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).

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).

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.

暂无摘要。

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.

In this study, we synthesized a new-generation library of colchicine derivatives via cycloaddition of colchicine utilizing position C-8 and C-12 diene system regioselectivity with aryne precursor to generate a small, focused library of derivatives. We assessed their anticancer activity against various cancer cell lines like MCF-7, MDA-MB-231, MDA-MB-453, and PC-3. Normal human embryonic kidney cell line HEK-293 was used to determine the toxicity. Among these derivatives, silicon-tethered compound B-4a demonstrated the highest potency against breast cancer cells. Subsequent mechanistic studies revealed that B-4a effectively modulates cell cycle regulatory kinases (CDK-2 and CDK-4) and their associated cyclins (cyclin-B1, cyclin-D1), inducing apoptosis. Additionally, B-4a displayed a noteworthy impact on tubulin polymerization, compared to positive control flavopiridol hydrochloride in a dose-dependent manner, and significantly disrupted the vimentin cytoskeleton, contributing to G1 arrest in breast cancer cells. Moreover, B-4a exhibited substantial anti-metastatic properties by inhibiting breast cancer cell migration and invasion. These effects are attributed to the down-regulation of major epithelial to mesenchymal transition (EMT) factors, including vimentin and Twist-1, and the upregulation of the epithelial marker E-cadherin in an apoptosis-dependent manner.

暂无摘要。

We assessed the efficacy and safety of colchicine and low-dose naltrexone (LDN), alone and in combination, in preventing progression to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this prospective, randomized, open-label trial, colchicine and LDN were compared to standard of care (SOC) in patients hospitalized with SARS-CoV-2 not requiring high levels of ventilatory support. Patients were randomly assigned to colchicine alone, LDN alone, colchicine/LDN in combination, or SOC. The primary outcome was time to disease recovery. Secondary outcomes included total time hospitalized, study enrollment, level of care, oxygen support, and adverse events.  One-hundred and thirty-seven patients were randomized (Nc = 34, Nc+ldn = 33, Nldn = 35, Nsoc = 35). Eighty-four patients (61%) achieved disease recovery by day 5. There was no significant difference in the proportion of patients who experienced the primary efficacy outcome among those who received colchicine, LDN, or between the four study arms.Patients receiving colchicine had a shorter length of enrollment but not a significant reduction in the length of stay. Diarrhea was the most common adverse reaction. In adults hospitalized with SARS-CoV-2 not requiring high-level ventilatory support, colchicine and LDN, alone and in combination, were not associated with significant reductions in progression to severe disease.

近年研究发现，在积极使用降脂药物的情况下，与残余胆固醇风险相比，由超敏C反应蛋白代表的残余炎症风险是复发性心血管事件更有力的预测因素。针对冠心病残余炎症风险的抗炎治疗路途坎坷，直至2017年，3项大规模临床研究（CANTOS、COLCOT和LoDoCo2）方才相继获得阳性结果。2023年，秋水仙碱成为第一个被美国食品和药品监督管理局批准用于冠心病抗炎治疗的药物，表明在冠心病治疗领域，超越单纯降脂的抗炎时代已经到来。我们相信积极降脂和抗炎的联合疗法将成为冠心病患者的标准治疗方案。.

BACKGROUND: There is no known effective pharmacological therapy for long COVID, which is characterized by wide-ranging, multisystemic, fluctuating, or relapsing symptoms in a large proportion of survivors of acute COVID. This randomized controlled trial aims to assess the safety and efficacy of an anti-inflammatory agent colchicine, to reduce symptoms among those at high risk of developing long COVID.
METHODS: This multi-centre, parallel arm, 1:1 individual randomized, placebo-controlled, double-blind superiority trial will enrol 350 individuals with persistent post-COVID symptoms. Participants will be randomized to either colchicine 0.5 mg once daily (< 70 kg) or twice daily (≥ 70 kg) or matched placebo for 26 weeks and will be followed up until 52 weeks after randomization. The primary trial objective is to demonstrate the superiority of colchicine over a placebo in improving distance walked in 6 min at 52 weeks from baseline. The secondary objectives are to assess the efficacy of colchicine compared to placebo with respect to lung function, inflammatory markers, constitutional symptoms, and mental health state. In a sub-sample of 100 participants, cardiac biomarkers of myocardial injury and myocardial oedema using MRI will be compared.
CONCLUSIONS: Persistent inflammatory response following SARS-CoV-19 is one of the postulated pathophysiological mechanisms of long COVID. Colchicine, a low-cost anti-inflammatory agent, acts via multiple inflammatory pathways and has an established safety profile. This trial will generate evidence for an important health priority that can rapidly translate into practice.
BACKGROUND: This clinical trial has been registered prospectively on www.
RESULTS: gov with registration CTRI/2021/11/038234 dated November 24, 2021.