Resumo Fundamento: A estratificação de risco continua sendo clinicamente desafiadora em pacientes com insuficiência cardíaca (IC) de etiologia não isquêmica. A galectina-3 é um marcador sérico de fibrose que pode ajudar no prognóstico. Objetivo: Determinar o papel da galectina-3 como preditora de eventos arrítmicos graves e mortalidade total. Métodos: Este é um estudo de coorte prospectivo que incluiu 148 pacientes com IC não isquêmica. Todos os pacientes foram submetidos a uma avaliação clínica e laboratorial abrangente para coleta de dados de referência, incluindo níveis de galectina-3 sérica. O desfecho primário foi a ocorrência de síncope arrítmica, intervenções apropriadas do cardioversor desfibrilador implantável, taquicardia ventricular sustentada ou morte súbita cardíaca. O desfecho secundário foi a morte por todas as causas. Para todos os testes estatísticos, considerou-se significativo o valor p<0,05 (bicaudal). Resultados: Em seguimento mediano de 941 dias, os desfechos primário e secundário ocorreram em 26 (17,5%) e 30 (20%) pacientes, respectivamente. A galectina-3 sérica>22,5 ng/mL (quartil mais alto) não foi preditora de eventos arrítmicos graves (HR: 1,98; p=0,152). Os preditores independentes do desfecho primário foram diâmetro diastólico final do ventrículo esquerdo (DDFVE)>73 mm (HR: 3,70; p=0,001), ventilação periódica durante o exercício (VPE) no teste de esforço cardiopulmonar (HR: 2,67; p=0,01) e taquicardia ventricular não sustentada (TVNS)>8 batimentos na monitorização por Holter (HR: 3,47; p=0,027). Os preditores de morte por todas as causas foram: galectina-3>22,5 ng/mL (HR: 3,69; p=0,001), DDFVE>73 mm (HR: 3,35; p=0,003), VPE (HR: 3,06; p=0,006) e TVNS>8 batimentos (HR: 3,95; p=0,007). A ausência de todos os preditores de risco foi associada a um valor preditivo negativo de 91,1% para o desfecho primário e 96,6% para a mortalidade total. Conclusões: Em pacientes com IC não isquêmica, níveis elevados de galectina-3 não foram preditores de eventos arrítmicos graves, mas foram associados à mortalidade total. A ausência de preditores de risco revelou um subgrupo prevalente de pacientes com IC com excelente prognóstico.

Abstract Background: Risk stratification remains clinically challenging in patients with heart failure (HF) of non-ischemic etiology. Galectin-3 is a serum marker of fibrosis that might help in prognostication. Objective: To determine the role of galectin-3 as a predictor of major arrhythmic events and overall mortality. Methods: We conducted a prospective cohort study that enrolled 148 non-ischemic HF patients. All patients underwent a comprehensive baseline clinical and laboratory assessment, including levels of serum galectin-3. The primary outcome was the occurrence of arrhythmic syncope, appropriate implantable cardioverter defibrillator therapy, sustained ventricular tachycardia, or sudden cardiac death. The secondary outcome was all-cause death. For all statistical tests, a two-tailed p-value<0.05 was considered significant. Results: In a median follow-up of 941 days, the primary and secondary outcomes occurred in 26 (17.5%) and 30 (20%) patients, respectively. Serum galectin-3>22.5 ng/mL (highest quartile) did not predict serious arrhythmic events (HR: 1.98, p=0.152). Independent predictors of the primary outcome were left ventricular end-diastolic diameter (LVEDD)>73mm (HR: 3.70, p=0.001), exercise periodic breathing (EPB) on cardiopulmonary exercise testing (HR: 2.67, p=0.01), and non-sustained ventricular tachycardia (NSVT)>8 beats on Holter monitoring (HR: 3.47, p=0.027). Predictors of all-cause death were galectin-3>22.5 ng/mL (HR: 3.69, p=0.001), LVEDD>73mm (HR: 3.35, p=0.003), EPB (HR: 3.06, p=0.006), and NSVT>8 beats (HR: 3.95, p=0.007). The absence of all risk predictors was associated with a 91.1% negative predictive value for the primary outcome and 96.6% for total mortality. Conclusions: In non-ischemic HF patients, elevated galectin-3 levels did not predict major arrhythmic events but were associated with total mortality. Absence of risk predictors revealed a prevalent subgroup of HF patients with an excellent prognosis.

Abstract The effects of non-nutritive sweeteners (NNS) on the gut microbiota are an area of increasing research interest due to their potential influence on weight gain, insulin resistance, and inflammation. Studies have shown that mice and rats fed saccharin develop weight gain and metabolic alterations, possibly related to changes in gut microbiota. Here, we hypothesized that chronic exposure to a commercial NNS would change the gut microbiota composition in Wistar rats when compared to sucrose exposure. To test this hypothesis, Wistar rats were fed either NNS- or sucrose-supplemented yogurt for 17 weeks alongside standard chow (ad libitum). The gut microbiome was assessed by 16S rDNA deep sequencing. Assembly and quantification were conducted using the Brazilian Microbiome Project pipeline for Ion Torrent data with modifications. Statistical analyses were performed in the R software environment. We found that chronic feeding of a commercial NNS-sweetened yogurt to Wistar rats, within the recommended dose range, did not significantly modify gut microbiota composition in comparison to sucrose-sweetened yogurt. Our findings do not support the hypothesis that moderate exposure to NNS is associated with changes in gut microbiota pattern compared to sucrose, at least in this experimental model.

Abstract Background: The intestinal dysbiosis is common in chronic liver disease and can induce to inflammatory responses and mediate the collagen deposition in the liver. Aim: To evaluate the probiotic Lactobacillus rhamnosus GG (LGG) for the treatment of liver fibrosis in a model of chronic cholestatic liver disease in rats. Methods: Male adult Wistar rats (n = 29) were submitted to common bile duct ligation (BDL groups) or manipulation of common bile duct without ligation (Ctrl groups).Two weeks after surgery, each group was randomly divided to receive 1 ml of PBS (Ctrl and BDL) or PBS containing 2.5 x 107 CFU of LGG (Ctrl-P and BDL-P) through gavages for 14 days. Euthanasia occurred 33 days after surgery when samples of blood and liver tissue were collected. Results: The hepatic gene expression of Tlr4, Tnfα, IL-6, Tgfβ, and metalloproteinase-2 and -9 were higher in the BDL groups in comparison to Ctrl. The ductular reaction evaluated by immunocontent of cytokeratin-7 (CK7) and the content of collagen were increased in BDL groups. Also, there was an imbalance in the antioxidant defenses (superoxide dismutase and catalase) and an increase in the oxidative stress marker sulfhydryl in BDL groups. The treatment with LGG significantly reduced gene expression of IL-6, collagen deposition, and ductular reaction in hepatic tissue of animals from BDL-P groups. Conclusion: The treatment with the probiotic LGG was able to reduce liver fibrosis, ductular reaction, and hepatic gene expression of IL-6 in a model of cholestatic liver disease in rats.

Resumen Introducción: la disbiosis intestinal es común en la enfermedad hepática crónica y puede inducir respuestas inflamatorias y mediar la deposición hepática de colágeno. Objetivo: evaluar el efecto del probiótico Lactobacillus rhamnosus GG (LGG) en el tratamiento de la fibrosis hepática en un modelo de enfermedad hepática colestásica en ratas. Métodos: se sometió a ratas Wistar macho adultas (n = 29) a ligadura del conducto biliar común (grupo BDL) o a manipulación del conducto biliar sin ligadura (grupo Ctrl). Dos semanas después, cada grupo se dividió aleatoriamente para recibir 1 ml de PBS (Ctrl y BDL) o PBS con 2,5 x 107 UFC de LGG (Ctrl-P y BDL-P) durante 14 días. Se aplicó la eutanasia 33 días después de la cirugía y se recogieron muestras de sangre y de tejido hepático. Resultados: las expresiones hepáticas de Tlr4, Tnfα, IL-6, Tgfβ, metaloproteinasa-2 y -9 fueron mayores en los grupos BDL. La reacción ductular evaluada por el inmunocontenido de citoqueratina 7 (CK7) y el contenido de colágeno se aumentó en los grupos BDL. Además, hubo un desequilibrio en las defensas antioxidantes (superóxido dismutasa y catalasa) y un aumento en el estrés oxidativo (sulfhidrilo) en los grupos BDL. El tratamiento con LGG redujo la expresión génica de IL-6, la deposición de colágeno y la reacción ductular en el hígado de los animales del grupo BDL-P. Conclusión: el tratamiento con LGG redujo la expresión génica de IL-6 en el hígado, la fibrosis hepática y la reacción ductular en un modelo de enfermedad hepática colestásica en ratas.