Saudi Pharmaceutical Journal最新文献

As personalized medicine progresses in Saudi Arabia, pharmacists endure a central role in pharmacogenomics (PGx) implementation. This cross-sectional study weighed the knowledge, attitudes, and perceptions (KAP) of pharmacists in the Asir region regarding PGx, a region with limited published data. A total of 209 pharmacists took part, the majority of whom were male (68.4%) and aged 18-39 years (96.2%). Results revealed that 71.3% of pharmacists displayed poor knowledge, whereas positive attitudes (90.9%) and perceptions (87.6%) were widely expressed. Significant associations developed between knowledge and attitude (p = 0.015) and between knowledge and perception (p = 0.036). A moderate correlation was also reflected between attitude and perception (p < 0.001, Cramér's V = 0.44). Logistic regression showed that pharmacists lacking previous PGx training (OR = 0.257, p < 0.001) or lacking experience with genetic conditions (OR = 0.389, p = 0.022) were significantly less likely to demonstrate good knowledge. Regardless of evident knowledge gaps, pharmacists showed a strong willingness to integrate PGx into clinical practice. These findings highlight an imperative need for structured PGx training programs, integration of PGx into pharmacy curricula, ongoing professional development workshops, and institutional strategies to support operative PGx adoption in healthcare settings across the Asir region and Saudi Arabia.

Antibiotic resistance (ABR) is a leading cause of death and a major public health threat globally. Without appropriate interventions, annual ABR-associated deaths have been projected to reach 10 million by 2050 worldwide. Hence, it is critical to develop novel therapeutic interventions that would be able to tackle ABR by targeting mainly the pathogenic microbes, while lessening harm to beneficial microbes. There is an increasing research interest in CRISPR-Cas (CC) systems owing to their potential in controlling and preventing horizontal gene transfer and spread of antibiotic resistance. In addition, CC systems offer several advantages, including high efficiency, rapid turnaround time, low cost, and easy design, which allow these systems to effectively and precisely target antibiotic-resistant bacteria. CRISPR-based gene therapy offers numerous benefits; however, the major limitation in clinical translation is the safe and effective delivery of CRISPR components to target organs or cells, thus hindering its potential in therapeutic interventions. Nanocarriers (NCs) can help the CC systems to overcome their off-target effects by precisely delivering the systems to the target cells. NCs can also be engineered for target site release, payload protection, and high specificity, which can further ensure delivery of the components of CC in the target cells or regions without harming surrounding tissues. This review summarizes the principles and mechanisms of CC systems, highlights their applications against antibiotic-resistant bacteria, and discusses emerging nanocarrier-based delivery strategies that may enhance the clinical utility of CRISPR-Cas technologies in managing ABR.

Objective: This study aimed to investigate how empagliflozin alleviates renal injury in diabetic nephropathy with hyperuricemia by activating AMPK and regulating autophagy and apoptosis.

Methods: This study incorporated clinical renal tissue samples, diabetic-hyperuricemic mouse models, and HK-2 tubular epithelial cells to investigate the effects of empagliflozin on renal injury. Diabetic nephropathy with hyperuricemia was modeled using streptozotocin and high-fat diet in mice, while HK-2 cells were treated with high glucose and uric acid in vitro. Empagliflozin was administered with or without AMPK inhibition to assess its regulatory role.

Results: In renal tissues and HK-2 cells under high-glucose and high-uric acid conditions, Empagliflozin treatment increased LC3 expression and AMPK phosphorylation, and decreased cleaved caspase-3 levels. In diabetic-hyperuricemic mice, Empagliflozin also ameliorated fibrosis and reduced pathological damage. These effects were reversed upon co-treatment with Compound C, an AMPK inhibitor, which suppressed autophagy activation and restored apoptotic signaling. These results indicate that Empagliflozin exerts reno-protective effects by activating AMPK to promote autophagy and inhibit apoptosis, and that AMPK plays a central mechanistic role in mediating these effects.

Conclusion: Empagliflozin alleviates renal injury in diabetic nephropathy with hyperuricemia by activating AMPK, promoting autophagy, and inhibiting apoptosis, suggesting its potential therapeutic value in managing this complication.

Recently, concerns regarding the risk of drug eruption associated with the use of tetracyclines were raised by the United States Food and Drug Administration (U.S. FDA). Therefore, it is necessary to reevaluate this risk. This study aimed to quantify the signal of drug eruption associated with the use of tetracyclines. Also, the signal of drug eruption with the use of two other antimicrobial drugs-macrolides and fluoroquinolones-was investigated for comparison. A pharmacovigilance case/noncase study was conducted using the U.S. FDA Adverse Event Reporting System (FAERS). Reports of drug eruptions using the preferred term were retrieved from the database from 2020-2025 quarter 1. The associations between the risk of drug eruption and the three antibiotic classes were quantified using disproportionality analysis utilizing both Bayesian and traditional statistical analyses, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), empirical Bayes geometric mean (EBGM) and information component (IC). All three antibiotic classes were significantly associated with the risk of drug eruption. However, compared with fluoroquinolones and macrolides, tetracyclines were more strongly associated with drug eruption. Disproportionality analysis revealed that the ROR for tetracycline was 6.65 (95% confidence interval (CI), 4.00-11.09) in 2020; in 2024, it was 30.75 (95% CI, 24.46-38.67). For macrolides, the RORs were 2.16 (95% CI, 1.20-3.92) and 10.12 (95% CI, 7.16-14.31) in 2020 and 2024, respectively. The RORs for fluoroquinolones were 4.57 (95% CI, 3.20-6.52) in 2020 and 2.27 (95% CI, 1.31-3.92) in 2024. Males were predominant in the tetracycline group (74%), and females were predominant in the macrolide group (56%). Approximately 41% and 40% of patients in the fluoroquinolone and macrolide classes, respectively, were hospitalized. All three antibiotic classes were associated with the signal of drug eruption. The signal of drug eruption occurred across all age groups with all three antibiotics. Also, the signal has affected both males and females across the years studied. However, there is no specific pattern for the signal.

Prostate cancer (PCa) is among the most common malignancies and remains a leading cause of cancer-related mortality in men worldwide. One of the main drivers is the dysregulation of the downstream signalling machinery. The PI3K, AKT, and mTOR signalling pathways play a pivotal role in cellular sustenance, growth, metabolism, and proliferation. In prostate cancer this pathway is generally altered due to the mutation or deletion of the PTEN (phosphatase and tensin homolog) gene and unnecessary activities of some components of PI3K, AKT, or mTOR. Extracellular communication of the androgen receptor (AR) with a wide array of oncogenic signatures is a primary evasion mechanism of cancer therapy and metastasis. This review focuses on the structure and function of the PI3K/AKT/mTOR pathway to better understand its role in prostate tumor biology. Furthermore, current therapeutic strategies that combinatorically target individual components of this pathway, such as allosteric and ATP-competitive AKT inhibitors, isoform-selective PI3K inhibitors, first- and second-generation mTOR inhibitors, are under consideration. The study particularly focuses on the combined use of immunotherapy (checkpoint inhibitors), chemotherapy (docetaxel), and androgen deprivation therapy (ADT), which are designed to break through the resistance-generating mechanisms and increase clinical efficacy. Overall, the findings support the need to conduct comprehensive preclinical and clinical studies on these alternative treatment regimens, and the eventual goal is to develop new treatment options for prostate cancer. The evidence of the pathway-specific therapy approach for the treatment of prostate cancer in recent clinical trials still failed to give a conclusive result. The current discussion also investigates the emerging areas of focus and perfection of combination regimens. The combination of all these developments makes it clear that the PI3K/AKT/mTOR signalling pathway is a key strategic point for developing therapeutics.

In silico twins (ISTs) are emerging as a transformative paradigm in precision medicine, offering dynamic, high-fidelity representations of individual patients through real-time integration of multimodal data. In this work, we define an in silico twin (IST) as a high-fidelity, artificial intelligence(AI)-augmented computational replica of an individual's biological systems that integrates mechanistic modeling (e.g., PBPK, QSP) with patient-specific data streams to simulate, predict, and optimize therapeutic outcomes in real time. By combining AI, physiological and biomechanical modeling, and advanced simulation engines, these systems enable continuous monitoring, predictive diagnostics, and personalized treatment planning. Unlike conventional digital tools, ISTs provide iterative, adaptive simulations that evolve with patient states, fostering a shift from reactive to proactive healthcare. This review explores the technological foundations underpinning ISTs -including machine learning architectures, multi-scale physiological modeling, data integration, and cloud-edge infrastructure- and maps their clinical applications across the patient care continuum. We also distinguish ISTs from digital twins, virtual patients, and traditional computational models, emphasizing their unique contribution to decision support, drug development, and therapeutic optimization. As digital healthcare ecosystems mature, ISTs represent a crucial step toward simulation-driven, individualized medicine. Their continued development offers substantial potential for improving outcomes, accelerating discovery, and reshaping the clinical landscape. Uniquely, this review introduces a practical taxonomy of IST architectures, a verification and validation checklist for model credibility, and a deployment blueprint to guide their clinical translation and real-world adoption.

Sterile Injectable Products (SIPs) represent a critical class of pharmaceuticals that frequently face shortages and ultimately compromise patient care. Disruptions within the pharmaceutical supply chain are significant factors contributing to these shortages. This study aimed to investigate the causes and impacts of SIPs shortages in Saudi Arabia, with the central hypothesis that pharmaceutical supply chain disruptions are the primary drivers of these shortages and that they negatively affect patient outcomes. A cross-sectional questionnaire was administered to two key stakeholder groups: supply chain management (SCM) personnel and healthcare professionals (HCPs). A total of 350 responses were collected and statistically analyzed. Our findings demonstrate a strong consensus among SCM respondents, with 73% agreeing that supply chain disruptions significantly affect SIPs availability. Poor demand forecasting and limited sourcing capabilities were identified as the primary contributing factors. From the perspective of HCPs, over 65% indicated that SIP shortages adversely impacted patient care, resulting in treatment delays, extended hospital stays, and increased healthcare costs. Additionally, many respondents reported that staff time is often wasted in the search for alternative therapies, which may also be of short supply. Interestingly, more than 70% of respondents from both groups expressed robust support for the adoption of advanced technologies such as artificial intelligence (AI) and machine learning (ML) to enhance forecasting and inventory management. Taken together, these findings underscore the urgent need for integrated strategies including proactive forecasting, sustainable inventory management, expanded local manufacturing, and AI-driven tools to strengthen the resilience of the SIP supply chain in Saudi Arabia and beyond.

Diabetes is a major cause of cardiovascular complications, accounting for nearly 70% of diabetes-related deaths. In a previous study, several novel cyclic-imide compounds were evaluated as hypoglycemic agents, and one compound, 5e, showed promising effects in controlling blood glucose in a type 1 diabetes (T1D) rat model. The purpose of this investigation was to clarify the processes by which 5e reduces hyperglycemia through tolerance tests, metabolic hormone assessment, and evaluation of anti-apoptotic effects on pancreatic tissue. Forty male Sprague-Dawley rats allocated to five categories: control, diabetic, diabetic administered glibenclamide (10 mg/kg), and diabetic treated with 5e at two doses (10 and 15 mg/kg). Over two weeks, blood glucose and tolerance tests were performed, and on day 15, blood and pancreatic tissues were collected for analysis of insulin, glucagon, lipase, and amylase, along with histological evaluation. Both 5e and glibenclamide reduced blood glucose by approximately 36%, while the higher dose of 5e lowered glycemia by 50%. All treated groups showed improved glycemic control in tolerance tests, with the 15 mg/kg 5e group demonstrating the greatest glucose clearance and insulin sensitivity. Compound 5e modulated insulin, glucagon, and lipase levels, indicating metabolic improvement, with the strongest effects at the higher dose. Histological analysis revealed enhanced islet morphology and significantly reduced pancreatic apoptosis, particularly in the higher dose 5e group. These findings suggest that 5e improves glycemic control and exerts protective effects on pancreatic structure and function in T1D rats, highlighting its potential as a therapeutic agent and warranting further pharmacological investigation.

Type 2 diabetes mellitus (T2D) affects over 460 million people worldwide and profoundly diminishes their quality of life. Its onset is driven by obesity, sedentary behavior, and genetic predisposition, leading to insulin resistance, progressive beta-cell dysfunction, and complications such as cardiovascular disease and nonalcoholic fatty liver disease (NAFLD). Effective management requires therapies that extend beyond glycemic control to address these interconnected risks. Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has demonstrated remarkable efficacy in clinical studies, particularly the SURPASS trials. It achieved a reduction in HbA1c of up to 2.3% and body weight losses exceeding 22% over 72 weeks. Additional benefits include improvement in blood pressure, lipid levels, and inflammatory markers, with potential benefit in NAFLD. Pharmacists play a vital role in translating these benefits into practice by counselling patients on safe use, managing adverse effects, and supporting adherence. Their involvement bridges the gap between trial evidence and real-world outcomes. This review examines the dual mechanism of tirzepatide, its broader metabolic effects, and the critical role of pharmacists in optimizing its use. With pharmacist-led care, tirzepatide has the potential to transform diabetes management across diverse populations.

Cervical cancer is one of the major and serious risks to women. Salidroside, a natural compound, shows promise in treating cervical cancer. However, its specific molecular mechanisms remain unclear and require further investigation. This study aimed to elucidate the pharmacological activity of salidroside and its underlying molecular mechanisms in cervical cancer, employing network pharmacology, molecular docking, and experimental approaches. Genes associated with cervical cancer were gathered from The Cancer Genome Atlas Program (TCGA), Gene Expression Omnibus (GEO) databases, and network pharmacology. Furthermore, we integrated the drug targets with the disease targets pertinent to cervical cancer, subsequently conducting analyses utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) to explain the pharmacological pathways through which salidroside operates in the milieu of cervical cancer. Survival analysis was performed to screen the core therapeutic targets of salidroside. Salidroside constituents and hub genes binding affinity were assessed by molecular docking studies. In vitro experiments, including Cell Counting Kit-8 (CCK-8) assays, flow cytometry, and western blotting, were performed to further validate the computational findings. Study findings revealed that salidroside inhibited the cervical cancer cell progression, reduced viability, and induced apoptosis.Ten target genes related to salidroside's anti-cancer effects have been identified. Survival analysis revealed that MMP1 and MMP3 exhibited the highest binding capability among all the target genes. Molecular docking indicated that the salidroside's active entities showed a strong binding tendency with the MMP1 and MMP3 genes. Western blot analysis revealed that it significantly reduced the expression of MMP-1 and MMP-3. In Vitro studies suggested that suppressing MMP1 and MMP3 genes might be responsible for salidroside's anticancer effects.