Native human and mouse skin infection models to study Candida auris-host interactions.

The World Health Organization (WHO) declared certain fungal pathogens as global health threats for the next decade. Candida auris (C. auris) is a newly emerging skin-tropic multidrug-resistant fungal pathogen that can cause life-threatening infections of high mortality in hospitals and healthcare settings. Here, we address an unmet need and present novel native ex vivo skin models, thus extending previous C. auris-host interaction studies. We exploit histology and immunofluorescence analysis of ex vivo skin biopsies of human adult and fetal, as well as mouse origin infected with C. auris via distinct routes. We demonstrate that an intact skin barrier efficiently protects from C. auris penetration and invasion. Although C. auris readily grows on native human skin, it can reach deeper layers only upon physical disruption of the barrier by needling or through otherwise damaged skin. By contrast, a barrier disruption is not necessary for C. auris penetration of native mouse skin. Importantly, we show that C. auris undergoes morphogenetic changes upon skin penetration, as it acquires pseudohyphal growth phenotypes in deeper human and mouse dermis. Taken together, this new human and mouse skin model toolset yields new insights into C. auris colonization, adhesion, growth and invasion properties of native versus damaged human skin. The results form a crucial basis for future studies on skin immune defense to colonizing pathogens, and offer new options for testing the action and efficacy of topical antimicrobial compound formulations.

Neurotoxicity of silver nanoparticles in the animal brain: a systematic review and meta-analysis.

OBJECTIVE: About 30% of all nanoparticle products contain silver nanoparticles (AgNPs). With the increasing use of AgNPs in industry and medicine, concerns about the adverse effects on the environment, and the possible toxicity of these particles to primary cells and towards organs such as the brain and nervous system increased. In this paper, the toxicity of AgNPs in neurons and brain of animal models was investigated by a systematic review and meta-analysis. METHODS: The full texts of 26 relevant studies were reviewed and analyzed. Data from nine separate experiments in five articles were analyzed by calculating the standardized mean differences between viability of treated animals and untreated groups. Subgroup analysis was conducted. In addition, a systematic review provided a complete, exhaustive summary of all articles. RESULTS: The results of the meta-analysis showed that AgNPs are able to cause neuronal death after entering the brain (standardized mean difference (SMD) = 2.87; 95% confidence interval (CI) 2.1-3.61; p < 0.001). AgNPs sized smaller or larger than 10 nm could both cause neuronal cell death. This effect could be observed for a long time (up to 6 months). Neurons from embryonic animals whose mothers had been exposed to AgNPs during pregnancy were affected as much as animals that were themselves exposed to AgNPs. Toxic effects of AgNPs on memory and cognitive function were also observed. Studies have shown that inflammation and increased oxidative stress followed by apoptosis are likely to be the main mechanisms of AgNPs toxicity. CONCLUSION: AgNPs can enter the brain with a long half-life and it can cause neuronal death after entering the brain. AgNPs can manifest proinflammatory cascades in the CNS and BBB. Some toxic effects were detected in the cerebral cortex, hypothalamus, hippocampus and others. Studies have shown that inflammation and increased oxidative stress lead to apoptosis, the main mechanism of AgNPs neurotoxicity, which can be caused by an increase in silver ions from AgNPs.

The investigation into the effect of the length of RGD peptides and temperature on the interaction with the αIIbß3 integrin: a molecular dynamic study.

The tripeptide Arg-Gly-Asp acid (RGD) is a protein sequence in the binding of proteins to cell surfaces, and is involved in various biological processes such as cell adhesion to the extracellular matrix, platelet activation, hemostasis, etc. The C2 domain of the Von Willebrand Factor (VWF), containing the RGD motif, plays an important role in the initial homeostasis process. It binds to the αIIbß3 integrin and stimulates platelet aggregation. We have investigated, using the molecular Dynamic (MD) simulation method, the effect of the RGD-peptide length, and temperature variation, on the binding to the αIIbß3 integrin receptor. We examined 10 different structural modes of the αIIbß3 at three different temperatures; 237 K, 310 K and 318 K. Our findings show that the amino acids that form a binding pocket include Asp224, Tyr234, Ser226, Tyr190, Tyr189, Trp260, Trp262, Asp259, Lys253, Arg214, Asp217, Ser161 and Ala218 and that the ligand-receptor interaction was increased at higher temperatures. It was also found that the increase in the number of ligands' amino acids and their types (% glycine) plays an important role in the stability, conformation, and ligand-receptor interaction.Communicated by Ramaswamy H. Sarma.

The Toxic Effect of Silver Nanoparticles on Nerve Cells: A Systematic Review and Meta-Analysis.

Despite the increasing use of silver nanoparticles in medical sciences, published studies on their interaction with nerve cells and evaluation of risks are dispersed. This systematic review and meta-analysis could be used to devise safety guidelines for the use of silver nanoparticles in industry and medicine to reduce adverse effects on the CNS.After extensive searches, the full text of 30 related studies was reviewed and data mining completed. Data were analyzed by calculating the mean of different ratios between treated and untreated groups. Linear regression between variables was evaluated by meta-regression. Subgroup analysis was also performed due to heterogeneity.Treatment with silver nanoparticles significantly reduced cell viability (SMD = -1.79%; 95% CI: -2.17 to -1.40; p < 0.0001). Concentration > 0.1 µg/mL could kill neurons, while lower concentration would not (SMD -0.258; 95% CI: -0.821 to 0.305; p = 369). In addition to the concentration, the coating, size of the nanoparticles, and cell type are also factors that influence SNP nerve cell toxicity. Measurement of apoptosis (SMD = 2.21; 95% CI: 1.62 to 2.80; p=0.001) and lactate dehydrogenase release rate (SMD = 0.9; 95% CI: 0.33 to 1.47; p < 0.0001) also confirmed the destructive effect of silver nanoparticles on nerve cells.

Quantification of zinc intoxication of Candida glabrata after phagocytosis by primary macrophages.

Zinc (Zn2+) is a trace element, playing pivotal roles during host-pathogen interactions. Macrophages can sequester Zn2+ and restrict bioavailability or increase phagolysosomal Zn2+ to kill pathogens. This method quantifies Zn2+-mediated clearance of the human fungal pathogen C. glabrata after phagocytosis by innate immune cells. Double staining with propidium iodide and a zinc-specific fluorescence dye allows for discrimination of live versus dead pathogens inside phagolysosomes. Moreover, elevated phagolysosomal Zn2+ decreases fungal viability as a function of intracellular Zn2+ concentrations in macrophages. For complete details on the use and execution of this protocol, please refer to Riedelberger et al. (2020).

Morphophysiological changes of wild Stachys multicaulis species under physical conditions during the cultivation process.

Depending on the physical environmental conditions, cultivation process can have significant effects on the wild plants' morphophysiological characteristics. Stachys multicaulis is an Iranian wild endemic medicinal plant species and its cultivation preformed under different Soil Textures (ST) and Soil Moisture Regimes (SMRs). Controlled pot culture conditions performed with light, moderate, heavy STs and a set of SMRs at 100% Field Capacity (FC), 70%FC and 30% FC. Plant cultivated in heavy STs had higher performance in all measured treats. Height of plant (HP), Calibrated Greenness (CG), Leaf Ratio (LR) and Angle (LA), aerial Moisture Content (MC) did not show a regular trend in comparison to the wild. Unlike the Density of Trichome (DT), Length of leave's Trichome (LT) showed a significant change under cultivation conditions (p < 0.01). Also, as a physiological response, Essential Oils Components (EOC), especially thymol and bicyclogermacrene decreased with decreasing soil MC for light ST and the lowest change were observed in heavy ST and 30%FC. Generally, cultivation reduced EOCs, but improved plant's morphological characteristics.

Effect of soil and physiographic factors on ecological plant groups in the eastern Elborz mountain rangeland of Iran.

To investigate the cause of differences among ecological plant groups in the east of the Elborz mountain rangeland, the role of edaphical and topographical characteristics was considered. Two ordination techniques, detrended correspondence analysis (DCA) and canonical correspondence analysis (CCA), were used. The values of slope, aspect, altitude and lithology information were provided by Geographic Information System (GIS), and geomorphological land units were determined by intersection of overlaid data layers. Plant sampling was undertaken within nine land units with similar lithology and altitude but which differed in slope and aspect, using 30 randomly selected 1 m2 plots per land unit. Soil samples were taken from two depths (0-20 and 20-50 cm) in each plot. Organic matter, bulk density, texture, calcium carbonate, total nitrogen and available phosphorus and potassium contents were determined. The results indicated that plant species have different responses to edaphical and topographical parameters. The invader species group had a balanced amount of influence from all soil components and topographic factors, whereas the native grasses were located in productive soils, which typically have a low grazing intensity, such as the north facing slopes. Coniferous bushy trees, cushion plants and some shrub plant groups were found on steep slopes with alkaline soils. The broad-leaved bushy trees plant group was abundant in fine texture soils on low and humid slopes.