Sesquiterpene nootkatone counteracted the melamine-induced neurotoxicity via repressing of oxidative stress, inflammatory, and apoptotic trajectories.

Melamine (ML), a chemical substance of high nitrogen content, is used as a food adulterant. Former evidences implied that ML could induce a variety of toxic effects including neurotoxicity and cognitive impairment. Therefore, the aim of this study was to delineate the protective effect of the nootkatone (NK) against ML-induced neural adverse effects. Rats were orally pretreated with NK (5 and 10 mg/kg) prior to the oral administration of ML (700 mg/kg) for a period of 28 days. Our findings unveiled remarkable alleviating effect of NK on MK-induced neurobehavioral disturbance in open field test. Furthermore, NK lessened ML-caused increases in the acetylcholine esterase level in the brain tissue of exposed rats. NK also decreased the neural oxidative stress as represented by elevated levels of SOD, CAT, and GSH along with decreased MDA and NO levels. Upregulated mRNA expression levels of neural NRF-2 and HO-1 were noticed after NK administration. Remarkable anti-inflammatory impact was prominent by decreased neural IL-1ß, and TNF-α along with downregulated NF-κB and TLR-4 gene expression levels in NK-treated rats. Noteworthily, pre-treatment with NK decreased the immune reaction of RAGE and HMGB-1 induced by oral ML exposure. Brain histological examination validated the obtained biochemical and molecular results. To sum up, these outcomes reveal that NK successfully alleviated the neural damage induced by ML via blocking of oxidative stress, and inflammatory signaling pathways. Consequently, our study may suggest NK as a new effective therapeutic supplement for treatment of ML-mediated neurotoxicity in rats via inhibition of HMGB-1-RAGE/TLR-4/NF-κB.

Testicular Toxicity of Chloroxylenol in Rats: Biochemical, Pathological and Flow Cytometric Study.

Background: Chloroxylenol (para-chloro-meta-xylenol, PCMX) is claimed to be highly harmful both to humans and the environment. Toxic effects of PCMX on testicular functions are scarcely discussed in the literature. Aim of Study: To study testicular toxic effects of PCMX on male Sprague-Dawley rats. Materials and Methods: Forty animals were randomly distributed into three groups: negative control (G I), vehicle group (G II) and PCMX group (G III). PCMX group was subdivided into three subgroups: GIIIa: received PCMX 100 mg/kg, GIIIb: received PCMX 200 mg/kg and G IIIc: received PCMX 500 mg/kg. Hormonal assay included assessment of serum testosterone and estradiol levels. Histopathological examination of testicular tissue, analysis of cellular viability, necrosis and apoptosis in testicular tissue by flow cytometry, analysis of cellular DNA content and phases of cell cycle analysis by flow cytometry were also performed. Results: Rats in the groups exposed to PCMX (G IIIa, G IIIb and G IIIc) had significantly lower estradiol and testosterone levels in comparison to control groups (G I and GII). Histopathological examination of testicular tissue of PCMX-exposed rats showed irregular crossly sectioned seminiferous tubules with their lumina containing scanty spermatids and spermatozoa. G IIIc animals showed eosinophilic proteinaceous material and vacuolated and necrotic interstitial cells of Leydig. Rats in PCMX-exposed groups (G IIIa, G IIIb and G IIIc) showed significantly lower testicular tissue viability in comparison to control groups (G I and G II). Rats in PCMX-exposed groups (G IIIa, G IIIb and G IIIc) showed significantly lower percentage of cells in the G0/G1 phase in comparison to control groups (G I and G II). Conclusion: Rats exposed to PCMX had significant reduction in testosterone and estradiol levels with marked histopathological alterations affecting testicular tissues. These effects are dose-dependent.

An integrated personal and population-based Egyptian genome reference.

A small number of de novo assembled human genomes have been reported to date, and few have been complemented with population-based genetic variation, which is particularly important for North Africa, a region underrepresented in current genome-wide references. Here, we combine long- and short-read whole-genome sequencing data with recent assembly approaches into a de novo assembly of an Egyptian genome. The assembly demonstrates well-balanced quality metrics and is complemented with variant phasing via linked reads into haploblocks, which we associate with gene expression changes in blood. To construct an Egyptian genome reference, we identify genome-wide genetic variation within a cohort of 110 Egyptian individuals. We show that differences in allele frequencies and linkage disequilibrium between Egyptians and Europeans may compromise the transferability of European ancestry-based genetic disease risk and polygenic scores, substantiating the need for multi-ethnic genome references. Thus, the Egyptian genome reference will be a valuable resource for precision medicine.