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Osteoporosis is a progressive bone disorder characterized by decreased bone mineral density and structural deterioration, leading to increased fracture risk. Conventional treatments, although effective, are limited by adverse effects and low long-term adherence. In recent years, polyphenols, plant-derived bioactive compounds, have emerged as promising candidates for bone health promotion due to their antioxidant, anti-inflammatory, and osteo-regulatory properties. This review synthesizes the current preclinical and clinical evidence on the potential of polyphenols, including quercetin, resveratrol, curcumin, isoflavones, and epigallocatechin gallate, to modulate bone metabolism and prevent or mitigate osteoporosis. Mechanistically, polyphenols enhance osteoblastogenesis, inhibit osteoclast differentiation, regulate the RANKL/OPG axis, and activate key osteogenic pathways such as Wnt/β-catenin and MAPKs. Additionally, their estrogen-like activity and ability to modulate gut microbiota offer further therapeutic potential. Preclinical models consistently demonstrate improvements in bone mass, architecture, and turnover markers, while clinical trials, although limited, support their role in preserving bone density, particularly in postmenopausal women. Despite promising outcomes, variability in bioavailability, dosage, and study design limits current translational application. Further large-scale clinical studies and standardized formulations are needed. Polyphenols represent a compelling adjunct or alternative approach in the integrated management of osteoporosis.

Abstract Chronic kidney disease (CKD) is highly prevalent in patients with chronic heart failure (CHF) and increases the risk of overall and cardiovascular (CV) mortality. Despite evidence supporting the effectiveness of angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers, and mineralocorticoid receptor antagonists in decreasing mortality in patients with CHF, CKD hampers the optimization of standard pharmacologic therapy for heart failure. Therefore, other treatment options are needed to optimize treatment outcomes in CHF patients with CKD. The first-in-class angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, has a complementary activity that counteracts the potential unwanted long-term effects of over-activation of the renin–angiotensin–aldosterone system. Sacubitril/valsartan reduced the risk of CV mortality compared to standard therapy with an ACE-I in patients with heart failure with reduced ejection fraction (HFrEF) in the PARADIGM-HF trial and has been shown to be safe and effective in a broad range of HFrEF patients. However, data on the efficacy and tolerability of sacubitril/valsartan in patients with more advanced CKD are limited. This review discusses the evidence for the role of sacubitril/valsartan in providing additional renal benefit in patients with HFrEF. Data from clinical trials and real-world experience in patients with HFrEF and advanced CKD support the benefits of dual angiotensin/neprilysin inhibition across the breadth of kidney disease stages, including patients with significant renal impairment that was not reported in the pivotal PARADIGM-HF trial, and suggests a central role for the cardiac benefits of sacubitril/valsartan in nephroprotection.

Mercury (Hg) exposure is a major environmental risk factor, closely linked to oxidative stress and cardiovascular disease. Red blood cells (RBC), due to their high oxygen exposure and lack of repair mechanisms, are particularly sensitive to oxidative injury and are key indicators of systemic redox imbalance. This study evaluates the protective effects of polyphenolic extracts from Annurca apple, specifically flesh and peel, from both ripe and unripe fruit, on HgCl2-exposed human RBCs. Key oxidative stress markers were measured, including ROS production, GSH levels, lipid peroxidation (TBARS), MetHb formation, SH group content, microvesicle (MV) generation, and morphological changes. Peel extracts, particularly those from ripe apples, consistently exhibited stronger antioxidant and cytoprotective effects than flesh extracts, effectively reversing Hg-induced oxidative damage and preserving RBC integrity. Notably, these extracts restored redox homeostasis and GSH levels, reduced ROS and TBARS accumulation, prevented MetHb formation, and mitigated MV release and morphological alterations. These protective effects appear to involve multifactorial mechanisms. These findings highlight the nutraceutical potential of Annurca apple extracts in counteracting heavy metal-induced oxidative stress and support their possible relevance for future studies aimed at health protection and waste valorization.

The sustainable use of agri-food by-products offers a significant opportunity. Increasing evidence shows that these by-products have various bioactive compounds that help reduce inflammation and, in turn, the severity of several proliferative diseases. Numerous epidemiological studies have suggested an inverse relationship between the consumption of fruits and vegetables and the incidence of breast cancer. Anti-breast cancer effects involve a variety of mechanisms, inhibiting proliferation, migration, metastasis, and angiogenesis of breast tumor cells; inducing apoptosis and cell cycle arrest; and enhancing the sensitivity of breast tumor cells to radiotherapy and chemotherapy. Extensive research suggests that the Mediterranean diet has various bioactive compounds known to provide protective effects against a wide range of non-communicable diseases. Among the phytochemicals identified as protective against breast cancer, natural polyphenols have shown antioxidant, anti-inflammatory, immunomodulatory, and anticancer properties. This review highlights the potential role of natural dietary products and their primary bioactive components in preventing and treating breast cancer, with special emphasis on the mechanisms of action. The integration of agri-food by-products into the diet not only offers opportunities for the prevention and treatment of breast cancer but also promotes sustainable use of resources, contributing to the reduction of waste and the improvement of global health.

Vitamin D is increasingly recognized for its role in cardiovascular health beyond its well-established effects on bone metabolism. This review synthesizes findings from observational studies, interventional trials, and meta-analyses to clarify the mechanisms through which vitamin D impacts cardiovascular health, including its influence on vascular function, inflammation, and metabolic pathways. Additionally, this review emphasizes the importance of a personalized approach to vitamin D supplementation, integrating individual cardiovascular risk profiles, baseline vitamin D levels, and comorbid conditions, such as hypertension and diabetes. While current evidence supports the association between low vitamin D levels and increased cardiovascular mortality, this work contributes novel insights by proposing tailored strategies for supplementation, particularly for high-risk subgroups. Practical recommendations for implementing these strategies in clinical practice are also discussed, providing a framework for optimizing cardiovascular outcomes through individualized vitamin D management.

Heart failure is a leading cause of morbidity and mortality, with relevant social and economic burden on global healthcare system. Although the development of novel diagnostic tools and the advance in therapies have deeply influenced the diagnosis and treatment of this disease, improving both prognosis and life expectancy of patients, hospitalization is still high, and mortality remains considerable. MicroRNAs are small endogenous RNA molecules that post‐transcriptionally regulate gene expression in both physiological and pathological processes. In recent years, microRNA have arisen as attractive therapeutic targets in the treatment of a wide spectrum of pathologies, including heart failure. In cardiac pathology, deregulation of microRNAs expression and function is associated to adverse outcome and heart failure progression. Circulating levels of specific microRNAs have emerged as useful biomarkers for the diagnosis of heart failure or as prognostic indicators. In the present review, we summarize the state of current research on the role of miRNAs as biomarkers for diagnosis and prognosis in patients with heart failure and their use as potential therapeutic targets for this condition.

Introduction: Olive oil’s health benefits are widely known and extensively documented; its advantages are widespread, covering numerous areas of human health. Clinical and experimental data indicate that a Mediterranean Diet (MedDiet) with Extra Virgin Olive Oil (EVOO) lowers the risk of illnesses associated with oxidative stress, chronic inflammation, and weakened immunity, including cancer and cardiovascular disease (CVD). The European Food Safety Authority (EFSA) confirms that olive oil’s polyphenols help protect blood lipids against oxidative damage; thus, EVOO, crucial in the MedDiet, could be a functional food component. Olive oils must contain at least 5 mg of Hydroxytyrosol (HYTY) and its derivatives (oleuropein and Tyrosol (TY)) per 20 g to qualify for the EFSA-approved health claim. To provide a summary of clinical study results, this systematic review assessed the impact of Virgin olive oil (VOO) consumption on cardiovascular risk and disease prevention. Methods: The systematic review’s studies were collected from PubMed, Cochrane, Web of Science, and Scopus following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Population Intervention Comparison Outcome Population (PICO) framework. Results: Seventeen clinical studies were identified, which highlighted the association between VOO consumption (including EVOO) and a reduced risk of cardiovascular disease. Particularly, improvements in biomarkers involved in cardiometabolic pathways and subsequent cardiovascular events were recorded. The beneficial effect was attributed to the polyphenols contained in EVOO. Indeed, EVOO supplementation as part of the Mediterranean diet could improve patients’ quality of life in secondary prevention by demonstrating a positive correlation with the cardioprotective role of polyphenols. Discussion: A balanced diet with VOO represents a simple yet potent method to counteract metabolic dysfunctions associated with CVD. Despite these results, further multicenter clinical studies with a wider range of patients are required to confirm and better understand EVOO’s effects on the prevention of cardiovascular risk.

Background: Restenosis after coronary stent implantation remains a major clinical challenge, especially in patients with diabetes, long lesions, or multiple stents. Standard therapy with aspirin and P2Y12 inhibitors does not reliably prevent this complication. Objectives: We reviewed experimental and clinical evidence on cilostazol, a selective phosphodiesterase-3 inhibitor, as a strategy to reduce restenosis after percutaneous coronary intervention (PCI). Methods: Preclinical and clinical studies were critically appraised, focusing on the effects of cilostazol on vascular smooth muscle and endothelial cells, platelet aggregation, lipid metabolism, and restenosis rates. Results: Experimental models show that cilostazol inhibits smooth muscle proliferation and intimal hyperplasia after arterial injury. Clinical trials demonstrate reduced restenosis after balloon angioplasty and stent implantation compared with aspirin, ticlopidine, or clopidogrel. Although approved by the FDA for intermittent claudication, cilostazol remains underused in the prevention of coronary restenosis. Conclusions: Current evidence supports cilostazol as an effective adjunctive therapy to reduce restenosis following PCI. Wider adoption and further large-scale trials are warranted to better define its role in contemporary interventional practice.

The Mediterranean Diet (MD) is globally recognized not only for its well-established benefits to human health but also for its potential as a sustainable dietary model from environmental perspectives. Primarily based on plant-based foods, olive oil, fish, and seasonal and local products, the MD stands out for its ability to reduce overall mortality and the incidence of chronic diseases. At the same time, it is a low environmental impact dietary approach, contributing to the reduction in greenhouse gas emissions, water savings, biodiversity conservation, and soil regeneration. This narrative review was conducted by searching the Scopus and PubMed databases, covering all publications up to 2011, applying predefined inclusion and exclusion criteria, and ultimately including 33 studies. The paper provides a synthesis of the key elements that make the MD a paradigm of sustainability, analyzing critical indicators such as carbon, water, and energy footprints, land use, food waste generation, and carbon sequestration. It also addresses the decline in adherence to the MD, even in Mediterranean countries, highlighting the socio-economic, cultural, and behavioral causes, as well as the necessary strategies to promote its rediscovery and adaptation to contemporary contexts.

This study explores the sustainable valorization of Annurca apple by-products by examining the polyphenolic content and antioxidant activity of peel, flesh, and core at two ripening stages. Ripening significantly enhanced the concentration of bioactive compounds, particularly in the peel, where total polyphenols increased from 124.4 to 423.3 mg of CAE/100 g FW, flavonoids from 18.2 to 51.3 mg of quercetin equivalents, and ortho-diphenols from 11.9 to 36.1 mg of CAE. The flesh and core showed more moderate increases. Antioxidant activity, assessed using five in vitro assays (DPPH, ABTS, FRAP, TAC, and H2O2), was consistently highest in the peel, especially in the ABTS assay. Although the flesh had fewer phenolics, it showed a 1.5-fold increase during ripening, accompanied by improved antioxidant performance. The core also proved notable antioxidant potential, particularly in ripe samples. UHPLC-MS/MS analysis identified 11 phenolic compounds, showing tissue- and ripening-specific distribution. SDS-PAGE revealed a ripening-related increase in Thaumatin-like Protein 1a (TLP1a), especially in the core and flesh. Its association with tissues showing high antioxidant ability suggests a possible role in enhancing the bioactivity of polyphenol-rich extracts. From an agri-food waste valorization perspective, the peel and core represent promising sources of bioactive compounds for developing functional foods and nutraceuticals.