👤 Maria Rosalba Moreira das Neves

Auricular vagus nerve stimulation (aVNS) has emerged as a noninvasive neuromodulatory strategy with the potential to modulate central sensitization and inflammatory pathways. However, its role in fibromyalgia (FM) remains insufficiently explored. To investigate whether stimulation laterality (left vs. right auricular branch of the vagus nerve, ABVN) differentially influences clinical and biological outcomes in women with FM. In this randomized, double-blind, sham-controlled trial, 51 women with FM were allocated to sham stimulation, right-sided aVNS (aVNS-R), or left-sided aVNS (aVNS-L). Participants underwent weekly sessions for four weeks and were followed for 12 weeks. Pain intensity was the primary outcome. Secondary outcomes included psychological symptoms, sleep, functional status, quality of life, and circulating biomarkers (pro- and anti-inflammatory cytokines, brain-derived neurotrophic factor [BDNF]). While no significant between-group differences were observed in pain intensity, left-sided stimulation (aVNS-L) was associated with a modest but significant reduction in global symptom severity. Importantly, aVNS-L produced consistent immunomodulatory effects, including decreased IL-1β and TNF-α levels, and increased IL-4, IL-10, and BDNF concentrations. This exploratory trial suggests that stimulation laterality may shape the biological response to aVNS in FM. Although clinical pain relief was not superior to sham, left-sided stimulation promoted an anti-inflammatory profile and enhanced neuroplasticity markers. These findings support further investigation of aVNS laterality as a targeted neuromodulatory approach for FM. Brazilian Clinical Trials Registry RBR-10d3crcf. Show less

Sex and apolipoprotein E ε4 (APOE4) interact to alter the risk for Alzheimer's disease and other neurodegenerative disorders. Herein, we show sex-specific differences in immune activation and lymphatic function in the meningeal dura of humanized female and male mice expressing two alleles of APOE4 (E4/E4), when compared with their respective sex-matched E3/E3 controls. We also describe distinct effects of APOE4 on brain lipid composition and inflammation in females and males that were partially reverted upon colony-stimulating factor 1 receptor (CSF1R) inhibition. Suppressing innate immunity reduced neuroinflammation and restored cognitive function in E4/E4 females, while exacerbating neuroinflammation and accelerating cognitive decline in E4/E4 males. Finally, in line with the E4/E4 humanized mouse model data, we show that APOE4 expression is linked to sexually dimorphic leukocyte activation profiles in the human brain. This study highlights the need for personalized therapies when targeting APOE, brain immunity, and meningeal lymphatics to promote cognitive resilience in both females and males. Show less

Lipoprotein(a) [Lp(a)] is recognized as an independent risk factor for coronary disease owing to its atherogenic, proinflammatory, and prothrombotic properties. Current guidelines recommend a single measurement in adults to refine cardiovascular (CV) risk assessment. We aimed to characterize Lp(a) levels in patients with acute coronary syndrome (ACS) and explore associations with sex, age, comorbidities, and traditional cardiovascular risk factors. We conducted a cross-sectional study of patients with ACS admitted to our center between January 2022 and December 2023, with Lp(a) measured at admission. Patients were stratified into two groups: Lp(a) >100 nmol/L and ≤100 nmol/L. Demographic and clinical data, including traditional cardiovascular risk factors (dyslipidemia, diabetes mellitus, arterial hypertension, smoking, and obesity), were collected from hospital records. Chi-square and independent t or Mann-Whitney U tests were used to compare categorical and quantitative variables; linear regression analysis assessed associations between continuous Lp(a) values and independent variables. Among 903 patients admitted with ACS during the study period, Lp(a) was measured in 388 (42%). Median Lp(a) level was 62.0 [18.4, 153.8] nmol/L. Of these, 38.7% had Lp(a) >100 nmol/L. Women had higher Lp(a) than men (p-trend=0.014). Lp(a) levels were similar across traditional cardiovascular risk factors categories. Among patients without traditional cardiovascular risk factors, women also had higher Lp(a) than men (p=0.003). Elevated Lp(a) was associated with history of coronary artery disease (p-trend=0.003) and with treatment with high-intensity statins alone (p-trend=0.032) or in combination with ezetimibe (p-trend=0.014). Lp(a) levels showed a heterogeneous distribution and was not associated with traditional cardiovascular risk factors or other lipid parameters. This reinforces Lp(a) as an independent risk factor, supporting active screening in patients with ACS, particularly in women not affected by traditional cardiovascular risk factors. Show less

Chronic exposure to second-hand smoke (SHS) contributes to the development of health issues, including cancer and cardiovascular diseases. Molecular mechanisms underlying SHS-related diseases remain poorly understood, highlighting the need for reliable risk assessment biomarkers. Herein, we demonstrate that the plasma proteome of individuals exposed to SHS undergoes significant modulation. Butyrylcholinesterase (BChE) and Vitamin D-binding protein (GC) that are involved in the physiological response to circulating toxic substances, as well as key mediators of systemic inflammation, including Complement C1r subcomponent (C1R), Complement C1q subcomponent subunit C (C1QC), Histidine-rich glycoprotein (HRG), and Vitamin K-dependent protein S (PROS1), were found to be significantly modulated in SHS-exposed individuals. Moreover, strong indicators of a pro-atherothrombotic response such Apolipoprotein A-IV (APOA4) and Alpha-2-antiplasmin (SERPINF2), were also differentially expressed. These findings provide novel insights into the biological pathways linking SHS-exposure to cardiovascular risks, and suggest a panel of candidate proteins with potential utility as SHS-risk assessment biomarkers. Show less

Apolipoprotein A-IV (apoA-IV) is an abundant lipid-binding protein in blood plasma. We previously reported that apoA-IV, as an endogenous inhibitor, competitively binds platelet αIIbβ3 integrin from its N-terminal residues, reducing the potential risk of thrombosis. This study aims to investigate how the apoA-IV Show less

The present study describes the expression of genes in the Longissimus dorsi muscle related to meat quality of hair lambs finished in an Integration Crop-Livestock system. Twenty-eight non-castrated lambs of two breeds, Somalis Brasileira and Santa Inês, at 120 ± 15 days of age, with an average initial live weight of 18 ± 3.1 kg, were kept in a pasture-based finishing system with supplementation. Upon reaching 28 kg body weight, animals were sent for slaughter. Samples of the Longissimus dorsi and Biceps femoris muscle were harvested for analyses of gene expression and physicochemical properties. Significant differences were detected between the breeds for tissue and chemical composition, whereas the physical aspects did not differ. We observed the expression of six genes related to lipid synthesis (acetyl-CoA carboxylase [ACACA], fatty acid synthase [FAS], stearoyl-CoA desaturase [SCD], lipoprotein lipase [LPL], cell death-inducing DFFA-like effector A [CIDEA], and thyroid hormone responsive [THRSP]) and six genes related to molecular synthesis (myostatin [MSTN], growth differentiation factor 8 [GDF8], insulin-like growth factor 1 [IGF1], insulin-like growth factor 2 [IGF2], delta-like 1 homolog [DLK1], and growth hormone receptor [GHr]) in both breeds. The Santa Inês breed and the Somalis Brasileira showed similar expression patterns of genes related to lipogenesis and myogenesis of the Longissimus dorsi muscle, with the exception of the THRSP gene, in which the Somalis Brasileira have more receptors for the action of thyroid hormones, which resulted in greater thickness of fat in the carcass (subcutaneous fat) and higher lipid content in the chemical composition of the meat. Show less

Beef cattle affected by feet and legs malformations (FLM) cannot perform their productive and reproductive functions satisfactorily, resulting in significant economic losses. Accelerated weight gain in young animals due to increased fat deposition can lead to ligaments, tendon and joint strain and promote gene expression patterns that lead to changes in the normal architecture of the feet and legs. The possible correlated response in the FLM due to yearling weight (YW) selection suggest that this second trait could be used as an indirect selection criterion. Therefore, FLM breeding values and the genetic correlation between FLM and yearling weight (YW) were estimated for 295,031 Nellore animals by fitting a linear-threshold model in a Bayesian approach. A genome-wide association study was performed to identify genomic windows and positional candidate genes associated with FLM. The effects of single nucleotide polymorphisms (SNPs) on FLM phenotypes (affected or unaffected) were estimated using the weighted single-step genomic BLUP method, based on genotypes of 12,537 animals for 461,057 SNPs. Twelve non-overlapping windows of 20 adjacent SNPs explaining more than 1% of the additive genetic variance were selected for candidate gene annotation. Functional and gene prioritization analysis of candidate genes identified six genes ( Show less

Platelet αIIbβ3 integrin and its ligands are essential for thrombosis and hemostasis, and play key roles in myocardial infarction and stroke. Here we show that apolipoprotein A-IV (apoA-IV) can be isolated from human blood plasma using platelet β3 integrin-coated beads. Binding of apoA-IV to platelets requires activation of αIIbβ3 integrin, and the direct apoA-IV-αIIbβ3 interaction can be detected using a single-molecule Biomembrane Force Probe. We identify that aspartic acids 5 and 13 at the N-terminus of apoA-IV are required for binding to αIIbβ3 integrin, which is additionally modulated by apoA-IV C-terminus via intra-molecular interactions. ApoA-IV inhibits platelet aggregation and postprandial platelet hyperactivity. Human apoA-IV plasma levels show a circadian rhythm that negatively correlates with platelet aggregation and cardiovascular events. Thus, we identify apoA-IV as a novel ligand of αIIbβ3 integrin and an endogenous inhibitor of thrombosis, establishing a link between lipoprotein metabolism and cardiovascular diseases. Show less