Dehydrocorydaline (DHC), an active component of Corydalis yanhusuo (Y.H. Chou & Chun C. Hsu) W.T. Wang ex Z.Y. Su & C.Y. Wu (Papaveraceae), exhibits protective and pain-relieving effects on coronary heart disease, but the underlying mechanism still remains unknown. Network pharmacology and experimental validation both in vivo and in vitro were applied to assess whether DHC can treat myocardial ischemia-reperfusion injury (MIRI) by regulating the forkhead box O (FoxO) signalling pathway to inhibit apoptosis. DHC and MIRI targets were retrieved from various databases. Molecular docking and microscale thermophoresis (MST) determined potential binding affinity. An in vivo mouse model of MIRI was established by ligating the left anterior descending coronary artery. C57BL/6N mice were divided into sham, MIRI, and DHC (intraperitoneal injection of 5 mg/kg DHC) groups. Haematoxylin and eosin, Masson, and immunohistochemical stainings verified DHC treatment effects and the involved signalling pathways. In vitro, H9c2 cells were incubated with DHC and underwent hypoxia/reoxygenation. TUNEL, JC-1, and reactive oxygen species stainings and western blots were used to explore the protective effects of DHC and the underlying mechanisms. Venny analysis identified 120 common targets from 121 DHC and 23,354 MIRI targets. DHC exhibited high affinity for CCND1, CDK2, and MDM2 (<-7 kcal/mol). In vivo, DHC attenuated decreases in left ventricular ejection fraction and fractional shortening, reduced infarct sizes, and decreased cTnI and lactate dehydrogenase levels. In vitro, DHC alleviated apoptosis and oxidative stress in the hypoxia/reoxygenation model by attenuating ΔΨm disruption; reducing the production of reactive oxygen species; upregulating Bax and CCND1 via the FoxO signalling pathway, as well as cleaved-caspase 8; downregulating the apoptosis-associated proteins Bcl-2, Bid, cleaved-caspase 3, and cleaved-caspase 9; and promoting the phosphorylation of FOXO1A and MDM2. By upregulating the FoxO signaling pathway to inhibit apoptosis, DHC exerts a cardioprotective effect, which could serve as a potential therapeutic option for MIRI.

Background: Chemotherapy is the main first-line treatment, but there is a problem of adverse reactions to systemic drugs. Chemotherapeutic agents may cause adverse effects on the body, influencing the prognosis. Whether the clinical application of anthracyclines is associated with an increased arrhythmic risk remains controversial. To evaluate the arrhythmic risk of anthracyclines as a class, and the comparative risk for each drug, we conducted a systematic review, meta-analysis, and network meta-analysis. Methods: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched, up to March 2022, for randomized controlled trials, cohort studies, and case–control studies that investigated the association between anthracyclines treatment and the risk of arrhythmia. We followed the PRISMA 2020 guidelines for data selection and extraction. Outcomes were pooled using fixed effects models in cohort studies and randomized controlled studies, and random models in single-arm studies. Direct and indirect comparisons in network meta-analysis were performed using frequentist methods. Results: In total, 4 cohort studies, 8 RCTs, and 18 single-arm studies were included in our analysis. Anthracyclines’ use was associated with a statistically significant 90% increase in the risk of arrhythmia (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.62–2.24) and a 114% increase in the risk of supraventricular arrhythmia (OR 2.14; 95% CI 1.18–3.89). And the single-arm studies also indicated that the incidence of arrhythmia rate is 20% and the 95% CI is 15/100–25/100. Epirubicin ranked most likely to have the highest risk of arrhythmia compared with non-anthracycline antineoplastic drugs in the analysis (OR 43.07 [95% CI 2.80–2105.83]) by network meta-analysis. Conclusions: Our findings show a significant association between anthracyclines’ use and an increased risk of arrhythmia, especially supraventricular arrhythmia. Epirubicin ranked with the highest probability of arrhythmia. These results indicated that cardiac rhythm should be strictly monitored during the application of anthracyclines in clinical practice, and a possible therapy for anthracycline-associated arrhythmia should be explored. Molecular imaging technology is an important means to study the mechanism of drug action on cardiac electrophysiology in the future. By imaging molecular targets in cardiac cells, the effects of drugs on the electrophysiological properties of cardiac cells can be understood, which provides information for the development of safer and more effective drugs.

The fibrosis process after myocardial infarction (MI) results in a decline in cardiac function due to fibrotic collagen deposition and contrast agents’ metabolic disorders, posing a significant challenge to conventional imaging strategies in making heart damage clear in the fibrosis microenvironment. To address this issue, we developed an imaging strategy. Specifically, we pretreated myocardial fibrotic collagen with collagenase I combined with human serum albumin (HSA-C) and subsequently visualized the site of cardiac injury by near-infrared (NIR) fluorescence imaging using an optical contrast agent (CI, CRT-indocyanine green) targeting transferrin receptor 1 peptides (CRT). The key point of this strategy is that pretreatment with HSA-C can reduce background signal interference in the fibrotic tissue while enhancing CI uptake at the heart lesion site, making the boundary between the injured heart tissue and the normal myocardium clearer. Our results showed that compared to that in the untargeted group, the normalized fluorescence intensity of cardiac damage detected by NIR in the targeted group increased 1.28-fold. The normalized fluorescence intensity increased 1.21-fold in the pretreatment group of the targeted groups. These data demonstrate the feasibility of applying pretreated fibrotic collagen and NIR contrast agents targeting TfR1 to identify ferroptosis at sites of cardiac injury, and its clinical value in the management of patients with MI needs further study.

Endothelial-to-mesenchymal transition (EndMT) is an endothelial plasticity program that contributes to vascular remodeling, inflammation, extracellular matrix remodeling, calcification, and plaque instability in atherosclerosis. Recent lineage-tracing, single-cell RNA sequencing, and spatial transcriptomic studies have revealed that EndMT is not a uniform or irreversible process, but rather a spectrum of partial, intermediate, and advanced endothelial transition states with stage- and region-specific effects. During atherosclerosis, EndMT may participate in lesion initiation, plaque progression, fibrous cap remodeling, and advanced plaque vulnerability. Mechanistically, EndMT is regulated by interconnected metabolic, signaling, transcriptional, epigenetic, and biomechanical pathways, including TGF-β/SMAD, FGF/FGFR1, BMP, Notch, Wnt/β-catenin, KLF2/KLF4, glycolysis–lactate–lactylation, fatty acid oxidation, HDACs, non-coding RNAs, and extracellular vesicle-mediated communication. Therapeutically, EndMT-targeted strategies should aim to prevent or reverse early maladaptive EndMT while selectively restraining sustained inflammatory, osteogenic, fibroblast-like, or matrix-degrading EndMT states. However, clinical translation remains limited by marker nonspecificity, vascular-bed heterogeneity, disease-stage dependence, inadequate modeling of human plaque rupture, and the lack of validated biomarkers. Future integration of lineage tracing, single-cell and spatial multi-omics, human-relevant models, plaque-risk stratification, and targeted delivery systems may enable precise modulation of EndMT to slow atherosclerosis progression and improve plaque stability.

Aims: This study aimed to investigate the therapeutic mechanism of red yeast rice extract (RYRE) in high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) through untargeted metabolomics analysis and experimental validation. Methods: An untargeted metabolomics analysis based on UHPLC-QTOF/MS was performed to identify differential metabolites in liver tissues. A NAFLD model was established in hamsters by HFD feeding. Forty hamsters were randomly allocated into four groups ( n = 10 per group): control (CON), model (MOD), red yeast rice extract (Xuezhikang, XZK), and simvastatin (SVT). Serum levels of lipids (TG, CHO, HDL-C, LDL-C), liver function parameters (ALT, AST, ALB, ALP, γ -GT, TBiL, DBiL, TBA), and inflammatory cytokines (TNF- α , IL-4, IL-1 β , TGF-β) were measured by biochemical assays and ELISA. Liver tissues were subjected to Oil Red O, hematoxylin–eosin (HE), and Masson staining for histopathological evaluation. Additionally, qPCR and immunohistochemistry were employed to investigate the underlying signaling pathways. Results: XZK significantly reduced serum levels of DBiL, TBiL, TBA, CHO, TG, and LDL-C, while increasing HDL-C in HFD-fed hamsters. Both XZK and SVT markedly decreased pro-inflammatory cytokines. Untargeted metabolomics identified 135 differential metabolites between the MOD and XZK groups (83 down-regulated, 52 up-regulated), which were primarily involved in carbon metabolism, lipid metabolism, and hormone metabolism. Mechanistically, XZK attenuated the JNK/AP-1/TNF- α signaling pathway, as evidenced by reduced mRNA expression of cFos, cJUN, JAK1/2/3, and TNF-α, along with decreased protein levels of p-JNK, cFos, cJUN, and TNF-α. Notably, the p-cJun/total cJun ratio showed a distinct regulatory pattern, suggesting complex modulation of AP-1 subunit phosphorylation. Conclusion: XZK effectively ameliorates hepatic steatosis, dyslipidemia, and inflammation in HFD-induced NAFLD hamsters. The therapeutic effects are mediated through restoration of metabolic homeostasis and suppression of the JNK/AP-1/TNF- α signaling pathway.