Marika Massaro

Osteoporosis is an age-related metabolic bone disorder characterized by an imbalance between bone resorption and formation. Natural polyphenols have gained attention as potential complementary strategies for its prevention. In this study, we investigated the effects of a sustainable, polyphenol-rich extract from red grape pomace (GPE) on human mesenchymal stem cell (MSC) fate and its underlying mechanisms of action. We found that GPE significantly promoted osteogenic differentiation while suppressing adipogenic differentiation in canonical bone marrow-derived MSCs (BMSCs). This biological effect was preserved in adipose tissue-derived MSCs (AdMSCs) obtained from elderly patients (>65 years) at high cardiovascular risk. Mechanistically, GPE downregulated adipogenic markers (PPARγ, CD36 and FABP4) and enhanced osteogenic markers (RUNX2, ALP, OSX, BMP-2, OPN, COL1A1 and OCN). Moreover, GPE activated NRF2-dependent redox signaling, as evidenced by increased NRF2 nuclear translocation and transcriptional activity. Accordingly, GPE treatment significantly upregulated, or consistently increased, the expression of multiple NRF2 target genes, including HO-1, GPX, CAT, GCLC, and NQO1. Importantly, pharmacological inhibition of NRF2 attenuated GPE-induced ALP activity, confirming NRF2 as a key mediator of its osteogenic effects. Overall, grape pomace-derived polyphenols act as upstream modulators of redox-sensitive and osteogenic transcription factors, rebalancing MSC differentiation toward osteogenesis and mitigating age-related bone fragility.

In epicardial adipose tissue from CAD patients, DHA and EPA exert robust anti-inflammatory actions, reducing MCP-1, IL-6, CXCL10, and MMP-9, elevating RvD1 and shifting cells toward a protective state by activating PPARγ/NRF2 and suppressing NF-kB activity.

Inflammation in hypertrophic adipose tissue is a key driver of obesity‐related cardiometabolic diseases. Under insulin resistance conditions, insulin signaling shifts toward pro‐inflammatory pathways, disrupting normal metabolic processes. Inositols (INSs), a class of carbocyclic sugars, serve as important secondary messengers in insulin signaling. This study investigates whether myo‐inositol (MYO), in addition to its known insulin‐sensitizing properties, also exerts anti‐inflammatory effects, and thus potentially attenuates adipose tissue inflammation. Human Simpson‐Golabi‐Behmel syndrome (SGBS) adipocytes were treated with MYO (100 μmol/L) for 4 h before pro‐inflammatory stimulation with different dymetabolic‐related cytokines including tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, and lipopolysaccharide (LPS). Pro‐inflammatory gene expression and protein secretion were assessed via qPCR, ELISA, EIA, and immunocytochemistry, while reactive oxygen species (ROS) overproduction, nuclear factor (NF)‐κB activation, and mitochondrial content were assessed using specific probes and transactivation assays, respectively. Functionally, the regulation of adhesion of monocytes to inflamed adipocytes was quantified using a cell adhesion assay. MYO significantly reduced the pro‐inflammatory expression and secretion of CCL‐2, CXCL‐10, and IL‐6, resulting in reduced adhesion of monocytes to inflamed adipocytes. Additionally, MYO suppressed TNF‐α‐induced surface expression of ICAM‐1, a critical adhesion molecule in adipose tissue inflammation. Mechanistically, MYO attenuated ROS overproduction and the related NF‐κB activation, the key regulator of adipocyte inflammation, and improved the mitochondrial dysfunction, thus overall restoring adipose tissue dysfunction. Although further research is needed, these findings suggest that MYO effectively improves the inflammatory and dysmetabolic profile of hypertrophic fat cells, highlighting its potential as a therapeutic option for metabolic disorders.

Opuntia ficus‐indica (OFI) has attracted much attention as a source of antioxidant and antiinflammatory compounds. We hypothesize that the antioxidant content of OFI cladode extract may improve adipocyte dysfunction resulting from inflammatory stimulation of hypertrophic adipocytes. To this end, the properties of OFI cladode hydroalcoholic extract were evaluated in terms of antioxidant activity, regulation of adipocyte inflammation, and adipocyte/monocyte interaction in human adipocytes rendered dysfunctional by the proinflammatory cytokine tumor necrosis factor‐α (TNF‐α). The major phenolic compounds identified were isorhamnetin derivatives and phenolic acids, including piscidic and eucomic acids. Our results show that OFI cladode extract exhibits antiradical activities and reduces the adhesion and transmigration activity of monocytes to inflamed adipocytes by inhibiting various cytokines, chemokines, and adhesion molecules such as interleukin (IL)‐6 and IL‐8 by ∼80%, monocyte chemotactic protein (MCP)‐1, C‐X‐C motif chemokine ligand (CXC‐L)10, macrophage colony‐stimulating factor (M‐CSF) from 40% to 50%, and intercellular adhesion molecule‐1 (ICAM‐1) by 70% at the higher concentration. In structurally and mechanistically by protein–ligand docking profiling study, piscidic acid proved to be the best potential candidate for a regulatory interaction with the activities of nuclear factor erythroid 2‐related factor 2 (NRF‐2) and nuclear factor‐κB (NF‐κB). In summary, these data highlight the potential of OFI as a dietary supplement in nutritional treatments aimed at combating the inflammatory stigmata of obesity.

Background: Loss of functional capacity negatively impacts the quality of life in older adults. Objective: This single-site randomized controlled study examined whether short- (one week) and long-term (three months) blackcurrant supplementations combined with habitual physical activity would improve functional capacity and quality of life in previously sedentary older women. Methods: Thirty sedentary, healthy older women were randomly assigned to receive blackcurrant supplementation (400 mg of blackcurrant extract) (Polyphenol group, n=15; 74.2±10.0 years) or no supplementation (capsules of 400 mg of corn flour) (Placebo group, n=15; 72.8±8.7 years). Each group consumed two capsules daily for one week and three months, with a washout period of one week between the two phases. The polyphenol group was required to increase habitual activity levels. Participants underwent a functional capacity assessment consisting of a sixminute walk, sit-to-stand test, Berg balance scale measurement and quality of life evaluation with the Scale of Life Satisfaction Index (LSI) at the start, after one week, and after three months of supplementation. Results: Walking distance and time to sit-to-stand improved by 2.5% (p=0.005) and 7.5% (p=0.005), respectively, after one week in the polyphenol group. After 3 months, walking distance in the six-minute walk test increased by 12.3% (p=0.001) while the time to sit-to-stand decreased by 16% (p=0.002) in polyphenol compared to placebo, respectively. No differences in Berg balance scale were observed. Quality of life, indexed by LSI, improved by 39% (p=0.001) in the polyphenol compared to the placebo group. Conclusion: Blackcurrant supplementation, combined with habitual activity, may enhance functional capacity and quality of life in older women, offering a potential strategy to maintain independence. However, future studies should address longer durations to validate these findings.

Pulmonary arterial hypertension (PAH) is a rare and progressive disorder that affects the pulmonary vasculature. Although recent developments in pharmacotherapy have extended the life expectancy of PAH patients, their 5‐year survival remains unacceptably low, underscoring the need for multitarget and more comprehensive approaches to managing the disease. This should incorporate not only medical, but also lifestyle interventions, including dietary changes and the use of nutraceutical support. Among these strategies, n‐3 polyunsaturated fatty acids (n‐3 PUFAs) are emerging as promising agents able to counteract the inflammatory component of PAH. In this narrative review, we aim at analysing the preclinical evidence for the impact of n‐3 PUFAs on the pathogenesis and the course of PAH. Although evidence for the role of n‐3 PUFAs deficiencies in the development and progression of PAH in humans is limited, preclinical studies suggest that these dietary components may influence several aspects of the pathobiology of PAH. Further clinical research should test the efficacy of n‐3 PUFAs on top of approved clinical management. These studies will provide evidence on whether n‐3 PUFAs can genuinely serve as a valuable tool to enhance the efficacy of pharmacotherapy in the treatment of PAH.

N-methylpyridinium (NMP) is produced through the pyrolysis of trigonelline during the coffee bean roasting process. Preliminary studies suggest that NMP may have health benefits, thanks to its antioxidant properties. Based on this background, the aim of this study was to evaluate whether NMP could have a protective effect against LPS-induced neuroinflammation in human glioblastoma cells (U87MG). With this aim, U87MG cells were pre-treated with NMP (0.5 μM) for 1 h and then exposed to LPS (1 μg/mL) for 24 h. Our findings show that NMP attenuates LPS-induced neuroinflammation by reducing the expression of pro-inflammatory cytokines, such as IL-1β, TNF-α and IL-6, through the inhibition of the NF-κB signaling pathway, which is critical in regulating inflammatory responses. NMP is able to suppress the activation of the NF-κB signaling pathway, suggesting its potential in preventing neuroinflammatory conditions. These outcomes support the notion that regular consumption of NMP, possibly through coffee consumption, may offer protection against neuroinflammatory states implicated in neurological disorders.

Osteoarthritis (OA) stands as a prevalent and progressively debilitating clinical condition globally, impacting joint structures and leading to their gradual deterioration through inflammatory mechanisms. While both non-modifiable and modifiable factors contribute to its onset, numerous aspects of OA pathophysiology remain elusive despite considerable research strides. Presently, diagnosis heavily relies on clinician expertise and meticulous differential diagnosis to exclude other joint-affecting conditions. Therapeutic approaches for OA predominantly focus on patient education for self-management alongside tailored exercise regimens, often complemented by various pharmacological interventions primarily targeting pain alleviation. However, pharmacological treatments typically exhibit short-term efficacy and local and/or systemic side effects, with prosthetic surgery being the ultimate resolution in severe cases. Thus, exploring the potential integration or substitution of conventional drug therapies with natural compounds and extracts emerges as a promising frontier in enhancing OA management. These alternatives offer improved safety profiles and possess the potential to target specific dysregulated pathways implicated in OA pathogenesis, thereby presenting a holistic approach to address the condition’s complexities.

Associations between subjective well-being (SWB) and dietary habits, employment status, and habitual activities are increasingly capturing the focus of researchers as well as policymakers worldwide. This study aimed to explore these associations in a sample of the population in Greece and Cyprus via an online survey. In total, 936 questionnaires (470: Cyprus, 466: Greece) were analyzed to study the associations between the Mediterranean Diet (MD) (using the 14-item MEDAS score, (14-MEDAS)), subjective well-being (SWB), and several socioeconomic factors. Key remarks of this survey highlight the positive impact of MD adherence on some well-being items. Namely, statistically significant differences were found on the following items: Satisfied with life (p < 0.001), Life worthwhile (p < 0.001), Feeling happy (p < 0.001), worried (p = 0.005), and depressed (p = 0.001), when comparing Low MD adherence (14-MEDAS < 5) to High MD adherence (14-MEDAS > 10). Other lifestyle habits such as spending time with friends and family, spending time in nature, and habitual physical activity were associated with aspects of SWB such as Life satisfaction, Life worthwhile, Feeling happy, and energetic. The findings support adherence to the MD, since it is associated with higher life satisfaction and self-reported happiness in this sample and should be considered when developing health policies on well-being.