The Post-COVID-19 cognitive impairment. A modern view of the problem, pathogenesis and treatment

COVID-19 infection is a significant and poorly understood problem of modern world medicine. As the virus spreads, data on the clinical picture of the disease and damage to the nervous system are accumulating. Symptoms such as fatigue, anxiety, depression, sleep disturbances and many other neurological and somatic symptoms are often recorded, persist for a long time even after the acute infectious stage of the disease has been stopped, and make it difficult for the patient to fully recover. These symptoms occur even with a mild disease and persist for many months. One of the most common and disabling symptoms of post-COVID syndrome is cognitive impairment, in the formation of which, in addition to the direct ability of the virus to penetrate the nervous system and pathology of the microvasculature, various pathological mechanisms are involved, including dysregulation of cholinergic transmission. A comprehensive approach is important in the treatment of cognitive impairment; it is advisable to use both medication and non-medication methods. The main approaches to the treatment of secondary cognitive disorders are based on the hypothesis of replenishing the defect in mediator systems, including those associated with the death of cholinergic neurons. With these abnormalities, it is advisable to replenish acetylcholine. Among the precursors of choline, choline alfoscerate occupies a special place due to its proven efficacy in the treatment of neurodegenerative diseases, as well as due to data on its multifactorial action. The article presents the actual literature data on the mechanisms of development and features of the clinical manifestations of post-COVID cognitive impairment, as well as materials of experimental and clinical studies of the drug choline alfoscerate (Gliatilin).

Copper-induced Production of Laccases for Lignin Depolymerisation and Micropollutant Degradation by Laccase-mediator Systems

Contaminants deriving from human activities represent a constantly growing threat to our environment and have a direct impact on plant and animal health. To alleviate this ecological imbalance, biocatalysis offers a green and sustainable alternative to conventional chemical processes. Due to their broad specificity, laccases are enzymes possessing excellent potential for synthetic biotransformations in various fields as well as for the degradation of organic contaminants. Herein, we produced laccases in submerged cultures of P. ostreatus and T. versicolor in three different media. The fungi/medium combination leading to the highest enzymatic activity was malt extract (2%) + yeast extract (3%) + glucose (0.8%). Laccase production was further increased by supplementing this medium with different concentrations of Cu2+, which also provided a better understanding of the induction effect. Additionally, we disclose preliminary results on the interaction of laccases with mediators (ABTS and violuric acid - VA) for two main applications: lignin depolymerisation with guaiacylglycerol-β-guaiacyl ether (GBG) as lignin model and micropollutant degradation with Remazol Brilliant Blue (RBB) as enzymatic bioremediation model. Promising results were achieved using VA to increase depolymerization of GBG dimer and to enhance RBB decolorisation.

Purification and Characterization of a Thermo- and pH-Stable Laccase From the Litter-Decomposing Fungus Gymnopus luxurians and Laccase Mediator Systems for Dye Decolorization

An extracellular laccase (GLL) was purified from fermentation broth of the litter-decomposing fungus Gymnopus luxurians by four chromatography steps, which resulted in a high specific activity of 118.82 U/mg, purification fold of 41.22, and recovery rate of 42.05%. It is a monomeric protein with a molecular weight of 64 kDa and N-terminal amino acid sequence of AIGPV TDLHI, suggesting that GLL is a typical fungal laccase. GLL demonstrated an optimum temperature range of 55°C–65°C and an optimum pH 2.2 toward 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). It displayed considerably high thermostability and pH stability with about 63% activity retained after 24 h at 50°C, and 86% activity retained after 24 h at pH 2.2, respectively. GLL was significantly enhanced in the presence of K+, Na+, and Mg2+ ions. It demonstrated Km of 539 μM and kcat/Km of 140 mM–1⋅s–1 toward ABTS at pH 2.2 and 37°C. Acetosyringone (AS) and syringaldehyde (SA) were the optimal mediators of GLL (0.4 U/ml) for dye decolorization with decolorization rates of about 60%–90% toward 11 of the 14 synthetic dyes. The optimum reaction conditions were determined to be mediator concentration of 0.1 mM, temperature range of 25°C –60°C, and pH 4.0. The purified laccase was the first laccase isolated from genus Gymnopus with high thermostability, pH stability, and effective decolorization toward dyes, suggesting that it has potentials for textile and environmental applications.

Benefits of Ginger and Its Constituent 6-Shogaol in Inhibiting Inflammatory Processes

Ginger (Zingiber officinale Roscoe) is widely used as medicinal plant. According to the Committee on Herbal Medicinal Products (HMPC), dried powdered ginger rhizome can be applied for the prevention of nausea and vomiting in motion sickness (well-established use). Beyond this, a plethora of pre-clinical studies demonstrated anti-cancer, anti-oxidative, or anti-inflammatory actions. 6-Shogaol is formed from 6-gingerol by dehydration and represents one of the main bioactive principles in dried ginger rhizomes. 6-Shogaol is characterized by a Michael acceptor moiety being reactive with nucleophiles. This review intends to compile important findings on the actions of 6-shogaol as an anti-inflammatory compound: in vivo, 6-shogaol inhibited leukocyte infiltration into inflamed tissue accompanied with reduction of edema swelling. In vitro and in vivo, 6-shogaol reduced inflammatory mediator systems such as COX-2 or iNOS, affected NFκB and MAPK signaling, and increased levels of cytoprotective HO-1. Interestingly, certain in vitro studies provided deeper mechanistic insights demonstrating the involvement of PPAR-γ, JNK/Nrf2, p38/HO-1, and NFκB in the anti-inflammatory actions of the compound. Although these studies provide promising evidence that 6-shogaol can be classified as an anti-inflammatory substance, the exact mechanism of action remains to be elucidated. Moreover, conclusive clinical data for anti-inflammatory actions of 6-shogaol are largely lacking.

EXPRESSION FEATURES OF CALCIUM-DEPENDENT RECEPTORS IN THE LUNGS IN EXPERIMENTAL COMPENSATED TRAUMATIC BRAIN INJURY

Purpose of the study: to assess the histochemical features of the localization of calciumdependent receptors of the left lung cell membrane on the 8th day of experimental compensated traumatic brain injury. Materials and methods: The object of the study was male albino outbred rats, three months old, weight 270-300 grams. Created two groups of animals: 1 - control: intact rats; 2- experimental: rats with TBI. To create a head injury, a model of a falling weight was used. Animals were withdrawn from the experiment on the 8th day of head injury. We studied paraffin sections of the left lung of rats. Using the Abcam kits (USA), an immunohistochemical study of the localization of endothelin -1 on sections of the left lung was carried out, the histochemical detection of calcium cations was performed using alizarin red C. Results. The morphofunctional characteristics of the lungs of rats with experimental traumatic brain injury were investigated. It was found that when the brain of experimental animals is damaged, lipid-associated lymphoid clusters appear in the root of the left lung of rats, and the content of endothelin-1 in cardiomyocytes of the pulmonary vein and epithelium of terminal bronchioles increases. A change in the histochemical characteristics of the localization of calcium cations in the cells and tissues of the left lung is revealed, which indicates a tendency towards the development of obstruction of terminal bronchioles and migration of macrophages into the parenchyma of the alveoli. Conclusion: Thus, with TBI, the mechanisms of humoral regulation of the respiratory system function significantly change. Histochemical study of endothelin 1 revealed that the expression in the lung tissues is calcium-dependent. receptor and mediator systems of cell membranes. These data are confirmed by staining the lungs with alizarin red C.

The role of the corticotropin-releasing hormone and its receptors in the regulation of stress response

Stress is an essential part of everyday life. The neuropeptide corticotropin-releasing hormone (CRH, also called CRF and corticoliberin) plays a key role in the integration of neuroendocrine, autonomic and behavioral responses to stress. The activation of the hypothalamic-pituitary-adrenal axis (HPA axis) by neurons of the paraventricular hypothalamic nucleus (PVN), the primary site of synthesis CRH, triggers stress reactions. In addition to the hypothalamus, CRH is widespread in extrahypothalamic brain structures, where it functions as a neuromodulator for coordination and interaction between the humoral and behavioral aspects of a stress response. The axons of neurons expressing CRH are directed to various structures of the brain, where the neuropeptide interacts with specific receptors (CRHR1, CRHR2) and can affect various mediator systems that work together to transmit signals to different brain regions to cause many reactions to stress. Moreover, the effect of stress on brain functions varies from behavioral adaptation to increased survival and increased risk of developing mental disorders. Disturbances of the CRH system regulation are directly related to such disorders: mental pathologies (depression, anxiety, addictions), deviations of neuroendocrinological functions, inflammation, as well as the onset and development of neurodegenerative diseases such as Alzheimer’s disease. In addition, the role of CRH as a regulator of the neurons structure in the areas of the developing and mature brain has been established. To date, studies have been conducted in which CRHR1 is a target for antidepressants, which are, in fact, antagonists of this receptor. In this regard, the study of the participation of the CRH system and its receptors in negative effects on hormone-dependent systems, as well as the possibility of preventing them, is a promising task of modern physiological genetics. In this review, attention will be paid to the role of CRH in the regulation of response to stress, as well as to the involvement of extrahypothalamic CRH in pathophysiology and the correction of mental disorders.

Applicability of Recombinant Laccases From the White-Rot Fungus Obba rivulosa for Mediator-Promoted Oxidation of Biorefinery Lignin at Low pH

Utilization of lignin-rich side streams has been a focus of intensive studies recently. Combining biocatalytic methods with chemical treatments is a promising approach for sustainable modification of lignocellulosic waste streams. Laccases are catalysts in lignin biodegradation with proven applicability in industrial scale. Laccases directly oxidize lignin phenolic components, and their functional range can be expanded using low-molecular-weight compounds as mediators to include non-phenolic lignin structures. In this work, we studied in detail recombinant laccases from the selectively lignin-degrading white-rot fungus Obba rivulosa for their properties and evaluated their potential as industrial biocatalysts for the modification of wood lignin and lignin-like compounds. We screened and optimized various laccase mediator systems (LMSs) using lignin model compounds and applied the optimized reaction conditions to biorefinery-sourced technical lignin. In the presence of both N–OH-type and phenolic mediators, the O. rivulosa laccases were shown to selectively oxidize lignin in acidic reaction conditions, where a cosolvent is needed to enhance lignin solubility. In comparison to catalytic iron(III)–(2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) oxidation systems, the syringyl-type lignin units were preferred in mediated biocatalytic oxidation systems.

Mediated amperometry as a prospective method for the investigation of electroporation

Pulsed electric field effects induced in a membrane, as well as intracellular structures, depend on cell type, field and media parameters. To achieve desired outcomes, membranes should be permeabilized in a controlled manner, and thus efficiency of electroporation should be investigated in advance. Here, we present a framework for using mediated amperometry as a prospective method for the investigation of electroporation and its effects on cellular machinery. Whole-cell sensors with single mediator systems comprised of hydrophilic or lipophilic mediators were successfully employed to investigate membrane permeability as well as cellular responses. Exposure of yeast cells to single electric field pulse (τ = 300 µs, E = 16 kV/cm) resulted in up to tenfold increase of current strength mediated with hydrophilic mediators. Exposure to PEF resulted in decrease of menadione mediated current strength (from 138 ± 15 to 32 ± 15 nA), which could be completely compensated by supplementing electrolyte with NADH.