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1.
J Clin Med ; 13(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38792465

RESUMEN

Background: Varicocele still today represents a common cause of infertility in young men. The treatment strategy remains a surgical approach such as scleroembolization; however, the complete restoration of spermatic parameters afterward requires an average of six or more months to fully regain optimal seminal parameters. Recently, many studies have demonstrated the beneficial effects of Resveratrol in male fertility, given its potential anti-inflammatory, antiapoptotic, and mitochondrial effects. Therefore, Resveratrol-based nutraceuticals could be promising as an adjuvant to mitigate subfertility in patients with varicocele. Methods: In the present study, we retrospectively analyzed the effects of the administration of a Resveratrol-based nutraceutical after the scleroembolization procedure. The improvement of sperm quality in terms of number, motility, and morphology were considered to be the study's main endpoints. A spreadsheet program was used for data analysis, and a p-value of <0.05 was considered significant. Results: We found a statistically significant improvement in the spermatic parameters (sperm count and total motility) and an increase in normal sperm after only 4 months of treatment. The supplementation with a Resveratrol-based nutraceutical associated with the surgical procedure showed encouraging results if compared to data from a control group and the results reported in the literature linked to scleroembolization practice alone. In fact, there was a clear improvement in the seminal parameters at 4 months. Conclusions: This suggests the positive impact of the Resveratrol-based nutraceutical in synergizing with scleroembolization in reducing the time needed to fully recover sperm function.

2.
J Med Chem ; 67(5): 4150-4169, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38417155

RESUMEN

The nuclear receptor ssDAF-12 has been recognized as the key molecular player regulating the life cycle of the nematode parasite Strongyloides stercoralis. ssDAF-12 ligands permit the receptor to function as an on/off switch modulating infection, making it vulnerable to therapeutic intervention. In this study, we report the design and synthesis of a set of novel dafachronic acid derivatives, which were used to outline the first structure-activity relationship targeting the ssDAF-12 receptor and to unveil hidden properties shared by the molecular shape of steroidal ligands that are relevant to the receptor binding and modulation. Moreover, biological results led to the discovery of sulfonamide 3 as a submicromolar ssDAF-12 agonist endowed with a high receptor selectivity, no toxicity, and improved properties, as well as to the identification of unprecedented ssDAF-12 antagonists that can be exploited in the search for novel chemical tools and alternative therapeutic approaches for treating parasitism such as Strongyloidiasis.


Asunto(s)
Strongyloides stercoralis , Estrongiloidiasis , Animales , Humanos , Estrongiloidiasis/tratamiento farmacológico , Estrongiloidiasis/parasitología , Strongyloides stercoralis/metabolismo , Esteroides/uso terapéutico , Estadios del Ciclo de Vida , Relación Estructura-Actividad
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