HEAL9 alleviates cognitive decline and normalizes colonic motility in the prodromal AD via microbiota-gut-inflammasome-brain axis. HEAL9 can represent a suitable therapeutical option for the treatment of early AD and related intestinal symptoms.

Introduction: Opioids are the most commonly used analgesic drugs for acute and chronic severe pain and are metabolized in the liver via cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGTs). Methods: A narrative review of the literature was conducted by searching the PubMed database up to December 2025, with English as the only language restriction. Relevant studies were identified using the keywords “opioids,” “pharmacogenetic,” “cytochrome mutations,” and “interactions.” Results: Polymorphisms in CYP2D6 and CYP3A4 genes can affect the pharmacokinetics, clinical effect, and safety of opioids. Furthermore, enzyme induction and inhibition by concomitant drugs or compounds (herbal products or food) are sources of variability factors in drug response that may be predictable. Conclusions: This review article summarizes current evidence on the role of pharmacogenetics and opioid-related interactions, offering a framework to better understand interindividual variability in opioid response and to inform future multimodal approaches.

The present study investigated the potential beneficial effect of probiotic Lacticaseibacillus paracasei DG I1572 (L. paracasei DG I1572) in a murine model of vascular inflammaging. Aged (40‐weeks‐old) and young (10‐weeks‐old) Sprague‐Dawley rats were treated with L. paracasei DG I1572 for 3 months. Vascular functions were assessed by pressurized myography, while intravascular ROS and NO production, as well as inflammatory parameters (IL‐1β, IL‐6, IL‐10, and TNF), were measured using dihydroethidium, 4‐amino‐5‐methylamino‐2′,7′‐difluorofluorescein dyes, and ELISA, respectively. Malondialdehyde (MDA) and claudin‐1 were examined. Old rats showed: (1) vascular endothelial dysfunctions due to a reduced NO availability; (2) increase in intravascular ROS, (3) the presence of systemic inflammation and oxidative stress, as documented by increased plasma levels of IL‐6 and MDA, respectively; (4) a slight decrease in claudin‐1 colonic expression, as compared with young rats. Treatment with L. paracasei DG I1572 in old rats improved: (1) endothelial function, increasing NO bioavailability; (2) systemic and in situ oxidative stress in vessels, reducing MDA and intravascular ROS production, respectively; (3) inflammatory parameters, reducing IL‐1β and IL‐6 as well as increasing IL‐10; (4) colonic expression of claudin‐1. L. paracasei DG I1572 supplementation can mitigate the low‐grade inflammation, and the vascular dysfunctions associated with age, likely through antioxidant and anti‐inflammatory properties.

Background: The term “inflammaging” has been introduced to describe the chronic, low-grade inflammatory process associated with the increase in age and the senescence of the immune system, that confers susceptibility to suffering age-related pathologies. In this context, previous studies have already demonstrated that the regular consumption of mineral water can be a valuable tool for detoxifying the body from reactive oxygen species (ROS) and for mitigating the systemic inflammation. Objective: Herein, we tested the beneficial effects of a mineral water with human-like electrolytic content (San Carlo^® water) in a pre-clinical model of vascular inflammaging and investigated the mechanisms underlying this effect. San Carlo^® water was administered ad libitum to both young (10-week old) and aged rats (40-week old) for 3 months. Methods: Vascular functionality, oxidative stress (fluorescent dye dihydroethidium assay, levels of MDA, and levels of 8-isoprostanes in the urine), and systemic inflammation (levels of IL-1β and TNF) were assessed. Results: San Carlo^® water ingestion mitigated the inflammation by reducing TNF plasma levels and improved endothelial-dependent vasorelaxation, acting against ROS production. Conclusion: The present study suggests that the use of San Carlo^® water can effectively counteract the low-grade inflammation typically associated with age and the related vascular dysfunction, likely through both antioxidant and anti-inflammatory properties.

(1) Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain and altered bowel habits, linked to dysbiosis and inflammation. Currently available treatments, focused on symptom management, displayed limited efficacy. Recent research highlights microbiota modulation as a potential therapeutic strategy to restore intestinal barrier integrity; (2) A dextran sulfate sodium (DSS)-induced mouse model of post-colitis IBS-like symptoms was performed to evaluate the effect of a novel mixture of Enterococcus lactis SF68^®, butyrate, and folate. Disease activity index and spleen weight were assessed. Markers of gut inflammation, intestinal barrier alterations, and gut butyrate bioavailability were measured. The activity of colonic mitochondria was also analyzed; (3) Supplementation with the novel mixture significantly reduced spleen weight and cytokine levels. The intestinal epithelial barrier was restored through an increase in claudin-1, occludin, and defensin 1–3 and a reduction in LBP plasma level. Treatment with the mixture enhanced the expression of butyrate transporters in mice. Mitochondrial activity markers, including citrate synthase and Cytochrome c oxidase, were improved by treatment; (4) The novel mixture containing Enterococcus lactis, butyrate, and folate exerted a protective effect against post-inflammatory IBS by reducing local inflammation, restoring intestinal barrier integrity, and enhancing butyrate bioavailability, suggesting its potential for managing post-inflammatory IBS symptoms effectively.

Vascular aging is driven by a self-sustaining interplay between oxidative stress and chronic low-grade inflammation, collectively referred to as inflammaging. Diosmin, a cit-rus-derived flavonoid with antioxidant and anti-inflammatory properties, has not previ-ously been investigated in this context. Young (10-week-old) and aged (40-week-old) male Sprague–Dawley rats received diosmin (50 mg/kg/day) or vehicle for 3 months. Vascular function was assessed in mesenteric resistance arteries using pressure myography, while oxidative stress was evaluated by dihydroethidium and mitoSOX staining. Circulating malondialdehyde (MDA), tumor necrosis factor (TNF) and lipopolysaccharide-binding protein (LBP) were measured and vascular expression of Enos, Gpx, Sod2 and Xdh was an-alyzed. Aging was associated with impaired endothelium-dependent vasorelaxation, increased vascular ROS production and elevated circulating MDA and LBP levels. Chronic diosmin supplementation partially restored endothelial function and significantly reduced both NADPH oxidase–derived and mitochondrial ROS in aged vessels. These effects were ac-companied by decreased plasma MDA and LBP levels, while TNF remained unchanged. Diosmin did not significantly affect Enos, Gpx, or Sod2 gene’s expression, but attenuated the age-related upregulation of Xdh. Overall, diosmin mitigates vascular inflammaging by reducing ROS burden and improving nitric oxide bioavailability, highlighting its potential to counteract age-related vascular dysfunction through modulation of redox–inflammatory crosstalk.