Saudi Pharmaceutical Journal最新文献

1H - 2,3,3a,8b-tetrahydrocyclopenta[b]benzofuran, known as Rocaglamide (RocA) has gained recognition for its potential as a plant-derived therapeutic agent in cancer treatment. This study evaluates the impact of RocA on MDA-MB-231 human breast adenocarcinoma cells. Rocaglamide's effect was comprehensively evaluated through cell culture and molecular approaches with a series of experimental procedures. Cell viability was assessed using the MTT assay which determined the compound's cytotoxic effects. Following this, apoptosis induction in cancer cells was examined through Annexin V-FITC staining and flow cytometric analysis, providing insight into Rocaglamide's apoptotic mechanism of action. Additionally, the proliferation of cancer cells was evaluated by Propidium Iodide (PI) staining, elucidating Rocaglamide's antiproliferative effects on breast cancer cells. Furthermore, protein expression levels were analyzed using the Human XL Oncology Array Kit, shedding light on Rocaglamide's molecular targets and effect on various signaling pathways as demonstrated by how rocaglamide particularly attenuate the activity of proteins crucial for angiogenesis and tumor progression. MTT assay revealed a time-dependent decrease in cell viability. When treating MDA-MB-231 breast cancer cells with increasing concentrations of RocA, significant morphological changes were observed. Wound healing assay to evaluate the impact of RocA on cell migration indicated the induction of slight apoptosis in breast cancer cells. Flow cytometry-based apoptosis assay revealed that the total cell death in treated cells reached around 15%, compared to 7.9% in the untreated group. The expression of key oncogenic proteins after treatment of MDA-MB-231 cells with RocA indicated a noticeable reduction of VEGFA, AXL, and PAI-1 when compared to the untreated control. However, SNAIL1 and Endoglin increased significantly relative to untreated controls. Collectively, the findings demonstrate Rocaglamide's potential as a therapeutic agent for breast cancer and offer valuable insights into its mechanisms of action.

Semiaquilegiae Radix demonstrates significant anti-inflammatory potential. However, comprehensive investigations into its anti-inflammatory effects remain sparse. This study seeks to systematically explore the chemical composition of Semiaquilegiae Radix and its underlying anti-inflammatory mechanisms utilizing Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS), network pharmacology, and molecular docking techniques. Initially, the chemical constituents of Semiaquilegiae Radix were identified and characterized via UHPLC-Q-TOF-MS/MS. Subsequently, the relevant targets were predicted and screened through databases such as PharmMapper and SwissTargetPrediction, in conjunction with protein-protein interaction (PPI) network analysis. Next, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genome (KEGG) enrichment analyses were performed using the Metascape platform. Eventually, molecular docking was carried out via AutoDock Vina and visualized results with PyMOL. From Semiaquilegiae Radix, 19 active compounds were identified, 18 showing activity against inflammation-related targets. 510 drug targets were identified, 188 of which intersected with inflammation-related targets and PPI network analysis pinpointed six core potential targets. These overlapping targets are involved in several critical signaling pathways, including the AGE-RAGE signaling pathway in diabetic complications and pathways related to lipid metabolism and atherosclerosis. Molecular docking showed the primary seven active compounds can effectively bind to key targets. This study elucidates the chemical constituents of Semiaquilegiae Radix and highlights its multi-compound, multi-target, and multi-pathway mechanisms of action against inflammation. This research method provides a robust theoretical foundation for further experimental validation and the development of novel anti-inflammatory therapies.

Nowadays, the use of unfractionated low molecular weight heparins through intravenous and subcutaneous routes has been limited by several delivery challenges. These include pharmacological activity fluctuations, bleeding issues, and numerous manufacturing restrictions. To address these issues, several efforts have been taken to find alternative routes for this medication. Unfortunately, the past and recent reviews were mainly explored the oral dosage forms of heparin and the other possible indications in practice. This review focuses on emerging efficient and non-invasive heparin options such as buccal, sublingual, oral, rectal and vaginal, transdermal, pulmonary and nasal. To do that, the past and recent studies were categorized into three main groups: (1) Conventional invasive heparin delivery methods; (2) Novel non-invasive heparin delivery systems; and (3) Heparin-based nanoparticles. The main challenges to use non-invasive heparin delivery systems were found to be negative charge and high molecular weight of heparin. Besides, the biological, biophysical, and pharmacological constraints could also limit the benefits of these alternatives. To overcome these issues, the following mechanisms have been used to enhance the delivery of heparin through several routes: (1) Improvement of cell-membrane penetration, (2) Changing of the tight-junctions, (3) Promoting the lipophilicity and (4) Preserving against acidic pH of the stomach. The applicability of alternative delivery options for heparin was mainly affected by overcoming the main penetration barriers. Nanoparticles were found to be effective in increasing the permeability, absorption, bioavailability and bioactivity of heparin.

Background: Patient education materials (PEMs) are essential for enhancing health literacy and supporting informed decision-making. The Patient Education Materials Assessment Tool (PEMAT) is a widely recognized instrument for evaluating the understandability and actionability of PEMs. However, the absence of an Arabic version of PEMAT has restricted its applicability among Arabic-speaking populations. This study aims to translate and validate the Arabic versions of PEMAT-P (for print materials) and PEMAT-AV (for audiovisual materials).

Methods: A systematic translation and cultural adaptation process was conducted following established guidelines. This included forward translation, back-translation, expert review, and cognitive debriefing. A total of 42 participants were recruited to evaluate the reliability of the Arabic PEMAT versions. Test-retest reliability was assessed using the Intraclass Correlation Coefficient (ICC), and internal consistency was evaluated with Cronbach's Alpha. Pearson correlation and the Standard Error of Measurement (SEM) were also calculated.

Results: The Arabic PEMAT-P demonstrated moderate reliability in the understandability domain (ICC = 0.69, Cronbach's Alpha = 0.82) and strong reliability in the actionability domain (ICC = 0.74, Cronbach's Alpha = 0.85). The Arabic PEMAT-AV showed substantial reliability in the understandability domain (ICC = 0.77, Cronbach's Alpha = 0.87), but moderate reliability in the actionability domain (ICC = 0.64, Cronbach's Alpha = 0.78). Minimal discrepancies were observed between the original and back-translated versions, supporting the tool's linguistic and conceptual equivalence.

Conclusion: The Arabic-translated PEMAT-P and PEMAT-AV are reliable tools for evaluating patient education materials. Their implementation can enhance health literacy and patient engagement in Arabic-speaking populations. Future research should focus on improving the actionability of audiovisual materials.

Background: Immune evasion in non-small cell lung cancer (NSCLC) is largely mediated by programmed death-ligand 1 (PD-L1), which is upregulated by interferon-gamma (IFN-γ)-induced STAT1 activation. Targeting this pathway may improve immunotherapy outcomes. Curcumin, a natural polyphenol, has been reported to modulate various oncogenic signaling pathways, but its role in inhibiting IFN-γ-driven PD-L1 expression in NSCLC remains unclear.

Methodology: The NSCLC cell line A549 were treated with curcumin (50 µM) for 2 h before stimulation with IFN-γ (500 U/ml). Western blot, qRT-PCR, and immunofluorescence microscopy were used to evaluate STAT1 phosphorylation, PD-L1 expression, and the localization of phosphorylated STAT1 (p-STAT1). The expression of interferon-stimulated genes (ISGs), including SOCS1 and ISG15, was also examined. Additionally, the Resazurin assay was performed to assess cell viability.

Results: IFN-γ significantly induced STAT1 phosphorylation, leading to a time-dependent upregulation of PD-L1 expression. Immunofluorescence confirmed that p-STAT1 is translocated to nucleus. Curcumin treatment inhibited STAT1 phosphorylation by 68% (p < 0.001), leading to a marked reduction in PD-L1 expression. Moreover, curcumin suppressed IFN-γ-induced SOCS1 (63%) and ISG15 (54%) expressions, indicating a broader effect on STAT1-mediated immune evasion. Finally, curcumin enhanced IFN-γ-mediated growth inhibition, reducing cell viability by 47% at 48 h (p < 0.01).

Conclusion: Curcumin effectively inhibits IFN-γ-induced STAT1 phosphorylation and PD-L1 expression, downregulates ISGs, and enhances IFN-γ-mediated tumor suppression. These findings suggest that curcumin may serve as a therapeutic adjuvant in NSCLC, potentially improving immune checkpoint inhibitor (ICI) efficacy.

Competency-based education (CBE) approaches in pharmacy education has drawn increasing attention. However, the adoption of CBE in Continuing Professional Development (CPD) design especially on asthma care remains underreported. This study aimed to assess the feasibility of a CBE-informed CPD programme designed for improving asthma care for children. A CPD programme guided by the CBE approach comprising of 4 sessions of didactic lectures and interactive inhaler workshops was implemented between April 6 to 27 2024 in Macao. An evaluation tool set to test the pre- and post-lecture knowledge assessment, inhaler technique, impact on practice, and overall satisfaction was completed by the participants. About 15% of registered pharmacists involved in direct-to-patient-care attended the CPD programme (n = 88), of whom 81 participated in the study. Significant improvement in short-term knowledge was recorded when comparing the overall proportion of correct answers pre- and post-training (50.9% vs 66.5%, p < 0.05). By the end of the inhaler workshop, the proportion of participants performed all inhaler steps correctly were 88.7% for metered dose inhaler, 80.8% for turbuhaler, 76.0% for accuhaler, and 71.2% for ellipta. Participants self-reported an enhanced level of confidence, willingness, and professional recognition in the provision of pharmaceutical care for the patients upon completion of the CPD. Over 96% of the participants were satisfied with the overall design of the CPD programme. The study demonstrates that the CBE-informed CPD programme is feasible and can improve pharmacist's competence in asthma management. The CBE approach is worth further adoption to improve the performance of CPD programme for pharmacists.

Second-generation antipsychotics (SGAs) have been developed as an alternative to the first-generation antipsychotics due to their fewer side effects. However, clinical case reports suggested a connection between SGAs and ileus. The aim of this study is to explore the links between ileus and SGAs via a pharmacovigilance analysis. Adverse event reports from January 1st, 2014 to December 31st, 2023 were collected from the U.S. Food and Drug Administration Adverse Event Reporting System database. The demographic characteristics of cases were summarized to perform descriptive analysis. The reaction outcomes, actions taken with the drug, and onset time of ileus, were also extracted and analyzed. In disproportionality analysis, the algorithms of reporting odds ratio (ROR) and information component (IC) were applied for ileus risk signal detection. A total of 419 cases with SGAs-related ileus were obtained from the database. The median age for patients was 58 years (range 6 ~ 94) and the median onset time of ileus was 40 days (range 0 ~ 6070). After excluding reports with incomplete data, a total of 219 cases were identified in reaction outcomes and a total of 179 cases were included in the analysis of actions taken with the drug. A majority of patients reached recovered state (n = 119, 54.34%) in reaction outcomes, and most patients received drug withdrawn (n = 120, 67.04%) in actions taken with the drug. Clozapine showed the strongest risk signal of ileus (n = 131, ROR₀₂₅ = 2.77, IC₀₂₅ = 1.42), whereas this signal was not significant in risperidone (n = 29, ROR₀₂₅ = 0.68, IC₀₂₅ = -0.38). In summary, our data suggested that SGAs administration increased the risk of ileus. These results would provide valuable insight into the prognosis and safe use of SGAs.

Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has emerged as a promising therapeutic agent due to its diverse pharmacological properties, including potent anti-inflammatory, neuroprotective, and immunomodulatory effects. CBD modulates immune responses, including the regulation of T cell activity, induction of macrophage apoptosis, suppression of pro-inflammatory cytokines, and modulation of signaling pathways involved in inflammation and immune homeostasis. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases to identify relevant preclinical and clinical studies on CBD's immunomodulatory effects. Preclinical and clinical studies demonstrate its efficacy in treating autoimmune diseases such as Type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease, along with its potential in neuropathic pain and cancer therapy. Recent advancements in nanotechnology-based delivery systems have further enhanced CBD's therapeutic potential by improving its solubility, bioavailability, and targeted delivery, enabling innovative approaches for wound healing, inflammation management, and cancer treatment. However, challenges such as variability in immune responses, limited long-term safety data, and potential drug-drug interactions persist. This review comprehensively examines CBD's pharmacokinetics, pharmacodynamics, and immunomodulatory mechanisms, highlighting its clinical potential, existing limitations, and future directions in advancing its integration into precision medicine and immune regulation.

In an attempt to rationalize the search for new potential Chemotherapeutic agents, a new series of 2-anilinobenzimidazol derivatives with CDK activity have been synthesized. The newly synthesized compounds have been assessed for their cytotoxic effects and CDK activity. These presented compounds showed strong inhibition of cell proliferation in various solid cancer cell lines, suggesting a promising approach for treating malignant tumors. Compounds 4 g, 4j, 4 m, and 4q displayed remarkably strong anticancer potencies against HepG2 cells, with IC₅₀ of 7.59, 8.54, 3.56 and 5.88 µM, respectively, compared to the positive control, DOX (IC₅₀ = 4.50 µM). while compound 4 m, and 4q had the highest anticancer activity against HeLa cells, with an IC₅₀ of 6.39 and 9.71 µM, respectively, compared to the positive control DOX (IC₅₀ = 5.57 µM). On the other hand, comparison of IC₅₀ values against MCF-7 cells revealed that compounds 4 g, 4 m, and 4q showed significant anticancer potency with IC₅₀ of 5.08, 2.18 and 8.19 µM, respectively compared to that of the positive control DOX (IC₅₀ = 4.17 µM). Moreover, compound 4 m and 4q were the most potent CDK9 and CDK12 inhibitors. Furthermore, a molecular docking simulation were performed to explore the ability of compounds 4 m to adopt the common binding pattern of CDK9 and CDK12/T1 inhibitors. In silico ADMET results showed that all compounds have favourable drug-like properties since they met Lipinski's rule of five criteria. Overall, the synthesized anilinopyrimidine derivatives exhibit significant potential as chemotherapeutic agents.

The current study investigated how students at King Saud University's College of Pharmacy perceive the effectiveness of the Academic Advising Unit and their experiences with academic advisors. Our study examined responses gathered from 164 participants, including 97 female and 67 male students, representing various academic years (2^nd to 6^th). The survey assessed several key aspects, including the availability of advisors, their knowledge and expertise, communication effectiveness, level of support and encouragement, ability to assist with goal setting, integration of feedback, accessibility of resources, and overall student satisfaction. The results of our study revealed that while the majority of students in the College of Pharmacy expressed satisfaction with and support for academic advising, a notable proportion of students exhibited ambivalence or dissatisfaction with the advising services. Regarding advisor availability, 57% of students expressed satisfaction, while 32% were indifferent, reflecting unmet needs. Similarly, in terms of communication, 62% were satisfied, but 28% were neutral, again suggesting an inconsistency in advisor responses. A similar trend was observed concerning advisor knowledge and expertise, with 58% satisfied and 31% neutral. Specifically, when questioned about guidance on research and extracurricular activities, only 48% expressed satisfaction. Overall, 61% felt that communication was beneficial in resolving their issues. Students were below-average in their satisfaction with the support provided during challenging times. Findings suggest that an average level of academic advising functioning and emphasized the need for more individualized and consistent academic advising to better meet student expectations.