Cerebrospinal fluid proteomic profile of frailty: Results from the PROLIPHYC cohort.

Frailty is a clinical state reflecting a decrease in physiological reserve capacities, known to affect numerous biological pathways and is associated with health issues, including neurodegenerative diseases. However, how global protein expression is affected in the central nervous system in frail subject remains underexplored. In this post hoc cross-sectional biomarker analysis, we included 90 adults (52-85 years) suspected of normal pressure hydrocephalus (NPH) and presenting with markers of neurodegenerative diseases. We investigated the human proteomic profile of cerebrospinal fluid associated with frailty defined by an established cumulated frailty index (FI, average = 0.32), not enriched for neurology clinical features. Using a label-free quantitative proteomic approach, we identified and quantified 999 proteins of which 13 were positively associated with frailty. Pathway analysis with the top positively frailty-associated proteins revealed enrichment for proteins related to inflammation and immune response. Among the 60 proteins negatively associated with frailty, functional pathways enriched included neurogenesis, synaptogenesis and neuronal guidance. We constructed a frailty prediction model using ridge regression with 932 standardized proteins. Our results showed that the "proteomic model" could become an equivalent predictor of FI in order to study chronological age. This study represents the first comprehensive exploration of the proteomic profile of frailty within cerebrospinal fluid. It sheds light on the physiopathology of frailty, particularly highlighting processes of neuroinflammation and inhibition of neurogenesis. Our findings unveil a range of biological mechanisms that are dysregulated in frailty, in NPH subjects at risk of neurodegenerative impairment, offering new perspectives on frailty phenotyping and prediction.

Gamma-hydroxybutyrate (GHB), 1,4-butanediol (1,4BD), and gamma-butyrolactone (GBL) intoxication: A state-of-the-art review.

γ-hydroxybutyrate (GHB) is synthesized endogenously from γ-aminobutyric acid (GABA) or exogenously from 1,4-butanediol (butane-1,4-diol; 1,4-BD) or γ-butyrolactone (GBL). GBL, and 1,4-BD are rapidly converted to GHB. The gastric absorption time, volume of distribution, and half-life of GHB are between 5 and 45 min, 0.49 ± 0.9 L/kg, and between 20 and 60 min, respectively. GHB and its analogues have a dose-dependent effect on the activation of GHB receptor, GABA-B, and GABA localized to the central nervous system. After ingestion, most patients present transient neurological disorders (lethal dose: 60 mg/kg). Chronic GHB consumption is associated with disorders of use and a withdrawal syndrome when the consumption is discontinued. GHB, GBL, and 1,4-BD are classified as narcotics but only the use of GHB is controlled internationally. They are used for drug facilitated (sexual) assault, recreational purposes, slamsex, and chemsex. To confirm an exogenous intake or administration of GHB, GBL, or 1-4-BD, the pre-analytical conservation is crucial. The antemortem cutoff doses for detection are 5 and 5-15 mg/L, with detection windows of 6 and 10 h in the blood and urine, respectively Control of GHB is essential to limit the number of users, abuse, associated risks, and death related to their consumption.

Studying the Impact of Persistent Organic Pollutants Exposure on Human Health by Proteomic Analysis: A Systematic Review.

Persistent organic pollutants (POPs) are organic chemical substances that are widely distributed in environments around the globe. POPs accumulate in living organisms and are found at high concentrations in the food chain. Humans are thus continuously exposed to these chemical substances, in which they exert hepatic, reproductive, developmental, behavioral, neurologic, endocrine, cardiovascular, and immunologic adverse health effects. However, considerable information is unknown regarding the mechanism by which POPs exert their adverse effects in humans, as well as the molecular and cellular responses involved. Data are notably lacking concerning the consequences of acute and chronic POP exposure on changes in gene expression, protein profile, and metabolic pathways. We conducted a systematic review to provide a synthesis of knowledge of POPs arising from proteomics-based research. The data source used for this review was PubMed. This study was carried out following the PRISMA guidelines. Of the 742 items originally identified, 89 were considered in the review. This review presents a comprehensive overview of the most recent research and available solutions to explore proteomics datasets to identify new features relevant to human health. Future perspectives in proteomics studies are discussed.

Association Between Homocysteine, Frailty and Biomechanical Response of the CNS in NPH-Suspected Patients.

Frailty is a geriatric syndrome that combines physiological decline, disruptions of homeostatic mechanisms across multiple physiologic systems and thus, strong vulnerability to further pathological stress. Previously, we provided the first evidence that increased risk of poor health outcomes, as quantified by a frailty index (FI), is associated with an alteration of the central nervous system (CNS) biomechanical response to blood pulsatility. In this study, we explored correlation between 14 biological parameters, the CNS elastance coefficient and FI. We included 60 adults (52-92 years) suspected of normal pressure hydrocephalus and presenting with markers of multiple coexisting brain pathologies, including Parkinson disease, Alzheimer disease, and vascular dementia. We showed that the homocysteine (Hcy) level was independently and positively associated with both the FI and the CNS elastance coefficient (adjusted R² of 10% and 6%). We also demonstrated that creatinine clearance and folate level were independently associated with Hcy level. Based on previous literature results describing the involvement of Hcy in endothelial dysfunction, glial activation, and neurodegeneration, we discuss how Hcy could contribute to the altered biomechanical response of the CNS and frailty.

Marine Neurotoxins' Effects on Environmental and Human Health: An OMICS Overview.

Harmful algal blooms (HAB), and the consequent release of toxic metabolites, can be responsible for seafood poisoning outbreaks. Marine wildlife can accumulate these toxins throughout the food chain, which presents a threat to consumers' health. Some of these toxins, such as saxitoxin (STX), domoic acid (DA), ciguatoxin (CTX), brevetoxin (BTX), tetrodotoxin (TTX), and ß-N-methylamino-L-alanine (BMAA), cause severe neurological symptoms in humans. Considerable information is missing, however, notably the consequences of toxin exposures on changes in gene expression, protein profile, and metabolic pathways. This information could lead to understanding the consequence of marine neurotoxin exposure in aquatic organisms and humans. Nevertheless, recent contributions to the knowledge of neurotoxins arise from OMICS-based research, such as genomics, transcriptomics, proteomics, and metabolomics. This review presents a comprehensive overview of the most recent research and of the available solutions to explore OMICS datasets in order to identify new features in terms of ecotoxicology, food safety, and human health. In addition, future perspectives in OMICS studies are discussed.