The risk of developing cardiovascular disease is significantly higher for individuals with diabetes compared to those without. Aspirin has been widely used for primary prevention in diabetic patients. However, evidence is limited in the Asian population. We aimed to compare the effectiveness and safety of aspirin versus placebo for primary cardiovascular prevention in the Asian population with type 2 diabetes. In this study, we performed propensity score matching with non-aspirin users from January 2006 to December 2015 (n = 37,095 in each group after matching, PSM). We analyzed the incidence risk of all-cause mortality, composite cardiovascular events, and hospitalized major bleeding. The propensity score-matched (PSM) cohort of patients who received aspirin within one year of diabetes diagnosis was compared with the non-aspirin diabetic (DM) cohort. Baseline characteristics were balanced between the two groups. The median follow-up duration was 78 months. Aspirin users exhibited a slightly but significantly lower rate of all-cause mortality (HR: 0.92; 95% CI: 0.87 to 0.96). However, they also had a significantly higher composite cardiovascular risk (HR: 1.34; 95% CI: 1.28-1.40), including non-fatal acute myocardial infarction (HR: 1.33; 95% CI: 1.18 to 1.50), non-fatal ischemic stroke (HR: 1.38; 95% CI: 1.30 to 1.45), heart failure (HR: 1.18; 95% CI: 1.09 to 1.27), and coronary revascularization (HR: 1.94; 95% CI: 1.73 to 2.17). Aspirin users also faced a significantly higher risk of hospitalized major bleeding (HR: 1.08; 95% CI: 1.03 to 1.14). The presence of one or more additional risk factors did not influence the effectiveness and safety outcomes of aspirin, according to stratified analysis. In conclusion, in this real-world Asian diabetic population, aspirin was associated with a significantly lower mortality risk but also with higher risks of cardiovascular events and hospitalized bleeding. Aspirin may not play a role in the primary prevention of cardiovascular disease in such patients, regardless of additional risk factors.

BACKGROUND: Atypical acinar cell foci (AACF) seen in pancreatic cancer are fatal and have been studied with some causative agents. However, for the first time, the effect of acetylsalicylic acid with nitric oxide (NO-ASA) on AACF was examined in this study. Although NO-ASA has very successful inhibitory effects against some types of cancer, it has not been investigated whether they can exert their inhibition effects on AACFs.
METHODS: For experimental purposes, 21 14-day-old male Wistar albino rats were used. Azaserine (30 mg/kg) was dissolved in 0.9% NaCl solution and injected intraperitoneally (i.p.) into 14 rats, except for the Control group (Cont) rats, for three weeks. Rats that were injected with azaserine once a week for three weeks and those that did not receive treatment were divided into experimental groups. 15 days after the end of the azaserine injection protocol, NO-ASA was applied to azaserine with NO-ASA (Az+NO-ASA) group rats three consecutive times with an interval of 15 days by gavage. At the end of the 5-month period, pancreatic tissue was dissected and weighed. Pancreas preparations prepared from histological sections were examined for AACF burden and analyzed via a video image analyzer. One-way analysis of variance (ANOVA) non-parametric statistical analyses were performed to test whether there was a difference between the averages of the experimental and Control groups.
RESULTS: AACF burden in both groups injected with azaserine was found to be statistically significant in all categories compared to that of the Control group (p < 0.05). The average Calculated Estimated average AACF volume (mm3) values, the Calculated estimated average AACF diameter (μm), the Estimated average number of AACF per unit volume, AACF rate as a % of Calculated Organ Volume were higher in the AzCont group rats than in the Az+NO-ASA group, when compared, and there was an important level statistical difference between the groups (p < 0.05). It was determined that for all parameters AACFs load in Az+NO-ASA group rats were significantly reduced compared to that of AzCont group rats (p < 0.05).
CONCLUSIONS: We observed that, as a result of the NO-ASA application, the experimental AACF focus ratio created by azaserine injection was significantly inhibited. The inhibitory effect of AACFs in Az+NO-ASA group rats may have resulted from the significant and independent chemopreventive and/or chemotherapeutic activity of NO-ASA against exocrine pancreatic AACF foci.

UNASSIGNED: Deep Vein Thrombosis (DVT) is a significant medical concern characterized by the formation of blood clots within the venous system. Surgical procedures are known to increase the risk of DVT. While enoxaparin has proven to be highly effective in treating DVT, concerns about bleeding and accurate dosage regulation may restrict its application. Recent research has focused on aspirin\'s potential in preventing DVT after various surgeries. This study aimed to determine whether aspirin was as effective as enoxaparin in preventing DVT after spine surgery.
UNASSIGNED: This randomized controlled trial enrolled study patients who underwent spine surgery at Shahid Kamyab Emergency Hospital in Mashhad, and had a Caprini score > 5, indicating a higher risk of DVT. In the control group, patients received subcutaneous injections of enoxaparin at a dosage of 40 mg, while the intervention group received oral aspirin tablets with a daily dosage of 81 mg. An experienced radiologist performed a Doppler ultrasound of the lower limbs\' veins seven days after surgery to diagnose DVT. The outcomes of the two groups were then compared.
UNASSIGNED: A total of 100 patients participated in the clinical trial and were equally assigned to the aspirin and enoxaparin groups. Both groups were homogeneous regarding the basic and clinical characteristics. The incidence of postoperative DVT was 4.0% in the aspirin group and 10.0% in the enoxaparin group (p=0.092). The incidence of hemorrhage was 2.0% in the aspirin group and 4.0% in the enoxaparin group (p=0.610).
UNASSIGNED: These findings indicate that aspirin may be a promising alternative to enoxaparin for DVT prevention after surgery, but additional research is essential to validate these results and further assess the benefits and risks associated with aspirin usage in this context.

The objective of this study was to investigate the association between a Parkinson\'s disease (PD)-specific polygenic score (PGS) and protective lifestyle factors on age at onset (AAO) in PD. We included data from 4367 patients with idiopathic PD, 159 patients with GBA1-PD, and 3090 healthy controls of European ancestry from AMP-PD, PPMI, and Fox Insight cohorts. The association between PGS and lifestyle factors on AAO was assessed with linear and Cox proportional hazards models. The PGS showed a negative association with AAO (β = - 1.07, p = 6 × 10-7) in patients with idiopathic PD. The use of one, two, or three of the protective lifestyle factors showed a reduction in the hazard ratio by 21% (p = 0.0001), 44% (p < 2 × 10-16), and 55% (p < 2 × 10-16), compared to no use. An additive effect of aspirin (β = 7.62, p = 9 × 10-7) and PGS (β = - 1.58, p = 0.0149) was found for AAO without an interaction (p = 0.9993) in the linear regressions, and similar effects were seen for tobacco. In contrast, no association between aspirin intake and AAO was found in GBA1-PD (p > 0.05). In our cohort, coffee, tobacco, aspirin, and PGS are independent predictors of PD AAO. Additionally, lifestyle factors seem to have a greater influence on AAO than common genetic risk variants with aspirin presenting the largest effect.

BACKGROUND: Mediators, genomic and epigenomic characteristics involving in metabolism of arachidonic acid by cyclooxygenase (COX) and lipoxygenase (ALOX) and hepatic activation of clopidogrel have been individually suggested as factors associated with resistance against aspirin and clopidogrel. The present multi-center prospective cohort study evaluated whether the mediators, genomic and epigenomic characteristics participating in arachidonic acid metabolism and clopidogrel activation could be factors that improve the prediction of the aspirin and clopidogrel resistance in addition to cardiovascular risks.
METHODS: We enrolled 988 patients with transient ischemic attack and ischemic stroke who were evaluated for a recurrence of ischemic stroke to confirm clinical resistance, and measured aspirin (ARU) and P2Y12 reaction units (PRU) using VerifyNow to assess laboratory resistance 12 weeks after aspirin and clopidogrel administration. We investigated whether mediators, genotypes, and promoter methylation of genes involved in COX and ALOX metabolisms and clopidogrel activation could synergistically improve the prediction of ischemic stroke recurrence and the ARU and PRU levels by integrating to the established cardiovascular risk factors.
RESULTS: The logistic model to predict the recurrence used thromboxane A synthase 1 (TXAS1, rs41708) A/A genotype and ALOX12 promoter methylation as independent variables, and, improved sensitivity of recurrence prediction from 3.4% before to 13.8% after adding the mediators, genomic and epigenomic variables to the cardiovascular risks. The linear model we used to predict the ARU level included leukotriene B4, COX2 (rs20417) C/G and thromboxane A2 receptor (rs1131882) A/A genotypes with the addition of COX1 and ALOX15 promoter methylations as variables. The linear PRU prediction model included G/A and prostaglandin I receptor (rs4987262) G/A genotypes, COX2 and TXAS1 promoter methylation, as well as cytochrome P450 2C19*2 (rs4244285) A/A, G/A, and *3 (rs4986893) A/A genotypes as variables. The linear models for predicting ARU (r = 0.291, R2 = 0.033, p < 0.01) and PRU (r = 0.503, R2 = 0.210, p < 0.001) levels had improved prediction performance after adding the genomic and epigenomic variables to the cardiovascular risks.
CONCLUSIONS: This study demonstrates that different mediators, genomic and epigenomic characteristics of arachidonic acid metabolism and clopidogrel activation synergistically improved the prediction of the aspirin and clopidogrel resistance together with the cardiovascular risk factors.
BACKGROUND: URL: https://www.
RESULTS: gov ; Unique identifier: NCT03823274.

BACKGROUND: Gastric mucosal injury is a chronic and progressive stomach disease that can be caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, there is an urgent need to find safe and effective drugs to prevent gastric mucosal injury due to NSAIDs. Cinnamaldehyde (CA) is a bioactive compound extracted from the rhizome of cinnamon and has various pharmacological functions, including anti-inflammatory, analgesic, antiapoptotic, and antioxidant activities. However, the potential pharmacological effect of CA on gastric mucosal injury remains unknown.
OBJECTIVE: The aim of this study was to investigate the protective effects of CA on aspirin-induced gastric mucosal injury and to explore its mechanism of action METHODS: The effect of CA on gastric mucosal injury was investigated in vitro and in vivo, in vitro mouse model of gastric mucosal injury induced by aspirin, in vitro model of GES-1 cell injury by aspirin and Erastin. The mechanism of action of CA was determined using Transcriptomics and bioinformatics.
RESULTS: CA exerted its protective effects against gastric mucosal injury by modulating the downstream targets, including mTOR, GSK3β, and NRF2, via the PI3K/AKT signaling pathway to inhibit autophagy, apoptosis, and ferroptosis in the gastric epithelial cells. Further cellular experiments confirmed that the PI3K/AKT pathway was a key target for CA against gastric mucosal injury.
CONCLUSIONS: This study provides the first evidence of CA, an active compound in cinnamon, possessing therapeutic potential in preventing and treating gastric mucosal injury, with its mechanism involving the regulation of apoptosis, autophagy, and ferroptosis in gastric epithelial cells mediated by the PI3K/AKT signaling pathway.

Sublingual hematoma, a rare but potentially life-threatening condition, can arise spontaneously or secondary to various triggers, including trauma, dental procedures, or anticoagulant therapy. We present a case of massive spontaneous sublingual hematoma in a 45-year-old woman receiving aspirin therapy for rheumatic heart disease. Despite the absence of trauma or procedural triggers, the patient presented with bleeding from the floor of the mouth and significant submental swelling, prompting urgent intervention to secure the airway and manage coagulopathy. Conservative measures, including discontinuation of aspirin and intravenous vitamin K administration, led to gradual hematoma resolution and favorable patient outcomes. This case highlights the importance of prompt recognition and early management of sublingual hematoma, particularly in the context of aspirin therapy-induced coagulopathy.

Introduction The intertwined nature of obesity and diabetes, termed diabesity, is a significant health concern. Aspirin has been recognized for its potential in mitigating inflammation-related health issues, a key concern in managing diabesity. However, the optimal aspirin dosage and its impact on specific inflammatory markers, viz. high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, over time remain a subject of ongoing research. Objective This study investigated the effects of different doses of aspirin (150mg and 300mg) on the levels of hs-CRP and IL-6 over a period of 6 months. Methods This cross-sectional observational quasi-experiment study involved 125 confirmed type-2 diabetes mellitus (T2DM) patients with obesity aged ≥40 years. Blood samples were collected for analyzing hs-CRP and IL-6 levels. Demographics and clinical characteristics, such as BMI, waist-hip ratio, blood parameters, fasting blood sugar (FBS), and hs-CRP, were analyzed. Results At baseline, both the 150 mg and 300 mg aspirin dose groups had similar median levels of hs-CRP. After two months, there was no significant difference (p=0.150). However, by six months, the 150mg dose group had a significantly higher median hs-CRP than the 300 mg dose group (p=0.003). The 150 mg dose group had a significantly higher median level of IL-6 levels at baseline (median; 40.0) compared to the 300 mg dose group (median; 2.27, p<0.0001). After two months, the levels of IL-6 in both groups were similar (median; 2.27 and 2.23 respectively, p<0.0001). By the end of six months, the groups had no significant difference (median; 0.53 and 2.22 respectively, p=0.128). Conclusion The dose of aspirin may significantly impact the levels of hs-CRP and IL-6 over time, with the effects being more pronounced after six months of treatment. These findings suggest that aspirin, a commonly used and cost-effective medication, could potentially be leveraged in a more targeted manner to manage inflammation (CRP and IL-6 levels) in individuals with diabesity.

The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight heparin (LMWH) has gained increasing relevance for its therapeutic potential. On this regard, the aim of this systematic review and meta-analysis is to analyze the efficacy of low molecular weight heparin (LMWH) from the beginning of pregnancy in terms of live birth rates (LBR) in U-RPL. Registered randomized controlled trials (RCTs) were included. We stratified findings based on relevant clinical factors including number of previous miscarriages, treatment type and control type. Intervention or exposure was defined as the administration of LMWH alone or in combination with low-dose aspirin (LDA). A total of 6 studies involving 1016 patients were included. The meta-analysis results showed that LMWH used in the treatment of U-RPL was not associated with an increase in LBR with a pooled OR of 1.01, a medium heterogeneity (26.42%) and no publication bias. Results of other sub-analyses according to country, treatment type, and control type showed no significant effect of LMWH on LBR in all subgroups, with a high heterogeneity. The results highlight a non-significant effect of LMWH in U-RPL on LBR based on moderate quality evidence.Registration number: PROSPERO: ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326433 ).

In previous studies, we have demonstrated that stress response-induced high glucocorticoid levels could be the underlying cause of traumatic heterotopic ossification (HO), and we have developed a glucocorticoid-induced ectopic mineralization (EM) mouse model by systemic administration of a high dose of dexamethasone (DEX) to animals with muscle injury induced by cardiotoxin injection. In this model, dystrophic calcification (DC) developed into HO in a cell autonomous manner. However, it is not clear how DC is formed after DEX treatment. Therefore, in this study, we aimed to explore how glucocorticoids initiate muscle EM at a cellular and molecular level. We showed that DEX treatment inhibited inflammatory cell infiltration into injured muscle but inflammatory cytokine production in the muscle was significantly increased, suggesting that other non-inflammatory muscle cell types may regulate the inflammatory response and the muscle repair process. Accompanying this phenotype, transforming growth factor β1 (TGF-β1) expression in fibro-adipogenic progenitors (FAPs) was greatly down-regulated. Since TGF-β1 is a strong immune suppressor and FAP\'s regulatory role has a large impact on muscle repair, we hypothesized that down-regulation of TGF-β1 in FAPs after DEX treatment resulted in this hyperinflammatory state and subsequent failed muscle repair and EM formation. To test our hypothesis, we utilized a transgenic mouse model to specifically knock out Tgfb1 gene in PDGFRα positive FAPs to investigate if the transgenic mice could recapitulate the phenotype that was induced by DEX treatment. Our results showed that the transgenic mice completely phenocopied this hyperinflammatory state and spontaneously developed EM following muscle injury. On the contrary, therapeutics that enhanced TGF-β1 signaling in FAPs inhibited the inflammatory response and attenuated muscle EM. In summary, these results indicate that FAPs-derived TGF-β1 is a key molecule in regulating muscle inflammatory response and subsequent EM, and that glucocorticoids exert their effect via down-regulating TGF-β1 in FAPs.
Heterotopic ossification (HO) is abnormal bone formation in soft tissue. Glucocorticoids, which have strong anti-inflammatory properties, have usually been used as HO therapeutics. However, our findings suggest that glucocorticoids can also promote HO formation. In this study, we tried to explain the underlying reason for these seemingly contradictory observations. We showed that glucocorticoids, in addition to exerting an anti-inflammatory effect on inflammatory cells, can also target another type of muscle cell to exert a pro-inflammatory effect. These cells are called fibro-adipogenic progenitors (FAPs), and we demonstrated that FAPs played a master regulatory role in the muscle inflammatory response by modulating the expression of transforming growth factor β1 (TGF-β1), a well-known immune suppressor. In summary, our findings highlighted the importance of FAP TGF-β1 levels in affecting the progression and regression of muscle HO, and provided new treatment options for HO based on their ability to elevate TGF-β1 levels in FAPs.