Aspirin Derivative 5-(Bis(3-methylbut-2-enyl)amino)-2-hydroxybenzoic Acid Improves Thermotolerance via Stress Response Proteins in Caenorhabditis elegans
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Aging is a major risk factor for many prevalent diseases. Pharmacological intervention to improve the health span and extend the lifespan could be a preventive elixir for aging and age-related diseases. The non-steroid anti-inflammation medicine aspirin was reported to delay aging in Caenorhabditis elegans (C. elegans) and mice. We are wondering if the analogues of aspirin could also present antiaging activity. Here, we synthesized several aspirin derivatives and investigated their thermotolerance and antiaging effect in C. elegans. One of the compounds, 5-(bis(3-methylbut-2-en-1-yl)amino)-2-hydroxybenzoic acid, moderately increased the survival of C. elegans under heat stress, but could not extend the lifespan under optimum conditions. This compound could increase the mRNA level of stress response gene gst-4, and the mRNA and protein expression level of heat shock protein hsp-16.2 under heat stress. The failure of activating the transcription factor DAF-16 might explain why this compound could not act as aspirin to extend the lifespan of C. elegans. Our results would help further the investigation of the pharmacological activity of aspirin analogues and the relationship between structures and activity.To the Editor.—
In his article (229:1221, 1974), "Aspirin—A Dangerous Drug?," Weiss correctly indicated that aspirin has "become the most widely used drug in the world." In 1972, the American public alone consumed more than 20 million pounds of it. Although aspirin is generally regarded as one of the safest drugs, it is nevertheless responsible for inducing occult gastrointestinal bleeding and may also cause acute and massive gastric hemorrhaging. Weiss further points out that "gastroscopic examination has disclosed the presence of hemorrhagic erosions immediately adjacent to undissolved aspirin tablets." Leonards and Levy1have also noted that "there is now considerable evidence that aspirin-induced gastric or gastrointestinal occult bleeding is usually a local effect resulting from contact of aspirin particles, or of the saturated solution of aspirin surrounding these particles, with the mucosa." Although forms of soluble aspirin, coated aspirin, buffered aspirin, aspirin substitutes, and combinations of aspirin with otherOccult
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Aims: Acetylsalicylic acid (Aspirin®) is routinely used after CABG as antiplatelet agent. Since the pyrazole analgesic dipyrone (Novalgin®) is often co-administered with aspirin and also known to interact with cyclooxygenase, the target of aspirin, we hypothesized that a drug interaction between aspirin and novalgin may contribute to aspirin resistance.
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Hepatocellular carcinoma (HCC) is the seventh most prevalent cancer globally and is the third leading cause of cancer-related mortality.The aim of this study was to evaluate the effect of aspirin use on the survival rates of individuals diagnosed with HCC.The patients were divided into two groups: those who used aspirin and those who did not. Aspirin use was defined as individuals who had used aspirin either before or after the diagnosis of HCC. Aspirin usage was determined based on prescription records. The criteria for aspirin use were defined as a minimum of 3 months and a minimum daily dose of 100 mg. Survival time; The time elapsed after the diagnosis of HCC was calculated as 'months'.Of the 300 cohorts studied in our study, 104 (34.6%) were using aspirin, while 196 (65.4%) were not. It was observed that bleeding occurred only in the patient group taking aspirin ( P = 0.002). When evaluated in terms of survival time, it was observed that it was significantly higher in the patient group using aspirin ( P = 0.001). Aspirin use was identified as factors that significantly impact survival ( P < 0.05). Aspirin use was identified as independent risk factors that significantly impact of survival ( P < 0.05).The aspirin group had a similar metabolic and liver reserve as the other group and had a longer survival despite being older and more comorbid diseases.
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ABSTRACT We have analyzed 31 mutations that have dominant effects on the behavior or morphology of the nematode Caenorhabditis elegans. These mutations appear to define 15 genes. We have studied ten of these genes in some detail and have been led to two notable conclusions. First, loss of gene function for four of these ten genes results in a wild-type phenotype; if these genes represent a random sample from the genome, then we would estimate that null mutations in about half of the genes in C. elegans would result in a nonmutant phenotype. Second, the dominant effects of mutations in nine of these ten genes are caused by novel gene functions, and in all nine cases the novel function is antagonized by the wild-type function.
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Cellular damage caused by reactive oxygen species is believed to be a major contributor to age-associated diseases. Previously, we characterized the Caenorhabditis elegans Brap2 ortholog (BRAP-2) and found that it is required to prevent larval arrest in response to elevated levels of oxidative stress. Here, we report that C. elegans brap-2 mutants display increased expression of SKN-1-dependent, phase II detoxification enzymes that is dependent on PMK-1 (a p38 MAPK C. elegans ortholog). An RNA-interference screen was conducted using a transcription factor library to identify genes required for increased expression of the SKN-1 target gst-4 in brap-2 mutants. We identified ELT-3, a member of the GATA transcription factor family, as a positive regulator of gst-4p::gfp expression. We found that ELT-3 interacts with SKN-1 to activate gst-4 transcription in vitro and that elt-3 is required for enhanced gst-4 expression in the brap-2(ok1492) mutant in vivo Furthermore, nematodes overexpressing SKN-1 required ELT-3 for life-span extension. Taken together, these results suggest a model where BRAP-2 acts as negative regulator of SKN-1 through inhibition of p38 MAPK activity, and that the GATA transcription factor ELT-3 is required along with SKN-1 for the phase II detoxification response in C. elegans.
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Проведено сравнительное исследование токсического действия ионов свинца, кадмия и меди на организм почвенной нематоды Caenorhabditis elegans линии дикого типа N2. Двухчасовая экспозиция нематод к растворам Pb(NO3)2, Cu(NO3)2 или Cd(NO3)2 в концентрации 10 и 20 мМ повышала чувствительность моторной программы плавания, индуцированного механическим стимулом, к агонисту никотиновых рецепторов ацетилхолина левамизолу в концентрации 2, 4 и 8 мкМ. Повышение чувствительности локомоции C. elegans к левамизолу проявлялось в снижении доли нематод, сохранивших способность поддерживать плавание в течение 10 с после стимула. В условиях экспериментов наиболее сильное токсическое действие на нематод оказывал нитрат меди, наименее токсичным был нитрат свинца. 30-минутная экспозиция C. elegans к Pb(NO3)2, Cu(NO3)2 или Cd(NO3)2 в концентрации 10 и 20 мМ с последующим восстановлением нематод в течение 24 часов на среде выращивания с бактериями также повышала чувствительность моторной программы плавания к левамизолу. Выявленное повышение чувствительности локомоции C. elegans к левамизолу после кратковременной экспозиции к ионам Pb2+, Cd2+ и Cu2+ не может быть следствием накопления этих токсикантов во внутренней среде из-за наличия у нематод кутикулы, ограничивающей проникновение токсикантов во внутреннюю среду организма. Кратковременная экспозиция нематод к высоким дозам Pb(NO3)2 могла вызвать гибель части дофаминергических нейронов, что привело к снижению уровня эндогенного дофамина. Снижение уровня эндогенного дофамина, в свою очередь, могло привести к повышению содержания эндогенного ацетилхолина и, как следствие, повышению чувствительности никотиновых холинорецепторов к их агонисту левамизолу. Возможным объяснением выявленного в работе повышения чувствительности локомоции C. elegans к левамизолу после кратковременного действия Cd(NO3)2 и Cu(NO3)2 может быть изменение функций холинергических и ГАМКергических нейронов в системе нейронов, участвующей в реализации моторной программы плавания нематод.
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To evaluate the effectiveness of the AggreGuide A-100, a point-of-care platelet aggregometer, in detecting aspirin-induced platelet dysfunction at high and low doses of aspirin. Sixty-five individuals who had not been taking aspirin in the previous 14 days were recruited for the High-Dose Aspirin Study and were administered a single high dose of aspirin (650 mg). Thirteen subjects who had been aspirin-free for 7 to 10 days were subsequently recruited for the Low-Dose Aspirin Study and were administered a low dose of aspirin (81mg/day) for 7 to 10 days. We obtained measurements of the subjects’ whole-blood samples using the AggreGuideA-100 at baseline and after the ingestion of aspirin in both groups. In the High-Dose Aspirin Study, 59 of the 65 subjects (91%) exhibited a reduction in their platelet aggregation index (PAI) value, as measured by the AggreGuide A-100, after taking a single 650 mg dose of aspirin. In the Low-Dose Aspirin Study, all 13 subjects (100%) exhibited a reduction in their PAI value, as measured by the AggreGuide A-100, after taking 81 mg per day of aspirin for 7 to 10 days. The results from the High- and Low-Dose Aspirin Groups indicate that the AggreGuide A-100 yields prompt, reliable measurement of aspirin-induced dysfunction, as indicated by a decreasing PAI value, in the presence of high or low doses of aspirin.
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이영경•김한성•박지영•강희정 한림대학교 의과대학 진단검사의학교실
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Background The present study was aimed to investigate the usage of aspirin for the secondary prevention of ischemic stroke, evaluate the correlated factors, and analyze the reasons for not taking and irregularly taking aspirin. Methods The patients in this group were all stroke survivors who have formerly been diagnosed with a cerebral infarction or transient ischemic attack (TIA) in our hospital. We investigated their use of aspirin over a three-year period following their hospitalization. According to the patients' aspirin usage, they were divided into treatment and non-treatment groups. In addition, the reasons for not taking or irregularly taking aspirin were analyzed in the two groups. Results A total of 1240 patients were studied, including 367 (29.60%) in the treatment group and 873 (70.40%) cases in the non-treatment group. In addition, 201 (16.20%) cases in the treatment group had been regularly taking aspirin (50-325 mg of aspirin daily) for 1 to 3 years or longer. The results demonstrated that the main reasons for not taking aspirin in this study were related to patients' concerns regarding the side effects of taking aspirin (46.45%), as well as the doctors' inadequacy in informing their patients to take aspirin (38.71%). The major reasons for patients to irregularly take aspirin were that the doctors did not notify the length of aspirin usage to their patients (41.57%), and that doctors did not prescribe aspirin upon the patients' follow-up visit (26.51%). Conclusion The most effective way to increase patient's compliance for aspirin consumption is to promote the guidelines for stroke treatment and to relay these advances in stroke therapy to the patient.
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Little is known about the contribution of over-the-counter (OTC) aspirin to cardiovascular prophylaxis. To investigate this, a two-phase cross-sectional study was carried out in nine general practices in North Staffordshire. In the first phase, all patients with cardiovascular disease (CVD) were identified from computer searches using morbidity registers and drug searches. The search also identfied the subgroup receiving prescribed prophylactic aspirin. In the second phase, a questionnaire was posted to all patients with CVD who were not on prescribed aspirin to establish their current use of OTC aspirin. Overall, 69% of the CVD group used aspirin, with 26% of aspirin being OTC. OTC aspirin use was more common in those aged under 65 years, men, and the more affluent. Also, there were significant differences in OTC aspirin use between the various practices. This study shows that a considerable amount of aspirin is used OTC in those with CVD. Its use is influenced by several factors that could be addressed when considering attempts to improve the overall uptake of aspirin.
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