Food supplements to complement brain functioning. The benefits of a combination of magnesium, folic acid, omega-3 fatty acids and vitamin E

Diet and nutrition play a fundamental role not only in human body composition and in physiology, but have also relevant effects on mood, mental well-being and cognitive performance. In particular, the preservation of mental well-being through a healthy lifestyle, including a well-balanced diet and, in case, through the intake of specific food supplements, is of particular relevance in the perspective of global human ageing, as the brain is affected significantly by a persistent presence of stress factors. Due to the increasing burden of mental and neurological disorders and to the universality of food as a modifiable risk factor, even limited improvements in nutritional habits may translate to a considerable rise of well-being and mental health in the global population. Moreover, the use of targeted, well-balanced food supplements aiming to support the mental health and well-being will probably represent a relevant tool in future decades, together with an increased awareness of the importance of nutrition, also considering the COVID-19 pandemic and the related stressful events and limitations we are still experiencing at global level. The aim of this review is to summarize the experimental and clinical data reported in the literature concerning the beneficial effects of a subset of micro- and macronutrients contained both in food and in supplements, namely magnesium, folic acid, docosahexaenoic acid, eicosapentaenoic acid, and alpha-tocopherol, on a series of disorders, including stress, anxiety, low sleep quality, and low cognitive performance

Anti-oxidant and anti-inflammatory activity of ketogenic diet. New perspectives for neuroprotection in alzheimer’s disease

The ketogenic diet, originally developed for the treatment of epilepsy in non-responder children, is spreading to be used in the treatment of many diseases, including Alzheimer’s disease. The main activity of the ketogenic diet has been related to improved mitochondrial function and decreased oxidative stress. B-Hydroxybutyrate, the most studied ketone body, has been shown to reduce the production of reactive oxygen species (ROS), improving mitochondrial respiration: it stimulates the cellular endogenous antioxidant system with the activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2), it modulates the ratio between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD+/NADH) and it increases the efficiency of electron transport chain through the expression of uncoupling proteins. Furthermore, the ketogenic diet performs anti-inflammatory activity by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome as well as inhibiting histone deacetylases (HDACs), improving memory encoding. The underlying mechanisms and the perspectives for the treatment of Alzheimer’s disease are discussed

Leukocyte telomere length and plasma interleukin-1β and interleukin-18 levels in mild cognitive impairment and Alzheimer's disease: new biomarkers for diagnosis and disease progression?

No abstract availabl

Importance of ACE polymorphisms for endurance performance

The skeletal muscle renin-angiotensin system (RAS) plays an important role in exercise metabolism. A functional insertion (I)/deletion (D) polymorphism in the angiotensin I- converting enzyme (ACE) gene (rs4646994) has been associated with ACE activity. The ACE DD genotype is associated with increased circulating ACE levels, which are generally two times as high as those found for II genotypes. Although most reports suggest that the I allele predisposes to human endurance (1) the literature also contains some opposite data (2). These inconsistencies from genetic association studies relating to the ACE gene and its I/D polymorphism maybe attributable, partially, to epigenetic factors that have been reported to influence ACE activity. Indeed, if both copies of the ACE D/D gene are transiently methylated, ACE increased levels associated with this polymorphism, may be down-regulated. However, there have not been any reports that address whether epigenetic regulation of the ACE gene is specifically involved in modifying human endurance, but, importantly, the human ACE gene promoter has been shown to harbor CpG islands. It is well established that environmental factors may modify the epigenetic profile and that nutrition training, muscle unloading and mechanical stimulation significantly impact on performance, playing an epigenetic role . Hence, it is conceivable that some of these factors might influence the CpG islands within the ACE promoter affecting its expression. The present study is aimed at modulating the epigenetic pattern of the ACE promoter by administering arginine to professional soccer players. ACE (DD, ID, and II) will be genotyped by PCR, then the epigenetic profile of ACE (gene promoter methylation) will be determined by bisulfite method, the serum levels of angiotensin 2 will be measured by ELISA. Hence, we compare the performance capacity of soccer players exhibiting different ACE polymorphisms, by strength, speed, and endurance tests. Subsequently, we will split the subjects under study in 2 groups: group 1 will follow a mediterrean diet, group 2 will follow the same mediterrean diet supplemented with arginine. After six months we will analyze if an epigenetic regulation of the ACE gene has occurred, modulating endurance performance

A multimethodological approach for the valorization of “Senatore Cappelli” wheat milling by-products as a source of bioactive compounds and nutraceutical activity

Wheat is the third most cultivated cereal in the world and represents the major contributor to human nutrition. Milling wheat by-products such as husks (17–20% of the total processing output weight), even if still containing high-value-added bioactive compounds, are often left untreated or unused, thus resulting in environmental and human health burdens. In these regards, the present study is aimed at evaluating in a multimethodological approach the nutraceutical properties of durum wheat husks belonging to the ancient cultivar “Senatore Cappelli”, thus assessing their potential as bioactive compound sources in terms of phytochemical, cytotoxic, and nutraceutical properties. By means of HPLC-FD analyses, wheat husk samples analyzed revealed a higher content of serotonin, amounting to 35% of the total BAs, and were confirmed to occur at biogenic amines quality index (BAQI) values <10 mg/100 g. In addition, spectrophotometric assays showed a signif- icant variable content in the phenolic (189.71–351.14 mg GAE/100 g) and antioxidant compounds (31.23–37.84 mg TE/100 g) within the wheat husk samples analyzed, according to the different cul- tivar areas of origin. Considering wheat husk extracts’ anti-inflammatory and antioxidant activity, in vitro analyses were performed on BV-2 murine microglia cells cultured in the presence or absence of LPS, thus evaluating their ability to promote microglia polarization towards an anti-inflammatory phenotype. Cytotoxicity assays showed that wheat extracts do not affect microglia viability. Wheat husks activity on microglial polarization was assessed by analyzing the expression of M1 and M2 markers’ mRNA by RT-PCR. Wheat husk antioxidant activity was assessed by analysis of NRF2 and SOD1 mRNA expression. Moreover, the sustainability assessment for the recovery of bioactive components from wheat by-products was carried out by applying the life cycle assessment (LCA) methodology using SimaPro v9.2.2. software

Alzheimer's Disease Promotion by Obesity: Induced Mechanisms—Molecular Links and Perspectives

The incidence of AD is increasing in parallel with the increase in life expectancy. At the same time the prevalence of metabolic syndrome and obesity is reaching epidemic proportions in western populations. Stress is one of the major inducers of visceral fat and obesity development, underlying accelerated aging processes. Adipose tissue is at present considered as an active endocrine organ, producing important mediators involved in metabolism regulation as well as in inflammatory mechanisms. Insulin and leptin resistance has been related to the dysregulation of energy balance and to the induction of a chronic inflammatory status which have been recognized as important cofactors in cognitive impairment and AD initiation and progression. The aim of this paper is to disclose the correlation between the onset and progression of AD and the stress-induced changes in lifestyle, leading to overnutrition and reduced physical activity, ending with metabolic syndrome and obesity. The involved molecular mechanisms will be briefly discussed, and advisable guide lines for the prevention of AD through lifestyle modifications will be proposed

The role of diet in preventing and reducing cognitive decline

Purpose of review This review summarises the most recent evidence regarding the effects of diet in preventing and reducing age-related cognitive decline and neurodegenerative diseases. Recent findings Recent evidence indicates that nutraceuticals and whole diet approaches may protect against the development of age-related cognitive decline and pathological neurodegeneration. The neuroprotective effects are diverse depending on the nutrient employed and may involve a reduction of neuroinflammation, an activation of the endogenous antioxidant defence system and a modulation of the gut microbiota structure and function. Summary This review summarises the existing evidence in favour of diet as a viable alternative approach to directly impact cognitive decline and neurodegenerative diseases. The single nutrient (polyphenols, B vitamins, long-chain polyunsaturated fatty acids) versus whole diet approach (Mediterranean diet, Dietary Approaches to Stop Hypertension, MIND, Nordic, ketogenic) is presented and discussed. Potential mechanisms of action underlying the beneficial effects of these diets are also described. Implementation of large-scale preventive interventions based on dietary patterns identified as being beneficial to brain health should be a research and public health priority, ideally in conjunction with other health-promoting lifestyle factors

Multidisciplinary Approaches to the stimulation of Wound Healing and Use of Dermal Substitutes in Chronic Phlebostatic Ulcers

Research focus: Skin injuries are evolving as an epidemic issue. Chronic skin lesion is a globally widespread disease, often referred to as a “wound difficult to heal" and one which has a strong impact on both overall health and quality of life. Genetic and clinical variables, such as diabetes, smoking, and inflammatory/immunological pathologies, are among the important risk factors limiting the regenerative powers of many therapeutic applications. Therefore, optimisation of current clinical strategies is critical. Experimental research: here we summarise the field’s current state by focusing on the use of stem-cell therapeutic applications in wound healing, placing considerable emphasis on current clinical approaches being developed at Rome’s Sapienza University. These involve protocols for the ex-vivo expansion of adipose tissue-derived mesenchyme stem cells using a patented GMP-compliant platelet lysate, Mesengen™, and cellular and a-cellulated dermal substitutes. A combination of multiple strategies, including genetic modifications of stem cells, biomimetic scaffolds, or novel vehicles like nanoparticles, are also discussed as future approaches. Case studies: here we present a report portraying our clinical experience of the treatment of chronic phlebostatic ulcers. The aim of the study reported here was to evaluate the effectiveness of treatment with dermal substitutes of cutaneous lesions originating from chronic venous insufficiency, therapy which took into consideration parameters such as: the reduction of wound size and the improvement of quality of life. Chronic skin lesion, a globally widespread disease, is often referred to as a "difficult wound" and has a strong impact on both overall health and quality of life. The difficulties encountered when seeking to heal this ailment have led to a quest for and development of new therapeutic approaches, including dermal substitutes. We can subdivide these into a-cellular matrices, such as Integra and Hyalomatrix and cell therapies such as Platelet Concentrate and Mesenchyme Cell Concentrate. Results: in all the patients treated, elements of improvement were observed: the appearance on the wound bed of small islands of granulation tissue, superficialization of the bottom of the ulcer and a growth of marginal tissue. During the first 30 days a reduction of more than 25% of the area of the lesion and a reduction of more than 50% at the end of the observation period were recorded in 10 of the patients who underwent preliminary surgical treatment out of the 13 subjects included in the study sample. On the whole, at the end of the observation period we witnessed an average 57% decrease of the lesion in all the patients; furthermore, during the treatment period, there was a gradual reduction of pain, measured using the NRS numerical scale. An overall average reduction in pain of 4 points on the NRS numerical scale was achieved. At the end of the eight-week evaluation period, the majority of the patients reported an improvement in the quality of their lives, since, in addition to the reduction of spontaneous pain, there was a diminution of pruritus, secretions -often malodorous and capable of affecting social life negatively - with recovery of functional capacity and almost complete recovery of habitual daily activities. During the period of treatment, no super-infections of the wounds or secondary complications related to the use of the various products were detected. Main conclusions. The numerous technological opportunities provided by regenerative medicine -including advanced dressings and dermal substitutes- if applied correctly, in compliance with a multidisciplinary approach where necessary, seem to offer advantages in terms of not only of clinical efficacy and patient life-quality but also in terms, it would appear, of health-care costs, an aspect which should not be either overlooked or underestimated

Multidisciplinary Approaches to the Stimulation of Wound Healing and Use of Dermal Substitutes in Chronic Phlebostatic Ulcers

Research focus: Skin injuries are evolving as an epidemic issue. Chronic skin lesion is a globally widespread disease, often referred to as a “wound difficult to heal” and one which has a strong impact on both overall health and quality of life. Genetic and clinical variables, such as diabetes, smoking and inflammatory/immunological pathologies, are among the important risk factors limiting the regenerative powers of many therapeutic applications. Therefore, optimisation of current clinical strategies is critical. Experimental research: Here we summarise the field’s current state by focusing on the use of stem-cell therapeutic applications in wound healing, placing considerable emphasis on current clinical approaches being developed at Rome’s Sapienza University. These involve protocols for the ex vivo expansion of adipose tissue-derived mesenchyme stem cells using a patented GMP-compliant platelet lysate, Mesengen™, and cellular and acellular dermal substitutes. A combination of multiple strategies, including genetic modifications of stem cells, biomimetic scaffolds or novel vehicles like nanoparticles, is also discussed as future approaches. Case studies: Here we present a report portraying our clinical experience of the treatment of chronic phlebostatic ulcers. The aim of the study reported here was to evaluate the effectiveness of treatment with dermal substitutes of cutaneous lesions originating from chronic venous insufficiency, therapy which took into consideration parameters such as the reduction of wound size and the improvement of quality of life. Chronic skin lesion, a globally widespread disease, is often referred to as a “difficult wound” and has a strong impact on both overall health and quality of life. The difficulties encountered when seeking to heal this ailment have led to a quest for and development of new therapeutic approaches, including dermal substitutes. We can subdivide these into acellular matrices, such as Integra and Hyalomatrix, and cell therapies such as platelet concentrate and mesenchyme cell concentrate. Results: In all the patients treated, elements of improvement were observed: the appearance on the wound bed of small islands of granulation tissue, superficialization of the bottom of the ulcer and a growth of marginal tissue. During the first 30 days, a reduction in more than 25% of the area of the lesion and a reduction in more than 50% at the end of the observation period were recorded in 10 of the patients who underwent preliminary surgical treatment out of the 13 subjects included in the study sample. On the whole, at the end of the observation period, we witnessed an average 57% decrease in the lesion in all the patients; furthermore, during the treatment period, there was a gradual reduction in pain, measured using the NRS numerical scale. An overall average reduction in pain of four points on the NRS numerical scale was achieved. At the end of the 8-week evaluation period, the majority of the patients reported an improvement in the quality of their lives, since, in addition to the reduction of spontaneous pain, there was a diminution of pruritus, secretions—often malodorous and capable of affecting social life negatively—with recovery of functional capacity and almost complete recovery of habitual daily activities. During the period of treatment, no superinfections of the wounds or secondary complications related to the use of the various products were detected. Main conclusions: The numerous technological opportunities provided by regenerative medicine—including advanced dressings and dermal substitutes—if applied correctly, in compliance with a multidisciplinary approach where necessary, seem to offer advantages not only in terms of clinical efficacy and patient life quality but also in terms, it would appear, of healthcare costs, an aspect which should not be either overlooked or underestimated

Perinatal S-Adenosylmethionine Supplementation Represses PSEN1 Expression by the Cellular Epigenetic Memory of CpG and Non-CpG Methylation in Adult TgCRD8 Mice

DNA methylation, the main epigenetic modification regulating gene expression, plays a role in the pathophysiology of neurodegeneration. Previous evidence indicates that 50 -flanking hypomethylation of PSEN1, a gene involved in the amyloidogenic pathway in Alzheimer’s dis- ease (AD), boosts the AD-like phenotype in transgenic TgCRND8 mice. Supplementation with S-adenosylmethionine (SAM), the methyl donor in the DNA methylation reactions, reverts the patho- logical phenotype. Several studies indicate that epigenetic signatures, driving the shift between normal and diseased aging, can be acquired during the first stages of life, even in utero, and manifest phenotypically later on in life. Therefore, we decided to test whether SAM supplementation during the perinatal period (i.e., supplementing the mothers from mating to weaning) could exert a protec- tive role towards AD-like symptom manifestation. We therefore compared the effect of post-weaning vs. perinatal SAM treatment in TgCRND8 mice by assessing PSEN1 methylation and expression and the development of amyloid plaques. We found that short-term perinatal supplementation was as effective as the longer post-weaning supplementation in repressing PSEN1 expression and amyloid deposition in adult mice. These results highlight the importance of epigenetic memory and methyl donor availability during early life to promote healthy aging and stress the functional role of non-CpG methylation