👤 Amira E Shehata

Emerging lipid-lowering therapies, such as Plozasiran, target apolipoprotein C-III (APOC-III) by inhibiting its hepatic production at the mRNA level, presenting a novel approach to lipid regulation. However, the safety and efficacy of plozasiran have yet to be fully established. We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL register of trials for studies comparing plozasiran to placebo in patients with dyslipidemic disorders. The primary outcomes were percentage changes from baseline in triglyceride (TG) and APOC-III levels at 24 weeks and the end of the study. Secondary outcomes included changes in other lipid parameters and safety outcomes at 24 weeks and the end of the study. A protocol was registered to PROSPERO under registration number [CRD420251026605]. Four studies encompassing 1,514 participants were included in our meta-analysis. Plozasiran significantly improved TGs, APOC-III, non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (ApoB) levels at both 24 weeks and study completion. Subgroup analyses based on dose and regimen revealed consistent findings. Quarterly administration of plozasiran at 10 mg, 25 mg, and 50 mg resulted in significant reductions in TGs, APOC-III, non-HDL-C, and HDL-C at both 24 weeks and study completion. For ApoB, all three doses produced significant reductions at 24 weeks; however, only the 25 mg and 50 mg quarterly regimens sustained these reductions through the end of the study. Regarding safety, patients receiving plozasiran experienced a higher incidence of any adverse events, headache, and mild rises in HbA1C levels. Subgroup analysis revealed a dose-dependent pattern for certain safety outcomes. While Plozasiran shows strong potential as a therapeutic option for severe dyslipidemic conditions, further studies are needed to compare its efficacy and safety with currently available treatments and, more importantly, evaluate its impact on clinical outcomes for implementation in clinical practice. Show less

Aluminum oxide nanoparticles (Al₂O₃NPs) are used across industrial and consumer sectors, raising concerns about their potential neurotoxic effects. Despite growing application, the mechanisms underlying Al₂O₃NP-induced neurodegeneration remain poorly understood. This study investigated the mechanistic pathways of Al₂O₃NP neurotoxicity in adult male Sprague-Dawley rats exposed intraperitoneally to 15, 30, or 60 mg/kg Al₂O₃NPs for 60 days. Comprehensive analyses included hematological profiling, serum biochemistry, oxidative stress markers (MDA, Nrf2/Keap1), neurotransmitter assays (dopamine, acetylcholine, AChE), quantitative PCR of APP, BACE1, and BDNF, inductively coupled plasma spectroscopy for brain aluminum levels, histopathology, immunohistochemistry (caspase-3, BCL2), and ultrastructural examination by transmission electron microscopy. Al₂O₃NP exposure induced dose-dependent anemia, disrupted iron and calcium homeostasis, and triggered oxidative stress, evidenced by elevated MDA and suppressed Nrf2/Keap1 signaling. Neurochemical analyses revealed marked dopamine and acetylcholine depletion alongside diminished AChE activity. Molecular assays showed significant upregulation of amyloidogenic markers (APP, BACE1) and severe BDNF suppression, indicating impaired neurotrophic support. Brain histopathology revealed progressive neuronal shrinkage, Purkinje cell loss, astrogliosis, and perivascular edema, while immunohistochemistry demonstrated heightened caspase-3 activation and reduced BCL2 expression. TEM confirmed ultrastructural axonal degeneration, demyelination, and necrotic neuronal profiles. Notably, aluminum bioaccumulation increased 116-fold at the highest dose, tightly correlating with neurodegeneration severity. These findings demonstrate that subchronic Al₂O₃NP exposure promotes neurodegeneration via a multifaceted oxidative stress mechanism, activating the amyloidogenic pathway, synaptic dysfunction, neurotrophic impairment, and apoptosis. This work underscores the urgent need for rigorous safety assessments of nanoparticle exposure in biomedical and environmental settings. Show less

Cytokines play a major role in the pathogenesis and progression of psoriasis. Interleukin (IL)-30 is a multifunctional cytokine. It binds to glycoprotein 130 (GP130) and inhibits the GP130 signaling pathways of psoriasis associated cytokines such as IL-6, IL-11, and IL-27. The study intended to assess associations of IL-30 and GP130 with the risk of psoriasis and Psoriasis Area Severity Index (PASI) score. Therefore, we measured the serum levels of IL-30 and GP130 in psoriasis patients and in a control group. An enzyme linked immunosorbent assay (ELISA) technique was used to measure IL-30 and GP130 levels in the serum of 43 patients and 43 normal controls. Statistical analysis of IL-30 and GP130 serum levels among patients and control groups and their correlation with PASI scores were performed. IL-30 serum levels showed a significant increase in patients with psoriasis compared with controls (p < 0.001) and a positive correlation with PASI scores. While serum levels of GP130 were not different in psoriatic patients and in the control group. Furthermore, the receiver operating characteristic (ROC) curve showed that IL-30 had diagnostic ability for prediction of psoriasis in comparison to controls, at cut of point of >14.34 showed a sensitivity of 97.7%, 100% specificity. In conclusion, IL-30 was elevated in psoriasis patients than controls, therefore, it can be considered a sensitive biomarker for diagnosis of psoriasis. Show less

Alzheimer's disease (AD) is a devastating neurodegenerative disorder without a cure. Hence, developing an effective treatment or protective agent is crucial for public health. The present study aims to characterize orange peel extract (OPE) through in vitro and in silico studies. Furthermore, it examines the protective effect of OPE against experimentally-induced Alzheimer's disease in rats. The total phenolic and flavonoid content of OPE was 255.86 ± 1.77 and 52.06 ± 1.74 (mg/100 g), respectively. Gallic acid, the common polyphenol in OPE detected by HPLC was 3388.60 μg/100 g. OPE antioxidant IC Show less