👤 Arthur Aquino

Lipoprotein(a) [Lp(a)] is an inherited cardiovascular risk factor. However, its association with coronary plaque characteristics beyond traditional risk enhancers remains unclear. We aimed to evaluate the association between Lp(a) levels and coronary plaque characteristics in asymptomatic primary prevention patients, and to compare its predictive value against other risk enhancers, including LDL particle concentration (LDL-P), high-sensitivity C-reactive protein (hsCRP), and coronary artery calcium (CAC) score. We retrospectively analyzed 547 asymptomatic patients undergoing coronary computed tomography angiography (CCTA) between 2018-2024. Plaque characteristics were assessed using artificial intelligence-based quantitative CCTA. Associations between Lp(a), LDL-P, hsCRP, CAC score, and plaque features were evaluated using multivariable regression adjusted for age and sex. Median age was 56 years, 69.8% were male. Higher Lp(a) was associated with greater total plaque volume (β=23.1 mm³, p=0.006), calcified plaque (β=11.1 mm³, p=0.014), non-calcified plaque (β=12.0 mm³, p=0.027), and low-density non-calcified plaque (LDNCP; β=0.4 mm³, p<0.001) volumes, as well as increased area stenosis (β=1.9%, p=0.031) and remodeling index (β=0.02, p=0.017). In multivariable models, CAC score was the strongest predictor of overall plaque burden including calcified and non-calcified plaque (p<0.000) but was not associated with LDNCP. Lp(a) remained independently associated with LDNCP (β=0.45 mm³, p=0.013), while LDL-P and hsCRP showed no significant associations. In asymptomatic primary prevention patients, Lp(a) was independently associated with high-risk coronary plaque features, specifically LDNCP, beyond traditional risk enhancers. These findings highlight the unique role of Lp(a) in identifying coronary plaque vulnerability and suggest complementary roles for Lp(a) and CAC in refining cardiovascular risk stratification. Show less

This study explores the interaction between immune and cancer cells in the tumor microenvironment (TME) of cervical carcinoma (CC), with emphasis on tumor-associated macrophages (M2-TAMs) and the STAT3-NF-κB signaling pathway. It investigates how Treg cell polymorphisms and TAM infiltration through these pathways influence overall survival (OS) in CC patients. This prospective study follows 100 CC patients from 2018 to 2023 using qRT-PCR and immunohistochemistry on tumor samples, and flow cytometry on blood samples to evaluate immunosuppressive cytokines and Treg cell polymorphisms. High stromal CD163+204+ TAM density, mediated by STAT3/NF-κB, correlates with biomarkers such as Ki-67, VEGFα, and FOXP3 (p < 0.001). XPO5 expression is associated with increased STAT3, SNAIL, and HPV 16/18 levels. FOXP3 T allele deletion and HLA-G polymorphism in the blood of patients correlate with higher STAT3 tumor expression and elevated IL-4 and IL-17 blood cytokines. The CXCL12-CXCR4 axis shows a strong association with STAT3, SNAIL in TME and blood cytokines, including IL-6 and IL-12. Elevated CXCL12, CXCR4, and SNAIL expression in TME significantly increases mortality risk. These findings underscore the role of M2TAM infiltration and immune modulation in tumor progression and clinical outcomes in CC. Show less

To isolate cancer stem cells (CSC) from a metastatic oral squamous cell carcinoma (OSCC) cell line and investigate their in vitro and in vivo phenotypic characteristics. Subpopulations with individual staining intensities for CD44 and CD326 were isolated from the OSCC cell line LN-1A by FACS: CD44 E-cadherin levels were higher in CSC-E cells while vimentin and Slug more produced by CSC-M The CSC subpopulations here described show increased cancer capabilities in vitro, tumorigenic and metastatic potential in vivo, and may be exploited in the search for novel therapeutic targets for OSCC. Show less

The accumulation of amyloid-β (Aβ) is the main event related to Alzheimer's disease (AD) progression. Over the years, several disease-modulating approaches have been reported, but without clinical success. The amyloid cascade hypothesis evolved and proposed essential targets such as tau protein aggregation and modulation of β-secretase (β-site amyloid precursor protein cleaving enzyme 1 - BACE-1) and γ-secretase proteases. BACE-1 cuts the amyloid precursor protein (APP) to release the C99 fragment, giving rise to several Aβ peptide species during the subsequent γ-secretase cleavage. In this way, BACE-1 has emerged as a clinically validated and attractive target in medicinal chemistry, as it plays a crucial role in the rate of Aβ generation. In this review, we report the main results of candidates in clinical trials such as E2609, MK8931, and AZD-3293, in addition to highlighting the pharmacokinetic and pharmacodynamic-related effects of the inhibitors already reported. The current status of developing new peptidomimetic, non-peptidomimetic, naturally occurring, and other class inhibitors are demonstrated, considering their main limitations and lessons learned. The goal is to provide a broad and complete approach to the subject, exploring new chemical classes and perspectives. Show less

Hypercytokinemia, found in SARS-CoV-2 infection, contributes to multiple organ dysfunctions with acute respiratory distress syndrome, shock etc. The aim of this study was to describe cytokine storm signatures in patients with acute COVID-19 and to investigate their influence on severity of the infection. Plasma levels of 47 cytokines were investigated in 73 patients with moderate and severe COVID-19 (41 and 32, respectively) and 11 healthy donors (HD). The most elevated levels comparing patients and the HD were observed for seven pro-inflammatory cytokines (IL-6, IL-8, IL-15, IL-18, IL-27, IFNγ, TNFα), three chemokines (GROα, IP-10, MIG), two anti-inflammatory cytokines (IL-1RA, IL-10), and two growth factors (G-CSF, M-CSF). The patients with severe disease had significantly higher levels of FGF-2/FGF-basic, IL-1β, and IL-7 compared to the HD. The two groups of patients differed from each other only based on the levels of EGF, eotaxin, and IL-12 p40. Pneumonia lung injury, characterized by computer tomography, positively correlated with levels of EGF, IP-10, MCP-3 levels and negatively with IL-12 p40. Pro-inflammatory factors including IL-6, TNFα, and IP-10 negatively correlated with the frequency of the circulating T-helper17-like cells (Th17-like) and follicular Th cells that are crucial to develop SARS-CoV-2-specific plasma cells and memory B cells. Obtained data on the cytokine levels illustrate their influence on progression and severity of COVID-19. Show less

Despite extensive evidence demonstrating the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects remain elusive. This study assessed changes in plaque morphology using intravascular imaging, with a comprehensive evaluation of cholesterol efflux capacity (CEC) and peripheral blood mononuclear cell (PBMC) transcriptomics in patients receiving high-dose statin therapy. In a prospective study, 85 patients with stable coronary artery disease underwent percutaneous coronary intervention for a culprit lesion, followed by intracoronary multimodality imaging, including optical coherence tomography (OCT) of an obstructive nonculprit lesion. All subjects received 40 mg of rosuvastatin daily for 8 to 12 weeks, when the nonculprit lesion was reimaged and intervention performed. Blood samples were drawn at both times to assess CEC and transcriptomic profile in PBMC. Baseline OCT minimal fibrous cap thickness (FCT) was 100.9 ± 41.7 μm, which increased to 108.6 ± 39.6 μm at follow-up, and baseline CEC was 0.81 ± 0.14, which increased at follow-up to 0.84 ± 0.14 (p = 0.003). Thin-cap fibroatheroma prevalence decreased from 20.0% to 7.1% (p = 0.003). Changes in FCT were independently associated with CEC increase by multivariate analysis (β: 0.30; p = 0.01). PBMC microarray analysis detected 117 genes that were differentially expressed at follow-up compared to baseline, including genes playing key roles in cholesterol synthesis (SQLE), regulation of fatty acids unsaturation (FADS1), cellular cholesterol uptake (LDLR), efflux (ABCA1 and ABCG1), and inflammation (DHCR24). Weighted coexpression network analysis revealed unique clusters of genes associated with favorable FCT and CEC changes. The study demonstrated an independent association between fibrous cap thickening and improved CEC that may contribute to morphological changes suggesting plaque stabilization among patients taking intensive statin therapy. Furthermore, the significant perturbations in PBMC transcriptome may help determine the beneficial effects of statin on plaque stabilization. (Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering [YELLOW II]; NCT01837823). Show less