Nicotinamide Adenine Dinucleotide: The Redox Sensor in Aging-Related Disorders.

Significance: Nicotinamide adenine dinucleotide (NADH) represents the reduced form of NAD+, and together they constitute the two forms of the nicotinamide adenine dinucleotide whose balance is named as the NAD+/NADH ratio. NAD+/NADH ratio is mainly involved in redox reactions since both the molecules are responsible forcarrying electrons to maintain redox homeostasis. Recent Advances: NADH acts as a reducing agent, and one of the most known processes exploiting NADH function is energy metabolism. The two main pathways generating energy and involving NADH are glycolysis and oxidative phosphorylation, occurring in cell cytosol and in the mitochondrial matrix, respectively. Critical Issues: Although NADH is primarily produced through the reduction of NAD+ and consumed by its own oxidation, several are the biosynthetic and consumption pathways, reflecting the NADH role in multiple cellular processes. This review gathers all the main current data referring to NADH incorrelation with metabolic and cellular pathways, such as its coenzyme activity, effect in cell death, and on modulating redox and calcium homeostasis. Future Directions: Gene expression control, as well as the potential impact on neurodegenerative, cardiac disorders and infections, suggest NADH application in clinical settings.Thorough clinical trials and continued investigation into the long-term impacts of NADH are crucial to validate its effectiveness and safety, thereby facilitating its wider acceptance as a therapeutic option in medical practice.

Non-classical HLA class I molecules and their potential role in viral infections.

Human Leukocyte Antigens (HLA) are classified in three different classes I, II and III, and represent the key mediators of immune responses, self-tolerance development and pathogen recognition. Among them, non-classical subtypes (HLA-Ib), e.g. HLA-E and HLA-G, are characterize by tolerogenic functions that are often exploited by viruses to evade the host immune responses. In this perspective, we will review the main current data referred to HLA-G and HLA-E and viral infections, as well as the impact on immune response. Data were selected following eligibility criteria accordingly to the reviewed topic. We used a set of electronic databases (Medline/PubMed, Scopus, Web of Sciences (WOS), Cochrane library) for a systematic search until November 2022 using MeSH keywords/terms (i.e. HLA, HLA-G, HLA-E, viral infection, SARS-CoV-2, etc.…). Recent studies support the involvement of non-classical molecules, such as HLA-E and HLA-G, in the control of viral infection. On one side, viruses exploit HLA-G and HLA-E molecule to control host immune activation. On the other side, the expression of these molecules might control the inflammatory condition generated by viral infections. Hence, this review has the aim to summarize the state of art of literature about the modulation of these non-classical HLA-I molecules, to provide a general overview of the new strategies of viral immune system regulation to counteract immune defenses.

The Evolution of Ketosis: Potential Impact on Clinical Conditions.

Ketone bodies are small compounds derived from fatty acids that behave as an alternative mitochondrial energy source when insulin levels are low, such as during fasting or strenuous exercise. In addition to the metabolic function of ketone bodies, they also have several signaling functions separate from energy production. In this perspective, we review the main current data referring to ketone bodies in correlation with nutrition and metabolic pathways as well as to the signaling functions and the potential impact on clinical conditions. Data were selected following eligibility criteria accordingly to the reviewed topic. We used a set of electronic databases (Medline/PubMed, Scopus, Web of Sciences (WOS), Cochrane Library) for a systematic search until July 2022 using MeSH keywords/terms (i.e., ketone bodies, BHB, acetoacetate, inflammation, antioxidant, etc.). The literature data reported in this review need confirmation with consistent clinical trials that might validate the results obtained in in vitro and in vivo in animal models. However, the data on exogenous ketone consumption and the effect on the ketone bodies' brain uptake and metabolism might spur the research to define the acute and chronic effects of ketone bodies in humans and pursue the possible implication in the prevention and treatment of human diseases. Therefore, additional studies are required to examine the potential systemic and metabolic consequences of ketone bodies.