Frontiers in Pharmacology最新文献

In the European Union, before cancer medicines containing a new active substance become available to patients, they must undergo a rigorous authorization process through the Centralized Procedure. This study examines trends in oncology Marketing Authorization Applications (MAAs) over the past 5 years. Oncology MAAs from January 2020 to January 2025 were used to collect and analyze publicly available data. The number of MAAs, therapeutic indications, company and product characteristics, scientific advice (SA), orphan designation (OD)/expedited programs, and overall procedural time were analyzed. A total of 60 MAAs were identified. During the reporting period, only three MAAs received negative opinions; however, two were reverted to positive after re-examination. Blood cancers were the main therapeutic indication. The typical profile of a MAA was as follows: a large-sized company holder (72%); monoclonal antibody (mAb) (31%); SA requested (92%); under OD at both time points: at the moment of application (60%) and at the moment of receiving the opinion by the Committee for Medicinal Products for Human Use (67% of the initial number of MAAs under OD); not granted any expedited program (57%); and with an average total procedure time of about 348 days. Additionally, procedural time analysis revealed shorter timelines for MAAs under the accelerated assessment (AA) program and those that obtained SA. Oncology MAAs have increased over the years, particularly for mAbs and blood cancer indications. Large-sized companies were the main MAA holders. Additionally, the SA and AA program might have demonstrated a positive impact in reducing procedural time.

Background: The clinical impact of high-dose influenza vaccination on cardiovascular outcomes in patients with established cardiovascular disease (CVD) remains controversial. To this end, our study aimed to assess the impact of influenza and high-dose influenza vaccine on cardiovascular outcomes in patients with CVD or at high risk for CVD.

Methods: We systematically searched three electronic databases from construction to 5 November 2025. The data extraction and meta-analysis were conducted following PRISMA workflow, utilizing both fixed- and random-effects models to ensure robust statistical analysis. The primary clinical outcomes included all-cause mortality (ACM) and major adverse clinical events (MACEs). Secondary endpoints included all-cause hospitalization (ACH), cardiovascular mortality (CVM), heart failure (HF), myocardial infarction (MI), stroke, ICU admission, and non-cardiovascular death.

Results: A total of 36 studies were included for this research. According to the scope of the research, hierarchical analyses were performed among several subgroups. For efficacy evaluation, we included 25 articles, with a total of 869,795 vaccinated and 1,306,470 unvaccinated participants. Influenza vaccination was associated with a significant reduction in ACM (OR = 0.74; 95% CI, 0.60-0.91), MACE (OR = 0.62; 95% CI, 0.46-0.83), and ICU admission (OR = 0.33; 95% CI, 0.22-0.49) compared to those in the control group. Influenza vaccine only provided a significant prevention of CVM (OR = 0.59; 95% CI, 0.39-0.89) and ACH (OR = 0.80; 95% CI, 0.74-0.87) among established CVD patients. No significant advantage of influenza vaccine in reducing the incidence of HF, non-cardiovascular death, MI, and stroke was observed. Then we also evaluated the efficacy of high-dose vaccination strategy in CVD management. Eleven studies were included for this purpose, and the pooled outcome analysis demonstrated that the high-dose strategy did not provide any benefit in reducing ACM and MACE.

Conclusion: The influenza vaccination provided significant benefits in reducing ACM and MACE. However, it failed to demonstrate advantage in managing HF, MI, and non-cardiovascular death in patients with CVD. Additionally, the high-dose influenza vaccination strategy did not present efficacy in preventing adverse outcomes of CVD compared to the standard strategy.

[This corrects the article DOI: 10.3389/fphar.2025.1539704.].

[This corrects the article DOI: 10.3389/fphar.2021.789552.].

Background: Atrial fibrillation (AF) is a cardiac arrhythmia characterized by disorganized atrial electrical activity, resulting in ineffective mechanical contraction and a heightened propensity for intra-atrial thrombus formation. The underlying pathophysiology is multifactorial, involving a complex interplay of pro-fibrotic, inflammatory, and pro-thrombotic pathways, notably oxidative stress and dysregulation of the fibrinolytic system. Given that these mechanisms remain incompletely elucidated, this study sought to investigate the association between biomarkers of oxidative stress and antifibrinolytic activity in AF patients treated with the oral anticoagulants warfarin or rivaroxaban, in comparison to a healthy control cohort.

Methods: A total of 85 AF patients-38 on rivaroxaban and 47 on warfarin-were enrolled alongside 62 matched healthy controls. Cellular metabolic activity was assessed via MTT [3-(4,5-Dimethylthiazol-2γl)-2,5-Diphenyl Tetrazoline Bromide] assay measured by spectrophotometry. Serum concentrations of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation), plasminogen activator inhibitor-1 (PAI-1), and thrombin-activatable fibrinolysis inhibitor (TAFI) were quantified using enzyme-linked immunosorbent assay (ELISA).

Results: The rivaroxaban group exhibited significantly greater MTT absorbance, indicative of enhanced cellular metabolic activity, and significantly lower circulating TAFI levels compared to the warfarin group.

Conclusion: These results suggest that in patients with AF, rivaroxaban may provide pleiotropic benefits beyond anticoagulation, potentially by augmenting cellular antioxidant mechanisms and suppressing antifibrinolytic activity.

Introduction: University campuses are high-risk environments for influenza transmission, yet vaccine coverage among students often remains suboptimal. This study aimed to identify the determinants of vaccine hesitancy among university students in Saudi Arabia using the Health Belief Model (HBM) framework.

Method: A cross-sectional study was conducted between January and September 2024. Data were collected via a validated online Arabic questionnaire assessing HBM constructs-susceptibility, severity, benefits, and barriers-alongside sociodemographic variables. Ethical approval was obtained for human participation.

Results: Of the 450 university students surveyed, 62.4% reported encountering significant barriers to vaccination. Despite a high recognition of vaccine benefits (66.7%), this awareness did not correlate with higher intention to vaccinate after adjusting for sociodemographic factors. Students perceiving fewer barriers exhibited substantially higher acceptance rates compared to those perceiving high barriers (60% vs. 27.8%). Furthermore, female students were nearly twice as likely to report moderate barriers (aOR = 1.994) compared to males, while healthcare students were significantly less likely to perceive such obstacles (aOR = 0.654). Students with chronic conditions also demonstrated higher vaccine acceptance (44.1%) compared to their healthy peers (20.2%).

Conclusion: Influenza vaccine uptake among Saudi university students is hindered primarily by perceived barriers rather than a lack of awareness regarding vaccine benefits. Public health strategies on campuses should shift focus from simply emphasizing advantages to actively mitigating logistical and misconception-based obstacles, particularly targeting non-healthcare disciplines and female students.

Background and aims: Excessive alcohol consumption poses a significant global health concern, ranking as the world's third-largest risk factor for diseases and disabilities, contributing to 5.9% of all deaths worldwide. Among various disorders linked to alcohol misuse, alcohol-associated liver disease (ALD) is the most prominent. ALD patients often exhibit increased intestinal permeability, systemic inflammation, gut dysbiosis, and hepatic steatosis. No FDA-approved therapies are available to treat ALD or to resolve the pathological domains of alcohol-induced gut barrier dysfunction, inflammation, and steatosis. The goal of this study is to investigate the potential therapeutic role of the microbial metabolite Urolithin A' (UroA), in alleviating ALD.

Methods: Caco-2 (monolayer colon epithelial) cells and AML12 (hepatocytes) cells were used to test the protective activities of UroA against EtOH-induced gut barrier dysfunction and lipid accumulation in vitro. Preclinical ALD mouse models were used to test the therapeutic potential of UroA against EtOH exposure. Additionally, we generated cell-specific deletion mice with aryl hydrocarbon receptor (AHR) deletion to define the role of intestinal epithelial cell AHR in UroA-mediated protective activities against ALD.

Results: The results presented here demonstrate the efficacy of UroA as a potential therapeutic agent to protect against EtOH-induced disruption of tight junction proteins, inflammation, and lipogenesis both in vitro and in vivo models.

Conclusion: Our findings suggest that the simultaneous targeting of gut barrier dysfunction, inflammation, and hepatic steatosis by treatment with UroA may offer new possibilities for combating ALD. Moreover, our results suggest that UroA-mediated protective activities against EtOH-induced gut barrier dysfunction and inflammation in ALD are dependent on intestinal epithelial cell-AHR.

Introduction: Mild cognitive impairment (MCI) is a cognitive decline syndrome that represents an intermediate stage between normal aging and dementia, with a high risk of progression to dementia. The World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) is the world's largest clinical trial registry, aggregating data from global registries. This study aimed to analyze MCI trials in the ICTRP to delineate the research landscape, key focus areas, and emerging trends in MCI to inform future intervention strategies.

Methods: A systematic study was performed to analyze MCI clinical trials registered in the ICTRP up to December 2024. Records were deduplicated, and extracted variables included study design, phase, country, sponsor, sample size, intervention type, and outcomes. Dual independent extraction was performed, with third-party adjudication for discrepancies.

Results: A total of 2,609 MCI trials were included, with 51.8% registered in the past five years. The United States led in the number of registrations among countries, whereas Asia topped the list among continents. Of all the trials, 2,064 were interventional trials, while 499 were observational trials. Predominant types of interventions were non-pharmacological therapies, including non-invasive brain stimulation (211), cognitive interventions (194), computer-assisted cognitive interventions (192), dietary interventions (187), and exercise interventions (184). In the realm of pharmacological therapies, chemical drugs were the most prevalent. Clinical trials were concentrated in Phase 0/II. Most trials were sponsored by universities. In addition, 60.1% of the trials included fewer than 100 participants, and data sharing occurred at a low level.

Conclusion: MCI trial registrations have been increasing annually. The treatment of MCI focuses on non-pharmacological therapies, with most pharmacological therapy studies in the early stages of clinical trials. Notably, integrated cognitive training that combines traditional methods with computer-assisted technologies has emerged as a particularly promising area of research.

Objectives: To compare the effects of eravacycline and tigecycline on serum bilirubin levels and investigate the incidence and clinical characteristics of total bilirubin increase associated with eravacycline.

Methods: We conducted a retrospective study in critically ill patients receiving eravacycline or tigecycline between November 2023 and May 2024 to evaluate serum bilirubin levels. Causality was assessed using the Naranjo Adverse Drug Reaction Probability Scale. A multivariable logistic regression was conducted to identify the risk factors for an increase in total bilirubin, and Kaplan-Meier curves were used to depict the time to an increase in total bilirubin.

Results: A total of 48 patients were evaluated in this study. Compared to tigecycline, eravacycline was associated with elevated serum total bilirubin and direct bilirubin. Following the definition of an increase in total bilirubin levels as ≥42 μmol/L, 15 patients were rated as possibly or probably having drug-associated increase in total bilirubin. The incidence of an increase in total bilirubin was 61.5% in the eravacycline group and only 20.0% in the tigecycline group. Administration of eravacycline was identified as an independent risk factor for an increase in total bilirubin. In addition, patients receiving eravacycline tended to experience an increase in total bilirubin significantly earlier, and the change in direct bilirubin levels was significantly greater than that in indirect bilirubin in these patients.

Conclusion: Eravacycline has been identified as an independent risk factor for the increase in total bilirubin. Monitoring serum bilirubin levels should be considered in patients receiving eravacycline, particularly in critically ill patients.

Background: Chronic cough hypersensitivity is common across respiratory diseases and often occurs without airway inflammation, yet effective treatments remain limited. Nitric oxide (NO), an important endogenous signaling molecule and environmental pollutant, has been implicated in respiratory pathophysiology, but its role in cough hypersensitivity remains unclear.

Aim: The aim of this study was to investigate whether long-term NO exposure induces cough hypersensitivity and to define the underlying mechanisms involved.

Methods: A guinea pig model of chronic NO exposure was established and compared with a cigarette smoke (CS) -induced cough model. Cough sensitivity was assessed using capsaicin challenge tests. Airway pathology and inflammation were evaluated by histological staining and molecular analyses in vivo and in 16HBE epithelial cells. Expression of TRPV1 and HIF1α was examined in tracheal tissues and ND7/23 sensory neuron-like cells using immunofluorescence and qPCR.

Results: Acute NO exposure did not trigger coughing. Notably, prolonged NO exposure significantly increased capsaicin-induced cough frequency and reduced cough latency. In contrast to CS, chronic NO exposure did not induce airway inflammation, epithelial remodeling, or cytokine upregulation. Instead, NO exposure markedly enhanced the expression of TRPV1 and HIF1α in airway sensory fibers and ND7/23 cells.

Conclusion: These findings demonstrate that prolonged NO exposure induces cough hypersensitivity via HIF1α-TRPV1-mediated neural sensitization, independent of airway inflammation. This study establishes a novel non-inflammatory model of chronic cough and identifies potential therapeutic targets for refractory cough.