An Update on Glutathione's Biosynthesis, Metabolism, Functions, and Medicinal Purposes

Glutathione (GSH) has been the focus of increased scientific interest in the last decades. It plays a crucial role in all major physiological processes by supplying antioxidant defenses through participating in cellular redox reactions in the human body and other living organisms. GSH also participates in detoxifying xenobiotics, protecting protein thiols from crosslinking and oxidation, regulating the cell cycle, storing cysteine, etc. The significant role of GSH in the most important physiological processes has been highlighted, such as maintaining the redox balance and reducing oxidative stress due to its ability to inactivate the reactive oxygen, nitrogen, and sulfur species. It can also enhance metabolic detoxification and regulate the function of the immune system. All of these characteristics make it a universal biomarker since its proper balance is essential for improving health and treating some age-related disorders. This review presents a current concept of the synthesis and metabolism of GSH; its main functions in a living organism, and as a precursor and cofactor; data on the use of GSH for medicinal purposes in the prevention and treatment of some diseases, as well as a nutritional strategy to maintain a normal pool of GSH in the body. The data were gathered by searching relevant information in multiple databases, such as PubMed, Scopus, ScienceDirect, and Google Scholar.

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The Possible Roles of α-alanine and L-carnosine in Anti-aging

alanine (BA), being a non-proteinogenic amino acid, is an important constituent of L-carnosine (LC), which is necessary for maintaining the muscle buffering capacity and preventing a loss of muscle mass associated with aging effects. BA is also very important for normal human metabolism due to the formation of a part of pantothenate, which is incorporated into coenzyme A. BA is synthesized in the liver, and its combination with histidine results in the formation of LC, which accumulates in the muscles and brain tissues and has a well-defined physiological role as a good buffer for the pH range of muscles that caused its rapidly increased popularity as ergogenic support to sports performance. The main antioxidant mechanisms of LC include reactive oxygen species (ROS) scavenging and chelation of metal ions. With age, the buffering capacity of muscles also declines due to reduced concentration of LC and sarcopenia. Moreover, LC acts as an antiglycation agent, ultimately reducing the development of degenerative diseases. LC has an anti-inflammatory effect in autoimmune diseases such as osteoarthritis. As histidine is always present in the human body in higher concentrations than BA, humans have to get BA from dietary sources to support the required amount of this critical constituent to supply the necessary amount of LC synthesis. Also, BA has other beneficial effects, such as preventing skin aging and intestinal damage, improving the stress-- fighting capability of the muscle cells, and managing an age-related decline in memory and learning. In this review, the results of a detailed analysis of the role and various beneficial properties of BA and LC from the anti-aging perspective.

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Alpha-lipoic Acid: An Antioxidant with Anti-Aging Properties for Disease Therapy

The anti-aging effects of alpha-lipoic acid (αLA), a natural antioxidant synthesized in human tissues, have attracted a growing interest in recent years. αLA is a short- -chain sulfur-containing fatty acid occurring in the mitochondria of all kinds of eukaryotic cells. Both the oxidized disulfide of αLA and its reduced form (dihydrolipoic acid, DHLA) exhibit prominent antioxidant function. The amount of αLA inside the human body gradually decreases with age resulting in various health disorders. Its lack can be compensated by supplying from external sources such as dietary supplements or medicinal dosage forms. The primary objectives of this study were the analysis of updated information on the latest two-decade research regarding the use of αLA from an anti-aging perspective. The information was collected from PubMed, Wiley Online Library, Scopus, ScienceDirect, SpringerLink, Google Scholar, and clinicaltrials.gov. Numerous in silico, in vitro, in vivo, and clinical studies revealed that αLA shows a protective role in biological systems by direct or indirect reactive oxygen/nitrogen species quenching. αLA demonstrated beneficial properties in the prevention and treatment of many age-related disorders such as neurodegeneration, metabolic disorders, different cancers, nephropathy, infertility, and skin senescence. Its preventive effects in case of Alzheimer's and Parkinson's diseases are of particular interest. Further mechanistic and clinical studies are highly recommended to evaluate the wide spectrum of αLA therapeutic potential that could optimize its dietary intake for prevention and alleviation disorders related to aging.

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Neutrophil Depletion Changes the N-Glycosylation Pattern of IgG in Experimental Murine Sepsis

Sepsis is a life-threatening condition with a rising disease burden worldwide. It is a multifactorial disease and is defined as a dysregulated host response to infection. Neutrophils have been shown to be involved in the pathogenesis of sepsis by exacerbating inflammation. However, the exact effector mechanism of action still remains a mystery. Changes in the glycosylation pattern of the immunoglobulin G (IgG) Fc region are described for several diseases including meningococcal sepsis. In this study, we investigated the possible contribution of neutrophils and neutrophil implication, potentially related to degranulation or neutrophil extracellular trap (NET) formation in changing the IgG Fc N-glycosylation pattern in a murine sepsis model. We have measured the serum level of cytokines/chemokines and immunoglobulins, the serum activity of neutrophil elastase (NE), and analyzed the IgG Fc glycosylation pattern by Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (LC-ESI-MS) and Lectin enzyme-linked immunosorbent assay (ELISA). We observed an increased activity of NE- and neutrophil-associated cytokines such as keratinocyte chemoattractant (KC) with the development of sepsis. Regarding the IgG Fc N-glycosylation, we observed an increase in fucosylation and α1,3-galactosylation and a decrease for sialyation. Interestingly, these changes were not uniform for all IgG subclasses. After depletion of neutrophils, we saw a change in the exposure of fucose and α2,6-linked sialic acid during the time course of our experimental sepsis model. In conclusion, neutrophils can influence changes in the IgG glycosylation pattern in experimental sepsis.
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Ethical and social incentives for the transformation of the business model of enterprise management in conditions of sustainable development

Abstract:

Purpose. Analysis of the theoretical-methodical and practical principles of ensuring the socio-ethical values of the functioning of Ukrainian companies and the development of potential scenarios for the development of events in the conditions of the implementation of corporate social responsibility (CSR).

Methodology. The research methodology includes the following methods:

- dialectical and hermeneutic method – to identify changes and connections in the socially oriented approach of companies and their consequences;- scenario modeling – to determine the consequences of decisions made by company management regarding changes in social and ethical values in the short- and long-term;

- system analysis – to analyze the interrelationships of changes in the socio-ethical values of business and their consequences for the company’s management and other interested parties;

- PESTLE analysis – to stratify international documents in the field of CSR and socio-ethical and other factors affecting the functioning of companies;

- grouping – to classify companies according to the observance of social and ethical principles of work within the framework of CSR.


Findings. It is noted that in terms of sustainable development, company management should pay attention to the issues of CSR, including social and ethical values. In the international legal field, documents have been developed under the auspices of the UN regarding CSR, some of which have been ratified in Ukraine. This group of documents is optional for use by company management, but affects access to international capital markets, rating and reporting transparency. Companies in the energy sector and metal rolling implement the principles, standards and norms of social and ethical business into their practice, ensuring a positive reputation and image, supporting social infrastructure and welfare of employees and the general population, etc.


Originality. The conducted analysis made it possible for the first time to stratify international documents on CSR and factors related to social and ethical values of companies using PESTLE analysis. Potential scenarios for the development of companies in the short- and long-term are developed and described in terms of the implementation of social and ethical incentives within the framework of CSR business.


Practical value. The given stratification of international documents for socio-ethical business conduct can be useful for the scientific community and in educational institutions. The developed scenarios of the functioning of companies in the conditions of the implementation of social and ethical incentives within the framework of CSR business will be useful to company managers, specialists and scientists investigating CSR issues.

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