👤 Naoya Ichimura

Cholesterol efflux capacity (CEC) is robust biomarker for atherosclerotic cardiovascular disease (ASCVD). However, cell-based CEC assays require complex procedures that limit clinical use. The immobilized liposome-bound gel beads (ILG) method, a newly developed cell-free CEC assay, demonstrates sufficient performance for clinical application. This study investigated the clinical significance of CEC measured by the ILG method in relation to HDL subclasses and coronary artery plaque characteristics. We analyzed CEC and HDL parameters, including the ratio of apolipoprotein E (apoE)-HDL-C to HDL-C (%apoE) and HDL CEC correlated positively with HDL-C and %apoE. Among the patients, 26 (42.6%) exhibited large lipid-rich plaques on OCT. Univariable analysis showed that CEC was significantly lower in patients with large lipid-rich plaques compared to those without. While this association did not reach statistical significance after multivariable adjustment (p = 0.109), the addition of CEC to traditional risk factors improved the model's explanatory power (Nagelkerke R CEC measured using the ILG method reflects HDL subclass features and is associated with the burden of lipid-rich coronary artery plaques. These findings suggest the significance of CEC evaluated using the ILG method, supporting its potential for enhanced ASCVD risk assessment and further clinical applications. Show less

High-grade astrocytoma with piloid features (HGAP) is a novel condition introduced in the 2021 World Health Organization classification. Given that it has been recently classified, reports clarifying its clinical features or diagnostic criteria are lacking, especially in cases of atypical presentation. Herein, the authors present a rare case of HGAP with repeated symptomatic hemorrhages. A woman in her 20s presented with an acute headache and vertigo. Computed tomography and magnetic resonance imaging revealed a 2.5 × 2.8 × 2.3-cm hemorrhagic cerebellar mass with calcifications. After moderate improvement of her symptoms, she developed recurrent hemorrhage, and the tumor size increased (3.0 × 3.6 × 4.0 cm) 18 days later, necessitating resection. Pathological and molecular analyses confirmed the diagnosis of HGAP with an FGFR1-TACC1 fusion, MTAP/CDKN2A/B deletion, and SETD2 rearrangement. Radiologically, the presence of calcification and cystic components and the absence of perilesional edema were atypical features of previously reported HGAP. Although recurrent symptomatic intracranial hemorrhages are rare in HGAP, enhancing lesions on magnetic resonance imaging suggest the need for resection to obtain tissue for molecular diagnosis and guide adjuvant treatment strategies. https://thejns.org/doi/10.3171/CASE24395. Show less

Small ubiquitin-related modifiers, SUMO-2/3 and SUMO-1, are involved in gene regulation and nuclear structures. However, little is known about the roles of SUMO, in heterochromatin formation of mammalian cells. Here we demonstrate that SUMOs directly interact with human MCAF1, which forms complexes with either the methyl-CpG-binding protein MBD1 or SETDB1, which trimethylates histone H3 at lysine 9 (H3-K9) in the presence of MCAF1. Modification of MBD1 with either SUMO-2/3 or SUMO-1 facilitated the interaction between MBD1 and MCAF1, suggesting that SUMOylation links the methylation of DNA and histones. In a cultured human cell line, SUMOs were localized in MBD1- and MCAF1-containing heterochromatin regions that were enriched in trimethyl-H3-K9 and the heterochromatin proteins HP1beta and HP1gamma. Specific knockdown of either SUMO-2/3 or SUMO-1 induced dissociation of MCAF1, trimethyl-H3-K9, and the HP1 proteins from the MBD1-containing heterochromatin foci, suggesting a requirement for SUMOs for heterochromatin assembly. These findings provide insights into the roles of SUMOylation in the regulation of heterochromatin formation and gene silencing. Show less