Optimized analytical strategy based on high-resolution mass spectrometry for unveiling associations between long-term chemical exposome in hair and Alzheimer's disease.

Exposure to environmental pollutants or contaminants is correlated with detrimental effects on human health, such as neurodegenerative diseases. Adopting hair as a biological matrix for biomonitoring is a significant innovation, since it can reflect the long-term chemical exposome, spanning months to years. However, only a limited number of studies have developed analytical strategies for profiling the chemical exposome in this heterogeneous biological matrix. In this study, a systematic investigation of the chemical extraction procedure from human hair was conducted, using a design of experiments and a high-resolution mass spectrometry (HRMS)-based suspect screening approach. The PlackettBurman (PB) design was applied to identify the significant variables influencing the number of detected features. Then, a central composite design was implemented to optimize the levels of each identified significant variable. Under the optimal conditions-15-minute pulverization, 25 mg of hair weight, 40 min of sonication, and a sonication temperature of 35 °C-approximately 32,000 and 15,000 aligned features were detected in positive and negative ion modes, respectively. This optimized analytical procedure was applied to hair samples from patients with Alzheimer's disease (AD) and individuals with normal cognitive function. Overall, 307 chemicals were identified using the suspect screening approach, with 37 chemicals differentiating patients with AD from controls. This study not only optimized an analytical procedure for characterizing the long-term chemical exposome in human hair but also explored the associations between AD and environmental factors.

Utilizing fish wastewater in aquaponic systems to enhance anti-inflammatory and antioxidant bioactive compounds in Sarcodia suae.

Aquaculture wastewater, rich in organic nutrients, is an essential environmental factor. When applied to seaweed cultivation systems, this wastewater holds the potential to notably increase the growth rate and carbon capture of Sarcodia suae. Sarcodia suae has the potential to be a healthy food due to its various biological activities; however, its chemical composition has yet to be completely defined. In this study, we applied a UHPLC-HRMS-based foodomics strategy to determine and classify possible bioactive metabolites in S. suae. From pooled seaweed samples (S. suae cultured in filtered running, FR, aquaponic recirculation, AR systems), we identified 179 and 146 compounds in POS and NEG modes, respectively. These compounds were then classified based on their structures using the Classyfire classification. Results show that S. suae in AR exhibited higher growth performance, and ten upregulated metabolites were determined. We also validated the anti-inflammatory and antioxidative bioactivities of some selected compounds. Our study provided important insights into the potential use of fish wastewater in aquaponic systems to profile and produce bioactive compounds in S. suae comprehensively. This has significant implications for the development of sustainable food and the promotion of environmental health.

Monitoring long-term chemical exposome by characterizing the hair metabolome using a high-resolution mass spectrometry-based suspect screening approach.

Hair has recently emerged as a biospecimen for characterizing the long-term chemical exposome in biomonitoring investigations spanning several months, as chemical compounds circulating in the bloodstream accumulate in hair. Although there has been interest in using human hair as a biospecimen for exposome studies, it has yet to be widely adopted compared to blood and urine. Here, we applied a high-resolution mass spectrometry (HRMS)-based suspect screening strategy to characterize the long-term chemical exposome in human hair. Hair samples were collected from 70 subjects and cut into 3 cm segments, which were then mixed to prepare pooled samples. The pooled hair samples underwent a sample preparation procedure, and the hair extracts were further analyzed using an HRMS-based suspect screening approach. An in-house chemical suspect list containing 1227 chemical entries from National Report on Human Exposure to Environmental Chemicals (Report) published by the U.S. CDC and the Exposome-Explorer 3.0 database developed by the WHO was subsequently used to screen and filter the suspect features against the HRMS dataset. Overall, we matched 587 suspect features in the HRMS dataset to 246 unique chemical formulas in the suspect list, and the structures of 167 chemicals were further identified through a fragmentation analysis. Among these, chemicals such as mono-2-ethylhexyl phthalate, methyl paraben, and 1-naphthol, which have been detected in the urine or blood for exposure assessment, were also identified in human hair. This suggests that hair reflects the accumulation of environmental compounds to which an individual is exposed. Exposure to exogenous chemicals may exert adverse effects on cognitive function, and we discovered 15 chemicals in human hair that may contribute to the pathogenesis of Alzheimer's disease. This finding suggests that human hair may be a promising biospecimen for monitoring long-term exposure to multiple environmental chemicals and perturbations in endogenous chemicals in biomonitoring investigations.

Identifying Hair Biomarker Candidates for Alzheimer's Disease Using Three High Resolution Mass Spectrometry-Based Untargeted Metabolomics Strategies.

High-resolution mass spectrometry (HRMS)-based untargeted metabolomics strategies have emerged as an effective tool for discovering biomarkers of Alzheimer's disease (AD). There are various HRMS-based untargeted metabolomics strategies for biomarker discovery, including the data-dependent acquisition (DDA) method, the combination of full scan and target MS/MS, and the all ion fragmentation (AIF) method. Hair has emerged as a potential biospecimen for biomarker discovery in clinical research since it might reflect the circulating metabolic profiles over several months, while the analytical performances of the different data acquisition methods for hair biomarker discovery have been rarely investigated. Here, the analytical performances of three data acquisition methods in HRMS-based untargeted metabolomics for hair biomarker discovery were evaluated. The human hair samples from AD patients (N = 23) and cognitively normal individuals (N = 23) were used as an example. The most significant number of discriminatory features was acquired using the full scan (407), which is approximately 10-fold higher than that using the DDA strategy (41) and 11% higher than that using the AIF strategy (366). Only 66% of discriminatory chemicals discovered in the DDA strategy were discriminatory features in the full scan dataset. Moreover, compared to the deconvoluted MS/MS spectra with coeluted and background ions from the AIF method, the MS/MS spectrum obtained from the targeted MS/MS approach is cleaner and purer. Therefore, an untargeted metabolomics strategy combining the full scan with the targeted MS/MS method could obtain most discriminatory features along with a high quality MS/MS spectrum for discovering the AD biomarkers.