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JOURNAL OF THROMBOSIS AND HAEMOSTASIS 2004年第2期2卷 335-341页

作者： Smith, JB Mustard, JF Jilma, B Fuchs, I Violi, F Pignatelli, P Pulcinelli, FM De Gaetano, G Cerletti, C Rosenson, RS Wolff, D Green, D Boss, AH Kensey, KR Temple Univ Sch Med Philadelphia PA 19122 USA

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aspirin-based PROTACs as COX-2 degraders for anti-inflammation

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BIOORGANIC & MEDICINAL CHEMISTRY 2025年 119卷 118061页

作者： Yu, Xuan-Jie Chen, Li-Li Ren, Zhi-Jie Li, Yan-Peng Chen, Jia-Yu Zhao, Yu-Xi Jiang, Jian-Bing Yunnan Univ Chinese Med Coll Tradit Chinese Med Kunming 650500 Peoples R China Shenzhen Univ Shenzhen Univ Med Sch Inst Inheritance Based Innovat Chinese Med Sch PharmMarshall Lab Biomed EngnGuangdong Prov Shenzhen 518060 Peoples R China Shenzhen Univ Sch Biomed EngnShenzhen Univ Med Sch Natl Reg Key Technol Engn Lab Med Ultrasound Guangdong Key Lab Biomed Measurements & Ultrasound Shenzhen 518060 Peoples R China Shenzhen Wininnovate Biotech Co Ltd Shenzhen 410034 Peoples R China

Cyclooxygenase-2 (COX-2) is a key enzyme in the biosynthesis of prostaglandins and plays a special role in the process of inflammatory response. COX-2 is a target of non-steroidal anti-inflammatory drugs (NSAIDs), which can effectively relieve inflammation, pain and fever responses by inhibiting COX-2. Despite the significant study progress of inhibitors targeting COX-2, the development of COX-2 degraders remains insufficient. Proteolysis targeting chimaeras (PROTACs) have recently emerged as a fascinating technology for targeted protein degradation and drug discovery. In this report, we present the design, synthesis and detection of aspirin-based PROTACs that demonstrate effective ubiquitin-proteasome pathway degradation of COX-2 in lipopolysaccharide-stimulated RAW264.7 cells, and the aspirin-based negative PROTACs does not promote the degradation of COX-2. Moreover, we show AspPROTACs could significantly affect proteasome degradation and inflammatory signaling pathways through quantitative proteomic data analysis. These COX-2 degraders offer valuable chemical tools and novel insights for research in anti-inflammatory drugs.

关键词： aspirin Proteolysis targeting chimaeras Cyclooxygenase-2 Degradation Anti-inflammation

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aspirin nanosensors

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CLINICA CHIMICA ACTA 2025年 571卷 120222页

作者： Koohkansaadi, Ghazal Tabean, Mahsa Mohagheghi, Arash Masoumi, Shahab Jahanabad, Zeinab Jahanbazi Mobed, Ahmad Charsouei, Saeid Univ New Hampshire Dept Psychol Durham NH USA Tabriz Univ Med Sci Womens Reprod Hlth Res Ctr Tabriz Iran Tabriz Univ Med Sci Res Ctr Psychiat & Behav Sci Tabriz Iran Tabriz Univ Med Sci Cardiovasc Res Ctr Tabriz Iran Islamic Azad Univ Yasouj Branch Yasuj Iran Social Determinants Hlth Res Ctr Hlth Management & Safety Promot Tabriz Iran Tabriz Univ Med Sci Fac Med Dept Neurol Tabriz Iran

aspirin, a widely used nonsteroidal anti-inflammatory drug (NSAID), plays a crucial role in the prevention and treatment of various cardiovascular and inflammatory conditions, including its significant application in stroke management. The accurate detection of aspirin in biological and environmental samples is essential for ensuring therapeutic efficacy and safety, particularly in patients at risk of stroke. This review aims to introduce and discuss the recent advancements in aspirin nanosensor technology, highlighting innovative approaches that enhance detection sensitivity and specificity. Traditional methods of aspirin detection often face limitations, including lengthy analysis times, the need for complex sample preparation, and insufficient sensitivity for trace detection. In contrast, the development of nanosensors has emerged as a promising solution, leveraging the unique properties of nanomaterials to facilitate rapid, reliable, and sensitive detection of aspirin. From a neuropharmaceutical perspective, the role of aspirin extends beyond its anti-inflammatory properties, as it also influences neurovascular health and may modulate neuroinflammatory processes associated with stroke. This review synthesizes current research findings, explores the mechanisms underlying nanosensor functionality, and addresses the challenges and future directions in the field of aspirin detection. By providing a comprehensive overview of cutting-edge research on aspirin nanosensors, this study underscores the importance of advancing detection technologies to improve patient outcomes, particularly in stroke prevention and management, and ensure effective therapeutic monitoring, while emphasizing the need for interdisciplinary approaches that integrate neuropharmaceutical insights to enhance the understanding of aspirin's multifaceted role in neuroprotection and its implications for stroke therapy.

关键词： aspirin Nanosensors Nanotechnology Stroke management Neuropharmacology

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aspirin Responsiveness in a Cohort of Pediatric Patients with Right Ventricle to Pulmonary Artery Conduits and Transcatheter Valve Replacement Systems

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PEDIATRIC CARDIOLOGY 2025年第2期46卷 485-493页

作者： Kelleher, Sean T. Regan, Irene E. Cox, Dermot Shaw, Kathryn Franklin, Orla Kenny, Damien P. Walsh, Kevin P. McMahon, Colin J. Childrens Hlth Ireland Crumlin Dept Paediat Cardiol Dublin Ireland Childrens Hlth Ireland Crumlin Dept Coagulat Haematol Dublin Ireland Royal Coll Surgeons Ireland Sch Pharm & Biomol Sci Dublin Ireland Childrens Hlth Ireland Crumlin Dept Paediat Pharm Dublin Ireland Univ Coll Dublin Sch Med Dublin Ireland Maastricht Univ Sch Hlth Profess Educ SHE Maastricht Netherlands Childrens Hlth Ireland Natl Childrens Res Ctr Dublin Ireland

The aim of this study was to determine the rate of aspirin responsiveness in a cohort of pediatric patients with in situ xenograft valved right ventricle to pulmonary artery (RV-PA) conduits and/or transcatheter valve replacements (TVR). aspirin is routinely prescribed to these patients. Optimizing anti-platelet therapy could promote valve longevity and reduce the risk of infective endocarditis in this at-risk group. This was a prospective, observational study. Patients were recruited from both ward and outpatient settings. Patients were eligible if under 18 years and taking aspirin. Non-response to aspirin was defined as > 20% platelet aggregation using light transmission platelet aggregometry (LTA) and < 50% platelet inhibition by thromboelastography with platelet mapping (TEGPM). Participants were invited to provide a confirmatory sample in cases of aspirin resistance and dose adjustments were made. Thirty patients participated. Median age was 9 years (2 months to 18 years). The majority (93%) had complex right ventricular outflow tract pathology. 13 (43%) had an RV-PA conduit and 24 (80%) had a TVR, with valve situated in conduit in 7 (23%) cases. Rate of aspirin non-response on initial testing was 23% (n = 7/30) with median LTA 74.55% (60-76%) and TEG 13.25% (0-44%) in non-responders. Non-responders were more likely to be under 1 year. Two patients required dose increases and one patient non-adherence to dose was identified. Four patients on repeat testing were responsive to aspirin by laboratory tests. The rate of aspirin non-response on laboratory testing in this cohort of patients was 23% and resulted in therapeutic intervention in 10%.

关键词： aspirin Conduit Transcatheter valve replacement Platelet Resistance Thrombosis

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aspirin 162 mg vs 81 mg for preeclampsia prophylaxis in high-risk obese individuals: a comparative effectiveness open-label randomized trial (ASPREO)

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AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY 2025年第3期232卷 315e1-315e8页

作者： Amro, Farah H. Blackwell, Sean C. Pedroza, Claudia Backley, Sami Bitar, Ghamar Daye, Nahla Bartal, Michal Fishel Chauhan, Suneet P. Sibai, Baha M. Univ Texas Hlth Sci Ctr Houston McGovern Med Sch Dept Obstet Gynecol & Reprod SciDiv Maternal Feta Houston TX 77030 USA Univ Texas Hlth Sci Ctr Houston Ctr Clin Res & Evidence Based Med Houston TX USA

BACKGROUND: In the United States, leading medical societies recommend 81 mg of aspirin daily for the prevention of preeclampsia in women at risk, whereas the NICE guidelines in the United Kingdom recommend a dose as high as 150 mg of aspirin. Recent data also suggest that in the obese population, inadequate dosing or aspirin resistance may impact the efficacy of aspirin at the currently recommended doses. OBJECTIVE: We evaluated whether daily administration of 162 mg aspirin would be more effective compared with 81 mg in decreasing the rate of preeclampsia with severe features in high-risk obese pregnant individuals. STUDY DESIGN: We performed a randomized trial between May 2019 and November 2022. Individuals at 12-20 weeks of gestational age with a body mass index >= 30 kg/m(2) at the time of enrollment and at least 1 of 3 high-risk factors: history of preeclampsia in a prior pregnancy, at least stage I hypertension documented in the index pregnancy, pregestational diabetes or gestational diabetes diagnosed before 20 weeks of gestational age were randomized to either 162 mg or 81 mg of aspirin daily till delivery, participants were not blinded to treatment allocation. Exclusion criteria were multifetal gestation, known major fetal anomalies, seizure disorder, baseline proteinuria, on aspirin because of other indications, or contraindication to aspirin. The primary outcome was preeclampsia with severe features (preeclampsia or superimposed preeclampsia with severe features;eclampsia;or hemolysis, elevated liver enzymes, low platelet count syndrome). Secondary outcomes included rates of preterm birth because of preeclampsia, small for gestational age, postpartum hemorrhage, abruption, and medication side effects. A sample size of 220 was needed using a preplanned Bayesian analysis of the primary outcome to estimate the posterior probability of benefit or harm with a neutral informative prior. RESULTS: Approximately 220/343 (64.1%) individuals were randomized. The pri

关键词： aspirin Bayesian analysis comparative effectiveness diabetes mellitus gestation hypertension preeclampsia preterm birth

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aspirin in Cancer Therapy: Pharmacology and Nanotechnology Advances

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INTERNATIONAL JOURNAL OF NANOMEDICINE 2025年 20卷 2327-2365页

作者： Laila, Umm E. Zhao, Zi Lon Liu, Huai Xu, Zhi-Xiang Henan Univ Sch Life Sci Kaifeng 475001 Henan Peoples R China

aspirin, a non-steroidal anti-inflammatory drug (NSAID), has garnered significant attention for its anti-cancer potential. This review explores the pharmacological properties, chemical dynamics, and evolving therapeutic applications of aspirin, with an emphasis on its integration into advanced cancer therapies. aspirin demonstrates broad-spectrum efficacy across diverse cancer types by modulating signaling pathways such as COX-dependent and COX-independent mechanisms, including Wnt, NF-kappa B, beta-catenin/ TCF, and IL-6/STAT3. Recent advancements highlight the role of nanotechnology in enhancing aspirin's targeted delivery, therapeutic effectiveness, and patient outcomes. Nanoparticle-based formulations, including liposomes, solid lipid nanoparticles, and mesoporous silica nanoparticles, offer improved solubility, stability, and bioavailability, enabling controlled drug release and tumor-specific targeting. These innovations reduce systemic toxicity and enhance therapeutic effects, paving the way for aspirin's integration into personalized cancer treatments. Ongoing clinical studies reinforce its safety profile, underscoring aspirin's role in cancer pharmacotherapy. This review calls for continued research into aspirin's repurposing in combination therapies and novel delivery systems to maximize its therapeutic potential.

关键词： aspirin cancer therapy signaling pathways nanotechnology targeted drug delivery

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aspirin enhances the antibacterial activity of colistin against multidrug-resistant Pseudomonas aeruginosa

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EUROPEAN JOURNAL OF PHARMACOLOGY 2025年 997卷 177480页

作者： Zhang, Ning Li, Xue Liu, Xin Cheng, Ping Li, Lailai Chai, Yihui Cao, Mingle Yang, Yuqi Guizhou Univ Tradit Chinese Med Guiyang 550025 Peoples R China Guizhou Univ Tradit Chinese Med Coll Acupuncture & Massage Guiyang 550025 Guizhou Peoples R China Guizhou Univ Tradit Chinese Med Affiliated Hosp 1 Guiyang 550000 Guizhou Peoples R China Guizhou Univ Tradit Chinese Med Dept Affiliated Hosp 2 Guiyang 550003 Peoples R China Guizhou Univ Tradit Chinese Med Sch Basic Med Guiyang 550025 Guizhou Peoples R China Anhui Agr Univ Coll Anim Sci & Technol Anim Derived Food Safety Innovat Team Hefei 230036 Anhui Peoples R China Peoples Hosp Duyun City Duyun 558000 Guizhou Peoples R China

Multidrug-resistant (MDR) Pseudomonas aeruginosa (PSA), recently reclassified by the World Health Organization (WHO) as a high-priority antimicrobial-resistant pathogen, continues to impose a substantial global health burden due to escalating resistance and stagnant therapeutic innovation. Colistin retains critical clinical utility against MDR P. aeruginosa infections;however, its dose-limiting nephrotoxicity and neurotoxicity necessitate strategies to optimise therapeutic indices. This study investigated the molecular mechanism underlying the synergistic activity of aspirin in potentiating colistin efficacy against MDR P. aeruginosa. In vitro analyses revealed marked synergistic bactericidal activity (FIC index <= 0.5), with metabolomic profiling demonstrating suppression of key metabolic pathways integral to bacterial membrane biogenesis, including glycerophospholipid metabolism and fatty acid biosynthesis. Ultrastructural imaging confirmed irreversible disruption of membrane integrity via combined treatment. In a rat model of P. aeruginosa-induced pneumonia, colistin-aspirin co- administration demonstrated superior efficacy to monotherapy, significantly reducing pulmonary bacterial load (3 to 4-log CFU/g reduction vs colistin alone;p < 0.01), attenuating histopathological injury, and suppressing pro-inflammatory cytokine levels (IL-6, IL-8, TNF-alpha) by 30-47%. Critically, this synergy enabled a reduction of colistin dosing to one-sixteenth while maintaining bactericidal potency. These findings provide mechanistic insights into aspirin-mediated colistin sensitisation and evidence supporting combinatorial regimens to circumvent colistin toxicity barriers. This work establishes a rational foundation for clinical translation of repurposed aspirin-colistin therapy against MDR P. aeruginosa infections.

关键词： Multi-drug resistant Pseudomonas aeruginosa Colistin aspirin Synergistic effect

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aspirin dosage for preeclampsia prophylaxis: an argument for 81-mg dosing

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AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY MFM 2025年第1期7卷 101568页

作者： Balhotra, Kimen S. Sibai, Baha M. Univ Texas Hlth Sci Ctr Houston Dept Obstet & Gynecol Div Maternal Fetal Med Houston TX 77030 USA

Research conducted over the past few decades has shown that low-dose aspirin can effectively reduce the risk of developing preeclampsia. Consequently, numerous prominent organizations have adopted the recommendation to use low-dose aspirin during pregnancy to prevent preeclampsia. However, the optimal dosage of low-dose aspirin (81mg versus 162mg) remains a subject of debate. Currently, there is insufficient high-quality data to justify the use of a higher dosage of low-dose aspirin. In this review, we review the existing evidence that supports the continued use of 81mg of aspirin over a higher dose and emphasize the need for high-quality research to alter current recommendations.

关键词： aspirin low-dose aspirin preeclampsia hypertensive disorders of pregnancy abnormal placentation

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Colorimetric 3D microPAD for Multiplexed Detection of Paracetamol and aspirin in Urine and Saliva

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SENSORS 2025年第6期25卷 1756-1756页

作者： Abalde-Pujales, Alberto Romero, Vanesa Lavilla, Isela Bendicho, Carlos Univ Vigo Ctr Invest Marina Dept Quim Analit & Alimentaria Grp QA2 Vigo 36310 Spain

In this work, a novel 3D mu PAD cellulose-based colorimetric chemosensor for multiplexed detection of paracetamol and aspirin in biological samples is proposed. The easy availability of analgesics such as paracetamol and non-steroidal anti-inflammatory drugs such as aspirin, over-the-counter drugs that can be acquired without medical prescription, can entail a health problem if they are administered incorrectly. The development of analytical procedures for the rapid, sensitive, and accurate determination of such drugs in clinical samples is of utmost importance. Different parameters involved in the design of the 3D mu PAD system and the colorimetric reaction conditions have been optimized. Under optimal conditions, detection limits of 0.004 mM and 0.013 mM were obtained for paracetamol and aspirin, respectively. The proposed procedure was validated against two certified reference materials and applied to the analysis of several synthetic urine and saliva samples. Synthetic urine and saliva samples were spiked at two concentration levels, showing recoveries in the range of 98-103% with a relative standard deviation of 3-6% (n = 6).

关键词： 3D microPAD paracetamol aspirin colorimetric chemosensor urine saliva smartphone detection

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aspirin Guided By Coronary Artery Calcium Scoring for Primary Cardiovascular Prevention in Persons with Subclinical Coronary Atherosclerosis

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AMERICAN JOURNAL OF MEDICINE 2025年第4期138卷 591-593页

作者： Siegel, Arthur J. Massachusetts Gen Hosp Div Gen Internal Med Boston MA USA McLean Hosp Dept Internal Med Belmont MA 02478 USA Harvard Med Sch Boston MA USA

Although endurance exercise is cardioprotective, episodes of strenuous physical exertion can trigger sudden cardiac death. While marathon training promotes overall heart health, running such races transiently increases cardiac arrest risk, mainly in middle-aged men with subclinical coronary atherosclerosis. Coronary artery calcium scanning has been advised for risk stratification to identify those who benefit from enhanced primary prevention. Based on a 40% reduction in first heart attacks in same-aged men in the final report on aspirin in the Physicians Health Study, low-dose aspirin has been recommended for such runners and elderly persons at increased risk for sudden cardiac death during recreational sports activity. This approach may also provide primary prevention for patients with conditions such as human immunodeficiency virus infection in which inflammation promotes progressive coronary atherosclerosis. This strategy is supported by a 31% reduction in major acute cardiac events with the addition of low-dose aspirin to the polypill in persons with moderate risk factors. Evidence-based in two randomized, controlled clinical trials, low-dose aspirin guided by coronary artery calcium scoring for primary prevention warrants timely consideration, given the sharply increasing burden of atherosclerosis forecast until 2050 by the American Heart Association.

关键词： aspirin primary cardiovascular prevention sudden cardiac death

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