Aortic dissection (AD) is a life‑threatening vascular disorder with high mortality and no effective pharmacological treatment. Addressing its multicellular and dynamic pathology requires strategies that precisely modulate inflammatory and degenerative processes, yet existing targeted delivery approaches lack the spatiotemporal and cellular precision required. Here, we establish Galectin‑3 (Gal‑3) as a therapeutic delivery target for cardiovascular nanomedicine and introduce a modular, pathology‑tailored nanoplatform synergizing nitric oxide (NO) therapy with multi‑pathway intervention. Gal‑3 is persistently expressed on inflamed endothelial cells, macrophages, and smooth muscle cells during AD progression, providing a tractable target for lesion‑specific engagement. The nanoparticles, created from a previously unexplored integration of a Gal‑3‑binding polysaccharide, a nitric oxide–generating peptide, and a hydrophobic drug carrier, uniquely combine triple responsiveness to pH, protease, and oxidative stress with on‑demand NO release and controlled resveratrol co‑delivery. In vitro, they enhanced uptake across pathological cell types and attenuated inflammatory and degenerative phenotypes. In vivo, they achieved early lesion targeting, > 20‑fold aortic accumulation, and marked reductions in AD incidence, vascular degeneration, and mortality. This work establishes Gal‑3‑targeted nanotherapy as a broadly applicable paradigm for pathology‑adaptive intervention in AD and one that may be adapted for broader cardiovascular applications. Graphical Abstract

Background/Aim: Non-small-cell lung cancer (NSCLC) comprises approximately 85% of lung cancer. Treatment with docetaxel prolongs the survival of patients with NSCLC. However, the development of resistance to docetaxel has compromised its efficacy. Caffeic acid phenethyl ester (CAPE) has been reported to suppress survival and radiotherapy resistance in lung cancer cells. We determined in this study if combination treatment of docetaxel with CAPE suppresses the proliferation and the survival of NSCLC cells more effectively. Materials and Methods: Proliferation, viability, flow cytometric and comet assays were used to examine the difference in anticancer effects of combined treatment as compared to docetaxel treatment alone. Western blot and gene overexpression were used to unravel the underlying molecular mechanism. Results: Treatment with docetaxel or CAPE alone dose-dependently suppressed the proliferation and survival of H1299 and A549 cells. Combined treatment of docetaxel with CAPE caused greater inhibition of survival of H1299 and A549 cells. Docetaxel alone and the combined treatment both dose-dependently increased apoptosis of H1299 cells; however, combined treatment induced much more apoptosis than docetaxel alone. Combined treatment suppressed the protein expression of phospho-protein kinase B (AKT, Ser 473), S-phase protein 2 (SKP2), MYC proto-oncogene bHLH transcription factor (c-MYC), epidermal growth factor receptor (EGFR), phospho-EGFR (Tyr 1045, and Tyr 992) but increased levels of cleaved caspase 3 and cytochrome c proteins in H1299 and A549 cells. The inhibition of expression of SKP2, c-MYC, phospho-EGFR (Tyr 992) proteins by combined treatment was significantly greater than that with treatment using either CAPE or docetaxel alone. Overexpression of c-MYC in rescued proliferation of H1299 cells under combination treatment. Conclusion: Our study revealed that the combination of CAPE with docetaxel is more effective at reducing the proliferation and survival of NSCLC cells, and this is via inhibition of c-MYC. Combined therapy of docetaxel and CAPE may benefit patients with NSCLC.

Aortic dissection (AD) is a life-threatening vascular condition with limited pharmacological options, and shared risk factors with cardiac disease include hypertension, atherosclerosis, smoking, and dyslipidemia. This study investigated Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, in a BAPN/Ang-II-induced mouse model of AD, revealing significant therapeutic potential. Fer-1 significantly reduced AD incidence and mortality by preserving aortic wall integrity. RNA sequencing identified 922 differentially expressed genes, with 416 upregulated and 506 downregulated. Bioinformatics analysis revealed that Fer-1 modulates key regulators, such as MEF2C and KDM5A, impacting immune responses, oxidative stress, apoptosis, and lipid metabolism. Additionally, Fer-1 alters miRNA expression, with the upregulation of miR-361-5p and downregulation of miR-3151-5p, targeting pathways involved in inflammation, oxidative stress, and smooth muscle cell (SMC) phenotypic stability. Functional pathway analysis highlighted the inhibition of actin cytoskeleton, ILK, and IL-17 signaling, essential for SMC differentiation and extracellular matrix remodeling. Gene interaction network analysis identified 21 central molecules, including CXCR3, ACACA, and BPGM, associated with lipid metabolism, inflammation, and vascular remodeling. This research elucidates the mechanism of ferroptosis in AD pathogenesis and establishes Fer-1 as a promising therapeutic intervention. AD and cardiac diseases share molecular mechanisms, risk factors, and pathological processes, positioning AD within the broader scope of cardiovascular pathology. By attenuating lipid peroxidation, oxidative stress, and inflammation, Fer-1 may have cardioprotective effects beyond AD, providing a foundation for future translational research in cardiovascular medicine.

Uncontrolled aortic aneurysms can progress to aortic dissection (AD), a severe vascular disorder characterized by hematoma formation in the aortic wall, with inflammation playing a crucial role. Galectin-3 (Gal-3), a 26-kDa lectin, regulates many aspects of inflammatory cell behavior. Inhibition of Gal-3 ameliorates diabetic neuroinflammation and cardiomyopathy. Modified citrus pectin (MCP) is a PH-modified dietetic supplement produced from citrus pectin. This study investigates the therapeutic potential of MCP, which has a known affinity for Gal-3, in AD. A murine model of AD was induced by β-aminopropionitrile fumarate (BAPN)/angiotensin II (Ang-II) and treated orally with either 100 mg/kg MCP or vehicle. In vitro, H2O2 treatment was applied to RAW264.7 cells to detect macrophage death and pyroptosis. MCP administration significantly reduced AD incidence and mortality, with decreased inflammatory cell infiltration in the aorta. MCP downregulated genes associated with inflammation and pyroptosis. In vitro, MCP mitigated macrophage death and pyroptosis induced by H₂O₂ treatment. The study suggests that MCP's protective effects are due to its interference with the Gal-3 and TLR4 interaction, inhibiting pyroptotic macrophage-induced inflammation. MCP could improve patient outcomes and reduce progression to severe forms of AD. Clinically, MCP could serve as supportive therapy to prevent and delay aortic dissection, particularly during the acute stage of uncomplicated type B AD in patients with Marfan syndrome or abdominal aortic aneurysm.

Background: Inhibitors for sodium‐glucose transport protein 2 (SGLT2) are being used widely in recent years to treat patients with type 2 diabetes (T2D). Studies demonstrated that SGLT2 inhibitors exhibit protective effect for certain cardiovascular diseases. However, no study has explored the effect of SGLT2 inhibitors on risk of aortic dissection in patients with T2D. Methods: We extracted and retrospectively analyzed the data of all patients with T2D from Taiwan National Health Institution databases between May 1, 2016, and December 31, 2021. Patients with T2D taking DPP4 (dipeptidyl peptidase 4) inhibitors were included for comparison to exclude glucose lowering effect on aortic dissection. In this cohort, 242 563 patients received SGLT2 inhibitors (T2D‐SGLT2i), and 376 062 patients received DPP4 inhibitors (T2D‐DPP4i). The inverse probability of treatment weighting statistical method was performed, which avoids sample loss due to matching. The hazard ratios (HRs) and 95% CIs for these patients with T2D were calculated using multivariate Cox models to approximate the associations. Results: The overall aortic dissection incidence per 100 000 patient‐years was 14.83 for patients with T2D‐SGLT2i and 29.56 for patients with T2D‐DPP4i. Patients with T2D‐SGLT2i were associated with a lower risk of aortic dissection as compared with patients with T2D‐DPP4i after the adjustment of potential risk factors and comorbidity. Subgroup analysis indicated that use of SGLT2 inhibitor lowers the risk of aortic dissection in some subgroups of patients with T2D. Conclusions: Our study suggested that use of SGLT2 inhibitors correlated with lower risk of aortic dissection.