Detection of single-nucleotide polymorphisms in growth hormone and insulin-like growth factor-1 genes related to growth traits in purebred and crossbred quails.

Background and Aim: There is a limited amount of research conducted on quail breeding domestically and internationally, particularly at the molecular level. This study aimed to detect single-nucleotide polymorphisms in the growth hormone (GH) and insulin-like growth factor-1 (IGF-1) genes across two quail varieties and their hybrids correlate these genetic factors with body weight (BW) and growth rate at 0 and 6 weeks, and assess crossing effects. Materials and Methods: White and Japanese quail were crossed. Simultaneously producing pure varieties and crosses (genotypes) was achieved through this breeding strategy. Fifty females from each genotype were randomly selected for blood sampling. Genomic DNA was extracted and amplified from the blood using the DNeasy blood kit (Qiagen, Germany). Nucleotide polymorphism between quail genotypes was determined through DNA sequencing. Results: Two types of alleles (A and B) for the GH gene in quails showed significant genotypic differences (AA, BB, and AB). The quail carried a mutated IGF-1 gene. For growth traits, substantial positive heterosis was detected. Conclusion: The genotype AA had the highest BW and weight gain. The white variety can act as a sire, and both white and Japanese varieties can function as dams to improve growth traits. The growth characteristics of the hybrids surpassed those of the original varieties.

Click-designed vanilloid-triazole conjugates as dual inhibitors of AChE and Aß aggregation.

Based on their reported neuroprotective properties, vanilloids provide a good starting point for the synthesis of anti-Alzheimer's disease (AD) agents. In this context, nine new 1,2,3-triazole conjugates of vanilloids were synthesized via click chemistry. The compounds were tested for their effect on acetylcholine esterase (AChE) and amyloid-beta peptide (Aß) aggregation. The triazole esters (E)-(1-(4-hydroxy-3-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl 3-(4-hydroxy-3 methoxyphenyl)acrylate 9 and (1-(4-hydroxy-3-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl-4-hydroxy-3-methoxybenzoate 8 displayed dual inhibitory activity for AChE and Aß aggregation with IC50 values of 0.47/0.31 µM and 1.2/0.95 µM, respectively, as compared to donepezil (0.27 µM) and tacrine (0.41 µM), respectively. The results showed that the triazole ester moiety is more favorable for the activity than the triazole ether moiety. This could be attributed to the longer length of the spacer between the two vanillyl moieties in the triazole esters. Furthermore, the binding affinities and modes of the triazole esters 9 and 8 were examined against AChE and Aß utilizing a combination of docking predictions and molecular dynamics (MD) simulations. Docking computations revealed promising binding affinity of triazole esters 9 and 8 as potential AChE, Aß40, and Aß42 inhibitors with docking scores of -10.4 and -9.4 kcal mol-1, -5.8 and -4.7 kcal mol-1, and -3.3 and -2.9 kcal mol-1, respectively. The stability and binding energies of triazole esters 9 and 8 complexed with AChE, Aß40, and Aß42 were measured and compared to donepezil and tacrine over 100 ns MD simulations. According to the estimated binding energies, compounds 9 and 8 displayed good binding affinities with AChE, Aß42, and Aß40 with average ΔG binding values of -32.9 and -31.8 kcal mol-1, -12.0 and -10.5 kcal mol-1, and -20.4 and -16.6 kcal mol-1, respectively. Post-MD analyses demonstrated high steadiness for compounds 9 and 8 with AChE and Aß during the 100 ns MD course. This work suggests the triazole conjugate of vanilloids as a promising skeleton for developing multi-target potential AD therapeutics.

Evaluation of antimicrobial, antiquorum sensing, and cytotoxic activities of new vanillin 1,2,3-triazole derivatives.

Vanillin (1), the main constituent of vanilla species, was used as a starting natural scaffold for the synthesis of five new (2-6) and one known (7) triazole derivatives via click chemistry using the copper (I)-catalyzed azide-alkyne cycloaddition method. Vanillin and its new derivatives; 4-{1-[2-Hydroxymethyl-5-(5 methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl]-1H[1,2,3]triazol-4-ylmethoxy}-3-methoxy-benzaldehyde (2); [4-(4-Formyl-2methoxy-phenoxymethyl)-[1,2,3]triazol-1-yl]-acetic acid methyl ester (3); 4-[1-(4-Acetyl-phenyl)-1H-[1,2,3]triazol-4-ylmethoxy]-3-methoxy-benzaldehyde (4); 4-[4-(1-Benzyl-1H-[1,2,3]triazol-4-ylmethoxy)-3-methoxy-phenyl]-but-3-en-2-one (5); and 4-[4-(1-Benzyl-1H-[1,2,3]triazol-4-ylmethoxy)-3-methoxy-phenyl]-4-hydroxy-butan-2-one (6), as well as the previously known derivative (7) were subjected to antimicrobial, antiquorum-sensing and cytotoxic evaluation. Compounds 4-7 possessed the most notable enhancement in the anti-bacterial activity against Bacillus cereus, Pseudomonas aeruginosa and antifungal activity against Candida albicans. However, compounds 1 and 2 exhibited high antiquorum-sensing activity against Chromobacterium violaceum using catechin as a positive control. Compounds 4-7 demonstrated selective cytotoxicity against MCF-7 and HepG2 cancer cells compared to normal lung fibroblast cells (WI-38). These findings proved the usefulness of synthesis bioactive derivatives from vanillin through chemical modifications.

Neuroprotective effect of naringin against cerebellar changes in Alzheimer's disease through modulation of autophagy, oxidative stress and tau expression: An experimental study.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by gradual cognitive decline. Strong antioxidants that inhibit free radicals, such as polyphenols, reduce the likelihood of developing oxidative stress-related degenerative diseases such as AD. Naringin, a flavonoid found in citrus fruit shown to be neuroprotective, reduce oxidative damage and minimize histopathological changes caused by ischemic reperfusion, enhance the long-term memory in AD animal models. This work aimed to comprehend the role of naringin in the defense of the cerebellum against aluminum chloride (AlCl3)-induced AD in rats by investigating the behavioral, neurochemical, immunohistochemical, and molecular mechanisms that underpin its possible neuroprotective effects. Twenty-four adult albino rats were divided into four groups (n = 6/group): (i) Control (C) received saline per oral (p.o.), (ii) Naringin(N)-received naringin (100 mg/kg/d) p.o, (iii) AlCl3-recived AlCl3 (100 mg/kg/d) p.o and (iv) AlCl3 + Naringin (AlCl3 + N) received both AlCl3 and naringin p.o for 21 days. Behavioral tests showed an increase in the time to reach the platform in Morris water maze, indicating memory impairment in the AlCl3-treated group, but co-administration of naringin showed significant improvement. The Rotarod test demonstrated a decrease in muscle coordination in the AlCl3-treated group, while it was improved in the AlCl3 + N group. Neurochemical analysis of the hippocampus and cerebellum revealed that AlCl3 significantly increased lipid peroxidation and oxidative stress and decreased levels of reduced glutathione. Administration of naringin ameliorated these neurochemical changes via its antioxidant properties. Cerebellar immunohistochemical expression for microtubule assembly (tau protein) and oxidative stress (iNOS) increased in A1C13-treated group. On the other hand, the expression of the autophagic marker (LC3) in the cerebellum showed a marked decline in AlCl3-treated group. Western blot analysis confirmed the cerebellar immunohistochemical findings. Collectively, these findings suggested that naringin could contribute to the combat of oxidative and autophagic stress in the cerebellum of AlCl3-induced AD.