👤 Doaa A Ghareeb

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

This study aims to examine the expression of autophagic genes and proteins during blastocyst development and differentiation. This is a prospective cohort study. Between March 2018 and November 2019, 30 females aged 30.13 ± 4.83 years underwent an intracytoplasmic sperm injection (ICSI) cycle at Madina Fertility Center. ICSI was used to develop and incubate 82 leftover embryos to day 5. Then, the embryos were divided into two groups based on their developmental structure: group D (n = 49) included embryos that developed into blastocysts, whereas group A (n = 33) included arrested embryos. These embryos were used to investigate the autophagic gene and protein expressions. The current study was approved by the Clinical Trial Ethical Committee of the Faculty of Medicine, Alexandria University, following the ethical standards of scientific research (Registration no. 0303721). Embryos that developed into blastocysts on day 5 (group D) had significantly higher relative expression of the LC3 gene (1.11 ± 0.52) and beclin-1 gene (1.43 ± 0.34) and beclin-1 protein expression (3.8 ± 0.028) than those that did not develop into blastocysts on day 5 (group A) [0.72 ± 0.18 (P = 0.03), 0.35 ± 0.12 (P = 0.0001), and 3.14 ± 0.05, (P = 0.0001), respectively]. In contrast, mTOR and PIK3C3 protein expression was significantly higher in group A (arrested embryos) than those in group D (developed embryos) (P = 0.007 and P = 0.0001, respectively). Furthermore, the expression of the eIF4E gene was significantly lower in group D embryos (0.32 ± 0.07) than that in group A embryos (4.38 ± 1.16) (P = 0.0001). This work identifies  autophagy as a well regulated process required to maintain cell allocation and differentiation during late preimplantation embryo developmental stages. Show less