-
1.
α-Tocopherol Protects Lipopolysaccharide-Activated BV2 Microglia.
La Torre, ME, Cianciulli, A, Monda, V, Monda, M, Filannino, FM, Antonucci, L, Valenzano, A, Cibelli, G, Porro, C, Messina, G, et al
Molecules (Basel, Switzerland). 2023;(8)
Abstract
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.
-
2.
The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line.
Polito, R, La Torre, ME, Moscatelli, F, Cibelli, G, Valenzano, A, Panaro, MA, Monda, M, Messina, A, Monda, V, Pisanelli, D, et al
International journal of molecular sciences. 2023;(4)
Abstract
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.
-
3.
High frequencies (HF) repetitive transcranial magnetic stimulation (rTMS) increase motor coordination performances in volleyball players.
Moscatelli, F, Toto, GA, Valenzano, A, Cibelli, G, Monda, V, Limone, P, Mancini, N, Messina, A, Marsala, G, Messina, G, et al
BMC neuroscience. 2023;(1):30
Abstract
INTRODUCTION It is widely demonstrated that high frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has facilitative effects and is therefore capable to inducing changes in motor responses. One of the most investigated areas is the dorsolateral prefrontal cortex (DLPFC) as it plays a special executive attention role in actively preserving access to stimulus representations and objectives in environments with plenty of distraction such as those of team sports. Volleyball is a team sport in which the attention and coordination components are essential for achieving performance. Thus, the aim of this study was to investigate if HF rTMS at DLPFC in volleyball players can improve homolateral motor coordination and cortical excitability. RESULTS This study was a double-blinded (participant and evaluator) matched-pair experimental design. Twenty right-handed female volleyball players were recruited for the study and were randomly assigned either the active rTMS (n = 10) or the sham stimulation group (n = 10). The stimulation was performed in one session with 10 Hz, 80% of the resting motor threshold (RMT) of the right first dorsal interosseous muscle, 5 s of stimulation, and 15 s of rest, for a total of 1500 pulses. Before and after stimulation, the coordination and the cortical excitability were evaluated. The significant finding of this paper was that HF-rTMS of the DLPFC improved performance in terms of the homolateral interlimb coordination, with a significantly decreased in resting motor threshold and MEP latency of the ipsilateral motor cortex. It seem that HF-rTMS could increase coordination performances when the velocity of the execution is higher (120 bpm and 180 bpm). CONCLUSION Moreover, in active rTMS group significant differences emerged after stimulation in RMT and in MEP latency, while no differences emerged after stimulation in MEP amplitude. In conclusion we believe that these results may be of great interest to the scientific community and may also have practical implications in the future.
-
4.
Agomelatine: A Potential Multitarget Compound for Neurodevelopmental Disorders.
Savino, R, Polito, AN, Marsala, G, Ventriglio, A, Di Salvatore, M, De Stefano, MI, Valenzano, A, Marinaccio, L, Bellomo, A, Cibelli, G, et al
Brain sciences. 2023;(5)
Abstract
Agomelatine (AGM) is one of the latest atypical antidepressants, prescribed exclusively for the treatment of depression in adults. AGM belongs to the pharmaceutical class of melatonin agonist and selective serotonin antagonist ("MASS"), as it acts both as a selective agonist of melatonin receptors MT1 and MT2, and as a selective antagonist of 5-HT2C/5-HT2B receptors. AGM is involved in the resynchronization of interrupted circadian rhythms, with beneficial effects on sleep patterns, while antagonism on serotonin receptors increases the availability of norepinephrine and dopamine in the prefrontal cortex, with an antidepressant and nootropic effect. The use of AGM in the pediatric population is limited by the scarcity of data. In addition, few studies and case reports have been published on the use of AGM in patients with attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Considering this evidence, the purpose of this review is to report the potential role of AGM in neurological developmental disorders. AGM would increase the expression of the cytoskeleton-associated protein (ARC) in the prefrontal cortex, with optimization of learning, long-term memory consolidation, and improved survival of neurons. Another important feature of AGM is the ability to modulate glutamatergic neurotransmission in regions associated with mood and cognition. With its synergistic activity a melatoninergic agonist and an antagonist of 5-HT2C, AGM acts as an antidepressant, psychostimulant, and promoter of neuronal plasticity, regulating cognitive symptoms, resynchronizing circadian rhythms in patients with autism, ADHD, anxiety, and depression. Given its good tolerability and good compliance, it could potentially be administered to adolescents and children.
-
5.
Interaction of Quercetin, Cyanidin, and Their O-Glucosides with Planar Lipid Models: Implications for Their Biological Effects.
Meleleo, D, Avato, P, Conforti, F, Argentieri, MP, Messina, G, Cibelli, G, Mallamaci, R
Membranes. 2023;(6)
Abstract
Flavonoids are specialized metabolites produced by plants, as free aglycones or as glycosylated derivatives, which are particularly endowed with a variety of beneficial health properties. The antioxidant, anti-inflammatory, antimicrobial, anticancer, antifungal, antiviral, anti-Alzheimer's, anti-obesity, antidiabetic, and antihypertensive effects of flavonoids are now known. These bioactive phytochemicals have been shown to act on different molecular targets in cells including the plasma membrane. Due to their polyhydroxylated structure, lipophilicity, and planar conformation, they can either bind at the bilayer interface or interact with the hydrophobic fatty acid tails of the membrane. The interaction of quercetin, cyanidin, and their O-glucosides with planar lipid membranes (PLMs) similar in composition to those of the intestine was monitored using an electrophysiological approach. The obtained results show that the tested flavonoids interact with PLM and form conductive units. The modality of interaction with the lipids of the bilayer and the alteration of the biophysical parameters of PLMs induced by the tested substances provided information on their location in the membrane, helping to elucidate the mechanism of action which underlies some pharmacological properties of flavonoids. To our knowledge, the interaction of quercetin, cyanidin, and their O-glucosides with PLM surrogates of the intestinal membrane has never been previously monitored.
-
6.
The Effect of Calcium Ions on hIAPP Channel Activity: Possible Implications in T2DM.
Meleleo, D, Cibelli, G, Valenzano, A, Mastrodonato, M, Mallamaci, R
Membranes. 2023;(11)
Abstract
The calcium ion (Ca2+) has been linked to type 2 diabetes mellitus (T2DM), although the role of Ca2+ in this disorder is the subject of intense investigation. Serum Ca2+ dyshomeostasis is associated with the development of insulin resistance, reduced insulin sensitivity, and impaired glucose tolerance. However, the molecular mechanisms involving Ca2+ ions in pancreatic β-cell loss and subsequently in T2DM remain poorly understood. Implicated in the decline in β-cell functions are aggregates of human islet amyloid polypeptide (hIAPP), a small peptide secreted by β-cells that shows a strong tendency to self-aggregate into β-sheet-rich aggregates that evolve toward the formation of amyloid deposits and mature fibrils. The soluble oligomers of hIAPP can permeabilize the cell membrane by interacting with bilayer lipids. Our study aimed to evaluate the effect of Ca2+ on the ability of the peptide to incorporate and form ion channels in zwitterionic planar lipid membranes (PLMs) composed of palmitoyl-oleoyl-phosphatidylcholine (POPC) and on the aggregation process of hIAPP molecules in solution. Our results may help to clarify the link between Ca2+ ions, hIAPP peptide, and consequently the pathophysiology of T2DM.
-
7.
Heart Rate Variability and Sympathetic Activity Is Modulated by Very Low-Calorie Ketogenic Diet.
Polito, R, Valenzano, A, Monda, V, Cibelli, G, Monda, M, Messina, G, Villano, I, Messina, A
International journal of environmental research and public health. 2022;(4)
Abstract
Obesity is characterized by an energy imbalance and by the accumulation of visceral adipose tissue. The energy balance is controlled by a complex set of balanced physiological systems that provide hunger and satiety signals to the brain and regulate the body's ability to consume energy. The central nervous system controls the metabolic state, influencing the activity of other systems and receiving information from them. Heart rate variability (HRV) is the natural variability of the heart rate in response to several factors. HRV is related to the interaction between the SNS and the parasympathetic. In the light of this evidence, the aim of this study is to investigate the possible effects of the two different dietary regimens such as very low-calorie ketogenic diet (VLCKD) vs. low caloric diet (LCD), on the functions of the nervous system, with particular attention to the autonomous control of heart rate variability (HRV). A total of 26 obese subjects underwent diet therapy in order to reduce body weight; they were also randomly divided into two groups: the VLCKD group and the LCD group. Our results showed that in both groups, there is a reduction in heart rate as an indicator of sympathetic activity; we found a statistically significant variation only in the VLCKD group. Therefore, this study supports the notion that the sympathovagal balance can be modulated by a specific diet, but further studies are needed to clarify the molecular pathway undergoing this modulation.
-
8.
The Potential Role of Nutrition in Lung Cancer Establishment and Progression.
Porro, C, La Torre, ME, Tartaglia, N, Benameur, T, Santini, M, Ambrosi, A, Messina, G, Cibelli, G, Fiorelli, A, Polito, R, et al
Life (Basel, Switzerland). 2022;(2)
Abstract
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.
-
9.
Italian Ketogenic Mediterranean Diet in Overweight and Obese Patients with Prediabetes or Type 2 Diabetes.
Ivan, CR, Messina, A, Cibelli, G, Messina, G, Polito, R, Losavio, F, Torre, E, Monda, V, Monda, M, Quiete, S, et al
Nutrients. 2022;(20)
Abstract
Obesity is a multifactorial disease strongly associated with insulin resistance and/or type 2 diabetes mellitus. Correct nutrition represents a valid strategy to fight these dysmetabolic pathologies responsible for numerous diseases, including inflammatory and cardiovascular ones. Medical nutrition therapy, including a Mediterranean diet (MD) and a very low-calorie ketogenic diet (VLKCD), is the first-line treatment for prediabetes/diabetes and overweight/obesity. Eighty patients (forty women and forty men) affected by overweight/obesity and type 2 diabetes mellitus or impaired glucose tolerance or impaired fasting glucose (51 (ys) ± 1.75; BMI (kg/m2) 33.08 ± 1.93; HA1c (%): 6.8% ± 0.25) were enrolled at the University Service of Diet Therapy, Diabetology and Metabolic Diseases, Policlinico Riuniti Hospital of Foggia, and subjected to a very-low-calorie Mediterranean diet and a very-low-calorie ketogenic Mediterranean diet for thirty days. Both diets result in a marked decrease in body weight (kg) and BMI (kg/m2). At the same time, only the very-low-calories ketogenic Mediterranean diet reduced waist and hip circumferences. Both diets helped reduce fat mass, but a major loss was achieved in a very low-calorie ketogenic Mediterranean diet. Among gluco-metabolic parameters, only the very-low-calorie ketogenic Mediterranean diet group showed a significant decrease in fasting blood glucose and HbA1c, insulin, C-peptide total cholesterol, LDL, and triglycerides. The results of our study seem to show that the very-low-calorie ketogenic Mediterranean diet is a good strategy to improve rapidly metabolic, anthropometric, and body composition parameters in patients with prediabetes or diabetes and overweight/obesity.
-
10.
Correction: La Torre et al. Role of Vitamin E and the Orexin System in Neuroprotection. Brain Sci. 2021, 11, 1098.
La Torre, ME, Villano, I, Monda, M, Messina, A, Cibelli, G, Valenzano, A, Pisanelli, D, Panaro, MA, Tartaglia, N, Ambrosi, A, et al
Brain sciences. 2022;(12)
Abstract
In the original article [...].