Project description:Aortic stenosis (AS) is a degenerative valve disease characterized by active remodelling of valve leaflets. The main hallmarks of stenotic aortic valves (AVs) include fibrosis, inflammation, osteogenesis and angiogenesis. Men and women develop these mechanisms differently. Galectin-3 (Gal-3) is a pro-inflammatory and pro-osteogenic lectin with a prominent role in the progression of AS. In this work, we aim to analyze potential sex-differences in the impact of Gal-3 in AS. 226 patients (61.50% men) with severe AS undergoing surgical valve replacement were recruited. In AVs, Gal-3 expression and its relationship with inflammatory, osteogenic and angiogenic markers was assessed. Valve interstitial cells (VIC) derived from AV tissue were primary cultured to perform in vitro experiments. Proteomic analysis revealed that Gal-3 is over-expressed in VICs of male AS patients. Gal-3 secretion also showed to be higher in men’s VICs as compared to women. In human AV tissue, Gal-3 protein levels were significantly higher in men, with stronger immunostaining in VICs with myofibroblastic phenotype and valve endothelial cells. Gal-3 levels in AVs were positively correlated with inflammatory markers in both sexes. Gal-3 expression was also positively correlated with osteogenic markers mainly in men’s AV, and with angiogenic molecules only in this sex.
Project description:Our study demonstrates differential expression of numerous autosomal miRNAs between the male and female developing human lung. Additionally, the expression of some miRNAs are modified by age across the pseudoglandular stage in a sex-specific way. Some of these differences in miRNA expression may impact susceptibility to pulmonary disease later in life. Our results suggest that sex-specific miRNA expression during human lung development may be a potential mechanism to explain sex-specific differences in lung development and may impact subsequent disease susceptibility
Project description:Sex differences in physiology, anatomy, behavior, and genetics are well-documented throughout the animal kingdom. These differences are often neglegted in reasearch. This imbalance can have detrimental effects, as seen in cases where certain drugs have stronger side effects in females than in males. The fruit fly, Drosophila melanogaster, presents a promising model for studying these sex-specific differences because it shares many disease-related genes and is easy to use. RNA of 10-day-old and 30-day-old D. melanogaster (w1118) was isolated and sequenced. In 10-day-old flies 3969 genes are significantly higher expressed in males than in females, and 7176 genes are significantly lower expressed in males. In 30-day-old males 3735 genes are significantly higher expressed than in females, and 7101 genes are significantly lower expressed. In detail, the present study shows that male flies exhibit higher expression levels of genes involved in toll signaling, Imd signaling, insulin signaling, and lipid metabolism. These findings highlight D. melanogaster as a valuable model organism for studying sex differences in these highly conserved signaling pathways. This model may additionally help to analyze the sex-specific effects of dietary interventions or drugs, ultimately leading to a better understanding of sex-specific interconnections and improving the development of more effective, sex-specific medical treatments.