Modulatory Effects of Polyphenols on Apoptosis Induction: Relevance for Cancer Prevention

Polyphenols, occurring in fruit and vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products, have been demonstrated to have clear antioxidant properties in vitro, and many of their biological actions have been attributed to their intrinsic reducing capabilities. However, it has become clear that, in complex biological systems, polyphenols exhibit several additional properties which are yet poorly understood. Apoptosis is a genetically controlled and evolutionarily conserved form of cell death of critical importance for the normal embryonic development and for the maintenance of tissue homeostasis in the adult organism. The malfunction of the death machinery may play a primary role in various pathological processes, since too little or too much apoptosis can lead to proliferative or degenerative diseases, respectively. Cancer cells are characterized by a deregulated proliferation, and/or an inability to undergo programmed cell death. A large body of evidence indicates that polyphenols can exert chemopreventive effects towards different organ specific cancers, affecting the overall process of carcinogenesis by several mechanisms: inhibition of DNA synthesis, modulation of ROS production, regulation of cell cycle arrest, modulation of survival/proliferation pathways. In addition, polyphenols can directly influence different points of the apoptotic process, and/or the expression of regulatory proteins. Although the bulk of data has been obtained in in vitro systems, a number of clinical studies suggesting a preventive and therapeutic effectiveness of polyphenols in vivo is available. However, a deeper knowledge of the underlying mechanisms responsible for the modulation of apoptosis by polyphenols, and their real effectiveness, is necessary in order to propose them as potential chemopreventive and chemotherapeutic candidates for cancer treatment

Characteristics of COVID-19 cases in Italy from a sex/gender perspective

Introduction: Coronavirus disease 19 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To date, few data on clinical features and risk factors for disease severity and death by gender are available. Aim: The current study aims to describe from a sex/gender perspective the characteristics of the SARS-CoV-2 cases occurred in the Italian population from February 2020 until October 2021. Method and results: We used routinely collected data retrieved from the Italian National Surveillance System. The highest number of cases occurred among women between 40 and 59 years, followed by men in the same age groups. The proportion of deaths due to COVID-19 was higher in men (56.46%) compared to women (43.54%). Most of the observed deaths occurred in the elderly. Considering the age groups, the clinical outcomes differed between women and men in particular in cases over 80 years of age; with serious or critical conditions more frequent in men than in women. Conclusions: Our data clearly demonstrate a similar number of cases in women and men, but with more severe disease and outcome in men, thus confirming the importance to analyse the impact of sex and gender in new and emerging diseases

Transcriptome Profiles of Human Visceral Adipocytes in Obesity and Colorectal Cancer Unravel the Effects of Body Mass Index and Polyunsaturated Fatty Acids on Genes and Biological Processes Related to Tumorigenesis

Obesity, a low-grade inflammatory condition, represents a major risk factor for the development of several pathologies including colorectal cancer (CRC). Although the adipose tissue inflammatory state is now recognized as a key player in obesity-associated morbidities, the underlying biological processes are complex and not yet precisely defined. To this end, we analyzed transcriptome profiles of human visceral adipocytes from lean and obese subjects affected or not by CRC by RNA sequencing (n = 6 subjects/category), and validated selected modulated genes by real-time qPCR. We report that obesity and CRC, conditions characterized by the common denominator of inflammation, promote changes in the transcriptional program of adipocytes mostly involving pathways and biological processes linked to extracellular matrix remodeling, and metabolism of pyruvate, lipids and glucose. Interestingly, although the transcriptome of adipocytes shows several alterations that are common to both disorders, some modifications are unique under obesity (e.g., pathways associated with inflammation) and CRC (e.g., TGFβ signaling and extracellular matrix remodeling) and are influenced by the body mass index (e.g., processes related to cell adhesion, angiogenesis, as well as metabolism). Indeed, cancer-induced transcriptional program is deeply affected by obesity, with adipocytes from obese individuals exhibiting a more complex response to the tumor. We also report that in vitro exposure of adipocytes to ω3 and ω6 polyunsaturated fatty acids (PUFA) endowed with either anti- or pro-inflammatory properties, respectively, modulates the expression of genes involved in processes potentially relevant to carcinogenesis, as assessed by real-time qPCR. All together our results suggest that genes involved in pyruvate, glucose and lipid metabolism, fibrosis and inflammation are central in the transcriptional reprogramming of adipocytes occurring in obese and CRC-affected individuals, as well as in their response to PUFA exposure. Moreover, our results indicate that the transcriptional program of adipocytes is strongly influenced by the BMI status in CRC subjects. The dysregulation of these interrelated processes relevant for adipocyte functions may contribute to create more favorable conditions to tumor establishment or favor tumor progression, thus linking obesity and colorectal cancer

Critical role of maternal selenium nutrition in neurodevelopment: Effects on offspring behavior and neuroinflammatory profile

Research in both animals and humans shows that some nutrients are important in pregnancy and during the first years of life to support brain and cognitive development. Our aim was to evaluate the role of selenium (Se) in supporting brain and behavioral plasticity and maturation. Pregnant and lactating female rats and their offspring up to postnatal day 40 were fed isocaloric diets differing in Se content - i.e., Optimal, SubOptimal, and Deficient - and neurodevelopmental, neu-roinflammatory, and anti-oxidant markers were analyzed. We observed early adverse behavioral changes in juvenile rats only in SubOptimal offspring. In addition, SubOptimal, more than Deficient supply reduced basal glial reactivity in sex dimorphic and brain-area specific fashion. In female offspring, Deficient and SubOptimal diets reduced the antioxidant Glutathione peroxidase (GPx) activity in the cortex and in the liver, the latter being the key organ regulating Se metabo-lism and homeostasis. The finding that Se SubOptimal was more detrimental than Se Deficient diet may suggest that maternal Se Deficient diet, leading to a lower Se supply at earlier stages of fetal development, stimulated homeostatic mechanisms in the offspring that were not initiated by SubOptimal Se. Our observations demonstrate that even moderate Se deficiency during early life negatively may affect, in a sex-specific manner, optimal brain development

Bioavailability of the Polyphenols: Status and Controversies

The current interest in polyphenols has been driven primarily by epidemiological studies. However, to establish conclusive evidence for the effectiveness of dietary polyphenols in disease prevention, it is useful to better define the bioavailability of the polyphenols, so that their biological activity can be evaluated. The bioavailability appears to differ greatly among the various phenolic compounds, and the most abundant ones in our diet are not necessarily those that have the best bioavailability profile. In the present review, we focus on the factors influencing the bioavailability of the polyphenols. Moreover, a critical overview on the difficulties and the controversies of the studies on the bioavailability is discussed

Sourdough Bread Made from Wheat and Nontoxic Flours and Started with Selected Lactobacilli Is Tolerated in Celiac Sprue Patients

This work was aimed at producing a sourdough bread that is tolerated by celiac sprue (CS) patients. Selected sourdough lactobacilli had specialized peptidases capable of hydrolyzing Pro-rich peptides, including the 33-mer peptide, the most potent inducer of gut-derived human T-cell lines in CS patients. This epitope, the most important in CS, was hydrolyzed completely after treatment with cells and their cytoplasmic extracts (CE). A sourdough made from a mixture of wheat (30%) and nontoxic oat, millet, and buckwheat flours was started with lactobacilli. After 24 h of fermentation, wheat gliadins and low-molecular-mass, alcohol-soluble polypeptides were hydrolyzed almost totally. Proteins were extracted from sourdough and used to produce a peptic-tryptic digest for in vitro agglutination tests on K 562(S) subclone cells of human origin. The minimal agglutinating activity was ca. 250 times higher than that of doughs chemically acidified or started with baker's yeast. Two types of bread, containing ca. 2 g of gluten, were produced with baker's yeast or lactobacilli and CE and used for an in vivo double-blind acute challenge of CS patients. Thirteen of the 17 patients showed a marked alteration of intestinal permeability after ingestion of baker's yeast bread. When fed the sourdough bread, the same 13 patients had values for excreted rhamnose and lactulose that did not differ significantly from the baseline values. The other 4 of the 17 CS patients did not respond to gluten after ingesting the baker's yeast or sourdough bread. These results showed that a bread biotechnology that uses selected lactobacilli, nontoxic flours, and a long fermentation time is a novel tool for decreasing the level of gluten intolerance in humans

Visceral fat adipocytes from obese and colorectal cancer subjects exhibit distinct secretory and ω6 polyunsaturated fatty acid profiles and deliver immunosuppressive signals to innate immunity cells

Obesity is a low-grade chronic inflammatory state representing an important risk factor for colorectal cancer (CRC). Adipocytes strongly contribute to inflammation by producing inflammatory mediators. In this study we investigated the role of human visceral fat adipocytes in regulating the functions of innate immunity cells. Adipocyte-conditioned media (ACM) from obese (n = 14) and CRC (lean, n = 14; obese, n = 13) subjects released higher levels of pro-inflammatory/immunoregulatory factors as compared to ACM from healthy lean subjects (n = 13). Dendritic cells (DC), differentiated in the presence of ACM from obese and CRC subjects, expressed elevated levels of the inhibitory molecules PD-L1 and PD-L2, and showed a reduced IL-12/IL-10 ratio in response to both TLR ligand- and γδ T lymphocyte-induced maturation. Furthermore, CRC patient-derived ACM inhibited DC-mediated γδ T cell activation. The immunosuppressive signals delivered by ACM from obese and CRC individuals were associated with a pro-inflammatory secretory and ω6 polyunsaturated fatty acid profile of adipocytes. Interestingly, STAT3 activation in adipocytes correlated with dihomo-γlinolenic acid content and was further induced by arachidonic acid, which conversely down-modulated PPARγ. These results provide novel evidence for a cross-talk between human adipocytes and innate immunity cells whose alteration in obesity and CRC may lead to immune dysfunctions, thus setting the basis for cancer development

Polyphenols and human health : A prospectus

The lay press often heralds polyphenols as panacea for all sorts of diseases. The rationale is that their antioxidant activity would prevent free radical damage to macromolecules. However, basic and clinical science is showing that the reality is much more complex than this and that several issues, notably content in foodstuff, bioavailability, or in vivo antioxidant activity are yet to be resolved. We summarize the recent findings concerning the effects of polyphenols on human health, analyze the current limitations at pitfalls, and propose future directions for research

Joint data analysis in nutritional epidemiology: identification of observational studies and minimal requirements

Background: Joint data analysis from multiple nutrition studies may improve the ability to answer complex questions regarding the role of nutritional status and diet in health and disease. Objective: The objective was to identify nutritional observational studies from partners participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) Consortium, as well asminimal requirements for joint data analysis. Methods: A predefined template containing information on study design, exposure measurements (dietary intake, alcohol and tobacco consumption, physical activity, sedentary behavior, anthropometric measures, and sociodemographic and health status), main health-related outcomes, and laboratory measurements (traditional and omics biomarkers) was developed and circulated to those European research groups participating in the ENPADASI under the strategic research area of "diet-related chronic diseases." Information about raw data disposition and metadata sharing was requested. A set of minimal requirements was abstracted from the gathered information. Results: Studies (12 cohort, 12 cross-sectional, and 2 case-control) were identified. Two studies recruited children only and the rest recruited adults. All studies included dietary intake data. Twenty studies collected blood samples. Data on traditional biomarkers were available for 20 studies, of which 17 measured lipoproteins, glucose, and insulin and 13 measured inflammatory biomarkers. Metabolomics, proteomics, and genomics or transcriptomics data were available in 5, 3, and 12 studies, respectively. Although the study authors were willing to share metadata, most refused, were hesitant, or had legal or ethical issues related to sharing raw data. Forty-one descriptors of minimal requirements for the study data were identified to facilitate data integration. Conclusions: Combining study data sets will enable sufficiently powered, refined investigations to increase the knowledge and understanding of the relation between food, nutrition, and human health. Furthermore, t he minimal requirements for study data may encourage more efficient secondary usage of existing data and provide sufficient information for researchers to draft future multicenter research proposals in nutrition