Репозиторий Университета

© 2020 Elsevier B.V. Many native Australian plants have a long history of use as medicinal and culinary herbs and some are considered to be equivalents to the Mediterranean herbs. However, while therapeutic properties of Mediterranean herbs are well documented, there is limited information on the medicinal use of the Australian native herbs. Extracts of five native Australian plants were characterised with FTIR-ATR spectroscopy in the fingerprint region and screened for enzyme inhibitory and antioxidant activities via effect-directed analysis (EDA) based on bioautography. High-performance thin-layer chromatography (HPTLC) coupled with microchemical and biochemical derivatization assays was used for EDA screening. Detected compounds with biological activities were identified via FTIR-ATR spectroscopy. All herbs showed antioxidant activity with lemon myrtle being the most active. The α-amylase inhibition, observed in native thyme, sea parsley and native bush was associated with the presence of phenolic acids, chlorogenic acid and caffeic acid. The investigation of botanicals by a fast, hyphenated HPTLC method, has allowed an effect-directed high-throughput screening, fast characterization of complex mixtures and detection of biologically active phytochemicals (bioprofiling).

© 2020 Elsevier B.V. Alprazolam is used in the treatment of patients with anxiety disorders comorbid with alcohol use disorder. Some proportion of these patients does not respond adequately to treatment with alprazolam, while many of them experience dose-dependent adverse drug reactions. Results of the previous studies have shown that CYP3A is involved in the biotransformation of alprazolam, the activity of which is dependent, inter alia, on the polymorphism of the encoding gene. Objective: The objective of our study was to investigate the effect of 99366316G>A polymorphism of the CYP3A4 gene on the concentration/dose indicator of alprazolam in patients with anxiety disorders comorbid with alcohol use disorder, using findings on enzymatic activity of CYP3A (as evaluated by the 6-beta-hydroxy-cortisol/cortisol ratio measurement) and on CYP3A4 expression level obtained by measuring the miR-27b plasma concentration levels in patients with anxiety disorders comorbid with alcoholism. Material and methods: Our study enrolled 105 patients with anxiety disorders comorbid with alcohol use disorder (age - 37.8±14.6 years). Therapy included alprazolam in an average daily dose of 5.6±2.4 mg per day. Treatment efficacy was evaluated using the psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels, we performed the real-time polymerase chain reaction. The activity of CYP3A was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of the given isoenzyme and its metabolite in urine (6- beta-hydroxy-cortisol/cortisol). Therapeutic drug monitoring (TDM) has been performed using HPLC-MS/MS. Results: Our study revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMA scores at the end of the treatment course): (GG) 3.0 [2.0; 5.0] and (GA) 4.0 [4.0; 5.0], p = 0.007; at the same time, the statistical significance in the safety profile was not obtained (the UKU scores): (GG) 3.0 [2.0; 3.8] and (GA) 3.0 [1.5; 4.0], p = 0.650. We revealed a statistical significance for concentration/dose indicator of alprazolam in patients with different genotypes: (GG) 1.583 [0.941; 2.301] and (GA) 2.888 [2.305; 4.394], p = 0.001). Analysis of the results of the pharmacotranscriptomic part of the study didn't show the statistically significant difference in the miR-27b plasma levels in patients with different genotypes: (GG) 25.6 [20.4; 28.8], (GA) 25.7 [19.7; 33.1], p = 0.423. At the same time, correlation analysis revealed a statistically significant relationship between the alprazolam efficacy profile evaluated by changes in HAMA scale scores and the miR-27b plasma concentration: rs = 0.20, p = 0.042. Also, we didn't reveal the correlation between the miRNA concentration and safety profile: rs = 0.15, p = 0.127. In addition, we revealed the relationship between the CYP3A enzymatic activity (as evaluated by 6-beta-hydroxycortisol/ cortisol ratio measurement) and the miR-27b plasma concentration: rs = −0.27, p = 0.006. At the same time, correlation analysis revealed a statistically significant relationship between the alprazolam concentration and the miR-27b plasma concentration: rs = 0.28, p = 0.003. Conclusion: The effect of genetic polymorphism of the CYP3A4 gene on the efficacy and safety profiles of alprazolam was demonstrated in a group of 105 patients with anxiety disorders comorbid with alcohol use disorder. At the same time, miR-27b remains a promising biomarker for assessing the level of CYP3A4 expression, because it correlates with the encoded isoenzyme's activity.

© 2020 Elsevier B.V. Alprazolam is used in the treatment of patients with anxiety disorders comorbid with alcohol use disorder. Some proportion of these patients does not respond adequately to treatment with alprazolam, while many of them experience dose-dependent adverse drug reactions. Results of the previous studies have shown that CYP3A is involved in the biotransformation of alprazolam, the activity of which is dependent, inter alia, on the polymorphism of the encoding gene. Objective: The objective of our study was to investigate the effect of 99366316G>A polymorphism of the CYP3A4 gene on the concentration/dose indicator of alprazolam in patients with anxiety disorders comorbid with alcohol use disorder, using findings on enzymatic activity of CYP3A (as evaluated by the 6-beta-hydroxy-cortisol/cortisol ratio measurement) and on CYP3A4 expression level obtained by measuring the miR-27b plasma concentration levels in patients with anxiety disorders comorbid with alcoholism. Material and methods: Our study enrolled 105 patients with anxiety disorders comorbid with alcohol use disorder (age - 37.8±14.6 years). Therapy included alprazolam in an average daily dose of 5.6±2.4 mg per day. Treatment efficacy was evaluated using the psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels, we performed the real-time polymerase chain reaction. The activity of CYP3A was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of the given isoenzyme and its metabolite in urine (6- beta-hydroxy-cortisol/cortisol). Therapeutic drug monitoring (TDM) has been performed using HPLC-MS/MS. Results: Our study revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMA scores at the end of the treatment course): (GG) 3.0 [2.0; 5.0] and (GA) 4.0 [4.0; 5.0], p = 0.007; at the same time, the statistical significance in the safety profile was not obtained (the UKU scores): (GG) 3.0 [2.0; 3.8] and (GA) 3.0 [1.5; 4.0], p = 0.650. We revealed a statistical significance for concentration/dose indicator of alprazolam in patients with different genotypes: (GG) 1.583 [0.941; 2.301] and (GA) 2.888 [2.305; 4.394], p = 0.001). Analysis of the results of the pharmacotranscriptomic part of the study didn't show the statistically significant difference in the miR-27b plasma levels in patients with different genotypes: (GG) 25.6 [20.4; 28.8], (GA) 25.7 [19.7; 33.1], p = 0.423. At the same time, correlation analysis revealed a statistically significant relationship between the alprazolam efficacy profile evaluated by changes in HAMA scale scores and the miR-27b plasma concentration: rs = 0.20, p = 0.042. Also, we didn't reveal the correlation between the miRNA concentration and safety profile: rs = 0.15, p = 0.127. In addition, we revealed the relationship between the CYP3A enzymatic activity (as evaluated by 6-beta-hydroxycortisol/ cortisol ratio measurement) and the miR-27b plasma concentration: rs = −0.27, p = 0.006. At the same time, correlation analysis revealed a statistically significant relationship between the alprazolam concentration and the miR-27b plasma concentration: rs = 0.28, p = 0.003. Conclusion: The effect of genetic polymorphism of the CYP3A4 gene on the efficacy and safety profiles of alprazolam was demonstrated in a group of 105 patients with anxiety disorders comorbid with alcohol use disorder. At the same time, miR-27b remains a promising biomarker for assessing the level of CYP3A4 expression, because it correlates with the encoded isoenzyme's activity.

© 2020 Elsevier Inc. Dysfunction in the circadian system has been linked to emotion regulation and mood disorders with genetic variation in clock genes as likely contributors. Here, we focused on endophenotypes of affective processing and investigated in two independent samples of healthy individuals (n1=99, n2=108) whether genotypes of a functional single nucleotide polymorphism (SNP) in the gene encoding CLOCK (CLOCK T3111C, rs1801260) differed in physiological responses to emotional stimuli. Both samples underwent an emotional startle paradigm with startle responses being measured via EMG. In the second sample, skin conductance responses as well as corrugator and zygomaticus activity were also assessed. In both samples, CLOCK T3111C was associated with overall startle responses to loud noise bursts with T/T homozygotes showing consistently more marked responses. However, in the all-female second sample, the effects of CLOCK on skin conductance responses to the same loud noise bursts depended on hormone status: similar to the startle results, in free-cycling women T/T homozygotes showed more pronounced skin conductance response (SCR) compared to C allele carriers. The opposite was true for women using combined oral contraceptives (COC). A further CLOCK × hormone status interaction effect was found for corrugator activity. In free-cycling women, T/T homozygotes presented with less corrugator activity to affective pictures compared to C allele carriers, while the opposite pattern emerged for COC users. The findings emphasize the potential role of CLOCK for affect and mood.

© 2020 Elsevier Inc. Dysfunction in the circadian system has been linked to emotion regulation and mood disorders with genetic variation in clock genes as likely contributors. Here, we focused on endophenotypes of affective processing and investigated in two independent samples of healthy individuals (n1=99, n2=108) whether genotypes of a functional single nucleotide polymorphism (SNP) in the gene encoding CLOCK (CLOCK T3111C, rs1801260) differed in physiological responses to emotional stimuli. Both samples underwent an emotional startle paradigm with startle responses being measured via EMG. In the second sample, skin conductance responses as well as corrugator and zygomaticus activity were also assessed. In both samples, CLOCK T3111C was associated with overall startle responses to loud noise bursts with T/T homozygotes showing consistently more marked responses. However, in the all-female second sample, the effects of CLOCK on skin conductance responses to the same loud noise bursts depended on hormone status: similar to the startle results, in free-cycling women T/T homozygotes showed more pronounced skin conductance response (SCR) compared to C allele carriers. The opposite was true for women using combined oral contraceptives (COC). A further CLOCK × hormone status interaction effect was found for corrugator activity. In free-cycling women, T/T homozygotes presented with less corrugator activity to affective pictures compared to C allele carriers, while the opposite pattern emerged for COC users. The findings emphasize the potential role of CLOCK for affect and mood.

© 2020 The Authors Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction. Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO). Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice. Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders.

© 2020 The Authors Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction. Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO). Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice. Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders.

© 2020 The Authors Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction. Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO). Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice. Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders.

© 2020 Wiley Periodicals, Inc. Performance optimization of electrode materials for lithium-ion batteries is one the most important scientific problems. In this paper, we suggest structural design of γ-Fe2O3/CNT composite for increase of its quantum capacitance that is required by modern energy storage devices capable of quick transfer or accumulation of energy and ensuring long-term autonomous operation. For this goal, we investigate the specific quantum capacitance of the γ-Fe2O3/CNT composites with a different content of maghemite by quantum chemical methods. The content of maghemite is varied by length of CNTs as well as by number of γ-Fe2O3 unit cell the weight ratio equals 13.71%, 20.74%, 26.69%, and 34.30%. It is found that the quantum capacitance grows with increasing maghemite concentration. Calculations show that the value of QC at the Fermi level for γ-Fe2O3/CNT is correlated with the theoretical specific capacity of the material. Proposed in this work approach to calculating the quantum capacitance with further analysis of its dependence on voltage can be an effective tool for optimizing the content of the composite with the aim of balancing the Faradaic and non-Faradaic component of its functional activity.

© 2020 Wiley Periodicals, Inc. Performance optimization of electrode materials for lithium-ion batteries is one the most important scientific problems. In this paper, we suggest structural design of γ-Fe2O3/CNT composite for increase of its quantum capacitance that is required by modern energy storage devices capable of quick transfer or accumulation of energy and ensuring long-term autonomous operation. For this goal, we investigate the specific quantum capacitance of the γ-Fe2O3/CNT composites with a different content of maghemite by quantum chemical methods. The content of maghemite is varied by length of CNTs as well as by number of γ-Fe2O3 unit cell the weight ratio equals 13.71%, 20.74%, 26.69%, and 34.30%. It is found that the quantum capacitance grows with increasing maghemite concentration. Calculations show that the value of QC at the Fermi level for γ-Fe2O3/CNT is correlated with the theoretical specific capacity of the material. Proposed in this work approach to calculating the quantum capacitance with further analysis of its dependence on voltage can be an effective tool for optimizing the content of the composite with the aim of balancing the Faradaic and non-Faradaic component of its functional activity.

© 2020 Wiley Periodicals, Inc. Performance optimization of electrode materials for lithium-ion batteries is one the most important scientific problems. In this paper, we suggest structural design of γ-Fe2O3/CNT composite for increase of its quantum capacitance that is required by modern energy storage devices capable of quick transfer or accumulation of energy and ensuring long-term autonomous operation. For this goal, we investigate the specific quantum capacitance of the γ-Fe2O3/CNT composites with a different content of maghemite by quantum chemical methods. The content of maghemite is varied by length of CNTs as well as by number of γ-Fe2O3 unit cell the weight ratio equals 13.71%, 20.74%, 26.69%, and 34.30%. It is found that the quantum capacitance grows with increasing maghemite concentration. Calculations show that the value of QC at the Fermi level for γ-Fe2O3/CNT is correlated with the theoretical specific capacity of the material. Proposed in this work approach to calculating the quantum capacitance with further analysis of its dependence on voltage can be an effective tool for optimizing the content of the composite with the aim of balancing the Faradaic and non-Faradaic component of its functional activity.

© 2020 Elsevier B.V. Telomerase activity has been demonstrated in a wide variety of most solid tumors and considered as a well-known cancer biomarker. The commonly utilized method for its detection is polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP). However, the TRAP technique suffers from false-negative results caused by the failure of PCR step. Moreover, it requires advanced equipment with a tedious and time-consuming procedure. Herein, we presented a portable nitrocellulose paper-based nanobiosensing platform for ultrafast and equipment-free detection of telomerase activity based on a simple colorimetric assay that enabled naked-eye visualization of the color change in response to enzyme activity. In this platform, hybridization was initially performed between telomere complementary oligonucleotide immobilized on gold nanoparticles (GNPs) and telomerase elongated biotinylated probe. Thereafter, the assembly was attached on activated paper strip via avidin-biotin interaction. The signal amplification was carried out by enlargement of the attached GNPs on the paper strip, forming tightly compact rod-shaped submicron structures of gold representing a visual color formation. Thanks to significant sensitivity enhancement, the color change was occurred for down to 6 cells, which can be easily observed by the naked eye. Due to the desired aspects of the developed assay including PCR-free, low cost, simple, and high sensitivity, it can be used for evaluation of telomerase activity in cell extracts for future clinical applications. Furthermore, this design has the ability to be easily integrated into lab-on-chip devices for point-of-care telomerase sensing.

© 2020 Elsevier B.V. Neutrophils release neutrophil extracellular traps (NETs) in response to numerous pathogenic microbes as the last suicidal resource (NETosis) in the fight against infection. Apart from the host defense function, NETs play an essential role in the pathogenesis of various autoimmune and inflammatory diseases. Therefore, understanding the molecular mechanisms of NETosis is important for regulating aberrant NET release. The initiation of NETosis after the recognition of pathogens by specific receptors is mediated by an increase in intracellular Ca2+ concentration, therefore, the use of Ca2+ ionophore A23187 can be considered a semi-physiological model of NETosis. Induction of NETosis by various stimuli depends on reactive oxygen species (ROS) produced by NADPH oxidase, however, NETosis induced by Ca2+ ionophores was suggested to be mediated by ROS produced in mitochondria (mtROS). Using the mitochondria-targeted antioxidant SkQ1 and specific inhibitors of NADPH oxidase, we showed that both sources of ROS, mitochondria and NADPH oxidase, are involved in NETosis induced by A23187 in human neutrophils. In support of the critical role of mtROS, SkQ1-sensitive NETosis was demonstrated to be induced by A23187 in neutrophils from patients with chronic granulomatous disease (CGD). We assume that Ca2+-triggered mtROS production contributes to NETosis either directly (CGD neutrophils) or by stimulating NADPH oxidase. The opening of the mitochondrial permeability transition pore (mPTP) in neutrophils treated by A23187 was revealed using the electron transmission microscopy as a swelling of the mitochondrial matrix. Using specific inhibitors, we demonstrated that the mPTP is involved in mtROS production, NETosis, and the oxidative burst induced by A23187.

© 2020 Background: The sprouts of Brassica vegetables are known from their nutritional and chemopreventive values. Moreover, sprouts fortification with some trace elements, like selenium, may increase their importance in human diet. Thus, the aim of our study was to examine if selenium enrichment of kale and kohlrabi sprouts may influence their biochemical properties (phenolic acids and L-tryptophan content, antioxidant potential) or cytotoxic activity. Additional aim of the study was to evaluate the profile of selenium compounds and to describe the multidimensional interactions between the mentioned parameters. Methods: Selenium content in the sprouts was evaluated by double-channel atomic fluorescence spectrometer AFS-230 with the flow hydride-generation system. Separation of selenium species in water soluble fraction was performed by size-exclusion LC-ICP-MS. The identification and quantification of phenolic acids and L-tryptophan was performed by HPLC. For antioxidant activity DPPH and FRAP methods were used. Cytotoxic activity of the sprouts extracts on a panel of human metastatic carcinoma cells was evaluated by MTT test. Results: Selenium content in the fortified sprouts was several orders of magnitude higher than in the unfortified ones. Only small percentage of supplemented selenium (ca. 10 %) was incorporated into the sprouts as seleno-L-methionine, while the other detected selenium species remained unidentified. Selenium fortification differently stimulated the production of phenolic acids (sinapic, chlorogenic, isochlorogenic and caffeic acid) in the tested sprouts, depending on the particular species, selenium dose and the investigated compound. PCA analysis revealed strong correlation between antioxidant parameters and phenolic acids and L-tryptophan, while Se correlated only with caffeic acid. The sprouts extracts (≥1 mg/mL) showed cytotoxic potency to all the studied cancer cell lines (SW480, SW620, HepG2, SiHa), regardless the selenium supplementation. Conclusion: Se-fortified kale and kohlrabi sprouts are good candidates for functional food ingredients. Moreover, these results indicate that the sprouts enriched with sodium selenite show higher nutritional value, without significant changes in their cytotoxic activity.

© 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 B.V. Photosensitive polymeric three-dimensional microstructured film (PTMF) is a new type of patterned polymeric films functionalized with an array of sealed hollow 3D containers. The microstructured system with enclosed chemicals provides a tool for the even distribution of biologically active substances on a given surface that can be deposited on medical implants or used as a cells substrate. In this work, we proposed a way for photothermally activating and releasing encapsulated substances at picogram amounts from the PTMF surface in different environments using laser radiation delivered with a multimode optical fiber. The photosensitive PTMFs were prepared by the layer-by-layer (LbL) assembly from alternatively charged polyelectrolytes followed by covering with a layer of hydrophobic polylactic acid (PLA) and a layer of gold nanoparticles (AuNPs). Moreover, the typical photothermal cargo release amounts were determined on the surface of the PTMF for a range of laser powers delivered to films placed in the air, deionized (DI) water, and 1% agarose gel. The agarose gel was used as a soft tissue model for developing a technique for the laser activation of PTMFs deep in tissues using optical waveguides. The number of PTMF chambers activated by a near-infrared (NIR) laser beam was evaluated as the function of optical parameters.

© 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 B.V. Photosensitive polymeric three-dimensional microstructured film (PTMF) is a new type of patterned polymeric films functionalized with an array of sealed hollow 3D containers. The microstructured system with enclosed chemicals provides a tool for the even distribution of biologically active substances on a given surface that can be deposited on medical implants or used as a cells substrate. In this work, we proposed a way for photothermally activating and releasing encapsulated substances at picogram amounts from the PTMF surface in different environments using laser radiation delivered with a multimode optical fiber. The photosensitive PTMFs were prepared by the layer-by-layer (LbL) assembly from alternatively charged polyelectrolytes followed by covering with a layer of hydrophobic polylactic acid (PLA) and a layer of gold nanoparticles (AuNPs). Moreover, the typical photothermal cargo release amounts were determined on the surface of the PTMF for a range of laser powers delivered to films placed in the air, deionized (DI) water, and 1% agarose gel. The agarose gel was used as a soft tissue model for developing a technique for the laser activation of PTMFs deep in tissues using optical waveguides. The number of PTMF chambers activated by a near-infrared (NIR) laser beam was evaluated as the function of optical parameters.

© 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 B.V. Photosensitive polymeric three-dimensional microstructured film (PTMF) is a new type of patterned polymeric films functionalized with an array of sealed hollow 3D containers. The microstructured system with enclosed chemicals provides a tool for the even distribution of biologically active substances on a given surface that can be deposited on medical implants or used as a cells substrate. In this work, we proposed a way for photothermally activating and releasing encapsulated substances at picogram amounts from the PTMF surface in different environments using laser radiation delivered with a multimode optical fiber. The photosensitive PTMFs were prepared by the layer-by-layer (LbL) assembly from alternatively charged polyelectrolytes followed by covering with a layer of hydrophobic polylactic acid (PLA) and a layer of gold nanoparticles (AuNPs). Moreover, the typical photothermal cargo release amounts were determined on the surface of the PTMF for a range of laser powers delivered to films placed in the air, deionized (DI) water, and 1% agarose gel. The agarose gel was used as a soft tissue model for developing a technique for the laser activation of PTMFs deep in tissues using optical waveguides. The number of PTMF chambers activated by a near-infrared (NIR) laser beam was evaluated as the function of optical parameters.