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The reduction of tissue cytotoxicity and the improvement of cell viability are of utmost significance, particularly in the realm of green chemistry. Despite substantial progress, the threat of local infections remains a concern. Therefore, hydrogel systems that provide mechanical support and a harmonious balance between antimicrobial efficacy and cell viability are greatly needed. Our study explores the preparation of physically crosslinked, injectable, and antimicrobial hydrogels using biocompatible hyaluronic acid (HA) and antimicrobial ε-polylysine (ε-PL) in different weight ratios (10 wt% to 90 wt%). The crosslinking was achieved by forming a polyelectrolyte complex between HA and ε-PL. The influence of HA content on the resulting HA/ε-PL hydrogel physicochemical, mechanical, morphological, rheological, and antimicrobial properties was evaluated, followed by an inspection of their in vitro cytotoxicity and hemocompatibility. Within the study, injectable, self-healing HA/ε-PL hydrogels were developed. All hydrogels showed antimicrobial properties against S. aureus, P. aeruginosa, E. coli, and C. albicans, where HA/ε-PL 30:70 (wt%) composition reached nearly 100% killing efficiency. The antimicrobial activity was directly proportional to ε-PL content in the HA/ε-PL hydrogels. A decrease in ε-PL content led to a reduction of antimicrobial efficacy against S. aureus and C. albicans. Conversely, this decrease in ε-PL content in HA/ε-PL hydrogels was favourable for Balb/c 3T3 cells, leading to the cell viability of 152.57% for HA/ε-PL 70:30 and 142.67% for HA/ε-PL 80:20. The obtained results provide essential insights into the composition of the appropriate hydrogel systems able to provide not only mechanical support but also the antibacterial effect, which can offer opportunities for developing new, patient-safe, and environmentally friendly biomaterials. [ABSTRACT FROM AUTHOR]

Inhalation is the main route of exposure to airborne pollutants. To evaluate the safety and assess the risks of occupational hazards different testing approaches are used. 3D airway epithelial tissues allow to mimic exposure conditions in vitro, generates human-relevant toxicology data, allows to elucidate the mode of action of pollutants. Gillian3500 pumps were used to collect the airborne particulate from woodworking and metalworking environments. EpiAirway tissues were used to model half working day (4 h), full working day (8 h), and 3 working day exposures to occupational pollutants. Tissue viability was assessed using an MTT assay. For preliminary assessment, RT-qPCR analyses were performed to analyze the expression of gelsolin, caspase-3, and IL-6. Tissue morphology was assessed by hematoxylin/eosin staining. An effect on the proliferation of lung epithelial cell line A549 was assessed. Acute exposure to workspace pollutants slightly affected tissue viability and did not change the morphology. No inhibiting effect was observed on the proliferation of A549 cells. Preliminary analysis showed that both types of particles suppressed the expression of gelsolin, with the effect of metalworking samples being more pronounced. A slight reduction in caspase-3 expression was observed. Particles from metalworking suppressed IL-6 expression. [ABSTRACT FROM AUTHOR]

Individuals working in nail salons are exposed to 2-hydroxyethyl methacrylate (HEMA). HEMA has been found to have several effects on the skin: skin itching, peeling, redness and allergic contact dermatitis. The purpose of the study was to compare the effects of nail coatings containing HEMA and 2-hydroxypropyl methacrylate (HPMA) on the skin. In this study we explored the irritation properties of HEMA and HPMA containing nail coatings in cell cultures in-vitro and in skin PATCH tests under dermatological control. The cytotoxicity of coatings was tested in BALB/c3T3 and HaCaT cell lines by a neutral red uptake assay. Cytotoxicity was expressed as a concentration-dependent reduction of the uptake of neutral red, compared to the untreated controls. Open patch tests were supervised by a certified dermatologist. Polymerized coating extracts have little effect on Balb/c 3T3 cell viability, while having mild cytotoxic effects on HaCaT keratinocytes. Among two tested samples, extracts of HEMA containing coating exhibited higher cytotoxicity - reduction of keratinocyte viability by 28.29 % in case of undiluted 24 h extract and even by 48.26 % in case of 50 % extract was observed. Coating cytotoxiaty observed on HaCaT showed that the keratinocyte cell line was more sensitive to HEMA than to HPMA containing coating. [ABSTRACT FROM AUTHOR]

The most common reasons for major skin loss are thermal trauma — burns and scalds that can result in rapid, extensive, deep wounds as well as chronic non-healing wounds. Treatment using common techniques is poor and depending on the trauma level can result in death. There is a substantial need for skin integrity restoration. The main goal of this study was to develop an autologous 3D skin model that could eventually be translated into clinical applications. The study examined a variety of factors — extracellular matrix components, cell count, culture medium modification and role of structurally and functionally high-quality 3D skin dermis layer tissue culture production. The results of this study are an essential prerequisite to standardise the use of both clinical, as well as in vitro test systems. Dermal cell lines applied in the study were isolated form patient biopsies obtained at Pauls Stradiņš Clinical University Hospital. Blood plasma type AB was used for fibrin matrix formation. As catalysts, CaCl2 or calcium gluconate, and tranexamic acid were applied. 3D tissue functionality was assessed by evaluation of gene expression and changes in growth factor secretion. Fibrin matrix formulations with 1% and 1.5% CaCl2 and 5 mg, 7 mg and 10 mg tranexamic acid concentration were tested. Better matrix properties were observed with higher concentration of CaCl2 and tranexamic acid. Differences in levels of collagen gene expression and growth factor secretion were observed. Changes in levels of fibroblast growth factor and gene expression were observed in fibrin matrix samples and the surface-cultivated cell culture monolayer, but structural protein synthesis was not detected. [ABSTRACT FROM AUTHOR]

It has now been proven that many pathogens that cause infections and inflammation gradually mutate and become resistant to antibiotics. Chemically synthesized drugs treating inflammation most often only affect symptoms, but side effects could lead to the failure of human organs' functionality. On the other hand, plant-derived natural compounds have a long-term healing effect. It was shown that sea buckthorn (SBT) twigs are a rich source of biologically active compounds, including oligomeric proanthocyanidins (PACs). This study aimed to assess the anti-pathogenic and anti-inflammatory activity of water/ethanol extracts and PACs obtained from the lignocellulosic biomass of eight SBT cultivars. The anti-pathogenic activity of extracts and PACs was studied against pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Bacillus cereus and fungus Candida albicans in 96-well plates by the two-fold serial broth microdilution method. The anti-bacterial activity of purified PACs was 4 and 10 times higher than for water and water/ethanol extracts, respectively, but the extracts had higher anti-fungal activity. Purified PACs showed the ability to reduce IL-8 and IL-6 secretion from poly-I:C-stimulated peripheral blood mononuclear cells. For the extracts and PACs of SBT cultivar 'Maria Bruvele' in the concentration range 0.0313–4.0 mg/mL, no toxic effect was observed. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 nsp14 guanine-N7-methyltransferase plays an important role in the viral RNA translation process by catalyzing the transfer of a methyl group from S-adenosyl-methionine (SAM) to viral mRNA cap. We report a structure-guided design and synthesis of 3-(adenosylthio)benzoic acid derivatives as nsp14 methyltransferase inhibitors resulting in compound 5p with subnanomolar inhibitory activity and improved cell membrane permeability in comparison with the parent inhibitor. Compound 5p acts as a bisubstrate inhibitor targeting both SAM and mRNA-binding pockets of nsp14. While the selectivity of 3-(adenosylthio)benzoic acid derivatives against human glycine N-methyltransferase was not improved, the discovery of phenyl-substituted analogs 5p,t may contribute to further development of SARS-CoV-2 nsp14 bisubstrate inhibitors. [ABSTRACT FROM AUTHOR]

The design of multifunctional hydrogels based on bioactive hyaluronic acid (HA) and antibacterial cationic polymer ɛ-poly- l -lysine (ε-PL) is a promising tool in tissue engineering applications. In the current study, we have designed hyaluronic acid and ɛ-polylysine composite hydrogel systems with antibacterial and cell attractive properties. Two distinct crosslinking approaches were used: the physical crosslinking based on electrostatic attractions and the chemical crosslinking of charged functional groups (-NH 2 and -COOH). The impact of the crosslinking strategy on fabricated hydrogel molecular structure, swelling behavior, gel fraction, morphology, porosity, viscoelastic properties, antibacterial activity, and in vitro biocompatibility was evaluated. Both chemically and physically crosslinked HA/ԑ-PL hydrogels demonstrated fast swelling behavior and long-term stability for at least 28 days, as well as similar order of stiffness (10–30 kPa). We demonstrated that physically crosslinked hydrogels inhibited over 99.999% of Gram-negative E. coli , while chemically crosslinking strategy led to the antibacterial efficiency decrease. However, cell viability was significantly improved, confirming the importance of the applied crosslinking approach to the antibacterial activity and in vitro biocompatibility. The distinct differences in the physicochemical and biological properties of the developed materials provide new opportunities to design next-generation functional composite hydrogel systems. [Display omitted] • Chemically and physically crosslinked HA/ԑ-PL hydrogels were developed. • Hydrogels were stable and cohesive for at least 28 days. • Hydrogel stiffness was in range from 10 kPa to 30 kPa. • Physically crosslinked hydrogels inhibited over 99.999% of Gram-negative E. coli. • Cell viability was significantly higher for chemically crosslinked hydrogels. [ABSTRACT FROM AUTHOR]

Airborne particulates present a potential hazard to health in a variety of indoor workplaces, from offices to the manufacturing floor. Dust and aerosols are two of the most common occupational risk factors in the workplace worldwide. It is very important to understand when it is sufficient to describe dust exposure only by given mass concentration that dust particles could be in the nanosized range in the workplace air even for brief exposures, such as welding aerosols. The main objective was to assess total dust and nanoparticle concentrations in the selected workplaces and to evaluate their impact on workers' health. This project describes nanoparticle concentrations and their potential impact on workers' health considering the exposure levels in three workplaces. Industrial and non-industrial environments have been included in the project. The office environment was used as an indicator for the background level of comparison with the metalworking and woodworking industries for measurements of dust particles including the nanoscale particles (> 100 nm). Fraction size of the samples according to a dispersity of > 10 μm, 0.25–10 μm, < 0.25 μm, and 1–100 nm was analysed in order to describe the particles' chemical composition at the different stages. The worst working conditions (the smallest particles, 12 nm), the highest total dust concentrations, and the lowest difference between total inhalable particle and nanoparticle concentrations were detected among woodworkers. These findings provide a basis on how to evaluate nanoparticle exposure and its impact on workers' health because the highest immune cell counts and relatively high IL-6 expression were observed among woodworkers compared with the other groups. The data show a negative tendency of nanoparticle exposure concentrations on workers' health based on the increase of inflammatory processes and damage to airway epithelial cell functionality. [ABSTRACT FROM AUTHOR]

Cosmetic manufacturers are continuously searching for new active ingredients to satisfy consumer needs. This leads to growing demand of botanical extracts with characterized chemical composition and proven efficacy. The aim of the study was to characterize the chemical composition of birch sap and a complex of seven plant extracts, with brand name Cell Repair Bio-Complex (CRB), and to evaluate their effects on skin cells. HPLC analysis was used to identify dominating compounds. Effect on proliferation of dermal fibroblasts and keratinocytes was assessed using the IncuCyte ZOOM system. Results show that flavonoid and phenolic acid rich CRB possesses antiradical activity and stimulates dermal fibroblast proliferation at low concentration. Birch sap stimulates both dermal fibroblasts and keratinocytes at high concentrations. Stimulatory effect of keratinocytes was observed also for the combination of birch sap and CRB. The findings indicate the potential of CRB to be used as an active ingredient, whereas birch sap used at high concentrations could substitute water base and add additional efficacy. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses mRNA capping to evade the human immune system. The cap formation is performed by the SARS-CoV-2 mRNA cap methyltransferases (MTases) nsp14 and nsp16, which are emerging targets for the development of broad-spectrum antiviral agents. Here, we report results from high-throughput virtual screening against these two enzymes. The docking of seven million commercially available drug-like compounds and S-adenosylmethionine (SAM) co-substrate analogues against both MTases resulted in 80 virtual screening hits (39 against nsp14 and 41 against nsp16), which were purchased and tested using an enzymatic homogeneous time-resolved fluorescent energy transfer (HTRF) assay. Nine compounds showed micromolar inhibition activity (IC50 < 200 μM). The selectivity of the identified inhibitors was evaluated by cross-checking their activity against human glycine N-methyltransferase. The majority of the compounds showed poor selectivity for a specific MTase, no cytotoxic effects, and rather poor cell permeability. Nevertheless, the identified compounds represent good starting points that have the potential to be developed into efficient viral MTase inhibitors. [ABSTRACT FROM AUTHOR]