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1.
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.
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2.
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 [...].
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3.
COVID-19: Role of Nutrition and Supplementation.
Moscatelli, F, Sessa, F, Valenzano, A, Polito, R, Monda, V, Cibelli, G, Villano, I, Pisanelli, D, Perrella, M, Daniele, A, et al
Nutrients. 2021;(3)
Abstract
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.
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4.
Very Low-Calorie Ketogenic Diet Modulates the Autonomic Nervous System Activity through Salivary Amylase in Obese Population Subjects.
Polito, R, Valenzano, A, Scarinci, A, Villano, I, Monda, M, Messina, A, Cibelli, G, Porro, C, La Torre, E, Pisanelli, D, et al
International journal of environmental research and public health. 2021;(16)
Abstract
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.
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5.
The Role of Very Low Calorie Ketogenic Diet in Sympathetic Activation through Cortisol Secretion in Male Obese Population.
Polito, R, Messina, G, Valenzano, A, Scarinci, A, Villano, I, Monda, M, Cibelli, G, Porro, C, Pisanelli, D, Monda, V, et al
Journal of clinical medicine. 2021;(18)
Abstract
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.
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6.
Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work.
Messina, G, Polito, R, Monda, V, Cipolloni, L, Di Nunno, N, Di Mizio, G, Murabito, P, Carotenuto, M, Messina, A, Pisanelli, D, et al
International journal of molecular sciences. 2020;(9)
Abstract
On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5-7%, and the percentage of positive patients admitted to intensive care units being 9-11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.
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7.
Adiponectin and Orexin-A as a Potential Immunity Link Between Adipose Tissue and Central Nervous System.
Polito, R, Nigro, E, Messina, A, Monaco, ML, Monda, V, Scudiero, O, Cibelli, G, Valenzano, A, Picciocchi, E, Zammit, C, et al
Frontiers in physiology. 2018;:982
Abstract
Adipose tissue (AT) is strongly associated with development and progression of immune disorders through adipokines secretion, such as adiponectin. This protein has beneficial energetic properties and is involved in inflammation and immunity processes. Three oligomers of circulating adiponectin with different molecular weight are described: High (HMW), Medium (MMW), and Low (LMW). The HMW is the most biologically active oligomers. On binding to its receptors AdipoR1, AdipoR2, and T-cadherin, adiponectin acts on both innate and acquired immunity. The suppression of NF-κB activation and pro-inflammatory cytokine expression in macrophages is mediated by AdipoR1. AdipoR2 mediates polarization of anti-inflammatory M2 macrophages T-cadherin is essential for the M2 macrophage proliferation. Furthermore, adiponectin reduces T cells responsiveness and B cells lymphopoiesis. The immune system is very sensitive to environmental changes and it is not only interconnected with AT but also with the central nervous system (CNS). Cytokines, which are mediators of the immune system, exercise control over mediators of the CNS. Microglia, which are immunity cells belonging to the macrophage family, are present within the CNS. The nervous system is also involved in immunity through the production of neuropeptides such as orexin-A/hypocretin-1. This neuropeptide is involved in metabolic disorders, inflammation and in the immune response. The relationship between adipokines, immunity, and the nervous system is validated by both the role of orexin-A on fat, food intake, and energy expenditure, as well as by role of adiponectin on the CNS. In this review, we focused on the functions of adiponectin and orexin-A as a potential immunity link between AT and CNS.
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8.
Genetic analysis of Italian patients with congenital tufting enteropathy.
d'Apolito, M, Pisanelli, D, Faletra, F, Giardino, I, Gigante, M, Pettoello-Mantovani, M, Goulet, O, Gasparini, P, Campanozzi, A
World journal of pediatrics : WJP. 2016;(2):219-24
Abstract
BACKGROUND Congenital tufting enteropathy (CTE), an inherited autosomal recessive rare disease, is a severe diarrhea of infancy which is clinically characterized by absence of inflammation and presence of intestinal villous atrophy. Mutations in the EpCAM gene were identified to cause CTE. Recent cases of syndromic tufting enteropathy harboring the SPINT2 (19q13.2) mutation were described. METHODS Four CTE Italian patients were clinically and immunohistochemically characterized. Direct DNA sequencing of EpCAM and SPINT2 genes was performed. RESULTS All patients were of Italian origin. Three different mutations were detected (p.Asp219Metfs*15, Tyr186Phefs*6 and p.Ile146Asn) in the EpCAM gene; one of them is novel (p.Ile146Asn). Two patients (P1 and P2) showed compound heterozygosity revealing two mutations in separate alleles. A third patient (P3) was heterozygous for only one novel EpCAM missense mutation (p.Ile146Asn). In a syndromic patient (P4), no deleterious EpCAM mutation was found. Additional SPINT2 mutational analysis was performed. P4 showed a homozygous SPINT2 mutation (p.Y163C). No SPINT2 mutation was found in P3. CLDN7 was also evaluated as a candidate gene by mutational screening in P3 but no mutation was identified. CONCLUSION This study presented a molecular characterization of CTE Italian patients, and identified three mutations in the EpCAM gene and one in the SPINT2 gene. One of EpCAM mutations was novel, therefore increasing the mutational spectrum of allelic variants of the EpCAM gene. Molecular analysis of the SPINT2 gene also allowed us to identify a SPINT2 substitution mutation (c.488A>G) recently found to be associated with syndromic CTE subjects.
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9.
Stable-isotope dilution LC-ESI-MS/MS techniques for the quantification of total homocysteine in human plasma.
Tomaiuolo, M, Vecchione, G, Margaglione, M, Pisanelli, D, Grandone, E
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2009;(28):3292-9
Abstract
Homocysteine is an endogenous sulphydryl aminoacid irreversibly catabolized by transsulfuration to cysteine or remethylated to methionine. Increased plasma levels of homocysteine are an independent risk factor for atherosclerosis and cardiovascular disease. Accurate and reliable quantification of this amino acid in plasma samples is essential in clinical practice to explore the presence of a hyperhomocysteinemia, for instance after an ischemic event, or to control a possible adjunctive risk factor in patients at higher risk. In this review, LC-ESI-MS/MS methods are discussed and compared with other analytical methods for plasma homocysteine. LC-ESI-MS/MS is a technique combining the physicochemical separation of liquid chromatography with the analysis of mass spectrometry. It is based on stable-isotope dilution and possesses inherent accuracy and precision. Quantitative analysis is achieved by using commercially available homocystine-d(8) as an internal standard. Taking advantage of the high sensitivity and specificity, approaches involving LC-ESI-MS/MS require less laborious sample preparation, no derivatization and produce reliable results.