Recently, high-throughput next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidies techniques came into use. This technique is essential for successful embryo transfer and accomplishing pregnancy, thus reducing the time and cost of additional cycles. In this study, we describe our first experience in introducing an NGS-based preimplantation genetic testing for aneuploidy (PGT-A) service using next-generation sequencing in King Abdulaziz Medical City located in Riyadh, Saudi Arabia. Our main goal was to report the successful implementation of this new technology in clinical practice and highlight the factors that may affect the results. In total, 200 blastomere biopsies were obtained from 36 in vitro fertilization (IVF) cycles from Saudi couples suffering from prolonged infertility or recurrent embryo transfer failure. NGS-based PGT-A was performed in all embryos. The results were analyzed in five age groups, showing that aneuploidy rates increased with maternal age. Moreover, the results also showed that complex abnormal embryos with (2–5) aneuploidy are the most common type of embryos. Additionally, our data showed that chromosome 16-related abnormality was the most frequent abnormality detected among all reported abnormalities. In conclusion, our study suggests that NGS-based PGT-A is an applicable and reliable technique for routine-based embryo screening, especially for couples suffering from recurrent miscarriages or multiple embryo transfer failures.

CDC42 (cell division cycle protein 42) belongs to the Rho GTPase family that is known to control the signaling axis that regulates several cellular functions, including cell cycle progression, migration, and proliferation. However, the functional characterization of the CDC42 gene in mammalian physiology remains largely unclear. Here, we report the genetic and functional characterization of a non-consanguineous Saudi family with a single affected individual. Clinical examinations revealed poor wound healing, heterotopia of the brain, pancytopenia, and recurrent infections. Whole exome sequencing revealed a de novo missense variant (c.101C > A, p.Pro34Gln) in the CDC42 gene. The functional assays revealed a substantial reduction in the growth and motility of the patient cells as compared to the normal cells control. Homology three-dimensional (3-D) modeling of CDC42 revealed that the Pro34 is important for the proper protein secondary structure. In conclusion, we report a candidate disease-causing variant, which requires further confirmation for the etiology of CDC42 pathogenesis. This represents the first case from the Saudi population. The current study adds to the spectrum of mutations in the CDC42 gene that might help in genetic counseling and contributes to the CDC42-related genetic and functional characterization. However, further studies into the molecular mechanisms that are involved are needed in order to determine the role of the CDC42 gene associated with aberrant cell migration and immune response.

Background: Breast cancer remains a significant global health concern, with approximately 2.3 million diagnosed cases and 670,000 deaths annually. Current targeted therapies face challenges such as resistance and adverse side effects. This study aimed to explore natural compounds as potential multitargeted breast cancer therapeutics, focusing on Lucidin, an anthraquinone derived from Rubia cordifolia, and comparing its efficacy with Lapatinib, an FDA-approved drug. Methods: We performed multitargeted molecular docking studies on key breast cancer proteins using a natural compound library from ZINC. Comparative analyses of Lucidin and Lapatinib included molecular interaction fingerprints, pharmacokinetics, WaterMap computations (5 ns) to assess water thermodynamics and binding interactions, and Molecular Dynamics Simulations (100 ns) in water to evaluate complex stability and dynamic behaviour. Results: Lucidin demonstrated significant binding affinity and interaction potential with multiple breast cancer targets, outperforming Lapatinib in stability and binding interactions. WaterMap analysis revealed favourable hydration site energetics for Lucidin, enhancing its efficacy. The multitargeted profile of Lucidin suggests a broader therapeutic approach with potential to overcome resistance and side effects associated with Lapatinib. Conclusions: Lucidin shows promise as a novel, multitargeted anti-breast cancer agent with improved efficacy over Lapatinib. These findings provide a foundation for further in vitro and in vivo validation to develop Lucidin as a potential therapeutic option for breast cancer treatment.

Cervical cancer, primarily caused by persistent infection with high-risk human papillomavirus strains, leads to abnormal cell growth in the cervix. Globally, it accounts for over 600,000 new cases and 340,000 deaths annually, with the highest burden in low- and middle-income countries due to limited screening and vaccination. Early detection is challenging as initial stages are asymptomatic, while advanced cases are challenging to treat. Current options, including surgery, radiotherapy, and chemotherapy, face issues like toxicity, limited efficacy, recurrence, and drug resistance caused by tumor heterogeneity and adaptive mechanisms. Multitargeted drug design offers a solution by modulating multiple cancer pathways, enhancing efficacy, minimizing resistance, and reducing side effects. In this study, we screened Selleckchem approved library against cervical cancer proteins that regulate the cell cycle, particularly during mitosis and cell division (PDBIDs: 2VFX, 2WVI, 3KND, 4N14) using HTVS, SP, and XP docking followed by MMGBSA post-processing. Pixuvri (Pixantrone Maleate) emerged as the top candidate with docking scores of -5.234 to -9.218 kcal/mol and MMGBSA scores of -39.22 to -53.87 kcal/mol. Pixuvri is approved for non-Hodgkin lymphoma and exhibits minimal cardiotoxicity compared to anthracyclines. Interaction fingerprints highlighted key residues (4GLN, 4GLU, 3TRP), while pharmacokinetics, DFT computations, and WaterMap hydration site analysis supported its potential. Molecular dynamics (100 ns, NVT ensemble at 300K) validated stability by deviation and fluctuation studies and found many interactions to stabilize the complex, with binding free energy computations confirming its affinity. While the results support Pixuvri’s repurposing for cervical cancer, experimental validation is essential for clinical application.

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterised by the accumulation of neurotoxic substances in the brain, ultimately leading to progressive cognitive decline. The complex aetiology and involvement of multiple molecular targets in AD pathogenesis have made discovering effective therapeutic agents particularly challenging. Targeting multiple proteins simultaneously with a single therapeutic agent may offer a promising strategy to address the disease’s multifaceted nature. Methods: This study employed advanced computational methodologies to perform multitargeted molecular docking of FDA-approved drugs against four key AD-associated proteins implicated in disease progression. Among the screened compounds, Rebamipide—a drug conventionally used for treating gastrointestinal disorders—demonstrated notable binding affinities across all targets. Pharmacokinetic predictions, interaction fingerprinting, WaterMap analysis, density functional theory (DFT) calculations, and 100 ns MD simulations were performed for each protein–ligand complex to evaluate its multitarget potential. Results: Rebamipide bound effectively to the NR1 ligand-binding core, suggesting modulation of glutamatergic signalling while reducing β-secretase production and regulating neurotransmitter homeostasis through inhibiting monoamine oxidase-A. Furthermore, Rebamipide enhanced cholinergic neurotransmission by inhibiting human acetylcholinesterase, potentially improving cognitive function. Pharmacokinetic analyses confirmed favourable drug-like properties. Molecular interaction fingerprints revealed consistent hydrogen bonding, hydrophobic contacts, and π-π stacking interactions. WaterMap analysis indicated thermodynamically favourable water displacement upon binding, enhancing ligand affinity. DFT analysis of Rebamipide showed a 4.24 eV HOMO-LUMO gap, with ESP values ranging from −6.63 × 10⁻² to +6.63 × 10⁻² A.U., indicating reactive sites. TDDFT predicted strong UV absorption at 314 nm with a peak intensity of ~6500 L mol⁻¹ cm⁻¹. MD simulations over 100 ns demonstrated minimal structural deviations and stable ligand–protein complexes, reinforcing its multitarget efficacy. Conclusions: The comprehensive in silico investigation highlights Rebamipide as a promising multitargeted therapeutic candidate for Alzheimer’s disease. Its ability to modulate multiple pathogenic pathways simultaneously underscores its potential utility; however, these computational findings warrant further experimental validation to confirm its efficacy and therapeutic relevance in AD.

The use of natural health products (NHP) is constantly increasing worldwide. Among the most NHP consumed are the resins of Commiphora myrrha (C. myrrha) tree. Consumption of C. myrrha may result in herb-drug interactions that can lead to serious health consequences. This study aims to determine the herb-drug interactions based on the induction of drug-metabolizing enzyme cytochrome P-450 (CYP) 2C9 by a non-toxic boiled aqueous extract of C. myrrha and to unveil the potential involvement of xenobiotic-sensing nuclear receptors such as Pregnane X Receptor (PXR), a well-known CYP 2C9 transcription factor. Tested at low concentrations (0.01-10 g/mL) devoid of anti-proliferative effects, boiled C. myrrha resin aqueous extract upregulated CYP 2C9 gene and protein expressions in a dose-dependent manner, reaching a mean expression level exceeding 3.0-fold change in Hep G2 cells, compared with the basal level expressed in untreated cells. Furthermore, chemical analysis using mass spectrometry and computational molecular docking using in silico studies revealed that few C. myrrha resin-derived metabolites are strongly bound to PXR. In particular, the identified metabolite named diayangambin exhibited a predicted molecular docking score close to that of a native PXR ligand. The use of the nuclear receptor binding assays confirmed the binding between C. myrrha metabolite(s) and PXR, while no binding to the other xenobiotic-sensing nuclear receptor, the constitutive androstane receptor (CAR), was observed, suggesting that C. myrrha metabolite(s) are potential PXR agonists. In conclusion, although in vivo studies are needed, this study cautions patients, healthcare providers, and governmental regulators against the consumption of C. myrrha and diayangambin-rich preparations with a high potential for herb-drug interactions through drug-metabolizing CYP 2C9 enzyme induction, which could affect drug efficacy.