Alessandra Gambero

Ocular involvement in psoriatic disease is often underrecognized, particularly when inflammation affects posterior segments and remains undetectable on routine examination or conventional imaging modalities. We report a 38-year-old woman with palmoplantar psoriasis and psoriatic arthritis, characterized by ultrasound-confirmed dactylitis and inflammatory left hip pain, receiving methotrexate and guselkumab. Disease activity was low (DAPSA 7.6; CRP 5.8 mg/L). She presented with increased intraocular pressure, progressive visual blurring, and headache of 8 months’ duration, without a previous history of uveitis. Multimodal imaging was performed, including slit-lamp examination, grayscale B-mode ocular ultrasound, optical coherence tomography (OCT), and strain elastography. Slit-lamp examination and grayscale B-mode ultrasound were unremarkable, with no detectable vitreous echoes (grade 0). OCT demonstrated preserved retinal architecture with subtle hyperreflective vitreous dots in the right eye, compatible with low-grade vitreous cellularity, while the left eye was unremarkable. In contrast, strain elastography revealed increased stiffness and marked heterogeneity within the vitreous and periocular tissues, suggesting biomechanical alterations not detected by conventional structural imaging. These findings suggest biomechanical alterations compatible with possible inflammatory tissue remodeling. In our patient, strain elastography revealed biomechanical heterogeneity that was not apparent on conventional B-mode ultrasound. These findings should be considered hypothesis-generating and warrant further investigation in prospective controlled studies.

Resumo Objetivo Avaliar o consumo alimentar de produtos finais de glicação avançada (AGEs) em pessoas idosas e correlacioná-lo com a composição corporal e a saúde muscular. Métodos Este estudo observacional transversal incluiu indivíduos com 60 anos ou mais (n=72). A coleta de dados incluiu questionário de frequência alimentar para alimentos ricos em AGEs (QFA-AGE) e medida de autofluorescência cutânea (SAF). A composição corporal foi avaliada por meio do índice de massa corporal (IMC), bioimpedância e circunferência da panturrilha. O risco de sarcopenia foi avaliado por meio de força de preensão manual, teste Time Up and Go (TUG) e escore SARC-F. Resultados A ingestão média diária de AGE na dieta foi de 12.104±5.719 kU/dia, sem diferenças significativas por sexo ou estado civil. Nenhuma correlação foi encontrada entre a ingestão de AGE na dieta e SAF, IMC ou desempenho físico. No entanto, o SAF correlacionou-se positivamente com o IMC, a massa gorda e o índice de obesidade sarcopênica. Conclusão Embora a ingestão de AGE na dieta não tenha se correlacionado com o acúmulo de AGE ou com o desempenho físico, o SAF foi associado à obesidade. Esses achados sugerem que o acúmulo de AGE em pessoas idosas pode ser mais influenciado pela composição corporal ou pela produção endógena do que pela ingestão alimentar. Monitoramento do SAF pode ser útil na avaliação do risco cardiovascular e em desfechos de saúde em pessoas idosas.

Objective To evaluate dietary intake of advanced glycation end products (AGEs) in older adults and potential correlations with body composition and muscle health. Methods A cross-sectional observational study involving individuals aged 60 and older (n=72) was conducted. Data collection included application of a food frequency questionnaire for AGE-rich foods (FFQ-AGE). Skin autofluorescence (SAF) was measured as a marker of AGE accumulation. Body composition was assessed using body mass index (BMI), bioimpedance, and calf circumference, while sarcopenia risk was evaluated using handgrip strength, Timed Up and Go (TUG) Test, and SARC-F score. Results The average dietary AGE intake was 12,104±5,719 kU/day, with no significant differences by sex or marital status. No correlation was found between dietary AGE intake and SAF, BMI, or physical performance. However, SAF positively correlated with BMI, fat mass, and sarcopenic obesity index, indicating an association with unfavorable body composition. Only 2.8% of participants were sarcopenic according to SARC-F, although 20.8% had low handgrip strength and 37.5% had impaired mobility on the TUG test. Conclusion Although dietary AGE intake did not correlate with AGE accumulation or physical performance, SAF was associated with obesity-related measures. These findings suggest that AGE accumulation in older adults may be more influenced by body composition or endogenous production than dietary intake. Monitoring SAF could be useful for assessing cardiovascular risk and health outcomes in aging populations.

Background/Objectives: Chronic wounds represent a significant clinical and public health challenge due to impaired tissue repair and high associated morbidity. This study investigates the therapeutic potential of the secretome derived from human mesenchymal stem cells obtained from the pulp of deciduous teeth (hDP-MSCs) in promoting skin wound healing. Methods: After confirming the mesenchymal identity and multipotent differentiation potential of hDP-MSCs by using flow cytometry and histological staining, the effects of the secretome on human keratinocyte (HaCaT) cultures were evaluated. Results: Scratch assays, performed under high- and low-glucose conditions, demonstrated that the secretome significantly promoted keratinocyte migration and wound closure without compromising cell viability. Additionally, the secretome modulated the expression of key genes involved in inflammation and tissue regeneration, including IL-1β, TNF-α, TGF-β1, and VEGF-α, in a time-dependent manner. Under inflammatory conditions induced by lipopolysaccharide, co-treatment with the secretome significantly reduced TNF-α expression and increased TGF-β1 expression, suggesting an anti-inflammatory effect. Conclusions: These findings indicate the potential of the hDP-MSC-derived secretome as a promising cell-free therapeutic strategy capable of accelerating skin regeneration and modulating the inflammatory response during the wound healing process.

This review explores the intricate relationship between viral infections and Bacillus Calmette-Guerin (BCG) efficacy, emphasizing immune modulation mechanisms that may influence treatment outcomes. Since its introduction in 1976, intravesical BCG has been a cornerstone in managing non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumors (TURBT). Despite its success, variability in response rates suggests that host immune status, influenced by persistent infections, immunosenescence, and antigenic overload, may play a crucial role in therapeutic effectiveness. Chronic viral infections can modulate T cell responses, leading to immune exhaustion and impaired antitumor immunity. This review discusses the interplay between viral antigenic load, immune dysfunction, and tumor microenvironment remodeling, highlighting their potential impact on immunotherapies. By integrating insights from virome analysis, immune profiling, and tumor characterization, this review proposes personalized strategies to enhance immunotherapy efficacy. A deeper understanding of viral-induced immune dysregulation may improve prognostic assessment, optimize treatment protocols, and reduce healthcare costs associated with bladder cancer. Future research should focus on targeted interventions to mitigate the immunosuppressive effects of chronic infections, ultimately improving patient outcomes in NMIBC management.

A high-fat meal can cause postprandial hyperlipemia, initiating an acute inflammatory response. New structured lipids (SLs) free from trans and palm fatty acids are emerging as food structurants. Objective: We evaluated the postprandial response and inflammatory profiles in Swiss mice after oral administration of SLs in high-fat meals. Methods: SLs with different contents of long-chain saturated fatty acids were synthesized through an interesterification process involving soybean, peanut oils and crambe hard fat. Results: SLs containing 23.79% (SL1), 32.01% (SL2), and 43.87% (SL3) of total saturated fatty acids reduced the absorption of serum triglycerides and appeared to mitigate postprandial inflammation by interleukin-6. A faster gastric emptying rate after consuming SL3 was corroborated by the fecal presence of behenic acid. Conclusions: Our results suggest that SLs, free from palm and trans fats, may have the potential to mitigate inflammation, reduce the postprandial response, and lower absorption upon acute consumption.

The combination of a polyphenol, quercetin, with dasatinib initiated clinical trials to evaluate the safety and efficacy of senolytics in idiopathic pulmonary fibrosis, a lung disease associated with the presence of senescent cells. Another approach to senotherapeutics consists of controlling inflammation related to cellular senescence or “inflammaging”, which participates, among other processes, in establishing pulmonary fibrosis. We evaluate whether polyphenols such as caffeic acid, chlorogenic acid, epicatechin, gallic acid, quercetin, or resveratrol combined with different senotherapeutics such as metformin or rapamycin, and antifibrotic drugs such as nintedanib or pirfenidone, could present beneficial actions in an in vitro model of senescent MRC-5 lung fibroblasts. A senescent-associated secretory phenotype (SASP) was evaluated by the measurement of interleukin (IL)-6, IL-8, and IL-1β. The senescent-associated β-galactosidase (SA-β-gal) activity and cellular proliferation were assessed. Fibrosis was evaluated using a Picrosirius red assay and the gene expression of fibrosis-related genes. Epithelial-mesenchymal transition (EMT) was assayed in the A549 cell line exposed to Transforming Growth Factor (TGF)-β in vitro. The combination that demonstrated the best results was metformin and caffeic acid, by inhibiting IL-6 and IL-8 in senescent MRC-5 cells. Metformin and caffeic acid also restore cellular proliferation and reduce SA-β-gal activity during senescence induction. The collagen production by senescent MRC-5 cells was inhibited by epicatechin alone or combined with drugs. Epicatechin and nintedanib were able to control EMT in A549 cells. In conclusion, caffeic acid and epicatechin can potentially increase the effectiveness of senotherapeutic drugs in controlling lung diseases whose pathophysiological component is the presence of senescent cells and fibrosis.

Therapeutically targeting senescent cells seems to be an interesting perspective in treating chronic lung diseases, which are often associated with human aging. The combination of the drug dasatinib and the polyphenol quercetin is used in clinical trials as a senolytic, and the first results point to the relief of physical dysfunction in patients with idiopathic pulmonary fibrosis. In this work, we tested new combinations of drugs and polyphenols, looking for senolytic activity using human lung fibroblasts (MRC-5 cell line) with induced senescence. We researched drugs, such as azithromycin, rapamycin, metformin, FK-506, aspirin, and dasatinib combined with nine natural polyphenols, namely caffeic acid, chlorogenic acid, ellagic acid, ferulic acid, gallic acid, epicatechin, hesperidin, quercetin, and resveratrol. We found new effective senolytic combinations with dasatinib and ellagic acid and dasatinib and resveratrol. Both drug combinations increased apoptosis, reduced BCL-2 expression, and increased caspase activity in senescent MRC-5 cells. Ellagic acid senolytic activity was more potent than quercetin, and resveratrol counteracted inflammatory cytokine release during senolysis in vitro. In conclusion, dasatinib and ellagic acid and dasatinib and resveratrol present in vitro senolytic potential like that observed for the combination in clinical trials of dasatinib and quercetin, and maybe they could be future alternatives in the senotherapeutic field.

Soy isoflavones are considered important sources of bioactive compounds, but they are poorly absorbable, due to their large hydrophilic structures. Some biotransformation strategies have been used to convert the glycosidic form into aglycones, making them available for absorption. This study evaluated the potential of enzymatic and/or microbial fermentation combined bioprocesses in a soymilk extract before and after gastrointestinal in vitro digestion. Commercial β-glucosidase (ET) and a mix of commercial probiotics (F) containing Lactobacillus acidophilus, Lactobacillus casei, Lactococcus lactis, Bifidobacterium bifidum, and Bifidobacterium lactis were used to biotransform the soymilk phenolic extract. An isoflavone profile was identified using HPLC-DAD, total phenolic content was identified using the Folin–Ciocalteu test, and antioxidant capacity was identified using ORAC and FRAP. Soymilk enzymatically treated (ET) followed by microbial fermentation (ET + T) resulted in better conversion of glycosylated isoflavones (6-fold lower than control for daidzin and 2-fold for genistin) to aglycones (18-fold greater than control for dadzein and genistein). The total phenolic content was increased (3.48 mg/mL for control and 4.48 mg/mL for ET + T) and the antioxidant capacity was improved with treatments of ET + T (120 mg/mL for control and 151 mg/mL with ORAC) and with FRAP (285 µL/mL for control and 317 µL/mL). After the in vitro digestion, ET + T samples resulted in a higher content of genistein (two-fold higher than control); also, increases in the total phenolic content (2.81 mg/mL for control and 4.03 mg/mL for ET + T) and antioxidant capacity measured with ORAC were greater compared to undigested samples. In addition, the isolated microbial fermentation process also resulted in positive effects, but the combination of both treatments presented a synergistic effect on soy-based products.