👤 Abdullah F Radwan

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and behavioral impairments associated with striatal neuronal loss, for which effective symptom-attenuating therapies remain lacking. Artemisinin (ART), a natural sesquiterpene lactone with established antioxidant and anti-inflammatory actions, has recently gained attention as a potential neuroprotective agent. This study evaluated the therapeutic relevance of ART in a rat model of HD induced by 3-nitropropionic acid (3-NP). 3-NP administration caused severe behavioral deficits, including an 81.8% reduction in rearing and a 74.9% reduction in ambulation (p < 0.0001), a 63.7% decrease in novel object exploration, and a 53.5% decline in Morris water maze target quadrant time versus controls. Biochemically, 3-NP elevated HMGB1 (4.8-fold), TLR4 (6.8-fold), RIPK1 (6.4-fold), RIPK3 (5.2-fold), MLKL (5.5-fold), p38-MAPK (4.2-fold), NF-κB (2.1-fold), and TNF-α (4.5-fold), while reducing GSH (57.6%), Nrf2 (77.7%), Sig1R (86.2%), D2R (64%), XIAP (77.8%), BDNF (57.6%) and SDH (61.44%) (all p < 0.0001). Treatment with ART (100 mg/kg) markedly restored behavioral performance, increasing rearing and ambulation by 3.2- and 2.6-fold, novel object exploration by 2.4-fold, and target quadrant time by 1.7-fold compared to the 3-NP group. At the molecular level, ART reduced HMGB1 (69.2%), TLR4 (60.4%), RIPK1 (66.3%), RIPK3 (66.4%), MLKL (58%), and TNF-α (62.5%), while significantly restoring GSH (2.1-fold), Nrf2 (3.7-fold), Sig1R (5.2-fold), D2R (2.6-fold), XIAP (3.7-fold), BDNF (2.3-fold) and SDH (1.94-fold) relative to 3-NP-treated rats. Collectively, these results demonstrate that ART confers robust neuroprotection against 3-NP-induced HD-like pathology by attenuating oxidative stress, suppressing HMGB1/TLR4/NF-κB signaling, inhibiting necroptosis, and upregulating neuroprotective markers. These findings highlight ART not only as a neuroprotective agent but also as a promising symptom-attenuating therapeutic candidate for Huntington's disease and other neurodegenerative disorders driven by oxidative and inflammatory stress. Show less

In recent years, strategic plans for poultry production have emphasized quantitative traits, particularly body weight and carcass traits (meat yield), in response to overpopulation challenges. Candidate genes such as adenylosuccinate lyase (ADSL), melanocortin-4-receptor (MC4R), and calpain 1 (CAPN1) have played vital roles in this context due to their associations with muscle growth and body composition. This study aims to investigate the influence of polymorphisms and gene expressions of the aforementioned genes on body weight (BW), growth rate (GR), breast weight (BrW), and thigh weight (TW) across four distinct chicken breeds: Fayoumi, Matrouh, Mamourah, and Leghorn. The use of PCR-SSCP analysis revealed genetic polymorphisms through the identification of various patterns (genotypes) within the three examined genes. The ADSL, MC4R, and CAPN1 genes exhibited five, three, and two different genotypes, respectively. These polymorphisms displayed promising connections with enhancing economically significant production traits, particularly BW, BrW and TW. Furthermore, gene expression analyses were conducted on breast and thigh tissues obtained from the chicken breeds at 60 days of age, where ADSL and MC4R exhibited a noteworthy up-regulation in Fayoumi and Matrouh breeds, and down-regulation in Mamourah and Leghorn. In contrast, CAPN1 expression decreased across most breeds with a slight increase noted in Fayoumi breed. In conclusion, this investigation underscores the substantial impact of ADSL, MC4R, and CAPN1 genes on economically important production traits within Egyptian domestic chicken breeds. Consequently, these genes emerge as significant molecular markers, holding potential utility in avian selection and breeding programs aimed at enhancing productive performance. Show less

Diabetes mellitus is a burdensome disease that affects various cellular functions through altered glucose metabolism. Several reports have linked diabetes to cancer development; however, the exact molecular mechanism of how diabetes-related traits contribute to cancer progression is not fully understood. The current study aimed to explore the molecular mechanism underlying the potential effect of hyperglycemia combined with hyperinsulinemia on the progression of breast cancer cells. To this end, gene dysregulation induced by the exposure of MCF7 breast cancer cells to hyperglycemia (HG), or a combination of hyperglycemia and hyperinsulinemia (HGI), was analyzed using a microarray gene expression assay. Hyperglycemia combined with hyperinsulinemia induced differential expression of 45 genes (greater than or equal to two-fold), which were not shared by other treatments. On the other hand, in silico analysis performed using a publicly available dataset (GEO: GSE150586) revealed differential upregulation of 15 genes in the breast tumor tissues of diabetic patients with breast cancer when compared with breast cancer patients with no diabetes. Show less

Experimental and clinical studies have conclusively demonstrated that lowering elevated low-density lipoprotein cholesterol levels results in fewer major adverse cardiac events. Over the past few decades, statins have become the mainstay of lipid-lowering therapy, contributing significantly to the reduction of lipids, and providing patients with a cost-effective approach. However, with growing evidence in support of combination therapies providing increased benefits to certain patient populations, such as those intolerant to statins, there is an urgent need to investigate the safety and efficacy of alternative lipid-lowering drugs. In this paper, we review the current alternative and adjuvant cholesterol targeting agents. We further discuss the clinical trials that have evaluated the safety and efficacy of these alternative and adjuvant therapies as well as their implications for practical use. These drugs target levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or lipoprotein(a) as treatments for hyperlipidemia and atherosclerotic cardiovascular disease. Show less

Paediatric cardiomyopathy is a progressive and often lethal disorder and the most common cause of heart failure in children. Despite their severe outcomes, their genetic etiology is still poorly characterised. The current study aimed at uncovering the genetic background of idiopathic primary hypertrophic cardiomyopathy in a cohort of Egyptian children using targeted next-generation sequencing. The study included 24 patients (15 males and 9 females) presented to the cardiomyopathy clinic of Cairo University Children's Hospital with a median age of 2.75 (0.5-14) years. Consanguinity was positive in 62.5% of patients. A family history of hypertrophic cardiomyopathy was present in 20.8% of patients. Ten rare variants were detected in eight patients; two pathogenic variants (8.3%) in MBPC3 and MYH7, and eight variants of uncertain significance in MYBPC3, TTN, VCL, MYL2, CSRP3, and RBM20.Here, we report on the first national study in Egypt that analysed sarcomeric and non-sarcomeric variants in a cohort of idiopathic paediatric hypertrophic cardiomyopathy patients using next-generation sequencing. The current pilot study suggests that paediatric hypertrophic cardiomyopathy in Egypt might have a particular genetic background, especially with the high burden of consanguinity. Including the genetic testing in the routine diagnostic service is important for a better understanding of the pathophysiology of the disease, proper patient management, and at-risk detection. Genome-wide tests (whole exome/genome sequencing) might be better than the targeted sequencing approach to test primary hypertrophic cardiomyopathy patients in addition to its ability for the identification of novel genetic causes. Show less