Irisin influences the in vitro differentiation of human mesenchymal stromal cells, promoting a tendency toward beiging adipogenesis.

Mammals exhibit two distinct types of adipose depots: white adipose tissue (WAT) and brown adipose tissue (BAT). While WAT primarily functions as a site for energy storage, BAT serves as a thermogenic tissue that utilizes energy and glucose consumption to regulate core body temperature. Under specific stimuli such as exercise, cold exposure, and drug treatment, white adipocytes possess a remarkable ability to undergo transdifferentiation into brown-like cells known as beige adipocytes. This transformation process, known as the "browning of WAT," leads to the acquisition of new morphological and physiological characteristics by white adipocytes. We investigated the potential role of Irisin, a 12 kDa myokine that is secreted in mice and humans by skeletal muscle after physical activity, in inducing the browning process in mesenchymal stromal cells (MSCs). A subset of the MSCs possesses the remarkable capability to differentiate into different cell types such as adipocytes, osteocytes, and chondrocytes. Consequently, comprehending the effects of Irisin on MSC biology becomes a crucial factor in investigating antiobesity medications. In our study, the primary objective is to evaluate the impact of Irisin on various cell types engaged in distinct stages of the differentiation process, including stem cells, committed precursors, and preadipocytes. By analyzing the effects of Irisin on these specific cell populations, our aim is to gain a comprehensive understanding of its influence throughout the entire differentiation process, rather than solely concentrating on the final differentiated cells. This approach enables us to obtain insights into the broader effects of Irisin on the cellular dynamics and mechanisms involved in adipogenesis.

Evaluation of Orexin-A Salivary Levels and its Correlation with Attention After Non-invasive Brain Stimulation in Female Volleyball Players.

BACKGROUND: The capacity to change attention from one area to another depending on the many environmental circumstances present is a crucial aspect of selective attention and is strictly correlated to reaction time. The cholinergic system of the basal forebrain is crucial for attentive abilities. Several inputs, particularly orexin neurons, whose cell bodies are found in the postero-lateral hypothalamus, can activate the cholinergic system. The aim of this study was to investigate if high frequencies rTMS at dorsolateral prefrontal cortex (DLPFC) in highly trained volleyball players can change Orexin-A levels, attention and reaction time. This study was a double-blinded (participant and evaluator) matched-pair experimental design. Twenty right-handed female volleyball players were recruited for the study (age 24.6 ± 2.7 years; height 177.0 ± 5.5 cm; body mass 67.5 ± 6.5 kg; BMI 21.5 ± 1.2). RESULTS: The main finding of this study was that 10 Hz rTMS to the DLPFC seems to increase Orexin-A salivary levels and the percentage of correct answers, while decreasing RT. After rTMS, the athletes show an increase in the percentage of correct answers immediately after the end of stimulation, and also after 15 and 30 min. Moreover, the athletes show decreases in reaction time after the end of stimulation and after 15 and 30 min to the end of stimulation, while no differences were found at the end of stimulation. Finally, the athletes show significant increases in Orexin-A salivary levels after stimulation with a peak after 30' of the end. CONCLUSION: The results of our study seem to indicate that there is a relationship between salivary Orexin-A levels and RT. These results could provide useful tools for modulating sports training; in fact, if confirmed, they could lead coaches to offer their athletes rTMS sessions appropriately integrated with training. In fact, alternating attention is a mental flexibility that enables people to change their point of focus and switch between tasks requiring various levels of cognition.

The Relationship between Executive Functions and Body Weight: Sex as a Moderating Variable.

This study explores the interplay between executive functions and body weight, examining both the influence of biological factors, specifically sex, and methodological issues, such as the choice between Body Mass Index (BMI) and waist circumference (WC) as the primary anthropometric measure. A total of 386 participants (222 females, mean age = 45.98 years, SD = 17.70) were enrolled, from whom sociodemographic (sex, age, years of formal education) and anthropometric (BMI and WC) data were collected. Executive functions were evaluated using the Frontal Assessment Battery-15 (FAB15). The results showed the increased effectiveness of WC over BMI in examining the relationships between executive functions, sex differences, and body weight. In particular, this study revealed that there was a significant moderating effect of sex at comparable levels of executive functioning. Specifically, women with higher executive performance had lower WCs than their male counterparts, suggesting that executive function has a greater impact on WC in women than in men. Our findings highlight the importance of conducting more in-depth investigations of the complex relationship between cognitive deficits and weight gain, considering confounding variables of behavioral, psychobiological, and neurophysiological origin.

Functional Characteristics and Coping Strategies among Rugby Athletes: A Cluster Analysis Approach.

The developing domain of mental health in sports has gained much interest, acknowledging its pivotal role in athlete performance and well-being. The aim of this research is to provide a quantitative description concerning the levels of mental health, physical activity, cognitive fusion, cognitive flexibility, and coping strategies that characterize rugby athletes by using a data-driven approach. A total of 92 rugby athletes took part in this study and filled out a set of self-administered questionnaires. A correlational analysis showed that general well-being was positively associated with years spent playing rugby (r = 0.23) and coping mechanisms (r = 0.29). Athletes' well-being was also negatively correlated with cognitive inflexibility (r = -0.41) and cognitive fusion (r = -0.39). A k-means cluster analysis identified two unique groups: group 1, characterized by higher levels of psychological well-being, lower levels of physical activity, greater cognitive flexibility, improved coping techniques, and reduced cognitive fusion, and group 2, which exhibits opposite characteristics. The discrepancies observed in psychological characteristics such as coping strategies, cognitive fusion, and cognitive inflexibility highlight their potential impact on the general health of rugby players. To comprehend the complex interplay between psychological and physical elements in rugby athletes, long-term studies with larger samples are crucial.

Exploring the Interplay between Bone Marrow Stem Cells and Obesity.

Obesity, a complex disorder with rising global prevalence, is a chronic, inflammatory, and multifactorial disease and it is characterized by excessive adipose tissue accumulation and associated comorbidities. Adipose tissue (AT) is an extremely diverse organ. The composition, structure, and functionality of AT are significantly influenced by characteristics specific to everyone, in addition to the variability connected to various tissue types and its location-related heterogeneity. Recent investigation has shed light on the intricate relationship between bone marrow stem cells and obesity, revealing potential mechanisms that contribute to the development and consequences of this condition. Mesenchymal stem cells within the bone marrow, known for their multipotent differentiation capabilities, play a pivotal role in adipogenesis, the process of fat cell formation. In the context of obesity, alterations in the bone marrow microenvironment may influence the differentiation of mesenchymal stem cells towards adipocytes, impacting overall fat storage and metabolic balance. Moreover, bone marrow's role as a crucial component of the immune system adds another layer of complexity to the obesity-bone marrow interplay. This narrative review summarizes the current research findings on the connection between bone marrow stem cells and obesity, highlighting the multifaceted roles of bone marrow in adipogenesis and inflammation.

Impact of Acute Kidney Injury on the COVID-19 In-Hospital Mortality in Octogenarian Patients: Insights from the COVOCA Study.

BACKGROUND AND AIMS: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. METHODS: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. RESULTS: 197 patients were included in the study (median age 83.0 [82.0-87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0-25.0] days. From the multivariable Cox regression analysis, after the application of Sidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan-Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001). CONCLUSIONS: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort.

The Potential Role of Nutrition in Overtraining Syndrome: A Narrative Review.

Competition between athletes and an increase in sporting knowledge have greatly influenced training methods while increasing the number of them more and more. As a result, the number of athletes who have increased the number and intensity of their workouts while decreasing recovery times is rising. Positive overtraining could be considered a natural and fundamental process when the result is adaptation and improved performance; however, in the absence of adequate recovery, negative overtraining could occur, causing fatigue, maladaptation, and inertia. One of the earliest forms of fatigue is overreaching. It is considered to be an accumulation of training that leads to reduced sports performance, requiring days or weeks to recover. Overreaching, if followed by adequate recovery, can lead to an increase in athletic performance. Nonetheless, if overreaching becomes extreme, combined with additional stressors, it could lead to overtraining syndrome (OTS). OTS, caused by systemic inflammation, leads to central nervous system (CNS) effects, including depressed mood, further inflammation, central fatigue, and ultimately neurohormonal changes. There are therefore not only physiological, biochemical, and immunological but also psychological symptoms or markers that must be considered, independently or together, being intrinsically linked with overtraining, to fully understand OTS. However, to date, there are very few published studies that have analyzed how nutrition in its specific food aspects, if compromised during OTS, can be both etiology and consequence of the syndrome. To date, OTS has not yet been fully studied, and the topic needs further research. The purpose of this narrative review is therefore to study how a correct diet and nutrition can influence OTS in all its aspects, from prevention to treatment.

Precision Medicine in Type 2 Diabetes Mellitus: Utility and Limitations.

Type 2 diabetes mellitus (T2DM) is one of the most widespread diseases in Western countries, and its incidence is constantly increasing. Epidemiological studies have shown that in the next 20 years. The number of subjects affected by T2DM will double. In recent years, owing to the development and improvement in methods for studying the genome, several authors have evaluated the association between monogenic or polygenic genetic alterations and the development of metabolic diseases and complications. In addition, sedentary lifestyle and socio-economic and pandemic factors have a great impact on the habits of the population and have significantly contributed to the increase in the incidence of metabolic disorders, obesity, T2DM, metabolic syndrome, and liver steatosis. Moreover, patients with type 2 diabetes appear to respond to antihyperglycemic drugs. Only a minority of patients could be considered true non-responders. Thus, it appears clear that the main aim of precision medicine in T2DM is to identify patients who can benefit most from a specific drug class more than from the others. Precision medicine is a discipline that evaluates the applicability of genetic, lifestyle, and environmental factors to disease development. In particular, it evaluated whether these factors could affect the development of diseases and their complications, response to diet, lifestyle, and use of drugs. Thus, the objective is to find prevention models aimed at reducing the incidence of pathology and mortality and therapeutic personalized approaches, to obtain a greater probability of response and efficacy. This review aims to evaluate the applicability of precision medicine for T2DM, a healthcare burden in many countries.

Predictive Value of Fatty Liver Index for Long-Term Cardiovascular Events in Patients Receiving Liver Transplantation: The COLT Study.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is the leading cause of early mortality in orthotopic liver transplantation (OLT) patients. The fatty liver index (FLI) is strongly associated with carotid and coronary atherosclerosis, as well as cardiovascular mortality, surpassing traditional risk factors. Given the lack of data on FLI as a predictor of cardiovascular events in OLT recipients, we conducted a retrospective study to examine this topic. METHODS AND RESULTS: We performed a multicenter retrospective analysis of adult OLT recipients who had regular follow-up visits every three to six months (or more frequently if necessary) from January 1995 to December 2020. The minimum follow-up period was two years post-intervention. Anamnestic, clinical, anthropometric and laboratory data were collected, and FLI was calculated for all patients. CLINICAL TRIAL: gov registration ID NCT05895669. A total of 110 eligible patients (median age 57 years [IQR: 50-62], 72.7% male) were followed for a median duration of 92.3 months (IQR: 45.7-172.4) post-liver transplantation. During this period, 16 patients (14.5%) experienced at least one adverse cardiovascular event (including fatal and non-fatal myocardial infarction and stroke). Receiver Operating Characteristic (ROC) analysis identified a cut-off value of 66.0725 for predicting cardiovascular events after OLT, with 86.7% sensitivity and 63.7% specificity (68% vs. 31%; p = 0.001). Kaplan-Meier analysis showed that patients with FLI > 66 had significantly reduced cardiovascular event-free survival than those with FLI ≤ 66 (log-rank: 0.0008). Furthermore, multivariable Cox regression analysis demonstrated that FLI > 66 and pre-OLT smoking were independently associated with increased cardiovascular risk. CONCLUSIONS: Our findings suggest that FLI > 66 and pre-OLT smoking predict cardiovascular risk in adult OLT recipients.

Acute non invasive brain stimulation improves performances in volleyball players.

OBJECTIVES: The ability to redirect one's attention in response to various environmental situations is a crucial aspect of selective attention in team sports. Thus, the aim of this study was to investigate whether repetitive transcranial magnetic stimulation (rTMS) in volleyball players can improve Posner test response and cortical excitability. This study had a double-blinded (participant and evaluator) matched-pair experimental design. METHODS: Twenty right-handed female volleyball players were recruited for the study and randomly assigned to either the active rTMS group (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), 5 s of stimulation, and 15 s of rest, for a total of 1,500 pulses. Before and after stimulation, the Posner test and cortical excitability were evaluated. RESULTS: The significant finding of this paper was that 10 Hz rTMS to the DLPFC seemed to improve Posner test response, and also resulted in a significantly decreased RMT and MEP latency of the ipsilateral motor cortex. After stimulation, the active group showed a significant decrease in the percentage of errors in the Posner test. Moreover, active group showed faster RT after rTMS, suggesting that HF stimulation could enhance performance. Additionally, significant differences in RMT emerged in the active rTMS group after stimulation, while no differences were observed in MEP latency and MEP amplitude. CONCLUSION: In conclusion, we believe that these results may be of great interest to the scientific community and could have practical implications in the future.

Oxidative Stress in Type 2 Diabetes: Impacts from Pathogenesis to Lifestyle Modifications.

Oxidative stress is a critical factor in the pathogenesis and progression of diabetes and its associated complications. The imbalance between reactive oxygen species (ROS) production and the body's antioxidant defence mechanisms leads to cellular damage and dysfunction. In diabetes, chronic hyperglycaemia and mitochondrial dysfunction contribute to increased ROS production, further exacerbating oxidative stress. This oxidative burden adversely affects various aspects of diabetes, including impaired beta-cell function and insulin resistance, leading to disrupted glucose regulation. Additionally, oxidative stress-induced damage to blood vessels and impaired endothelial function contribute to the development of diabetic vascular complications such as retinopathy, nephropathy, and cardiovascular diseases. Moreover, organs and tissues throughout the body, including the kidneys, nerves, and eyes, are vulnerable to oxidative stress, resulting in diabetic nephropathy, neuropathy, and retinopathy. Strategies to mitigate oxidative stress in diabetes include antioxidant therapy, lifestyle modifications, and effective management of hyperglycaemia. However, further research is necessary to comprehensively understand the underlying mechanisms of oxidative stress in diabetes and to evaluate the efficacy of antioxidant interventions in preventing and treating diabetic complications. By addressing oxidative stress, it might be possible to alleviate the burden of diabetes and improve patient outcomes.

The hydrophilic extract from a new tomato genotype (named DHO) kills cancer cell lines through the modulation of the DNA damage response induced by Campthotecin treatment.

Introduction: DNA double-strand breaks are the most toxic lesions repaired through the non-homologous and joining (NHEJ) or the homologous recombination (HR), which is dependent on the generation of single-strand tails, by the DNA end resection mechanism. The resolution of the HR intermediates leads to error-free repair (Gene Conversion) or the mutagenic pathways (Single Strand Annealing and Alternative End-Joining); the regulation of processes leading to the resolution of the HR intermediates is not fully understood. Methods: Here, we used a hydrophilic extract of a new tomato genotype (named DHO) in order to modulate the Camptothecin (CPT) DNA damage response. Results: We demonstrated increased phosphorylation of Replication Protein A 32 Serine 4/8 (RPA32 S4/8) protein in HeLa cells treated with the CPT in combination with DHO extract with respect to CPT alone. Moreover, we pointed out a change in HR intermediates resolution from Gene Conversion to Single Strand Annealing through the modified DNA repair protein RAD52 homolog (RAD52), DNA excision repair protein ERCC-1 (ERCC1) chromatin loading in response to DHO extract, and CPT co-treatment, with respect to the vehicle. Finally, we showed an increased sensitivity of HeLa cell lines to DHO extract and CPT co-treatment suggesting a possible mechanism for increasing the efficiency of cancer therapy. Discussion: We described the potential role of DHO extract in the modulation of DNA repair, in response to Camptothecin treatment (CPT), favoring an increased sensitivity of HeLa cell lines to topoisomerase inhibitor therapy.

Assessment of Lifestyle, Eating Habits and the Effect of Nutritional Education among Undergraduate Students in Southern Italy.

BACKGROUND: The years spent at university represent a critical period that can influence both the quality of lifestyle and the eating habits of subsequent adulthood, and also, in the long term, the health of the individual. The aim of this study was to investigate the lifestyle of university students living away from home. METHODS: Each subject recruited for the study was given a questionnaire to obtain general information, eating habits and physical activity levels before (T0) and after six month of training seminars (T1). Blood pressure, body composition and questionnaire responses were investigated. RESULTS: The main findings of this study are a significant decrement in blood pressure; an increment in physical activity practice; an increased number of subjects who pay attention to the calorific value of food and also an improvement in BIA parameters. CONCLUSIONS: In conclusion, this study demonstrated the challenges that university students face in leading a healthy lifestyle and caring for their nutritional needs, particularly when they are away from their families. No intervention specifically targets young adults, even though much emphasis is placed on the promotion of a healthy lifestyle based on a varied and balanced diet and sufficient exercise. Our study showed that it is possible to improve lifestyle through educational events aimed at making students aware of the health risks deriving from unhealthy lifestyles.

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.

Impedance Analysis to Evaluate Nutritional Status in Physiological and Pathological Conditions.

A thorough knowledge of body composition assessment techniques is the cornerstone for initiating a customized nutritional program. The second step is to consider the potential of their application in different physiological and pathological conditions and their effectiveness in the management of a monitoring pathway during dietary interventions. To date, bioimpedance analysis is the most effective and reliable method for assessing body composition due to its advantages in terms of speed of execution, non-invasiveness and low cost. Therefore, this review article aims to analyze the main concepts and application areas of bioimpedance measurement techniques, in particular vector frequency-based analysis (BIVA) systems, in order to assess their validity in both physiological and pathological conditions.

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.

Effects of a Combination of Empagliflozin Plus Metformin vs. Metformin Monotherapy on NAFLD Progression in Type 2 Diabetes: The IMAGIN Pilot Study.

Non-alcoholic fatty liver disease (NAFLD) comprises a heterogeneous group of metabolic liver diseases and is characterized by the presence of steatosis in at least 5% of hepatocytes. The aim of our study was to assess the effect of the combination therapy of empagliflozin + metformin vs. metformin monotherapy on NAFLD progression in type 2 diabetic (T2DM) patients. Sixty-three metformin-treated T2DM patients who were SGLT2i-naïve and had an ultrasound diagnosis of NAFLD (aged 60.95 ± 11.14 years; males, 57.1%) were included in the present analysis. Thirty-three started the combination therapy. All patients were observed for 6 months and routinely monitored with anthropometry, blood biochemistry, and FibroScan®/CAP. At the 6-month follow-up, the combination therapy group presented a significant reduction in BMI (30.83 ± 3.5 vs. 28.48 ± 3.25), glycated hemoglobin (8.2 (7.4-8.8)) vs. 7.2 (6.8-7.9), ALT (68.5 (41.5-88.0) vs. 45.00 (38.00, 48.00)), CAP parameter (293.5 (270.0-319.25) vs. 267.00 (259.50, 283.75)) and steatosis degree (p = 0.001) in comparison with the control group, whose parameters remained almost stable over time. In patients affected by T2DM, the combination of empagliflozin + metformin vs. metformin monotherapy ameliorated liver steatosis, ALT levels, body weight, and glycated hemoglobin after a 6-month follow-up.