The off-label use of lisdexamphetamine dimesylate (LDX), a prodrug of dextroamphetamine, for cognitive enhancement has raised concerns due to its potential risk effects in neurotypical individuals. This study investigates the acute toxic effects of LDX exposure in zebrafish (), used here as a translational model. Zebrafish were exposed to 70, 100, and 140 mg/L of LDX to assess changes in anxiety-related, social-related and exploratory behaviors and cognitive function through novel tank test, social preference test, spatial memory test, and light-dark test, respectively.
View Article and Find Full Text PDFIn the general human population, aging is associated with a rise in systemic inflammation, primarily involving innate immune pathways related to interferon (IFN), toll-like receptor, and cytokine signaling. In systemic lupus erythematosus (SLE), a prototypical systemic autoimmune disease, aging is distinctly associated with improvements in disease activity, suggesting a unique relationship between aging and inflammation in this disease. Using a multi-omic approach incorporating transcriptional profiling, single cell RNA sequencing, proteomics and methylation analysis, we studied age-related changes in the immune profiles of 287 SLE patients between 20 and 83 years old, and compared the results against 928 healthy controls aged between 21 and 89 years old.
View Article and Find Full Text PDFBackground: Systemic lupus erythematosus (SLE) has numerous symptoms across organs and an unpredictable flare-remittance pattern. This has made it challenging to understand drivers of long-term SLE outcomes. Our objective was to identify whether changes in DNA methylation over time, in an actively flaring SLE cohort, were associated with remission and whether these changes meaningfully subtype SLE patients.
View Article and Find Full Text PDFSci Total Environ
December 2024
J Neurol Neurosurg Psychiatry
January 2025
Background: Lipids are of particular interest for the study of neuroinjury and neuroinflammation as structural lipids are major components of myelin, and a variety of lipid species modulate inflammation. In this study, we performed an in-depth lipidomics analysis to identify lipids associated with injury and disease activity.
Methods: Plasma samples were collected from paediatric-onset multiple sclerosis (MS) cases within 4 years of disease onset from 17 sites.
The consumption of hormone-derived medicines, such as levonorgestrel (LNG), is increasing worldwide, and its discharge into the environment reaches non-target organisms. In our previous study, we exposed the parental generation of zebrafish to environmentally relevant concentrations of LNG during the developmental phase. Subsequently, they had grown in a tank with clean water until adulthood.
View Article and Find Full Text PDFNeurol Neuroimmunol Neuroinflamm
September 2024
Background And Objectives: Psychosocial adversity and stress, known to predispose adults to neurodegenerative and inflammatory immune disorders, are widespread among children who experience socioeconomic disadvantage, and the associated neurotoxicity and proinflammatory profile may predispose these children to multiple sclerosis (MS). We sought to determine associations of socioeconomic disadvantage and psychosocial adversity with odds of pediatric-onset MS (POMS), age at POMS onset, and POMS disease activity.
Methods: This case-control study used data collected across 17 sites in the United States by the Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis Study.
Over the years, scientific research with fish models has grown at a rapid pace, and issues such as animal welfare are becoming increasingly important in various areas of animal husbandry and experimentation. Here, we evaluated whether behavior is affected by long-term maintenance (75 days) in an enriched environment or a chronic stress (CS) situation. In addition, we evaluated some biochemical parameters related to redox status.
View Article and Find Full Text PDFIntroduction: Epigenetic marks are key biomarkers linking the prenatal environment to health and development. However, DNA methylation associations and persistence of marks for prenatal exposure to multiple Endocrine Disrupting Chemicals (EDCs) in human populations have not been examined in great detail.
Methods: We measured Bisphenol-A (BPA), triclosan, benzophenone-3 (BP3), methyl-paraben, propyl-paraben, and butyl-paraben, as well as 11 phthalate metabolites, in two pregnancy urine samples, at approximately 13 and 26 weeks of gestation in participants of the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study (N = 309).
Numerous chemical compounds are found in aquatic environments; among them are pesticides. Pesticides are widely used worldwide, and this use has progressively increased in recent decades, resulting in the accumulation of potentially toxic compounds in surface waters. Dimethylamine-based herbicides (DBH) and imidacloprid-based insecticides (IBI) have low soil absorption and high water solubility, facilitating the arrival of these compounds in aquatic environments.
View Article and Find Full Text PDFAlthough evidence exists for a causal association between 25-hydroxyvitamin D (25(OH)D) serum levels, and multiple sclerosis (MS), the role of variation in vitamin D receptor (VDR) binding in MS is unknown. Here, we leveraged previously identified variants associated with allele imbalance in VDR binding (VDR-binding variant; VDR-BV) in ChIP-exo data from calcitriol-stimulated lymphoblastoid cell lines and 25(OH)D serum levels from genome-wide association studies to construct genetic instrumental variables (GIVs). GIVs are composed of one or more genetic variants that serve as proxies for exposures of interest.
View Article and Find Full Text PDFBackground And Objective: Prior Epstein-Barr virus (EBV) infection is associated with an increased risk of pediatric-onset multiple sclerosis (POMS) and adult-onset multiple sclerosis (MS). It has been challenging to elucidate the biological mechanisms underlying this association. We examined the interactions between candidate human leukocyte antigen (HLA) and non-HLA variants and childhood EBV infection as it may provide mechanistic insights into EBV-associated MS.
View Article and Find Full Text PDFBackground: Our previous study identified a significant association between lower time spent outdoors, as a proxy of sun exposure, and a higher risk of pediatric-onset multiple sclerosis (POMS). UV radiation modulates the expression of several genes, but it is unknown whether these genes modify the effect of sun exposure on POMS risk.
Methods: In an age- and sex-matched case-control study, we evaluated the additive and multiplicative interactions between time spent outdoors and genetic non-HLA risk variants for developing POMS within the metabolic pathways of UV radiation, including CD28(rs6435203), CD86(rs9282641), and NFkB1(rs7665090) and the top two HLA risk factors (presence of DRB1×15 and absence of A*02).
Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease resulting in debilitating clinical manifestations that vary in severity by race and ethnicity with a disproportionate burden in African American, Mestizo, and Asian populations compared with populations of European descent. Differences in global and local genetic ancestry may shed light on the underlying mechanisms contributing to these disparities, including increased prevalence of lupus nephritis, younger age of symptom onset, and presence of autoantibodies.
Methods: A total of 1,139 European, African American, and Mestizos patients with SLE were genotyped using the Affymetrix LAT1 World array.
High-quality datasets are crucial for building realistic and high-performance supervised malware detection models. Currently, one of the major challenges of machine learning-based solutions is the scarcity of datasets that are both representative and of high quality. To foster future research and provide updated and public data for comprehensive evaluation and comparison of existing classifiers, we introduce the MH-100K dataset [1], an extensive collection of Android malware information comprising 101,975 samples.
View Article and Find Full Text PDFBackground: Adverse childhood experiences are demonstrated risk factors for depression, a common co-morbidity of multiple sclerosis, but are understudied among people with multiple sclerosis.
Objective: Estimate the association between adverse childhood experiences and depression among 1,990 adults with multiple sclerosis.
Methods: Participants were members of Kaiser Permanente Northern California from two studies between 2006 and 2021 and were diagnosed with multiple sclerosis by a neurologist.
Noni is a fruit with potential medicinal use preventing elevated blood glucose levels in diabetes mellitus. Its effects have been attributed to an antioxidant property in several other diseases. However, the effects of noni-chronic supplementation on exercise performance in the presence of diabetes conditions are not known.
View Article and Find Full Text PDFThe use of terpenoid compounds in different neural-related conditions is becoming useful for several illnesses. Another possible activity of these compounds is the reduction of nervous impairment. Cannabis sativa plants are known for their concentration of two important terpenoids, the delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).
View Article and Find Full Text PDFThe trade of aquarium organisms is growing worldwide. This market depends on a continuous supply of healthy and colorful aquatic animals, but this sector has few initiatives. However, in the last decade, there has been a growing interest in researching captive breeding of these animals, aiming to develop a more sustainable aquarium hobby.
View Article and Find Full Text PDFDespite all efforts to combat the pandemic of COVID-19, we are still living with high numbers of infected persons, an overburdened health care system, and the lack of an effective and definitive treatment. Understanding the pathophysiology of the disease is crucial for the development of new technologies and therapies for the best clinical management of patients. Since the manipulation of the whole virus requires a structure with an adequate level of biosafety, the development of alternative technologies, such as the synthesis of peptides from viral proteins, is a possible solution to circumvent this problem.
View Article and Find Full Text PDFThe imidacloprid-based insecticides (IBIs) are among the most used insecticides worldwide, and chronic and acute toxic effects (days exposure protocols) have been reported in several species in studies of IBIs at lethal concentrations. However, there is little information on shorter time exposures and environmentally relevant concentrations. In this study, we investigated the effect of a 30-min exposure to environmentally relevant concentrations of IBI on the behavior, redox status, and cortisol levels of zebrafish.
View Article and Find Full Text PDFComp Biochem Physiol C Toxicol Pharmacol
September 2023
The growing consumption of psychoactive drugs, such as Venlafaxine (VFX), can negatively affect the organisms. Our main hypothesis is to investigate if VFX at human-used doses could exert effects on the behavioral, nervous, and antioxidant systems of two different organisms, zebrafish and C. elegans.
View Article and Find Full Text PDFComp Biochem Physiol C Toxicol Pharmacol
August 2023
The use of agrichemical pyrethroid-based insecticides to combat crop infestations and ectoparasites in animals is increasing. In this context, two pyrethroid-based insecticides are widely used, λ-cyhalothrin and Cypermethrin. The mechanism of action of these insecticides is characterized by the opening of ion channels and death by neural hyperexcitability.
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