Background/aim: Obese individuals often exhibit vitamin D deficiency, potentially due to sequestration in fat cells. Little is known about how vitamin D enters adipocytes and associates with the intracellular lipid droplet.
Materials And Methods: Newly differentiated human and mouse (3T3-L1) adipocytes and primary mouse adipocytes were treated with vitamin D covalently linked to green fluorescent BODIPY (VitD-B) or Green BODIPY (GB) as control.
Many complex diseases exhibit pronounced sex differences that can affect both the initial risk of developing the disease, as well as clinical disease symptoms, molecular manifestations, disease progression, and the risk of developing comorbidities. Despite this, computational studies of molecular data for complex diseases often treat sex as a confounding variable, aiming to filter out sex-specific effects rather than attempting to interpret them. A more systematic, in-depth exploration of sex-specific disease mechanisms could significantly improve our understanding of pathological and protective processes with sex-dependent profiles.
View Article and Find Full Text PDFBackground: Prolonged levodopa treatment in Parkinson's disease (PD) often leads to motor complications, including levodopa-induced dyskinesia (LID). Despite continuous levodopa treatment, some patients do not develop LID symptoms, even in later stages of the disease.
Objective: This study explores machine learning (ML) methods using baseline clinical characteristics to predict the development of LID in PD patients over four years, across multiple cohorts.
Formation and retrieval of remote contextual memory depends on cortical engram neurons that are defined during learning. Manipulation of astrocytic G and G associated G-protein coupled receptor (GPCR) signaling has been shown to affect memory processing, but little is known about the role of cortical astrocytic G-GPCR signaling in remote memory acquisition and the functioning of cortical engram neurons. We assessed this by chemogenetic manipulation of astrocytes in the medial prefrontal cortex (mPFC) of male mice, during either encoding or consolidation of a contextual fear memory, while simultaneously labeling cortical engram neurons.
View Article and Find Full Text PDFInulin, a polysaccharide characterized by a β-2,1 fructosyl-fructose structure terminating in a glucosyl moiety, is naturally present in plant roots and tubers. Current methods provide average degrees of polymerization (DP) but lack information on the distribution and absolute concentration of each DP. To address this limitation, a reproducible (CV < 10 %) high throughput (<2 min/sample) MALDI-MRMS approach capable of characterizing and quantifying inulin molecules in plants using matched-matrix consisting of α-cyano-4-hydroxycinnamic acid butylamine salt (CHCA-BA), chicory inulin-C and inulin-C was developed.
View Article and Find Full Text PDFParkinson's disease (PD) is a highly heterogeneous disorder influenced by several environmental and genetic factors. Effective disease-modifying therapies and robust early-stage biomarkers are still lacking, and an improved understanding of the molecular changes in PD could help to reveal new diagnostic markers and pharmaceutical targets. Here, we report results from a cohort-wide blood plasma metabolic profiling of PD patients and controls in the Luxembourg Parkinson's Study to detect disease-associated alterations at the level of systemic cellular process and network alterations.
View Article and Find Full Text PDFWe present compelling evidence for the existence of an extended innate viperin-dependent pathway, which provides crucial evidence for an adaptive response to viral agents, such as SARS-CoV-2. We show the in vivo biosynthesis of a family of novel endogenous cytosine metabolites with potential antiviral activities. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy revealed a characteristic spin-system motif, indicating the presence of an extended panel of urinary metabolites during the acute viral replication phase.
View Article and Find Full Text PDFJ Nutr Health Aging
December 2023
Objectives: There is a growing incidence of cognitive decline and dementia associated with the ageing population. Lifestyle factors such as diet, physical activity, and cognitive activities may individually or collectively be undertaken to increase one's odds of preventing cognitive decline and future dementia. This study will examine whether clinical trials using multidomain lifestyle intervention can significantly decrease the risk of cognitive decline and therefore dementia.
View Article and Find Full Text PDFBackground: Circulating lipids and lipoproteins mediate cardiovascular risk, however routine plasma lipid biochemistry provides limited information on pro-atherogenic remnant particles.
Objective: We analysed plasma lipoprotein subclasses including very low-density and intermediate-density lipoprotein (VLDL and IDL); and assessed their associations with health and cardiometabolic risk.
Methods: From 1,976 community-dwelling adults aged 45-67 years, 114/1071 women (10.
Demographic and clinical factors influence the metabolome. The discovery and validation of disease biomarkers are often challenged by potential confounding effects from such factors. To address this challenge, we investigated the magnitude of the correlation between serum and urine metabolites and demographic and clinical parameters in a well-characterized observational cohort of 444 post-menopausal women participating in the Women's Health Initiative (WHI).
View Article and Find Full Text PDFBackground: High recurrence and progression rates are major clinical challenges for non-muscle-invasive bladder cancer (NMIBC). Dietary isothiocyanates (ITCs), phytochemicals primarily from cruciferous vegetables (CV), show strong anticancer activities in preclinical BC models, yet their effect on NMIBC prognosis remains unknown.
Objectives: This study aimed to investigate the associations of dietary ITC exposure at diagnosis with NMIBC recurrence and progression.
Free-range eggs are ethically desirable but as with all high-value commercial products, the establishment of provenance can be problematic. Here, we compared a simple one-step isopropanol method to a two-step methyl-tert-butyl ether method for extracting lipid species in chicken egg yolks before liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The isopropanol method extracted 937 lipid species from 20 major lipid subclasses with high reproducibility (CV < 30 %).
View Article and Find Full Text PDFDevelopmental Origin of Health and Disease (DOHaD) explains how the health of the mother influences the offspring's risk of non-communicable diseases in later life. However, this remains underutilized in clinical practice. This study aimed to investigate the knowledge, attitude, and practice (KAP) of medical students, Obstetrics and Gynecology (O&G) and Pediatrics residents, toward DOHaD, identify potential barriers to DOHaD counseling, and translate DOHaD concepts into clinical practice.
View Article and Find Full Text PDFImportance: Tobacco smoking is an established risk factor associated with bladder cancer, yet its impact on bladder cancer prognosis is unclear.
Objective: To examine associations of use of tobacco (cigarettes, pipes, and cigars), e-cigarettes, and marijuana with risk of recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) and to explore use of smoking cessation interventions.
Design, Setting, And Participants: The Be-Well Study is a prospective cohort study of patients with NMIBC diagnosed from 2015 to 2019 and followed-up for 26.
Native mass spectrometry (MS) of proteins and protein assemblies reveals size and binding stoichiometry, but elucidating structures to understand their function is more challenging. Native top-down MS (nTDMS), i.e.
View Article and Find Full Text PDFBackground: The appropriate use of narcotics for postoperative pain control is controversial because of potential medication-induced complications. The authors sought to determine the effects of narcotics in the pediatric population following cranial vault remodeling operations.
Methods: A retrospective review was performed on 160 consecutive patients who underwent cranial vault remodeling for craniosynostosis.
Theta capillary nanoelectrospray ionization (θ-nanoESI) can be used to "supercharge" protein ions directly from solution for detection by mass spectrometry (MS). In native top-down MS, the extent of protein charging is low. Given that ions with more charge fragment more readily, increasing charge can enhance the extent of sequence information obtained by top-down MS.
View Article and Find Full Text PDFIntroduction: This study investigated whether a novel therapy called ischemic conditioning (IC) improves walking capacity and lower extremity muscle performance in patients with peripheral vascular disease who experience intermittent claudication.
Methods: Forty-three patients with claudication were enrolled and received either IC or IC Sham for 2 weeks in this randomized, controlled, double-blinded, prospective study. IC sessions involved five cycles of alternating 5-min inflations of a blood pressure cuff to 225 mm Hg (25 mm Hg for IC Sham) and 5-min deflations, around the thigh of the affected lower extremity.
Post-reactivation amnesia of contextual fear memories by blockade of noradrenergic signaling has been shown to have limited replicability in rodents. This is usually attributed to several boundary conditions that gate the destabilization of memory during its retrieval. How these boundary conditions can be overcome, and what neural mechanisms underlie post-reactivation changes in contextual fear memories remain largely unknown.
View Article and Find Full Text PDFThe extent to which lifestyle practices at night influence sleep quality in pregnant women remains unknown. This study aimed to examine whether nocturnal behaviours were associated with poor sleep during pregnancy. We performed a cross-sectional analysis of a prospective cohort of pregnant women at 18-24 gestation weeks recruited from KK Women's and Children's Hospital, Singapore, between 2019 and 2021.
View Article and Find Full Text PDFBackground: Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet enhances potassium intake and reduces sodium intake and blood pressure (BP), but the underlying metabolic pathways are unclear.
Objectives: Among free-living populations, we delineated metabolic signatures associated with the DASH diet adherence, 24-hour urinary sodium and potassium excretions, and the potential metabolic pathways involved.
Methods: We used 24-hour urinary metabolic profiling by proton nuclear magnetic resonance spectroscopy to characterize the metabolic signatures associated with the DASH dietary pattern score (DASH score) and 24-hour excretion of sodium and potassium among participants in the United States (n = 2164) and United Kingdom (n = 496) enrolled in the International Study of Macro- and Micronutrients and Blood Pressure (INTERMAP).