Wisam Hussein Selman

Aflatoxin B1 (AFB1), a potent mycotoxin, poses a significant threat to animal health through contaminated feed. Our study aims to investigate the neurotoxic effects of AFB1in chickens, with a special emphasis on the brain. Seven-day-old chickens were fed AFB1-contaminated feed (5 mg of AFB1/kg of feed) for two weeks, after which neurobehavioral assessments and biochemical analyses were conducted and compared to control chickens. In the open-field test, chickens exposed to AFB1 exhibited a reduction in locomotor activity and exploratory behavior. Additionally, AFB1 exposure increased the tonic immobility response. Biochemical analyses revealed that AFB1-contaminated feed reduced whole-brain acetylcholinesterase activity, suggesting impaired cholinergic neurotransmission. Indicators of oxidative stress in the brain revealed a reduction in glutathione levels, superoxide dismutase levels, and total antioxidant capacity, alongside an increase in malondialdehyde levels, indicating heightened oxidative stress in the brain. The neurotoxic effects of AFB1 were further supported by the upregulation of pro-inflammatory cytokine genes, including interleukin-1 beta, interleukin-6, interleukin-17, and inducible nitric oxide synthase, as determined by real-time quantitative polymerase chain reaction. Our study demonstrates that AFB1-contaminated feed influences chicken neurobehavioral outcomes and brain biochemistry and represents the inaugural evidence that AFB1 exposure markedly reduces AChE activity in the whole brain of chickens.

The objective of this investigation was to find out whether L-carnitine-loaded nanoparticle (LCn) could reduce the reproductive toxicity of cypermethrin (CYP), the widely used insecticide in veterinary medicine in male rats. Twenty male Wistar rats that weighed between 210 and 240 g were split into four groups and treated daily for 2 months. The control group was given 0.9% normal saline solution daily. The second group received CYP (3.83 mg/kg b. w. p. o.) daily. The third group was administered with LCn and CYP (50 mg/kg b. wt. p. o. and 3.83 mg/kg b. wt. p. o., respectively) daily, whereas the fourth group received LCn alone (50 mg/kg b. wt. p. o.) daily. On day 60, all rats were sacrificed and samples were collected. CYP-treated animals exhibited inhibition of testicular anti-oxidative stress mechanisms, testicular steroidogenesis enzyme activity (3β-hydroxysteroid dehydrogenase [3β-HSD] and 17β-HSD), and downregulation of steroidogenic acute regulatory (StAR) gene expression. In addition, it decreased testosterone, follicle-stimulating hormone, and LH levels and had detrimental consequences for sperm quality. LCn attenuated CYP-induced reproductive toxicity via the alleviation of testicular oxidative stress status, improvement of steroidogenic enzyme activity, and upregulation of StAR gene expression, which are probably responsible for the concomitant improvement in testicular hormonal levels and improvement in sperm properties. Intriguingly, LCn treatment alone could enhance the functions of the male reproductive system.

Craniosynostosis, the premature ossification of cranial sutures, is a developmental disorder of the skull vault, occurring in approximately 1 in 2250 births. The causes are heterogeneous, with a monogenic basis identified in ~25% of patients. Using whole-genome sequencing, we identified a novel, de novo variant in BCL11B, c.7C>A, encoding an R3S substitution (p.R3S), in a male patient with coronal suture synostosis. BCL11B is a transcription factor that interacts directly with the nucleosome remodelling and deacetylation complex (NuRD) and polycomb-related complex 2 (PRC2) through the invariant proteins RBBP4 and RBBP7. The p.R3S substitution occurs within a conserved amino-terminal motif (RRKQxxP) of BCL11B and reduces interaction with both transcriptional complexes. Equilibrium binding studies and molecular dynamics simulations show that the p.R3S substitution disrupts ionic coordination between BCL11B and the RBBP4–MTA1 complex, a subassembly of the NuRD complex, and increases the conformational flexibility of Arg-4, Lys-5 and Gln-6 of BCL11B. These alterations collectively reduce the affinity of BCL11B p.R3S for the RBBP4–MTA1 complex by nearly an order of magnitude. We generated a mouse model of the BCL11B p.R3S substitution using a CRISPR-Cas9-based approach, and we report herein that these mice exhibit craniosynostosis of the coronal suture, as well as other cranial sutures. This finding provides strong evidence that the BCL11B p.R3S substitution is causally associated with craniosynostosis and confirms an important role for BCL11B in the maintenance of cranial suture patency.