👤 Fatmaelzahraa Abdelfattah

Dyslipidemia is a major risk factor for the development of NAFLD, atherosclerosis and cardiovascular diseases. Rosuvastatin (ROS) is a lipid-lowering drug that protects against the development of NAFLD and atherosclerosis. However, the mechanism of this protection remains obscure. Therefore, the current study aims to explore the mechanism by which ROS-loaded glycerosomes (ROS-GLY) protect against NAFLD and atherosclerosis. Hence, for this purpose, hepatic lncRNA-H19/miR-130a/PPAR-γ and aortic PPAR-γ/LXRα/ABCA1 signaling pathways were assessed. In addition, these target pathways were predicted using molecular docking analysis. Thirty-five male Sprague Dawley rats were separated into control, dyslipidemic (poloxamer 407 (P 407)), P 407+ROS-GLY, P 407+NC, and P 407+ROS-GLY+NC groups. ROS-GLY improved lipid profile, hepatic MDA, SOD, catalase and total antioxidant capacity (TAC) in compared to P 407 group. In the dyslipidemic group, ROS-GLY downregulated hepatic lncRNA-H19 expression which leads to an upregulate of the miR-130a level and subsequent reduction of the PPAR-γ level. Consequently, the hepatic expression level of lipogenic genes such as, ACC-1, FASN and SCD-1 was significantly downregulated in the ROS-GLY group than the dyslipidemic one. Aortic PPAR-γ/LXRα/ABCA1 signaling pathway was significantly upregulated in the ROS-GLY group compared to the dyslipidemic group. Furthermore, ROS-GLY modulated IL-6 and IL-10 immunoprotein expression in hepatic and aortic tissues. Interestingly, ROS showed a substantial binding affinity with PPAR-γ, LXR-α, and FASN, according to a molecular docking study. The current study indicated that ROS-GLY protected against the progression of NAFLD and atherosclerosis in dyslipidemic rats via modulation of lipid profile, oxidative stress, pro-/anti-inflammatory cytokines, hepatic lncRNA-H19/miR-130a/PPAR-γ, and aortic PPAR-γ/LXRα/ABCA1 signaling pathways. Show less

Major depressive disorder (MDD) is a complex neuropsychiatric disorder with multifactorial origins involving oxidative stress, neuroinflammation, neurotransmitter imbalance, and HPA axis dysfunction. Conventional treatments are often limited by side effects and suboptimal efficacy, confirming the need for alternative therapies. This study investigates the antidepressant-like and neuroprotective potential of selenium nanoparticles biosynthesized using epigallocatechin gallate (SeNPs-EGCG) in a rat model of depression induced by chronic mild stress. Six groups of seven rats each were used in a model of depression caused by chronic unpredictable mild stress (CUMS): control, depressed, depressed treated with escitalopram, epigallocatechin gallate (EGCG), sodium selenite (Na Behavioral assays demonstrated that SeNPs-EGCG significantly reversed depression-like behaviors, evidenced by increased sucrose preference and grooming frequency in the SeNPs-EGCG-treated group compared to the depressed group. Biochemically, SeNPs-EGCG restored antioxidant defense by increasing GSH, SOD, and CAT levels, while reducing lipid peroxidation to near-normal levels. Neuroinflammatory markers such as TNF-α, IL-1β, IL-8, and NF-κB were markedly downregulated in the SeNPs-EGCG group. Molecular results also showed a slowing down of proapoptotic signals (Bax and Caspase-3) and upregulation of anti-apoptotic Bcl-2 and neurotrophic factor BDNF. Importantly, SeNPs-EGCG modulated key monoamines, increasing serotonin and DA levels. Compared to both EGCG and sodium selenite controls, SeNPs-EGCG demonstrated superior efficacy, comparable to the standard antidepressant escitalopram. The results underscore the multi-targeted mechanism of SeNPs-EGCG and suggest its promising role as a novel nano-based therapeutic strategy for depression. Show less

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, driven by the accumulation of amyloid-beta plaques and neurofibrillary tangles. It involves the dysfunction of key enzymes such as Acetylcholinesterase (AChE) and β-secretase (BACE1), making them critical targets for therapeutic intervention. In this study we investigated an in-house library of 820 secondary metabolites obtained from Ayurvedic plants against AChE and BACE1 with the aim to discover novel leads for AD. Virtual screening resulted in 15 ligands, mostly belonging to the ursane-type or dammarene-type triterpene saponins of Centella asiatica, reestablishing the potency of this plant in drug discovery against AD. The binding affinities were further verified by molecular dynamics (MD) simulation trajectories, including root mean square fluctuations (RMSF), root mean square deviation (RMSD), hydrogen bonding analysis, Coulomb interaction calculation, Lennard-Jones interactions, and the total interaction energy. Moreover, extensive Principal Component Analysis (PCA) and Gibbs free energy landscape were performed. Our results demonstrated three compounds, namely (S)-eriodictyol 7-O-(6-β-O-trans-p-coumaroyl)-β-d-glucopyranoside, sitoindoside-X and 1,5-di-o-caffeoyl quinic acid as more effective in treating AD due to their comparable drug-like properties. Drug-likeness, structural chemistry, pharmacophore, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis support their potential for future drug development. To establish the effectiveness of these lead compounds against AD, additional experimental testing should be performed. Show less

Elevated lipoprotein(a) [Lp(a)] and low high-density lipoprotein-cholesterol (HDL-C) are established cardiovascular (CV) risk factors, but their combined impact on mortality and sex differences remains unclear. This retrospective study analyzed 97 396 patients with measured Lp(a) and HDL-C. Groups were stratified by Lp(a) (≥50 vs. <50 mg/dl) and HDL-C [low (<40), optimal (40-60), high (>60 mg/dl)]. Mortality was assessed using the Kaplan-Meier curve and Cox models. Over a median of 5.9 years, 7794 deaths occurred. Compared to optimal HDL-C/low Lp(a) (reference), high HDL-C/low Lp(a) had the lowest mortality [adjusted hazard ratio (aHR): 0.85; 95% confidence interval (CI): 0.80-0.91], while low HDL-C/high Lp(a) had the highest risk (aHR: 1.55; 1.41-1.71). High HDL-C protective effect was insignificant with elevated Lp(a) (aHR: 0.98; 0.89-1.08). Sex-stratified analyses revealed divergent effects: women with high HDL-C/high Lp(a) retained the HDL-C protective effect (aHR: 0.82; 0.72-0.93), whereas men faced increased risk (aHR: 1.22; 1.05-1.42). Elevated Lp(a) enhances mortality risk despite elevated HDL-C levels, with sex-specific differences: women retain mortality benefits from high HDL-C despite elevated Lp(a), whereas men with concurrent elevations in HDL-C and Lp(a) experienced mortality risks comparable to those with low HDL-C. Findings underscore sex-specific CV risk stratification incorporating HDL-C and Lp(a), challenging the HDL-C universal protective role. Show less

This study aims to assess the value of carbamoyl phosphate synthetase 1 (CPS1), as a non-invasive serum marker, for the evolution of chronic HCV infection and hepatic fibrosis. Seventy-two patients with HCV positive serum RNA and 15 health volunteers were enrolled in this study. Out of 72 patients, 10 patients had decompensated liver with ascites. Quantitative analysis of CPS1 was performed in the harvested sera and corresponding liver biopsies using ELISA and immunohistochemistry techniques respectively. Also, mitochondrial count using electron microscopy, urea analysis and conventional liver tests were done. Patients were grouped into (F1 + F2) and (F3 + F4) representing stages of moderate and severe fibrosis respectively. Tissue and serum CPS1 (s.CPS1) correlated significantly in moderate and severe fibrosis. Patients with severe fibrosis showed significantly higher levels of s.CPS1 (p-value ≤ 0.05) and significantly lower mitochondrial counts (p-value = 0.0065) than those with moderate fibrosis. S.urea positively correlated with s.CPS1 only in the decompensated group, at which s.urea reached maximal levels. In conclusion, s.CPS1 is a potential non-invasive marker for the assessment of severity and progression of HCV in relation to mitochondrial dysfunction. Also, increased s.urea with the progression of the disease is mainly due to a concurrent renal malfunction, which needs further investigation. Show less