Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Background and Objectives: Although various cardiac parameters on echocardiography have clinical importance, their measurement by conventional manual methods is time-consuming and subject to variability. We evaluated the feasibility, accuracy, and predictive value of an artificial intelligence (AI)-based automated system for echocardiographic analysis in patients with ST-segment elevation myocardial infarction (STEMI). Methods: The AI-based system was developed using a nationwide echocardiographic dataset from five tertiary hospitals, and automatically identified views, then segmented and tracked the left ventricle (LV) and left atrium (LA) to produce volume and strain values. Both conventional manual measurements and AI-based fully automated measurements of the LV ejection fraction and global longitudinal strain, and LA volume index and reservoir strain were performed in 632 patients with STEMI. Results: The AI-based system accurately identified necessary views (overall accuracy, 98.5%) and successfully measured LV and LA volumes and strains in all cases in which conventional methods were applicable. Inter-method analysis showed strong correlations between measurement methods, with Pearson coefficients ranging 0.81–0.92 and intraclass correlation coefficients ranging 0.74–0.90. For the prediction of clinical outcomes (composite of all-cause death, re-hospitalization due to heart failure, ventricular arrhythmia, and recurrent myocardial infarction), AI-derived measurements showed predictive value independent of clinical risk factors, comparable to those from conventional manual measurements. Conclusions Our fully automated AI-based approach for LV and LA analysis on echocardiography is feasible and provides accurate measurements, comparable to conventional methods, in patients with STEMI, offering a promising solution for comprehensive echocardiographic analysis, reduced workloads, and improved patient care.

Objective: Previous studies have reported that vitamin D deficiency increased the risk of Alzheimer’s disease (AD) dementia in older adults. However, little is known about how vitamin D is involved in the pathophysiology of AD. Thus, this study aimed to examine the association and interaction of serum vitamin D levels with in vivo AD pathologies including cerebral beta-amyloid (Aβ) deposition and neurodegeneration in nondemented older adults. Methods: 428 Nondemented older adults were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease, a prospective cohort that began in 2014. All participants underwent comprehensive clinical assessments, measurement of serum 25-hydroxyvitamin D (25[OH]D), and multimodal brain imaging including Pittsburgh compound B (PiB) positron emission tomography and magnetic resonance imaging. Global PiB deposition was measured for the Aβ biomarker. Intracranial volume-adjusted hippocampal volume (HVa) was used as a neurodegeneration biomarker. Results: Overall, serum 25(OH)D level was not associated with either Aβ deposition or HVa after controlling for age, sex, apolipoprotein E ε4 positivity, and vascular risk factors. However, serum 25(OH)D level had a significant moderating effect on the association between Aβ and neurodegeneration, with lower serum 25(OH)D level significantly exacerbating cerebral Aβ-associated hippocampal volume loss (B = 34.612, p = 0.008). Conclusion Our findings indicate that lower serum vitamin D levels may contribute to AD by exacerbating Aβ-associated neurodegeneration in nondemented older adults. Further studies to explore the potential therapeutic effect of vitamin D supplementation on the progression of AD pathology will be necessary.