Lúcio Roberto Cançado Castellano

Purpose: To evaluate the efficacy and safety of adjunctive methotrexate (MTX) in vitreoretinal surgery for rhegmatogenous retinal detachment (RRD) complicated by or at high risk for proliferative vitreoretinopathy (PVR). Methods: This PRISMA-compliant systematic review and meta-analysis (PROSPERO CRD420261281220) searched PubMed, Embase, CENTRAL, and Web of Science through October 16, 2025. Randomized trials, comparative observational studies, and case series were included. Comparative and single-arm data were analyzed separately using random-effects models. Primary outcomes were final retinal reattachment and best-corrected visual acuity (BCVA); postoperative PVR and adverse events were secondary outcomes. Results: Sixteen reports met the eligibility criteria, with 14 unique studies contributing to quantitative synthesis. MTX was associated with a lower risk of postoperative PVR (6 studies; 131 MTX vs. 138 controls; RR 0.56, 95% CI 0.40–0.77; p = 0.004; I²=0%) and better BCVA in the primary analysis (MD − 0.20 logMAR, 95% CI − 0.34 to − 0.06; I²=12.3%), but not with improved final retinal reattachment (8 studies; 215 MTX vs. 207 controls; RR 1.07, 95% CI 0.90–1.28; p = 0.412; I²=56.7%). However, the association with better BCVA was attenuated and no longer statistically significant after studies at critical risk of bias were excluded. Single-arm analyses yielded a pooled reattachment rate of 80% (95% CI 75–85%) and postoperative PVR rate of 22% (95% CI 15–31%). Adverse events were predominantly mild, reversible corneal complications, reported mainly with repeated MTX injections. Certainty of evidence was very low across major efficacy outcomes. Conclusions: Adjunctive MTX was associated with reduced postoperative PVR but not with improved final retinal reattachment. Although the primary analysis suggested modestly better postoperative BCVA, this finding was not robust to the exclusion of studies at critical risk of bias. Given the very low certainty of evidence, these findings are hypothesis-generating rather than practice-changing. Larger randomized trials with standardized MTX regimens and outcome definitions are needed.

Simvastatin (SIM)‐loaded poly(L,D‐lactic acid) (PLA) and poly(ethylene glycol) (PEG) fibrous mats were fabricated via Solution Blow Spinning (SBS) as functional platforms for controlled local drug delivery. Scaffolds with PLA/PEG weight ratios 100:0, 90:10, 80:20, and 70:30 (15 wt.% total polymer) were prepared incorporating 2.5 wt.% SIM. The fibrous mats were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), x‐ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), water contact angle measurements, in vitro SIM release over 21 days (UV–Vis), and cell cytotoxicity assays. Smooth, defect‐free, and uniform cylindrical fibers were obtained for all compositions, achieving high encapsulation efficiencies (> 89%). The incorporation of PEG reduced average fiber diameters, enhanced matrix wettability, and modulated the drug release profiles. Mathematical modeling revealed a key transition in drug transport mechanisms: lower PEG content formulations (PLA ₁₀ ‐2.5 and PLA ₂₀ ‐2.5) were governed by concentration‐dependent First‐Order kinetics ( r ² ≥ 0.909), whereas the PLA ₃₀ ‐2.5 matrix attained ideal Zero‐Order kinetics ( r ² = 0.978), delivering a constant and sustained drug release. Furthermore, all scaffolds maintained high cytocompatibility. Overall, tuning the PLA/PEG blend ratio allows precise control over release kinetics, demonstrating the potential of these PLA/PEG/SIM mats as versatile platforms for localized biomedical applications.

Objetivo: Avaliar, in vitro, a atividade antibiofilme de uma liga de CuAlNi funcionalizada com grafeno frente à Candida albicans. Métodos: Estudo experimental laboratorial com cepa de referência Candida albicans ATCC 90028. Após revitalização em ágar Sabouraud dextrose, a suspensão fúngica foi padronizada em 0,5 da escala de McFarland. Discos metálicos esterilizados foram posicionados sobre placas inoculadas e incubados a 35 ± 2 °C por 24 a 48 h. A avaliação concentrou-se na observação qualitativa da formação de biofilme ao redor dos discos e na análise comparativa de imagens com auxílio do software ImageJ. Resultados: A liga com grafeno (CuAlNiGO) apresentou menor densidade aparente e menor dispersão do biofilme quando comparada à liga sem grafeno (CuAlNi), sugerindo redução da colonização superficial por Candida albicans nas condições avaliadas. Conclusão: A funcionalização da liga CuAlNi com grafeno demonstrou efeito antibiofilme qualitativo promissor frente à Candida albicans. Os achados indicam potencial de aplicação do material em biomateriais odontológicos, embora estudos quantitativos adicionais, com controles e avaliação direta de biocompatibilidade, ainda sejam necessários. Palavras-chave: Ligas; Grafeno; Candida albicans; Biofilmes; Biomateriais.

This study aimed to engineer nanofibrous scaffolds that prioritize architecture, rather than relying solely on the drug, to achieve reproducible, long-acting local therapies. Cotton-wool-like fiber, three-dimensional (3D) poly(L-lactic acid)/polyethene glycol (PLLA/PEG) blend scaffolds were fabricated using solution blow spinning (SBS) as a customizable encapsulation platform for controlled antibiotic release. Morphological and wettability analyses were performed by scanning electron microscopy (SEM) and pendant-drop contact angle measurements, respectively. Fiber diameters were quantified using ImageJ. The chemical composition and thermal behavior were investigated by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). In vitro, assays were conducted to assess the antimicrobial activity of vancomycin-loaded scaffolds against Staphylococcus aureus (disk diffusion method), as well as their cytocompatibility (Live/Dead assay in Vero cells) and hemocompatibility (ASTM F756-17 hemolysis test). All biological data were statistically analyzed using ANOVA with Tukey’s post-test, Mann–Whitney, and paired t-tests, with significance set at p ≤ 0.05. Structural optimization identified PLLA/PEG 85:15 as the most stable composition, producing homogeneous mats with high porosity and rapid wettability. Incorporation of vancomycin (10 wt.%) reduced the fiber diameter (0.23 ± 0.11 µm) compared with unloaded scaffolds (0.32 ± 0.17 µm), indicating drug–polymer interactions that modulated jet elongation. FTIR, DSC, and TGA analyses confirmed polymer miscibility and stabilization of VMC within the fibrous matrix, with no signs of degradation. Drug release exhibited a biphasic profile, with an initial burst during the first 72 h. PLLA/PEG–VMC scaffolds produced larger inhibition zones against S. aureus (18.55 mm ± 1.2 to 6.63 mm ± 0.2 at 120 h) compared with free VMC (12.91 mm ± 3.8 to 4.07 mm ± 0.6291), while blank scaffolds were inactive. Hemolysis remained within the range 2% < PLLA/PEG–VMC < 5%, indicating acceptable hemocompatibility according to ASTM standards. Although VCM-loaded PLLA/PEG scaffolds slightly reduced Vero cell viability, no statistically significant differences were observed compared with the control group. These findings demonstrate that the architecture of nanofibers presents itself as a potential platform for antimicrobial therapy with topical vancomycin in potential applications such as wound dressings or implant coatings.

Cellular components and inflammatory mediators involved in the transmigration of HTLV-1-infected cells across the blood–brain barrier (BBB) are not fully understood. This study proposes a BBB model to identify the immunological mechanisms associated with HTLV-1 pathogenesis. PBMCs from individuals with HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) (n = 4) or HTLV-1-infected individuals without HAM/TSP (n = 4) were isolated. An indirect cell co-culture was performed between human brain microvascular endothelial (hBMEC) cells and neuroblastoma (SH-SY5Y) cells. PBMCs from healthy individuals (n = 4) were used as a negative control, and MT-2 cells were used as a positive control. Supernatants and cells were collected to quantify inflammatory cytokines and assess cell death after 24, 48, and 72 h. Multiple comparisons were performed using the Kruskal–Wallis test, followed by Fisher’s LSD post hoc analysis. We observed that the production of cytokines IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, as well as the rate of neuronal death, was higher in co-cultures mimicking HAM/TSP carriers compared to HTLV-1-infected individuals without HAM/TSP and controls. Our results suggest that the HAM/TSP condition induces the release of IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, along with the infiltration of mononuclear cells, which may lead to neuronal death.

The Candida albicans species is part of the human microbiota and is associated with different types of infections. It is the most commonly isolated yeast in samples of oral cavity infections. The number of infections attributed to the Candida genus has grown significantly on a global scale and due to the rigorous and improper use of current antimicrobials, antimicrobial resistance has also increased. Pogostemon cablin Benth., popularly known as patchouli, is a medicinal herb of great relevance, with several pharmacological properties reported in the literature. The aim of this study was to evaluate the antifungal potential of P. cablin essential oil against 11 oral isolates of Candida albicans and a standard strain (ATCC90028). The chemical characterization of P.cablin was carried out using Gas Chromatography coupled with Mass Spectrophotometry (GC-MS) and 19 molecules were identified, including patchouli alcohol (15.11%), Δ-Guaiene (9.85%), α-Guaiene (8.06%) and α-Patchoulene (5.03%). The antifungal activity was analyzed using the microdilution technique to determine the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC). The mechanism of action of the possible antifungal activity of the phytocomplex in question was analyzed using the sorbitol and ergosterol assays. In addition, some virulence factors were also investigated, such as biofilm formation capacity and morphogenesis. P. cablin showed MIC and MFC values between 2 and 128 µg/mL for the strains tested. The results suggest that this activity occurs through the complexation of the oil's constituents with the ergosterol of the fungal membrane. The essential oil slightly reduced the Morphology Index (MI) of the strains tested. For the most filamentous strain, there was a significant decrease in filament length, from 285.0 µm to 220.5 µm. In the formation of biofilms, the essential oil showed a reduction of 26% to 59% at concentrations of 4 to 40 µg/mL and in the reduction of biofilms formed, the values ranged from 49% to 68%. The essential oil of P. cablin showed a complex chemical composition and significant activity on C. albicans, which was considered fungicidal for most of the strains tested. It is suggested that this antifungal action is due to the complexation of the essential oil with the ergosterol of the fungal plasma membrane. In addition, P. cablin acted on the formation and reduction of biofilm and also exerted an influence on the morphogenesis of Candida albicans.

Atualizações em Doenças Infecto Parasitárias: Fisiopatogênese ISBN: 978-65-84626-01-0 CAPÍTULO 7: INTERAÇÃO Toxoplasma Gondii E Homo Sapiens: AGORA E PARA SEMPRE? Autores: Anna Victória Bernardes e…

Atualizações em Doenças Infecto Parasitárias: Fisiopatogênese ISBN: 978-65-84626-01-0 CAPÍTULO 6: INTERAÇÃO PARASITO-VETOR: UMA BREVE ABORDAGEM DOS MECANISMOS ENVOLVIDOS NA TRANSMISSÃO DE LEISHMANI…

Atualizações em Doenças Infecto Parasitárias: Fisiopatogênese ISBN: 978-65-84626-01-0 CAPÍTULO 1: ATUALIDADES ACERCA DO CICLO DE VIDA DO Plasmodium NO HOSPEDEIRO VERTEBRADO E INTERAÇÕES COM CÉLULAS…

Atualizações em Doenças Infecto Parasitárias: Fisiopatogênese ISBN: 978-65-84626-01-0 CAPÍTULO 3: TOXOPLASMOSE E SISTEMA NERVOSO CENTRAL: NOVOS OLHARES PARA INTERAÇÕES CELULARES E NEUROLÓGICAS Auto…