Adipocyte sphingosine kinase 1 regulates histone modifiers to disrupt circadian function.

Circadian rhythms align biological functions with the 24-hour day-night cycle, but modern artificial light disrupts these patterns, contributing to health issues like obesity and cardiovascular disease. The circadian clock operates through a transcriptional-translational feedback loop involving core components such as BMAL1 and CLOCK. Recent research has shown circadian variations in sphingolipid metabolism, specifically sphingosine-1-phosphate (S1P), which plays crucial signaling roles.

Sphingosine kinase 1 is induced by glucocorticoids in adipose derived stem cells and enhances glucocorticoid mediated signaling in adipose expansion.

Sphingosine kinase 1 (SphK1) plays a crucial role in regulating metabolic pathways within adipocytes and is elevated in the adipose tissue of obese mice. While previous studies have reported both pro- and inhibitory effects of SphK1 and its product, sphingosine-1-phosphate (S1P), on adipogenesis, the precise mechanisms remain unclear. This study explores the timing and downstream effects of SphK1/S1P expression and activation during adipogenesis.

Functional-Molecular Mechanisms of Sympathetic-Parasympathetic Dysfunction in PVC-Induced Cardiomyopathy Revealed by Dual Stressor PVC-Exercise Challenge.

Background: The significance of autonomic dysfunction in premature ventricular contraction-induced cardiomyopathy (PVC-CM) remain unknown.

Objectives: Utilizing a novel "dual stressor" provocative challenge combining exercise with premature ventricular contraction (PVCs), the authors characterized the functional and molecular mechanisms of cardiac autonomic (cardiac autonomic nervous system) remodeling in a PVC-CM animal model.

Methods: In 15 canines (8 experimental, 7 sham), we implanted pacemakers and neurotelemetry devices and subjected animals to 12 weeks of bigeminal PVCs to induce PVC-CM.

Anti-nuclear matrix protein 2 antibody-positive amyopathic dermatomyositis presenting in a patient with prostate cancer: A case report.

Nuclear matrix protein (NXP-2) positive amyopathic dermatomyositis (DM) may present without classic symptoms like muscle weakness, dysphagia, and edema, and mimic conditions like cutaneous lupus. Given DM's association with malignancy and interstitial lung disease, prompt and accurate diagnosis is important. Testing for myositis-specific antibodies aids diagnosis in ambiguous cases.

Larsucosterol: endogenous epigenetic regulator for treating chronic and acute liver diseases.

Larsucosterol, a potent endogenous epigenetic regulator, has been reported to play a significant role in lipid metabolism, inflammatory responses, and cell survival. The administration of larsucosterol has demonstrated a reduction in lipid accumulation within hepatocytes and the attenuation of inflammatory responses induced by lipopolysaccharide (LPS) and TNFα in macrophages, alleviating LPS- and acetaminophen (ATMP)-induced multiple organ injury, and decreasing mortalities in animal models. Results from and clinical trials have shown that larsucosterol has potential as a biomedicine for the treatment of acute and chronic liver diseases.

Exploring the Genomic Landscape of Hepatobiliary Cancers to Establish a Novel Molecular Classification System.

Taxonomy of hepatobiliary cancer (HBC) categorizes tumors by location or histopathology (tissue of origin, TO). Tumors originating from different TOs can also be grouped by overlapping genomic alterations (GA) into molecular subtypes (MS). The aim of this study was to create novel HBC MSs.

Cholestenoic acid as endogenous epigenetic regulator decreases hepatocyte lipid accumulation in vitro and in vivo.

Cholestenoic acid (CA) has been reported as an important biomarker of many severe diseases, but its physiological and pathological roles remain unclear. This study aimed to investigate the potential role of CA in hepatic lipid homeostasis. Enzyme kinetic studies revealed that CA specifically activates DNA methyltransferases 1 (DNMT1) at low concentration with EC = 1.

Induced pluripotent stem cells derived from patients carrying mitochondrial mutations exhibit altered bioenergetics and aberrant differentiation potential.

Background: Human mitochondrial DNA mutations are associated with common to rare mitochondrial disorders, which are multisystemic with complex clinical pathologies. The pathologies of these diseases are poorly understood and have no FDA-approved treatments leading to symptom management. Leigh syndrome (LS) is a pediatric mitochondrial disorder that affects the central nervous system during early development and causes death in infancy.

Sensory functions and their relation to balance metrics: a secondary analysis of the LIMBIC-CENC multicenter cohort.

Introduction: Among patients with traumatic brain injury (TBI), balance problems often persist alongside hearing and vision impairments that lead to poorer outcomes of functional independence. As such, the ability to regain premorbid independent gait may be dictated by the level of sensory acuity or processing decrements that are shown following TBI assessment. This study explores the relationships between standardized sensory acuity and processing outcomes to postural balance and gait speed.

Left ventricular remodeling in premature ventricular contraction-induced cardiomyopathy: Effect of coupling intervals and atrioventricular dissociation.

Background: Left ventricular dyssynchrony (LVD) and postextrasystolic potentiation (PESP) associated with premature ventricular contractions (PVCs) may play a role in the development of premature ventricular contraction-induced cardiomyopathy (PVC-CM). Long-coupled (LC) PVCs have a greater LVD than short-coupled (SC) PVCs, whereas SC-PVCs have a stronger PESP than LC-PVCs.

Objective: The purpose of this study was to compare SC-PVCs and LC-PVCs to evaluate the roles of LVD, PESP, and atrioventricular dissociation (AVD) in the development of PVC-CM.

Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer's disease.

Background: Despite being a brain disorder, Alzheimer's disease (AD) is often accompanied by peripheral organ dysregulations (e.g., loss of bladder control in late-stage AD), which highly rely on spinal cord coordination.

Adult-Onset CNS Sulfatide Deficiency Causes Sex-Dependent Metabolic Disruption in Aging.

The interconnection between obesity and central nervous system (CNS) neurological dysfunction has been widely appreciated. Accumulating evidence demonstrates that obesity is a risk factor for CNS neuroinflammation and cognitive impairment. However, the extent to which CNS disruption influences peripheral metabolism remains to be elucidated.

Mechanisms of adaptive hypertrophic cardiac remodeling in a large animal model of premature ventricular contraction-induced cardiomyopathy.

Frequent premature ventricular contractions (PVCs) promoted eccentric cardiac hypertrophy and reduced ejection fraction (EF) in a large animal model of PVC-induced cardiomyopathy (PVC-CM), but the molecular mechanisms and markers of this hypertrophic remodeling remain unexplored. Healthy mongrel canines were implanted with pacemakers to deliver bigeminal PVCs (50% burden with 200-220 ms coupling interval). After 12 weeks, left ventricular (LV) free wall samples were studied from PVC-CM and Sham groups.

Electrosprayed Mesenchymal Stromal Cell Extracellular Matrix Nanoparticles Accelerate Cellular Wound Healing and Reduce Gram-Negative Bacterial Growth.

Treatments for acute respiratory distress syndrome are still unavailable, and the prevalence of the disease has only increased due to the COVID-19 pandemic. Mechanical ventilation regimens are still utilized to support declining lung function but also contribute to lung damage and increase the risk for bacterial infection. The anti-inflammatory and pro-regenerative abilities of mesenchymal stromal cells (MSCs) have shown to be a promising therapy for ARDS.

Exhaled breath condensate identifies metabolic dysregulation in patients with radiation-induced lung injury.

Radiation-induced lung injury (RILI) is a consequence of therapeutic thoracic irradiation (TR) for many cancers, and there are no FDA-approved curative strategies. Studies report that 80% of patients who undergo TR will have CT-detectable interstitial lung abnormalities, and strategies to limit the risk of RILI may make radiotherapy less effective at treating cancer. Our lab and others have reported that lung tissue from patients with idiopathic pulmonary fibrosis (IPF) exhibits metabolic defects including increased glycolysis and lactate production.

Apolipoprotein M Attenuates Anthracycline Cardiotoxicity and Lysosomal Injury.

Apolipoprotein M (ApoM) binds sphingosine-1-phosphate (S1P) and is inversely associated with mortality in human heart failure (HF). Here, we show that anthracyclines such as doxorubicin (Dox) reduce circulating ApoM in mice and humans, that ApoM is inversely associated with mortality in patients with anthracycline-induced heart failure, and ApoM heterozygosity in mice increases Dox-induced mortality. In the setting of Dox stress, our studies suggest ApoM can help sustain myocardial autophagic flux in a post-transcriptional manner, attenuate Dox cardiotoxicity, and prevent lysosomal injury.

Mechanism of resistance to phagocytosis and pulmonary persistence in mucoid .

Introduction: Pseudomonas aeruginosa is known for its ability to form biofilms, which are dependent on the production of exopolysaccharides. During chronic colonization of the airway and biofilm formation, P. aeruginosa converts to a mucoid phenotype, indicating production of the exopolysaccharide alginate.

Risk Factors and Cardiovascular Events in Orthotopic Liver Transplantation.

Background And Aims: Patients undergoing liver transplantation often have significant cardiovascular risk factors and may experience cardiac-related morbidity and mortality. The aim of this study was to assess the frequency of cardiovascular risk factors and outcomes in this population, and to identify factors predictive of post-transplant cardiac morbidity and mortality.

Methods: We studied 261 patients who underwent liver transplantation at a single Veterans' Affairs Medical center between 1997 and 2015 to evaluate new cardiovascular events post-transplantation.

Sulfatide Deficiency, an Early Alzheimer's Lipidomic Signature, Causes Brain Ventricular Enlargement in the Absence of Classical Neuropathological Hallmarks.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and a decline in activities of daily life. Ventricular enlargement has been associated with worse performance on global cognitive tests and AD. Our previous studies demonstrated that brain sulfatides, myelin-enriched lipids, are dramatically reduced in subjects at the earliest clinically recognizable AD stages via an apolipoprotein E (APOE)-dependent and isoform-specific process.

Altered lateralization of the cingulum in deployment-related traumatic brain injury: An ENIGMA military-relevant brain injury study.

Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI.

Profiling of Urinary Glucuronidated Bile Acids across Age Groups.

We investigated the age-dependent changes in urinary excretion of glucuronidated bile acids at the C-3 position. Bile acid 3-glucuronides accounted for 0.5% of urinary bile acids in neonates, and the proportion of bile acid 3-glucuronides plateaued at 1-3 years of age.

Colon Adenocarcinoma Metastasis Through Ileocolic Fistula to Small Bowel in the Setting of Crohn's Disease.

Patients with Crohn's disease are at higher risk of developing colorectal cancer and gastrointestinal fistula. Few cases in the past described colorectal cancer metastasized within the gastrointestinal tract through a fistula. We report a case of sigmoid colon adenocarcinoma in a patient with Crohn's disease that metastasized to the ileum through an ileocolic fistula tract.