Defensin Alpha 4 (DEFA4) is the fourth member of the Alpha Defensins family known as a part of antimicrobial peptides in the innate immune system. DEFA4 has a strong preference to kill Gram-negative bacteria more than Gram-positive bacteria. In addition, DEFA4 exhibits antiviral activity against human immunodeficiency virus type 1 (HIV-1) in vitro. Moreover, DEFA4 can act as an inhibitor of corticosterone production (Corticostatin). On the other hand, alternations in DEFA4 gene expression have been reported in different disorders such as diseases related to inflammation and immunity dysfunction, brain-related disorders, and various cancers. The up-regulation of DEFA4 appears to be involved in the malignant transformation or aggressive form of cancer. Interestingly, the modified version of DEFA4 fragment (111) was potent and efficient against antibiotic-resistant bacteria. This review provides a general background abSaudi Arabia out DEFA4 and sheds light on changes in DEFA4 gene expression in different diseases. The paper also discusses other aspects related to DEFA4 as an antimicrobial and antiviral agent. The research was conducted based on available articles obtained from databases starting from 1988 to the present.

The Red Sea is rich in symbiotic microorganisms that have been identified as sources of bioactive compounds with antimicrobial, antifungal, and antioxidant properties. In this study, we aimed to explore the potential of marine sponge-associated bacteria as sources of antibacterial compounds, emphasizing their significance in combating antibiotic resistance (AMR). The crude extracts of Micrococcus, Bacillus, and Staphylococcus saprophyticus exhibited significant antibacterial activity, with inhibition zones measuring 12 mm and 14 mm against Escherichia coli, Staphylococcus aureus, Candida albicans, and other infectious strains. The DPPH assay showed that the bacterial isolates AN3 and AN6 exhibited notable antioxidant activity at a concentration of 100 mg/mL. To characterize the chemical constituents responsible for the observed bioactivity, a GC–MS analysis was performed on ethyl acetate extracts of the potent strains. The analysis identified a range of antimicrobial compounds, including straight-chain alkanes (e.g., Tetradecane), cyclic structures (e.g., Cyclopropane derivatives), and phenolic compounds, all of which are known to disrupt microbial membranes or interfere with metabolic pathways. The bioprospecting and large-scale production of these compounds are challenging. In conclusion, this study underscores the potential for marine bacteria associated with sponges from the Red Sea to be a source of bioactive compounds with therapeutic relevance.

Dysregulated expression of nuclear receptor superfamily 4 group A member 2 (NR4A2) has recently been associated with autistic spectrum disorder (ASD), speech impairment, and neurodevelopmental delay (NDD); however, its precise role in the prevalence and etiopathogenesis of ASD has not been fully elucidated. Herein, we aimed to explore the role of NR4A2 variants in the genetic underpinnings of ASD among Saudi children of different age ranges and phenotype severities. A total of 338 children with ASD from 315 unrelated families (293 simplex, 2 quads, and 1 quintet) were screened for NR4A2 variants via exome sequencing (ES) of the genomic DNA extracted from peripheral blood mononuclear cells (PBMCs), after which the probands with identified NR4A2 variants were further subjected to trio genetic analyses. ES analysis revealed 10 de novo NR4A2 variants (5 indels/nonsense, 2 missense, and 3 variants affecting splicing) in 8 unrelated probands (2.37%) and 2 affected siblings from 8 unrelated families (6 simplex (2.04%) and 2 quads (8.7%)). Three NR4A2 variants were notably recurrent among both affected and unaffected carriers. All identified indels and two splicing variants met the criteria for pathogenic/loss-of-function (LoF) variants according to the ACMG classification (PVS1), whereas the missense variants were classified as of uncertain significance (VUS). This study is among the first to identify such a high frequency of recurrent variants in an ASD cohort, suggesting their significant contribution to the etiopathogenesis of ASD within this population.

The objective of the current study was to determine the impact of a diet supplemented with herbal mixture powder (HMP) as a natural antioxidant and growth promoter on growth performance, carcass traits, blood indices, antioxidant gene expression, meat quality, and intestinal microbial load in Arbor Acres broiler chickens. The herbal mixture consists of 200 g cardamom seeds, 200 g black pepper, 300 g turmeric, and 300 g cinnamon. A total of 280 broiler chicks, one-day-old, were allotted to four experimental groups in a completely randomized design experiment. Each group was subdivided into five replicates, each of fourteen sexed chicks (7 males and 7 females). The treatments were as follows: control group without additives (basal diet); HMP1, HMP2 and HMP3: basal diet + 1, 2 and 3 g herbal mix powder/kg diet, respectively. The results revealed that HMP supplementation significantly affected body weight gain, feed conversion ratio, and performance index (P ≤ 0.05), with optimal responses at 2 and 3 g/kg. Carcass yield and abdominal fat percentage reduction were also significant (P ≤ 0.05). Blood biochemical test results showed improvement in liver and kidney function, increases in total protein, albumin, and globulin, and a lipid profile with reduced cholesterol, triglycerides, and LDL, and increased HDL (P ≤ 0.001). The activities of the enzymes GPx and GST were increased, enabling synchronous measurements of antioxidant status and resulting in significant reductions in MDA. Elevated levels of immunoglobulins (IgG and IgM) indicate increased immune system responsiveness. The results further indicate that HMP modulates gut microbiota by decreasing total bacterial numbers and simultaneously increasing the number of beneficial bacteria. In addition, the expression of antioxidant-related genes (CAT, SOD, and GPX) was significantly increased. Overall, HMP is likely to have a beneficial effect on broiler production, due in part to its antioxidant, antimicrobial, and immunomodulatory effects; therefore, it should be considered a natural feeding enhancer to improve the productive efficiency of broilers and serve as an AGP substitute.

MIR-124-1 is a brain-abundant MIRNA, whose expression is important for neuronal tissue division, growth and actions. However, expression of miR-124-1 regulatory mechanisms controlling its actions in neuronal cells in health and diseases still poorly addressed. To understand mechanism for transcriptional and functional regulation of miR-124 in neuronal and glioblastoma cells, this study combined gene expression profiling data and computational transcription factor and microRNA target predictions. The present research focuses on transcription factors and DNA methylation, which are central to miR-124-1 expression regulation. A core promoter sequence of miR-124-1 was predicted to be 500 bp and 100 bp, upstream and downstream of its transcription start sites. Seventy three binding sites of fifty transcription factors in promoter region were found, using MatInspector software. Among these transcription factors, MEIS1, POU3F2, SALL2, ETV1, and MAZ, are known to be brain-enriched transcriptional activators. By using omics data analysis, expression of MAZ, PLAG1 KLF2 as well as a transcriptional repressor ZNF239 showed significant correlation with decline in miR-124-1 expression in glioblastoma cells. Furthermore, a potential CpG island was reported in the promoter, providing another mechanism for transcriptional inhibition of miR-124. As miR-124-1 regulates a number of neuronal physiological and pathological processes, we made an attempt to define its potential targets. A computational prediction of miR-124-1 targets suggested 265 targets with two or more conserved seed sites. Pathway-based analysis of these target genes revealed a significant enrichment for axonal guidance and cancer signaling pathways. At least ten of these targets, SRGAP1, GNAI3, PLXNA3, SEMA5A, SEMA6A, CEBPA, CBL, RASSF5, MITF, and RPS6KB1, showed expected inverse correlation between their expression values and miR-124-1 suppression in glioblastoma cells. Taken together, our data form foundation of subsequent future validation researches for miR-124-1 expression regulation including transcription factors and CpG Island within its promoter as well as functional regulation comprising biological pathways controlled by its target genes.

Background: White spot syndrome virus (WSSV) is a highly virulent pathogen threatening global shrimp populations, with no effective treatments available. Objectives: The present study aimed to identify antiviral compounds from Cyperus rotundus and Salvia rosmarinus targeting WSSV dUTPase using computational methods. Methods: A comprehensive analysis of phytochemicals included binding site prediction, protein structure validation, absorption, distribution, metabolism, and excretion (ADME) profiling, and compliance with the Lipinski rule. Molecular docking and dynamics simulations evaluated binding affinity and stability. Results: After screening 1103 compounds, 28 candidates qualified for docking. Notably, selinene, podolide, and zierone showed strong binding affinity to dUTPase with docking scores of -9.3, -8.8, and -7.8 kcal/mol, respectively, compared to the highest positive controls, 2’-deoxyuridine scored -6.6 kcal/mol. The ADME studies indicated favorable pharmacokinetic profiles. Molecular dynamics (MD) simulations over 100 ns confirmed stable binding interactions. Conclusions: The promising results from docking and dynamics simulations provide a foundation for advancing podolide and its analogs toward empirical validation. This research has potential for developing innovative phytochemical-derived antiviral interventions against WSSV, although in vivo validation is necessary to confirm efficacy and safety.