Significant Increase in Oxidative Stress Indices in Erythrocyte Membranes of Obese Patients with Metabolically-Associated Fatty Liver Disease.

Metabolic dysfunction-associated hepatic steatosis (MAFLD) indicates the metabolic risk associated with hepatic steatosis, overweight and obesity, and clinical evidence of metabolic dysregulation. Since MAFLD is one of the diseases that show a high frequency of alterations in the lipid content of cell membranes, the aim of this study was to evaluate the indices of oxidative damage of erythrocyte membranes in overweight and obese MAFLD subjects. The study was conducted on serum samples and red blood cell membranes of overweight and obese MAFLD subjects. For each patient, biochemical measurements and lipidomic analyses of erythrocytes membranes were performed. Significant differences in fatty acid profiles of RBC membranes were found between overweight and obese patients. In particular, the Peroxidation Index (PI) was higher in the erythrocyte membranes of obese subjects than in overweight subjects. The same behavior was observed for Unsaturation Index (UI) and Free Radical Stress Index (Free RSI), supporting the fact that the systemic increase in oxidative stress was associated with obesity. The study shows that there is a different susceptibility to erythrocyte membrane peroxidation for overweight and obese subjects, and the increased values of oxidative stress indices observed in the erythrocyte membranes of obese patients with MAFLD may be a possible indicator of pro-oxidative events occurring in obesity-related diseases.

Contribution of Nutritional, Lifestyle, and Metabolic Risk Factors to Parkinson's Disease.

BACKGROUND: Modifiable risk factors for Parkinson's disease (PD) are poorly known. OBJECTIVES: The aim is to evaluate independent associations of different nutritional components, physical activity, and sedentary behavior and metabolic factors with the risk of PD. METHODS: In this population-based prospective cohort study using the data of the United Kingdom Biobank (from 2006-2010), 502,017 men and women who were free from PD (International Classification of Diseases 10th edition; "G20") at baseline were included. We implemented a Cox proportion hazard's model to evaluate the associations of different levels of physical activity, sitting time, sleep habits, diet quality, alcohol and coffee consumption, smoking, and body mass index with PD risk, adjusting for several confounding variables. RESULTS: During a median follow-up of 12.8 years, lifestyle factors including vigorous physical activity (hazard ration [HR] = 0.84; 95% confidence interval [CI], 0.75-0.94), low-to-moderate sitting time (HR = 0.89; 95% CI, 0.81-0.97), and high sleep quality (HR = 0.89; 95% CI, 0.80-0.99) were associated with a reduced risk of PD. Small amounts of coffee (HR = 0.88; 95% CI, 0.82-0.95), red meat (HR = 0.86; 95% CI, 0.76-0.97), and current smoking (HR = 0.65; 95% CI, 0.56-0.75) were also associated with a lower risk of PD, whereas alcohol intake (HR = 1.29; 95% CI, 1.06-1.56) with higher PD risk. Secondary analysis, including metabolic risk factors, confirmed these findings and highlighted the potential protective effect of plasma vitamin D and uric acid, but of low-density lipoprotein-cholesterol, triglycerides, and C-reactive protein as well. CONCLUSIONS: Vigorous physical activity, reduced sitting time, good sleep quality together with small coffee intake and vitamin D supplementation are potentially neuroprotective lifestyle interventions for the prevention of PD. © 2024 International Parkinson and Movement Disorder Society.

Semaglutide Modulates Extracellular Matrix Production of LX-2 Cells via Exosomes and Improves Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely related to some metabolic disorders, such as central obesity and type 2 diabetes (T2D). Glucagon-like peptide 1 receptor agonists (GLP-1RAs), such as semaglutide, may have therapeutic roles in MASLD associated with T2D. This study aims to investigate the molecular mechanisms underlying the effectiveness of semaglutide on MASLD in terms of progression from liver steatosis to fibrosis. We characterized exosomes from ten patients with type 2 diabetes (T2D) before (T0) and after 12 months (T12) of treatment with once-weekly subcutaneous semaglutide. Six of ten patients were considered responders to therapy (R) based on MASLD severity downgrading by at least one class according to a validated ultrasonographic (US) score. Normal hepatocytes (HEPA-RG) and stellate (LX-2) cells were challenged with exosomes from R and NR patients, isolated before and after 12 months of therapy. Exosomes from both R and NR patients isolated at T0 significantly affected LX-2 viability. After 12 months of treatment, only those isolated from R patients restored cell viability, whereas those from NR patients did not. No effects were observed on HEPA-RG cells. Exosomes at T12 from R but not from NR patients significantly decreased the production of α-SMA, a marker of LX-2 activation, a liver stellate cell model, and ph-SMAD2 and CTGF, involved in fibrosis processes. TGF-ß1 was not modulated by the exosomes of R and NR patients. As a downstream effect, Vimentin, Collagen 1A1, and Fibronectin extracellular matrix components were also downregulated, as measured by droplets digital PCR. In conclusion, these results shed light on the potential effectiveness of semaglutide in improving liver fibrosis in MASLD.

High Extra Virgin Olive Oil Consumption Is Linked to a Lower Prevalence of NAFLD with a Prominent Effect in Obese Subjects: Results from the MICOL Study.

Extra virgin olive oil (EVOO) has healthy benefits for noncommunicable diseases (NCDs). However, limited evidence is available about the effects of liver disease and non-alcoholic fatty liver disease (NAFLD). We evaluate whether dose-increased consumption of EVOO is associated with a lower prevalence of NAFLD and if these effects vary based on body weight. The study included 2436 subjects with a 33% NAFLD prevalence. Daily EVOO was categorized into tertiles: low (0-24 g/day), moderate (25-37 g/day), and high consumption (>37 g/day). Subjects were also classified by body mass index (BMI) as normo-weight (18.5-24.9), overweight (25-29.9), and obese (≥30). Logistic regression analysis was applied to calculate odds ratios (ORs) for NAFLD, considering a 20-gram increment in EVOO intake and accounting for EVOO categories combined with BMI classes. The ORs were 0.83 (0.74;0.93) C.I. p = 0.0018 for continuous EVOO, 0.89 (0.69;1.15) C.I. p = 0.37, and 0.73 (0.55;0.97) C.I. p = 0.03 for moderate and high consumption, respectively, when compared to low consumption. Overall, the percent relative risk reductions (RRR) for NAFLD from low to high EVOO consumption were 18% (16.4%;19.2%) C.I. and 26% (25%;27.4%) C.I. in overweight and obese subjects. High EVOO consumption is associated with a reduced risk of NAFLD. This effect is amplified in overweight subjects and even more in obese subjects.

The oleic/palmitic acid imbalance in exosomes isolated from NAFLD patients induces necroptosis of liver cells via the elongase-6/RIP-1 pathway.

Excessive toxic lipid accumulation in hepatocytes underlies the development of non-alcoholic fatty liver disease (NAFLD), phenotypically characterized by necrosis and steato-fibrosis, whose molecular mechanism is not yet fully understood. Patients with NAFLD display an imbalanced palmitic (PA) to oleic acid (OA) ratio. Moreover, increasing experimental evidence points out a relevant involvement of the exosomal content in disease progression. Aim of the study was to highlight the PA/OA imbalance within circulating exosomes, the subsequent intracellular alterations, and the impact on NALFD. Liver cells were challenged with exosomes isolated from both healthy subjects and NAFLD patients. The exosomal PA/OA ratio was artificially modified, and biological effects were evaluated. A NAFLD-derived exosomal PA/OA imbalance impacts liver cell cycle and cell viability. OA-modified NAFLD-derived exosomes restored cellular viability and proliferation, whereas the inclusion of PA into healthy subjects-derived exosomes negatively affected cell viability. Moreover, while OA reduced the phosphorylation and activation of the necroptosis marker, Receptor-interacting protein 1 (phospho-RIP-1), PA induced the opposite outcome, alongside increased levels of stress fibers, such as vimentin and fibronectin. Administration of NAFLD-derived exosomes led to increased expression of Elongase 6 (ELOVL6), Stearoyl-CoA desaturase 1 (SCD1), Tumor necrosis factor α (TNF-α), Mixed-lineage-kinase-domain-like-protein (MLKL) and RIP-1 in the hepatocytes, comparable to mRNA levels in the hepatocytes of NAFLD patients reported in the Gene Expression Omnibus (GEO) database. Genetic and pharmacological abrogation of ELOVL6 elicited a reduced expression of downstream molecules TNF-α, phospho-RIP-1, and phospho-MLKL upon administration of NAFLD-derived exosomes. Lastly, mice fed with high-fat diet exhibited higher phospho-RIP-1 than mice fed with control diet. Targeting the Elongase 6-RIP-1 signaling pathway offers a novel therapeutic approach for the treatment of the NALFD-induced exosomal PA/OA imbalance.

Plasma Bacterial DNA Load as a Potential Biomarker for the Early Detection of Colorectal Cancer: A Case-Control Study.

The gut microbiota has gained increasing attention in recent years due to its significant impact on colorectal cancer (CRC) development and progression. The recent detection of bacterial DNA load in plasma holds promise as a potential non-invasive approach for early cancer detection. The aim of this study was to examine the quantity of bacterial DNA present in the plasma of 50 patients who have CRC in comparison to 40 neoplastic disease-free patients, as well as to determine if there is a correlation between the amount of plasma bacterial DNA and various clinical parameters. Plasma bacterial DNA levels were found to be elevated in the CRC group compared to the control group. As it emerged from the logistic analysis (adjusted for age and gender), these levels were strongly associated with the risk of CRC (OR = 1.02, p < 0.001, 95% C.I.: 1.01-1.03). Moreover, an association was identified between a reduction in tumor mass and the highest tertile of plasma bacterial DNA. Our findings indicate that individuals with CRC displayed a higher plasma bacterial DNA load compared to healthy controls. This observation lends support to the theory of heightened bacterial migration from the gastrointestinal tract to the bloodstream in CRC. Furthermore, our results establish a link between this phenomenon and the size of the tumor mass.

Serum Cytokine and miRNA Levels Are Differently Expressed in Right- and Left-Sided Colon Cancer.

The tumor location in colorectal cancer (right- or left-sided colon cancer) is a key factor in determining disease progression. Right- and left-sided colon tumors are different in their clinical and molecular characteristics. Dysregulation of serum levels of proinflammatory cytokines, such as Transforming Growth Factor ß (TGF-ß) and Tumor Necrosis Factor-α (TNF-α), and Peroxisome Proliferator Activated Receptor-γ (PPAR-γ), known to be a growth-limiting and differentiation-promoting factor, as well as changes in miRNAs expression, are the major signaling pathways involved in the pathogenesis of this neoplasia. In the serum from 60 colorectal cancer (CRC) patients, we compared the differences in the expression of the levels of TGF-ß, TNF-α, and PPAR-γ and in the expression of the main human miRNAs between right and left CRC. A significant over-expression in the TGF-ß and TNF-α levels was observed in the serum from right-sided colon cancer patients. For the PPAR-γ, the patients with CRC located on the right-side showed lower levels than those detected in the serum from left-sided CRC subjects. Furthermore, significant differences also existed in the expression of specific circulating miRNAs between right- and left-sided CRC. In particular, the right upregulated miRNAs were all involved in the cell growth and proliferation related pathways. These findings confirm that the analysis of circulating levels of TGF-ß, TNF-α, and PPAR-γ, as well as the study of the specific miRNAs in the serum, are able to identify specific characteristics of CRC patients, useful for choosing a personalized treatment protocol.

Corrigendum: Correlation between antioxidant and anticancer activity and phenolic profile of new Apulian table grape genotypes (V. Vinifera L.).

[This corrects the article DOI: 10.3389/fpls.2022.1064023.].

Bioaccessibility and Bioavailability of Diet Polyphenols and Their Modulation of Gut Microbiota.

It is generally accepted that diet-derived polyphenols are bioactive compounds with several potentially beneficial effects on human health. In general, polyphenols have several chemical structures, and the most representative are flavonoids, phenolic acids, and stilbenes. It should be noted that the beneficial effects of polyphenols are closely related to their bioavailability and bioaccessibility, as many of them are rapidly metabolized after administration. Polyphenols-with a protective effect on the gastrointestinal tract-promote the maintenance of the eubiosis of the intestinal microbiota with protective effects against gastric and colon cancers. Thus, the benefits obtained from dietary supplementation of polyphenols would seem to be mediated by the gut microbiota. Taken at certain concentrations, polyphenols have been shown to positively modulate the bacterial component, increasing Lactiplantibacillus spp. and Bifidobacterium spp. involved in the protection of the intestinal barrier and decreasing Clostridium and Fusobacterium, which are negatively associated with human well-being. Based on the diet-microbiota-health axis, this review aims to describe the latest knowledge on the action of dietary polyphenols on human health through the activity of the gut microbiota and discusses micro-encapsulation of polyphenols as a strategy to improve the microbiota.

Plasma-Derived Exosomes from NAFLD Patients Modulate the Cannabinoid Receptors' Expression in Cultured HepaRG Cells.

Exosomes produced by hepatocytes upon lipotoxic insult play a relevant role in pathogenesis of nonalcoholic fatty liver disease (NAFLD), suggesting an inflammatory response by the activation of monocytes and macrophages and accelerating the disease progression. In the pathogenesis of NAFLD and liver fibrosis, the endogenous cannabinoids and their major receptors CB1 and CB2 appear to be highly involved. This study aimed at evaluating the expression of cannabinoids receptors (CB1R and CB2R) in plasma-derived exosomes extracted from patients with NAFLD, as well as investigating the in vitro effects of the circulating exosomes in cultured human HepaRG cells following their introduction into the culture medium. The results demonstrated that plasma-derived exosomes from NAFLD patients are vehicles for the transport of CB1R and are able to modulate CB receptors' expression in HepaRG cells. In particular, circulating exosomes from NAFLD patients are inflammatory drivers for HepaRG cells, acting through CB1R activation and the downregulation of CB2R. Moreover, CB1R upregulation was associated with increased expression levels of PPAR-γ, a well-known mediator of liver tissue injury. In conclusion, this study provides evidence for CB1R transport by exosomes and suggests that the in vitro effects of circulating exosomes from NAFLD patients are mediated by the expression of cannabinoid receptors.

Anti-Proliferative and Pro-Apoptotic Effects of Digested Aglianico Grape Pomace Extract in Human Colorectal Cancer Cells.

Grape pomace (GP)-the major by-product of winemaking processes-still contains bioactive molecules with known beneficial properties for human health, such as an antiradical scavenging activity or an antiproliferative activity of tumors. In vitro studies have demonstrated that GP polyphenols specifically influence colon cancer cell proliferation. In addition to previously published work, we tested the phenolic compounds of Aglianico GP following an in vitro simulated gastrointestinal digestion on colorectal cancer cell lines at different degrees of differentiation. Our experiments, using HT29 and SW480 cells, confirmed the anti-proliferative effect of GP gastrointestinal digested extract and provided intriguing insights on the way it influences the cancer cell features (i.e., viability, proliferation, and apoptosis). We observed that Aglianico GP extract showed a great ability to affect cell proliferation and apoptosis. Interestingly, both HT29 and SW480 cells produced a significant increase in Bax, and a significant increase in the Bax/Bcl-2 ratio and caspase-3. The gastrointestinal digested GP extract was previously characterized both for antioxidant activity and phenolic composition. As a result, the TPC and the antioxidant activity reached high values in the Aglianico GP digested extract, and the main compounds assessed by UHPLC-DAD were anthocyanins, phenolic acids, and flavonoids. This work shed light on the use of digested GP extract as a dietary ingredient, a very sustainable source of nutritional compounds with potential health benefits for colon cancer cell proliferation.

Beneficial Effects of Table Grape Use on Serum Levels of Omega-3 Index and Liver Function: A Randomized Controlled Clinical Trial.

This clinical trial was aimed to investigate the effects of fresh table grape intake on the serum levels of the Omega-3 index, defined as the sum of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) levels. Forty consecutive healthy subjects were randomly assigned to the control group, receiving only dietary recommendations, and the grape group receiving a daily dose of 5 g of fresh table grape per kg of body weight, for 21 days. Compared with baseline, the grape treatment produced no significant difference in the serum levels of glucose, liver transaminase, and triglycerides, with the exception of cholesterol value, which was significantly reduced in both control and grape group (180.5 ± 20.32 vs. 196.1 ± 30.0 and 181.4 ± 21.9 vs. 194.3 ± 37.5, respectively). After 4 weeks from the end of grape treatment, the analysis of single fatty acids showed a significant increase in oleic acid content (14.15 ± 1.8 vs. 12.85 ± 1.6, p < 0.05) and a significant induction of the Omega-3 index (8.23 ± 1.9 vs. 6.09 ± 1.2, p < 0.05), associated with increased serum levels of adiponectin (24.09 ± 1.08 vs. 8.8 ± 0.7, p < 0.001). In contrast, the expression of fibroblast growth factor 21 (FGF21), a molecule associated with metabolic syndrome and liver disease, was significantly reduced (37.9 ± 6.8 vs. 107.8 ± 10.1, p < 0.001). The data suggest that the intake of fresh grape improves the Omega-3 index in the serum and exerts beneficial effects on liver function through the overexpression of adiponectin and the reduction in FGF21 levels.

Dietary acrylamide and incident osteoporotic fractures: an 8-year prospective cohort study.

BACKGROUND: Acrylamide, a component of fried foods, has been associated with several negative health outcomes. However, the relationship between dietary acrylamide and osteoporotic fractures has been explored by a few cross-sectional studies. AIMS: To investigate if dietary acrylamide is associated with the onset of fractures in North American participants at high risk/having knee osteoarthritis (OA), over 8 years of follow-up. METHODS: A Cox's regression analysis, adjusted for baseline confounders was run and the data were reported as hazard ratios (HRs) and 95% confidence intervals (CIs). Dietary acrylamide intake was assessed at the baseline using a food frequency questionnaire and categorized in tertiles (T), whilst fractures' history was recorded using self-reported information. RESULTS: Altogether, 4,436 participants were included. Compared to participants with lower acrylamide intake (T1; < 3,313 µg), those with a higher acrylamide intake (T3; > 10,180 µg) reported a significantly higher risk of any fracture (HR = 1.37; 95% CI 1.12-1.68; p for trend = 0.009), forearm (HR = 1.73; 95% CI 1.09-2.77; p for trend = 0.04), spine (HR = 2.21; 95% CI 1.14-4.31; p for trend = 0.04), and hip fracture (HR = 4.09; 95% CI 1.29-12.96; p for trend = 0.046). CONCLUSIONS: Our study is the first to report that high dietary acrylamide may be associated with an increased risk of osteoporotic fractures.

Nutraceuticals: Focus on Anti-Inflammatory, Anti-Cancer, Antioxidant Properties in Gastrointestinal Tract.

In recent years, nutraceuticals have gained great popularity, owing to their physiological and potential health effects, such as anti-inflammatory, anti-cancer, antioxidant, and prebiotic effects, and their regulation of lipid metabolism. Since the Mediterranean diet is a nutritionally recommended dietary pattern including high-level consumption of nutraceuticals, this review aimed to summarize the main results obtained by our in vitro and in vivo studies on the effects of the major constituents of the Mediterranean diet (i.e., extra virgin olive oil compounds, polyunsaturated fatty acids, and fruit components). Based on experimental studies, the therapeutic purpose of nutraceuticals depends on their bioavailability, solubility, toxicity, and delivery system. This review provides more in-depth knowledge on the effects linked to nutraceuticals administration on human health, focusing the gastrointestinal tract and suggesting specific dietary components for personalized adjuvant therapies.

The Ketogenic Diet Improves Gut-Brain Axis in a Rat Model of Irritable Bowel Syndrome: Impact on 5-HT and BDNF Systems.

Altered gut-brain communication can contribute to intestinal dysfunctions in the intestinal bowel syndrome. The neuroprotective high-fat, adequate-protein, low-carbohydrate ketogenic diet (KD) modulates the levels of different neurotransmitters and neurotrophins. The aim was to evaluate the effects of KD on levels of 5-HT, the receptors 5-HT3B and 5-HT4, the 5-HT transporter SERT, the neurotrophin BDNF, and its receptor TrkB in the colon and brain of a rat model of irritable bowel syndrome (IBS). Samples from Wistar rats exposed to maternal deprivation as newborns and then fed with a standard diet (IBS-Std) or KD (IBS-KD) for ten weeks were analyzed. As controls, unexposed rats (Ctrl-Std and Ctrl-KD) were studied. IBS-Std rats had a disordered enteric serotoninergic signaling shown by increased mucosal 5-HT content and reduced SERT, 5-HT3B, and 5-HT4 levels compared to controls. In the brain, these animals showed up-regulation of the BDNF receptor TrkB as a counteracting response to the stress-induced reduction of the neurotrophin. KD showed a dual effect in improving the altered 5-HT and BDNF systems. It down-regulated the increased mucosal 5-HT without affecting transporter and receptor levels. KD improved brain BDNF levels and established negative feedback, leading to a compensatory downregulation of TrkB to maintain a physiological steady state.

Adherence to a healthy lifestyle and multiple sclerosis: a case-control study from the UK Biobank.

BACKGROUND: Multiple sclerosis (MS) is a common and disabling condition. The importance of healthy lifestyle for this disease is poorly explored. OBJECTIVE: To test whether adherence to healthier lifestyle patterns is associated with a lower presence of multiple sclerosis (MS). METHODS: By using a case-control design, we investigated the combined association of four healthy lifestyle-related factors (no current smoking, healthy diet, exercising regularly, body mass index <30 kg/m2) and the prevalence of MS. A logistic regression analysis, adjusted for potential confounders, was used and data reported as odds ratios (ORs) with their 95% confidence intervals (CIs). RESULTS: 728 participants with MS were matched with healthy controls (n = 2,912) using a propensity score approach. In a multivariable analysis, compared to those who scored low in the composite lifestyle score (0-1 healthy lifestyle factors), people who adopted all four low risk lifestyle factors showed a 71% lower odds of having MS (OR = 0.29; 95% CI: 0.15-0.56). Moreover, there was a strong linear trend, suggesting that the higher number of healthy lifestyle behaviors was associated with lower odds of having MS. CONCLUSION: Following a healthy lifestyle is associated with a lower prevalence of MS. This association should be explored further in cohort studies.

Magnetic implants in vivo guiding sorafenib liver delivery by superparamagnetic solid lipid nanoparticles.

HYPOTHESIS: Solid lipid nanoparticles (SLNs), co-encapsulating superparamagnetic iron oxide nanoparticles and sorafenib, have been exploited for magnetic-guided drug delivery to the liver. Two different magnetic configurations, both comprising two small magnets, were under-skin implanted to investigate the effect of the magnetic field topology on the magnetic SLNP accumulation in liver tissues. A preliminary simulation analysis was performed to predict the magnetic field topography for each tested configuration. EXPERIMENTS: SLNs were prepared using a hot homogenization approach and characterized using complementary techniques. Their in vitro biological behavior was assessed in HepG-2 liver cancer cells; wild-type mice were used for the in vivo study. The magnet configuration that resulted in a higher magnetic targeting efficiency was investigated by evaluating the iron content in homogenated murine liver tissues. FINDINGS: SLNs, characterized by an average size smaller than 200 nm, retained their superparamagnetic behavior and relevant molecular resonance imaging properties as negative contrast agents. The evaluation of iron accumulation in the liver tissues was consistent with the magnetic induction profile of each magnet configuration, concurring with the results predicted by simulation analysis and obtained by measurements in living mice.

Effects of weight change on all causes, digestive system and other causes mortality in Southern Italy: a competing risk approach.

Weight change is associated with all causes of death, cardiovascular, and cancer mortality and a heterogeneous group of other causes of death. We aimed to estimate the effect of weight change on all causes and cause-specific mortality in a cohort with a high prevalence of deaths due to diseases of the digestive system.MethodsIn this prospective cohort study, 2230 subjects aged 30 to 50 years were examined. The study consisted of a 32-year longitudinal study period (January 1985 to December 2017) and mortality follow-up. Outcomes were mortality from all causes and deaths from gastrointestinal disease. Root Mean Squared Error (RMSE) was evaluated to capture individual residual variation in Body Mass Index (BMI) after adjustment for baseline BMI, and the relationship of residual variation with mortality was calculated as cumulative incidence function and cause-specific hazard (CSH) rate.ResultsIn total, 793 participants died during the follow-up, 96 of them due to Digestive system causes. Magnitude of residual variation weight in the last quintile was associated with all-cause mortality (relative risk, 2.00; 95% CI, 1.54-2.59) and Digestive system causes (relative risk, 3.82; 95% CI, 1.86-7.81).ConclusionThe findings suggest an association between weight change and gastrointestinal disease mortality. Epidemiological works studying the correlation between weight change and mortality should consider this aspect.

Correlation between antioxidant and anticancer activity and phenolic profile of new Apulian table grape genotypes (V. Vinifera L.).

Grapes represent a significant source of phenolic compounds known for their health-promoting properties, such as antioxidant capacity on normal cells and prooxidant activity on tumor cells. The genotype highly affects the polyphenolic composition in grapes and, consequently, the nutritional quality of berries. This work aimed to characterize the phenolic composition, the antioxidant, and anticancer activity of grape skin extracts (GSEs) of nine new table grape genotypes selected from a breeding program to obtain new cultivars of seedless table grapes, well adapted to the climatic change and with higher nutraceutical properties. The grape polyphenolic profile was characterized by Ultra-High-Performance Liquid Chromatography/Quadrupole-Time of Flight mass spectrometry analysis. GSE antioxidant activity was determined by the ABTS, DPPH, and ORAC assays; GSE cell growth inhibition test was carried out in the Caco2 human cancer cell line. The nine GSEs showed different flavonoid and non-flavonoid profiles, and all possessed antioxidant activity, with the 'Aika N.', 'Turese N.', and 'Egnatia N.' the most active. As anticancer activity against the tested cancer cell line, 'Daunia N.' and 'Apenestae N.' showed the EC50 after 24 h of 35.60 µg/mL and 150.91 µg/mL, respectively. The relationship between polyphenolic profile and the antioxidant and anticancer activity of GSE was also investigated. Interestingly, among the different classes of polyphenolics, flavan-3-ols e proanthocyanidins showed the highest positive correlation with the anticancer activity of extracts. These findings can be helpful for the preparation of new extracts for the pharmaceutical and nutraceutical industry and geneticists working in vine breeding programs.

Modified WCRF/AICR Score and All-Cause, Digestive System, Cardiovascular, Cancer and Other-Cause-Related Mortality: A Competing Risk Analysis of Two Cohort Studies Conducted in Southern Italy.

BACKGROUND: In real life, nutrition goes beyond purely biological domains. Primary prevention is the most efficient approach for reducing the risk of mortality. We aimed to study the association of lifestyle, as measured by a modified World Cancer Research Fund/American Institute for Cancer Research (mWCRF/AICR) scoring system with all-cause, digestive system disease-related (DSD-related), cardiovascular disease-related (CVD-related), cancer-related and other cause-related mortality using data from two population-based cohort studies conducted in Southern Italy. METHODS: A random sample of 5271 subjects aged 18 years or older was enrolled in 2005-2006 and followed up until 2020. Usual food intakes were estimated using a validated dietary questionnaire. Competing risks survival models were applied. RESULTS: High adherence to the mWCRF/AICR score was found to be statistically significant and negatively associated with all-cause mortality (HR 0.56, 95%CI 0.39; 0.82), DSD-related mortality (SHR 0.38, 95%CI 0.15; 0.97) and cancer-related mortality (SHR 0.43, 95%CI 0.19; 0.97) in the male sub-cohort and other-cause mortality (SHR 0.43, 95%CI 0.21; 0.88) only in the female group. CONCLUSIONS: This mWCRF/AICR score can be seen as a simple, easy tool for use in clinical practice to evaluate both qualitative and quantitative aspects of the diet.