Frontiers in Pharmacology最新文献

Purpose: To evaluate and compare the efficacy of 0.01%, 0.025%, and 0.05% atropine eye drops in slowing myopia progression among Chinese children aged 6-18 years, focusing on changes in spherical equivalent (SE) and axial length (AL).

Methods: In this prospective, real world based, multi-center study, 175 children with myopia were followed for 12 months at three tertiary ophthalmic hospitals in China. Participants received nightly instillations of 0.01%, 0.025%, or 0.05% atropine in affected eyes. Primary outcomes included changes in SE and AL. Secondary outcomes involved corneal curvature, intraocular pressure, and biometric parameters. Statistical analyses included repeated-measures ANOVA, linear regression, and seemingly unrelated regression models.

Results: All three concentrations demonstrated effectiveness in reducing myopia progression. At 12 months, SE progression was lowest in the 0.05% group (-0.27 ± 0.72 D), followed by 0.025% (-0.35 ± 0.59 D) and 0.01% (-0.44 ± 1.02 D), with a significant difference between 0.05% and 0.01% (P = 0.014). AL elongation was numerically lowest in the 0.025% group (0.21 ± 0.19 mm), while differences among groups were not statistically significant (P = 0.299). Regression analysis showed that AL change explained over 34% of SE variation in the 0.025% and 0.05% groups, compared to 14% in the 0.01% group.

Conclusion: Low-concentration atropine is effective in controlling myopia progression in children. Among the three concentrations, 0.025% atropine offers better efficacy and tolerability, providing comparable axial elongation control to 0.05% with potentially fewer side effects. These findings support its use as a first-line pharmacologic option for pediatric myopia management in clinical practice.

Background: Understanding physician attitudes toward natural over the counter (OTC) products in respiratory medicine remains understudied in multinational contexts. This study represents the first multinational survey of physician perceptions regarding natural syrup formulations for cough and sore throat management.

Objective: To assess physician acceptance of a natural syrup containing Verbascum and Malva sylvestris extracts across diverse international healthcare settings by evaluating seven key product attributes.

Methods: Cross-sectional survey of 398 practicing physicians across 13 countries was conducted through the Sermo global physician network in May 2025. Participants evaluated clinical appropriateness, safety in vulnerable populations, co-prescription capabilities, throat protection properties, allergen-free composition, natural ingredient preference, and nighttime convenience compared to the leading lozenge in each country.

Results: while regional variations were observed, overall physician acceptance was highest for absence of problematic pharmaceutical ingredients (86%), followed by safety in vulnerable populations and co-prescription safety (82%), with lower agreement for natural ingredients (77%), throat protection (73%), allergen-free composition (71%), and night-time convenience (63%). Regional patterns showed consistently higher acceptance in Middle Eastern countries and below-average values in most European countries (except Ireland), with Saudi Arabia highest and Finland and Italy lowest.

Conclusion: Physicians across diverse healthcare systems reported favourable attitudes toward this natural syrup formulation, with particular emphasis on the perceived safety profile for vulnerable patient groups. The notable international variation suggests the potential influence of cultural and regional factors on prescribing attitudes. While these exploratory findings should be interpreted cautiously given the descriptive study design and industry sponsorship, they provide preliminary support for the continued investigation of natural formulations in respiratory care, particularly for patients with comorbidities who may require alternatives to conventional antitussive therapies.

Introduction: Direct oral anticoagulants (DOACs), including apixaban and rivaroxaban, are widely prescribed for the prevention of cardioembolic stroke and the treatment of venous thromboembolism. Although routine therapeutic monitoring is not required, real-world patients often present with multiple comorbidities or drug-drug interactions that may alter drug exposure. Observational data indicate that high DOAC plasma concentrations may increase bleeding risk, whereas low concentrations may predispose individuals to thromboembolic or ischemic events. In this study, we aimed to analyze the relationship between DOAC plasma concentrations and clinical outcomes in hospitalized patients from the OptimAT cohort.

Methods: This prospective study included 200 inpatients from Geneva University Hospitals receiving apixaban (n = 100) or rivaroxaban (n = 100). Pharmacokinetic parameters (AUC 0 h-8 h, C-max, and C-trough) were derived from plasma concentrations measured using validated LC-MS/MS quantification of dried blood spot samples. Clinical follow-up was performed for 2 years to record thromboembolic, ischemic, and bleeding events, which were classified according to the ISTH criteria. Patients were categorized into percentile-based exposure groups, defined separately for apixaban and rivaroxaban. Kaplan-Meier survival curves and Cox regression models were used to assess associations between extreme versus moderate plasma concentrations and clinical outcomes.

Results: During the 2-year follow-up, 27 clinical events were recorded, corresponding to an incidence rate of 9.3 per 100 patient-years for any bleeding event (95% CI: 5.57-14.44) and 3.9 per 100 patient-years for ischemic or thromboembolic events (95% CI: 1.68-7.67). These included one major bleeding event (0.5%), eighteen minor bleeding events (9%), six arterial ischemic events (3%), and two venous thromboembolic events (1%). No significant association was found between high apixaban/rivaroxaban plasma concentrations and bleeding events or between low apixaban/rivaroxaban plasma concentrations and ischemic/thromboembolic events for any pharmacokinetic parameter. The study power was limited by the small sample size and a high rate of apixaban and rivaroxaban treatment modifications or discontinuations (41%), which reduced the number of evaluable patients.

Conclusion: In this real-world cohort, apixaban and rivaroxaban plasma concentrations were not associated with clinical outcomes. While highlighting the limitations of analyzing clinical outcomes within the framework of a pharmacokinetic study, these data are informative for future meta-analyses aimed at minimizing publication bias from neutral results.

Background: Age-related memory decline has emerged as a critical global public health challenge, yet few ethnopharmacological interventions have demonstrated robust clinical efficacy in improving memory and cognitive function.

Objectives: This randomized, double-blind, placebo-controlled trial aimed to elucidate the neurocognitive-enhancing mechanisms of a botanical product containing Cistanche tubulosa [Schenk] Wight and Ginkgo biloba L. (CG) extracts.

Methods: 117 healthy participants (aged 30-65 years) were randomized to receive either CG tablets or placebo for 30 days. Clinical memory assessments and MRI scans were conducted at baseline and post-intervention. Gray matter volume (GMV), functional MRI (fMRI), and functional connectivity (FC) were analyzed using SPM12.

Results: CG tablets significantly improved scores in across multiple dimensions, including directional memory, associative learning, graphic free recall, portrait memory, total memory, and Memory Quotient (all p < 0.01). Subgroup analyses by age (<50 vs. ≥50) and gender confirmed the consistency of these effects. After intervention, slight reductions in GMV were observed in precentral gyrus and supplementary motor area. Notably, greater improvement in clinical memory scores was associated with lower post-intervention GMV in these regions. Concurrently, fMRI revealed increased activity in the cerebellar culmen, which positively correlated with improvements in directional memory (p = 0.031) and total memory score (p = 0.007). The associations between memory improvement, localized GMV reduction, and increased cerebellar activity suggests that CG may optimize neural efficiency or drive functional network reorganization.

Conclusion: These findings indicated that CG supplementation enhances memory function in healthy adults. These cognitive gains are linked to specific structural and functional neural changes, particularly in motor-related areas and the cerebellum, reflecting improved neural processing. While these findings highlight CG's short-term benefits, further research is warranted to explore its long-term efficacy and broader clinical utility.This study was registered at the Chinese Clinical Trials Registry (https://www.chictr.org.cn/): ChiCTR2400084102.

Clinical trial registration: https://www.chictr.org.cn/hvshowproject.html?id=251905&v=1.0, identifier ChiCTR2400084102.

Introduction: Pharmacogenomic (PGx) variants can influence drug efficacy and safety, yet their prevalence in Latin American populations with cancer is underexplored. Our aim is to characterize the frequency and phenotypic distribution of actionable pharmacogenes in Brazilian patients with metastatic prostate cancer (MPC) and Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer (BC).

Methods: This analysis included 452 patients (259 BC, 193 MPC) from a multicenter study across 19 Brazilian sites. Exome sequencing was performed, and PGx variants were analyzed using the Pharmacogenomics Clinical Annotation Tool (PharmCAT) following the Clinical Pharmacogenetics Implementation Consortium (CPIC®) guidelines. Genotypes, star alleles, and predicted phenotypes were reported for 15 clinically relevant pharmacogenes.

Results: Actionable PGx phenotypes were detected in 99.33% of participants. The decreased-function ABCG2 rs2231142 T allele occurred at 8.96%, and the VKORC1 rs9923231 T allele at 32.63%. In SLCO1B1, normal function predominated (63.11%), with 21.11% exhibiting decreased function. Normal metabolizer phenotypes were most frequent in CYP2C19 (45.35%), CYP2C9 (70.51%), and CYP3A4 (94.62%), whereas CYP2B6 was dominated by intermediate metabolizers (43.02%) and CYP3A5 by poor/intermediate metabolizers (93.79%). Normal diplotypes predominated in thiopurine-related genes (NUDT15: 92.92%; TPMT: 88.72%), although nonfunctional alleles were observed. In UGT1A1, decreased-function alleles accounted for approximately 37% of participants. Clinically relevant DPYD and RYR1 variants were rare (<2.0%).

Conclusion: Nearly all Brazilian patients with cancer carried at least one actionable PGx variant, highlighting the potential impact of PGx-guided therapy in oncology. These results underscore the value of integrating pharmacogenomic strategies into clinical practice in Brazil.

Faced with the highly malignant threat of metastatic triple-negative breast cancer (TNBC), the effect of traditional chemical agents is limited, and new anti-metastasis drug remains to be explored. Celastrol (Cel) is a bioactive compound derived from Tripterygium wilfordii with significant anti-neoplastic effects in various cancers. In this study, we investigated the potential anti-metastatic effects of Cel on anoikis resistant TNBC cells (TNBC-AR) cells, including MDA-MB-231-AR cells and BT-549-AR cells. Using CCK-8 and colony formation assay, we demonstrated that Cel could inhibit the proliferation of MDA-MB-231-AR cells and BT-549-AR cells with IC₅₀ value of 1.510 μM and 1.673 μM, respectively. The results of wound healing and transwell assays showed that Cel could potently inhibit the invasion and migration of TNBC-AR cells. Aggregation and flow cytometry experiments showed that Cel could inhibit the clusters formation and enhance the anoikis of TNBC-AR cells on the suspension conditions. Then we conducted bioinformatics analysis, Western blotting, and intervention experiments to explore the molecular mechanisms of Cel's anti-metastasis effects. The results of these experiments discovered that Cel treatment suppressed the p-EMT state in TNBC-AR cells, and this effect correlated with a reduction in EGFR/MEK/ERK pathway activation. Our findings suggest that Cel may be a promising candidate for therapeutic treatments of metastatic TNBC.

Inflammatory and host immunological responses to bacterial tooth infections contribute to the development of periodontal disease. MiRNAs (miRNAs) play a critical role in regulating these immunological and inflammatory responses. miRNAs influence both innate and adaptive immunity in periodontal disease, affecting the functions of T and B cells, neutrophils, macrophages, and dendritic cells. This review examines the regulatory roles of miRNAs in periodontal tissues and evaluates their potential as therapeutic agents and biomarkers. Upregulated miRNAs identified include miR-146a, miR-29, miR-15, miR-148, and miR-223, while miR-31, miR-92, and miR-451 are downregulated. The review emphasizes the altered expression of miRNAs in periodontitis models. Selective targeting of miRNA pathways, enabled by gain or loss-of-function approaches, represents a promising strategy for therapeutic intervention. Additionally, the stability of miRNAs in gingival crevicular fluid and their association with specific features of periodontal disease underscore their potential as indicators of disease progression or tissue recovery.

Objectives: To evaluate the associations of clinical and pharmacogenetic factors (CYP2C19*2, *17 polymorphisms) with the safety parameters of sertraline in adolescents with a depressive episode and suicidal intentions for 3 weeks in a psychiatric hospital.

Methods: The study included 112 adolescents, who were hospitalized due to a depressive episode and suicidal intentions. All patients received sertraline for 21 days. The safety of pharmacotherapy was assessed on the 7th and 21st day using the Antidepressant ADRs checklist. Each patient underwent genetic testing for CYP2C19*2, *3, *17. The safety of sertraline was analyzed depending on the carrier status of CYP2C19 polymorphisms, the type of CYP2C19 metabolism, as well as depending on additional pharmacotherapy.

Results: It was found that patients with the CYP2C19*2 genotype took a slightly lower dose of sertraline compared to those with the wild-type genotype on 21st day (100 [87.5; 100] mg/day vs. 100 [100; 100], p = 0.048). Patients carrying the CYP2C19*17 allele, on the other hand, were more likely to experience vegetative and somatic ADRs on day 7 of treatment (2 vs. 1, p = 0.042). The use of anxiolytics (alimemazine and hydroxyzine) was significantly associated with an increased number of vegetative/somatic, and mental ADRs on day 7, as well as an increased total number of ADRs by day 21. Linear regression analysis confirmed that anxiolytics were the most significant predictors of ADR development on day 21 (Estimate = 0.86, 95% CI 0.32-1.41, p = 0.002).

Conclusion: Polypharmacy (particularly, adding a non-benzodiazepine anxiolytic) was a more significant risk factor for ADRs when taking sertraline, compared to the carrier status of CYP2C19 gene polymorphisms.

Oleanolic acid is a natural pentacyclic triterpenoid widely found in dietary plants and has attracted translational interest in breast cancer research. This review addresses how oleanolic acid and its derivatives exert anticancer effects in breast cancer models, and how structural modification and delivery strategies may mitigate key barriers that currently limit clinical translation. Drawing primarily on in vitro studies and preclinical animal evidence, we summarize major mechanistic themes, including induction of apoptosis and cell-cycle arrest, and regulation of autophagy, ferroptosis, oxidative stress, cancer metabolism, and tumor microenvironment-associated processes. We further highlight representative medicinal-chemistry advances showing that selected derivatives, such as SZC014 and HIMOXOL, can exhibit improved physicochemical properties and enhanced anticancer activity in specific breast cancer models. In parallel, we review formulation and delivery approaches aimed at improving exposure and tumor delivery, including nanoparticle-based systems and emerging co-delivery or self-assembly strategies developed to address poor solubility and limited bioavailability. Importantly, we critically discuss why pharmacokinetic limitations remain a central obstacle, including poor aqueous solubility, variable absorption, extensive first-pass metabolism, uncertain tumor exposure, and limited PK/PD linkage. We also note that derivatization and nanocarriers may introduce new uncertainties related to metabolic fate, drug-drug interactions, off-target accumulation, manufacturability, and long-term safety. Across the field, conclusions are additionally constrained by model heterogeneity, incomplete subtype coverage, limited normal-cell controls, and insufficient mechanistic causality testing. Overall, oleanolic acid and its derivatives should be viewed as preclinical leads with potential relevance to breast cancer, and future progress will require standardized multi-model validation, rigorous PK and biodistribution profiling with PK/PD integration, systematic toxicology, and rational combination strategies before clinical utility can be concluded.

Background: Diabetic kidney disease (DKD) is a critical complication of type 2 diabetes, often compounded by hyperuricemia, which may accelerate renal function decline. While finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), provides renal and cardiovascular benefits, its impact on uric acid (UA) metabolism in real-world DKD patients, particularly those with high baseline SUA, remains controversial.

Methods: In this retrospective, single-center study, we included 124 patients with type 2 DKD (baseline eGFR ≥60 mL/min/1.73 m²) who initiated finerenone. Patients with recent gout or urate-lowering therapy were excluded. Changes in SUA, urinary albumin-to-creatinine ratio (UACR), and eGFR were assessed before and after 1-3 months of treatment. Statistical analyses employed linear mixed models for longitudinal data and multivariable regression.

Results: Linear mixed model analysis showed finerenone treatment was associated with a significant reduction in SUA (adjusted mean difference: -47.9 μmol/L, 95% CI: -63.5 to -32.3; p < 0.001). This reduction was substantially greater in patients with baseline hyperuricemia (-88.6 μmol/L) than in those without (-16.6 μmol/L; p for interaction = 0.003). UACR decreased by 39.4% (p < 0.001), while eGFR showed a small but significant decline (-2.7 mL/min/1.73 m², p = 0.019). The SUA-lowering association was independent of concomitant SGLT2 inhibitor or GLP-1 receptor agonist use in multivariable analyses. Hyperkalemia (potassium ≥5.5 mmol/L) occurred in 0.8% of patients.

Conclusion: In this real-world cohort, finerenone use was associated with significant reductions in albuminuria and SUA, particularly among patients with hyperuricemia. These findings suggest a potential dual benefit in this high-risk subgroup and highlight the importance of baseline SUA in interpreting finerenone's metabolic effects. The observed SUA reduction warrants further prospective investigation.