Microbiota alterations associated with vascular diseases: postbiotics as a next-generation magic bullet for gut-vascular axis.

The intestinal microbiota represents a key element in maintaining the homeostasis and health conditions of the host. Vascular pathologies and other risk factors such as aging have been recently associated with dysbiosis. The qualitative and quantitative alteration of the intestinal microbiota hinders correct metabolic homeostasis, causing structural and functional changes of the intestinal wall itself. Impairment of the intestinal microbiota, combined with the reduction of the barrier function, worsen the pathological scenarios of peripheral tissues over time, including the vascular one. Several experimental evidence, collected in this review, describes in detail the changes of the intestinal microbiota in dysbiosis associated with vascular alterations, such as atherosclerosis, hypertension, and endothelial dysfunction, the resulting metabolic disorders and how these can impact on vascular health. In this context, the gut-vascular axis is considered, for the first time, as a merged unit involved in the development and progression of vascular pathologies and as a promising target. Current approaches for the management of dysbiosis such as probiotics, prebiotics and dietary modifications act mainly on the intestinal district. Postbiotics, described as preparation of inanimate microorganisms and/or their components that confers health benefits on the host, represent an innovative strategy for a dual management of intestinal dysbiosis and vascular pathologies. In this context, this review has the further purpose of defining the positive effects of the supplementation of bacterial strains metabolites (short­chain fatty acids, exopolysaccharides, lipoteichoic acids, gallic acid, and protocatechuic acid) restoring intestinal homeostasis and acting directly on the vascular district through the gut-vascular axis.

Impact of thermal processing on polyphenols, carotenoids, glucosinolates, and ascorbic acid in fruit and vegetables and their cardiovascular benefits.

Bioactive compounds in fruit and vegetables have a positive impact on human health by reducing oxidative stress, inflammation, and the risk of chronic diseases such as cancer, cardiovascular (CV) diseases, and metabolic disorders. However, some fruit and vegetables must be heated before consumption and thermal processes can modify the amount of nutraceuticals, that is, polyphenols, carotenoids, glucosinolates, and ascorbic acid, that can increase or decrease in relation to different factors such as type of processing, temperature, and time but also the plant part (e.g., flower, leaf, tuber, and root) utilized as food. Another important aspect is related to the bioaccessibility and bioavailability of nutraceuticals. Indeed, the key stage of nutraceutical bioefficiency is oral bioavailability, which involves the release of nutraceuticals from fruit and vegetables in gastrointestinal fluids, the solubilization of nutraceuticals and their interaction with other components of gastrointestinal fluids, the absorption of nutraceuticals by the epithelial layer, and the chemical and biochemical transformations into epithelial cells. Several studies have shown that thermal processing can enhance the absorption of nutraceuticals from fruit and vegetable. Once absorbed, they reach the blood vessels and promote multiple biological effects (e.g., antioxidant, anti-inflammatory, antihypertensive, vasoprotective, and cardioprotective). In this review, we described the impact of different thermal processes (such as boiling, steaming and superheated steaming, blanching, and microwaving) on the retention/degradation of bioactive compounds and their health-promoting effects after the intake. We then summarized the impact of heating on the absorption of nutraceuticals and the biological effects promoted by natural compounds in the CV system to provide a comprehensive overview of the potential impact of thermal processing on the CV benefits of fruit and vegetables.

Generation of human gastric assembloids from primary fetal organoids.

PURPOSE: Understanding human gastric epithelium homeostasis remains partial, motivating the exploration of innovative in vitro models. Recent literature showcases the potential of fetal stem cell-derived organoids in developmental and disease modelling and translational therapies. To scale the complexity of the model, we propose to generate assembloids, aiming to increase gastric maturation to provide new structural and functional insights. METHODS: Human fetal gastric organoids (fGOs) were expanded in 3D Matrigel cultures. Confluent organoid cultures were released from the Matrigel dome and resuspended in a collagen I hydrogel. Subsequently, the organoid mixture was seeded in a ring shape within a 24-well plate and allowed to gelate. The structure was lifted in the medium and cultured in floating conditions, allowing for organoid self-assembling into a gastric assembloid. After 10 days of maturation, the assembloids were characterized by immunostaining and RT-PCR, comparing different fetal developmental stages. RESULTS: Successful generation of human fetal gastric assembloids (fGAs) was achieved using spontaneous self-aggregation within the collagen I hydrogel. Immunostaining analysis of early and late fGAs showed the establishment of apico-basal cell polarity, secretion of gastric mucins, and the presence of chromogranin A in both samples. Transcriptional markers analysis revealed distinct disparities in markers associated with mature cell types between late and early fetal stages. CONCLUSIONS: fGOs can reliably be generated from human fetal samples. This pioneering assembloid approach paves the way for advancing our comprehension of human gastric epithelium homeostasis and its perturbation, offering a better in vitro platform for the study of gastric epithelial development and therapeutic translation.

Stomach engineering: region-specific characterization of the decellularized porcine stomach.

PURPOSE: Patients affected by microgastria, severe gastroesophageal reflux, or those who have undergone subtotal gastrectomy, have commonly described reporting dumping syndromes or other symptoms that seriously impair the quality of their life. Gastric tissue engineering may offer an alternative approach to treating these pathologies. Decellularization protocols have great potential to generate novel biomaterials for large gastric defect repair. There is an urgency to define more reliable protocols to foster clinical applications of tissue-engineered decellularized gastric grafts. METHODS: In this work, we investigated the biochemical and mechanical properties of decellularized porcine stomach tissue compared to its native counterpart. Histological and immunofluorescence analyses were performed to screen the quality of decellularized samples. Quantitative analysis was also performed to assess extracellular matrix composition. At last, we investigated the mechanical properties and cytocompatibility of the decellularized tissue compared to the native. RESULTS: The optimized decellularization protocol produced efficient cell removal, highlighted in the absence of native cellular nuclei. Decellularized scaffolds preserved collagen and elastin contents, with partial loss of sulfated glycosaminoglycans. Decellularized gastric tissue revealed increased elastic modulus and strain at break during mechanical tensile tests, while ultimate tensile strength was significantly reduced. HepG2 cells were seeded on the ECM, revealing matrix cytocompatibility and the ability to support cell proliferation. CONCLUSION: Our work reports the successful generation of acellular porcine gastric tissue able to support cell viability and proliferation of human cells.

Hydrogen Sulfide and Irisin, Potential Allies in Ensuring Cardiovascular Health.

Irisin is a myokine secreted under the influence of physical activity and exposure to low temperatures and through different exogenous stimuli by the cleavage of its precursor, fibronectin type III domain-containing protein 5 (FNDC5). It is mainly known for maintaining of metabolic homeostasis, promoting the browning of white adipose tissue, the thermogenesis process, and glucose homeostasis. Growing experimental evidence suggests the possible central role of irisin in the regulation of cardiometabolic pathophysiological processes. On the other side, hydrogen sulfide (H2S) is well recognized as a pleiotropic gasotransmitter that regulates several homeostatic balances and physiological functions and takes part in the pathogenesis of cardiometabolic diseases. Through the S-persulfidation of cysteine protein residues, H2S is capable of interacting with crucial signaling pathways, exerting beneficial effects in regulating glucose and lipid homeostasis as well. H2S and irisin seem to be intertwined; indeed, recently, H2S was found to regulate irisin secretion by activating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/FNDC5/irisin signaling pathway, and they share several mechanisms of action. Their involvement in metabolic diseases is confirmed by the detection of their lower circulating levels in obese and diabetic subjects. Along with the importance of metabolic disorders, these modulators exert favorable effects against cardiovascular diseases, preventing incidents of hypertension, atherosclerosis, heart failure, myocardial infarction, and ischemia-reperfusion injury. This review, for the first time, aims to explore the role of H2S and irisin and their possible crosstalk in cardiovascular diseases, pointing out the main effects exerted through the common molecular pathways involved.

Improved Cardiovascular Effects of a Novel Pomegranate Byproduct Extract Obtained through Hydrodynamic Cavitation.

The healthy properties of pomegranate fruit, a highly consumed food, have been known for a long time. However, the pomegranate supply chain is still rather inefficient, with the non-edible fraction, whose weight is roughly half the total and is endowed with plenty of valuable bioactive compounds, either disposed of or underutilized. A novel extract obtained from non-edible byproducts (called PPE), using hydrodynamic cavitation, a green, efficient, and scalable technique, was investigated for its cardiovascular effects in vivo. PPE showed efficacy in an acute phenylephrine (PE)-induced hypertensive rat model, similar to the extract of whole fruit (PFE) obtained using the same extractive technique, along with good intestinal bioaccessibility after oral administration. Finally, when chronically administered for 6 weeks to spontaneously hypertensive rats, PPE was shown to significantly contain the increase in systolic blood pressure, comparable to the reference drug Captopril, and at a dose remarkably lower than the reported effective dose of ellagic acid. The extract from the non-edible fraction of the pomegranate fruit also showed good anti-inflammation and anti-fibrotic effects. The findings of this study, along with the extraction technique, could contribute to enhancing the value of the pomegranate supply chain, relieve the related environmental burden, and potentially improve public health.

An Overview of the Health Benefits, Extraction Methods and Improving the Properties of Pomegranate.

Pomegranate (Punica granatum L.) is a polyphenol-rich edible food and medicinal plant of ancient origin, containing flavonols, anthocyanins, and tannins, with ellagitannins as the most abundant polyphenols. In the last decades, its consumption and scientific interest increased, due to its multiple beneficial effects. Pomegranate is a balausta fruit, a large berry surrounded by a thick colored peel composed of exocarp and mesocarp with edible arils inside, from which the pomegranate juice can be produced by pressing. Seeds are used to obtain the seed oil, rich in fatty acids. The non-edible part of the fruit, the peel, although generally disposed as a waste or transformed into compost or biogas, is also used to extract bioactive products. This review summarizes some recent preclinical and clinical studies on pomegranate, which highlight promising beneficial effects in several fields. Although further insight is needed on key aspects, including the limited oral bioavailability and the role of possible active metabolites, the ongoing development of suitable encapsulation and green extraction techniques enabling the valorization of waste pomegranate products point to the great potential of pomegranate and its bioactive constituents as dietary supplements or adjuvants in therapies of cardiovascular and non-cardiovascular diseases.