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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. 3 key messages: 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. [ABSTRACT FROM AUTHOR]

The Mediterranean Diet (MD) is characterized by a high intake of fruits and vegetables (FVs), which is considered as an important contributor to the beneficial effects of the MD pattern. In this cross-sectional study, we compared the food choices, evaluated by dietary habit questionnaires, of a sample of 995 adults, including 601 and 394 participants from Southern Italy and the Dominican Republic, respectively. In addition, we focused on their FV consumption, assessed by the Mediterranean Diet Adherence Screener (MEDAS) questionnaire, and on its association with skin carotenoid levels as measured by the Veggie Meter®. We found that a significantly higher percentage of Italians had five meals/day and breakfast compared to Dominicans (five meals/day: 43 vs. 25, p < 0.05; breakfast: 89 vs. 79, p < 0.05), whereas a lower percentage of participants from Italy consumed snacks between the two meals compared to the Dominican Republic population (47 vs. 70, p < 0.005). Most of the participants from both populations had breakfast at home. However, 59.3% of Italians and 27.5% of Dominicans (p = 0.005) had breakfast between 7:00 and 9:00 a.m., whereas 5.8% and 27.5% (p = 0.001) had breakfast after 9:00 a.m., respectively. Milk/yogurt and eggs were the most consumed foods for breakfast in Italy and the Dominican Republic, respectively. Regarding the main meals, most of the Italians and Dominicans had a first course for lunch and a second course for dinner. Of note, we observed that approximately half of the Italians ate FVs in their main meals and had a higher carotenoid score than the Dominicans. Interestingly, in the multiple linear regression analysis, we found that the carotenoid score was positively associated with sex (β = 0.078; p = 0.009), age (β = 0.008; p = 0.001), vegetable consumption (β = 0.12; p = 0.041) and the perception of a healthy diet (β = 0.12; p = 0.001) in the Dominic Republic population, while the carotenoid score was directly associated with sex (β = 54.97; p < 0.0001) and both vegetable (β = 25.42; p = 0.0008) and fruit (β = 38.61; p < 0.0001) consumption in the Italian sample. Our findings confirm the need to promote nutrition-based interventions to encourage FV intake, particularly in non-Mediterranean countries. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The overexpression of phosphodiesterase (PDE) 5 is frequently found in various human cancers, such as those of the breast. However, PDE5's role in the tumor microenvironment is still unknown. As PDE5 represents a high-value therapeutic target, we investigated whether the expression and function of PDE5 in breast cancer-associated fibroblasts (CAFs) may be clinically relevant to malignant progression. PDE5 expression was increased in human breast cancer stroma compared with normal stroma and was correlated to a shorter overall survival. Treatment of CAFs, isolated from breast tumor biopsies, with selective PDE5 inhibitors inhibited their proliferation, motility, and invasiveness, and negatively controlled tumor–stroma interactions in both 'in vitro' and 'in vivo' models. PDE5 stable overexpression transformed immortalized mouse embryonic fibroblasts (MEFs) towards an activated fibroblast phenotype, impacting their intrinsic characteristics and paracrine effects on breast cancer cell growth and migration through an enhanced production of the C-X-C motif chemokine 16 (CXCL16). On the other hand, CAF exposure to PDE5 inhibitors was associated with reduced CXCL16 expression and secretion. Importantly, CXCL16 levels in breast cancer stroma showed a strong correlation with PDE5 levels and poor patient outcomes. In conclusion, PDE5 is overexpressed in breast cancer stroma, enhances the tumor-stimulatory activities of fibroblasts, and impacts clinical outcomes; thus, we propose this enzyme as an attractive candidate for prognosis and a potential target for treatments in breast cancer patients. [ABSTRACT FROM AUTHOR]

Metaplastic breast carcinomas (mBrCA) are a highly aggressive subtype of triple-negative breast cancer with histologic evidence of epithelial-to-mesenchymal transition and aberrant differentiation. Inactivation of the tumor suppressor gene cellular communication network factor 6 (CCN6; also known as Wnt1-induced secreted protein 3) is a feature of mBrCAs, and mice with conditional inactivation of Ccn6 in mammary epithelium (Ccn6-KO) develop spindle mBrCAs with epithelial-to-mesenchymal transition. Elucidation of the precise mechanistic details of how CCN6 acts as a tumor suppressor in mBrCA could help identify improved treatment strategies. In this study, we showed that CCN6 interacts with the Wnt receptor FZD8 and coreceptor LRP6 on mBrCA cells to antagonize Wnt-induced activation of β-catenin/TCF-mediated transcription. The histone methyltransferase EZH2 was identified as a β-catenin/TCF transcriptional target in Ccn6-KO mBrCA cells. Inhibiting Wnt/β-catenin/TCF signaling in Ccn6-KO mBrCA cells led to reduced EZH2 expression, decreased histone H3 lysine 27 trimethylation, and deregulation of specific target genes. Pharmacologic inhibition of EZH2 reduced growth and metastasis of Ccn6-KO mBrCA mammary tumors in vivo. Low CCN6 is significantly associated with activated β-catenin and high EZH2 in human spindle mBrCAs compared with other subtypes. Collectively, these findings establish CCN6 as a key negative regulator of a β-catenin/TCF/EZH2 axis and highlight the inhibition of β-catenin or EZH2 as a potential therapeutic approach for patients with spindle mBrCAs.  Significance: CCN6 deficiency drives metaplastic breast carcinoma growth and metastasis by increasing Wnt/β-catenin activation to upregulate EZH2, identifying EZH2 inhibition as a mechanistically guided treatment strategy for this deadly form of breast cancer., (©2024 American Association for Cancer Research.)