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British Journal of Clinical Pharmacology May 2022Aspirin has known effects beyond inhibiting platelet cyclooxygenase-1 (COX-1) that have been incompletely characterized. Transcriptomics can comprehensively characterize... (Randomized Controlled Trial)
Randomized Controlled Trial
Aspirin has known effects beyond inhibiting platelet cyclooxygenase-1 (COX-1) that have been incompletely characterized. Transcriptomics can comprehensively characterize the on- and off-target effects of medications. We used a systems pharmacogenomics approach of aspirin exposure in volunteers coupled with serial platelet function and purified platelet mRNA sequencing to test the hypothesis that aspirin's effects on the platelet transcriptome are associated with platelet function. We prospectively recruited 74 adult volunteers for a randomized crossover study of 81- vs. 325 mg/day, each for 4 weeks. Using mRNA sequencing of purified platelets collected before and after each 4-week exposure, we identified 208 aspirin-responsive genes with no evidence for dosage effects. In independent cohorts of healthy volunteers and patients with diabetes, we validated aspirin's effects on five genes: EIF2S3, CHRNB1, EPAS1, SLC9A3R2 and HLA-DRA. Functional characterization of the effects of aspirin on mRNA as well as platelet ribosomal RNA demonstrated that aspirin may act as an inhibitor of protein synthesis. Database searches for small molecules that mimicked the effects of aspirin on platelet gene expression in vitro identified aspirin but no other molecules that share aspirin's known mechanisms of action. The effects of aspirin on platelet mRNA were correlated with higher levels of platelet function both at baseline and after aspirin exposure-an effect that counteracts aspirin's known antiplatelet effect. In summary, this work collectively demonstrates a dose-independent effect of aspirin on the platelet transcriptome that counteracts the well-known antiplatelet effects of aspirin.
Topics: Adult; Aspirin; Blood Platelets; Cross-Over Studies; Gene Expression; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; RNA, Messenger
PubMed: 34705291
DOI: 10.1111/bcp.15127 -
International Immunopharmacology Jul 2023The gut microbiome has been implicated in the development of cardiovascular disease (CVD) and atherosclerosis (AS), a chronic inflammatory condition. Aspirin may improve...
Aspirin ameliorates atherosclerotic immuno-inflammation through regulating the Treg/Th17 axis and CD39-CD73 adenosine signaling via remodeling the gut microbiota in ApoE mice.
The gut microbiome has been implicated in the development of cardiovascular disease (CVD) and atherosclerosis (AS), a chronic inflammatory condition. Aspirin may improve the immuno-inflammatory status in AS by regulating microbiota dysbiosis. However, the potential role of aspirin in modulating gut microbiota and microbial-derived metabolites remains less explored. In this study, we investigated the effect of aspirin treatment on AS progression by modulating gut microbiota and microbial-derived metabolites in apolipoprotein E-deficient (ApoE) mice. We analyzed the fecal bacterial microbiome and targeted metabolites, including short-chain fatty acids (SCFAs) and bile acids (BAs). The immuno-inflammatory status of AS was evaluated by analyzing regulatory T cells (Tregs), Th17 cells, and the CD39-CD73 adenosine signaling pathway involved in purinergic signaling. Our results indicated that aspirin altered gut microbiota, leading to an increase in the phylum Bacteroidetes and a decrease in the Firmicutes to Bacteriodetes (F/B) ratio. Aspirin treatment also increased levels of targeted SCFA metabolites, such as propionic acid, valeric acid, isovaleric acid, and isobutyric acid. Furthermore, aspirin impacted BAs by reducing the level of harmful deoxycholic acid (DCA) and increasing the levels of beneficial isoalloLCA and isoLCA. These changes were accompanied by a rebalancing of the ratio of Tregs to Th17 cells and an increase in the expression of ectonucleotidases CD39 and CD73, thereby ameliorating inflammation. These findings suggest that aspirin has an athero-protective effect with an improved immuno-inflammatory profile, partially attributed to its manipulation of the gut microbiota.
Topics: Animals; Mice; Gastrointestinal Microbiome; Aspirin; Th17 Cells; Adenosine; T-Lymphocytes, Regulatory; Atherosclerosis; Inflammation; Apolipoproteins E; Signal Transduction
PubMed: 37187127
DOI: 10.1016/j.intimp.2023.110296 -
British Journal of Cancer Jul 2014Salicylates from plant sources have been used for centuries by different cultures to treat a variety of ailments such as inflammation, fever and pain. A chemical... (Review)
Review
Salicylates from plant sources have been used for centuries by different cultures to treat a variety of ailments such as inflammation, fever and pain. A chemical derivative of salicylic acid, aspirin, was synthesised and mass produced by the end of the 19th century and is one of the most widely used drugs in the world. Its cardioprotective properties are well established; however, recent evidence shows that it can also act as a chemopreventive agent. Its antithrombotic and anti-inflammatory actions occur through the inhibition of cyclooxygenases. The precise mechanisms leading to its anticancer effects are not clearly established, although multiple mechanisms affecting enzyme activity, transcription factors, cellular signalling and mitochondrial functions have been proposed. This review presents a brief account of the major COX-dependent and independent pathways described in connection with aspirin's anticancer effects. Aspirin's unique ability to acetylate biomolecules besides COX has not been thoroughly investigated nor have all the targets of its primary metabolite, salicylic acid been identified. Recent reports on the ability of aspirin to acetylate multiple cellular proteins warrant a comprehensive study to investigate the role of this posttranslational modification in its anticancer effects. In this review, we also raise the intriguing possibility that aspirin may interact and acetylate cellular molecules such as RNA, and metabolites such as CoA, leading to a change in their function. Research in this area will provide a greater understanding of the mechanisms of action of this drug.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Aspirin; Humans; Molecular Targeted Therapy; Neoplasms
PubMed: 24874482
DOI: 10.1038/bjc.2014.271 -
Seminars in Reproductive Medicine Jul 2017Human reproduction is an inefficient process. There are several drivers of complications along the path to and during pregnancy, one of which is inflammation. Treatments... (Review)
Review
Human reproduction is an inefficient process. There are several drivers of complications along the path to and during pregnancy, one of which is inflammation. Treatments to mitigate the deleterious effects of aberrant inflammation with something inexpensive and widely available like aspirin could have dramatic global impact. The Effects of Aspirin in Gestation and Reproduction (EAGeR) trial enrolled women aged 18 to 40 years with one to two prior pregnancy losses and no diagnosis of infertility. Patients were randomized to either low-dose aspirin or placebo. Here, we review the collective findings of the EAGeR trial to date and discuss several important lessons learned from the unique data resulting from this groundbreaking trial. Findings reported from this trial provide significant advances in the understanding of aspirin’s potential mechanisms in modulating reproductive processes and the role of inflammation in these processes. This review describes the collective findings of the EAGeR trial in the context of the existing literature regarding aspirin and inflammation in reproduction to inform relevant next steps in fertility and obstetric research, as well as potential implications for clinical care.
Topics: Adolescent; Adult; Aspirin; C-Reactive Protein; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Rate; Premature Birth; Randomized Controlled Trials as Topic; Reproduction; Young Adult
PubMed: 29036741
DOI: 10.1055/s-0037-1606384 -
Annals of Oncology : Official Journal... Jun 2012Aspirin has been associated to a reduced risk of colorectal and possibly of a few other common cancers. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Aspirin has been associated to a reduced risk of colorectal and possibly of a few other common cancers.
METHODS
To provide an up-to-date quantification of this association, we conducted a meta-analysis of all observational studies on aspirin and 12 selected cancer sites published up to September 2011.
RESULTS
Regular aspirin is associated with a statistically significant reduced risk of colorectal cancer [summary relative risk (RR) from random effects models = 0.73, 95% confidence interval (CI) 0.67-0.79], and of other digestive tract cancers (RR = 0.61, 95% CI = 0.50-0.76, for squamous cell esophageal cancer; RR = 0.64, 95% CI = 0.52-0.78, for esophageal and gastric cardia adenocarcinoma; and RR = 0.67, 95% CI = 0.54-0.83, for gastric cancer), with somewhat stronger reductions in risk in case-control than in cohort studies. Modest inverse associations were also observed for breast (RR = 0.90, 95% CI = 0.85-0.95) and prostate cancer (RR = 0.90, 95% CI = 0.85-0.96), while lung cancer was significantly reduced in case-control studies (0.73, 95% CI = 0.55-0.98) but not in cohort ones (RR = 0.98, 95% CI = 0.92-1.05). No meaningful overall associations were observed for cancers of the pancreas, endometrium, ovary, bladder, and kidney.
CONCLUSIONS
Observational studies indicate a beneficial role of aspirin on colorectal and other digestive tract cancers; modest risk reductions were also observed for breast and prostate cancer. Results are, however, heterogeneous across studies and dose-risk and duration-risk relationships are still unclear.
Topics: Aspirin; Humans; Neoplasms; Risk
PubMed: 22517822
DOI: 10.1093/annonc/mds113 -
Annual Review of Pharmacology and... Jan 2023Chemoprevention refers to the use of natural or synthetic agents to reverse, suppress, or prevent the progression or recurrence of cancer. A large body of preclinical... (Review)
Review
Chemoprevention refers to the use of natural or synthetic agents to reverse, suppress, or prevent the progression or recurrence of cancer. A large body of preclinical and clinical data suggest the ability of aspirin to prevent precursor lesions and cancers, but much of the clinical data are inferential and based on descriptive epidemiology, case control, and cohort studies or studies designed to answer other questions (e.g., cardiovascular mortality). Multiple pharmacological, clinical, and epidemiologic studies suggest that aspirin can prevent certain cancers but may also cause other effects depending on the tissue or disease and organ site in question. The best-known biological targets of aspirin are cyclooxygenases, which drive a wide variety of functions, including hemostasis, inflammation, and immune modulation. Newly recognized molecular and cellular interactions suggest additional modifiable functional targets, and the existence of consensus molecular cancer subtypes suggests that aspirin may have differential effects based on tumor heterogeneity. This review focuses on new pharmacological developments and innovations in biopharmacology that clarify the potential role of aspirin in cancer chemoprevention.
Topics: Humans; Aspirin; Anti-Inflammatory Agents, Non-Steroidal; Neoplasms; Inflammation; Chemoprevention
PubMed: 36202092
DOI: 10.1146/annurev-pharmtox-052020-023107 -
Angewandte Chemie (International Ed. in... Sep 2021Cells transmit piconewton forces to receptors to mediate processes such as migration and immune recognition. A major challenge in quantifying such forces is the sparsity...
Cells transmit piconewton forces to receptors to mediate processes such as migration and immune recognition. A major challenge in quantifying such forces is the sparsity of cell mechanical events. Accordingly, molecular tension is typically quantified with high resolution fluorescence microscopy, which hinders widespread adoption and application. Here, we report a mechanically triggered hybridization chain reaction (mechano-HCR) that allows chemical amplification of mechanical events. The amplification is triggered when a cell receptor mechanically denatures a duplex revealing a cryptic initiator to activate the HCR reaction in situ. Importantly, mechano-HCR enables direct readout of pN forces using a plate reader. We leverage this capability and measured mechano-IC for aspirin, Y-27632, and eptifibatide. Given that cell mechanical phenotypes are of clinical importance, mechano-HCR may offer a convenient route for drug discovery, personalized medicine, and disease diagnosis.
Topics: Aspirin; Eptifibatide; Humans; Nucleic Acid Hybridization
PubMed: 34242462
DOI: 10.1002/anie.202107660 -
British Medical Journal Jul 1970
Topics: Adult; Analgesics; Anti-Inflammatory Agents; Aspirin; Fever; Gastrointestinal Hemorrhage; Humans; Intestinal Absorption; Kidney Diseases; Salicylates; Uricosuric Agents
PubMed: 5310662
DOI: No ID Found -
Clinical Cancer Research : An Official... Apr 2015The anti-inflammatory properties of aspirin have resulted in its widespread use as an analgesic, antipyretic, and cardioprotective agent. Beyond these applications,... (Review)
Review
The anti-inflammatory properties of aspirin have resulted in its widespread use as an analgesic, antipyretic, and cardioprotective agent. Beyond these applications, multiple observational studies and randomized controlled trials have demonstrated a chemopreventative role for aspirin, particularly in the development of colorectal neoplasia. Given the critical importance of Wnt dysregulation in colorectal carcinogenesis, the interplay between aspirin and canonical Wnt signaling has become a focus of investigation. These studies have illuminated our understanding of the anticancer mechanisms of aspirin, yielding the identification of potential biomarkers for which aspirin's chemopreventative efficacy can be safely optimized into routine clinical practice and providing leads into the discovery of novel preventive and therapeutic targets. In this review, we summarize key experimental and clinical studies of this interaction, as well as highlighting future strategies to advance their clinical translation.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Colorectal Neoplasms; Humans; Molecular Targeted Therapy; Neoplasms; Wnt Signaling Pathway
PubMed: 25501125
DOI: 10.1158/1078-0432.CCR-14-0877 -
The Journal of Maternal-fetal &... Dec 2023Transcervical resection of adhesion (TCRA) and postoperative adjuvant estrogen and progestin are the main treatments for cavity adhesions, but the recurrence rate after... (Meta-Analysis)
Meta-Analysis Review
The effect of aspirin on uterine arterial blood flow and endometrium in moderate and severe intrauterine adhesion after transcervical resection of adhesion: a systematic review and meta-analysis.
BACKGROUND
Transcervical resection of adhesion (TCRA) and postoperative adjuvant estrogen and progestin are the main treatments for cavity adhesions, but the recurrence rate after surgery is still high. It was showed that aspirin could promote endometrial proliferation and repair after TCRA in patients with severe cavity adhesions, but the effect on reproduction was uncertain.
OBJECTIVE
To assess the effect of aspirin on uterine arterial blood flow and endometrium in moderate and severe intrauterine adhesion after transcervical resection of adhesion.
METHODS
The databases used included Cumulative Index to PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang database. Studies published before June 2022 were included. Each participant received an aspirin-based intervention aimed at improving uterine status, which was compared to a sham intervention. The primary outcome measure was a change in endometrium thickness. Secondary outcomes included uterine artery resistance index, blood flow index, and endometrial arterial resistance index.
RESULT
A total of 19 studies ( = 1361 participants) that met the inclusion criteria were included in this study. The aspirin-based intervention was strongly associated with better clinical outcome at second-look endometrium thickness (MD 0.81, CI 0.46-1.16; < .00001) and blood flow Index (FI) (MD 4.1, CI 2.3-5.9; < .00001). Besides, the analysis of arterial pulsatility index (PI) showed a significantly reduced after transcervical resection of adhesion (MD -0.9, CI -1.2 to 0.6; < .00001); whereas no significant difference was found in endometrial arterial resistance index (RI) (95% CI, -0.30 to 0.01; = .07).
CONCLUSION
Our study proved the effect of aspirin on uterine arterial blood flow and endometrium in moderate and severe intrauterine adhesion after transcervical resection of adhesion. However, the review requires evidence from additional randomized controlled trials and high-quality research. More strictly designed research studies are needed to assess the effectiveness of aspirin administration after transcervical resection of adhesion.
Topics: Female; Humans; Aspirin; Uterine Artery; Uterine Diseases; Endometrium; Uterus
PubMed: 37286223
DOI: 10.1080/14767058.2023.2209818