Milk and cheesemaking whey as a sustainable source of extracellular vesicles: Exploring large-scale isolation methods with industrial and potential therapeutic applications.

Milk extracellular vesicles (EVs) represent promising drug delivery platforms, yet current isolation methods face scalability challenges. Ultracentrifugation (UC), the gold standard, is expensive and energy-intensive, limiting pharmaceutical and pharmacological implementation. This study aimed to standardize scalable EV isolation methods and evaluate cheesemaking whey as a sustainable alternative to milk for therapeutic applications.

Anti-steatotic effect of Opuntia ficus-indica extracts rich in betalains and phenolics from fruit peel and pulp of different varieties in in vitro models.

Opuntia ficus-indica exhibits antioxidant, anti-inflammatory and anti-hyperglycemic properties, making it a promising candidate for the prevention and treatment of metabolic dysfunction-associated fatty liver disease. However, its effects on triglyceride accumulation remain largely unexplored. The aim of the present study is to evaluate the anti-steatotic effect of peel and pulp extracts from different varieties of Opuntia ficus-indica fruits (Pelota, Colorada and Sanguinos) in hepatic murine in vitro models, using both AML12 hepatocytes and hepatic organoids.

Oral Delivery of Ellagic Acid Encapsulated in Milk Exosomes: Sex-Based Differences in Bioavailability, Urolithin Production, and Gut Microbiota Modulation.

Milk exosomes (EXOs) enhance polyphenols' bioavailability, but their potential for oral administration remains underexplored. Ellagic acid (EA) is poorly bioavailable. We investigate whether EA encapsulated in EXOs (EXO-EA) consumed orally improves EA bioavailability and (or) modulates gut microbiota.

Hydroxytyrosol Enhances Plasma Extracellular Vesicle Secretion, Modulates Their miRNAs Cargo, and Reduces LDL Oxidation in Humans: Postprandial and 1-Week Effects.

Hydroxytyrosol (HT) consumption is associated with healthy outcomes. Specifically, its ability to modulate microRNA (miRNA) expression has been described. However, whether HT influences the secretion of extracellular vesicles (EVs) and their transported miRNAs remains unknown.

Intestinal IncRNAs and circRNAs Regulated by Dietary-Lipid Stimuli.

A diet rich in lipids can lead to many deleterious conditions, which involve many regulatory molecules, such as non-coding (nc)RNAs. We aimed to analyze the effects of high dietary lipid exposure on the expression of intestinal ncRNAs (long non-coding [lncRNAs] and circular [circRNAs]). lncRNAs and circRNAs were screened, both in vivo (mice) and in vitro (human intestinal organoids).

Dietary plant microRNAs as potential regulators of cellular cholesterol efflux.

Aim: Epidemiological evidence suggests adherence to vegetable-rich diets is associated to atheroprotective effects and bioactive components are most likely to play a relevant role. The notion of inter-kingdom regulation has opened a new research paradigm and perhaps microRNAs (miRNAs) from edible vegetables could influence consumer gene expression and lead to biological effects. We aimed to investigate the potential impact of broccoli-derived miRNAs on cellular cholesterol efflux in vitro.

Therapeutic potential of plant-derived extracellular vesicles as nanocarriers for exogenous miRNAs.

Cell-to-cell communication strategies include extracellular vesicles (EVs) in plants and animals. The bioactive molecules in a diet rich in vegetables and fruits are associated with disease-preventive effects. Plant-derived EVs (PDEVs) are biogenetically and morphologically comparable to mammalian EVs and transport bioactive molecules, including miRNAs.

Hydroxytyrosol Induces Dyslipidemia in an ApoB100 Humanized Mouse Model.

Scope: Extra virgin olive oil has numerous cardiopreventive effects, largely due to its high content of (poly)phenols such as hydroxytyrosol (HT). However, some animal studies suggest that its excessive consumption may alter systemic lipoprotein metabolism. Because human lipoprotein metabolism differs from that of rodents, this study examines the effects of HT in a humanized mouse model that approximates human lipoprotein metabolism.

Plant-Based Diets Reduce Blood Pressure: A Systematic Review of Recent Evidence.

Purpose Of Review: Accumulating data on the consumption of plant-based diets and their impact on blood pressure indicate a consensus that plant-based diets are linked to reduced blood pressure. The suggested mechanisms of action are manifold, and, in this systematic review, we provide a summary of the most recent findings on plant-based diets and their impact on blood pressure, along with an analysis of the molecules accountable for the observed effects.

Recent Findings: The overwhelming majority of intervention studies demonstrate that plant-based diets result in lower blood pressure readings when compared to diets that are based on animal products.

TMAO Upregulates Members of the miR-17/92 Cluster and Impacts Targets Associated with Atherosclerosis.

Atherosclerosis is a hallmark of cardiovascular disease, and lifestyle strongly impacts its onset and progression. Nutrients have been shown to regulate the miR-17/92 cluster, with a role in endothelial function and atherosclerosis. Choline, betaine, and L-carnitine, found in animal foods, are metabolized into trimethylamine (TMA) by the gut microbiota.

Therapeutic potential of broccoli-derived extracellular vesicles as nanocarriers of exogenous miRNAs.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression. The wide-ranging biological activities of microRNAs stimulated research on disease mechanisms and is suggesting appealing therapeutic applications. When unprotected, miRNAs suffer from rapid degradation and appropriate strategies need to be developed to improve their therapeutic potential.

The emergent role of mitochondrial RNA modifications in metabolic alterations.

Mitochondrial epitranscriptomics refers to the modifications occurring in all the different RNA types of mitochondria. Although the number of mitochondrial RNA modifications is less than those in cytoplasm, substantial evidence indicates that they play a critical role in accurate protein synthesis. Recent evidence supported those modifications in mitochondrial RNAs also have crucial implications in mitochondrial-related diseases.

Up-to-date on the evidence linking miRNA-related epitranscriptomic modifications and disease settings. Can these modifications affect cross-kingdom regulation?

The field of epitranscriptomics is rapidly developing. Several modifications (e.g.

Trimethylamine -Oxide (TMAO) Modulates the Expression of Cardiovascular Disease-Related microRNAs and Their Targets.

Diet is a well-known risk factor of cardiovascular diseases (CVDs). Some microRNAs (miRNAs) have been described to regulate molecular pathways related to CVDs. Diet can modulate miRNAs and their target genes.

Connection between miRNA Mediation and the Bioactive Effects of Broccoli ( var. italica): Exogenous miRNA Resistance to Food Processing and GI Digestion.

Broccoli ( var. italica) and its bioactive compounds are associated with beneficial health effects, which might be enabled, at least in part, through miRNA regulation, despite recent controversial studies suggesting that exogenous dietary miRNAs may reach host circulation and target cells to regulate gene expression. Here, a computational analysis was performed to explore the processes and pathways associated with genes targeted either by (1) host-expressed miRNAs (endogenous) modulated by the bioactive compounds in broccoli or (2) miRNAs derived from broccoli (exogenous).

Mediterranean diet enriched in extra-virgin olive oil or nuts modulates circulating exosomal non-coding RNAs.

Purpose: Exosomes are extracellular vesicles secreted by cells, which can transport different molecules, including nucleic acids. Dietary habits may induce gene regulation through the modulation of exosomal RNAs. We aimed at characterizing exosomal lncRNAs, mRNA and miRNAs modulation after a 1-year adherence to a low-fat diet (LFD) or to Mediterranean-based diets enriched in extra-virgin olive oil (MedDiet + EVOO) or in a mixture of nuts (MedDiet + Nuts).

Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy.

MicroRNAs (miRNAs) are small non-coding RNAs with a known role as mediators of gene expression in crucial biological processes, which converts them into high potential contenders in the ongoing search for effective therapeutic strategies. However, extracellular RNAs are unstable and rapidly degraded, reducing the possibility of successfully exerting a biological function in distant target cells. Strategies aimed at enhancing the therapeutic potential of miRNAs include the development of efficient, tissue-specific and nonimmunogenic delivery methods.

Intestinal miRNAs regulated in response to dietary lipids.

The role of miRNAs in intestinal lipid metabolism is poorly described. The small intestine is constantly exposed to high amounts of dietary lipids, and it is under conditions of stress that the functions of miRNAs become especially pronounced. Approaches consisting in either a chronic exposure to cholesterol and triglyceride rich diets (for several days or weeks) or an acute lipid challenge were employed in the search for intestinal miRNAs with a potential role in lipid metabolism regulation.

Wine's Phenolic Compounds and Health: A Pythagorean View.

In support of the J curve that describes the association between wine consumption and all-cause mortality, researchers and the lay press often advocate the health benefits of (poly)phenol consumption via red wine intake and cite the vast amount of in vitro literature that would corroborate the hypothesis. Other researchers dismiss such evidence and call for total abstention. In this review, we take a skeptical, Pythagorean stance and we critically try to move the debate forward by pointing the readers to the many pitfalls of red wine (poly)phenol research, which we arbitrarily treat as if they were pharmacological agents.

Intestinal Lipid Metabolism Genes Regulated by miRNAs.

MicroRNAs (miRNAs) crucial roles in translation repression and post-transcriptional adjustments contribute to regulate intestinal lipid metabolism. Even though their actions in different metabolic tissues have been elucidated, their intestinal activity is yet unclear. We aimed to investigate intestinal miRNA-regulated lipid metabolism-related genes, by creating an intestinal-specific Dicer1 knockout (Int-Dicer1 KO) mouse model, with a depletion of microRNAs in enterocytes.

Olive oil consumption and its repercussions on lipid metabolism.

Consumption of highly processed foods, such as those high in trans fats and free sugars, coupled with sedentarism and chronic stress increases the risk of obesity and cardiometabolic disorders, while adherence to a Mediterranean diet is inversely associated with the prevalence of such diseases. Olive oil is the main source of fat in the Mediterranean diet. Data accumulated thus far show consumption of extra virgin, (poly)phenol-rich olive oil to be associated with specific health benefits.

Concentrates of buttermilk and krill oil improve cognition in aged rats.

Cognitive decline is one of the hallmarks of aging and can vary from mild cognitive impairment to dementia to Alzheimer's disease. In addition to some lifestyle interventions, there is room for the use of nutraceuticals/functional foods as pharma-nutritional tools to lessen the burden of cognitive decline before it worsens. We previously reported the promising molecular actions of milk fat globule membranes and krill oil concentrates in a rat model of aging.

Identification and validation of common molecular targets of hydroxytyrosol.

Hydroxytyrosol (HT) is involved in healthful activities and is beneficial to lipid metabolism. Many investigations focused on finding tissue-specific targets of HT through the use of different omics approaches such as transcriptomics and proteomics. However, it is not clear which (if any) of the potential molecular targets of HT reported in different studies are concurrently affected in various tissues.

Postprandial Circulating miRNAs in Response to a Dietary Fat Challenge.

Postprandial lipemia has many physiopathological effects, some of which increase the risk of cardiovascular disease. MicroRNAs (miRNAs) can be found in almost all biological fluids, but their postprandial kinetics are poorly described. We aimed to profile circulating miRNAs in response to a fat challenge.