Ameliorative role of aspirin in paraquat‐induced lung toxicity via mitochondrial mechanisms

Paraquat (PQ) has accounted for numerous suicide attempts in developing countries. Aspirin (ASA) as an adjuvant treatment in PQ poisoning has an ameliorative role. And, it's uncoupling of mitochondrial oxidative phosphorylation role has been well established. The current study aimed at examining the aspirin mechanism on lung mitochondria of rats exposed to PQ. Male rats were randomly allocated in five groups: Control group, PQ group (50 mg/kg; orally, only on the first day), and PQ + ASA (100, 200, and 400 mg/kg; i.p.) groups for 3 weeks. Mitochondrial indices and respiratory chain‐complex activities were determined. PQ induced lung interstitial fibrosis; however, ASA (400 mg/kg) led to decrease in this abnormal alteration. In comparison with PQ group, complex II and IV activity, and adenosine triphosphate content in ASA groups had significantly increased; however, reactive oxygen species production, mitochondrial membrane permeabilization, and mitochondrial swelling were significantly reduced. In conclusion, aspirin can alleviate lung injury induced by PQ poisoning by improving mitochondrial dynamics.     

Aspirin inhibits adipogenesis of tendon stem cells and lipids accumulation in rat injury tendon through regulating PTEN/PI3K/AKT signalling

Tendon injury repairs are big challenges in sports medicine, and fatty infiltration after tendon injury is very common and hampers tendon injury healing process. Tendon stem cells (TSCs), as precursors of tendon cells, have shown promising effect on injury tendon repair for their tenogenesis and tendon extracellular matrix formation. Adipocytes and lipids accumulation is a landmark event in pathological process of tendon injury, and this may induce tendon rupture in clinical practice. Based on this, it is important to inhibit TSCs adipogenesis and lipids infiltration to restore structure and function of injury tendon. Aspirin, as the representative of non‐steroidal anti‐inflammatory drugs (NSAIDs), has been widely used in tendon injury for its anti‐inflammatory and analgesic actions, but effect of aspirin on TSCs adipogenesis and fatty infiltration is still unclear. Under adipogenesis conditions, TSCs were treated with concentration gradient of aspirin. Oil red O staining was performed to observe changes of lipids accumulation. Next, we used RNA sequencing to compare profile changes of gene expression between induction group and aspirin‐treated group. Then, we verified the effect of filtrated signalling on TSCs adipogenesis. At last, we established rat tendon injury model and compared changes of biomechanical properties after aspirin treatment. The results showed that aspirin decreased lipids accumulation in injury tendon and inhibited TSCs adipogenesis. RNA sequencing filtrated PTEN/PI3K/AKT signalling as our target. After adding the signalling activators of VO‐Ohpic and IGF‐1, inhibited adipogenesis of TSCs was reversed. Still, aspirin promoted maximum loading, ultimate stress and breaking elongation of injury tendon. In conclusion, by down‐regulating PTEN/PI3K/AKT signalling, aspirin inhibited adipogenesis of TSCs and fatty infiltration in injury tendon, promoted biomechanical properties and decreased rupture risk of injury tendon. All these provided new therapeutic potential and medicine evidence of aspirin in treating tendon injury and tendinopathy.     

Role of p38 MAPK in enhanced human cancer cells killing by the combination of aspirin and ABT‐737

Regular use of aspirin after diagnosis is associated with longer survival among patients with mutated‐PIK3CA colorectal cancer, but not among patients with wild‐type PIK3CA cancer. In this study, we showed that clinically achievable concentrations of aspirin and ABT‐737 in combination could induce a synergistic growth arrest in several human PIK3CA wild‐type cancer cells. In addition, our results also demonstrated that long‐term combination treatment with aspirin and ABT‐737 could synergistically induce apoptosis both in A549 and H1299 cells. In the meanwhile, short‐term aspirin plus ABT‐737 combination treatment induced a greater autophagic response than did either drug alone and the combination‐induced autophagy switched from a cytoprotective signal to a death‐promoting signal. Furthermore, we showed that p38 acted as a switch between two different types of cell death (autophagy and apoptosis) induced by aspirin plus ABT‐737. Moreover, the increased anti‐cancer efficacy of aspirin combined with ABT‐737 was further validated in a human lung cancer A549 xenograft model. We hope that this synergy may contribute to failure of aspirin cancer therapy and ultimately lead to efficacious regimens for cancer therapy.     

Aspirin boosts the synergistic effect of EGFR/p53 inhibitors on lung cancer cells by regulating AKT/mTOR and p53 pathways

The regimen of afatinib and vinorelbine has been used to treat breast or lung cancer cells with some limitations. Aspirin alone or in combination with other agents has shown unique efficacy in the treatment of cancer. We designed a preclinical study to investigate whether the triple therapy of aspirin, afatinib, and vinorelbine could synergistically inhibit the growth of p53 wild-type nonsmall cell lung cancer (NSCLC) cells. Three NSCLC cells A549, H460, and H1975 were selected to study the effect of triple therapy on cell proliferation and apoptosis. Compared to single agents, triple therapy synergistically inhibited the proliferation of lung cancer cells with combination index <1. Meanwhile, the therapeutic index of triple therapy was superior to that of single agents, indicating a balance between efficacy and safety in the combination of three agents. Mechanistic studies showed that triple therapy significantly induced apoptosis by decreasing mitochondrial membrane potential, increasing reactive oxygen species, and regulating mitochondria-related proteins. Moreover, epidermal growth factor receptor (EGFR) downstream signaling proteins including JNK, AKT, and mTOR were dramatically suppressed and p53 was substantially increased after NSCLC cells were exposed to the triple therapy. We provided evidence that the triple therapy of aspirin, afatinib and vinorelbine synergistically inhibited lung cancer cell growth through inactivation of the EGFR/AKT/mTOR pathway and accumulation of p53, providing a new treatment strategy for patients with p53 wild-type NSCLC.     

水杨酸和阿斯匹林对小麦盐害的缓解作用

盐胁迫条件下水杨酸和阿斯匹林能提高小麦种子发芽率、发芽指数和活力指数,降低幼苗叶片质膜透性和盐胁迫对细胞膜的伤害,提高幼苗体内超氧化物歧化酶、过氧化物酶等细胞保护酶的活性,减少膜脂过氧化作用产物丙二醛的积累,降低根系Ｎａ＋和提高根系Ｋ＋ 的向上运输选择性。所有这些变化都有利于缓解盐胁迫对小麦的伤害,提高其对盐胁迫的适应性。     

双联抗血小板治疗急性冠脉综合征临床疗效观察

目的：探讨双联抗血小板治疗急性冠脉综合征（ACS）的临床疗效和安全性。方法：60例ACS患者随机分为治疗组和对照组。对照组给予阿司匹林单抗血小板治疗,治疗组采用阿司匹林＋氯吡格雷双联抗血小板治疗,治疗3个月后评价临床疗效。结果：治疗组临床疗效总有效率为93.3%,显著高于对照组（76.7%）,相比较有显著性差异（P〈0.05）;治疗后,两组LVEF、CO、E/A显著上升,与治疗前比较均有显著性差异（P〈0.05）;且治疗组与对照组比较有显著性差异（P〈0.05）。结论：阿司匹林和氯吡格雷双联抗血小板药物治疗ACS,可以强化对血小板聚集的抑制,并增强抗栓效果,值得临床应用。     

Does Aspirin Provide Adequate Chemoprophylaxis for Venous Thromboembolic Events in Operative Pelvic and Acetabular Fractures?

BackgroundSeveral strategies exist to prevent venous thromboembolism (VTE) in operative pelvic and acetabular fractures, however literature lacks consensus on the optimal thromboprophylaxis. Even more debated, and perhaps controversial, is whether aspirin provides adequate thromboprophylaxis in the setting of these injuries. The primary objective was to evaluate the efficacy of aspirin in the prevention of venous thromboembolism (VTE) events, including deep vein thrombosis (DVT) and pulmonary embolism (PE) in operative pelvic and acetabular fractures compared to other anticoagulants.MethodsA retrospective chart review of pelvic and acetabular fractures that underwent operative fixation was completed. The incidence of VTE and hematoma formation was evaluated and compared between patients who received aspirin versus enoxaparin or heparin. Multivariate analysis was performed to control for confounding demographic, comorbidity, and injury-related variables. The outcome measurements included development of DVT and/or PE and hematoma formation.ResultsOf patients with operative pelvic and acetabular fractures, 4.2% developed a DVT and 3.5% developed a PE, with 1.4% developing both. Of these patients 37.5% were treated with aspirin versus the 62.5% treated with heparin or enoxaparin. There was no significant difference in the incidence of DVT or PE between cohorts (p=0.498 and p=0.262). Aspirin trended toward significance as protective against post-operative hematoma (p=0.085).ConclusionThis study suggests that aspirin is an acceptable method of VTE thromboprophylaxis with no inferior results to other common anticoagulants used in operative pelvis and acetabular fractures. As a chemoprophylactic agent, aspirin is an efficacious option in these complex injuries that shows no increase in the incidence in symptomatic VTE events. Level of Evidence: III     

Aspirin regulates SNARE protein expression and phagocytosis in dendritic cells

Abstract

Since being introduced globally as Aspirin in 1899, acetylsalicylic acid (ASA) has been widely used as an analgesic, immune-regulatory, anti-pyretic and anti-thrombotic drug. ASA and its metabolite, salicylate, were also reported to be able to modulate antigen presenting functions of dendritic cells (DC). However, the intracellular targets of ASA in DC are still poorly understood. Since phagocytosis is the initial step taken by antigen-presenting cells in the uptake of antigens for processing and presentation, ASA might exerts its immune-regulatory effects by regulating phagocytosis. Here we show that ASA inhibits phagocytosis and modulates expression of endosomal SNAREs, such as Vti1a, Vti1b, VAMP-3, VAMP-8 and Syn-8 (but not syn-6 and syn-16) in DC. We further show that the phagocytic inhibitory effect of ASA is dependent on the expression of Vti1a and Vti1b. Consistently, Vti1a and Vti1b localize to the phagosomes and up-regulation of Vti1a and Vti1b inhibits phagocytosis in DC. Our results suggest that ASA modulates phagocytosis in part through the control of endosomal SNARE protein expression and localization in DC. All experiments were performed using either a murine DC line (DC2.4) or primary DC derived from murine bone marrow cells.     

Competition of cytarabine and aspirin in binding to serum albumin in multidrug therapy

The aim of this study was to describe a competition between cytarabine (araC) and aspirin (ASA) in binding with bovine serum albumin (BSA). High-affinity binding sites for both drugs were determined using a spectrofluorimetric method. Cytarabine as well as aspirin binds in the IIA hydrophobic subdomain of the transporting protein. Binding constants for araC-BSA and ASA-BSA were calculated by the Scatchard method. Analysis of ultraviolet (UV) difference spectra showed that araC, which has a higher affinity to BSA in comparison to ASA [Ka(araC) > Ka(ASA)] displaces ASA in high-affinity binding sites.The competition between drugs in low-affinity binding sites was investigated using (1)H nuclear magnetic resonance (NMR) and 13C-NMR spectra. We concluded that in the low-affinity binding sites cytarabine decreases the affinity of albumin toward aspirin. However, the interaction between araC and BSA becomes more difficult in the presence of aspirin.