Hyperpolarization-activated currents drive neuronal activation sequences in sleep.

Sequential neuronal patterns are believed to support information processing in the cortex, yet their origin is still a matter of debate. We report that neuronal activity in the mouse postsubiculum (PoSub), where a majority of neurons are modulated by the animal's head direction, was sequentially activated along the dorsoventral axis during sleep at the transition from hyperpolarized "DOWN" to activated "UP" states, while representing a stable direction. Computational modeling suggested that these dynamics could be attributed to a spatial gradient of hyperpolarization-activated currents (Ih), which we confirmed in ex vivo slice experiments and corroborated in other cortical structures. These findings open up the possibility that varying amounts of Ih across cortical neurons could result in sequential neuronal patterns and that traveling activity upstream of the entorhinal-hippocampal circuit organizes large-scale neuronal activity supporting learning and memory during sleep.

Anti-Viral Surfaces in the Fight against the Spread of Coronaviruses.

This review is conducted against the background of nanotechnology, which provides us with a chance to effectively combat the spread of coronaviruses, and which primarily concerns polyelectrolytes and their usability for obtaining protective function against viruses and as carriers for anti-viral agents, vaccine adjuvants, and, in particular, direct anti-viral activity. This review covers nanomembranes in the form of nano-coatings or nanoparticles built of natural or synthetic polyelectrolytes--either alone or else as nanocomposites for creating an interface with viruses. There are not a wide variety of polyelectrolytes with direct activity against SARS-CoV-2, but materials that are effective in virucidal evaluations against HIV, SARS-CoV, and MERS-CoV are taken into account as potentially active against SARS-CoV-2. Developing new approaches to materials as interfaces with viruses will continue to be relevant in the future.

A Functionalized Membrane Layer as Part of a Dressing to Aid Wound Healing.

PURPOSE: This study is an approach to a dressing platform based on support functionalized with oxygenating factors within an alginate layer, constituting a safe and even contact surface for interface with a wound. METHODS: An alginate layer with incorporated oxygenating elements deposited on the support patch was assessed. As an oxygenating factor, perfluorooctyl was applied, and the layer coatings in two options, cross-linked and not, were evaluated. The function of human dermal fibroblast cells cultured in the presence of these constructs was analyzed, as well as their morphology using flow cytometry, fluorescence microscopy, and scanning electron microscopy. In addition, the membrane coating material was assessed using FTIR, AFM, and SEM-EDX characterization. RESULTS: The applied membrane coatings adsorbed on the patch ensured the viability of the human fibroblasts cultured on the membranes during 10 days of culture. However, on the sixth day of culture, the percentage of live cells grown in the presence of cross-linked alginate with oxygenating factor ((ALG-PFC)net) was significantly higher than that of the cells cultured in the presence of the alginate coatings alone. SEM-EDX analysis of the (ALG-PFC)net confirmed the presence of oxygenating and cross-linking factors. In addition, the regular granular branched structure of the layer coating material involving the oxygenating and cross-linking factors was observed using the AFM technique. CONCLUSION: The topography of the layer coating material involving the oxygenating and cross-linking factors ensures an even contact surface for interface with the wound. Considering 5-day intervals between dressing replacements, the platform with an oxygenating configuration ensuring the growth and morphology of the human fibroblasts can be recommended at this time as an element of a dressing system.

Polyelectrolyte Membrane Nanocoatings Aimed at Personal Protective and Medical Equipment Surfaces to Reduce Coronavirus Spreading.

The study of the surface of membrane coatings constructed with adsorbed coronavirus (COV) was described to test their suitability for the antiviral activity for application in personal protective and medical equipment. The nanocoating based on polyethyleneimine (PEI) or polystyrene sulfonate (PSS) with metallic nanoparticles incorporated was investigated using the AFM technique. Moreover, the functioning of human lung cells in a configuration with the prepared material with the adsorbed coronavirus was studied using microscopic techniques and flow cytometry. The mean values of the percentage share of viable cells compared with the control differed by a maximum of 22%. The results showed that PEI and PSS membrane layer coatings, modified with chosen metallic nanoparticles (AuNPs, AgNPs, CuNPs, FeNPs) that absorb COV, could support lung cells' function, despite the different distribution patterns of COV on designed surfaces as well as immobilized lung cells. Therefore, the developed membrane nanocoatings can be recommended as material for biomedical applications, e.g., medical equipment surfaces to reduce coronavirus spreading, as they adsorb COV and simultaneously maintain the functioning of the eukaryotic cells.

Composite Membrane Dressings System with Metallic Nanoparticles as an Antibacterial Factor in Wound Healing.

Wound management is the burning problem of modern medicine, significantly burdening developed countries' healthcare systems. In recent years, it has become clear that the achievements of nanotechnology have introduced a new quality in wound healing. The application of nanomaterials in wound dressing significantly improves their properties and promotes the healing of injuries. Therefore, this review paper presents the subjectively selected nanomaterials used in wound dressings, including the metallic nanoparticles (NPs), and refers to the aspects of their application as antimicrobial factors. The literature review was supplemented with the results of our team's research on the elements of multifunctional new-generation dressings containing nanoparticles. The wound healing multiple molecular pathways, mediating cell types, and affecting agents are discussed herein. Moreover, the categorization of wound dressings is presented. Additionally, some materials and membrane constructs applied in wound dressings are described. Finally, bacterial participation in wound healing and the mechanism of the antibacterial function of nanoparticles are considered. Membranes involving NPs as the bacteriostatic factors for improving wound healing of skin and bones, including our experimental findings, are discussed in the paper. In addition, some studies of our team concerning the selected bacterial strains' interaction with material involving different metallic NPs, such as AuNPs, AgNPs, Fe3O4NPs, and CuNPs, are presented. Furthermore, nanoparticles' influence on selected eukaryotic cells is mentioned. The ideal, universal wound dressing still has not been obtained; thus, a new generation of products have been developed, represented by the nanocomposite materials with antibacterial, anti-inflammatory properties that can influence the wound-healing process.

A Composite Membrane System with Gold Nanoparticles, Hydroxyapatite, and Fullerenol for Dual Interaction for Biomedical Purposes.

Background: Wound dressing plays a vital role in post-operative aftercare. There is the necessity to develop dressings for application on the border of soft and hard tissue. This study aimed to develop multifunctional polyelectrolyte layers enhanced by hydroxyapatite nanoparticles, gold nanoparticles (AuNPs), and/or fullerenol nanocomposites to achieve a wound dressing that could be applied on the bone-skin interface. Methods: Constructed shells were examined using TEM, STEM, and EDX techniques. The human osteoblasts or fibroblasts were immobilized within the shells. The systems morphology was assessed using SEM. The functioning of cells was determined by flow cytomery. Moreover, the internalization of AuNPs was assessed. Results: Involvement of fullerenol and/or hydroxyapatite nanoparticles influenced the immobilized cell systems morphology. Membranes with fullerenol and hydroxyapatite nanoparticles were observed to block the internalization of AuNPs by immobilized hFOB cells. Conclusions: The designed bilayer membranes incorporating fullerenol, and bacteriostatic elements, prevented the internalization of AuNPs by hFOB cells and ensured the proper counts and morphology of eukaryotic cells. The developed material can be recommended for dressings at the bone-skin interface.

Nanocomposite Membrane Scaffolds for Cell Function Maintaining for Biomedical Purposes.

Nanocomposite multilayered membrane coatings have been widely used experimentally to enhance biomedical materials surfaces. By the selection of reliable components, such systems are functionalized to be adjusted to specific purposes. As metal nanoparticles can reduce bacterial cell adhesion, the idea of using gold and silver nanoparticles of unique antimicrobial properties within membrane structure is outstandingly interesting considering dressings facilitating wound healing. The study was aimed to explore the interface between eukaryotic cells and wound dressing materials containing various nanoelements. The proposed systems are based on polyethyleneimine and hydroxyapatite thin layers incorporating metallic nanoparticles (silver or gold). To examine the structure of designed materials scanning electron and transmission electron microscopies were applied. Moreover, Fourier-transform infrared and energy-dispersive X-ray spectroscopies were used. Additionally, water contact angles of the designed membranes and their transport properties were estimated. The functioning of human fibroblasts was examined via flow cytometry to assess the biocompatibility of developed shells in the aspect of their cytotoxicity. The results indicated that designed nanocomposite membrane scaffolds support eukaryotic cells' functioning, confirming that the elaborated systems might be recommended as wound healing materials.

Polyelectrolyte Membrane with Hydroxyapatite and Silver Nanoparticles as a Material for Modern Wound Dressings.

Modern wound dressings not only play a covering role but also facilitate the function of the wound, contributing to a faster healing process. In this paper, we present a polyelectrolyte system with nanosized elements that could stimulate the growth of eukaryotic cells while providing antimicrobial properties, which may be recommended as a potential dressing material. The proposed platform consisted of polyethyleneimine, hydroxyapatite, and silver nanoparticles and was characterized using various macroscopic techniques. The constructed membrane scaffold was evaluated with immobilized WEHI 164 cells as a model system for cells sustained at the interface of bone and skin. Moreover, the bacteriostatic function of the designed membrane material was evaluated using different bacterial strains.

Gold Nanoparticle-Modified Poly(vinyl chloride) Surface with Improved Antimicrobial Properties for Medical Devices.

Despite the significant technological progress achieved in the past decades in the medical field, device-related infections carry a heavy social and economic burden. Surface modification of medical equipment is one of the most interesting approaches employed to improve the antibacterial activity of a material. Herein, we developed a process for the gold nanoparticle modification of a poly(vinyl chloride) laryngeal tube, which typically serves as an airway management device. In our study, we focused specifically on increasing the antimicrobial properties of the material while maintaining its biocompatibility. We applied two different modification methods to the poly(vinyl chloride) laryngeal tube. An increase in the antimicrobial activity of the surface was observed for both methods. In addition, the adsorption of bacterial cells on the material surface was assessed. We determined that the number of colonies cultured in the presence of the gold nanoparticle-modified samples or absorbed to the material surface decreased significantly compared with the control group. The trend was observed for both Gram-positive and Gram-negative strains. Moreover, it was established that the designed material did not exhibit a lethal impact on a control cell line. Finally, we noted discrepancies in the growth of bacteria cultured in the presence of modified or unmodified PVC material as well as differences in cell adherence to its surface. The proposed poly(vinyl chloride) modifications are most effective against Gram-positive bacteria, especially L. monocytogenes. Nevertheless, it ought to be emphasized that due to their different properties, each strain requires an individual approach.

Stabilized nanosystem of nanocarriers with an immobilized biological factor for anti-tumor therapy.

OBJECTIVE: The inadequate efficiency of existing therapeutic anti-cancer regiments and the increase in the multidrug resistance of cancer cells underscore the need to investigate novel anticancer strategies. The induction of apoptosis in tumors by cytotoxic agents produced by pathogenic microorganisms is an example of such an approach. Nevertheless, even the most effective drug should be delivered directly to targeted sites to reduce any negative impact on other cells. Accordingly, the stabilized nanosystem (SNS) for active agent delivery to cancer cells was designed for further application in local anti-tumor therapy. A product of genetically modified Escherichia coli, listeriolysin O (LLO), was immobilized within the polyelectrolyte membrane (poly(ethylenimine)|hyaluronic acid) shells of 'LLO nanocarriers' coupled with the stabilizing element of natural origin. METHODS AND RESULTS: The impact of LLO was evaluated in human leukemia cell lines in vitro. Correspondingly, the influence of the SNS and its elements was assessed in vitro. The viability of targeted cells was evaluated by flow cytometry. Visualization of the system structure was performed using confocal microscopy. The membrane shell applied to the nanocarriers was analyzed using atomic force microscopy and Fourier transform infrared spectroscopy techniques. Furthermore, the presence of a polyelectrolyte layer on the nanocarrier surface and/or in the cell was confirmed by flow cytometry. Finally, the structural integrity of the SNS and the corresponding release of the fluorescent solute listeriolysin were investigated. CONCLUSION: The construction of a stabilized system offers LLO release with a lethal impact on model eukaryotic cells. The applied platform design may be recommended for local anti-tumor treatment purposes.