The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line.

The ketogenic diet (KD), a diet high in fat and protein but low in carbohydrates, is gaining much interest due to its positive effects, especially in neurodegenerative diseases. Beta-hydroxybutyrate (BHB), the major ketone body produced during the carbohydrate deprivation that occurs in KD, is assumed to have neuroprotective effects, although the molecular mechanisms responsible for these effects are still unclear. Microglial cell activation plays a key role in the development of neurodegenerative diseases, resulting in the production of several proinflammatory secondary metabolites. The following study aimed to investigate the mechanisms by which BHB determines the activation processes of BV2 microglial cells, such as polarization, cell migration and expression of pro- and anti-inflammatory cytokines, in the absence or in the presence of lipopolysaccharide (LPS) as a proinflammatory stimulus. The results showed that BHB has a neuroprotective effect in BV2 cells, inducing both microglial polarization towards an M2 anti-inflammatory phenotype and reducing migratory capacity following LPS stimulation. Furthermore, BHB significantly reduced expression levels of the proinflammatory cytokine IL-17 and increased levels of the anti-inflammatory cytokine IL-10. From this study, it can be concluded that BHB, and consequently the KD, has a fundamental role in neuroprotection and prevention in neurodegenerative diseases, presenting new therapeutic targets.

α-Tocopherol Protects Lipopolysaccharide-Activated BV2 Microglia.

Microglia, the resident macrophage-like population in the central nervous system, play a crucial role in the pathogenesis of many neurodegenerative disorders by triggering an inflammatory response that leads to neuronal death. Neuroprotective compounds to treat or prevent neurodegenerative diseases are a new field of study in modern medicine. Microglia are activated in response to inflammatory stimuli. The pathogenesis of various neurodegenerative diseases is closely related to the constant activation of microglia due to their fundamental role as a mediator of inflammation in the brain environment. α-Tocopherol, also known as vitamin E, is reported to possess potent neuroprotective effects. The goal of this study was to investigate the biological effects of vitamin E on BV2 microglial cells, as a possible neuroprotective and anti-inflammatory agent, following stimulation with lipopolysaccharide (LPS). The results showed that the pre-incubation of microglia with α-tocopherol can guarantee neuroprotective effects during microglial activation induced by LPS. α-Tocopherol preserved the branched morphology typical of microglia in a physiological state. It also reduced the migratory capacity; the production of pro-inflammatory and anti-inflammatory cytokines such as TNF-α and IL-10; and the activation of receptors such as TRL4 and CD40, which modulate the PI3K-Akt signaling pathway. The results of this study require further insights and research, but they present new scenarios for the application of vitamin E as an antioxidant for the purpose of greater neuroprotection in vivo for the prevention of possible neurodegenerative diseases.

Curcumin as Prospective Anti-Aging Natural Compound: Focus on Brain.

The nutrients and their potential benefits are a new field of study in modern medicine for their positive impact on health. Curcumin, the yellow polyphenolic compound extracted from Curcuma longa species, is widely used in traditional Ayurvedic medicine to prevent and contrast many diseases, considering its antioxidant, immunomodulatory, anti-inflammatory, anti-microbial, cardio-protective, nephron-protective, hepato-protective, anti-neoplastic, and anti-rheumatic proprieties. In recent years, the investigations of curcumin have been focused on its application to aging and age-associated diseases. Aging is a physiological process in which there is a decreasing of cellular function due to internal or external stimuli. Oxidative stress is one of the most important causes of aging and age-related diseases. Moreover, many age-related disorders such as cancer, neuroinflammation, and infections are due to a low-grade chronic systemic inflammation. Curcumin acting on different proteins is able to contrast both oxidative stress than inflammation. In the brain, curcumin is able to modulate inflammation induced by microglia. Finally in brain tumors curcumin is able to reduce tumor growth by inhibition of telomerase activity. This review emphasizes the anti-aging role of curcumin focusing on its mechanism to counteract aging in the brain. Moreover, new formulations to increase the bioavailability of curcumin are discussed.

Exploring the ketogenic diet's potential in reducing neuroinflammation and modulating immune responses.

The ketogenic diet (KD) is marked by a substantial decrease in carbohydrate intake and an elevated consumption of fats and proteins, leading to a metabolic state referred to as "ketosis," where fats become the primary source of energy. Recent research has underscored the potential advantages of the KD in mitigating the risk of various illnesses, including type 2 diabetes, hyperlipidemia, heart disease, and cancer. The macronutrient distribution in the KD typically entails high lipid intake, moderate protein consumption, and low carbohydrate intake. Restricting carbohydrates to below 50 g/day induces a catabolic state, prompting metabolic alterations such as gluconeogenesis and ketogenesis. Ketogenesis diminishes fat and glucose accumulation as energy reserves, stimulating the production of fatty acids. Neurodegenerative diseases, encompassing Alzheimer's disease, Parkinson's disease are hallmarked by persistent neuroinflammation. Evolving evidence indicates that immune activation and neuroinflammation play a significant role in the pathogenesis of these diseases. The protective effects of the KD are linked to the generation of ketone bodies (KB), which play a pivotal role in this dietary protocol. Considering these findings, this narrative review seeks to delve into the potential effects of the KD in neuroinflammation by modulating the immune response. Grasping the immunomodulatory effects of the KD on the central nervous system could offer valuable insights into innovative therapeutic approaches for these incapacitating conditions.

The Potential Role of Nutrition in Overtraining Syndrome: A Narrative Review.

Competition between athletes and an increase in sporting knowledge have greatly influenced training methods while increasing the number of them more and more. As a result, the number of athletes who have increased the number and intensity of their workouts while decreasing recovery times is rising. Positive overtraining could be considered a natural and fundamental process when the result is adaptation and improved performance; however, in the absence of adequate recovery, negative overtraining could occur, causing fatigue, maladaptation, and inertia. One of the earliest forms of fatigue is overreaching. It is considered to be an accumulation of training that leads to reduced sports performance, requiring days or weeks to recover. Overreaching, if followed by adequate recovery, can lead to an increase in athletic performance. Nonetheless, if overreaching becomes extreme, combined with additional stressors, it could lead to overtraining syndrome (OTS). OTS, caused by systemic inflammation, leads to central nervous system (CNS) effects, including depressed mood, further inflammation, central fatigue, and ultimately neurohormonal changes. There are therefore not only physiological, biochemical, and immunological but also psychological symptoms or markers that must be considered, independently or together, being intrinsically linked with overtraining, to fully understand OTS. However, to date, there are very few published studies that have analyzed how nutrition in its specific food aspects, if compromised during OTS, can be both etiology and consequence of the syndrome. To date, OTS has not yet been fully studied, and the topic needs further research. The purpose of this narrative review is therefore to study how a correct diet and nutrition can influence OTS in all its aspects, from prevention to treatment.

Extracellular Vesicles Cargo in Modulating Microglia Functional Responses.

Extracellular vesicles (EVs) represent a heterogeneous group of membranous structures derived from cells that are released by all cell types, including brain cells. EVs are now thought to be an additional mechanism of intercellular communication. Both under normal circumstances and following the addition of proinflammatory stimuli, microglia release EVs, but the contents of these two types of EVs are different. Microglia are considered the brain-resident immune cells that are involved in immune surveillance and inflammatory responses in the central nervous system. In this research, we have analyzed the effects of EVs isolated from microglia in response to LPS (Lipopolysaccharide) on microglia activation. The EVs produced as result of LPS stimulation, knows as EVs-LPS, were then used as stimuli on microglia BV2 resting cells in order to investigate their ability to induce microglia to polarize towards an inflammatory state. After EVs-LPS stimulation, we analyzed the change to BV2 cells' morphology, proliferation, and migration, and investigated the expression and the release of pro-inflammatory cytokines. The encouraging findings of this study showed that EVs-LPS can activate microglia in a manner similar to that of LPS alone and that EVs derived from control cells cannot polarize microglia towards a pro-inflammatory state. This study has confirmed the critical role of EVs in communication and shown how EVs produced in an inflammatory environment can exacerbate the inflammatory process by activating microglia, which may have an impact on all brain cells.

Correction: La Torre et al. Role of Vitamin E and the Orexin System in Neuroprotection. Brain Sci. 2021, 11, 1098.

In the original article [...].

The Potential Role of Nutrition in Lung Cancer Establishment and Progression.

Lung cancer is a devastating disease with a high incidence and low survival rates, so recent studies have focused on analyzing the risk factors that might prevent this disease from developing or have protective/therapeutic effects. Nutrition is an important key factor in the prevention and treatment of lung cancer. Various factors appear to be involved in the development of the latter, such as cigarette smoking or certain external environmental factors. The increase in oxidative stress is therefore an integral part of the carcinogenesis process. The biological role of bioactive factors derived from adipose tissue, mainly adipokines, is implicated in various cancers, and an increasing body of evidence has shown that certain adipocytokines contribute to the development, progression and prognosis of lung cancer. Not all adipokines stimulate tumor growth; in fact, adiponectin inhibits carcinogenesis by regulating both cell growth and the levels of inflammatory cytokines. Adiponectin expression is deregulated in several cancer types. Many nutritional factors have been shown to increase adiponectin levels and therefore could be used as a new therapeutic strategy for combating lung cancer. In addition, foods with antioxidant and anti-inflammatory properties play a key role in the prevention of many human diseases, including lung cancer. The purpose of this review is to analyze the role of diet in lung cancer in order to recommend dietary habit and lifestyle changes to prevent or treat this pathology.

Role of Vitamin E and the Orexin System in Neuroprotection.

Microglia are the first line of defense at the level of the central nervous system (CNS). Phenotypic change in microglia can be regulated by various factors, including the orexin system. Neuroinflammation is an inflammatory process mediated by cytokines, by the lack of interaction between neurotransmitters and their specific receptors, caused by systemic tissue damage or, more often, associated with direct damage to the CNS. Chronic activation of microglia could lead to long-term neurodegenerative diseases. This review aims to explore how tocopherol (vitamin E) and the orexin system may play a role in the prevention and treatment of microglia inflammation and, consequently, in neurodegenerative diseases thanks to its antioxidant properties. The results of animal and in vitro studies provide evidence to support the use of tocopherol for a reduction in microglia inflammation as well as a greater activation of the orexinergic system. Although there is much in vivo and in vitro evidence of vitamin E antioxidant and protective abilities, there are still conflicting results for its use as a treatment for neurodegenerative diseases that speculate that vitamin E, under certain conditions or genetic predispositions, can be pro-oxidant and harmful.