👤 Eman Sheta

Ipriflavone (IPRI), an isoflavone derivative, is clinically used to prevent postmenopausal bone loss in addition to its antioxidant and cognitive benefits. However, its poor aqueous solubility retained its bioavailability. New strategies have been developed to improve the bioavailability and solubility of neurological medications to enhance their potency and limit adverse effects. This study aimed to prepare targeted IPRI-poly-lactic-co-glycolic acid (PLGA) nanoparticles coupled with Tet-1 peptide to increase the therapeutic potency of IPRI in a rat model of Alzheimer's disease (AD). Streptozotocin (STZ) exacerbates Alzheimer-related alterations by promoting central insulin resistance resulted from defective signaling pathways related to neuroinflammation and neurotoxicity. Bilateral intracerebroventricular (icv) injection of STZ was used to introduce the AD model. Icv-STZ injection significantly affected brain insulin, oxidative stress, inflammatory, and apoptotic indicators and caused behavioral abnormalities. STZ promoted the formation of amyloid β42 (Aβ42) by increasing BACE1 and reducing ADAM10 and ADAM17 expression levels. STZ also triggered the accumulation of neurofibrillary tangles and synaptic dysfunction, which are crucial for neurological impairments. Icv-STZ injection showed evident degenerative changes in the pyramidal cell layer and significantly reduced the count of viable cells in both CA1 and prefrontal cortex, indicating increased neuronal cell death. IPRI successfully ameliorated cognitive dysfunction by improving the phosphorylated forms of cAMP-response element-binding protein (pCREB) and extracellular signal-regulated kinase 1/2 (pERK1/2) related to synaptic plasticity. Targeted IPRI nanoparticles exceeded free IPRI potential in reducing oxidative stress, acetylcholinesterase/monoamine oxidase activities, Tau phosphorylation, and Aβ42 levels revealing less degenerative changes and increased viable neuron counts. IPRI-targeted nanoparticles improved the neuroprotective potential of free IPRI, making this strategy applicable to treat many neurodegenerative diseases. Finally, the in silico study predicted its ability to cross the BBB and to bind various protein targets in the brain. Show less

Although a giant Egyptian domestic non-migratory duck breed is phenotypically identical to the migratory Mallard, yet it is three times larger. The current study sought to determine the genetic and metabolic differences between this duck and Mallard, which arrives in Egypt in September for wintering and departs in March. Mitochondrial DNA control region (D-loop) was extracted, amplified, sequenced, and analyzed in both ducks. Both ducks were given a high-fat diet (HFD) for 6 weeks to assess their metabolic response to this diet. Polymorphism results indicated that the D-loop is highly variable and both populations expansion is balanced. The hierarchical analysis of molecular variants (AMOVA) and interpopulation difference parameters revealed significant genetic differentiation and minimal gene flow between migrant and resident populations. Phylogeny and Network analyses revealed that domestic ducks are a distinct group that separated from mallards. Physiologically, domestic duck blood and adipose tissue had a higher level of triglycerides and adipocyte volume than that of the depleting arriving migratory Mallard ducks, while leaving Mallard parameters were the highest, suggesting a high level of preparatory fat deposition and utilization before starting the trip. In response to HFD, the expression of FA uptake genes cd36, fabp1 was upregulated similarly in livers of domestic and migratory Mallard ducks, while the expression of lipid accumulation genes dgat2 and plin2 was higher in domestic than in migratory Mallards. However, the highest body mass and adipocytes volume gain was observed in the arriving migratory Mallards. In pectoral muscle, the expression of cd36 and fabp3 was higher in domestic than in leaving ducks, while in arriving Mallards, both genes were not upregulated in response to HFD. Dgat2 was upregulated only in domestic muscle, while lipid oxidation genes cpt1, lpl, and the controlling ppara were more upregulated in leaving Mallard. In conclusion, both ducks can be genetically and metabolically differentiated. Migratory mallards are more flexible and efficient in lipid metabolism than domestic ducks. Show less