Molecular diagnostic yield of whole-exome sequencing in Saudi autistic children with epilepsy.

Objectives: Autism spectrum disorder (ASD) is a neurological condition that affects social communication and causes repetitive behavior. Autistic children often have comorbidities such as epilepsy. Although the co-occurrence of epilepsy and ASD is frequent, the genetic basis for this association is not fully understood. Many cases of ASD and epilepsy remain unresolved without a molecular diagnosis. The purpose of this study was to determine the molecular diagnostic yield in two Saudi families with a single affected offspring with both ASD and epilepsy using whole-exome sequencing (WES). Methods: Pediatric patients were diagnosed by a pediatric psychiatrist and neurologist, and diagnosed according to the diagnostic and statistical manual of mental disorders (DSM-V) criteria. WES was used to analyze the coding region of DNA from the two trios. Enrichment analysis was performed on the final list of genes. Results: De novo variations were detected in eleven genes (two in ZBTB17 and FRG, and one each in CAD, CTNNA3, GILGA8J, CCZ1, CASKIN1, growth differentiation factor (GDF7), NBPF10, DUX4L4, and ZNF681). Variations in CTNNA3, GOLGA8J, CASKIN1, CCZ1, and NBPF10 genes were correlated to autism. In addition, similar studies found that CAD, CASKIN1, and GOLGA8J were candidate genes for epilepsy. FRG1 and DUX4 variations were associated with facioscapulohumeral muscular dystrophy. The expression of ZBTB17 and GDF was high in nervous system, and variations in these genes might be correlated to autism and epilepsy. Conclusion: Not all the genes presumed to cause ASD and epilepsy in this study were previously identified, suggesting that more genes were suspected of being involved in ASD and epilepsy co-occurrence.

Biogenic Zinc oxide nanoparticles from Celosia argentea: toward improved antioxidant, antibacterial, and anticancer activities.

Biogenic Zinc oxide (ZnO) nanoparticles (NPs) were synthesized from Celosia argentea (C. argentea) plant extract. Structural analysis confirms the successful synthesis of biogenic zinc oxide NPs from C. argentea extract. The biogenic ZnO NPs have an average particle size of 21.55 ± 4.73 nm, a semispherical shape, and a specific surface area of about 50 m2/g. The biogenic ZnO NPs have a powerful radical scavenging activity (Ic50 = 91.24 mg/ml) comparable to ascorbic acid (ASC) as a standard (Ic50 = 14.37 mg/ml). The antibacterial efficacy was tested against gram-positive and gram-negative bacteria using an agar disc diffusion method. Gram-positive strains with biogenic ZnO NPs have a greater bactericidal impact than gram-negative strains in a concentration-dependent manner. Anticancer activity against Liver hepatocellular cells (HepG2) and Human umbilical vein endothelial cells (HUVEC) was evaluated using a [3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl tetrazolium bromide] (MTT) assay. The results reflect the concentration-dependent cytotoxic effect of biogenic ZnO NPs against HepG2 cells even at low concentrations (Ic50 = 49.45 µg/ml) compared with doxorubicin (Ic50 = 14.67 µg/ml) and C. argentea extract (Ic50 = 112.24 µg/ml). The cell cycle and gene expression were analyzed to determine the potential anticancer mechanism. The flow cytometric analysis of the cell cycle revealed that biogenic ZnO NPs induce oxidative stress that activates the apoptotic genes NF-κB, CY-C, and P53, leading to cell death. The Celosia argentea improved the antioxidant, antibacterial, and anticancer activities of ZnO NPs without altering their structural properties. The effect of green synthesis on the bioactivity of biogenic ZnO NPs in vivo is recommended for future work.

Chemical Characterization of Clove, Basil and Peppermint Essential Oils; Evaluating Their Toxicity on the Development Stages of Two-Spotted Spider Mites Grown on Cucumber Leaves.

The two spotted spider mite (TSSM), Tetranychus urticae Koch, is a cosmopolitan mite. It rapidly reproduces and can develop resistance to chemical pesticides. This study aims to evaluate the toxicity and acaricidal activity of three essential oils from basil, clove, and peppermint against T. urticae reproduction, which is grown on three cucumber cultivars, Chief (SC 4145), Raian (CB898), and Toshka (SC 349), under laboratory conditions at 27 + 3 °C and 70 + 5% RH. GC-MS characterized the volatile oils of basil, clove, and peppermint. Methyl cinnamate, eugenol, and menthol were the main essential oils in basil, clove, and peppermint, respectively. The results indicated significant differences in the duration of development between T. urticae feeding on the three cucumber cultivars (p ≤ 0.05), including eggs, protonymph, and deutonymph time. The Toshka (SC 349) cultivar recorded the lowest developmental time. The longevity period exhibited the same trend with non-significant differences between Raian (CB898) and Toshka (SC 349). Moreover, the lethal concentration (LC50) and LC90 values in tested essential oils (EOs) showed that clove EOs were the most toxic. In contrast, basil and peppermint EOs were the least effective, and immature stages were more sensitive to EOs than adult stages. The infected Toshka (SC 349) discs treated with essential oils and abamectin under in vitro conditions indicated that clove oil is comparable to abamectin regarding its effect on the egg numbers (18.7 and 17.6 egg), immature development time, longevity, life span, and life cycle (20.6 and 20.8 days) of T. urticae. We conclude that the resistant cultivation of cucumber plants can be recommended in integrated pest management programs. The most effective of the tested oils, clove EOs, should be used as alternatives to pesticides to control T. urticae in the protected cultivation of cucumbers.

Novel Design of RNA Aptamers as Cancer Inhibitors and Diagnosis Targeting the Tyrosine Kinase Domain of the NT-3 Growth Factor Receptor Using a Computational Sequence-Based Approach.

Aptamers, the nucleic acid analogs of antibodies, bind to their target molecules with remarkable specificity and sensitivity, making them promising diagnostic and therapeutic tools. The systematic evolution of ligands by exponential enrichment (SELEX) is time-consuming and expensive. However, regardless of those issues, it is the most used in vitro method for selecting aptamers. Therefore, recent studies have used computational approaches to reduce the time and cost associated with the synthesis and selection of aptamers. In an effort to present the potential of computational techniques in aptamer selection, a simple sequence-based method was used to design a 69-nucleotide long aptamer (mod_09) with a relatively stable structure (with a minimum free energy of -32.2 kcal/mol) and investigate its binding properties to the tyrosine kinase domain of the NT-3 growth factor receptor, for the first time, by employing computational modeling and docking tools.