Colchicine

秋水仙碱
  • 文章类型: Journal Article
    急性冠脉综合征(ACS)是全球心血管死亡的重要原因。ACS可能起因于动脉粥样硬化斑块的破坏,最终导致急性缺血和心肌梗死。在动脉粥样硬化的发病机制中,炎症起着关键作用,不仅仅是动脉粥样硬化斑块形成的开始和并发症,而且在心肌对缺血性损伤的反应中。急性炎症过程,再加上再灌注的时间,协调缺血和再灌注损伤,指示梗死程度和急性左心室(LV)重塑。相反,慢性炎症,除了神经体液激活,支配持续性左心室重塑。慢性LV重塑和复发性缺血发作之间的相互作用描绘了疾病向心力衰竭和心血管死亡的进展。秋水仙碱通过调节单核细胞/巨噬细胞的活性发挥影响心肌和动脉粥样硬化斑块的抗炎特性,中性粒细胞,和血小板。这种调节可能会导致更有利的LV重塑并阻止ACS的复发。这篇叙述性综述旨在描述炎症在ACS病理生理学不同阶段的作用,并描述秋水仙碱的机制基础。探索其在调节每个阶段中的所谓作用。
    Acute Coronary Syndrome (ACS) significantly contributes to cardiovascular death worldwide. ACS may arise from the disruption of an atherosclerotic plaque, ultimately leading to acute ischemia and myocardial infarction. In the pathogenesis of atherosclerosis, inflammation assumes a pivotal role, not solely in the initiation and complications of atherosclerotic plaque formation, but also in the myocardial response to ischemic insult. Acute inflammatory processes, coupled with time to reperfusion, orchestrate ischemic and reperfusion injuries, dictating infarct magnitude and acute left ventricular (LV) remodeling. Conversely, chronic inflammation, alongside neurohumoral activation, governs persistent LV remodeling. The interplay between chronic LV remodeling and recurrent ischemic episodes delineates the progression of the disease toward heart failure and cardiovascular death. Colchicine exerts anti-inflammatory properties affecting both the myocardium and atherosclerotic plaque by modulating the activity of monocyte/macrophages, neutrophils, and platelets. This modulation can potentially result in a more favorable LV remodeling and forestalls the recurrence of ACS. This narrative review aims to delineate the role of inflammation across the different phases of ACS pathophysiology and describe the mechanistic underpinnings of colchicine, exploring its purported role in modulating each of these stages.
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  • 文章类型: Journal Article
    水杨酸(SA)是一种重要的植物调节剂,广泛用于促进植物中高价值营养品的合成。然而,它在黄花菜中的应用,一种在中药中很有价值的观赏植物,尚未报告。在这里,我们研究了外源性SA诱导的生理,长黄花菜(LYD)的转录和生化变化。我们发现2mg/L叶面SA处理显着提高了LYD植物的生长和产量。转录组测序和差异表达基因(DEGs)分析显示,苯丙烷生物合成,异喹啉生物碱生物合成,硫代谢,在SA处理的叶片中显着诱导了植物激素信号转导和酪氨酸代谢。在SA处理下诱导了许多转录因子和抗氧化系统相关的DEGs。生化分析表明,叶片中可溶性糖的含量,可溶性蛋白(Cpr),抗坏血酸(AsA)和秋水仙碱显着增加了15.15%(从30.16±1.301到34.73±0.861mg/g),19.54%(从60.3±2.227到72.08±1.617mg/g),30.45%(从190.1±4.56到247.98±11.652μg/g)和73.05%(从3.08±0.157到5.33±0.462μg/g),分别,在SA治疗下。此外,我们确定了15个潜在的候选基因来促进生长,LYD的产量和植物化学含量。我们的结果为秋水仙碱在黄色黄花菜中的生物积累提供了支持,也为在Hemerocallisspp中生物技术辅助生产这种重要的营养食品提供了宝贵的资源。
    Salicylic acid (SA) is an essential phytoregulator that is widely used to promote the synthesis of high-value nutraceuticals in plants. However, its application in daylily, an ornamental plant highly valued in traditional Chinese medicine, has not been reported. Herein, we investigated the exogenous SA-induced physiological, transcriptional and biochemical changes in long yellow daylily (LYD). We found that 2 mg/L foliar SA treatment significantly improved LYD plant growth and yield. Transcriptome sequencing and differentially expressed genes (DEGs) analysis revealed that the phenylpropanoid biosynthesis, isoquinoline alkaloid biosynthesis, sulfur metabolism, plant hormone signal transduction and tyrosine metabolism were significantly induced in SA-treated leaves. Many transcription factors and antioxidant system-related DEGs were induced under the SA treatment. Biochemical analyses showed that the leaf contents of soluble sugar, soluble protein (Cpr), ascorbic acid (AsA) and colchicine were significantly increased by 15.15% (from 30.16 ± 1.301 to 34.73 ± 0.861 mg/g), 19.54% (from 60.3 ± 2.227 to 72.08 ± 1.617 mg/g), 30.45% (from 190.1 ± 4.56 to 247.98 ± 11.652 μg/g) and 73.05% (from 3.08 ± 0.157 to 5.33 ± 0.462 μg/g), respectively, under the SA treatment. Furthermore, we identified 15 potential candidate genes for enhancing the growth, production and phytochemical content of LYD. Our results provide support for the bioaccumulation of colchicine in yellow daylily and valuable resources for biotechnological-assisted production of this important nutraceutical in Hemerocallis spp.
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    文章类型: Journal Article
    痛风是由尿酸单钠晶体沉积在关节和非关节结构中引起的炎性关节炎。急性痛风发作通常是累及下肢关节的单关节/多关节,其特征是累及第一跖趾关节。然而,痛风耀斑也可以是多关节,涉及上肢关节,特别是在有多种合并症和尿酸降低治疗(ULT)禁忌症的患者中。加剧痛风发作的危险因素包括肥胖,高酒精和嘌呤丰富的食物消费,和利尿剂的使用。诊断需要滑液分析,并直接观察尿酸单钠晶体。急性耀斑用类固醇治疗,非甾体抗炎药,或者秋水仙碱.长期管理包括改变生活方式,包括高度重视减肥,避免饮酒,富含嘌呤的食物,和利尿剂。ULT适用于2次或2次以上痛风发作/年的患者,托皮,或者是痛风性关节病的影像学证据.别嘌呤醇虽然是一线ULT剂,它确实有诱发严重皮肤不良反应的风险,尤其是在慢性肾脏病患者和携带HLA-B*5801等位基因的患者中。其他ULT药剂包括非布索坦和丙磺舒。通常滴定ULT以实现目标血清尿酸(SUA)水平低于6mg/dL。然而,在患有Tophi的患者中,应实施低于5mg/dL的较低SUA目标以迅速溶解尿酸盐晶体。
    Gout is inflammatory arthritis caused by monosodium urate crystal deposition in articular and non-articular structures. Acute gout flares are often monoarticular/polyarticular involving lower extremity joints characteristically involving 1st metatarsophalangeal joint. However, gout flares can also be polyarticular, involving upper extremity joints, especially in patients with multiple comorbidities and contraindications to urate-lowering therapies (ULT). Risk factors exacerbating gout flares include obesity, high alcohol and purine-rich food consumption, and the use of diuretics. Diagnosis requires synovial fluid analysis with direct visualization of monosodium urate crystals. Acute flares are managed with steroids, non-steroidal anti-inflammatory drugs, or colchicine. Long-term management includes lifestyle modifications including a heavy emphasis on weight loss, avoidance of alcohol, purine-rich foods, and diuretics. ULT is indicated in patients with 2 or more gout flares/year, tophi, or radiographic evidence of gouty arthropathy. Although allopurinol is the first-line ULT agent, it does carry a risk of inducing severe cutaneous adverse reactions, especially in patients with chronic kidney disease and patients harboring the HLA-B*5801 allele. Other ULT agents include febuxostat and probenecid. ULT is usually titrated to achieve goal serum uric acid (SUA) levels below 6 mg/dL. However, in patients with tophi, a lower SUA target of less than 5 mg/dL should be implemented for prompt urate crystal dissolution.
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  • 文章类型: Journal Article
    在观赏植物中,人工多倍体化使新品种得以创造。由于其在国际花卉市场上的高商业价值和观赏特性,比如形状,尺寸,颜色,和它们花的耐久性,兰花在人工多倍体化研究中受到了极大的关注。在这里,我们描述了用于文心兰多倍体诱导的协议,巴西东南部的附生植物物种,具有极大的观赏兴趣,并在花店广泛销售。该物种因具有大花的花序而脱颖而出,棕色有黄色斑点。此外,O.crispum在遗传改良计划中具有巨大的潜力,因为该物种被广泛用于种间杂交。将含有成熟O.crispum种子的封闭胶囊在流动的无菌水中10分钟,然后在1.5%的次氯酸钠溶液中10分钟。将小部分的种子引入具有大量和微量营养素(B>M)加0.7%琼脂的50mL水溶性肥料中。将源自先前在体外发芽的种子的外植体给予0.05%和0.1%的秋水仙碱4天和8天。流式细胞术和染色体计数证实该方案成功地产生了合成多倍体植物。
    In ornamental plants, artificial polyploidization has enabled the creation of new cultivars. Due to their high commercial value in the international flower market and their ornamental characteristics, such as the shape, size, color, and durability of their flower, orchids have received great attention in studies of artificial polyploidization. Here we described the protocol used for polyploid induction in Oncidium crispum, an epiphyte species native of southeastern Brazil, of great ornamental interest and widely sold in flower shops. The species stands out for having inflorescence with large flowers, brown in color with yellow spots. In addition, O. crispum has great potential for use in genetic improvement programs since the species is widely used in interspecific crosses. Closed capsules containing mature O. crispum seeds were subjected to running sterilized water for 10 min and then to a 1.5% sodium hypochlorite solution for 10 min. Small portions of seeds were introduced into 50 mL of water-soluble fertilizer with macro- and micronutrients (B>M) plus 0.7% agar. Explants originating from seeds previously in vitro germinated were submitted to 0.05% and 0.1% of colchicine for 4 days and 8 days. Flow cytometry and chromosome counts confirmed that the protocol successfully produced synthetic polyploid plants.
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  • 文章类型: Case Reports
    口腔溃疡是全科医生在其办公室看到的最常见的投诉之一。复发性口疮性口炎影响大约20%的普通人群。当溃疡尽管常规治疗仍持续存在时,考虑诸如Behçet病之类的全身性疾病以防止护理延误至关重要。早期识别和适当管理潜在疾病对于改善患者预后和生活质量至关重要。我们介绍了一例41岁的苏格兰男性,他抱怨复发性口腔溃疡和鹅口疮。传染病专家的初步治疗解决了鹅口疮,但没有解决溃疡。尽管有三年的进一步治疗尝试,包括活检和抗病毒治疗,溃疡持续存在。最后,风湿病的转诊导致了全面的自身免疫测试,显示HLAB51阳性和Behçet病的诊断。用局部类固醇和秋水仙碱治疗产生显著改善。
    Oral ulcers are one of the most common complaints seen by general practitioners in their offices. Recurrent aphthous stomatitis affects roughly 20% of the general population. When ulcers persist despite conventional treatment, it is crucial to consider systemic diseases such as Behçet\'s disease to prevent delays in care. Early recognition and appropriate management of underlying conditions are essential for improving patient outcomes and quality of life. We present a case of a 41-year-old Scottish male who came in with complaints of recurrent oral ulcers and oral thrush. Initial treatment by an infectious disease specialist resolved the oral thrush but not the ulcers. Despite further treatment attempts for three years, including biopsy and antiviral therapy, ulcers persisted. Finally, referral to rheumatology led to comprehensive autoimmune testing, revealing positive HLA B51 and a diagnosis of Behçet\'s disease. Treatment with topical steroids and colchicine yielded significant improvement.
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  • 文章类型: Journal Article
    背景:许多研究强调了炎症在动脉粥样硬化所有阶段的重要作用。虽然已经实施了各种抗炎干预措施以减轻炎症引起的损伤,结果是相互矛盾的。鉴于炎症在这些患者中的重要作用以及关于低剂量秋水仙碱作为抗炎药的疗效的数据有限,我们旨在研究低剂量秋水仙碱对伊朗STEMI患者临床结局的疗效.
    结果:2022年和2023年在库姆ShahidBeheshti医院接受STEMI和合格血运重建的参与者被纳入研究。这项研究包括172名STEMI患者(114名男性和58名女性),平均年龄为58.93±7.79。结果表明,秋水仙碱(负荷剂量为2mg,每天0.5mg,持续30天)和安慰剂组在相同的年龄和性别方面没有显着差异。分析显示,在40天的随访期后,临床结果没有显着差异。
    结论:这项研究表明,秋水仙碱的添加在提高STEMI患者的预后方面没有显著的益处。
    背景:这项研究在伊朗临床试验注册登记,与注册号(IRCT20231001059578N1)。
    BACKGROUND: Numerous studies have underscored the essential role of inflammation across all stages of atherosclerosis. While various anti-inflammatory interventions have been implemented to mitigate inflammation-induced injuries, outcomes have been conflicting. Given the essential role of inflammation in these patients and limited data regarding the efficacy of low-dose Colchicine as an anti-inflammatory drug, we aimed to study the efficacy of low-dose Colchicine on clinical outcomes of patients with STEMI in Iran.
    RESULTS: Participants presented with STEMI and qualified revascularization at Shahid Beheshti Hospital in Qom during 2022 and 2023 were included into the study. This study included 172 STEMI patients (114 males and 58 females) within the mean age of 58.93 ± 7.79. Results indicate that colchicine (2 mg for loading dose and 0.5 mg daily for 30 days) and placebo group were not significant differences in identical profiles regarding age and gender. Analyses revealed no significant differences in clinical outcome after the 40-day follow-up period.
    CONCLUSIONS: This study revealed that the addition of colchicine did not yield a significant benefit in enhancing the outcomes of patients with STEMI.
    BACKGROUND: This study was prospectively registered on Iranian registry of clinical trials, with registration number (IRCT20231001059578N1).
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  • 文章类型: Journal Article
    背景:经历心肌梗死(MI)的患者仍处于未来主要不良心血管事件(MACE)的高风险中。虽然低剂量秋水仙碱和螺内酯已被证明可以降低MI后MACE,需要更多数据来确认其在未选择的MI后人群中的安全性和有效性.因此,我们启动了CLEARSYNERGY(OASIS9)试验以解决这些不确定性.
    方法:CLEARSYNERGY试验是一项2×2因子随机对照试验,在7,062名MI后参与者中,低剂量秋水仙碱每天0.5mg与安慰剂和螺内酯每天25mg与安慰剂在经皮冠状动脉介入治疗(PCI)指数72小时内。我们蒙蔽了参与者,医疗保健提供者,研究人员,以及治疗分配的结果裁决者。秋水仙碱的主要结局是首次发生复合心血管死亡,复发性MI,中风,或计划外的缺血驱动的血运重建。螺内酯的共同主要结果是(1)心血管死亡或新的或恶化的心力衰竭的总数的复合和(2)复合心血管死亡的首次发生,新的或恶化的心力衰竭,复发性MI或卒中。我们于2022年11月8日完成了来自14个国家104个中心的7,062名参与者的招募,并计划在2024年秋季公布结果。
    结论:CLEARSYNERGY是一项大型国际随机对照试验,该试验将告知低剂量秋水仙碱和螺内酯对接受PCI的MI后患者的影响。(ClinicalTrials.gov标识符:NCT03048825)。
    BACKGROUND: Patients experiencing myocardial infarction (MI) remain at high risk of future major adverse cardiovascular events (MACE). While low-dose colchicine and spironolactone have been shown to decrease post-MI MACE, more data are required to confirm their safety and efficacy in an unselected post-MI population. Therefore, we initiated the CLEAR SYNERGY (OASIS 9) trial to address these uncertainties.
    METHODS: The CLEAR SYNERGY trial is a 2 × 2 factorial randomized controlled trial of low-dose colchicine 0.5 mg daily versus placebo and spironolactone 25 mg daily versus placebo in 7,062 post-MI participants who were within 72 hours of the index percutaneous coronary intervention (PCI). We blinded participants, healthcare providers, research personnel, and outcome adjudicators to treatment allocation. The primary outcome for colchicine is the first occurrence of the composite of cardiovascular death, recurrent MI, stroke, or unplanned ischemia-driven revascularization. The co-primary outcomes for spironolactone are (1) the composite of the total numbers of cardiovascular death or new or worsening heart failure and (2) the first occurrence of the composite of cardiovascular death, new or worsening heart failure, recurrent MI or stroke. We finished recruitment with 7,062 participants from 104 centers in 14 countries on November 8, 2022, and plan to present the results in the fall of 2024.
    CONCLUSIONS: CLEAR SYNERGY is a large international randomized controlled trial that will inform the effects of low-dose colchicine and spironolactone in largely unselected post-MI patients who undergo PCI. (ClinicalTrials.gov Identifier: NCT03048825).
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  • 文章类型: Journal Article
    目的:评估秋水仙碱与安慰剂在降低症状发作前3个月内高风险非心源性缺血性卒中或短暂性脑缺血发作后后续卒中风险的有效性和安全性(CHANCE-3)。
    方法:多中心,双盲,随机化,安慰剂对照试验。
    方法:2022年8月11日至2023年4月13日期间,中国有244家医院。
    方法:8343例年龄在40岁或以上的轻度至中度缺血性卒中或短暂性脑缺血发作且高敏C反应蛋白≥2mg/L的患者被纳入研究。
    方法:患者在症状发作24小时内按1:1随机分配接受秋水仙碱(0.5mg,每天两次,第1-3天,然后每天0.5mg)或安慰剂90天。
    方法:主要疗效结果是随机分组后90天内的任何新卒中。主要安全性结果是治疗期间的任何严重不良事件。所有疗效和安全性分析均按治疗意向进行。
    结果:4176例患者被分配到秋水仙碱组,4167例被分配到安慰剂组。秋水仙碱组264例患者(6.3%)和安慰剂组270例患者(6.5%)在90天内发生卒中(风险比0.98(95%置信区间0.83~1.16);P=0.79)。秋水仙碱组91例(2.2%)患者和安慰剂组88例(2.1%)患者出现严重不良事件(P=0.83)。
    结论:该研究没有提供证据表明,与安慰剂相比,低剂量秋水仙碱可以降低急性非心源性轻度至中度缺血性中风或短暂性脑缺血发作且高敏C反应蛋白≥2mg/L的患者在90天内发生卒中的风险。
    背景:ClinicalTrials.gov,NCT05439356.
    To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3).
    Multicentre, double blind, randomised, placebo controlled trial.
    244 hospitals in China between 11 August 2022 and 13 April 2023.
    8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled.
    Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days.
    The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat.
    4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83).
    The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L.
    ClinicalTrials.gov, NCT05439356.
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  • 文章类型: Letter
    暂无摘要。
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  • 文章类型: Journal Article
    2型糖尿病(T2DM),一种普遍的慢性代谢紊乱,与持续的低度炎症密切相关,为其发展和进步做出了重要贡献。本文综述了T2DM的炎症机制。重点关注NLRP3炎性体和白细胞介素-1β(IL-1β)在介导炎症反应中的作用。我们讨论了IL-1抑制剂和秋水仙碱的治疗潜力,强调了它们抑制NLRP3炎性体和减少IL-1β产生的机制。最近的研究表明,这些药物可以有效缓解炎症,为T2DM的预防和管理提供了有希望的途径。通过探索代谢紊乱和慢性炎症之间的复杂联系,这篇综述强调需要新的抗炎策略来解决T2DM及其并发症.
    Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, is closely linked to persistent low-grade inflammation, significantly contributing to its development and progression. This review provides a comprehensive examination of the inflammatory mechanisms underlying T2DM, focusing on the role of the NLRP3 inflammasome and interleukin-1β (IL-1β) in mediating inflammatory responses. We discuss the therapeutic potential of IL-1 inhibitors and colchicine, highlighting their mechanisms in inhibiting the NLRP3 inflammasome and reducing IL-1β production. Recent studies indicate that these agents could effectively mitigate inflammation, offering promising avenues for the prevention and management of T2DM. By exploring the intricate connections between metabolic disturbances and chronic inflammation, this review underscores the need for novel anti-inflammatory strategies to address T2DM and its complications.
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