The formation of a thrombus is closely related to oxidative stress and inflammation. Colchicine is one of the most commonly prescribed medication for gout treatment, with anti‐inflammation and antioxidative stress properties. Therefore, we speculated that it is possible for colchicine to treat thrombosis. In this study, we used carrageenan to induce thrombosis in BALB/c mice and fed mice with colchicine, ticagrelor, and their combination, respectively. We found colchicine inhibited carrageenan‐induced thrombi in mouse tail, and the inhibition was enhanced by ticagrelor. In vitro, colchicine inhibited thrombin‐induced retraction of human platelet clots. Mechanically, colchicine inhibited platelet activation by reducing the expression of platelet receptors, protease‐activated receptor 4 (PAR4) and CD36, and inactivating of AKT and ERK1/2 pathways. Furthermore, in human umbilical vein endothelial cells (HUVECs), colchicine showed antioxidative stress effects through increasing protein expression of glutathione peroxidase‐1 (GPx‐1), and mRNA levels of forkhead box O3 (FOXO3a) and superoxide dismutase 2 (SOD2). In RAW264.7 cells, colchicine reduced LPS‐enhanced inflammatory response through attenuating toll‐like receptor 4 (TLR4) activation. In addition, colchicine reduced LPS or ox‐LDL‐induced monocyte adhesion to HUVECs by inhibiting intercellular adhesion molecule‐1 (ICAM‐1) and vascular adhesion molecule‐1 (VCAM‐1) levels. Taken together, our study demonstrates that colchicine exerts antithrombotic function by attenuating platelet activation and inhibiting oxidative stress and inflammation. We also provide a potential new strategy for clinical treatment.

Objective: This study aims to analyse the burden of ischemic heart disease (IHD) in China and other G20 countries from 1990–2021 and predict the burden for the next decade. Methods: Using data from the Global Burden of Disease (GBD) 2021 study, we evaluated the age-standardised rates (ASRs) of incidence, prevalence, mortality and disability-adjusted life years (DALYs) by estimated annual percentage change (EAPC). The Bayesian age-period-cohort (BAPC) model was used to forecast the incidence, mortality and DALY rates of IHD in China from 2021–2040. Results: The ASRs of incidence, mortality and DALYs of IHD in China increased with EAPCs of 0.66 (95% CI: 0.50, 0.82), 0.97 (95% CI: 0.63, 1.31) and 0.51 (95% CI: 0.24, 0.78), respectively. Compared with other G20 countries, China was ranked 14th for the ASR of incidence in 1990 and then rose to 7th in 2021. The ASR of prevalence for IHD in China jumped from 8th in 1990 to 5th in 2021, and both the ASR of mortality and DALYs for IHD in China ranked 7th in 2021. The top five risk factors affecting mortality in China in 2021 were high systolic blood pressure, dietary risk, air pollution, high LDL cholesterol and tobacco. Over the next 20 years, the ASR of incidence, mortality and DALYs for IHD will increase continuously in males. Conclusion: The burden of IHD is expected to increase steadily in China, highlighting the urgency for early monitoring and preventative strategies, particularly focusing on the elderly and male populations.

H3K27ac has been widely recognized as a representative epigenetic marker of active enhancer, while its regulatory mechanisms in pathogenesis of metabolic dysfunction‐associated steatotic liver disease (MASLD) remain elusive. Here, a genome‐wide comparative study on H3K27ac activities and transcriptome profiling in high fat diet (HFD)‐induced MASLD model is performed. A significantly enhanced H3K27ac density with abundant alterations of regulatory transcriptome is observed in MASLD rats. Based on integrative analysis of ChIP‐Seq and RNA‐Seq, TDO2 is identified as a critical contributor for abnormal lipid accumulation, transcriptionally activated by YY1‐promoted H3K27ac. Furthermore, TDO2 depletion effectively protects against hepatic steatosis. In terms of mechanisms, TDO2 activates NF‐κB pathway to promote macrophages M1 polarization, representing a crucial event in MASLD progression. A bovine serum albumin nanoparticle is fabricated to provide sustained release of Allopurinol (NPs‐Allo) for TDO2 inhibition, possessing excellent biocompatibility and desired targeting capacity. Venous injection of NPs‐Allo robustly alleviates HFD‐induced metabolic disorders. This study reveals the pivotal role of TDO2 and its underlying mechanisms in pathogenesis of MASLD epigenetically and genetically. Targeting H3K27ac‐TDO2‐NF‐κB axis may provide new insights into the pathogenesis of abnormal lipid accumulation and pave the way for developing novel strategies for MASLD prevention and treatment.

Colchicine (Col) is a traditional herbal medicine derived from the plant Colchicum autumnale. With the property of anti-inflammation, Col has been demonstrated certain therapeutic effects in cardiovascular diseases (CVDs). Vascular calcification is positively related to the morbidity and mortality of CVDs. However, the specific cardiovascular conditions for which Col is effective remain unclear, particularly its impact on vascular calcification. In this study, we used high phosphate to induced calcium deposition in vascular smooth muscle cells (VSMCs), and Vitamin D3 plus nicotine or 5/6 nephrectomy along with high phosphate diet to construct vascular calcification mouse models. Our results showed that Col reduced calcium accumulation in vitro, and vascular calcification both in ex-vivo and in vivo models, which was evidenced by the Alizarin red S staining and calcium content determination. In vitro results showed that Col inhibited vascular calcification is contributed to the reduction of NLRP3 inflammasome activation through enhanced phosphorylation at Ser 5. In addition, we indicated that phosphorylation of NLRP3 is regulated by the activity of protein phosphatase 2Ac (PP2Ac). Furthermore, we identified that Sirt2 as a master regulator of PP2Ac activation through regulation its acetylation at Lys 136. More importantly, we demonstrated that Col-inhibited vascular calcification is dependent on Sirt2 expression by using the Sirt2 knockout mice. We demonstrate that Col protects vascular calcification. Our study provides novel insight into the clinical application of Col. We also suggest that Sirt2 is a novel target for vascular calcification treatment, and that Col may act as an activator of Sirt2, which could be beneficial in other diseases.