Antimicrobial Peptides Human Beta-Defensin-2 and -3 Protect the Gut During Candida albicans Infections Enhancing the Intestinal Barrier Integrity: In Vitro Study

The intestinal mucosa is composed of a monolayer of epithelial cells, which is highly polarized and firmly united to each other thanks to the presence of proteins complexes, called Tight junctions (TJs). Alteration of the mucus layer and TJs causes an increase in intestinal permeability, which can lead to a microbial translocation and systemic disorders. Candida albicans, in addition to its role of commensal, is an opportunistic pathogen responsible for disseminated candidiasis, especially in immunocompromised subjects where the dysbiosis leads to damage of the intestinal mucosal barrier. In this work, we used a line of intestinal epithelial cells able to stably express the genes that encodes human beta defensin-2 (HBD-2) and -3 (HBD-3) to monitor the invasion of C. albicans in vitro. Defensins are a group of antimicrobial peptides (AMPs) found in different living organisms, and are involved in the first line of defense in the innate immune response against pathogens. The results obtained show that the presence of antimicrobial peptides improves the expression of TJs and increases the Trans Epithelial Electrical Resistence value. In addition, the invasive ability of C. albicans in transfected cells is significantly reduced, as well as the expression levels of genes involved in the apoptotic pathway. Through the study of interaction between antimicrobial peptides and microbiota we will be able in the future to better understand the mechanisms by which they exert the host defense function against intestinal pathogens

COVID-19 Vaccines and Atrial Fibrillation: Analysis of the Post-Marketing Pharmacovigilance European Database

Atrial fibrillation (AF) has been described in COVID-19 patients. Recently, some case reports and US pharmacovigilance analyses described AF onset as a rare adverse event following COVID-19 vaccination. The possible correlation is unclear. We systematically analyzed the reports of AF related to COVID-19 vaccines collected in the European pharmacovigilance database, EudraVigilance (EV), from 2020 to November 2022. We carried out descriptive and disproportionality analyses. Moreover, we performed a sensitivity analysis, excluding the reports describing other possible alternative AF causes (pericarditis, myocarditis, COVID-19, or other drugs that may cause/exacerbate AF). Overall, we retrieved 6226 reports, which represented only 0.3% of all those related to COVID-19 vaccines collected in EV during our study period. AF reports mainly referred to adults (in particular, >65 years old), with an equal distribution in sex. Reports were mainly related to tozinameran (54.04%), elasomeran (28.3%), and ChAdOx1-S (14.32%). The reported AF required patient hospitalization in 35% of cases and resulted in a life-threatening condition in 10% of cases. The AF duration (when reported) was highly variable, but the majority of the events had a short duration (moda = 24 h). Although an increased frequency of AF reporting with mRNA vaccines emerges from our study, other investigations are required to investigate the possible correlation between COVID-19 vaccination and the rare AF occurrence

AT1-receptor blockade: Protective effects of irbesartan in cardiomyocytes under hypoxic stress.

Hypoxia induces myocardial injury through the activation of inflammatory and oxidative processes. The pivotal role of the renin angiotensin system (RAS) in the pathogenesis of cardiovascular diseases has been firmly established in clinical trials and practice; in fact many experimental and clinical data have highlighted that its inhibition has a cardioprotective role. Activated RAS also stimulates inflammation directly inducing proinflammatory and oxidative gene expression. This study aimed to investigate the protective role of a pre-treatment (10 and 100 μM) with irbesartan on injury induced by 24 h of hypoxia in HL-1 cardiomyocytes; in particular, we have analyzed the natriuretic peptide (BNP) expression, a biomarker able to modulate inflammatory reaction to cardiac injury and some markers involved in oxidative stress and inflammation. Our results demonstrated that a pre-treatment with 100 μM irbesartan significantly increased SOD activity and catalase expression of 15 and 25%, respectively, compared to hypoxic cells (P<0.05). On the other hand, it was able to reduce the release of peroxynitrite and iNOS protein expression of 20 and 50% respectively (P<0.05). In addition irbesartan exerts an anti-inflammatory activity reducing Toll-like receptors (TLRs)-2 and -4 mRNA expression, TNF-alpha expression and activity (20%) and increasing the expression of the cytokine IL-17 (40%) (P<0.05 vs hypoxia). Our findings also showed that BNP induced by ischemia was significantly and in a concentration-dependent manner reduced by irbesartan. The findings of our study demonstrated that the AT1 receptor antagonist irbesartan exerts a protective role in an in vitro hypoxic condition reducing oxidative stress and inflammation

Q-switched Nd:YAG laser protects human keratinocytes from oxidative stress and inflammation via AhR–Nrf2 pathway

In recent years, some treatments for esthetic and pathologic skin conditions have increasingly been based on the use of non-ablative neodymium-doped yttrium aluminum garnet (Nd:YAG) laser due to its greater penetration ability than other types of lasers, few contraindications, minimal side effects, no damage for epidermidis and the rapid recovery of the treated patients. The skin is frequently exposed to many stressors such as radiation, toxic substances, metabolites, foods, mechanical insults, and allergen exposition that cause oxidative damage and have a decisive influence on the aging process. The imbalance between reactive oxygen species, reactive nitrogen species, and the malfunctioning of the antioxidant defense system promotes the establishment of an excessive inflammatory process, which can induce various diseases including cancer and neurodegenerative disorders. The present study investigated the cytoprotective function of Q-switched Nd:YAG laser against stress aging and cell injury in HaCaT cells. We evaluated the effect of the laser on antioxidant defenses, inflammation, metalloproteinases’ expression, and the AhR-Nrf2 pathway. Q-switched Nd:YAG is able to upregulate the AhR pathway and the expression of IL-6 and TGF-β, which are involved in wound repair process, and to downregulate the expression of MMP-2 and 9, so preventing the collagen degradation. Q-switched Nd:YAG can stimulate the cellular antioxidant defenses by activating the AhR-Nrf2 system