Universidade Brasil

Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss, and growing evidence highlights neuroinflammation as a key contributor to disease progression. Annexin A1 (AnxA1), a glucocorticoid-regulated protein with anti-inflammatory and pro-resolving functions, and its N-terminal peptide Ac2-26 have shown neuroprotective potential, but the mechanisms underlying their effects in PD remain unclear. Here, we investigated the effects of AnxA1 and Ac2-26 in a 6-hydroxydopamine (6-OHDA) mouse model of PD using C57BL/6 wild-type (AnxA1+/+) and AnxA1 knockout (AnxA1-/-) mice. Animals received a unilateral 6-OHDA injection into the striatum, followed by intraperitoneal injection of Ac2-26 or saline. Motor behavior, dopaminergic neuron survival, cytokine levels, and glial changes were analyzed. Ac2-26 improved motor performance and protected against 6-OHDA-induced dopaminergic degeneration in the striatum and substantia nigra (SN) of AnxA1+/+ mice, preventing the loss of tyrosine hydroxylase (TH)+ neurons. These protective effects were reduced in AnxA1-/- mice. Ac2-26 also modulated neuroinflammation in a genotype-dependent manner, increasing anti-inflammatory cytokines and limiting pro-inflammatory mediators in the SN of AnxA1+/+ animals. In females, genetic deletion of AnxA1 led to reduced TH expression, impaired behavioral recovery, and disruption of the estrous cycle. Overall, Ac2-26 confers neuroprotection through AnxA1-dependent regulation of neuroinflammation, dopaminergic integrity, and hormonal balance, supporting its potential as a therapeutic target in PD.

Pharmacological control of leukotriene biosynthesis is well established in mammals, but its translational value for teleost inflammation remains unclear. We evaluated oral 5-lipoxygenase (5-LOX) inhibition with zileuton in Nile tilapia challenged with a bacterin of A. hydrophila to induce acute aerocystitis. Fish received vehicle or zileuton (2.25 or 4.50mg/kg) before challenge. Outcomes were assessed at 6, 24, and 48h post-inoculation (hpi) to investigate cellular profiles in exudates and blood, reactive oxygen species (ROS), acute-phase proteins (APPs), and the formation of splenic melano-macrophage centers (MMCs). Zileuton significantly reduced exudate granulocytes and thrombocytes at 6 hpi and macrophages at 24 hpi. Systemically, treatment attenuated transient peaks in neutrophils and lymphocytes (6 hpi) and thrombocytes (24-48 hpi). We observed correlations between lower ROS production and reduced blood neutrophil counts and macrophages in the exudate, suggesting a restrained oxidative burst. Zileuton down-modulated positive APPs (ceruloplasmin, complement C3, α2-macroglobulin, haptoglobin) in time- and dose-dependent patterns, while negative APPs (albumin, transferrin) and apolipoprotein A1 showed no consistent change. Histology revealed MMCs enlargement/remodeling with bacterin that was tempered by zileuton. The anti-inflammatory response was dose-dependent, since fish treated with 4.50mg/kg were more effective than 2.25mg/kg. Tilapia receiving 4.50mg/kg of zileuton exhibited a pronounced decrease in inflammatory cell accumulation in the exudate (granulocytes, lymphocytes, and macrophages), reduced ROS production, stronger suppression of positive acute-phase proteins (notably ceruloplasmin, complement C3, and haptoglobin), and more evident remodeling of splenic MMCs. No clinical adverse effects were observed. To our knowledge, this is the first demonstration in fish that oral 5-LOX inhibition by zileuton mitigates acute inflammatory reaction, and underscores leukotriene pathway as a promising lever for improving fish health outcomes.

Pharmacological treatments for attention-deficit/hyperactivity disorder (ADHD) are efficacious and safe; however, substantial interindividual variability in treatment response persists, with many patients experiencing suboptimal outcomes or early discontinuation. Although genetic factors have been proposed as contributors to this variability, clinically actionable predictors remain elusive. Here, we present the first meta-analysis evaluating whether polygenic liability for ADHD and related psychiatric and behavioral-cognitive phenotypes is associated with clinically meaningful response to methylphenidate in 1000 ADHD cases from Norway, Brazil, and Spain assessed in real-world settings. Polygenic scores (PGS) for ADHD, autism, bipolar disorder, educational attainment, major depressive disorder, neuroticism, and schizophrenia were calculated separately for each cohort. Treatment response was assessed using evaluations of global clinical improvement and harmonized by categorizing individuals as responders or non-responders. Cohort-specific associations were combined using fixed-effects meta-analysis. No PGS showed a significant association with treatment response. Effect sizes were small, consistent across cohorts, and characterized by minimal between-study heterogeneity. Sensitivity analyses incorporating clinical and treatment-related covariates yielded convergent results. As the first meta-analytic evaluation of polygenic predictors evaluating clinically meaningful ADHD stimulant response, these findings delineate the current limits of PGS in pharmacogenomic applications. Rather than supporting immediate clinical utility, our results highlight key methodological and conceptual constraints, including limited sample sizes, heterogeneous outcome definitions, and the indirect nature of susceptibility-based PGS for predicting treatment response. By mapping these boundaries, this study provides a framework to recalibrate research priorities and guide the next generation of ADHD pharmacogenomic studies toward larger, harmonized, and more informative definitions of treatment response.

Pregnant individuals were prioritised for COVID-19 research due to concerns about increased susceptibility and limited clinical trial data. This narrative review synthesises evidence on maternal infection, immunological adaptations, placental susceptibility, and antibody transfer following maternal SARS-CoV-2 vaccination. Symptomatic COVID-19 during pregnancy increases risks of severe outcomes, whereas vertical transmission remains rare. Placental pathology is characterised mainly by maternal vascular malperfusion and inflammation, with limited evidence of direct viral infection. Maternal vaccination-particularly with mRNA vaccines-induces robust IgG responses with efficient transplacental and lactational transfer, conferring passive neonatal protection. Key uncertainties include optimal vaccine timing, durability of neonatal immunity, and variant-specific responses. Strengthening standardised research and ensuring inclusion of pregnant individuals is essential for global maternal health policy.

Rhipicephalus microplus significantly affects dairy cattle, with spray-applied acaricides commonly used for its control. However, increasing resistance and variations in application methods may compromise treatment efficacy. This study evaluated the efficacy of acaricide formulation containing pyrethroids and organophosphates, as well as its deposition in bovine hair when applied at different working pressures. Cattle were divided into three groups (n = 10 each): Group 1 received treatment at 50 psi using a backpack sprayer, Group 2 at 300 psi using a power sprayer, and Group 3 served as an untreated control. Female ticks (4.5-8 mm) were counted on days 3, 7, 14, 21, and 35 post-treatment (DPT). Hair samples were collected from six body regions (dewlap, belly, between the legs, loin, legs, and neck) at 0, 1, 2, and 3 DPT. Residual concentrations of cypermethrin, chlorpyrifos, and fenthion were measured using direct analysis in real-time mass spectrometry (DART-MS). A significant difference (p ≤ 0.05) in tick reduction was observed between the treated groups only at 3 DPT. Peak efficacy occurred on day 21 in both treated groups, with efficacy ranging from 56.7% to 97.5% (50 psi) and 78.9-87.4% (300 psi). Cypermethrin levels were consistently higher at 50 psi across all days and most body regions. Chlorpyrifos and fenthion showed higher concentrations on day 0 at 300 psi, especially in the loin and neck. The pressure did not lead to significant differences in overall efficacy against R. microplus. However, it significantly affected the deposition of active ingredients in bovine hair.

Antifungal drugs such as ketoconazole (KTZ) are increasingly detected in aquatic environments, raising concerns about their potential ecotoxicological effects on non-target organisms. In this study, we evaluated the physiological, biochemical, and morphological responses of the freshwater microalga Raphidocelis subcapitata exposed to environmentally relevant concentrations of KTZ. Initially, based on chronic exposure analyses, toxicity was observed at concentrations ≥ 1.9 µg/L, and the IC50 value was 7.2 µg/L after 120 h of exposure. Subsequently, assays using sub-inhibitory concentrations (2.8 and 5.6 µg L⁻¹) were conducted for 96 h and 192 h to evaluate selected endpoints, including changes in growth rate, photosynthetic pigments, cell morphology, lipid production, and oxidative stress, with exposure duration influencing these responses. These findings revealed a dual nature of KTZ toxicity: while low concentrations may stimulate photosynthetic activity, higher levels trigger oxidative stress. In addition, exposure time also influenced the effects observed in R. subcapitata. Our results underscore the importance of multivariate approaches in ecotoxicology and contribute to a deeper understanding of the environmental risks associated with pharmaceutical contaminants in freshwater ecosystems.

O presente artigo desenvolve uma reflexão teórica e normativa acerca da intersecção entre o princípio constitucional da universalidade, o direito fundamental à saúde e a implementação do cuidado biopsicossocial no âmbito da odontologia contemporânea. Partindo da premissa de que a saúde bucal é indissociável da saúde geral e da dignidade da pessoa humana, o estudo analisa como o modelo biomédico tradicional, estritamente focado na patologia biológica, mostra-se insuficiente para responder às complexas demandas de qualidade de vida e inserção social do indivíduo. Através de uma revisão bibliográfica e documental, pautada na Lei nº 8.080/90 e nas diretrizes da Política Nacional de Saúde Bucal (Brasil Sorridente), bem como na Política Nacional de Práticas Integrativas e Complementares em Saúde (PNPIC), discute-se o papel do cirurgião-dentista como agente promotor de cidadania. Conclui-se que a universalidade do acesso, quando aliada a um olhar humanizado que compreende as dimensões psíquicas e sociais do paciente, transfigura o ato clínico em uma ferramenta de resgate da autoestima e de justiça social, reafirmando a saúde bucal como um pilar inalienável do direito à vida em sua plenitude.

Background/Objectives: Schistosomiasis is a neglected tropical disease affecting >200 million people worldwide. Praziquantel is the sole recommended drug against Schistosoma mansoni; however, it lacks activity against juvenile forms and cannot prevent reinfection. Thus, there is an urgent need to identify novel therapeutic targets. Long noncoding RNAs (lncRNAs) are known to regulate various biological processes in S. mansoni, including parasite pairing and fertility; therefore, screening for novel lncRNAs could reveal new potential targets. Methods: We compiled all publicly available RNA-seq data from the Sequence Read Archive (SRA) and performed a hierarchical transcriptome assembly using the multi-sample assembler Ryūtō, combined with version 10 of the S. mansoni genome. We applied HOMER for peak-calling and identification of histone marks and used weighted gene co-expression network analysis (WGCNA) to infer putative functions of lncRNAs in sexual dimorphism. Results: Using a robust pipeline, we identified 10,170 novel lncRNA genes comprising 16,990 novel lncRNA transcripts, including 8783 intergenic, 7918 antisense, and 289 intronic lncRNA transcripts. Most (78.7%) have histone regulatory marks (H3K4me3, H3K27me3, H3K27ac, or H4K20me1) near their transcription start sites, indicating potential expression regulation. Comparing male and female samples, we identified 1991 differentially expressed genes (FDR < 5%, |log2FC| ≥ 1.5), including 296 known lncRNAs and 339 novel lncRNAs. WGCNA identified hub lncRNAs within co-expression modules, and Gene Ontology enrichment analyses (FDR ≤ 5%) suggest that these lncRNAs are involved in cell differentiation and morphogenesis pathways. Conclusions: We provide a comprehensive catalog of S. mansoni lncRNAs. These findings offer opportunities to discover potential new therapeutic targets, advancing the future development of anti-schistosome therapies.

A determinação social da saúde constitui abordagem fundamental para compreender como fatores sociais, econômicos e territoriais participam da produção das desigualdades em saúde observadas nas populações. No Brasil, diferenças relacionadas à renda, às condições de vida e ao acesso a serviços públicos influenciam diretamente a distribuição de agravos e a organização da oferta de cuidados em saúde. O território expressa materialmente essas desigualdades, concentrando contextos distintos de exposição a riscos sanitários e de acesso a recursos sociais. Diante desse cenário, o estudo tem como objetivo analisar a relação entre determinação social da saúde e vulnerabilidade territorial, considerando a distribuição espacial da carga de doença e a organização da oferta de serviços públicos. Para isso, desenvolveu-se uma investigação baseada na análise teórica de produções científicas que discutem desigualdades sociais, organização territorial e distribuição de agravos à saúde. A discussão evidencia que diferenças socioeconômicas e territoriais influenciam a ocorrência de doenças, a utilização de serviços de saúde e a disponibilidade de recursos assistenciais, produzindo padrões desiguais de morbidade e mortalidade entre regiões e grupos sociais. A incorporação da análise espacial nas investigações em saúde pública permite identificar áreas de maior concentração de agravos e compreender como condições sociais e territoriais participam da configuração desses padrões. A compreensão dessas relações contribui para o fortalecimento do planejamento em saúde e para a formulação de políticas públicas orientadas pela equidade na organização dos serviços e na distribuição de recursos no sistema de saúde.

ABSTRACT The study developed and characterized a noninvasive lactate biosensor based on layer‐by‐layer (LbL) films of chitosan (Chi) and AuNPs@PTS, a gold nanoparticle–polythiophene composite. LbL assemblies with varying bilayer numbers were fabricated and used to immobilize lactate oxidase (LOx), yielding Chi/AuNPs@PTS/LOx electrodes. Film growth and properties were probed by UV–vis absorption, fluorescence, and electrochemical measurements. Absorbance and fluorescence increased with the number of bilayers, consistent with exponential film buildup. Cyclic voltammetry (CV) revealed that two bilayers enabled faster charge transfer and lower resistance than thicker films, identifying this architecture as optimal for enzyme immobilization. LOx was deposited by drip casting and cross‐linked with glutaraldehyde. Lactate sensing by CV was verified in standards and human sweat samples. The platform exhibited a linear analytical response from 0.5 to 30 mM, covering typical sweat concentrations, and demonstrated noninvasive measurement capability. Together, these results show that a minimal (two‐bilayer) Chi/AuNPs@PTS film provides an efficient matrix for LOx, supporting sensitive, sweat‐relevant lactate detection. The straightforward LbL fabrication and enzyme cross‐linking are compatible with low‐cost processing. Overall, the study establishes functional design principles by correlating the number of LbL bilayers with charge‐transfer properties and electrochemical performance to balance sensitivity with stability for wearable monitoring applications.