Search Results (16,037)

Background/Objectives: Triple-negative breast cancer (TNBC) lacks targeted therapies and has a poor prognosis. Wild ginseng (Panax ginseng) is traditionally valued for its medicinal properties, but its scarcity limits therapeutic application. Adventitious root culture technology provides a sustainable source of wild ginseng-derived bioactive compounds. This study investigated the anticancer effects of wild ginseng adventitious root extract (WGAR) on MDA-MB-231 TNBC cells and elucidated the underlying molecular mechanisms. Methods: WGAR was prepared from cultured adventitious roots of 100-year-old wild ginseng, and its chemical composition was analyzed by LC-MS/MS. Anticancer effects were evaluated using MTT assay, acridine orange/propidium iodide (AO/PI) staining, Matrigel invasion assay, Western blot analysis, and proteome profiler array. Molecular docking was performed to predict interactions between WGAR constituents and target proteins poly (ADP-ribose) polymerase (PARP)-1 and β-catenin. Results: LC-MS/MS analysis tentatively identified 17 compounds, including ginsenosides (Rg3, Rh1, Rf) and terpenoids (ursolic acid). WGAR reduced cell viability with an IC50 of 79 μg/mL at 48 h, inducing 51.2% cell death. WGAR activated the intrinsic apoptotic pathway through sequential caspase-9 and caspase-3 activation, followed by PARP cleavage, and was associated with changes in epithelial–mesenchymal transition (EMT)-related markers (reduced N-cadherin, Slug, and β-catenin) alongside decreased inhibitory Ser9 phosphorylation of GSK-3β. Proteome array analysis revealed suppression of ECM remodeling proteins (tenascin C, u-PA) and inflammatory mediators (IL-6, CXCL8). Molecular docking predicted that selected WGAR constituents, particularly terpenoid-type compounds, may potentially interact with PARP-1 and β-catenin; however, these in silico findings are hypothesis-generating and require experimental validation. Conclusions: WGAR exerts multi-target anticancer effects on TNBC cells through apoptosis induction and EMT suppression associated with modulation of GSK-3β/β-catenin signaling, suggesting its potential as a source of therapeutic agents for TNBC. Full article

In this study, we designed and synthesized 11 N-aryl-S-aryl-2-mercaptoacetamide derivatives as new tyrosinase inhibitors (TYRIs). Experiments with pyrocatechol violet confirmed that four derivatives showed copper-chelating abilities similar to or superior to those of well-known copper-chelating TYRIs like kojic acid (KA) and N-phenylthiourea. However, these four derivatives showed little or no inhibition of mushroom TYR (mTYR) activity and melanin production in B16F10 cells. Instead, derivatives with low copper chelation ability exhibited potent inhibitory effects on mTYR activity and melanin production in B16F10 cells. These findings suggest that the results of metal ion chelation by inhibitors in an enzyme-free environment do not always match those under metalloenzyme conditions because of the interactions between inhibitors and amino acid residues around the metalloenzyme active site. Owing to their favorable interactions with amino acids in the mTYR active site, two of the derivatives inhibited mTYR more effectively than KA. Probably for the same reason, three derivatives inhibited B16F10 cellular TYR more effectively than KA, and one derivative inhibited pigment production in zebrafish larvae much better than KA. This last derivative, which effectively exhibits TYR-inhibitory activity and suppresses melanin production in several species, is considered a promising compound for use as a TYRI in various fields. Full article

(1) Background: We aimed to determine rates of bacteremia and multidrug resistance (MDR) bacteremia and associated risk factors among neonates receiving parenteral nutrition (PN). (2) Methods: This is a multicenter study conducted in three neonatal intensive care units in Saudi Arabia, including 414 neonates who received PN. Associations were assessed using Chi-square or Fisher’s Exact tests when applicable and logistic regression analyses were conducted to determine factors predicting outcomes. Odds ratios with their 95% confidence intervals were computed, and a p value < 0.05 was considered statistically significant. (3) Results: PN was started within the first 10 days of life in 74.4% of cases. Fat emulsion was administered to 38.9% of the newborns. Blood cultures were positive in 24.9% of patients. Among the positive cultures, 4.9% were confirmed to have MDR bacteria. The mortality rate following bacteremia was 7.8%. The use of fat emulsion (p = 0.003), birth weight < 700 g (p < 0.001), and a gestational age within 27 weeks (p < 0.001) predicted bacteremia. (4) Conclusions: There was an association between the PN and bacteremia. Significant predictors of bacteremia were the use of fat emulsion, birth weight < 700 g, and a gestational age within 27 weeks. Full article

The simultaneous HPLC method for quantifying Quercetin (Que), Thymoquinone (Thy), and Pterostilbene (Pte) aims at the precise measurement of these polyphenols alone or in complex mixtures, targeting their therapeutic potential in disorders such as diabetes and epilepsy. The method focuses on quantifying Que, Thy, and Pte, utilizing optimized reversed-phase HPLC conditions as per ICH Q2(R1) standards. Key validation aspects include linearity, specificity, precision, and accuracy, ensuring compliance for quality control in nanomedicine and nutraceuticals, and the method’s applications support pharmacokinetic studies and stability testing, contributing to personalized medicine and addressing pharmaco-resistance. The HPLC method development and validation were performed on a phenyl column using the mobile phase consisting of solvent A (0.1% orthophosphoric acid in HPLC water) and solvent B (acetonitrile) at a ratio of 55:45 in an isocratic elution mode at a flow rate of 1 mL/min and at a column temperature of 35 °C. Ultraviolet detection was measured at 254 nm. Moreover, the method was validated for accuracy, precision, linearity, specificity, and sensitivity. The retention time for tested Que, Thy, and Pte was observed at 4.15 min, 8.70 min, and 10.75 min, respectively. Limits of detection for Que, Thy, and Pte were 1.55 μg/mL, 2.40 μg/mL, and 70.79 µg/mL, whereas limits of quantification were 4.69 μg/mL, 7.28 μg/mL, and 214.52 µg/mL, respectively. Linearity and correlation coefficients for Que, Thy, and Pte were found in the range of 50–250 μg/mL (0.9999), 50–250 μg/mL (0.9999), and 620–3100 μg/mL (0.9996), respectively. A reasonable level of accuracy was indicated by the tested method suggesting extremely high recovery levels (98–102%). The separation of tested compounds was achieved within 11 min. The developed and validated RP-HPLC–UV method was successfully applied for the identification and quantification of Que, Thy, and Pte for their combined estimation in complex formulations. From the validation study, it was found that the tested method is specific, accurate, precise, reliable, and reproducible. Full article

Parenteral nutrition (PN) is essential for patients who are unable to tolerate oral or enteral feeding, providing them with necessary nutrients intravenously, including dextrose, amino acids, electrolytes, vitamins, trace elements, and lipid emulsions. Clinical pharmacists (CPs) play a critical role in PN management by ensuring proper formulation, monitoring therapy, preventing complications, and optimizing patient outcomes. In Saudi Arabia, limited literature exists on CPs’ involvement in total parenteral nutrition (TPN) administration, health information management (HIM) systems, and pharmacist staffing ratios. This paper examines the evolving role of CPs in PN management, addressing key challenges such as the optimal patient-to-CP ratio, the impact of HIM systems on PN prescribing, and the advantages and limitations of centralized versus decentralized PN prescription models. It highlights the need for standardized staffing levels, structured pharmacist training, and improved HIM integration to enhance workflow efficiency and prescribing accuracy. Additionally, the study examines how the adoption of advanced HIM systems can streamline documentation, reduce prescribing errors, and enhance interdisciplinary collaboration. This paper provides a framework for optimizing PN delivery, enhancing healthcare quality, and strengthening CPs’ contributions to nutrition support by addressing these factors. Implementing these recommendations will improve patient outcomes and establish a more efficient PN management system in Saudi Arabia, reinforcing the vital role of CPs in multidisciplinary care. Full article

Background and Aim: Large language models (LLMs) demonstrate significant potential in assisting with medical image interpretation. However, the diagnostic accuracy of general-purpose LLMs on image-based internal medicine cases and the added value of brief clinical history remain unclear. This study evaluated three general-purpose LLMs (ChatGPT, Gemini, and DeepSeek) on expert-curated cases to quantify diagnostic accuracy with image-only input versus image plus brief clinical context. Methods: We conducted a comparative evaluation using 138 expert-curated cases from Harrison’s Visual Case Challenge. Each case was presented to the models in two distinct phases: Phase 1 (image only) and Phase 2 (image plus a brief clinical history). The primary endpoint was top-1 diagnostic accuracy for the textbook diagnosis, comparing performance with versus without a brief clinical history. Secondary/Exploratory analyses compared models and assessed agreement between model-generated differential lists and the textbook differential. Statistical analysis included Wilson 95% confidence intervals, McNemar’s tests, Cochran’s Q with Benjamini–Hochberg correction, and Wilcoxon signed-rank tests. Results: The inclusion of clinical history substantially improved diagnostic accuracy for all models. ChatGPT’s accuracy increased from 50.7% in Phase 1 to 80.4% in Phase 2. Gemini’s accuracy improved from 39.9% to 72.5%, and DeepSeek’s accuracy rose from 30.4% to 75.4%. In Phase 2, diagnostic accuracy reached at least 65% across most disease nature and organ system categories. However, agreement with the reference differential diagnoses remained modest, with average overlap rates of 6.99% for ChatGPT, 36.39% for Gemini, and 32.74% for DeepSeek. Conclusions: The provision of brief clinical history significantly enhances the diagnostic accuracy of large language models on visual internal medicine cases. In this benchmark, performance differences between models were smaller in Phase 2 than in Phase 1. While diagnostic precision improves markedly, the models’ ability to generate comprehensive differential diagnoses that align with expert consensus is still limited. These findings underscore the utility of context-aware, multimodal LLMs for educational support and structured diagnostic practice in supervised settings while also highlighting the need for more sophisticated, semantics-sensitive benchmarks for evaluating diagnostic reasoning. Full article

2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the representative CHI3L1 inhibitor, has interesting biological activities, including anti-cancer and anti-inflammatory effects on neuroinflammation. Following our hit-to-lead program, we report the most active novel derivative, named CBJL-025, 2-((6,7-dimethoxy-4-oxo-3-(4-(trifluoromethyl)phenethyl)-3,4-dihydroquinazolin-2-yl)thio)-N-(4-ethylphenyl)butanamide. The title compound, CBJL-025, was successfully synthesized by S-alkylation of the p-trifluoromethyl phenethyl group possessing quinazoline and the corresponding bromide. The structure of CBJL-025 was confirmed by ¹H and ¹³C nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). Full article

Objectives: Personalized medicine is gaining rapid attention over the current drug prescription approach of ‘one-size-fits-all’. Three-dimensional (3D) printing is one such product development technique that has the potential to transform the pharmaceutical and biomedical sectors. Methods: To establish the future of 3D printing in mainstream pharmacy practice, initially, pharmaceutical preclinical and clinical scientific databases (peer-reviewed articles, patents, and marketed products) over the past 10 years were critically scrutinized. Additionally, to provide context, we developed a hypothetical case study illustrating the capabilities of the 3D printing super-compounding pharmacy in personalized patient care, emphasizing the critical role of pharmacists in this process. Results: Acknowledging the potential of 3D printing in pharmacy practice, this review effectively summarizes the advances and opportunities of pharmaceutically feasible 3D printing methods, as well as the challenges in translating this technology into a future super-compounding pharmacy facility. Furthermore, the review highlights the promising capabilities of such pharmaceutical 3D printers in enabling on-site printing of 3D medicines tailored to individual needs, which may range from dose adjustments to multidrug single tablets (polypills). Conclusions: We believe that 3D printing technology has the potential to revolutionize precision and personalized medication approaches in pharmacy practice, which will significantly benefit patient healthcare outcomes. Additionally, the adoption of such technology in pharmacies will lead to a reinvention of the role of pharmacists, thereby creating more job opportunities. Ultimately, 3D printing will create a new paradigm of super-compounding pharmacy practice, providing a new sense of excitement for those looking to enter the pharmacy profession. Full article

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. CVDs are associated with multiple factors, including oxidative stress, mediated endothelial dysfunction, vascular inflammation, and atherothrombosis. Although traditional antioxidant supplementation (such as vitamins C, E, and β-carotene) has shown promising results in rigorous animal model studies, it has consistently failed to demonstrate clinical benefit in most human trials. Consequently, there is a substantial unmet need for novel paradigms involving mechanistically and biologically relevant pharmaceutical-grade antioxidant therapies (“next-generation antioxidants”). Rapid advancements in redox biology, nanotechnology, genetic modulation of redox processes, and metabolic regulation have enabled the development of new antioxidant therapeutics, including mitochondrial-targeted agents, NADPH oxidase (NOX) inhibitors, selenoprotein and Nrf2 activators, engineered nanoparticles, catalytic antioxidants, and RNA-based and gene-editing strategies. These interventions have the potential to modulate specific oxidative pathways that contribute to CVD pathogenesis. This review provides a comprehensive assessment of current oxidative stress–modulating modalities and their potential to inform personalized cardiovascular prevention and treatment strategies. Full article

Background/Objectives: Wound infections caused by multidrug-resistant Gram-negative bacteria, such as Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii, pose a major clinical challenge. This study evaluated the interactions between gamma-polyglutamic acid (γ-PGA), cefiderocol, and silver nanoparticles (AgNPs) within multilayer wound dressing configurations. The primary goal was to clarify the dual role of γ-PGA as a healing promoter and a potential protector of bacterial cells against antimicrobial agents. Methods: Multilayer dressing models were assembled in 96-well plates to simulate vertical stratification of antimicrobial layers4. Bacterial viability was assessed through relative OD₆₀₀ measurements following incubation with varying concentrations and spatial arrangements of cefiderocol, AgNPs, and γ-PGA. Data were analyzed using generalized linear modeling (GLM) with a gamma distribution and random forest regression to determine the relative importance of each factor in modulating bacterial survival. Results: γ-PGA concentration emerged as the dominant factor influencing bacterial viability, accounting for nearly 100% of variable importance in random forest analysis. Despite high antimicrobial pressure from cefiderocol and AgNPs, bacterial viability stabilized at approximately 40% in the presence of γ-PGA. The vertical positioning of γ-PGA significantly impacted survival; direct physical contact between the polymer and bacteria, particularly at high concentrations, enhanced bacterial persistence in P. aeruginosa and E. coli. Cefiderocol showed strain-specific potency, while AgNPs provided consistent growth inhibition. Conclusions: γ-PGA plays a paradoxical role in wound care by providing moisture retention while simultaneously acting as a cytoprotective agent that reduces antimicrobial efficacy, likely by facilitating biofilm formation. These findings underscore the necessity of optimizing the spatial layering and concentration of biopolymers in advanced dressings. Strategic design is crucial to balance regenerative benefits with maximal antimicrobial control to improve clinical outcomes in chronic wound management. Full article

Background/Objectives: The rhizome of Gastrodia elata Blume (Tianma) is a functional food with medicinal value in China, used to improve the health of the central nervous system and reported to exhibit anti-cellular senescent activity. P-hydroxybenzaldehyde (P-HBA) is a key aromatic compound isolated from Tianma; however, its potential to mitigate cellular senescence remains unclear. Methods: We employed ultra-performance liquid chromatography-mass spectrometry to identify the chemical characterization of Tianma extract. Cell viability assay, senescence-associated-β-galactosidase (SA-β-Gal) assay, and immunofluorescence staining and autophagy analysis were used to evaluate the anti-senescent activity of P-HBA and other Tianma components. Results: Our findings demonstrate that Tianma methanol extract (TME) and P-HBA significantly reduce cellular senescent inducer hydroxyurea (HU)-induced DNA damage, SA-β-Gal activity increase, and autophagic dysfunction in human SH-SY5Y cells. Notably, an autophagy inhibitor, chloroquine, can reduce anti-cellular senescent activity of P-HBA. Conclusions: These results suggest that P-HBA exhibits the effect of reducing cellular senescent phenotypes, and its effect is achieved by enhancing autophagy. Full article

Cardiovascular disease (CVD) is increasingly recognized as a significant comorbidity in people living with HIV (PWH), contributing to increased morbidity and mortality. Epidemiological studies indicate that PWH have a 1.2–2-fold higher risk of myocardial infarction (MI) and other CVD events compared to HIV-negative individuals. While the mechanisms underlying HIV-associated CVD are not fully understood, they are likely to include a combination of cardiovascular-related adverse effects of HIV medications, vascular dysfunction caused by HIV-induced monocyte activation, and cytokine secretion, in addition to existing comorbidities and lifestyle choices. This comprehensive review examines the complex relationship between HIV infection and CVD, highlighting key pathophysiological mechanisms such as chronic immune activation, inflammation, endothelial dysfunction, and the role of antiretroviral therapy (ART) in promoting cardiovascular risk. Alongside conventional risk factors such as smoking, hypertension, and dyslipidemia, HIV-specific elements, especially metabolic abnormalities associated with ART, significantly contribute to the development of CVD. Prevention strategies are crucial, focusing on the early identification and management of cardiovascular risk factors as well as optimizing ART regimens to minimize adverse metabolic effects. Clinical guidelines now recommend routine cardiovascular risk assessment in PWH, emphasizing aggressive management tailored to their unique health profiles. However, challenges exist in fully understanding the cardiovascular outcomes in this population. Future research directions include exploring the role of inflammation-modulating therapies and refining sustainable prevention strategies to mitigate the growing burden of CVD in PWH. Full article

The antibacterial activity of 18 phenolic compounds, including flavonoids and phenolic acids, against organisms of Escherichia coli, Klebsiella pneumoniae, and Proteus vulgaris that are resistant to several drugs was assessed in this study using the agar diffusion method. The strain’s strong resistance was confirmed by antibiotic susceptibility testing, which used fourteen drugs and only found inhibition zones for five of them. Out of the polyphenols, four compounds were effective against P. vulgaris, five against K. pneumoniae, and twelve against E. coli bacteria. The greatest inhibitory zone (18.75 ± 0.25 mm) against E. coli was shown by propyl gallate, an ester of gallic acid. Activity was significantly impacted by structural changes. Propyl substitution increased antibacterial activities across all strains, while methoxy substitution decreased them. The antibacterial effectiveness was reduced by the hydroxylation of flavonoids and the C3–C4 dihydroxylation of cinnamic acid. Propyl gallate primarily had antagonistic effects, while combination experiments demonstrated additive, synergistic, and antagonistic interactions. Propyl gallate (ΔG = −7.5 kcal/mol) exhibited substantial binding affinities with TEM-1 and NDM-1 β-lactamases via hydrogen and hydrophobic interactions, according to molecular docking. These results demonstrate propyl gallate as a viable antibacterial adjuvant option and validate the structure–activity relationship of phenolic compounds. Full article

To enhance PharmD student leadership and advocacy skills, combat the paucity of trained pre-health advisors for pharmacy admissions, augment community relationships, and increase pharmacy admissions volume, we designed, implemented, and assessed PAALS, a Pre-health Academic Advising and Leadership System. PAALS was grounded in Astin’s Theory of Student Involvement and evaluated using the RE-AIM implementation science framework. RE-AIM measured outcomes across Reach, Effectiveness, Adoption, Implementation, and Maintenance as indicators of PAALS’s scale, fidelity, sustainability, and institutional embedding. Analysis of PAALS using the RE-AIM framework demonstrated the following outcomes: (1) Reach: 42 P1-P3 PharmD students participated as mentors; external partnerships expanded from 2 to 8 regional high schools and community programs; and more than 25 mentored learners successfully matriculated into the PharmD program. (2) Effectiveness: students enacted sustained leadership, advocacy, and mentoring roles. (3) Adoption: voluntary uptake of mentoring and governance roles by PharmD students occurred with repeated engagement by external partner institutions. (4) Implementation: Core program components were delivered consistently using existing institutional resources. (5) Maintenance: PAALS remained operational across five academic years despite student turnover, with leadership succession and institutional embedding sustained across cohorts. Our findings demonstrate that student-led advising and advocacy ecosystems address critical gaps in pharmacy-specific pre-health advising models. Full article