Background and Objectives: Diabetic nephropathy (DN) is a major cause of end-stage renal disease, yet its molecular basis remains unclear. Nicotinamide adenine dinucleotide (NAD⁺) metabolism is crucial for energy regulation, redox balance, and inflammation. This study investigated the dysregulation of key NAD⁺ salvage enzymes (CD38, NAMPT, and SIRT1) across albuminuria stages in type 2 diabetes (T2D). Materials and Methods: A cross-sectional study was conducted on 225 participants: healthy controls (n = 45), T2D with normoalbuminuria (n = 60), microalbuminuria (n = 60), and macroalbuminuria (n = 60). Serum CD38, NAMPT, and SIRT1 were measured by ELISA, while CD38 and SIRT1 gene expression in peripheral blood mononuclear cells was analyzed by qPCR. Results: CD38 and NAMPT levels increased progressively with albuminuria, whereas SIRT1 levels declined significantly. CD38 and NAMPT correlated positively with HbA1c, creatinine, and urinary albumin-to-creatinine ratio (UACR), while SIRT1 showed inverse correlations and a positive association with eGFR. Regression analysis identified CD38 and NAMPT as independent positive predictors of albuminuria, and SIRT1 as a negative predictor. ROC analysis revealed strong diagnostic performance for CD38 (AUC = 0.89) and SIRT1 (AUC = 0.88). Conclusions: These findings highlight disrupted NAD⁺ salvage pathways in DN and suggest that restoring NAD⁺ balance, through CD38 inhibition, SIRT1 activation, or NAD⁺ precursor supplementation, may offer promising renoprotective strategies.

Cancer remains the foremost cause of death globally and presents a major obstacle to increasing life expectancy. The identification of natural anticancer agents is therefore a key research priority. Essential oils (EOs), widely used in traditional medicine, possess diverse biological activities that warrant systematic investigation. Anisosciadium orientale is traditionally regarded as a safe, edible herb; however, its therapeutic potential has not been extensively explored. In this study, the chemical profile of the EO obtained from the aerial parts of A. orientale was characterized using GC–MS analysis. Antioxidant activity was evaluated through hydrogen peroxide and ABTS radical-scavenging assays, whereas anticancer effects and underlying mechanisms were evaluated in multiple cancer cell lines using MTT cytotoxicity assays, flow cytometry, and molecular docking studies. Sixty constituents were identified in the EO, with myristicin and its isomer among the major components. The EO exhibited notable antioxidant and anticancer activities, demonstrating cytotoxicity against lung carcinoma A549 cells with an IC₅₀ of 84.8 µg/mL and inducing significant apoptosis accompanied by G₂/M cell-cycle arrest. Treatment with the EO markedly boosted levels of caspase-3, p53, Bax, and the Bax/Bcl-2 ratio, while downregulating Bcl-2 expression. Molecular docking revealed strong binding affinities of major constituents—particularly myristicin and its isomer—toward the EGFR kinase active site, suggesting a high degree of complementarity with the EGFR kinase domain. Collectively, this study represents the first comprehensive study integrating chemical profiling, in vitro cytotoxicity, mechanistic assays, and molecular docking for A. orientale. These findings position A. orientale EO as a promising scaffold for the development of natural anticancer interventions, providing a foundation for future preclinical exploration.

Background: Sickle cell disease (SCD) is an inherited blood disorder characterized by chronic hemolysis, inflammation, and vaso-occlusive crises (VOC), leading to several complications and reduced life expectancy of affected individuals. Limited effective treatment options are currently available; however, pharmacogenomic (PGx) insights derived from recent genomic findings, particularly in underrepresented populations such as Saudi Arabians, may offer new hope for predicting molecular-guided treatments. This study aimed to identify approved drugs suitable for repurposing based on their interaction with SCD-associated genetic variants and discover novel druggable targets within genetic pathways linked to disease severity by utilizing genome-wide association study (GWAS) data from Saudi SCD patients. Methods: Our PGx analysis used bioinformatic pipelines to evaluate drug-gene interactions and identify potential therapeutic targets to treat SCD based on GWAS data derived from the Saudi population. Selected approved drugs were suggested for repurposing based on their interactions with genes of interest known to impact SCD pathophysiology, using the Drug-Gene Interaction Database (DGIdb 5.0). New drug targets were also proposed based on assessing the simulated pockets of gene products according to the 3D protein structures provided by the protein data bank (PDB) and the AlphaFold database. New molecules with higher druggability scores, estimated based on the DoGSiteScorer database, were predicted to have a higher success rate in developing new SCD treatments. Results: Our analysis identified 78 approved medications that showed potential for repurposing in SCD; this list was narrowed down to 21 candidates based on their safety profiles and interactions with key genetic pathways in SCD. Among them, simvastatin, allopurinol, omalizumab, canakinumab, and etanercept were suggested as the most promising agents. Furthermore, novel drug targets encoded by olfactory receptor (OR) gene clusters (OR51V1, OR52A1, OR52A5, OR51B5, and OR51S1), TRIM genes, SIDT2, and CADM3, had high druggability scores. Conclusion: This study provides a robust framework for drug repurposing and novel drug discovery in SCD, particularly tailored to the Saudi population. The findings underscore the potential of leveraging genomic data to identify targeted therapies, offering a pathway to more personalized and effective treatments for SCD patients. Future clinical trials are essential to validate these findings and translate them into clinical practice.