Репозиторий Университета

© 2020 Elsevier Ltd Manganese (Mn) is the twelfth most abundant element on the earth and an essential metal to human health. Mn is present at low concentrations in a variety of dietary sources, which provides adequate Mn content to sustain support various physiological processes in the human body. However, with the rise of Mn utility in a variety of industries, there is an increased risk of overexposure to this transition metal, which can have neurotoxic consequences. This risk includes occupational exposure of Mn to workers as well as overall increased Mn pollution affecting the general public. Here, we review exposure due to air pollution and inhalation in industrial settings; we also delve into the toxic effects of manganese on the brain such as oxidative stress, inflammatory response and transporter dysregulation. Additionally, we summarize current understandings underlying the mechanisms of Mn toxicity.

© 2020 Elsevier Ltd Manganese (Mn) is the twelfth most abundant element on the earth and an essential metal to human health. Mn is present at low concentrations in a variety of dietary sources, which provides adequate Mn content to sustain support various physiological processes in the human body. However, with the rise of Mn utility in a variety of industries, there is an increased risk of overexposure to this transition metal, which can have neurotoxic consequences. This risk includes occupational exposure of Mn to workers as well as overall increased Mn pollution affecting the general public. Here, we review exposure due to air pollution and inhalation in industrial settings; we also delve into the toxic effects of manganese on the brain such as oxidative stress, inflammatory response and transporter dysregulation. Additionally, we summarize current understandings underlying the mechanisms of Mn toxicity.

© 2020 Elsevier Ltd Manganese (Mn) is the twelfth most abundant element on the earth and an essential metal to human health. Mn is present at low concentrations in a variety of dietary sources, which provides adequate Mn content to sustain support various physiological processes in the human body. However, with the rise of Mn utility in a variety of industries, there is an increased risk of overexposure to this transition metal, which can have neurotoxic consequences. This risk includes occupational exposure of Mn to workers as well as overall increased Mn pollution affecting the general public. Here, we review exposure due to air pollution and inhalation in industrial settings; we also delve into the toxic effects of manganese on the brain such as oxidative stress, inflammatory response and transporter dysregulation. Additionally, we summarize current understandings underlying the mechanisms of Mn toxicity.

© 2019 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM) Microbial cells sense the presence of xenobiotics and, in response, upregulate genes involved in pleiotropic drug resistance (PDR). In yeast, PDR activation to a major extent relies on the transcription factor Pdr1. In addition, many xenobiotics induce oxidative stress, which may upregulate PDR independently of Pdr1 activity. Mitochondria are important sources of reactive oxygen species under stressful conditions. To evaluate the relevance of this redox pathway, we studied the activation of PDR in the yeast Candida glabrata, which we treated with a mitochondrially targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium and dodecyltriphenylphosphonium (C12TPP) as a control. We found that both compounds induced activation of PDR genes and decreased the intracellular concentration of the PDR transporter substrate Nile red. Interestingly, the deletion of PDR transporter gene CDR1 inhibited the decrease in Nile red accumulation induced by antioxidant plastoquinonyl-decyl-triphenylphosphonium but not that by C12TPP. Moreover, antioxidant alpha-tocopherol inhibited C12TPP-mediated activation of PDR in Δcdr1 but not in the wild-type strain. Furthermore, pre-incubation of yeast cells with low concentrations of hydrogen peroxide induced a decrease in the intracellular concentration of Nile red in Δcdr1 and Δpdr1 as well as in control cells. Deletion of PDR1 inhibited the C12TPP-induced activation of CDR1 but not that of FLR1, which is a redox-regulated PDR transporter gene. It appears that disruption of the PDR1/CDR1 regulatory circuit makes auxiliary PDR regulation mechanisms crucial. Our data suggest that redox regulation of PDR is dispensable in wild-type cells because of redundancy in the activation pathways, but is manifested upon deletion of CDR1.

© 2019 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM) Microbial cells sense the presence of xenobiotics and, in response, upregulate genes involved in pleiotropic drug resistance (PDR). In yeast, PDR activation to a major extent relies on the transcription factor Pdr1. In addition, many xenobiotics induce oxidative stress, which may upregulate PDR independently of Pdr1 activity. Mitochondria are important sources of reactive oxygen species under stressful conditions. To evaluate the relevance of this redox pathway, we studied the activation of PDR in the yeast Candida glabrata, which we treated with a mitochondrially targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium and dodecyltriphenylphosphonium (C12TPP) as a control. We found that both compounds induced activation of PDR genes and decreased the intracellular concentration of the PDR transporter substrate Nile red. Interestingly, the deletion of PDR transporter gene CDR1 inhibited the decrease in Nile red accumulation induced by antioxidant plastoquinonyl-decyl-triphenylphosphonium but not that by C12TPP. Moreover, antioxidant alpha-tocopherol inhibited C12TPP-mediated activation of PDR in Δcdr1 but not in the wild-type strain. Furthermore, pre-incubation of yeast cells with low concentrations of hydrogen peroxide induced a decrease in the intracellular concentration of Nile red in Δcdr1 and Δpdr1 as well as in control cells. Deletion of PDR1 inhibited the C12TPP-induced activation of CDR1 but not that of FLR1, which is a redox-regulated PDR transporter gene. It appears that disruption of the PDR1/CDR1 regulatory circuit makes auxiliary PDR regulation mechanisms crucial. Our data suggest that redox regulation of PDR is dispensable in wild-type cells because of redundancy in the activation pathways, but is manifested upon deletion of CDR1.

© 2019 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM) Microbial cells sense the presence of xenobiotics and, in response, upregulate genes involved in pleiotropic drug resistance (PDR). In yeast, PDR activation to a major extent relies on the transcription factor Pdr1. In addition, many xenobiotics induce oxidative stress, which may upregulate PDR independently of Pdr1 activity. Mitochondria are important sources of reactive oxygen species under stressful conditions. To evaluate the relevance of this redox pathway, we studied the activation of PDR in the yeast Candida glabrata, which we treated with a mitochondrially targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium and dodecyltriphenylphosphonium (C12TPP) as a control. We found that both compounds induced activation of PDR genes and decreased the intracellular concentration of the PDR transporter substrate Nile red. Interestingly, the deletion of PDR transporter gene CDR1 inhibited the decrease in Nile red accumulation induced by antioxidant plastoquinonyl-decyl-triphenylphosphonium but not that by C12TPP. Moreover, antioxidant alpha-tocopherol inhibited C12TPP-mediated activation of PDR in Δcdr1 but not in the wild-type strain. Furthermore, pre-incubation of yeast cells with low concentrations of hydrogen peroxide induced a decrease in the intracellular concentration of Nile red in Δcdr1 and Δpdr1 as well as in control cells. Deletion of PDR1 inhibited the C12TPP-induced activation of CDR1 but not that of FLR1, which is a redox-regulated PDR transporter gene. It appears that disruption of the PDR1/CDR1 regulatory circuit makes auxiliary PDR regulation mechanisms crucial. Our data suggest that redox regulation of PDR is dispensable in wild-type cells because of redundancy in the activation pathways, but is manifested upon deletion of CDR1.

© 2019 Aims: The high sugar and lipid content of the Western diet (WD) is associated with metabolic dysfunction, non-alcoholic steatohepatitis, and it is an established risk factor for neuropsychiatric disorders. Our previous studies reported negative effects of the WD on rodent emotionality, impulsivity, and sociability in adulthood. Here, we investigated the effect of the WD on motor coordination, novelty recognition, and affective behavior in mice as well as molecular and cellular endpoints in brain and peripheral tissues. Main methods: Female C57BL/6 J mice were fed the WD for three weeks and were investigated for glucose tolerance, insulin resistance, liver steatosis, and changes in motor coordination, object recognition, and despair behavior in the swim test. Lipids and liver injury markers, including aspartate-transaminase, alanine-transaminase and urea were measured in blood. Serotonin transporter (SERT) expression, the density of Iba1-positive cells and concentration of malondialdehyde were measured in brain. Key findings: WD-fed mice exhibited impaired glucose tolerance and insulin resistance, a loss of motor coordination, deficits in novel object exploration and recognition, increased helplessness, dyslipidemia, as well as signs of a non-alcoholic steatohepatitis (NASH)-like syndrome: liver steatosis and increased liver injury markers. Importantly, these changes were accompanied by decreased SERT expression, elevated numbers of microglia cells and malondialdehyde levels in, and restricted to, the prefrontal cortex. Significance: The WD induces a spectrum of behaviors that are more reminiscent of ADHD and ASD than previously recognized and suggests that, in addition to the impairment of impulsivity and sociability, the consumption of a WD might be expected to exacerbate motor dysfunction that is also known to be associated with adult ADHD and ASD.

© 2019 Aims: The high sugar and lipid content of the Western diet (WD) is associated with metabolic dysfunction, non-alcoholic steatohepatitis, and it is an established risk factor for neuropsychiatric disorders. Our previous studies reported negative effects of the WD on rodent emotionality, impulsivity, and sociability in adulthood. Here, we investigated the effect of the WD on motor coordination, novelty recognition, and affective behavior in mice as well as molecular and cellular endpoints in brain and peripheral tissues. Main methods: Female C57BL/6 J mice were fed the WD for three weeks and were investigated for glucose tolerance, insulin resistance, liver steatosis, and changes in motor coordination, object recognition, and despair behavior in the swim test. Lipids and liver injury markers, including aspartate-transaminase, alanine-transaminase and urea were measured in blood. Serotonin transporter (SERT) expression, the density of Iba1-positive cells and concentration of malondialdehyde were measured in brain. Key findings: WD-fed mice exhibited impaired glucose tolerance and insulin resistance, a loss of motor coordination, deficits in novel object exploration and recognition, increased helplessness, dyslipidemia, as well as signs of a non-alcoholic steatohepatitis (NASH)-like syndrome: liver steatosis and increased liver injury markers. Importantly, these changes were accompanied by decreased SERT expression, elevated numbers of microglia cells and malondialdehyde levels in, and restricted to, the prefrontal cortex. Significance: The WD induces a spectrum of behaviors that are more reminiscent of ADHD and ASD than previously recognized and suggests that, in addition to the impairment of impulsivity and sociability, the consumption of a WD might be expected to exacerbate motor dysfunction that is also known to be associated with adult ADHD and ASD.

© 2019 Objective: According to one of the hypotheses, somatoform disorders (SD) are related to disturbed perception of bodily signals. We suspect that the disturbances and abnormalities of multisensory integration dynamics may be an additional SD mechanism. The objective of the research was to investigate multisensory bodily illusion dynamics in SD patients. Methods: A clinical group of SD patients (n = 16) and a control group (n = 17) participated in experiments aimed at eliciting a visual-tactile rubber hand illusion (RHI) and a visual-kinesthetic virtual hand illusion (VHI). Results: For both illusions studied, the illusion dynamics in SD patients differed from those of healthy subjects. The visual-tactile illusion on the subjective level appeared to be less strong in SD patients, and no proprioceptive drift (PD) was detected. The subjective dynamics of the visual-kinesthetic illusion in patients were similar to those of the control group, but the PD dynamics were different: after the termination of stimuli from the artificial limb, the proprioceptive system did not return to its initial state; on the contrary, PD continued to increase. Conclusion: In comparison with the norm, patients with somatoform disorders display differences in multisensory mechanisms underlying the development of body perception. The results suggest that the disturbance of visual-tactile integration of the stimuli represents one of the mechanisms of body perception distortion in somatoform disorders. It may be assumed that one of the reasons for persistent symptom perception in SD patients is the rigidity of multisensory stimuli perception, at least in the visual-motor domain.

© 2018 Elsevier Ltd An excessive inflammatory response is frequently associated with cellular dysfunction and cell death. The latter may cause single and multiple organ failure. The most susceptible organs are liver, lung, kidney, heart and intestine. This review will focus on the liver as a target organ for an excessive inflammatory response. It is commonly accepted that organ failure is caused by the action of inflammatory cytokines released in excess during the inflammatory response. It has been suggested that inflammation mediated liver failure is not due to an increased death rate of parenchymal cells, but due to an intracellular metabolic disorder. This metabolic disorder is associated with mitochondrial and endoplasmic reticulum (ER) dysfunction during the acute phase response elicited by systemic inflammation. An overproduction of acute phase proteins in the liver as well as elevated reactive oxygen species (ROS) generation induce ER stress, triggering the unfolded protein response (UPR), which may initiate or aggravate inflammation. It is known that certain inflammatory mediators, such as the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α induce ER stress. These findings suggest that ER stress and the subsequent UPR on the one hand, and the inflammatory response on the other create a kind of feed forward loop, which can be either beneficial (e.g., elimination of the pathogen and restoration of tissue homeostasis) or deleterious (e.g., excessive cell dysfunction and cell death). This review aims to unfurl the different pathways contributing to this loop and to highlight the relevance of UPR signaling (IRE1α, ATF6, and PERK) and mediators of the inflammatory response (NF-κB, STAT3, IL-1β, IL-6, TLR) which have a particular role as pathophysiological triggers in the liver.

© 2019 Elsevier Ltd Hexavalent chromium raises high concern because of its wide industrial applications and reported toxicity. Long-term (135 days) oral exposure of Wistar rats to chromium in the form of K2Cr2O7 (exposed group~20 mg/kg/day) led to a decrease in thymus mass and thymocytes' number and caused structural and functional changes in the lymph nodes and spleen, namely lymphoreticular hyperplasia and plasmocytic macrophage transformation. Programmed cell death was increased in both thymocytes and splenocytes and decreased in lymphocytes in the T-zones of spleen and lymph nodes. Moreover, Cr (VI) administration decreased myeloid cells' and neutrophils' number, while it increased lymphoid and erythroid cells' number in bone marrow. Cr (VI) immune system effects seem to be related to oxidative stress induction, as depicted by the increased levels of diene conjugates and malondialdehyde in the spleen and liver and by the decreased activity of catalase and superoxide dismutase in rats’ erythrocytes. In addition, exposure to Cr (VI) decreased copper, nickel and iron concentrations in blood and liver, while Cr levels in blood, spleen and liver were increased, as expected. The observed changes in the series of immunological parameters studied contribute to the development of new approaches for the prevention of low level Cr exposure toxicity.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. The heme oxygenase (HO) system is essential for heme and iron homeostasis and necessary for adaptation to cell stress. HO degrades heme to biliverdin (BV), carbon monoxide (CO) and ferrous iron. Although mostly beneficial, the HO reaction can also produce deleterious effects, predominantly attributed to excessive product formation. Underrated so far is, however, that HO may exert effects additionally via modulation of the cellular heme levels. Heme, besides being an often-quoted generator of oxidative stress, plays also an important role as a signaling molecule. Heme controls the anti-oxidative defense, circadian rhythms, activity of ion channels, glucose utilization, erythropoiesis, and macrophage function. This broad spectrum of effects depends on its interaction with proteins ranging from transcription factors to enzymes. In degrading heme, HO has the potential to exert effects also via modulation of heme-mediated pathways. In this review, we will discuss the multitude of pathways regulated by heme to enlarge the view on HO and its role in cell physiology. We will further highlight the contribution of HO to pathophysiology, which results from a dysregulated balance between heme and the degradation products formed by HO.

© 2019 Elsevier Ltd Sandpiles are ubiquitous in nature and engineering applications but still not fully understood due to the complexity of structures and materials properties. This work presents a systematic study on the piles of Platonic solids using the discrete element method (DEM), mainly focusing on the effect of particle shape on the repose angles and bottom pressure distributions of the piles. Five Platonic particles (tetrahedron, cube, octahedron, dodecahedron, and icosahedron) were discharged to form wedge-shaped piles. It was found that the repose angle did not increase with the decrease of particle sphericity. The pile formed by the cubes had the maximum repose angle and its bottom stress dip phenomena were more significant in terms of dip width and depth than that of other particle piles. The pressure distributions at different heights of the piles were quite similar to those of the whole piles, while the shear stress distributions near the boundaries exhibited different characteristics for the cube piles. The analyses of packing structures in terms of coordination number, radial distribution function, as well as contact types inside the piles were discussed to understand the change of pressure dips. The influence of static friction on the repose angle was more significant and it enhanced the stress dip phenomenon.

© 2019 Elsevier Ltd The negative societal impacts associated with the increasing prevalence of violence and aggression is increasing, and, with this rise, is the need to understand the molecular and cellular changes that underpin ultrasound-induced aggressive behavior. In mice, stress-induced aggression is known to alter AMPA receptor subunit expression, plasticity markers, and oxidative stress within the brain. Here, we induced aggression in BALB/c mice using chronic ultrasound exposure and examined the impact of the psychoactive anti-oxidant compounds thiamine (vitamin B1), and its derivative benfotiamine, on AMPA receptor subunit expression, established plasticity markers, and oxidative stress. The administration of thiamine or benfotiamine (200 mg/kg/day) in drinking water decreased aggressive behavior following 3-weeks of ultrasound exposure and benfotiamine, reduced floating behavior in the swim test. The vehicle-treated ultrasound-exposed mice exhibited increases in protein carbonyl and total glutathione, altered AMPA receptor subunits expression, and decreased expression of plasticity markers. These ultrasound-induced effects were ameliorated by thiamine and benfotiamine treatment; in particular both antioxidants were able to reverse ultrasound-induced changes in GluA1 and GluA2 subunit expression, and, within the prefrontal cortex, significantly reversed the changes in protein carbonyl and polysialylated form of neural cell adhesion molecule (PSA-NCAM) expression levels. Benfotiamine was usually more efficacious than thiamine. Thus, the thiamine compounds were able to counteract ultrasound-induced aggression, which was accompanied by the normalization of markers that have been showed to be associated with ultrasound-induced aggression. These commonly used, orally-active compounds may have considerable potential for use in the control of aggression within the community. This article is part of the Special Issue entitled ‘Current status of the neurobiology of aggression and impulsivity’.

In recent years scientists actively study the influence of domestic violence on psychological status and occurrence of mental disorders in women and girls. Psychological, physical, sexual and other types of violence are distinguished, the consequences of which are studied in many countries under the auspices of WHO. In international studies the serious consequences of domestic violence for women are investigated. It was found out that women develop stressful disorders, depression and dependence on psychoactive substances. Negative influence of domestic violence at girls is expressed in formation of behavioral disorders, violations of sexual development, suicidal trends. At analysis of consequences of domestic violence by WHO was developed the concept of "cycle of violence" and cruelty inside family when in process of long influence of psychological traumatic factors at women and girls aggressive actions occurred so that victim and aggressor changed places. The objective of the study was to analyze the current state of the problem on the basis of the literature data, to study the data on the consequences of domestic violence and cruelty against women and girls, to identify gender-specific violations.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. We studied the effect of LPS on the state of stress-marker organs in rats at various periods after a single exposure to long-term stress on the model of 24-h immobilization. The animals were intraperitoneally injected with LPS in a dose of 100 μg/kg immediately after the negative emotiogenic exposure. Changes in physiological parameters were evaluated 3 h, 1 day, and 8 days after immune stimulation. Acute stress was accompanied by a decrease in the weight of the thymus during all stages of the post-stress period. An increase in the relative weight of theadrenal glands in animals under these conditions was observed only on day 8 after restraint stress. The induction of immune reactions due to systemic treatment with LPS was shown to prevent involution of the spleen in the late stage after a single exposure to long-term stress (day 8). Hypertrophy of the adrenal glands, which serves as one of the typical reactions of mammals to negative emotiogenic factors, was not revealed during the post-stress period after antigenic stimulation. These data hold much promise for the development of new approaches to the use of immunoactive substances to prevent or reduce the severity of physiological changes after emotiogenic loads.

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. The superficial femoral artery (SFA) is a typical atherosclerosis-prone site. We aimed to explore whether the tortuosity of the SFA associates with the occurrence of atherosclerosis and investigate how vascular tortuosity influences the characteristics of blood flow. Ten patients diagnosed with atherosclerotic disease in their SFAs while free of systemic atherosclerosis risk factors were enrolled together with ten atherosclerosis-free patients. The tortuosity of each SFA was quantitatively evaluated by calculating the averaged curvature (AC), maximum curvature (MC) and fraction of high curvature (FC) based on the geometrical model reconstructed from medical images. Hemodynamic studies were performed using both geometrically simplified and anatomically realistic models of the SFA to systematically address the hemodynamic effects of vascular tortuosity. Morphological analyses revealed that all curvature indices of the SFA were significantly larger in patients with atherosclerosis than in atherosclerosis-free patients (AC [mm−1]: 0.034 ± 0.016 vs. 0.018 ± 0.006; MC [mm−1]: 0.055 ± 0.023 vs. 0.034 ± 0.008; FC [%]: 22.77 ± 10.22 vs. 11.39 ± 6.82; p < 0.001). Simulations of blood flows in the geometrically simplified SFAs showed that increasing vascular curvature caused a progressive increase in the area ratios of low wall shear stress (LWSA) and high oscillatory shear index (HOSA). Hemodynamic studies on the anatomically realistic SFAs further demonstrated that high-curvature SFAs (n = 10) had overall larger LWSA and HOSA compared with low-curvature SFAs (n = 10) (LWSA [%]: 4.13 ± 1.91 vs. 1.79 ± 1.13, p = 0.009; HOSA [%]: 4.95 ± 1.92 vs. 2.37 ± 1.51, p = 0.007). These results suggest that increased vascular tortuosity augments the severity and distribution of atherosclerosis-promoting flow disturbances in the SFA and may be an independent risk factor for atherosclerosis.

© 2018 by the authors. Objectives: Resin-modified glass ionomer cements (RMGIC) are considered excellent restorative materials with unique therapeutic and anti-cariogenic activity. However, concerns exist regarding the use of polyacrylic acid as a dentine conditioner as it may influence the bonding performance of RMGIC. The aim of this study was to evaluate the effect of different protocols for cycling mechanical stress on the bond durability and interfacial ultramorphology of a modern RMGIC applied to dentine pre-treated with/without polyacrylic acid conditioner (PAA). Methods: The RMGIC was applied onto human dentine specimens prepared with silicon-carbide (SiC) abrasive paper with or without the use of a PAA conditioner. The specimens were immersed in deionised water for 24 h then divided in 3 groups. The first group was cut into matchsticks (crosssectional area of 0.9 mm2) and tested immediately for microtensile bond strength (MTBS). The second was first subjected to load cycling (250,000 cycles; 3 Hz; 70 N) and then cut into matchsticks and tested for MTBS. The third group was subjected to load cycling (250,000 cycles; 3 Hz; 70 N), cut into matchsticks, and then immersed for 8 months storage in artificial saliva (AS); these were finally tested for MTBS. The results were analysed statistically using two-way ANOVA and the Student- Newman-Keuls test (α = 0.05). Fractographic analysis was performed using FE-SEM, while further RMCGIC-bonded dentine specimens were aged as previously described and used for interfacial ultramorphology characterisation (dye nanoleakage) using confocal microscopy. Results: The RMGIC applied onto dentine that received no pre-treatment (10% PAA gel) showed no significant reduction in MTBS after load cycling followed by 8 months of storage in AS (p > 0.05). The RMGIC- dentine interface created in PAA-conditioned SiC-abraded dentine specimens showed no sign of degradation, but with porosities within the bonding interface both after load cycling and after 8 months of storage in AS. Conversely, the RMGIC-dentine interface of the specimens with no PAA pre-treatment showed no sign of porosity within the interface after any of the aging protocols, although some bonded-dentine interfaces presented cohesive cracks within the cement after prolonged AS storage. However, the specimens of this group showed no significant reduction in bond strength (p < 0.05) after 8 months of storage in AS or load cycling (p > 0.05). After prolonged AS storage, the bond strength value attained in RMGIC-dentine specimens created in PAA pretreated dentine were significantly higher than those observed in the specimens created with no PAA pre-treatment in dentine. Conclusions: PAA conditioning of dentine prior to application of RMGIC induces no substantial effect on the bond strength after short-term storage, but its use may increase the risk of collagen degradation at the bonding interface after prolonged aging. Modern RMGIC applied without PAA dentine pre-treatment may have greater therapeutic synergy with saliva during cycle occlusal load, thereby enhancing the remineralisation and protection of the bonding interface.