Frontiers in Pharmacology最新文献

Objective: Atraumatic splenic rupture (ASR), though rare, is an adverse event linked to direct oral anticoagulants (DOACs). Given their widespread use and potentially fatal consequences if undiagnosed, heightened clinical awareness of DOAC-associated ASR is crucial. Our aim was to analyze the occurrence and clinical characteristics of ASR induced by DOACs.

Methods: We conducted a retrospective analysis of all reported DOAC-associated ASR cases through 15 April 2025, without language restrictions.

Results: A total of 27 patients (11 males and 16 females) were included with a median age of 64 years. Among them, apixaban (n = 17) was the most common DOAC, followed by rivaroxaban (n = 8) and dabigatran (n = 2), with atrial fibrillation (81.5%, n = 22) being the primary indication. The comorbidities observed among patients with DOAC-associated ASR risk included hypertension (25.9%), coronary heart disease (18.5%), malignancy (18.5%), and infections (18.5%). Among 27 patients, 11 (40.7%) received concomitant medications that may potentiate DOAC effects, with 5 patients taking four interacting drugs simultaneously. Only 4 of the 11 patients had documented anticoagulant dosages, half of which were full-dose regimens. Management included immediate DOAC cessation (100.0%), transfusion (77.8%), splenic artery embolization (44.4%), and splenectomy (70.4%) - with 31.6% of splenectomies representing salvage procedures following failed embolization. All patients were successfully discharged with no mortality.

Conclusion: ASR is a potentially life-threatening but preventable DOAC complication. Early recognition-particularly in elderly patients with comorbidities and polypharmacy-and urgent imaging for abdominal pain are crucial for improving clinical outcomes.

Objective: To alleviate periprosthetic joint infection (PJI) with methicillin-resistant Staphylococcus aureus (MRSA), shikonin (SKN) had been used to intervene the biofilm formation of MRSA in vivo and in vitro, which provides theoretical support and practical foundation for SKN as a novel drug against drug-resistant bacterial infection.

Methods: The rat model of periprosthetic joint infection was established, utilizing techniques such as scanning electron microscopy and pathology test to evaluate the MRSA inhibitory of bacterial load and biofilm formation effects of SKN. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) experiments were conducted to assess the antibacterial activity of SKN. The crystal violet staining method was employed to evaluate the effects of SKN on MRSA biofilm formation and eradication. Transcriptomic and amino acid metabolomics analyses were used to investigate the mechanism of SKN inhibition in MRSA biofilm formation. Total thiol detection was used to assess the impact of SKN on the intracellular cysteine levels in MRSA. Finally, MIC and crystal violet staining were used to evaluate the antibacterial effects and biofilm eradication efficacy of SKN against clinical MRSA strains.

Results: In vivo experimental results demonstrated that high doses of SKN significantly reduced the biofilm formation in MRSA PJI in rats, improved local inflammatory responses, and promoted tissue repair. Observations using scanning electron microscopy confirmed that SKN effectively inhibited the formation of biofilms on implant surface. MIC experiments revealed that the lowest inhibitory concentration of SKN was 70 μM, indicating significant antibacterial activity, although no direct bactericidal effects were observed. Results of crystal violet staining showed that SKN could significantly inhibit biofilm formation of MRSA at sublethal concentrations and exhibited efficacy of biofilm removal. Transcriptomic and acid amino metabolomic analyses prompted that the inhibition of MRSA biofilm formation by SKN might be related to regulate the cysteine metabolism in MRSA. Total thiol detection was used to validate the omics findings in vitro. Finally, SKN intervention in MRSA clinical strains showed that the SKN could inhibit MRSA clinical strains and remove biofilm.

Conclusion: SKN inhibits MRSA by suppressing biofilm formation, effectively alleviating periprosthetic joint infection by MRSA, and the mechanism of SKN antibacterial activity may be related to regulate the cysteine metabolism in MRSA.

Aim: To explore the effects of combining Shugan Jieyu capsule treatment with group psychological counseling on alexithymia in patients undergoing hemodialysis.

Methods: A total of 120 patients with nephropathy who underwent hemodialysis at our hospital's dialysis center from January 2023 to December 2024 were enrolled in this study and randomly divided into the control and study groups. The control group received estazolam treatment with routine nursing, whereas the study group received the Shugan Jieyu capsule along with group psychological counseling in addition to estazolam treatment and routine nursing. Various parameters were then measured and compared between the two groups, including alexithymia, depression, anxiety, sleep quality, personal and social performances, self-care ability, quality of life, serum levels of orphanin FQ and interleukin-2, incidence of adverse reactions, and nursing satisfaction.

Results: At both 4 and 8 weeks post-intervention, all measured parameters improved significantly from the baseline in both groups (p < 0.05). Importantly, the study group demonstrated better outcomes than the control group, including significantly lower scores for alexithymia, anxiety, depression, and sleep quality as well as higher scores for personal and social performances, self-care ability, and quality of life. Additionally, the serum levels of orphanin FQ and interleukin-2 were significantly lower in the study group (p < 0.05).

Conclusion: Shugan Jieyu capsule treatment combined with group psychological counseling was shown to effectively alleviate alexithymia, anxiety, and depression; improve sleep quality; reduce serum levels of orphanin FQ and interleukin-2; and enhance personal and social performances, self-care ability, quality of life, and nursing satisfaction in hemodialysis patients.

Postoperative management of osteoporotic vertebral compression fracture (OVCF) remains challenging because conventional bone mineral density (BMD) and imaging assessments are intrinsically delayed, while bone turnover markers (BTMs) that reflect real-time remodeling dynamics are difficult to measure frequently in routine care. In parallel, commonly used anti-osteoporotic medications may be limited by delayed onset of measurable response and concerns regarding long-term tolerability in certain populations. This article is a narrative review and conceptual perspective that synthesizes recent advances in biosensor-enabled point-of-care testing-highlighting organic optoelectrochemical transistors (OPECT)-and mechanistic pharmacology evidence for kidney-tonifying and blood-activating traditional Chinese medicine (TCM) formulas. On this basis, we propose a closed-loop framework that links high-frequency BTM monitoring to biomarker-informed optimization of postoperative integrative management. Importantly, this work does not report original clinical implementation data; the proposed framework is intended to guide future translational research, standardization, and prospective clinical validation.

Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by remodeling, inflammation, and metabolic dysregulation. Current pharmacotherapies primarily target vasodilation but fail to reverse structural remodeling or arrest disease progression. Plant metabolites have been proposed as potential therapeutic leads due to their structural diversity and reported multi-target actions; however, their safety and efficacy profiles in PAH remain incompletely validated. Beyond vasodilation, plant metabolites have been reported to modulate vascular remodeling, inflammation, oxidative stress, cellular metabolism, and epigenetic regulation, predominantly in preclinical models. However, most supporting evidence remains preclinical, often derived from rodent models and high-concentration in vitro assays, with limited validation of direct target engagement and clinical translatability. This review critically evaluates the multifaceted mechanisms of plant metabolites in PAH beyond vasodilation, with an explicit focus on the quality of evidence, the relevance of preclinical models, and the significant confounding issue of pan-assay interference compounds (PAINS). We highlight that while many metabolites show promising multi-target effects in vitro and in rodent models, the translational potential of most is severely limited by unvalidated target engagement, poor pharmacokinetics, and a lack of rigorous clinical data.

Antimicrobial resistance (AMR) is a worsening global health crisis, with drug repurposing emerging as a key mitigation strategy. Pyrimidine nucleosides are promising antibacterial scaffolds due to their easily modifiable structures and multi-therapeutic potential. However, related research faces challenges, including fragmented structure-activity relationships (SAR), unclear metabolism-efficacy correlations, and limited clinical translation strategies. This review categorizes these derivatives into cytosine and uracil/thymine analogs. It analyzes how lipidation, selenylation, and other structural modifications regulate antibacterial activity by modulating target binding, membrane permeability, and metabolic stability. Crucially, it elucidates their metabolic activation mechanism. As prodrugs, these derivatives require intracellular enzymatic phosphorylation to form active metabolites that inhibit nucleic acid synthesis, and their efficacy is dependent on intracellular enzyme levels and activity. Additionally, the review identifies core clinical translation barriers (host toxicity, narrow spectrum, insufficient AMR research) and proposes targeted optimization strategies (e.g., enzyme-guided modification and combination therapy). By integrating disparate structure-activity relationship and metabolic mechanism research, this work provides a novel systematic framework for developing pyrimidine nucleosides. Furthermore, it offers critical support to address the global antimicrobial resistance (AMR) crisis.

Severe sepsis-induced shock is one of the most challenging problems in critical care despite the progress made in treatment. Recognizing high-risk patients early on is critical for successful results, and the standard diagnostic approaches to such an ailment fail to identify it prior to shock setting in. Biomarkers have become promising diagnostic, prognostic predictors and treatment surveillance platforms in sepsis in the past few years. This review discusses the significance of biomarkers, e.g., cytokines, chemokines, acute-phase proteins and immune dysfunction markers in the pathogenesis of sepsis-induced shock. Additionally, we investigate the potential of new biomarkers, including microRNAs, circular RNAs, endothelial biomarkers, gene signatures, a combination of multimarker panels and machine learning models to improve the diagnostic and prognostic proficiency. As effective as they may seem, they (biomarkers) create challenges in clinical application, including variability, standardization, cost and regulatory approval. This review discusses future approaches to sepsis biomarker research, focusing on personalized medicine, global availability, and clinical validation to address barriers currently experienced in improving sepsis management worldwide.

Purpose: Breast cancer is the most common malignancy in women. Hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer patients rely on endocrine therapy as their fundamental systemic treatment strategy. This study aims to comprehensively evaluate the patterns of neurotoxicity and psychotoxicity across different classes of endocrine therapy.

Methods: Pharmacovigilance data related to endocrine therapy for breast cancer from the FDA Adverse Event Reporting System (FAERS) and WHO VigiAccess database were utilized. The disproportionality algorithms, including reporting odds ratio and information component, were employed in FAERS to investigate the patterns, influencing factors, and outcomes of neurological and psychiatric event burdens in selective estrogen receptor modulators (SERMs), selective estrogen receptor degraders (SERDs), and aromatase inhibitors (AIs). Sensitivity analysis was conducted using VigiAccess as a supplementary data source.

Results: A total of 64,731 FAERS and 116,605 VigiAccess safety reports on endocrine therapies were analyzed. Neurotoxic and psychiatric events accounted for approximately 20% and 10% of these reports, respectively. The most common neurologic adverse events were headache, dizziness, and sensory impairment, while insomnia, depression, and anxiety were the most frequent psychiatric events. The disproportionality analysis indicated that SERMs showed several strong neurovascular safety signals, such as cerebral venous thrombosis and dural arteriovenous fistula. Both SERMs and AIs showed positive signals for depression, whereas SERDs did not. All therapies exhibited an "early failure" pattern in time-to-onset analyses (β = 0.54-0.66).

Conclusion: This study conducted a comprehensive pharmacovigilance assessment of neurotoxicity and psychiatric events in endocrine therapy for breast cancer. The findings indicated heterogeneous patterns of neuropsychiatric safety signals and reporting burdens across drug classes, offering new insights relevant to clinical monitoring practices.