👤 Paolo Calabrò

Elevated lipoprotein(a) [Lp(a)] levels have been strongly related to cardiovascular (CV) risk. However, its association with Hypertension Mediated Organ Damage (HMOD) and CV events in the primary prevention setting remains unclear. To evaluate in these patients, the correlation between Lp(a) levels and: (i) heart, vessels and kidney HMOD and; (ii) CV events and all-cause mortality in a primary prevention setting. 747 low CV risk subjects were recruited between 2009 and 2014. HMOD was assessed through Pulse Wave Velocity, carotid Intima-Media Thickness (IMT), presence of carotid plaques, Left Ventricular Hypertrophy (LVH) and Ejection Fraction and glomerular filtration rate. All-cause mortality and CV events up to 2021 were retrieved by electronic health records, for a median follow-up time of 10 years (I-III quartiles 9.6-11.1). Mean age was 50.8 ± 13.0 years and 63.5% of the subjects were men. The prevalence of hypertension was 37.9%, dyslipidemia 67.2%, smoking 17.8%, and diabetes mellitus 8.7%. Median Lp(a) value was 17 mg/dL (5.9-56.0), and 26.5% of patients had values above 50 mg/dL. Regarding HMOD, 10.3% subjects had arterial stiffness, 7.2% increased IMT, 19.8% carotid plaques while only 0.7% had LVH. No significant correlation was found between Lp(a) levels and indices of subclinical HMOD. Furthermore, no relationship was found between CV events and all-cause mortality and Lp(a) levels. In this primary prevention cohort, elevated Lp(a) levels were not associated with significant structural damage to the heart, carotid arteries, or increased aortic stiffness and were not associated with CV events and all-cause mortality. Show less

Multiple Sclerosis (MS) therapies effectively modulate peripheral immune responses but largely fail to promote neural repair within the central nervous system. This review evaluates whether psychedelic compounds (PSYs), via 5-HT2A activation, can fill a critical therapeutic gap: the need for agents that simultaneously suppress neuroinflammation and promote regeneration. We dissect the evidence suggesting PSYs can reprogram the neuroimmune milieu by downregulating key pro-inflammatory cytokines (e.g., TNF-α, IL-6) in glial cells while concurrently upregulating crucial neurotrophic factors (e.g., BDNF) that promote synaptic plasticity and oligodendrocyte support. However, we argue that the current evidence, largely derived from non-specific inflammation models, is insufficient to predict clinical efficacy in an autoimmune disease like MS. We critically analyze the significant translational barriers-from cardiovascular and psychiatric risks to profound legal and ethical challenges-that temper the immediate clinical promise. Finally, we propose a forward-looking perspective, suggesting that the true value of PSYs may lie not in their direct clinical use, but in uncovering novel therapeutic pathways. The emergence of non-hallucinogenic, functionally selective 5-HT2A agonists, inspired by psychedelic pharmacology, represents a more viable strategy to harness these mechanisms for MS therapy, demanding rigorous preclinical validation in disease-relevant models. Show less

Long-lived individuals (LLIs) are considered an ideal model to study healthy human aging. Blood fatty acid (FA) profile of a cohort of LLIs (90-111 years old, n = 49) from Sicily was compared to adults (18-64 years old, n = 69) and older adults (65-89 years old, n = 54) from the same area. Genetic variants in key enzymes related to FA biosynthesis and metabolism were also genotyped to investigate a potential genetic predisposition in determining the FA profile. Gas chromatography was employed to determine the FA profile, and genotyping was performed using high-resolution melt (HRM) analysis. Blood levels of total polyunsaturated FA (PUFA) and total trans-FA decreased with age, while the levels of saturated FA (SFA) remained unchanged. Interestingly, distinctively higher circulatory levels of monounsaturated FA (MUFA) in LLIs compared to adults and older adults were observed. In addition, among LLIs, rs174537 in the FA desaturase 1/2 (FADS1/2) gene was associated with linoleic acid (LA, 18:2n-6) and docosatetraenoic acid (DTA, 22:4n-6) levels, and the rs953413 in the elongase of very long FA 2 (ELOVL2) was associated with DTA levels. We further observed that rs174579 and rs174626 genotypes in FADS1/2 significantly affect delta-6 desaturase (D6D) activity. In conclusion, our results suggest that the LLIs have a different FA profile characterized by high MUFA content, which indicates reduced peroxidation while maintaining membrane fluidity. Show less

Point mutations are the most common cause of inherited diseases. Bioinformatics tools can help to predict the pathogenicity of mutations found during genetic screening, but they may work less well in determining the effect of point mutations in non-coding regions. In silico analysis of intronic variants can reveal their impact on the splicing process, but the consequence of a given substitution is generally not predictable. The aim of this study was to functionally test five intronic variants ( Show less

Hypertrophic cardiomyopathy is a relatively frequent disease with a prevalence of 0.2% worldwide and a remarkable genetic heterogeneity, with more than 30 causative genes reported to date. Current PCR-based strategies are inadequate for genomic investigations involving many candidate genes. Here, we report a next-generation sequencing procedure associated with DNA sequence capture that is able to sequence 202 cardiomyopathy-related genes simultaneously. We developed a complementary data analysis pipeline to select and prioritize genetic variants. The overall procedure can screen a large number of target genes simultaneously, thereby potentially revealing new disease-causing and modifier genes. By using this procedure, we analyzed hypertrophic cardiomyopathy patients in a shorter time and at a lower cost than with current procedures. The specificity of the next-generation sequencing-based procedure is at least as good as other techniques routinely used for mutation searching, and the sensitivity is much better. Analysis of the results showed some novel variants potentially involved in the pathogenesis of hypertrophic cardiomyopathy: a missense mutation in MYH7 and a nonsense variant in INS-IGF2 (patient 1), a splicing variant in MYBPC3 and an indel/frameshift variant in KCNQ1 (patient 2), and two concomitant variations in CACNA1C (patient 3). Sequencing of DNA from the three patients within a pool allowed detection of most variants identified in each individual patient, indicating that this approach is a feasible and cost-effective procedure. Show less