, Ashraf, Ejma, ávila-Rodriguez, Yarla, Tarasov, Chubarev, Samsonova, Barreto and Aliev. Sleep disturbances, as well as sleep-wake rhythm disturbances, are typical symptoms of Alzheimer's disease (AD) that may precede the other clinical signs of this neurodegenerative disease. Here, we describe clinical features of sleep disorders in AD and the relation between sleep disorders and both cognitive impairment and poor prognosis of the disease. There are difficulties of the diagnosis of sleep disorders based on sleep questionnaires, polysomnography or actigraphy in the AD patients. Typical disturbances of the neurophysiological sleep architecture in the course of the AD include deep sleep and paradoxical sleep deprivation. Among sleep disorders occurring in patients with AD, the most frequent disorders are sleep breathing disorders and restless legs syndrome. Sleep disorders may influence circadian fluctuations of the concentrations of amyloid-β in the interstitial brain fluid and in the cerebrovascular fluid related to the glymphatic brain system and production of the amyloid-β. There is accumulating evidence suggesting that disordered sleep contributes to cognitive decline and the development of AD pathology. In this mini-review, we highlight and discuss the association between sleep disorders and AD.

© 2017 Elsevier Masson SAS A new water-soluble conjugate, consisting of a chlorin-based photosensitizing part, and a 4-arylaminoquinazoline moiety with high potential affinity to an epidermal growth factor receptors (EGFR) and vascular endothelial growth factor receptors (VEGFR), suitable for photodynamic therapy (PDT), was synthesized starting from methylpheophorbide-a in seven steps. An increased accumulation of this compound in A431 cells with high level of EGFR expression, in comparison with CHO and HeLa cells with low EGFR expression was observed. The prepared conjugate exhibits dark and photoinduced cytotoxicity at micromolar concentrations with IC50dark/IC50light ratio of 11–18. In tumor-bearing mice, the conjugate preferentially accumulates in the tumor tissue.

© 2018 Aisanov et al. The high prevalence of COPD together with its high level of misdiagnosis and late diagnosis dictate the necessity for the development and implementation of clinical practice guidelines (CPGs) in order to improve the management of this disease. High-quality, evidence-based international CPGs need to be adapted to the particular situation of each country or region. A new version of the Russian Respiratory Society guidelines released at the end of 2016 was based on the proposal by Global Initiative for Obstructive Lung Disease but adapted to the characteristics of the Russian health system and included an algorithm of pharmacologic treatment of COPD. The proposed algorithm had to comply with the requirements of the Russian Ministry of Health to be included into the unified electronic rubricator, which required a balance between the level of information and the simplicity of the graphic design. This was achieved by: exclusion of the initial diagnostic process, grouping together the common pharmacologic and nonpharmacologic measures for all patients, and the decision not to use the letters A–D for simplicity and clarity. At all stages of the treatment algorithm, efficacy and safety have to be carefully assessed. Escalation and de-escalation is possible in the case of lack of or insufficient efficacy or safety issues. Bronchodilators should not be discontinued except in the case of significant side effects. At the same time, inhaled corticosteroid (ICS) withdrawal is not represented in the algorithm, because it was agreed that there is insufficient evidence to establish clear criteria for ICSs discontinuation. Finally, based on the Global Initiative for Obstructive Lung Disease statement, the proposed algorithm reflects and summarizes different approaches to the pharmacological treatment of COPD taking into account the reality of health care in the Russian Federation.

Physiology of breathing during sleep predisposes to the development or worsening of the respiratory disorders in patients with chronic obstructive pulmonary disease (COPD) even if waking respiratory function remains relatively normal. Physicians, who assess patient's state only during the day, in some cases can underestimate this problem. Respiratory abnormalities can provoke insomnia, which additionally affects patient's quality of life. Supplemental oxygen and pressure support ventilation improve blood gases during sleep, but in many cases, insomnia persists. In many cases, such patients need the treatment with hypnotics. Widely used drugs in insomnia are benzodiazepines. They are rather effective but can cause respiratory depression and respiratory failure in patients with COPD. Z-hypnotics are comparable to classical benzodiazepines but much more safe and rarely worsen respiratory parameters. Melatonin and melatonin receptor agonists, antihistamines, antidepressants and neuroleptics can be effective in some patients with insomnia, but insufficient data about their safety in case of respiratory pathology restrict the use of these drugs in patients with COPD. The orexin receptor antagonist suvorexant is a novel hypnotic with the potential benefits for patients with COPD because it strongly improves sleep but does not depress respiration and has a minimal negative impact on daytime cognitive function.

© 2018, Media Sphera Publishing Group. All rights reserved. Antidepressants are among the most commonly prescribed drugs due to their effectivenes in treating depression and anxiety disorders. One of the reasons for early discontinuation of taking antidepressants are side-effects. Agomelatine is a relatively novel antidepressant with high efficacy and good tolerance. Clinical effects of agomelatine include a reduction in symptoms of depression, anti-anxiety and hypnotic effects, as well as the rapid elimination of anhedonia, which determines high adherence to therapy, restoration of normal social functioning, and complete remission of disease.

AIM: Efficiency assessment of Granulotec (PD) endodontic sealer for root canal permanent obturation in patients with apical granuloma basing on clinical and radiological data. MATERIAL AND METHODS: Endodontic treatment of 35 teeth with apical granuloma was performed in 22 patients with root canal obturation by means of lateral condensation with Granulotec sealer. Bone remodeling in periapical area has been estimated in 1, 3, 6 and 8 months with PAI index. RESULTS: Endodontic post-operative pain has been observed in 5 (14.3%) cases of 35, pain duration varied 1 to 5 days, NSAIDs use hasn't been required. During observation period 2 teeth have been excluded from the test group (one case of periapical abscess with sinus tract and one case periapical abscess without sinus tract). In the end of observation period complete bone remodeling was observed in 30 cases, the periapical lesion size significant reduction was achieved in 2 cases, periapical lesion stabilization - in 1 case. The overall success rate was 91.4%. The mean PAI value decreased from 4.2±0.2 to 1.4±0.2. CONCLUSION: The Granulotec (PD) use for one visit chronic apical periodontitis treatment allows achieving positive results with low complications risk.

© 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología Case history of a small girl outlet with epilepsy, followed by scleroderma skin damage and uveitis, neurovasculitis with white matter foci in brain on the side of skin lesion in two months, immunologic disease activity. Resistance to conventional immunosuppressive therapy forced us to initiate the treatment with tocilizumab. It was well tolerated and led to significant improvement of brain, ocular and skin manifestations.

AIM: To analyze proceedings of the I-X Conferences 'Modern problems of somnology'. MATERIAL AND METHODS: The authors have analyzed 888 abstracts from the abstract books of the conferences held from 1998 to 2016 in Moscow and Saint-Petersburg. The territorial, sectoral and scientific indicators of the activity of participants as well as longitudinal research trends were analyzed. Mathematical and statistical data analysis was carried out using the methods of descriptive statistics (95% confidence intervals) and χ2 tests. RESULTS: On average, 300 researchers from 6 countries and 14 regions of Russia participated in each conference, most from higher education (19), research (16) and medical (12) institutions. The highest number of publications were related to clinical somnology and sleep medicine (50% to different neurological conditions), the numeral material was included in 83% and statistical analysis was performed in 32.5%. A trend towards more active participation of research and medical institutions from all the country and involvement of new regions was observed. The interest to the clinical subjects, including treatment choices in sleep disorders as well as organizing aspects of sleep medicine, has been increasing. The number of studies on different aspects of sleep apnea has increased significantly as well. CONCLUSION: The features of scientific and clinical activity in the field of somnology presented in the materials of conferences are stable in terms of the institutional and territorial representation. It complies to international trends of research and clinical development. This allows better planning of the structure and main issues of the further conferences.

PURPOSE: To evaluate various methods of stripping Descemet's membrane of a donor corneoscleral flap for Descemet's membrane endothelial keratoplasty (DMEK). MATERIAL AND METHODS: The study included 60 corneoscleral flaps (mean donor age was 62.9 years) from the eye bank of Research Institute of Eye Diseases, which were not suitable for clinical use due to positive serological results. Four alternative methods of donor material dissection in preparation for DMEK were compared: SCUBA (group A), our newly suggested method utilizing intracapsular ring (group B), 'liquid bubble' (group C), 'big bubble' (group D). Parameters under evaluation were mean transplant preparation time, density of endothelial cells before and after dissection, presence of complications during detachment of Descemet's membrane. RESULTS: Mean detachment time in group A was 8.5 min, in group B - 7 min, in group C - 8 min, and in group D - 5 min. Loss of endothelial cells as compared with baseline was in average 10.5% in group A, 9.3% in group B, 10.7% in group C, and 10.3% in group D. Group A had two cases with complications occurring during separation of Descemet's membrane, group B had one such case, group C - 2 cases, and group D - 3 cases. Histologic examination confirmed absence of stromal fibers on the detached Descemet's membrane in groups A, B and C. CONCLUSION: Among the described methods of preparing donor material for DMEK surgery, all except 'big bubble' proved equal in terms of resulting transplant quality. The 'big bubble' dissection technique requires more time to complete, while the resulting transplant has stromal fibers. Our newly suggested method of Descemet's membrane stripping that utilizes intracapsular ring proved safe and effective alternative for preparing donor material for DMEK.