APOE (Apolipoprotein E)

miR‑378a‑5p exerts protective effects against AAA by maintaining VSMCs homeostasis via the ABLIM1‑MKL1 pathway. Therefore, targeting miR‑378a‑5p may be an attractive therapeutic strategy for AAA treatment.

In vitro experiments showed that the nanoparticles significantly inhibited the proliferation of U87MG glioma cells, induced apoptosis, and specifically silenced the mRNA and protein expression of PLK1. The results of in vivo animal experiments showed that PAPA@siPLK1 could effectively inhibit tumor growth and had potential brain permeability; The PAPA@siPLK1 nanocarrier delivery system developed in this study achieves PLK1 gene silencing through efficient siRNA delivery, providing an important basis for novel therapeutic strategies for glioma.

Therapeutic strategies targeting lipid metabolism or the blood-brain barrier still face considerable challenges in clinical translation. Meanwhile, emerging tools such as lipidomics contribute to systematically analyzing the associated dysregulated lipid networks, thereby aiding in the identification of novel therapeutic targets.

Extracorporeal photopheresis (ECP) involves the reinfusion of autologous peripheral blood lymphocytes rendered apoptotic by in vitro exposure to psoralen and ultraviolet A light...Additionally, we documented an increase in circulating regulatory T cells, which are recognized as suppressing pro-atherogenic immune responses. These findings support the translational potential of a preclinical atheroprotection model and provide a proof of concept for clinical trials evaluating ECP in autoimmune diseases associated with accelerated atherosclerosis, where achieving dual benefits, clinical improvement and reduced cardiovascular risk, may be feasible.

This ox-LDL-induced upregulation of ACP5 was effectively reversed by the JAK2 inhibitor fedratinib...Conditional ablation of ACP5 significantly reduced aortic plaque area, decreased M1 macrophage proportion in peritoneal lavage fluid, diminished 4-HNE expression in the aortic root, reduced numbers of atrophic mitochondria, and increased aortic GPX4 expression. In conclusion, ACP5 exacerbates atherosclerosis by modulating macrophage polarization and promoting macrophage ferroptosis.

Further comparison of ApoE lipoproteins from APOE4 microglia revealed that ApoE4 lipoproteins were enriched in C1q and Lpl compared to ApoE2 and ApoE3 microglial lipoproteins which were enriched in Ankk1 and ApoC1. These results provide the molecular foundation for better understanding of how ApoE functions as an apolipoprotein with the lipoprotein cargo being dependent on the cellular source and ApoE isoform, ultimately contributing to CNS homeostasis and disease pathogenesis.

Endothelium-specific TBK1 knockdown or GSK8612 treatment inhibits EndMT and plaque formation. Safe TBK1 inhibitors could be developed into effective agents for the treatment of atherosclerotic vascular disease.

Crucially, this lysosomal rupture also suppressed protective autophagy of tumor cells themselves, thereby reinforcing the cascade activation between caspase-3/GSDME-dependent pyroptosis and cGAS-STING signaling pathway. This lysosomal disruption-nanobomb represents a new strategy for advancing GBM immunotherapy.

This proteome-wide MR and colocalization study identifies novel plasma proteins and immune pathways implicated in RTI susceptibility, providing insights into potential biomarkers and therapeutic targets for infection prevention and management. Further validation in diverse populations and tissue-specific proteomic studies is warranted.

In vivo, APOE overexpression in a mouse xenograft model resulted in significantly smaller tumors, with changes in autophagy and ferroptosis markers consistent with in vitro findings. APOE overexpression suppresses osteosarcoma growth by promoting ferroptosis and autophagy through the mTOR/Stat3 signaling pathway, highlighting its promise as a target for OS therapeutic intervention.

ABCA8+ lpCAFs and APOE+ LAMs contribute to ICB resistance in TNBC through the establishment of an immunosuppressive TME via lipid metabolism reprogramming. Therapeutic intervention targeting the ABCA8-lipid axis presents a promising strategy to enhance ICB efficacy, potentially advancing TNBC treatment outcomes and improving patient survival.

sTNFR1 is associated with cognitive decline and tau-related selective neurodegeneration, but provides limited incremental predictive value beyond established risk factors; external validation and replication are warranted.