Potential Protective Effects of Spirulina (Spirulina platensis) against In Vitro Toxicity Induced by Heavy Metals (Cadmium, Mercury, and Lead) on SH-SY5Y Neuroblastoma Cells.

Spirulina, a filamentous microalga, is used all over the world as a nutraceutical dietary supplement. Recent studies have focused on examining its chelating activity and antioxidant properties, especially as a candidate for protection against neurotoxicity caused by heavy metals. The MTT test and LDH assay were used to examine the viability of the SH-SY5Y cells for 24, 48, and 72 h, to Cd, Hg, and Pb, individually or in combination with Spirulina, and the effects of necrotic cell death. In comparison to the control group, the viability of SH-SY5Y cells decreased after 24 h of exposure, with Cd being more toxic than Hg and Pb being less lethal. The effects of heavy metal toxicity on cell survival were ranked in order after 72 h under identical experimental circumstances as follows: Hg, Pb, and Cd. The viability of the cells was then tested after being exposed to Spirulina at doses of 5 at 50 (%v/v) for 24, 48, and 72 h, respectively. SH-SY5Y cells that had been treated with mixtures of heavy metals and Spirulina underwent the same assay. Cell viability is considerably increased by using Spirulina treatments at the prescribed periods and doses. Instead, the same procedure, when applied to SH-SY5Y cells, caused the release of LDH, which is consistent with the reduction in cell viability. We demonstrated for the first time, considering all the available data, that Spirulina 5, 25, and 50 (%v/v) enhanced the number of viable SH-SY5Y cells utilized as a model system for brain cells. Overall, the data from the present study provide a first insight into the promising positive role of Spirulina against the potentially toxic effects of metals.

The Effect of Calcium Ions on hIAPP Channel Activity: Possible Implications in T2DM.

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 ß-cell loss and subsequently in T2DM remain poorly understood. Implicated in the decline in ß-cell functions are aggregates of human islet amyloid polypeptide (hIAPP), a small peptide secreted by ß-cells that shows a strong tendency to self-aggregate into ß-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.

The Role of BIA Analysis in Osteoporosis Risk Development: Hierarchical Clustering Approach.

Osteoporosis is a common musculoskeletal disorder among the elderly and a chronic condition which, like many other chronic conditions, requires long-term clinical management. It is caused by many factors, including lifestyle and obesity. Bioelectrical impedance analysis (BIA) is a method to estimate body composition based on a weak electric current flow through the body. The measured voltage is used to calculate body bioelectrical impedance, divided into resistance and reactance, which can be used to estimate body parameters such as total body water (TBW), fat-free mass (FFM), fat mass (FM), and muscle mass (MM). This study aims to find the tendency of osteoporosis in obese subjects, presenting a method based on hierarchical clustering, which, using BIA parameters, can group patients who show homogeneous characteristics. Grouping similar patients into clusters can be helpful in the field of medicine to identify disorders, pathologies, or more generally, characteristics of significant importance. Another added value of the clustering process is the possibility to define cluster prototypes, i.e., imaginary patients who represent models of "states", which can be used together with clustering results to identify subjects with similar characteristics in a classification context. The results show that hierarchical clustering is a method that can be used to provide the detection of states and, consequently, supply a more personalized medicine approach. In addition, this method allowed us to elect BIA as a potential prognostic and diagnostic instrument in osteoporosis risk development.

High frequencies (HF) repetitive transcranial magnetic stimulation (rTMS) increase motor coordination performances in volleyball players.

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.

Agomelatine: A Potential Multitarget Compound for Neurodevelopmental Disorders.

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.

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.

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.

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

In the original article [...].

Lifestyle in Obese Individuals during the COVID-19 Pandemic.

BACKGROUND: Stay-at-home orders in response to the Coronavirus 2 (SARS-CoV-2) pandemic have forced abrupt changes to daily routines. The aim of this study is to describe the behavior of lifestyles of individuals with obesity on the waiting list for bariatric surgery in the Department of Medical and Surgical Sciences of University of Foggia during the COVID-19 pandemic. MATERIALS AND METHODS: From June 2020 to December 2020 an online survey format was administered to all the patients (n = 52) enrolled for bariatric surgery subjects with obesity, to obtain information about the COVID-19 pandemic's impact on patients with obesity starting 9 March 2020 until 18 May 2020. RESULTS: Our data showed that 58% of patients stated that the pandemic negatively affected their mood, 60% of patients confirmed that they changed their dietary behaviors during the stay-at-home period, as they consumed more unhealthy foods or spent less time cooking home cooked meals. In addition, 71% of patients stated that the closure of the gyms worsened their obesity condition and their mental well-being with an increase of a feeling of anxiety. CONCLUSIONS: Results showed that the COVID-19 pandemic has had a significant impact on health behaviors, including quality of life, mental health physical activity, weight maintenance, and consumption of sweets in obese patients.

Factorial Model of Obese Adolescents: The Role of Body Image Concerns and Selective Depersonalization-A Pilot Study.

BACKGROUND: The relationship binding body weight to psychological well-being is unclear. The present study aims at identifying the contribution, and specificity, of some dimensions (i.e., eating-related symptoms, body image disorders, eating habits, personality traits, and emotional difficulties) characterizing the psychological profile of obese adolescents (749 participants, 325 females; 58.3% normal-weight, 29.9% overweight, and 11.7% obese; mean age = 16.05, SD = 0.82). METHODS: By introducing the scores obtained by standardized self-report tools into a generalized linear model, a factorial reduction design was used to detect the best fitting discriminant functions and the principal components explaining the higher proportion of the variance. RESULTS: We found two discriminant functions correctly classifying 87.1% of normal-weight, 57.2% of overweight, and 68.2% of obese adolescents. Furthermore, two independent factors, explaining 69.68% of the total variance, emerged. CONCLUSIONS: The first factor, "Body Image Concerns", included the drive for thinness, body dissatisfaction, and interpersonal distrust. The second factor, "Selective Depersonalization", included a trend toward depersonalization and dissatisfaction with the torso. The neurophysiological implications of our findings will be discussed.

The Beneficial Effects of Physical Activity in Lung Cancer Prevention and/or Treatment.

Lung cancer is the most lethal cancer: it has a significant incidence and low survival rates. Lifestyle has an important influence on cancer onset and its progression, indeed environmental factors and smoke are involved in cancer establishment, and in lung cancer. Physical activity is a determinant in inhibiting or slowing lung cancer. Certainly, the inflammation is a major factor responsible for lung cancer establishment. In this scenario, regular physical activity can induce anti-inflammatory effects, reducing ROS production and stimulating immune cell system activity. On lung function, physical activity improves lung muscle strength, FEV1 and forced vital capacity. In lung cancer patients, it reduces dyspnea, fatigue and pain. Data in the literature has shown the effects of physical activity both in in vivo and in vitro studies, reporting that its anti-inflammatory action is determinant in the onset of human diseases such as lung cancer. It has a beneficial effect not only in the prevention of lung cancer, but also on treatment and prognosis. For these reasons, it is retained as an adjuvant in lung cancer treatment both for the administration and prognosis of this type of cancer. The purpose of this review is to analyze the role of physical activity in lung cancer and to recommend regular physical activity and lifestyle changes to prevent or treat this pathology.

Heart Rate Variability and Sympathetic Activity Is Modulated by Very Low-Calorie Ketogenic Diet.

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.

Effects of Mixed of a Ketogenic Diet in Overweight and Obese Women with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a commonly occurring endocrine disorder characterized by hirsutism, anovulation, and polycystic ovaries. Often comorbid with insulin resistance, dyslipidemia, and obesity, it also carries significant risk for the development of cardiovascular and metabolic sequelae, including diabetes and metabolic syndrome. The relationship between central obesity and the development of insulin resistance is widely verified. Adipose tissue excess and the coexistent dysregulation of adipocyte functions directly contribute to the pathogenesis of the metabolic complications observed in women with PCOS. In the light of these evidence, the most therapeutic option prescribed to obese women with PCOS, regardless of the phenotype e from the severity of clinical expression, is lifestyle correction by diet and physical activity. The aim of this study is to evaluate the beneficial effects of ketogenic diet in 17 obese women with PCOS. Our results showed that the ketogenic diet inducing therapeutic ketosis, improves the anthropometric and many biochemical parameters such as LH, FSH, SHBG, insulin sensitivity and HOMA index. In addition, it induces a reduction in androgenic production, whereas the contextual reduction of fat mass reduced the acyclic production of estrogens deriving from the aromatization in the adipose tissue of the androgenic excess, with an improvement of the LH/FSH ratio. This is the first study on the effects of the ketogenic diet on PCOS, however, further studies are needed to elucidate the mechanism underlying ketogenic diet effects.

The Role of Very Low Calorie Ketogenic Diet in Sympathetic Activation through Cortisol Secretion in Male Obese Population.

Adipose tissue is considered an endocrine organ, and its excess compromises the immune response and metabolism of hormones and nutrients. Furthermore, the accumulation of visceral fat helps to increase the synthesis of cortisol. The hypothalamus-pituitary-adrenal (HPA) axis is a neuroendocrine system involved in maintaining homeostasis in humans under physiological conditions and stress, and cortisol is the main hormone of the HPA axis. It is known that a stress-induced diet and cortisol reactivity to acute stress factors may be related to dietary behavior. In obesity, to reduce visceral adipose tissue, caloric restriction is a valid strategy. In light of this fact, the aim of this study was to assess the effects of a commercial dietary ketosis program for weight loss on the sympathetic nervous system and HPA axis, through evaluation of salivary cortisol and GSR levels. Thirty obese subjects were recruited and assessed before and after 8 weeks of Very Low Calorie Ketogenic Diet (VLCKD) intervention to evaluate body composition and biochemical parameters. Salivary cortisol levels and GSR significantly decreased after dietary treatment; in addition, body composition and biochemical features were ameliorated. The VLCKD had a short-term positive effect on the SNS and HPA axes regulating salivary cortisol levels. Finally, the effects of the VLCKD on the SNS and HPA axis may lead to more individualized treatment strategies that integrate obesity and stress and support the usefulness of such therapeutic interventions in promoting the reduction of the individual disease burden.

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.

Very Low-Calorie Ketogenic Diet Modulates the Autonomic Nervous System Activity through Salivary Amylase in Obese Population Subjects.

In obesity, to reduce visceral adipose tissue (VAT), caloric restriction is a valid strategy. Salivary amylase is an enzyme that cleaves large starch carbohydrates molecules and its production is modulated by the central nervous system. In addition, heart rate variability (HRV) is simply a measure of the variation in time between each heartbeat. This variation is controlled by the autonomic nervous system. In the light of this evidence, the aim of this study is to characterize the effect of a very low-calorie ketogenic diet (VLCKD) on the autonomic nervous system in obese patients. Twenty subjects affected by obesity were recruited before and after 8 weeks of VLCKD intervention to evaluate salivary amylase by the ELISA test and HRV analysis. These parameters significantly increased after dietary treatment, and positively correlate to each other. VLCKD exerts a positive effect on salivary amylase and HRV, ameliorating body composition and biochemical features. In brief, this dietary intervention improves the autonomic nervous system activity. This is the first study about the effects of VLCKD upon the autonomic nervous system, but further studies are needed to elucidate the mechanism undergone VLCKD effects.

COVID-19: Role of Nutrition and Supplementation.

At the end of 2019, a new coronavirus (COVID-19) appeared on the world scene, which mainly affects the respiratory system, causing pneumonia and multi-organ failure, and, although it starts with common symptoms such as shortness of breath and fever, in about 2-3% of cases it leads to death. Unfortunately, to date, no specific treatments have been found for the cure of this virus and, therefore, it is advisable to implement all possible strategies in order to prevent infection. In this context, it is important to better define the role of all behaviors, in particular nutrition, in order to establish whether these can both prevent infection and improve the outcome of the disease in patients with COVID-19. In the literature, it is widely shown that states of malnutrition, overweight, and obesity negatively affect the immune system, leading to viral infections, and several studies have shown that nutritional interventions can act as immunostimulators, helping to prevent viral infections. Even if several measures, such as the assumption of a specific diet regimen, the use of dietary supplements, and other similar interventions, are promising for the prevention, management, and recovery of COVID-19 patients, it is important to highlight that strong data from randomized clinical trials are needed to support any such assumption. Considering this particular scenario, we present a literature review addressing several important aspects related to diet and SARS-CoV-2 infection, in order to highlight the importance of diet and supplementation in prevention and management of, as well as recovery from COVID-19.

Transcranial Magnetic Stimulation as a Tool to Investigate Motor Cortex Excitability in Sport.

Transcranial magnetic stimulation, since its introduction in 1985, has brought important innovations to the study of cortical excitability as it is a non-invasive method and, therefore, can be used both in healthy and sick subjects. Since the introduction of this cortical stimulation technique, it has been possible to deepen the neurophysiological aspects of motor activation and control. In this narrative review, we want to provide a brief overview regarding TMS as a tool to investigate changes in cortex excitability in athletes and highlight how this tool can be used to investigate the acute and chronic responses of the motor cortex in sport science. The parameters that could be used for the evaluation of cortical excitability and the relative relationship with motor coordination and muscle fatigue, will be also analyzed. Repetitive physical training is generally considered as a principal strategy for acquiring a motor skill, and this process can elicit cortical motor representational changes referred to as use-dependent plasticity. In training settings, physical practice combined with the observation of target movements can enhance cortical excitability and facilitate the process of learning. The data to date suggest that TMS is a valid technique to investigate the changes in motor cortex excitability in trained and untrained subjects. Recently, interest in the possible ergogenic effect of non-invasive brain stimulation in sport is growing and therefore in the future it could be useful to conduct new experiments to evaluate the impact on learning and motor performance of these techniques.

Effects of a Plastic-Free Lifestyle on Urinary Bisphenol A Levels in School-Aged Children of Southern Italy: A Pilot Study.

Bisphenol A (BPA) is an endocrine disruptor (ED) frequently used in food packaging. BPA is used as a monomer in the manufacture of some food packaging. This study aimed to evaluate the urinary BPA concentration in an Italian pediatric cohort, testing the levels of this ED over a period of 6 months, evaluating the effects of a diet regimen with a reduction of Plastic Food Packaging (PFP). One hundred thirty Italian children were enrolled and divided into two groups "School Canteen" and "No School Canteen." The first group consumed one meal at school using a plastic-free service for 5 days/weeks, while the other group did not modify their normal meal-time habits. The BPA levels were tested in urine samples at three time points: T0, is the time before the application of the plastic-free regimen diet; T3, 3 months later; and T6, 6 months later. A reduction of urine BPA levels was detected in the "School Canteen" group. In particular, the reduction was significant analyzing both the intra (among the three testing times) group and inter (between "School Canteen" and "No School Canteen") group variability. Our results show the effects of a diet regimen with a reduction of PFP, demonstrating a connection between urinary BPA levels and food packaging.