Differences of skin carotenoids and adherence to the Mediterranean Diet pattern in adults from Southern Italy and Dominican Republic.

BACKGROUND: The measurement of the skin carotenoids using the Veggie Meter® has emerged as a rapid objective method for assessing fruit and vegetable intake, highly recommended by the Mediterranean Diet (MD), which represents one of the healthiest dietary patterns, worldwide. This study aimed to examine differences in skin carotenoid content and degree of adherence to the MD pattern between two adult populations from Southern Italy and the Dominican Republic. METHODS: This cross-sectional study enrolled a total of 995 adults, 601 subjects from Italy and 394 from the Dominican Republic. All participants underwent anthropometric measurements and skin carotenoid assessment by Veggie Meter®. Adherence to the MD and lifestyle were evaluated using the Mediterranean Diet Adherence Screener (MEDAS) and the Mediterranean Lifestyle Index (MEDLIFE) questionnaires. Correlations between the skin carotenoid and MEDAS score were estimated using Pearson's correlation coefficient. Multiple linear regression models were created to determine variables that affect skin carotenoid score for both populations. RESULTS: Mean total skin carotenoids were higher in the Italian compared to the Dominican Republic population (342.4 ± 92.4 vs 282.9 ± 90.3; p < 0.005) regardless of sex (women: 318.5 ± 88.9 vs 277.3 ± 91.9, p < 0.005 and men: 371.7 ± 88.3 vs 289.5 ± 88.1, p < 0.005), and remaining statistically significant after age-adjustment of the Dominican Republic sample. Using the MEDAS questionnaire, we found a higher MD adherence score in the Italian than in the Dominican Republic population also after age-adjusting data (7.8 ± 2.1 vs 6.2 ± 3.7; p < 0.005) and even when categorized by sex (Italian vs age-adjusted Dominican Republic women: 7.9 ± 2.1 vs 6.3 ± 2.6; Italian vs age-adjusted Dominican Republic men: 7.7 ± 2.2 vs 6.0 ± 4.7; p < 0.005). Using the MEDLIFE test, total Italians presented a lower score with respect to the age-adjusted Dominican Republic population (3.2 ± 1.2 vs 3.4 ± 1.4; p < 0.05). In multiple regression analysis, skin carotenoids were associated with sex and negatively associated with BMI in the Italian population (sex: ß: 54.95; 95% CI: 40.11, 69.78; p < 0.0001; BMI: ß: - 1.60; 95% CI: - 2.98,0.86; p = 0.03), while they resulted associated with age and sex in the Dominican Republic population (age: ß: 2.76; 95% CI: 1.92, 3.56; p < 0.001; sex: ß: 23.29; 95% CI: 5.93, 40.64; p = 0.009). Interestingly, skin carotenoids were positively correlated with MEDAS score in both populations (Italy: r = 0.03, p < 0.0001, Dominican Republic: r = 0.16, p = 0.002). CONCLUSIONS: This study provides the assessment of the adherence to the MD and skin carotenoid content in adults living in Southern Italy and the Dominican Republic, showing a higher MD adherence score and a skin carotenoid content in inhabitants from the Mediterranean region. Our findings highlight the need to globally encourage fruit and vegetable intake, particularly in non-Mediterranean area.

Mediterranean diet: a potential player in the link between oral microbiome and oral diseases.

Background: The oral microbiome is a complex and dynamic assemblage of microorganisms that colonize different sites of the oral cavity maintaining both oral and systemic health. Therefore, when its composition is altered, oral diseases occur. Among oral inflammatory pathologies, periodontal diseases affect the tissues surrounding the teeth, representing the main cause of tooth loss and one of the most important threats to the oral health. Lifestyle and eating habits influence the composition of the human oral microbiota and the development and progression of oral diseases. In this context, the Mediterranean Diet (MD) model, comprising both healthy dietary choices and lifestyle, is linked to the prevention of several metabolic and chronic-degenerative pathological processes, including oral diseases. Indeed, the MD is a plant-based diet, enriched of anti-inflammatory and antioxidant nutrients, which may induce beneficial effects against dental caries and periodontal diseases. Aim: This review summarizes the role of the oral microbiome in the development of the oral diseases and the potential of MD in modulating the oral microbiome leading to implications for oral health. Conclusions: The data collected highlight the need to promote the MD pattern along with the correct hygiene habits to prevent the development of oral diseases.

The oral microbiome is a complex and dynamic assemblage of microorganisms that colonize different sites of the oral cavity maintaining both oral and systemic health.The Mediterranean Diet (MD) model, comprising both healthy dietary choices and lifestyle, is linked to the prevention of several metabolic and chronic degenerative pathological processes, including oral diseases.The MD may represent a potential player in the link between oral microbiome and oral diseases.

A Comprehensive Review on the State of the Art of Breast Cancers in Italy.

Breast cancer (BC) currently represents one of the most prevalent cancers among women worldwide and the leading cause of cancer death among women, also negatively affecting the quality of life (QoL) in patients. Over the past two decades, BC research has led to extraordinary advances in our understanding of the disease, resulting in more effective treatments. However, its occurrence is still increasing. Several new treatments are now under development worldwide, but they are not devoid of well-- known side effects, and a great number of patients develop endocrine resistance. Nevertheless, the design and synthesis of more suitable strategies and new drugs to treat breast cancers, overcome resistance and side effects, and obtain better therapeutic outcomes are needed. In this review, we summarize the therapies and the clinical studies currently ongoing in Italy for the treatment of BCs, mainly HER2+ MBC, HER2-low MBC, and TNBC, focusing on the most recent ones, also in consideration of diverse facets, including some aspects related to QoL. Finally, some studies related to the usefulness of physical activity in BC will be cited.

Fifteen Years of Iodine Prophylaxis in Italy: Results of a Nationwide Surveillance (Period 2015-2019).

CONTEXT: In 2005, a nationwide program of iodine prophylaxis on a voluntary basis was implemented in Italy by law. However, recent data on iodine status are lacking. OBJECTIVE: The aim of this study was to evaluate efficiency, effectiveness, and possible adverse effects (increased occurrence of thyroid autoimmunity and hyperthyroidism) of the Italian iodine prophylaxis program. METHODS: From 2015 to 2019, a nationwide survey was performed. The use of iodized salt was evaluated in a sample of 164 593 adults and in 998 school canteens. A sample of 4233 schoolchildren (aged 11-13 years) was recruited to assess urinary iodine concentration, prevalence of goiter, and thyroid hypoechogenicity on ultrasound, with the latter being an indirect indicator of thyroid autoimmunity. Neonatal TSH values of 197 677 infants screened in regions representative of Northern, Central, and Southern Italy were analyzed to investigate the percentage of TSH values >5.0 mIU/L. Data on methimazole prescriptions were analyzed as indirect indicators of new cases of hyperthyroidism. RESULTS: The prevalence of the use of iodized salt was 71.5% in adult population and 78% in school canteens. A median urinary iodine concentration of 124 µg/L, a prevalence of goiter of 2.2%, and a prevalence of thyroid hypoechogenicity of 5.7% were observed in schoolchildren. The percentage of neonatal TSH values >5.0 mIU/L resulted still higher (5.1%) than the World Health Organization threshold of 3.0%, whereas the prescriptions of methimazole showed a reduction of 13.5%. CONCLUSION: Fifteen years of iodine prophylaxis have led to iodine sufficiency in Italy, although there still is concern about iodine nutritional status during pregnancy.

Impact of COVID-19 Lockdown on Metabolic/Inflammatory Profile in Adolescents: Cellular Studies and Predictive Biomarkers.

CONTEXT: The COVID-19 pandemic and its lockdown restrictions changed people's lifestyles with potential negative impact on health. OBJECTIVE: This longitudinal study aimed to assess the COVID-19 lockdown influence on the adherence to the Mediterranean diet (MD) pattern and its effects on the metabolic inflammatory profile in a cohort of healthy adolescents. METHODS: We analyzed anthropometric measurements, body composition, and MD adherence along with serum metabolic and inflammatory profile in 77 healthy adolescents from southern Italy before and after the COVID-19 pandemic lockdown. Additionally, we evaluated the biological properties of prelockdown and postlockdown serum on human HepG2 and HuH-7 hepatic cells. RESULTS: We did not observe any significant differences in anthropometric and body composition parameters as well as MD adherence score in adolescents between prelockdown and postlockdown COVID-19. Intriguingly, although the metabolic profile of adolescents postlockdown was within the normal range, we evidenced increased levels of fasting glucose, triglycerides, total cholesterol, and low-density lipoprotein (LDL) along with a reduction in high-density lipoprotein (HDL) in postlockdown compared with prelockdown adolescent serum. In addition, elevated levels of tumor necrosis factor (TNF)-α, interleukin-1ß, and ferritin were found in postlockdown adolescents compared with their prelockdown counterparts. Consistent with the biochemical parameters, we observed enhanced lipid accumulation with altered mitochondrial functions and increased reactive oxygen species production in HepG2 and HuH-7 cells treated with pooled serum from postlockdown with respect to prelockdown period. Receiver operator characteristic curve analysis identified total cholesterol, LDL, HDL, TNF-α, and ferritin to be predictive serum markers for metabolic and inflammatory profiling after the lockdown period. CONCLUSION: Our findings highlight that the COVID-19 lockdown, forcing sedentary behavior, had a negative impact on adolescents' metabolic and inflammatory profile which may result in long-term poor health outcomes.

Association between Skin Carotenoid Score Measured with Veggie Meter® and Adherence to the Mediterranean Diet among Adolescents from Southern Italy.

The Veggie Meter® (Longevity Link Corporation, Salt Lake City, UT, USA), is a new portable device for the non-invasive and rapid detection of skin carotenoid content, which represents an acceptable biomarker for the evaluation of fruit and vegetable (FV) intake. FVs are important components of a healthy diet, including the Mediterranean Diet (MD), which is a plant-based dietary pattern. Here, we evaluated the adherence to the MD via the administration of two online food questionnaires, and we measured the skin carotenoid content using the Veggie Meter® in a cohort of 498 healthy adolescents (233 males and 265 females) from Southern Italy. Using KIDMED and the MD Pyramid tests to assess the adherence to the MD, we found an average adherence (5.43 ± 2.57 and 7.20 ± 1.93, respectively) to the MD in our sample population. Moreover, we observed that the skin carotenoid score was 364.75 ± 98.29, which was within the normal range and inversely related to the BMI (r = -0.1461, p = 0.0011). Similar results were observed when the population was categorized by sex. Interestingly, we demonstrated, for the first time, a positive correlation between the carotenoid score and the adherence to the MD assessed using both the KIDMED and MD Pyramid tests in the total population (r = -0.2926, p < 0.0001 and r = -0.1882, p < 0.0001, respectively). The same direct correlation was found in adolescents according to their sex. Our findings highlight the potential of the Veggie Meter® as a feasible and promising tool for evaluating adherence to the MD and, ultimately, to promote healthy eating habits among adolescents.

Benzothiazole-Phthalimide Hybrids as Anti-Breast Cancer and Antimicrobial Agents.

The benzothiazole nucleus is a major heterocyclic scaffold whose therapeutic potential has been thoroughly explored due to its structural simplicity and ease of synthesis. In fact, several benzothiazole derivatives have been synthesized over time, demonstrating numerous pharmacological properties such as anticancer, antimicrobial, anti-inflammatory, and antioxidant activities. Herein, we propose a new series of benzothiazole-phthalimide hybrids obtained by linking the phthalimide moiety to differently substituted benzothiazole nuclei through the N atom. These compounds have been screened for their anticancer properties against two human breast cancer cell lines. Furthermore, we delved into the mechanism of action of the most active hybrid, compound 3h, by assessing its capability to damage the nuclear DNA, trigger the apoptotic process in the high metastatic MDA-MB-231 cells, and prevent cellular migration. Moreover, in view of the documented antimicrobial activities of the two scaffolds involved, we explored the antibacterial and antifungal effects of the studied compounds by means of the broth microdilution method. Among the studied compounds, 3h showed the highest antimicrobial activity, both against gram-positive and gram-negative bacterial strains belonging to the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and against fungal strains of the Candida species with MICs values ranging from 16 to 32 µg/mL.

FoxO3a Drives the Metabolic Reprogramming in Tamoxifen-Resistant Breast Cancer Cells Restoring Tamoxifen Sensitivity.

Tamoxifen-resistant breast cancer cells (TamR-BCCs) are characterized by an enhanced metabolic phenotype compared to tamoxifen-sensitive cells. FoxO3a is an important modulator of cell metabolism, and its deregulation has been involved in the acquisition of tamoxifen resistance. Therefore, tetracycline-inducible FoxO3a was overexpressed in TamR-BCCs (TamR/TetOn-AAA), which, together with their control cell line (TamR/TetOn-V), were subjected to seahorse metabolic assays and proteomic analysis. FoxO3a was able to counteract the increased oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) observed in TamR by reducing their energetic activity and glycolytic rate. FoxO3a caused glucose accumulation, very likely by reducing LDH activity and mitigated TamR biosynthetic needs by reducing G6PDH activity and hindering NADPH production via the pentose phosphate pathway (PPP). Proteomic analysis revealed a FoxO3a-dependent marked decrease in the expression of LDH as well as of several enzymes involved in carbohydrate metabolism (e.g., Aldolase A, LDHA and phosphofructokinase) and the analysis of cBioPortal datasets of BC patients evidenced a significant inverse correlation of these proteins and FoxO3a. Interestingly, FoxO3a also increased mitochondrial biogenesis despite reducing mitochondrial functionality by triggering ROS production. Based on these findings, FoxO3a inducing/activating drugs could represent promising tools to be exploited in the management of patients who are refractory to antiestrogen therapy.

miRNAs in the Box: Potential Diagnostic Role for Extracellular Vesicle-Packaged miRNA-27a and miRNA-128 in Breast Cancer.

Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer "theranostic" tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further studies are still required to address this challenging issue. The present study examined the expression profiles of EV-packaged miRNAs to identify novel miRNA signatures in breast cancer and verified their diagnostic accuracy. Circulating EVs were isolated from healthy controls and breast cancer patients and characterized following the MISEV 2018 guidelines. RNA-sequencing and real-time PCR showed that miRNA-27a and miRNA-128 were significantly down-regulated in patient-derived EVs compared to controls in screening and validation cohorts. Bioinformatics analyses of miRNA-target genes indicated several enriched biological processes/pathways related to breast cancer. Receiver operating characteristic (ROC) curves highlighted the ability of these EV-miRNAs to distinguish breast cancer patients from non-cancer controls. According to other reports, the levels of EV-miRNA-27a and EV-miRNA-128 are not associated with their circulating ones. Finally, evidence from the studies included in our systematic review underscores how the expression of these miRNAs in biofluids is still underinvestigated. Our findings unraveled the role of serum EV-derived miRNA-27a and miRNA-128 in breast cancer, encouraging further investigation of these two miRNAs within EVs towards improved breast cancer detection.

Association between HMGCR, CRP, and CETP gene polymorphisms and metabolic/inflammatory serum profile in healthy adolescents.

BACKGROUND: The complex interplay between health, lifestyle and genetics represents a critical area of research for understanding and promoting human well-being. Importantly, genetics plays a key role in determining individual susceptibility to disease and response to lifestyle. The aim of the present study was to identify genetic factors related to the metabolic/inflammatory profile of adolescents providing new insights into the individual predisposition to the different effects of the substances from the environment. METHODS: Association analysis of genetic variants and biochemical parameters was performed in a total of 77 healthy adolescents recruited in the context of the DIMENU study. RESULTS: Polymorphisms of 3-hydroxy-3-methylglutaril coenzyme A reductase (HMGCR; rs142563098), C-reactive protein gene (CRP; rs1417938, rs1130864), cholesteryl ester transfer protein (CETP; rs5030708), interleukin (IL)-10 (IL-10; rs3024509) genes were significantly associated (p < 0.05) with various serum metabolic parameters. Of particular interest were also the correlations between the HMGCRpolymorphism (rs3846663) and tumor necrosis factor (TNF)-α levels, as well Fatty-acid desaturase (FADS) polymorphism (rs7481842) and IL-10 level opening a new link between lipidic metabolism genes and inflammation. CONCLUSION: In this study, we highlighted associations between single nucleotide polymorphisms (SNPs) and serum levels of metabolic and inflammatory parameters in healthy young individuals, suggesting the importance of genetic profiling in the prevention and management of chronic disease.

A hybrid breast cancer/mesenchymal stem cell population enhances chemoresistance and metastasis.

Patients with triple-negative breast cancer remain at risk for metastatic disease despite treatment. The acquisition of chemoresistance is a major cause of tumor relapse and death, but the mechanisms are far from understood. We have demonstrated that breast cancer cells (BCCs) can engulf mesenchymal stem/stromal cells (MSCs), leading to enhanced dissemination. Here, we show that clinical samples of primary invasive carcinoma and chemoresistant breast cancer metastasis contain a unique hybrid cancer cell population coexpressing pancytokeratin and the MSC marker fibroblast activation protein-α. We show that hybrid cells form in primary tumors and that they promote breast cancer metastasis and chemoresistance. Using single-cell microfluidics and in vivo models, we found that there are polyploid senescent cells within the hybrid cell population that contribute to metastatic dissemination. Our data reveal that Wnt Family Member 5A (WNT5A) plays a crucial role in supporting the chemoresistance properties of hybrid cells. Furthermore, we identified that WNT5A mediates hybrid cell formation through a phagocytosis-like mechanism that requires BCC-derived IL-6 and MSC-derived C-C Motif Chemokine Ligand 2. These findings reveal hybrid cell formation as a mechanism of chemoresistance and suggest that interrupting this mechanism may be a strategy in overcoming breast cancer drug resistance.

CEBP-ß and PLK1 as Potential Mediators of the Breast Cancer/Obesity Crosstalk: In Vitro and In Silico Analyses.

Over the last two decades, obesity has reached pandemic proportions in several countries, and expanding evidence is showing its contribution to several types of malignancies, including breast cancer (BC). The conditioned medium (CM) from mature adipocytes contains a complex of secretes that may mimic the obesity condition in studies on BC cell lines conducted in vitro. Here, we report a transcriptomic analysis on MCF-7 BC cells exposed to adipocyte-derived CM and focus on the predictive functional relevance that CM-affected pathways/processes and related biomarkers (BMs) may have in BC response to obesity. CM was demonstrated to increase cell proliferation, motility and invasion as well as broadly alter the transcript profiles of MCF-7 cells by significantly modulating 364 genes. Bioinformatic functional analyses unraveled the presence of five highly relevant central hubs in the direct interaction networks (DIN), and Kaplan-Meier analysis sorted the CCAAT/enhancer binding protein beta (CEBP-ß) and serine/threonine-protein kinase PLK1 (PLK1) as clinically significant biomarkers in BC. Indeed, CEBP-ß and PLK1 negatively correlated with BC overall survival and were up-regulated by adipocyte-derived CM. In addition to their known involvement in cell proliferation and tumor progression, our work suggests them as a possible "deus ex machina" in BC response to fat tissue humoral products in obese women.

Anti-Inflammatory and Antioxidant Effects of Leaves and Sheath from Bamboo (Phyllostacys edulis J. Houz).

Bamboo (Phyllostacys edulis J. Houz) has become an emerging forest resource of economic and ecological significance with health benefits. Since the beneficial effects of the non-edible parts of bamboo have not been thoroughly explored, we characterized in this study bamboo leaf (BL) and sheath (BS) extracts. The total phenol and flavonoid content (TPC and TFC), antioxidant activity (ABTS, DPPH, FRAP and ß-carotene bleaching test) and anti-inflammatory properties were determined. Leaves exhibited a TPC value of 73.92 mg equivalent (eq) gallic acid/g fresh weight (FW) and a TFC value of 56.75 mg eq quercetin/g FW. Ultra-High-Performance Liquid Chromatography (UHPLC) coupled with photo diode array detector (PDA) analysis revealed evidence for the presence of protocatechuic acid, isoorientin, orientin and isovitexin in BL, whereas BS was rich in phenolic acids. Both samples demonstrated a significant ability to scavenge radicals against ABTS·+, with an inhibitory concentration of 50% of 3.07 µg/mL for BL and 6.78 µg/mL for BS. At a concentration of 0.1 and 0.2 mg/mL, BS decreased reactive oxygen species production without hampering cell viability in HepG2 liver cells, while at the same concentrations, BL exhibited cytotoxicity in HepG2 cells. In addition, 0.1 and 0.2 mg/mL BS and BL reduced Interleukin-6 and Monocyte Chemoattractant Protein-1 production in human lipopolysaccharide-stimulated THP-1 macrophages, without affecting cell viability. These findings highlight the anti-inflammatory and antioxidant properties of BL and BS, corroborating their different potential applications in the nutraceutical, cosmetic and pharmaceutical industries.

Promising Effects of N-Docosahexaenoyl Ethanolamine in Breast Cancer: Molecular and Cellular Insights.

Unhealthy dietary habits have been identified as a risk factor for the development and progression of cancer. Therefore, adopting a healthy eating pattern is currently recommended to prevent the onset of different types of cancers, including breast carcinoma. In particular, the Mediterranean diet, based on high consumption of omega-3 polyunsaturated fatty acids (N-3 PUFAs), such as those found in cold-water fish and other seafood, nuts, and seeds, is recommended to reduce the incidence of several chronic-degenerative diseases. Indeed, the consumption of N-3 PUFAs, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduced the risk of different types of cancer, including breast cancer. Moreover, they can counteract breast cancer progression and reduce the side effects of chemotherapy in breast cancer survival. Studies have demonstrated that DHA, exhibiting greater antitumor activity than EPA in breast cancer, can be attributed to its direct impact on breast cancer cells and also due to its conversion into various metabolites. N-docosahexaenoyl ethanolamine, DHEA, is the most studied DHA derivative for its therapeutic potential in breast cancer. In this review, we emphasize the significance of dietary habits and the consumption of N-3 polyunsaturated fatty acids, particularly DHA, and we describe the current knowledge on the antitumoral action of DHA and its derivative DHEA in the treatment of breast cancer.

Analysis of circulating extracellular vesicle derived microRNAs in breast cancer patients with obesity: a potential role for Let-7a.

BACKGROUND: The incidence of obesity, a known risk factor for several metabolic and chronic diseases, including numerous malignancies, has risen sharply in the world. Various clinical studies demonstrate that excessive Body Mass Index (BMI) may worsen the incidence, prognosis, and mortality rates of breast cancer. Thus, understanding the link tying up obesity and breast cancer onset and progression is critically important, as it can impact patients' survival and quality of life. Recently, circulating extracellular vesicle (EV) derived miRNAs have attracted much attention for their diagnostic, prognostic and therapeutic potential in oncology research. Although the potential role of EV-derived miRNAs in the early detection of breast cancer has been repeatedly mentioned, screening of miRNAs packaged within serum EVs has not yet been reported in patients with obesity. METHODS: Circulating EVs were isolated from normal weight (NW), and overweight/obese (OW/Ob) breast cancer patients and characterized by Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and protein marker expression. Evaluation of EV-associated miRNAs was conducted in a screening (RNA-seq) and a validation (qRT-PCR) cohort. Bioinformatic analysis was performed to uncover significantly enriched biological processes, molecular functions and pathways. ROC and Kaplain-Meier survival analyses were used for clinical significance. RESULTS: Comparison of serum EV-derived miRNAs from NW and OW/Ob patients detected seven differentially expressed miRNAs (let-7a-5p, miR-122-5p, miR-30d-5p, miR-126-3p, miR-27b-3p, miR-4772-3p, and miR-10a-5p) in the screening cohort. GO analysis revealed the enrichment of protein phosphorylation, intracellular signal transduction, signal transduction, and vesicle-mediated transport among the top biological processes. In addition, the target genes were significantly enriched in pathways related to PI3K/Akt, growth hormones, and insulin signalings, which are all involved in obesity-related diseases and/or breast cancer progression. In the validation cohort, qRT-PCR confirmed a significant down-regulation of EV-derived let-7a in the serum of OW/Ob breast cancer patients compared to NW patients. Let-7a levels also exhibited a negative correlation with BMI values. Importantly, decreased let-7a miRNA expression was associated with higher tumor grade and poor survival in patients with breast cancer. CONCLUSION: These results suggest that serum-EV derived miRNAs may reflect a differential profile in relation to a patient's BMI, which, once validated in larger cohorts of patients, could provide insights into novel specific biomarkers and innovative targets to prevent the progression of obesity-mediated breast cancer.

The Omega-3 Docosahexaenoyl Ethanolamide Reduces CCL5 Secretion in Triple Negative Breast Cancer Cells Affecting Tumor Progression and Macrophage Recruitment.

Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype lacking effective targeted therapies, is considered to feature a unique cellular microenvironment with high infiltration of tumor-associated macrophages (TAM), which contribute to worsening breast cancer patient outcomes. Previous studies have shown the antitumoral actions of the dietary omega-3 docosahexaenoic acid (DHA) in both tumor epithelial and stromal components of the breast cancer microenvironment. Particularly in breast cancer cells, DHA can be converted into its conjugate with ethanolamine, DHEA, leading to a more effective anti-oncogenic activity of the parent compound in estrogen receptor-positive breast cancer cells. Here, we investigated the ability of DHEA to attenuate the malignant phenotype of MDA-MB-231 and MDA-MB-436 TNBC cell lines, which in turn influenced TAM behaviors. Our findings revealed that DHEA reduced the viability of TNBC cells in a concentration-dependent manner and compromised cell migration and invasion. Interestingly, DHEA inhibited oxygen consumption and extracellular acidification rates, reducing respiration and the glycolytic reserve in both cell lines. In a co-culture system, TNBC cells exposed to DHEA suppressed recruitment of human THP-1 cells, reduced their viability, and the expression of genes associated with TAM phenotype. Interestingly, we unraveled that the effects of DHEA in TNCB cells were mediated by reduced C-C motif chemokine ligand 5 (CCL5) expression and secretion affecting macrophage recruitment. Overall, our data, shedding new light on the antitumoral effects of DHA ethanolamine-conjugated, address this compound as a promising option in the treatment of TNBC patients.

Serum from Adolescents with High Polyphenol Intake Exhibits Improved Lipid Profile and Prevents Lipid Accumulation in HepG2 Human Liver Cells.

The traditional Mediterranean diet (MD) is characterized by a high phenolic-rich food intake, including in particular vegetables and fruits, but also legumes, whole grain cereals, nuts, and extra virgin olive oil. Evidence for beneficial effects of polyphenols in humans depends on the amount consumed and on their bioavailability. Here, we evaluated the association between the estimated polyphenol intake by fruits and vegetables food source and serum biochemical parameters in healthy adolescents, recruited into the DIMENU research project. Categorizing adolescents into three groups according to their estimated total polyphenol intake, we found that adolescents who declared high consumption of polyphenols had a higher adherence to the MD and had a better serum lipid profile than adolescents consuming low amounts of polyphenols. Moreover, using human HepG2 liver cells treated with oleic acid as an in vitro model for studying lipid accumulation, we showed that intracellular lipid accumulation is alleviated by serum from adolescents consuming a polyphenol-rich diet following MD recommendations. Our data underline the importance of promoting adherence to the typical MD foods as a superior strategy to prevent metabolic and chronic diseases and to ensure a better quality of life among adolescents.

Ancient Wheat as Promising Nutraceuticals for the Prevention of Chronic and Degenerative Diseases.

In the context of a balanced diet, wheat, mainly used as whole grains, is a good source of nutrients, including fibers and bioactive compounds. Cereals belong to the Poaceae family and are crucial for maintaining a healthy status, granted by their nutritional and chemical properties. Recent studies have demonstrated that the intake of whole grains and grain-based products may reduce the risk of oxidative stress, thus lowering chronic and age-related disorders, such as obesity, cardiovascular diseases, type II diabetes and cancer. Indeed, several studies report that regular whole grain consumption is associated with lower levels of total and LDL-cholesterol, triglycerides, fasting glucose, blood pressure and body mass index. Moreover, ancient wheat species have become increasingly interested in human health, containing several nutraceutical compounds, such as vitamins and minerals. The numerous phytochemicals present in ancient wheat (polyphenols, carotenoids, phytosterols and phenolic compounds) provide, in fact, antioxidant properties, which are essential in the prevention of various chronic and degenerative diseases. This review aims to report information on ancient wheat species, discussing their composition and nutraceutical properties compared with modern varieties and highlighting the beneficial impact on human health.

Proteomic Profiling of Extracellular Vesicles Released by Leptin-Treated Breast Cancer Cells: A Potential Role in Cancer Metabolism.

Tumor extracellular vesicles (EVs), as endocytic vesicles able to transport nucleic acids, proteins, and metabolites in recipient cells, have been recognized fundamental mediators of cell-to-cell communication in breast cancer. The biogenesis and release of EVs are highly regulated processes and both the quantity of EVs and their molecular cargo might reflect the metabolic state of the producing cells. We recently demonstrated that the adipokine leptin, whose circulating levels correlate with adipose tissue expansion, is an inducer of EV release from breast cancer cells. Here, we show a specific proteomic signature of EVs released by MCF-7 breast cancer cells grown in the presence of leptin (Lep-EVs), in attempt to find additional molecular effectors linking obesity to breast cancer biology. An analysis of the proteomic profile of Lep-EVs by LC-MS/MS revealed a significant enrichment in biological processes, molecular functions, and cellular components mainly related to mitochondrial machineries and activity, compared to protein content of EVs from untreated breast cancer cells. Metabolic investigations, carried out to assess the autocrine effects of these vesicles on breast cancer cells, revealed that Lep-EVs were able to increase ATP levels in breast cancer cells. This result is associated with increased mitochondrial respiration evaluated by Seahorse analyzer, supporting the concept that Lep-EVs can modulate MCF-7 breast cancer cell oxidative metabolism. Moreover, taking into account the relevance of tumor immune cell crosstalk in the tumor microenvironment (TME), we analyzed the impact of these vesicles on macrophage polarization, the most abundant immune component in the breast TME. We found that tumor-derived Lep-EVs sustain the polarization of M0 macrophages, derived from the human THP-1 monocytic cells, into M2-like tumor-associated macrophages, in terms of metabolic features, phagocytic activity, and increased expression of CD206-positive population. Overall, our results indicate that leptin by inducing the release of EV-enriched in mitochondrial proteins may control the metabolism of MCF-7 breast cancer cells as well as that of macrophages. Characterization of tumor-derived EV protein cargo in an obesity-associated milieu, such as in the presence of elevated leptin levels, might allow identifying unique features and specific metabolic mechanisms useful to develop novel therapeutic approaches for treatment of breast cancer, especially in obese patients.

From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.

Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in the last decades and the deriving developed treatments, which significantly improved patients' outcome, the occurrence of resistance to therapies remains the major cause of relapse and mortality. Thus, efforts in identifying new markers to be exploited as molecular targets in cancer therapy are needed. This review will first give a glance on the diagnostic and therapeutic significance of histone deacetylase (HDAC) and voltage gated ion channels (VGICs) in cancer. Nevertheless, HDAC and VGICs have also been reported as molecular targets through which antiepileptic drugs (AEDs) seem to exert their anticancer activity. This should be claimed as a great advantage. Indeed, due to the slowness of drug approval procedures, the attempt to turn to off-label use of already approved medicines would be highly preferable. Therefore, an updated and accurate overview of both preclinical and clinical data of commonly prescribed AEDs (mainly valproic acid, lamotrigine, carbamazepine, phenytoin and gabapentin) in breast, prostate, brain and other cancers will follow. Finally, a glance at the emerging attempt to administer AEDs by means of opportunely designed drug delivery systems (DDSs), so to limit toxicity and improve bioavailability, is also given.