Hind Mansour Naffadi

Background: Coronary artery disease (CAD) arises from the convergence of genetic susceptibility, lipid dysregulation, and modifiable environmental exposures. The polymorphism rs4977574, located proximal to the CDKN2A/CDKN2B gene cluster, has been repeatedly implicated in CAD risk across several populations, yet its relationship to intermediate cardiometabolic phenotypes and pharmacological treatment patterns in Saudi individuals remains poorly characterized. Objective: This study aimed to evaluate the association of rs4977574 with CAD status, lipid-related phenotypes, smoking history, obesity, and atorvastatin exposure in a Saudi cardiovascular cohort, and to assess the robustness of observed associations through sensitivity-adjusted analyses excluding participants with major metabolic confounders. Methods: A case–control genetic association study was conducted in Saudi participants with clinically confirmed CAD and healthy controls. Genomic DNA was genotyped for rs4977574 using TaqMan^® allelic discrimination assays. Genotype–phenotype associations were examined using chi-square testing, binary logistic regression under additive and dominant inheritance models, and one-way ANOVA for continuous lipid traits. Hardy–Weinberg equilibrium (HWE) was assessed in controls. Sensitivity analyses were conducted by sequentially excluding participants with obesity, smoking, diabetes mellitus, hypertension, dyslipidaemia, and statin use. Results: After covariate adjustment, rs4977574 was not independently associated with CAD case–control status under any inheritance model. Genotype-stratified analyses identified significant differences in HDL-cholesterol and triglyceride concentrations among cases, with no equivalent effects on total cholesterol or LDL-cholesterol. A significant association was observed between rs4977574 genotype and atorvastatin prescribing patterns. Sensitivity-adjusted analyses were directionally consistent with primary findings. HWE deviation persisted in controls after sequential metabolic exclusions, implicating population stratification or regional genetic heterogeneity rather than sample selection bias. Conclusions: Although rs4977574 did not associate independently with CAD susceptibility, its relationship with HDL-cholesterol, triglycerides, and atorvastatin exposure indicates that this locus contributes to cardiometabolic phenotypic heterogeneity in this Saudi cohort. These findings support phenotype-oriented and pharmacogenetically informed approaches in regional cardiovascular genetics and highlight the need for larger, ancestry-stratified investigations across Middle Eastern populations.

Rationale: Copy number variants (CNVs) are structural genomic alterations that can lead to a range of genetic disorders by disrupting gene dosage and function. Large duplications affecting multiple genes are known to result in partial trisomies, frequently associated with developmental delay, intellectual disability, and congenital anomalies. These types of CNVs often arise from unbalanced chromosomal translocations, typically inherited from phenotypically normal carriers of balanced rearrangements. This study describes the clinical and cytogenomic findings of a rare case of a dysmorphic infant with concurrent partial trisomies of chromosomes 9p and 12p. Patient concerns: A female infant presenting with global developmental delay, growth retardation, distinctive craniofacial dysmorphism, and multiple congenital anomalies. Conventional karyotype, along with genome sequencing-based CNV analysis, has been performed. In addition, parental karyotyping has been performed. Diagnoses: The infant’s karyotype revealed an extra copy of a structurally abnormal chromosome 9. Genome sequencing-based CNV analysis identified 2 pathogenic CNVs: a duplication of chromosome 9p24.3-q21.13 and a second duplication of chromosome 12p13.33-p12.1, indicating 2 partial trisomies of chromosome 9p and 12p. Parental karyotyping revealed a maternally inherited balanced translocation involving chromosomes 9 and 12. Interventions and outcomes: The patient received supportive care; at 12 months of age, she developed a severe respiratory infection and died. Lessons: This case contributes to the expanding phenotypic and cytogenomic spectrum of partial trisomies 9p and 12p. We highlight the role of CNV analysis based on genome sequencing in the clinical evaluation of individuals with dysmorphic and malformative conditions. We also emphasize the importance of parental cytogenetic studies in such cases for elucidating inheritance patterns and recurrence risks.

Many species belonging to the genus Ocimum are used for aromatic, medicinal, and cosmetic purposes. The essential oil (OFEO) obtained by hydrodistillation of the flowering aerial parts of Forsskal’s Basil “Ocimum forskolei Benth” growing in extreme environmental conditions in Mecca Region, Saudi Arabia was analyzed by GC-MS. The main constituents were phenylpropanoids (methyl eugenol 55.65% and eugenol 11.66%), monoterpene (linalool 9.75%), and sesquiterpenes (germacrene D 3.72% and β-caryophyllene 2.57%). The OFEO was tested against MCF7, HT29, and HCT116 cancer cells and compared with normal fibroblast cells (MRC5). The MTT assay showed that HCT116 was more sensitive to OFEO (IC50 5.34 μg/mL), which reduced the number of HCT116 colonies at 6 μg/mL, while causing complete colony death at 12 and 24 μg/mL. Western Blotting and qRT-PCR were used to evaluate the level change of different proteins with respect to GAPDH. OFEO upregulated the apoptotic protein (caspase 3), and downregulated the cell proliferation proteins (AKT and pAKT), cell cycle arrest (PCNA, Cyclin D1), and the anti-apoptotic Bcl2 proteins. OFEO was also tested against reference strains of Gram-negative and Gram-positive bacteria including Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Staphylococcus aureus by using the well-diffusion and assessing their MICs, which ranged from 250 to 500 μg/mL.

A significant public health issue worldwide is metabolic syndrome, a cluster of metabolic illnesses that comprises insulin resistance, obesity, dyslipidemia, hyperglycemia, and hypertension. The creation of natural treatments and preventions for metabolic syndrome is crucial. Chitosan, along with its nanoformulations, is an oligomer of chitin, the second-most prevalent polymer in nature, which is created via deacetylation. Due to its plentiful biological actions in recent years, chitosan and its nanoformulations have drawn much interest. Recently, the chitosan nanoparticle-based delivery of CRISPR-Cas9 has been applied in treating metabolic syndromes. The benefits of chitosan and its nanoformulations on insulin resistance, obesity, diabetes mellitus, dyslipidemia, hyperglycemia, and hypertension will be outlined in the present review, highlighting potential mechanisms for the avoidance and medication of the metabolic syndromes by chitosan and its nanoformulations.