👤 Fatemeh Ashrafian

Probiotics are beneficial microorganisms that modulate various signaling pathways to improve human health status. In this study we aimed to evaluate the precise molecular effects of Lactobacillus spp., Bifidobacterium spp., and a mixture of our native potential probiotics on the autophagy signaling pathway during the presence of inflammation. The evaluation of autophagy gene expression was performed after exposing the HT -29 cell line with the sonicated pathogens and probiotics, before and simultaneously with inflammation induction by quantitative real-time polymerase chain reaction (qPCR) and cytokine assays. The results of the current study showed that our native potential probiotic cocktails could upregulate the expression level of the autophagy genes including pik3c3, atg14, beclin, pik3r4, atg5, atg16, atg7, and atg3 compared with sonicated pathogen treatments, and also these native potential probiotic strains could exert anti-inflammatory effects, especially before inflammation induction. In conclusion, our native potential probiotic cocktail indicated the preventive and therapeutic effect on inflammation, but our selected probiotics could affect autophagy genes stronger before inflammation compared to expose simultaneously with inflammation. Therefore, the administration of probiotics as a prophylactic agent with the least side effects could be considered a suitable treatment for patients with inflammatory-related disease, even before or at the beginning of inflammation. Show less

Energy depletion has been highlighted as an important contributor to the pathology of hypertrophic cardiomyopathy (HCM), a common inherited cardiac disease. Pharmacological reversal of energy depletion appears an attractive approach and the use of perhexiline has been proposed as it is thought to shift myocardial metabolism from fatty acid to glucose utilisation, increasing ATP production and myocardial efficiency. We used the Mybpc3-targeted knock-in mouse model of HCM to investigate changes in the cardiac metabolome following perhexiline treatment. Echocardiography indicated that perhexiline induced partial improvement of some, but not all hypertrophic parameters after six weeks. Non-targeted metabolomics, applying ultra-high performance liquid chromatography-mass spectrometry, described a phenotypic modification of the cardiac metabolome with 272 unique metabolites showing a statistically significant change (p < 0.05). Changes in fatty acids and acyl carnitines indicate altered fatty acid transport into mitochondria, implying reduction in fatty acid beta-oxidation. Increased glucose utilisation is indirectly implied through changes in the glycolytic, glycerol, pentose phosphate, tricarboxylic acid and pantothenate pathways. Depleted reduced glutathione and increased production of NADPH suggest reduction in oxidative stress. These data delineate the metabolic changes occurring during improvement of the HCM phenotype and indicate the requirements for further targeted interventions. Show less