Deciphering metabolic shifts in Gaucher disease type 1: a multi-omics study.

Gaucher disease (GD), an autosomal recessive lysosomal disorder, primarily affects the lysosomal enzyme β-glucocerebrosidase (GCase), leading to glucosylceramide accumulation in lysosomes. GD presents a wide spectrum of clinical manifestations. This study deploys immune-based proteomics and mass spectrometry-based metabolomics technologies to comprehensively investigate the biochemical landscape in 43 deeply phenotyped type 1 GD patients compared to 59 controls.

Metabolic remodeling in glioblastoma: a longitudinal multi-omics study.

Monitoring tumor evolution and predicting survival using non-invasive liquid biopsy is an unmet need for glioblastoma patients. The era of proteomics and metabolomics blood analyzes, may help in this context. A case-control study was conducted.

Stiripentol efficacy against status epilepticus and associated mortality in mice.

Stiripentol (STP, Diacomit©) is an antiseizure medication indicated for Dravet syndrome, a rare developmental and epileptic encephalopathy characterized by drug-resistant seizures, including status epilepticus (SE). SE is a life-threatening event that may lead to increased risk of morbidity and mortality. Here, we evaluated the effect of STP on SE and SE-associated mortality using a CBA mouse model induced by systemic administration of methionine sulfoximine (MSO), an irreversible inhibitor of glutamine synthetase.

Genome-wide expression analysis in a Fabry disease human podocyte cell line.

Fabry disease (FD) is an X-linked lysosomal disease caused by an enzyme deficiency of alpha-galactosidase A (α-gal A). This deficiency leads to the accumulation of glycosphingolipids in lysosomes, resulting in a range of clinical symptoms. The complex pathogenesis of FD involves lysosomal dysfunction, altered autophagy, and mitochondrial abnormalities.

In utero alcohol exposure impairs vessel-associated positioning and differentiation of oligodendrocytes in the developing neocortex.

Prenatal alcohol exposure (PAE) is a major cause of nongenetic mental retardation and can lead to fetal alcohol syndrome (FAS), the most severe manifestation of fetal alcohol spectrum disorder (FASD). FASD infants present behavioral disabilities resulting from neurodevelopmental defects. Both grey and white matter lesions have been characterized and are associated with apoptotic death and/or ectopic migration profiles.

Oligodendrocyte lineage is severely affected in human alcohol-exposed foetuses.

Prenatal alcohol exposure is a major cause of neurobehavioral disabilities. MRI studies in humans have shown that alcohol is associated with white matter microstructural anomalies but these studies focused on myelin abnormalities only after birth. Only one of these studies evaluated oligodendrocyte lineage, but only for a short period during human foetal life.

Extracellular Vesicles From LPS-Treated Macrophages Aggravate Smooth Muscle Cell Calcification by Propagating Inflammation and Oxidative Stress.

Vascular calcification (VC) is a cardiovascular complication associated with a high mortality rate among patients with diseases such as atherosclerosis and chronic kidney disease. During VC, vascular smooth muscle cells (VSMCs) undergo an osteogenic switch and secrete a heterogeneous population of extracellular vesicles (EVs). Recent studies have shown involvement of EVs in the inflammation and oxidative stress observed in VC.

Guidance in selecting analytical techniques for identification and quantification of non-intentionally added substances (NIAS) in food contact materials (FCMS).

There are numerous approaches and methodologies for assessing the identity and quantities of non-intentionally added substances (NIAS) in food contact materials (FCMs). They can give different results and it can be difficult to make meaningful comparisons. The initial approach was to attempt to prepare a prescriptive methodology but as this proved impossible; this paper develops guidelines that need to be taken into consideration when assessing NIAS.

Integrative Metabolomics Reveals Deep Tissue and Systemic Metabolic Remodeling in Glioblastoma.

(1) Background: Glioblastoma is the most common malignant brain tumor in adults. Its etiology remains unknown in most cases. Glioblastoma pathogenesis consists of a progressive infiltration of the white matter by tumoral cells leading to progressive neurological deficit, epilepsy, and/or intracranial hypertension.

Prenatal alcohol exposure is a leading cause of interneuronopathy in humans.

Alcohol affects multiple neurotransmitter systems, notably the GABAergic system and has been recognised for a long time as particularly damaging during critical stages of brain development. Nevertheless, data from the literature are most often derived from animal or in vitro models. In order to study the production, migration and cortical density disturbances of GABAergic interneurons upon prenatal alcohol exposure, we performed immunohistochemical studies by means of the proliferation marker Ki67, GABA and calretinin antibodies in the frontal cortical plate of 17 foetal and infant brains antenatally exposed to alcohol, aged 15 weeks' gestation to 22 postnatal months and in the ganglionic eminences and the subventricular zone of the dorsal telencephalon until their regression, i.

A Proteomics-Based Analysis Reveals Predictive Biological Patterns in Fabry Disease.

: Fabry disease (FD) is an X-linked progressive lysosomal disease (LD) due to glycosphingolipid metabolism impairment. Currently, plasmatic globotriaosylsphingosine (LysoGb3) is used for disease diagnosis and monitoring. However, this biomarker is inconstantly increased in mild forms and in some female patients.

Dried aerobic heterotrophic bacteria from treatment of food and beverage effluents: Screening of correlations between operation parameters and microbial protein quality.

Consortia of aerobic heterotrophic bacteria (AHB) have potential as sustainable microbial protein (MP) source in animal feed. A systematic screening of the nutritional value and safety of AHB biomass from full-scale activated sludge plants from 25 companies in the food sector was performed. The variable protein content (21-49%) was positively correlated with biomass-specific nitrogen loading rate and negatively with sludge retention time (SRT).

Mineral oil hydrocarbons in foods: is the data reliable?

The contamination of foods with mineral oil hydrocarbons (MOH) is a serious concern, requiring in most cases tedious mitigation measures that span across the whole food supply chain. A major issue today is the significant variability of the results generated by laboratories. This study was therefore designed to achieve a deeper insight into the analytical procedures used by commercial laboratories, identifying possible gaps and suggesting improvements that will enhance the reliability of the MOH data, an important prerequisite for risk assessment.

High variability in nutritional value and safety of commercially available Chlorella and Spirulina biomass indicates the need for smart production strategies.

Microalgal biomass production is a resource-efficient answer to the exponentially increasing demand for protein, yet variability in biomass quality is largely unexplored. Nutritional value and safety were determined for Chlorella and Spirulina biomass from different producers, production batches and the same production batch. Chlorella presented a similar protein content (47 ± 8%) compared to Spirulina (48 ± 4%).

Behaviour of doxycycline, oxytetracycline, tetracycline and flumequine during manure up-cycling for fertilizer production.

The fate of four widely used veterinary antibiotics (doxycycline, flumequine, oxytetracycline and tetracycline) during manure upcycling was investigated at laboratory and pilot scale. The pilot was operated continuously, while the laboratory scale in batch mode. Both set-ups consisted of anaerobic digestion, ammonia stripping and a solid liquid separation step.

PLGF, a placental marker of fetal brain defects after in utero alcohol exposure.

Most children with in utero alcohol exposure do not exhibit all features of fetal alcohol syndrome (FAS), and a challenge for clinicians is to make an early diagnosis of fetal alcohol spectrum disorders (FASD) to avoid lost opportunities for care. In brain, correct neurodevelopment requires proper angiogenesis. Since alcohol alters brain angiogenesis and the placenta is a major source of angiogenic factors, we hypothesized that it is involved in alcohol-induced brain vascular defects.

Prenatal alcohol exposure impairs autophagy in neonatal brain cortical microvessels.

Brain developmental lesions are a devastating consequence of prenatal alcohol exposure (PAE). We recently showed that PAE affects cortical vascular development with major effects on angiogenesis and endothelial cell survival. The underlying molecular mechanisms of these effects remain poorly understood.

NMDA receptor blockade in the developing cortex induces autophagy-mediated death of immature cortical GABAergic interneurons: An ex vivo and in vivo study in Gad67-GFP mice.

In neonates, excitotoxicity is a major process involved in hypoxic-ischemic brain lesions, and several research groups have suggested the use of NMDA antagonists for neuroprotection. However, despite their clinical interest, there is more and more evidence suggesting that, in the immature brain, these molecules exert deleterious actions on migrating GABAergic interneurons by suppressing glutamatergic trophic inputs. Consequently, preventing the side effects of NMDA antagonists would be therapeutically useful.

3-MA inhibits autophagy and favors long-term integration of grafted Gad67-GFP GABAergic precursors in the developing neocortex by preventing apoptosis.

In human neonates, immature GABAergic interneurons are markedly affected by an excitotoxic insult. While in adults the interest of cell transplantation has been demonstrated in several neurological disorders, few data are available regarding the immature brain. The low survival rate constitutes a strong limitation in the capacity of transplanted neurons to integrate the host tissue.

NO-dependent protective effect of VEGF against excitotoxicity on layer VI of the developing cerebral cortex.

In industrialized countries, cerebral palsy affects 2.5‰ of preterm and term infants. At a neurochemical level, the massive release of glutamate constitutes a major process leading to excitotoxicity and neonatal brain lesions.

Glutamine induces nuclear degradation of the NF-κB p65 subunit in Caco-2/TC7 cells.

In the intestine, NF-κB is the main transcription factor involved in the anti-inflammatory effect of glutamine and we previously demonstrated that glutamine via its conversion to glutamate diminished the p65 protein content in Caco-2/TC7 cell nuclei without affecting the stimulating effect of IL-1β on NF-κB [21]. However, the molecular mechanism by which glutamine acts is not established. We therefore tried to identify such a mechanism.

Hemojuvelin: a new link between obesity and iron homeostasis.

The adipose tissue may play an active role in systemic iron regulation and this role may be determinant in obese patients. Indeed, we reported previously that hepcidin, the iron-regulatory hormone, is expressed in adipose tissue and its messenger RNA (mRNA) expression is increased in adipose tissue of morbidly obese patients. The objectives of this study were to characterize the status of hemojuvelin (HJV), another iron-regulatory protein, within the adipose tissue of morbidly obese patients.

Immunoassay for human serum hemojuvelin.

Background: Hemojuvelin, a critical regulator of iron homeostasis, is involved in the regulation of hepcidin expression and iron homeostasis. It is expressed both as a membrane-bound form and as a soluble one. Serum hemojuvelin can be produced by secretion following furin cleavage or by proteolytic cleavage of the membrane-bound form by matriptase 2 (TMPRSS6).