Репозиторий Университета

Recently, zinc and its alloys have been proposed as promising candidates for biodegradable metals (BMs), owning to their preferable corrosion behavior and acceptable biocompatibility in cardiovascular, bone and gastrointestinal environments, together with Mg-based and Fe-based BMs. However, there is the desire for surface treatment for Zn-based BMs to better control their biodegradation behavior. Firstly, the implantation of some Zn-based BMs in cardiovascular environment exhibited intimal activation with mild inflammation. Secondly, for orthopedic applications, the biodegradation rates of Zn-based BMs are relatively slow, resulting in a long-term retention after fulfilling their mission. Meanwhile, excessive Zn2+ release during degradation will cause in vitro cytotoxicity and in vivo delayed osseointegration. In this review, we firstly summarized the current surface modification methods of Zn-based alloys for the industrial applications. Then we comprehensively summarized the recent progress of biomedical bulk Zn-based BMs as well as the corresponding surface modification strategies. Last but not least, the future perspectives towards the design of surface bio-functionalized coatings on Zn-based BMs for orthopedic and cardiovascular applications were also briefly proposed.

Recently, zinc and its alloys have been proposed as promising candidates for biodegradable metals (BMs), owning to their preferable corrosion behavior and acceptable biocompatibility in cardiovascular, bone and gastrointestinal environments, together with Mg-based and Fe-based BMs. However, there is the desire for surface treatment for Zn-based BMs to better control their biodegradation behavior. Firstly, the implantation of some Zn-based BMs in cardiovascular environment exhibited intimal activation with mild inflammation. Secondly, for orthopedic applications, the biodegradation rates of Zn-based BMs are relatively slow, resulting in a long-term retention after fulfilling their mission. Meanwhile, excessive Zn2+ release during degradation will cause in vitro cytotoxicity and in vivo delayed osseointegration. In this review, we firstly summarized the current surface modification methods of Zn-based alloys for the industrial applications. Then we comprehensively summarized the recent progress of biomedical bulk Zn-based BMs as well as the corresponding surface modification strategies. Last but not least, the future perspectives towards the design of surface bio-functionalized coatings on Zn-based BMs for orthopedic and cardiovascular applications were also briefly proposed.

© 2021, The Author(s). Background: An accumulating body of literature indicates that magnesium deficiency is associated with a number of hormone-related conditions (HRC) in women, and epidemiological studies are needed to assess its prevalence and risk factors. Here, we present a secondary analysis of data pooled from four large observational studies that assessed magnesium deficiency among pregnant women and women with HRC across the Russian Federation. Methods: The main objective of this analysis was to estimate the prevalence of magnesium deficiency in this population and to describe risk factors and comorbidities associated with low serum magnesium. Univariate logistic regression analysis was performed to identify the risk factors and comorbid conditions associated with an increased risk of low serum magnesium level. Results: A total of 983 pregnant women and 9444 women with HRC were eligible for analysis. Prevalence of hypomagnesemia (magnesium serum level cut-off < 0.66 mmol/L/< 0.8 mmol/L) was 34.0%/78.9% in pregnant women and 21.4%/54.8% in women with HRC. The highest prevalence of magnesium deficiency was observed for osteoporosis and climacteric syndrome. Risk factors included diastolic blood pressure, previous pregnancy complications, infections and edema for pregnant women, and age, body mass index, and various comorbidities for women with HRC. Conclusions: These results confirm the high prevalence of hypomagnesemia in pregnant women and women with HRC and underline the importance of routine screening, since risk factors are mostly non-specific.

© 2021, The Author(s). Background: An accumulating body of literature indicates that magnesium deficiency is associated with a number of hormone-related conditions (HRC) in women, and epidemiological studies are needed to assess its prevalence and risk factors. Here, we present a secondary analysis of data pooled from four large observational studies that assessed magnesium deficiency among pregnant women and women with HRC across the Russian Federation. Methods: The main objective of this analysis was to estimate the prevalence of magnesium deficiency in this population and to describe risk factors and comorbidities associated with low serum magnesium. Univariate logistic regression analysis was performed to identify the risk factors and comorbid conditions associated with an increased risk of low serum magnesium level. Results: A total of 983 pregnant women and 9444 women with HRC were eligible for analysis. Prevalence of hypomagnesemia (magnesium serum level cut-off < 0.66 mmol/L/< 0.8 mmol/L) was 34.0%/78.9% in pregnant women and 21.4%/54.8% in women with HRC. The highest prevalence of magnesium deficiency was observed for osteoporosis and climacteric syndrome. Risk factors included diastolic blood pressure, previous pregnancy complications, infections and edema for pregnant women, and age, body mass index, and various comorbidities for women with HRC. Conclusions: These results confirm the high prevalence of hypomagnesemia in pregnant women and women with HRC and underline the importance of routine screening, since risk factors are mostly non-specific.

Over recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner. Firstly, MSCs were successfully isolated from human bone marrow (BM), but in the next steps, they were also extracted from other sources, mostly from the umbilical cord (UC) and adipose tissue (AT). The International Society for Cellular Therapy (ISCT) has suggested minimum criteria to identify and characterize MSCs as follows: plastic adherence, surface expression of CD73, D90, CD105 in the lack of expression of CD14, CD34, CD45, and human leucocyte antigen-DR (HLA-DR), and also the capability to differentiate to multiple cell types including adipocyte, chondrocyte, or osteoblast in vitro depends on culture conditions. However, these distinct properties, including self-renewability, multipotency, and easy accessibility are just one side of the coin; another side is their huge secretome which is comprised of hundreds of mediators, cytokines, and signaling molecules and can effectively modulate the inflammatory responses and control the infiltration process that finally leads to a regulated tissue repair/healing or regeneration process. MSC-mediated immunomodulation is a direct result of a harmonic synergy of MSC-released signaling molecules (i.e., mediators, cytokines, and chemokines), the reaction of immune cells and other target cells to those molecules, and also feedback in the MSC-molecule-target cell axis. These features make MSCs a respectable and eligible therapeutic candidate to be evaluated in immune-mediated disorders, such as graft versus host diseases (GVHD), multiple sclerosis (MS), Crohn’s disease (CD), and osteoarthritis (OA), and even in immune-dysregulating infectious diseases such as the novel coronavirus disease 2019 (COVID-19). This paper discussed the therapeutic applications of MSC secretome and its biomedical aspects related to immune-mediated conditions. Sources for MSC extraction, their migration and homing properties, therapeutic molecules released by MSCs, and the pathways and molecular mechanisms possibly involved in the exceptional immunoregulatory competence of MSCs were discussed. Besides, the novel discoveries and recent findings on immunomodulatory plasticity of MSCs, clinical applications, and the methods required for their use as an effective therapeutic option in patients with immune-mediated/immune-dysregulating diseases were highlighted.

Purpose: To assess the clinical and radiographic success rate of microsurgical endodontic treatment of upper molar teeth in relationship with the maxillary sinus, with 12 months follow-up. Methods: Patients treated with microsurgical endodontic treatment of upper molar teeth in the period between 2017 and 2019 were recruited from two dental clinics according to specific selection criteria. The outcomes were determined based on clinical and radiographic results taken three, six and 12 months post-operatively, compared with those taken immediately before and after surgery. Clinical and radiographic outcomes were recorded. The distance between the most apical part of the root and of the lesion to the maxillary sinus was measured on CBCT images before the surgery. Patient-related outcomes were recorded. Results: Out of 35 patients evaluated, 21 were selected according with the selection criteria for a total of 27 roots and 29 canals treated. After 12 months, 18 patients showed a complete healing whereas three demonstrated incomplete healing. Consequently, the success rate in this study was 85.7% after one year. In 28.5% (6 patients) there was a perforation of the Schneiderian membrane that didn’t seem to affect the outcome. All patients kept the molar one year later. The pain level decreased significantly over the time during the first week after surgery. Conclusion: Microsurgical Endodontic treatment of the upper molar teeth should be considered a valid and predictable treatment option even in case of Schneiderian membrane perforation. Future clinical studies with a larger sample size are needed to compare the results obtained.

Purpose: To assess the clinical and radiographic success rate of microsurgical endodontic treatment of upper molar teeth in relationship with the maxillary sinus, with 12 months follow-up. Methods: Patients treated with microsurgical endodontic treatment of upper molar teeth in the period between 2017 and 2019 were recruited from two dental clinics according to specific selection criteria. The outcomes were determined based on clinical and radiographic results taken three, six and 12 months post-operatively, compared with those taken immediately before and after surgery. Clinical and radiographic outcomes were recorded. The distance between the most apical part of the root and of the lesion to the maxillary sinus was measured on CBCT images before the surgery. Patient-related outcomes were recorded. Results: Out of 35 patients evaluated, 21 were selected according with the selection criteria for a total of 27 roots and 29 canals treated. After 12 months, 18 patients showed a complete healing whereas three demonstrated incomplete healing. Consequently, the success rate in this study was 85.7% after one year. In 28.5% (6 patients) there was a perforation of the Schneiderian membrane that didn’t seem to affect the outcome. All patients kept the molar one year later. The pain level decreased significantly over the time during the first week after surgery. Conclusion: Microsurgical Endodontic treatment of the upper molar teeth should be considered a valid and predictable treatment option even in case of Schneiderian membrane perforation. Future clinical studies with a larger sample size are needed to compare the results obtained.

© 2021 Elsevier Ltd This review examines investigations into the functionalization of polysaccharides by substituents containing multiple (C[dbnd]C) bonds and thiol (SH) groups that are prone to (co)polymerization in the presence of thermal, redox and photoinitiators or Michael addition reactions. A comparative analysis of the approaches to grafting the mentioned substituents onto the polysaccharide macromolecules was conducted. The use of the modified polysaccharides for the design of the 3D structures, including for the development of the pore bearing matrixes of cells or scaffolds utilized in regenerative medicine was examined. These modified polymers were also examined toward the design of excipient matrixes in pharmacological compositions, including with controllable release of active pharmaceuticals, as wel as of antibacterial and antifungal agents and others. In addition, a few examples of the use of modified derivatives in other areas are given.

© 2021 Elsevier Inc. Methylmercury (MeHg) is a persistent environmental neurotoxicant that may cause adverse neurodevelopmental effects. Previous studies showed that developmental MeHg exposure caused damage to brain functions that were unmasked after a silent period of years or decades. However, the underlying mechanisms of the latent neurotoxicity associated with MeHg exposure from earlier developmental stages have yet to be fully understood. Herein, we established a Caenorhabditis elegans (C. elegans) model of developmental MeHg latent toxicity. Synchronized L1 stage worms were exposed to MeHg (0, 0.05, 0.5 and 5 μM) for 48 h. Swimming moving speeds at adulthood were analyzed in worms exposed to MeHg exposure at early larvae stages. Worms developmentally exposed to MeHg had a significant decline in swimming moving speed on day 10 adult stage, but not on day 1 or 5 adult stage, even though the mercury level in the worms exposed to 0.05 or 0.5 μM MeHg were below the quantification limit on day 10 adult. Day 10 adult worms treated with MeHg showed a significant decrease in bending angle and bending frequency during swimming. Furthermore, their reduced moving speeds tended to increase during the 300-s swimming experiment. Dopamine signaling is known to be involved in the regulation of worms' moving speed. Accordingly, the moving speed of worms with cat-2 (mammalian tyrosine hydroxylase homolog) mutation or dat-1 deletion were assayed on day 10 adult. The cat-2 mutant worms did not show a decline in moving speeds, body bends or bending angles during swimming on day 10 adult stage. Analyses of moving speeds of worms with dat-1 deletion showed that the moving speeds were further reduced after MeHg exposure. However, the effects of MeHg and dat-1 deletion were not synergistic, as the interaction between these parameters did not attain statistical significance. Altogether, our results suggest that developmental MeHg exposure reduced moving speed, and this latent toxicity was less pronounced in the context of deficient production of dopamine synthesis. Tyrosine hydroxylase plays an important role in regulating dopamine-mediated modulation of neurobehavioral functions. These findings uncovered a pivotal role of dopamine and its metabolism in the latent neurotoxic effects of MeHg.

© 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 The Authors. International Journal of Cancer published by John Wiley  &  Sons Ltd on behalf of Union for International Cancer Control. Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3′-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein μ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRβ) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.

© 2020 The Authors. International Journal of Cancer published by John Wiley  &  Sons Ltd on behalf of Union for International Cancer Control. Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3′-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein μ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRβ) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.

© 2020 Elsevier B.V. For thermoelements operating on the Peltier and Seebeck effects, including multisection ones used at temperatures up to 900 K, the physicochemical principles of creating effective thin-film multilayer contact systems obtained by magnetron ion-plasma sputtering have been developed. The formation of contact systems was carried out on thermoelectric materials based on: Bi2Te3; Sb2Te3; PbTe; GeTe with the increased thermoelectric figure of merit. A structure of contact systems consisting of contact layers providing ohmic contact, adhesion, barrier and interconnection properties of contact systems is proposed and justified. The selection criteria for materials of contact layers are substantiated. For multisection thermoelements operating on the Seebeck effect at temperatures above 500 K, the necessity of introducing diffusion-barrier layers into the structure of contact systems providing reliability and invariability of the properties of contact systems is substantiated. Based on the physicochemical analysis, the thermodynamic and kinetic factors of the stability and degradation of diffusion-barrier layers are determined. The influence of methods for preparing the surface of thermoelectric materials on the adhesion, contact resistance, and thermal stability of contact systems is established. Using Auger electron spectroscopy, the analysis of the causes of thermal stability and degradation of contact systems was carried out. The deposition modes were determined. The effective contact systems were obtained and investigated. The respective systems are based on: Ni; Mo/Ni and Ni/(Ta–W–N)/Ni having the adhesive strength of more than 12 MPa; the contact resistance not exceeding 10−9 Ω m2 and thermal stability at temperatures up to 900 K.

© 2020 Elsevier B.V. For thermoelements operating on the Peltier and Seebeck effects, including multisection ones used at temperatures up to 900 K, the physicochemical principles of creating effective thin-film multilayer contact systems obtained by magnetron ion-plasma sputtering have been developed. The formation of contact systems was carried out on thermoelectric materials based on: Bi2Te3; Sb2Te3; PbTe; GeTe with the increased thermoelectric figure of merit. A structure of contact systems consisting of contact layers providing ohmic contact, adhesion, barrier and interconnection properties of contact systems is proposed and justified. The selection criteria for materials of contact layers are substantiated. For multisection thermoelements operating on the Seebeck effect at temperatures above 500 K, the necessity of introducing diffusion-barrier layers into the structure of contact systems providing reliability and invariability of the properties of contact systems is substantiated. Based on the physicochemical analysis, the thermodynamic and kinetic factors of the stability and degradation of diffusion-barrier layers are determined. The influence of methods for preparing the surface of thermoelectric materials on the adhesion, contact resistance, and thermal stability of contact systems is established. Using Auger electron spectroscopy, the analysis of the causes of thermal stability and degradation of contact systems was carried out. The deposition modes were determined. The effective contact systems were obtained and investigated. The respective systems are based on: Ni; Mo/Ni and Ni/(Ta–W–N)/Ni having the adhesive strength of more than 12 MPa; the contact resistance not exceeding 10−9 Ω m2 and thermal stability at temperatures up to 900 K.

Production of reactive oxygen species (ROS) in the mitochondria plays multiple roles in physiology, and excessive production of ROS leads to the development of various pathologies. ROS in the mitochondria are generated by various enzymes, mainly in the electron transporvt chain, and it is important to identify not only the trigger but also the source of free radical production. It is important to measure mitochondrial ROS in live, intact cells, because activation of ROS production could be initiated by changes in extramitochondrial processes which could be overseen when using isolated mitochondria. Here we describe the approaches, which allow to measure production of ROS in the matrix of mitochondria in live cells. We also demonstrate how to measure kinetic changes in lipid peroxidation in mitochondria of live cells. These methods could be used for understanding the mechanisms of pathology in a variety of disease models and also for testing neuro- or cardioprotective chemicals.

Production of reactive oxygen species (ROS) in the mitochondria plays multiple roles in physiology, and excessive production of ROS leads to the development of various pathologies. ROS in the mitochondria are generated by various enzymes, mainly in the electron transporvt chain, and it is important to identify not only the trigger but also the source of free radical production. It is important to measure mitochondrial ROS in live, intact cells, because activation of ROS production could be initiated by changes in extramitochondrial processes which could be overseen when using isolated mitochondria. Here we describe the approaches, which allow to measure production of ROS in the matrix of mitochondria in live cells. We also demonstrate how to measure kinetic changes in lipid peroxidation in mitochondria of live cells. These methods could be used for understanding the mechanisms of pathology in a variety of disease models and also for testing neuro- or cardioprotective chemicals.

© 2020 The Authors Hydroperoxy-eicosatetraenoyl-phosphatidylethanolamine (HpETE-PE) is a ferroptotic cell death signal. HpETE-PE is produced by the 15-Lipoxygenase (15LOX)/Phosphatidylethanolamine Binding Protein-1 (PEBP1) complex or via an Fe-catalyzed non-enzymatic radical reaction. Ferrostatin-1 (Fer-1), a common ferroptosis inhibitor, is a lipophilic radical scavenger but a poor 15LOX inhibitor arguing against 15LOX having a role in ferroptosis. In the current work, we demonstrate that Fer-1 does not affect 15LOX alone, however, it effectively inhibits HpETE-PE production by the 15LOX/PEBP1 complex. Computational molecular modeling shows that Fer-1 binds to the 15LOX/PEBP1 complex at three sites and could disrupt the catalytically required allosteric motions of the 15LOX/PEBP1 complex. Using nine ferroptosis cell/tissue models, we show that HpETE-PE is produced by the 15LOX/PEBP1 complex and resolve the long-existing Fer-1 anti-ferroptotic paradox.

© 2020 The Authors Hydroperoxy-eicosatetraenoyl-phosphatidylethanolamine (HpETE-PE) is a ferroptotic cell death signal. HpETE-PE is produced by the 15-Lipoxygenase (15LOX)/Phosphatidylethanolamine Binding Protein-1 (PEBP1) complex or via an Fe-catalyzed non-enzymatic radical reaction. Ferrostatin-1 (Fer-1), a common ferroptosis inhibitor, is a lipophilic radical scavenger but a poor 15LOX inhibitor arguing against 15LOX having a role in ferroptosis. In the current work, we demonstrate that Fer-1 does not affect 15LOX alone, however, it effectively inhibits HpETE-PE production by the 15LOX/PEBP1 complex. Computational molecular modeling shows that Fer-1 binds to the 15LOX/PEBP1 complex at three sites and could disrupt the catalytically required allosteric motions of the 15LOX/PEBP1 complex. Using nine ferroptosis cell/tissue models, we show that HpETE-PE is produced by the 15LOX/PEBP1 complex and resolve the long-existing Fer-1 anti-ferroptotic paradox.

© 2020 The Authors Hydroperoxy-eicosatetraenoyl-phosphatidylethanolamine (HpETE-PE) is a ferroptotic cell death signal. HpETE-PE is produced by the 15-Lipoxygenase (15LOX)/Phosphatidylethanolamine Binding Protein-1 (PEBP1) complex or via an Fe-catalyzed non-enzymatic radical reaction. Ferrostatin-1 (Fer-1), a common ferroptosis inhibitor, is a lipophilic radical scavenger but a poor 15LOX inhibitor arguing against 15LOX having a role in ferroptosis. In the current work, we demonstrate that Fer-1 does not affect 15LOX alone, however, it effectively inhibits HpETE-PE production by the 15LOX/PEBP1 complex. Computational molecular modeling shows that Fer-1 binds to the 15LOX/PEBP1 complex at three sites and could disrupt the catalytically required allosteric motions of the 15LOX/PEBP1 complex. Using nine ferroptosis cell/tissue models, we show that HpETE-PE is produced by the 15LOX/PEBP1 complex and resolve the long-existing Fer-1 anti-ferroptotic paradox.