Corrigendum: Engagement in a structured physical activity program and its effects upon health-related quality of life in elderly women: an observational study.

[This corrects the article DOI: 10.3389/fpsyg.2023.1135433.].

Regular exercise delays microvascular endothelial dysfunction by regulating antioxidant capacity and cellular metabolism.

Aging is the basis for several unfavorable conditions, including cardiovascular diseases (CVDs). In this sense, regular physical activity (regular PA) has been proven to delay cellular aging and prevent endothelial dysfunction related to CVDs. Despite numerous studies involving athletes, little is known about cellular and molecular mechanisms of regular PA among master athletes. The present study aimed at evaluating the effects of regular PA on local microcirculatory functions in elderly athletes as compared to age-matched sedentary controls. Moreover, molecular/epigenetic mechanisms (nitric oxide, oxidative stress, PGC-1α, SIRT1 and miR29) were also assessed. The results of the present study showed that regular PA significantly increased local blood flow in post-ischemia and post-heating conditions, as well as NO plasma concentrations, denoting a better endothelial function/microcirculatory efficiency. Moreover, athletes presented a greater plasma antioxidant and increased transcriptional levels of the metabolism regulator PGC-1α. Finally, regular PA enhanced plasma level of SIRT1 and miR29, suggested as epigenetic regulators of redox balance and cellular metabolism. In addition, stimulated local blood flow was directly related to plasma antioxidant capacity, and SIRT1 and miR29 levels. Overall, our data confirm the beneficial effects of regular PA on the cardiovascular profile in elderly athletes and shed light on molecular signals involved in the positive adaptations to exercise.

Engagement in a structured physical activity program and its effects upon health-related quality of life in elderly women: An observational study.

Aging is a complex process associated with an impairment in functional capacity and low health-related quality of life (HRQoL) due to a high frequency of chronic diseases in the elderly population. Regular physical activity (PA) may limit some physiological effects of sedentary lifestyle and increase life expectancy. An observational was conducted to measure the HRQoL among older adults living in the community, by comparing a convenience sample of elderly females practicing a structured program of PA from 2 to 3 times per week in 60-min sessions (i.e., active females, AFs) to a sample of participants adopting lifestyle behaviors expending little energy (i.e., sedentary females, SFs). A validated questionnaire (the RAND 36-item) was used as outcome measure. All participants were assessed in terms of cognitive status (Montreal Cognitive Assessment, MoCA) to exclude mild cognitive impairment, divided attention/executive functioning (Trail Making Test, Stroop Test) and psychopathological dimensions of anxiety (Geriatric Anxiety Inventory, GAI), and depression (Geriatric Depression Scale, GDS). Non-parametric analysis revealed that AFs and SFs differed significantly in the RAND Energy/Fatigue (E/F), Emotional Wellbeing (EW), and Social Functioning (SoF), that was however influenced by education level. Moreover, E/F and EW were negatively associated to anxiety and depression, while SoF was influenced by divided attention. PA results in a healthful behavior for combating feelings of fatigue and low energy as well as emotional distress that can affect health status perception in older women.

Oxidative Stress-Related Signaling Pathways Predict Oocytes' Fertilization In Vitro and Embryo Quality.

Oocyte development and fertilization are largely influenced by the microenvironment of the follicular fluid (FF), and the exploration of its molecular/metabolic composition may help in improving in vitro fertilization (IVF) outcomes. Here, the concentrations of molecules related to oxidative stress/inflammation were measured in FF from follicles at oocyte retrieval during IVF. Here, the FF antioxidant potential was correlated with the number of retrieved/mature oocytes and the number of fertilized ones. FF collected from the follicles of normal fertilized oocytes presented an elevated antioxidant capability, lower levels of pro-inflammatory molecules (i.e., IL-6, IL-8, IL-12, TGF-ß, and HIF-1α), and a higher IL-10 concentration. FF samples from follicles at oocyte retrieval that resulted in top-quality embryos displayed a peculiar antioxidant capability and a further decrease in proinflammatory molecules when compared with FF, giving rise to poor-quality embryos. Finally, pro-inflammatory molecules were lower and accompanied by a high antioxidant capability in samples giving rise to successful embryo implantation. The antioxidant capability and IL-10 displayed a good predictive ability for fertilization and embryo quality. Overall, our data showed the great influence of oxidative stress on the oocytes' fertilization, and shed light on the importance of controlling the inflammatory and oxidative status of FF to obtain good-quality embryos with significant implantation potential.

A Minireview Exploring the Interplay of the Muscle-Gut-Brain (MGB) Axis to Improve Knowledge on Mental Disorders: Implications for Clinical Neuroscience Research and Therapeutics.

What benefit might emerge from connecting clinical neuroscience with microbiology and exercise science? What about the influence of the muscle-gut-brain (MGB) axis on mental health? The gut microbiota colonizes the intestinal tract and plays a pivotal role in digestion, production of vitamins and immune system development, but it is also able to exert a particular effect on psychological well-being and appears to play a critical role in regulating several muscle metabolic pathways. Endogenous and exogenous factors may cause dysbiosis, with relevant consequences on the composition and function of the gut microbiota that may also modulate muscle responses to exercise. The capacity of specific psychobiotics in ameliorating mental health as complementary strategies has been recently suggested as a novel treatment for some neuropsychiatric diseases. Moreover, physical exercise can modify qualitative and quantitative composition of the gut microbiota and alleviate certain psychopathological symptoms. In this minireview, we documented evidence about the impact of the MGB axis on mental health, which currently appears to be a possible target in the context of a multidimensional intervention mainly including pharmacological and psychotherapeutic treatments, especially for depressive mood.

Fertility Impairment after Trekking at High Altitude: A Proof of Mechanisms on Redox and Metabolic Seminal Changes.

Many authors described negative but reversible effects of high-altitude hypoxic exposure on animal and human fertility in terms of sperm concentration, function, and biochemical alterations. The aim of this study was to evaluate the acute and chronic effects of high-altitude exposure on classical sperm parameters, redox status, and membrane composition in a group of travellers. Five healthy Italian males, all lowlanders not accustomed to the altitude, were evaluated after 19 days-trekking through low, moderate, and high altitudes in the Himalayas. Sperm samples were collected before (Pre), 10 days after (Post), and 70 days after the end of the expedition (Follow-up). Sperm concentration, cholesterol and oxysterol membrane content, and redox status were measured. Hypoxic trek led to a significant reduction in sperm concentration (p < 0.001, η2p = 0.91), with a reduction from Pre to Post (71.33 ± 38.81 to 60.65 ± 34.63 × 106/mL) and a further reduction at Follow-up (to 37.13 ± 39.17 × 106/mL). The seminal volume was significantly affected by the hypoxic trek (p = 0.001, η2p = 0.75) with a significant reduction from Pre to Post (2.86 ± 0.75 to 1.68 ± 0.49 mL) and with partial recovery at Follow-up (to 2.46 ± 0.45 mL). Moreover, subjects had an increase in ROS production (+86%), and a decrease in antioxidant capacity (−37%) in the Post period with partial recovery at Follow-up. These results integrated the hormonal response on thyroid function, hypothalamus−pituitary−gonadal axis, and the prolactin/cortisol pathways previously reported. An uncontrolled ROS production, rather than a compromised antioxidant activity, was likely the cause of impaired sperm quality. The reduction in fertility status observed in this study may lie in an evolutionary Darwinian explanation, i.e., limiting reproduction due to the "adaptive disadvantage" offered by the combined stressors of high-altitude hypoxia and daily physical exercise.

Metabolic and Molecular Mechanisms of Diet and Physical Exercise in the Management of Polycystic Ovarian Syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine systemic disorder mainly characterized by a hormonal and metabolic disbalance that leads to oligo/anovulation, hyperandrogenism and the formation of ovarian cysts. Despite the progress that has been reached in its diagnosis and management, little is known about the molecular mechanisms and signaling pathways underlying the pathogenic mechanisms. In this sense, recent research has suggested that the influence of multiple factors, including age, environment, lifestyle and the disease state environment can change the clinical presentation of PCOS via epigenetic modifications. Variants in the genes encoding for proteins involved in steroidogenesis and glucose homeostasis play a crucial role in the development of the disease. Other genes involved in inflammation and cell proliferation seem to undergo an epigenetic control. Moreover, lifestyle factors influence the PCOS course and prognosis, including diet and physical activity, which are fundamental in reducing oxidative stress, inflammation and in improving metabolic and hormonal parameters. In the present review, literature evidence on molecular and epigenetic mechanisms related to PCOS etiology will be discussed, with a particular attention on the positive influence of diet and physical activity as nonpharmacological ways of intervention in the management of the disease.

What Does the Brain Have to Keep Working at Its Best? Resilience Mechanisms Such as Antioxidants and Brain/Cognitive Reserve for Counteracting Alzheimer's Disease Degeneration.

Here we performed a narrative review highlighting the effect of brain/cognitive reserve and natural/synthetic antioxidants in exerting a neuroprotective effect against cognitive deterioration during physiological and pathological aging. Particularly, we discussed pathogenesis of Alzheimer's disease, brain and cognitive reserve as means of resilience towards deterioration, and evidence from the literature about antioxidants' role in sustaining cognitive functioning in the preclinical phase of dementia. During aging, the effects of disease-related brain changes upon cognition are reduced in individuals with higher cognitive reserve, which might lose its potential with emerging cognitive symptoms in the transitional phase over the continuum normal aging-dementia (i.e., Mild Cognitive Impairment). Starting from this assumption, MCI should represent a potential target of intervention in which antioxidants effects may contribute-in part-to counteract a more severe brain deterioration (alongside to cognitive stimulation) causing a rightward shift in the trajectory of cognitive decline, leading patients to cross the threshold for clinical dementia later.

Effects of long-term vegan diet on breath composition.

The composition of exhaled breath derives from an intricate combination of normal and abnormal physiological processes that are modified by the consumption of food and beverages, circadian rhythms, bacterial infections, and genetics as well as exposure to xenobiotics. This complexity, which results wide intra- and inter-individual variability and is further influenced by sampling conditions, hinders the identification of specific biomarkers and makes it difficult to differentiate between pathological and nominally healthy subjects. The identification of a 'normal' breath composition and the relative influence of the aforementioned parameters would make breath analyses much faster for diagnostic applications. We thus compared, for the first time, the breath composition of age-matched volunteers following a vegan and a Mediterranean omnivorous diet in order to evaluate the impact of diet on breath composition. Mixed breath was collected from 38 nominally healthy volunteers who were asked to breathe into a 2 l handmade Nalophan bag. Exhalation flow rate and carbon dioxide values were monitored during breath sampling. An aliquot (100 ml) of breath was loaded into a sorbent tube (250 mg of Tenax GR, 60/80 mesh) before being analyzed by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). Breath profiling using TD-GC-MS analysis identified five compounds (methanol, 1-propanol, pentane, hexane, and hexanal), thus enabling differentiation between samples collected from the different group members. Principal component analysis showed a clear separation between groups, suggesting that breath analysis could be used to study the influence of dietary habits in the fields of nutrition and metabolism. Surprisingly, one Italian woman and her brother showed extremely low breath isoprene levels (about 5 pbv), despite their normal lipidic profile and respiratory data, such as flow rate and pCO2. Further investigations to reveal the reasons behind low isoprene levels in breath would help reveal the origin of isoprene in breath.

The Mediterranean Diet Positively Affects Resting Metabolic Rate and Salivary Microbiota in Human Subjects: A Comparison with the Vegan Regimen.

Salivary microbiota, comprising bacteria shed from oral surfaces, has been shown to be individualized, temporally stable, and influenced by macronutrient intake and lifestyle. Nevertheless, the effect of long-term dietary patterns on oral microbiota composition and the relationship between oral microbiota composition and metabolic rate remains to be examined. Herein, salivary microbiota composition and metabolic profile were analyzed in human subjects with vegan (VEG) or Mediterranean (MED) long-term dietary patterns. MED subjects presented significantly higher percentages of Subflava and Prevotella species as compared to VEG ones. Moreover, MED subjects showed a lower carbohydrate and a higher lipid consumption than VEG subjects, and, accordingly, a significantly higher basal metabolic rate (BMR) and a lower respiratory quotient (RQ). Prevotella abundance was demonstrated to be inversely related to RQ and carbohydrate consumption, whereas Subflava percentages were demonstrated to be positively correlated to BMR. Lactobacillus abundance, which was inversely related to Subflava presence in MED subjects, was associated with decreased BMR (Harris-Benedict) values. Overall, our data evidence the influence of macronutrient intake on metabolic profile and oral microbiota and confirm the positive effects of the Mediterranean diet on BMR and on the abundance of microbial species associated with a better macronutrient metabolism.

Oxidative Stress and Cognitive Decline: The Neuroprotective Role of Natural Antioxidants.

Free- radicals (Oxygen and Nitrogen species) are formed in mitochondria during the oxidative phosphorylation. Their high reactivity, due to not-engaged electrons, leads to an increase of the oxidative stress. This condition affects above all the brain, that usually needs a large oxygen amount and in which there is the major possibility to accumulate "Reacting Species." Antioxidant molecules are fundamental in limiting free-radical damage, in particular in the central nervous system: the oxidative stress, in fact, seems to worsen the course of neurodegenerative diseases. The aim of this review is to sum up natural antioxidant molecules with the greatest neuroprotective properties against free radical genesis, understanding their relationship with the Central Nervous System.

Paroxysmal Atrial Fibrillation Induced by Ice-Cold Water Ingestion in a Triathlete: A Case Report.

BACKGROUND Swallowing-induced tachyarrhythmias are rare, and their possible mechanisms are still not completely elucidated. Even though a mechanical stimulation has been suggested, involvement of the autonomic nervous system has not been completely excluded. Moreover, tachyarrhythmias are not so frequent in athletes. CASE REPORT We present a case of a 35-year-old male triathlete who reported palpitations after swallowing ice-cold water following physical activity. His physical examination and basal electrocardiogram were essentially normal. The 24-h Holter monitoring showed a sinus rhythm with sporadic isolated supraventricular ectopic beat and a 2-h run of atrial fibrillation (160-200 beats/min). This episode of paroxysmal atrial fibrillation was related to and occurred after the ingestion of ice-cold water following physical exercise. We were able to reproduce this event. Notably, the tachyarrhythmia was only triggered by swallowing ice-cold water; nothing happened with room-temperature water. No therapy was given to the triathlete to avoid influencing his physical performance in any way. CONCLUSIONS This case suggests that both an esophageal mechanical stimulation and autonomic nervous system involvement were at the base of this tachyarrhythmia. The influence of water temperature on the esophageal thermoceptors has to be considered.

Apolipoprotein E Polymorphism and Oxidative Stress in Human Peripheral Blood Cells: Can Physical Activity Reactivate the Proteasome System through Epigenetic Mechanisms?

Alzheimer's disease (AD) is characterized by proteasome activity impairment, oxidative stress, and epigenetic changes, resulting in ß-amyloid (Aß) production/degradation imbalance. Apolipoprotein E (ApoE) is implicated in Aß clearance, and particularly, the ApoE ε4 isoform predisposes to AD development. Regular physical activity is known to reduce AD progression. However, the impact of ApoE polymorphism and physical exercise on Aß production and proteasome system activity has never been investigated in human peripheral blood cells, particularly in erythrocytes, an emerging peripheral model used to study biochemical alteration. Therefore, the influence of ApoE polymorphism on the antioxidant defences, amyloid accumulation, and proteasome activity was here evaluated in human peripheral blood cells depending on physical activity, to assess putative peripheral biomarkers for AD and candidate targets that could be modulated by lifestyle. Healthy subjects were enrolled and classified based on the ApoE polymorphism (by the restriction fragment length polymorphism technique) and physical activity level (Borg scale) and grouped into ApoE ε4/non-ε4 carriers and active/non-active subjects. The plasma antioxidant capability (AOC), the erythrocyte Aß production/accumulation, and the nuclear factor erythroid 2-related factor 2 (Nrf2) mediated proteasome functionality were evaluated in all groups by the chromatographic and immunoenzymatic assay, respectively. Moreover, epigenetic mechanisms were investigated considering the expression of histone deacetylase 6, employing a competitive ELISA, and the modulation of two key miRNAs (miR-153-3p and miR-195-5p), through the miRNeasy Serum/Plasma Mini Kit. ApoE ε4 subjects showed a reduction in plasma AOC and an increase in the Nrf2 blocker, miR-153-3p, contributing to an enhancement of the erythrocyte concentration of Aß. Physical exercise increased plasma AOC and reduced the amount of Aß and its precursor, involving a reduced miR-153-3p expression and a miR-195-5p enhancement. Our data highlight the impact of the ApoE genotype on the amyloidogenic pathway and the proteasome system, suggesting the positive impact of physical exercise, also through epigenetic mechanisms.

Aerobic Exercise and Healthy Nutrition as Neuroprotective Agents for Brain Health in Patients with Parkinson's Disease: A Critical Review of the Literature.

Parkinson's disease (PD) is characterized by motor and nonmotor features that have an influence on patients' quality of life at different levels. To date, some evidences have arisen on the effectiveness of physical trainings and nutrients intake in ameliorating functional and cognitive outcomes in PD patients. Physical activity is effective in improving both motor and nonmotor features and recent epidemiological investigations have revealed the pivotal role that dietary patterns may play in reducing the risk of PD highlighting the pathogenesis of the neurodegeneration. Specifically, aerobic exercise shows beneficial effects in improving motor functions and executive control in PD patients, as well as proper nutrition may help in improving neuroprotective agents counteracting neurodegeneration and allows patients to better interact with the medication. Our narrative review critically focused on aerobic exercise and nutrition in PD in order to point out the best prescriptions for brain health of affected patients. Implications for a therapeutic plan and rehabilitation for these patients are also discussed.

Saliva as a non-invasive tool for monitoring oxidative stress in swimmers athletes performing a VO2max cycle ergometer test.

Biomarkers of oxidative stress are generally measured in blood and its derivatives. However, the invasiveness of blood collection makes the monitoring of such chemicals during exercise not feasible. Saliva analysis is an interesting approach in sport medicine because the collection procedure is easy-to-use and does not require specially-trained personnel. These features guarantee the collection of multiple samples from the same subject in a short span of time, thus allowing the monitoring of the subject before, during and after physical tests, training or competitions. The aim of this work was to evaluate the possibility of following the changes in the concentration of some oxidative stress markers in saliva samples taken over time by athletes under exercise. To this purpose, ketones (i.e. acetone, 2-butanone and 2-pentanone), aldehydes (i.e. propanal, butanal, and hexanal), α,ß-unsaturated aldehydes (i.e. acrolein and methacrolein) and di-carbonyls (i.e. glyoxal and methylglyoxal) were derivatized with 2,4-dinitrophenylhydrazine, and determined by ultra-high performance liquid chromatography coupled to diode array detector. Prostaglandin E2, F2/E2-isoprostanes, F2-dihomo-isoprostanes, F4-neuroprostanes, and F2-dihomo-isofuranes were also determined by a reliable analytical procedure that combines micro-extraction by packed sorbent and ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry. Overall the validation process showed that the methods have limits of detection in the range of units of ppb for carbonyls and tens to hundreds of ppt for isoprostanes and prostanoids, very good quantitative recoveries (90-110%) and intra- and inter-day precision lower than 15%. The proof of applicability of the proposed analytical approach was investigated by monitoring the selected markers of oxidative stress in ten swimmers performing a VO2max cycle ergo meter test. The results highlighted a clear increase of salivary by-products of oxidative stress during exercise, whereas a sharp decrease, approaching baseline values, of these compounds was observed in the recovery phase. This study opens up a new approach in the evaluation of oxidative stress and its relation to aerobic activity.

Impact of ApoE Polymorphism and Physical Activity on Plasma Antioxidant Capability and Erythrocyte Membranes.

The allele epsilon 4 (ε4) of apolipoprotein E (ApoE) is the strongest genetic risk factor for Alzheimer's disease (AD). ApoE protein plays a pivotal role in the synthesis and metabolism of amyloid beta (Aß), the major component of the extracellular plaques that constitute AD pathological hallmarks. Regular exercise is an important preventive/therapeutic tool in aging and AD. Nevertheless, the impact of physical exercise on the well-being of erythrocytes, a good model of oxidative stress and neurodegenerative processes, remains to be investigated, particularly depending on ApoE polymorphism. Herein, we evaluate the oxidative status, Aß levels, and the membrane's composition of erythrocytes in a cohort of human subjects. In our hands, the plasma antioxidant capability (AOC), erythrocytes membrane fluidity, and the amount of phosphatidylcholine (PC) were demonstrated to be significantly decreased in the ApoE ε4 genotype and non-active subjects. In contrast, erythrocyte Aß content and lipid peroxidation increased in ε4 carriers. Regular physical exercise was associated with an increased plasma AOC and membrane fluidity, as well as to a reduced amount of erythrocytes Aß. Altogether, these data highlight the influence of the ApoE genotype on erythrocytes' well-being and confirm the positive impact of regular physical exercise.

Parkinson's Disease-Mild Cognitive Impairment (PD-MCI): A Useful Summary of Update Knowledge.

Mild cognitive impairment (MCI) is a common feature in Parkinson's Disease (PD), even at the time of diagnosis. Some levels of heterogeneity in nature and severity of cognitive impairment and risk of conversion to Parkinson's Disease Dementia (PDD) exist. This brief overview summarized the current understanding of MCI in PD, by considering the following major points: historical development of the clinical entity, evaluation, epidemiology, predictors and outcomes, neuroimaging findings, pathophysiology, treatment, and pharmacological and non-pharmacological intervention. MCI in PD represents a concept in evolution and plays a pivotal role in advancing our understanding of the disease mechanisms, with the ultimate goal of building effective strategies to prevent conversion into PDD. Challenges for future research are also discussed.

Epigenetic Modifications of the α-Synuclein Gene and Relative Protein Content Are Affected by Ageing and Physical Exercise in Blood from Healthy Subjects.

Epigenetic regulation may contribute to the beneficial effects of physical activity against age-related neurodegeneration. For example, epigenetic alterations of the gene encoding for α-synuclein (SNCA) have been widely explored in both brain and peripheral tissues of Parkinson's disease samples. However, no data are currently available about the effects of physical exercise on SNCA epigenetic regulation in ageing healthy subjects. The present paper explored whether, in healthy individuals, age and physical activity are related to blood intron1-SNCA (SNCAI1 ) methylation, as well as further parameters linked to such epigenetic modification (total, oligomeric α-synuclein and DNA methyltransferase concentrations in the blood). Here, the SNCAI1 methylation status increased with ageing, and consistent with this result, low α-synuclein levels were found in the blood. The direct relationship between SNCAI1 methylation and α-synuclein levels was observed in samples characterized by blood α-synuclein concentrations of 76.3 ng/mg protein or lower (confidence interval (CI) = 95%). In this selected population, higher physical activity reduced the total and oligomeric α-synuclein levels. Taken together, our data shed light on ageing- and physical exercise-induced changes on the SNCA methylation status and protein levels of α-synuclein.

α-Synuclein Heterocomplexes with ß-Amyloid Are Increased in Red Blood Cells of Parkinson's Disease Patients and Correlate with Disease Severity.

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), ß-amyloid1-42 (Aß1-42) and tau, in both brain and peripheral tissues. In addition to oligomers, the role of the interactions of α-syn with Aß or tau has gradually emerged. Nevertheless, despite intensive research, NDs have no accepted peripheral markers for biochemical diagnosis. In this respect, Red Blood Cells (RBCs) are emerging as a valid peripheral model for the study of aging-related pathologies. Herein, a small cohort (N = 28) of patients affected by Parkinson's disease (PD) and age-matched controls were enrolled to detect the content of α-syn (total and oligomeric), Aß1-42 and tau (total and phosphorylated) in RBCs. Moreover, the presence of α-syn association with tau and Aß1-42 was explored by co-immunoprecipitation/western blotting in the same cells, and quantitatively confirmed by immunoenzymatic assays. For the first time, PD patients were demonstrated to exhibit α-syn heterocomplexes with Aß1-42 and tau in peripheral tissues; interestingly, α-syn-Aß1-42 concentrations were increased in PD subjects with respect to healthy controls (HC), and directly correlated with disease severity and motor deficits. Moreover, total-α-syn levels were decreased in PD subjects and inversely related to their motor deficits. Finally, an increase of oligomeric-α-syn and phosphorylated-tau was observed in RBCs of the enrolled patients. The combination of three parameters (total-α-syn, phosphorylated-tau and α-syn-Aß1-42 concentrations) provided the best fitting predictive index for discriminating PD patients from controls. Nevertheless further investigations should be required, overall, these data suggest α-syn hetero-aggregates in RBCs as a putative tool for the diagnosis of PD.

An in vitro comparative study of the antioxidant activity and SIRT1 modulation of natural compounds.

Oxidative stress arises from an imbalance between the production of free radicals and antioxidant defences. Several studies have suggested that dietary antioxidants (such as polyphenols and berberine) may counteract oxidative stress through the involvement of the Sirtuin 1/Adenosine Monophosphate-Activated Protein Kinase (SIRT1/AMPK) pathway. The aim of this study was to evaluate the direct and specific antioxidant activity of some natural compounds, as well as their ability to modulate the expression of SIRT1 and the activation of AMPK. Quercetin, tyrosol, ferulic acid, catechin, berberine and curcumin were evaluated for their specific and direct antioxidant activity with TOSC assay. Their ability to modulate SIRT1 and AMPK was assessed by immunoblotting assay, while their cytotoxicity by CellTiter-Blue Cell Viability Assay. No statistically significant decrease (p > 0.05) in the number of viable cells was found upon challenging with the natural compounds. Quercetin exhibited the highest antioxidant activity against peroxyl radical and peroxinitrate derivates, while curcumin showed the best anti-hydroxyl activity with respect to the other compounds and, most importantly, respect to the reference antioxidants. Finally, all the tested compounds significantly increased the SIRT1 expression and the activation of AMPK. Our results clearly disclose the specific antioxidant activity of these natural compounds and their ability to increase SIRT1 expression and AMPK activation.