PubMed

Biol Psychiatry. 2023 Dec 22:S0006-3223(23)01792-4. doi: 10.1016/j.biopsych.2023.12.015. Online ahead of print.ABSTRACTBACKGROUND: There have been many metabolomics studies of depression, but these have been limited by their scale. A comprehensive in silico analysis of global metabolite levels in large populations could provide robust insights into the pathological mechanisms underlying depression and candidate clinical biomarkers.METHODS: Depression-associated metabolomics was studied in two datasets from the UK Biobank database: participants with lifetime depression (n=123,459) and those with current depression (n=94,921). The Whitehall II cohort (n=4,744) was used for external validation. CatBoost machine learning was used for modeling, and Shapley Additive Explanations were used to interpret the model. Five-fold cross-validation was used to validate model performance, training the model on three of the five sets with the remaining two for validation and testing, respectively. The diagnostic performance was assessed using area under receiver operating characteristic (AUC) curves.RESULTS: Twenty-four significantly associated metabolic biomarkers were identified in the lifetime depression and current depression datasets and sex-specific analyses, 12 of which overlapped in the two datasets. The addition of metabolic features slightly improved the performance of a diagnostic model using traditional (non-metabolomic) risk factors alone (lifetime depression: AUCs 0.655 versus 0.658 with metabolomics; current depression: AUCs 0.711 versus 0.716 with metabolomics).CONCLUSIONS: The machine learning model identified 24 metabolic biomarkers associated with depression. If validated, metabolic biomarkers may have future clinical applications as supplementary information to guide early and population-based depression detection.PMID:38142718 | DOI:10.1016/j.biopsych.2023.12.015

Neuroendocrinology. 2023 Dec 24. doi: 10.1159/000535611. Online ahead of print.ABSTRACTINTRODUCTION: The perception of hunger is a complex physiological process that requires precise coordination between the central and peripheral tissues.METHODS: In this study, tilapia fasted for 24 hours was chosen to establish a hunger model to study the mechanism of homeostasis recovery under the joint regulation of the central nervous system (CNS) and peripheral tissues.RESULTS: The gastric and intestinal contents of tilapia were predominantly depleted after a fasting period of 9 hours and 24 hours, respectively. The serum glucose level significantly decreased at the 9-h and 24-h fasting, respectively, and the glucokinase-dependent glucosensing mechanism in the liver was identified as well as the significant activation of phospho-AMPK. However, fasting for 24 hours did not activate glucosensing mechanisms and AMPK signaling pathways in the hypothalamus. On the other hand, significant reductions were observed in the mRNA levels of the lipid synthesis-related genes fas and accα, and the serum triglyceride levels as well. The mRNA levels of npy, agrp, pomc and cart in the hypothalamus fluctuated during the fasting period without significant differences. With in situ hybridization npy signals upregulated in the ventral zone of posterior periventricular nucleus after 24-hour fasting, while pomc signals enhanced in the lateral tuberal nucleus. Based on the serum metabolomic analysis, the levels of branched-chain amino acids, butyrate and short-chain acylcarnitine decreased while those of medium- and long-chain acylcarnitine increased.CONCLUSION: Fasting for 24 hours resulted in changes in npy and pomc signals within the hypothalamus, triggered the glucosensing mechanism in the liver of tilapia. This study is beneficial for elucidating the response of neuropeptides in the CNS to the changes of nutritional factors when hungry.PMID:38142691 | DOI:10.1159/000535611

Int Immunopharmacol. 2023 Dec 23;127:111406. doi: 10.1016/j.intimp.2023.111406. Online ahead of print.ABSTRACTOsteoarthritis (OA) causes severe and functional dysfunction due to abnormal inflammation. The objective of this study was to evaluate the effect of Harpagide (HPG) on TNF-α-induced inflammation in vitro and in vivo. The effect of HPG on the proliferation of rat chondrocytes was studied. The anti-inflammatory effect of HPG and its molecular mechanisms were elucidated by qPCR, Western blotting, flow cytometry, metabolome analysis in vitro. In addition, the OA rat model was established, and the effect of HPG on OA was verified in vivo. We revealed 10 μM HPG demonstrated biocompatibility. The results demonstrated that HPG restored the upregulation of MMP-13, COX2, IL-1β and IL-6 induced by TNF-α. Moreover, HPG reversed TNF-α induced degradation of the extracellular matrix of chondrocytes. TNF-α treatment induced down-regulation of the mRNA/protein levels of proliferative markers Bcl2, CDK1 and Cyclin D1 were also recovered. HPG can inhibit TNF-α-induced inflammatory response through glycolytic metabolic pathways. HPG can restore TNF-α-induced upregulation of GRP78/IRE1α, and downregulation of AMPK proteins. In vivo experiments demonstrated that after HPG treatment, the appearance and physiological structure of articular cartilage were more integrated with highly organized chondrocytes and rich cartilage matrix compared with OA group. Finally, the molecular docking of HPG and selected key factors in glycolysis results showed that HPG had good binding potential with PFKM, PFKP, PFKFB3, PKM, HK2, and PFKL. In conclusion, the results shown HPG protects and activates chondrocytes, inhibits TNF-α-induced inflammatory response by glycolysis pathway in rat articular chondrocytes, and plays a role in the treatment of OA.PMID:38142643 | DOI:10.1016/j.intimp.2023.111406

Neoplasia. 2023 Dec 23;47:100958. doi: 10.1016/j.neo.2023.100958. Online ahead of print.ABSTRACTHead and neck cancer ranks as the sixth most prevalent malignancy, constituting 5 % of all cancer cases. Its inconspicuous onset often leads to advanced stage diagnoses, prompting the need for early detection to enhance patient prognosis. Currently, research into early diagnostic markers relies predominantly on genomics, proteomics, transcriptomics, and other methods, which, unfortunately, necessitate tumor tissue homogenization, resulting in the loss of temporal and spatial information. Emerging as a recent addition to the omics toolkit, spatial metabolomics stands out. This method conducts in situ mass spectrometry analyses on fresh tissue specimens while effectively preserving their spatiotemporal information. The utilization of spatial metabolomics in life science research offers distinct advantages. This article comprehensively reviews the progress of spatial metabolomics in head and neck cancer research, encompassing insights into cancer cell metabolic reprogramming. Various mass spectrometry imaging techniques, such as secondary ion mass spectrometry, stroma-assisted laser desorption/ionization, and desorption electrospray ionization, enable in situ metabolite analysis for head and neck cancer. Finally, significant emphasis is placed on the application of presently available techniques for early diagnosis, margin assessment, and prognosis of head and neck cancer.PMID:38142528 | DOI:10.1016/j.neo.2023.100958

Carbohydr Polym. 2024 Feb 15;326:121636. doi: 10.1016/j.carbpol.2023.121636. Epub 2023 Nov 23.ABSTRACTNanofiber packaging has not yet gained practical application in fruit preservation because of some limitations, such as low production rate and utilization, and failure due to poor adhesion to the fruit. Herein, to solve this issue, a novel fruit packaging method based on solution blow spinning (SBS), called in-situ packaging, was pioneered. Specifically, carboxymethyl chitosan (CMCH) and polycaprolactone (PCL) were chosen as substrate materials and cherry tomatoes were selected as demonstration subjects. CMCH/PCL nanofibers were deposited directly onto the surface of cherry tomatoes by SBS, forming a tightly adherent and stable fiber coating in 8 min. Also, this in-situ packaging could be easily peeled off by hand. The in-situ packaging was an excellent carrier for active substances and was effective in inhibiting gray mold on cherry tomatoes. The in-situ packaging film formed a barrier on the surface of cherry tomatoes to limit moisture penetration, resulting in reduced respiration of fruits, which led to reduced weight and firmness loss. In addition, metabolomics and color analysis revealed that the in-situ packaging delayed ripening of cherry tomatoes after harvest. Overall, the in-situ packaging method developed in the present work provides a new solution for post-harvest fruit preservation.PMID:38142080 | DOI:10.1016/j.carbpol.2023.121636

J Adv Res. 2023 Dec 21:S2090-1232(23)00403-4. doi: 10.1016/j.jare.2023.12.013. Online ahead of print.ABSTRACTINTRODUCTION: Acid ceramidase (hereafter referred as ASAH1) is an enzyme in sphingolipid metabolism that converts pro-survival ceramide into sphingosine. ASAH1 has been shown to be overexpressed in certain cancers. However, the role of ASAH1 in colorectal cancer is still remain elusive OBJECTIVE: The present study is aimed to understand how ASAH1 regulates colorectal cancer (CRC) progression and resistance to checkpoint inhibitor therapy.METHODS: Both pharmacological and genetic silencing of ASAH1 was used in the study. In vitro experiments were done on human and mouse CRC cell lines. The in vivo studies were conducted in NOD-SCID and BALB/c mice models. The combination of ASAH1 inhibitor and checkpoint inhibitor was tested using a syngeneic tumor model of CRC. Transcriptomic and metabolomic analyses were done to understand the effect of ASAH1 silencing.RESULTS: ASAH1 is overexpressed in human CRC cases, and silencing the expression resulted in the induction of immunological cell death (ICD) and mitochondrial stress. The ASAH1 inhibitor (LCL-521), either as monotherapy or in combination with an anti-PD-1 antibody, resulted in a reduction of tumors and, through induction of type I and II interferon response, activation of M1 macrophages and T cells, leading to enhanced infiltration of cytotoxic T cells. Our findings supported that the combination of LCL-521 and ICIs, which enhances the antitumor responses, and ASAH1 can be a druggable target in CRC.PMID:38142035 | DOI:10.1016/j.jare.2023.12.013

Environ Pollut. 2023 Dec 21:123211. doi: 10.1016/j.envpol.2023.123211. Online ahead of print.ABSTRACTThe primary objective of this study was to examine the effect of acute ammonia stress on hepatic physiological alterations in yellow catfish by performing a comprehensive analysis of the metabolome and transcriptome. The present study showed that ammonia stress led to liver metabolic disruption, functional incapacitation, and oxidative damage. Transcriptomic and metabolomic analyses revealed transcriptional and metabolic differences in the liver of yellow catfish under control and high ammonia stress conditions. After 96 h of acute exposure to ammonia, the mRNA levels of 596 liver genes were upregulated, whereas those of 603 genes were downregulated. Enrichment analysis of the differentially expressed genes identified multiple signalling pathways associated with autophagy, including the endocytosis, autophagy-animal, and mammalian target of rapamycin signalling pathways. A total of 186 upregulated and 117 downregulated metabolites, primarily associated with amino acid biosynthesis pathways, were identified. Multi-omics integration revealed the solute carrier family 38 member 9 (SLC38A9)-mammalian target of rapamycin axis as a signalling nexus for amino acid-mediated modulation of autophagy flux, and q-PCR was used to assess the expression of autophagy-related genes (LC3a and sqstm1), revealing an initial inhibition followed by the restoration of autophagic flux during ammonia stress. Subsequent utilisation of arginine as a specific SLC38A9 activator during ammonia stress demonstrated that augmented SLC38A9 expression hindered autophagy, exacerbated ammonia toxicity, and caused a physiological decline (total cholesterol, total triglyceride, acid phosphatase, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels were significantly increased), oxidative stress, and apoptosis. Autophagy activation may be an adaptive mechanism to resist ammonia stress.PMID:38142034 | DOI:10.1016/j.envpol.2023.123211

Environ Pollut. 2023 Dec 21:123186. doi: 10.1016/j.envpol.2023.123186. Online ahead of print.ABSTRACTThe second-generation neonicotinoid thiamethoxam, is prevalent in soils because of its extensive application and persistence. However, the comprehensive effects of thiamethoxam residue in soils on cultivated plants are still poorly understood. This study examined variations of growth state, physiological parameters, antioxidant activity, and metabolites in lettuce after thiamethoxam exposure; the removal effects of different washing procedures were also investigated. The results indicated that thiamethoxam in soils significantly increased the fresh weight, seedling height and chlorophyll content in lettuce, and also altered its lipid, carbohydrate, nucleotide and amino acids composition based on untargeted metabolomics. KEGG pathway analysis uncovered a disruption of lipid pathways in lettuce exposed to both low and high concentrations of thiamethoxam treatments. In addition, the terminal residues of thiamethoxam in lettuce were below the corresponding maximum residue limits stipulated for China. The thiamethoxam removal rates achieved by common washing procedures in lettuce ranged from 26.9 to 42.6%. This study thus promotes the understanding of the potential food safety risk caused by residual thiamethoxam in soils.PMID:38142029 | DOI:10.1016/j.envpol.2023.123186

Sci Total Environ. 2023 Dec 21:169458. doi: 10.1016/j.scitotenv.2023.169458. Online ahead of print.ABSTRACTCapturing the breadth of chemical exposures in utero is critical in understanding their long-term health effects for mother and child. We explored methodological adaptations in a Non-Targeted Analysis (NTA) pipeline and evaluated the effects on chemical annotation and discovery for maternal and infant exposure. We focus on lesser-known/underreported chemicals in maternal and umbilical cord serum analyzed with liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). The samples were collected from a demographically diverse cohort of 296 maternal-cord pairs (n = 592) recruited in San Francisco Bay area. We developed and evaluated two data processing pipelines, primarily differing by detection frequency cut-off, to extract chemical features from non-targeted analysis (NTA). We annotated the detected chemical features by matching with EPA CompTox Chemicals Dashboard (n = 860,000 chemicals) and Human Metabolome Database (n = 3140 chemicals) and applied a Kendrick Mass Defect filter to detect homologous series. We collected fragmentation spectra (MS/MS) on a subset of serum samples and matched to an experimental MS/MS database within the MS-Dial website and other experimental MS/MS spectra collected from standards in our lab. We annotated ~72 % of the features (total features = 32,197, levels 1-4). We confirmed 22 compounds with analytical standards, tentatively identified 88 compounds with MS/MS spectra, and annotated 4862 exogenous chemicals with an in-house developed annotation algorithm. We detected 36 chemicals that appear to not have been previously reported in human blood and 9 chemicals that were reported in less than five studies. Our findings underline the importance of NTA in the discovery of lesser-known/unreported chemicals important to characterize human exposures.PMID:38142008 | DOI:10.1016/j.scitotenv.2023.169458

Environ Res. 2023 Dec 21:118015. doi: 10.1016/j.envres.2023.118015. Online ahead of print.ABSTRACTHeavy metals (HMs) contamination of water bodies severely threatens human and ecosystem health. There is growing interest in the use of duckweeds for HMs biomonitoring and phytoremediation due to their fast growth, low cultivation costs, and excellent HM uptake efficiency. In this review, we summarize the current state of knowledge on duckweeds and their suitability for HM biomonitoring and phytoremediation. Duckweeds have been used for phytotoxicity assays since the 1930s. Some toxicity tests based on duckweeds have been listed in international guidelines. Duckweeds have also been recognized for their ability to facilitate HM phytoremediation in aquatic environments. Large-scale screening of duckweed germplasm optimized for HM biomonitoring and phytoremediation is still essential. We further discuss the morphological, physiological, and molecular effects of HMs on duckweeds. However, the existing data are clearly insufficient, especially in regard to dissection of the transcriptome, metabolome, proteome responses and molecular mechanisms of duckweeds under HM stresses. We also evaluate the influence of environmental factors, exogenous substances, duckweed community composition, and HM interactions on their HM sensitivity and HM accumulation, which need to be considered in practical application scenarios. Finally, we identify challenges and propose approaches for improving the effectiveness of duckweeds for bioremediation from the aspects of selection of duckweed strain, cultivation optimization, engineered duckweeds. We foresee great promise for duckweeds as phytoremediation agents, providing environmentally safe and economically efficient means for HM removal. However, the primary limiting issue is that so few researchers have recognized the outstanding advantages of duckweeds. We hope that this review can pique the interest and attention of more researchers.PMID:38141920 | DOI:10.1016/j.envres.2023.118015

Mol Metab. 2023 Dec 21:101857. doi: 10.1016/j.molmet.2023.101857. Online ahead of print.ABSTRACTOBJECTIVE: Long-term high-level exercise training leads to improvements in physical performance and multi-tissue adaptation following changes in molecular pathways. While skeletal muscle baseline differences between exercise-trained and untrained individuals have been previously investigated, it remains unclear how training history influences human multi-omics responses to acute exercise.METHODS: We recruited and extensively characterized 24 individuals categorized as endurance athletes with >15 years of training history, strength athletes or control subjects. Timeseries skeletal muscle biopsies were taken from M. vastus lateralis at three time-points after endurance or resistance exercise was performed and multi-omics molecular analysis performed.RESULTS: Our analyses revealed distinct activation differences of molecular processes such as fatty- and amino acid metabolism and transcription factors such as HIF1A and the MYF-family. We show that endurance athletes have an increased abundance of carnitine-derivates while strength athletes increase specific phospholipid metabolites compared to control subjects. Additionally, for the first time, we show the metabolite sorbitol to be substantially increased with acute exercise. On transcriptional level, we show that acute resistance exercise stimulates more gene expression than acute endurance exercise. This follows a specific pattern, with endurance athletes uniquely down-regulating pathways related to mitochondria, translation and ribosomes. Finally, both forms of exercise training specialize in diverging transcriptional directions, differentiating themselves from the transcriptome of the untrained control group.CONCLUSIONS: We identify a "transcriptional specialization effect" by transcriptional narrowing and intensification, and molecular specialization effects on metabolomic level Additionally, we performed multi-omics network and cluster analysis, providing a novel resource of skeletal muscle transcriptomic and metabolomic profiling in highly trained and untrained individuals.PMID:38141850 | DOI:10.1016/j.molmet.2023.101857

J Ethnopharmacol. 2023 Dec 22;322:117596. doi: 10.1016/j.jep.2023.117596. Online ahead of print.NO ABSTRACTPMID:38141517 | DOI:10.1016/j.jep.2023.117596

Aquat Toxicol. 2023 Dec 13;266:106804. doi: 10.1016/j.aquatox.2023.106804. Online ahead of print.ABSTRACTAmong the various pollutants detected in aquatic ecosystems, cadmium (Cd) is considered as one of the most hazardous. Freshwater macrophytes have been recognized as possible candidates for eliminating Cd from environment. Nevertheless, the impact of light quality on their ability to tolerate Cd toxicity remains unclear, and the underlying mechanisms have yet to be fully elucidated. In this study, we utilized physiological testing and metabolomics to explore the potential mechanisms by which light quality influences the ability of Egeria densa, a significant Cd hyperaccumulator, to withstand Cd toxicity. The study demonstrated that following Cd treatment, E. densa grown under red light exhibited superior photosynthetic efficiency compared to those grown under blue light, as evidenced by significantly increased photosynthetic rate, higher starch content, and greater activity of photosynthetic enzymes. Moreover, metabolomic analyses revealed that under Cd stress, E. densa grown under red light exhibited an enhanced glycolysis for increased energy production. Sucrose metabolism was also improved to generate sufficient sugar including glucose, fructose and mannose for osmotic adjustment. Moreover, under red light, the heightened production of α-ketoglutarate via tricarboxylic acid (TCA) cycle redirected nitrogen flow towards the synthesis of resilient substances such as γ-Aminobutyric Acid (GABA) and methionine. The production of these substances was ∼2.0 and 1.3 times greater than that of treatment with Cd under blue light, thereby improving E. densa's capacity to withstand Cd stress. This study represents the initial investigation into the possible mechanisms by which light quality influences the ability of E. densa to withstand Cd toxicity through regulating CN metabolism. Furthermore, these findings have the potential to improve phytoremediation strategies aimed at reducing Cd pollution.PMID:38141498 | DOI:10.1016/j.aquatox.2023.106804

Comp Biochem Physiol Part D Genomics Proteomics. 2023 Dec 20;49:101182. doi: 10.1016/j.cbd.2023.101182. Online ahead of print.ABSTRACTLow water temperature is a critical environmental factor limiting the size of cultivated aquatic individuals. However, it has found that a proportion of Eriocheir sinensis cultured in low water temperature with high-altitude can mature into three-year-old crabs, which present larger body size than conventional two-year-old crabs. Based on integrated transcriptomic and metabolomic analysis, the significantly difference focuses on metabolic pathways involving glycine, serine, and threonine metabolism, amino sugar and nucleotide sugar metabolism, cysteine and methionine metabolism, pantothenate and CoA biosynthesis, arginine and proline metabolism, and vitamin digestion and absorption. It revealed that the growth performance of three-year-old crabs is mainly regulated by improving its antioxidant defense to maintain physical fitness, while reducing protein consumption by intensifying energy supplement ability and enhancing the ability to digest and absorb nutrients at low temperature. This study provides new insights on the molecular and metabolic pathways that control E. sinensis growth at high-altitude and low water temperature, laying the theoretical basis for further artificial three-year-old crabs breeding.PMID:38141371 | DOI:10.1016/j.cbd.2023.101182

Ecotoxicol Environ Saf. 2023 Dec 22;270:115832. doi: 10.1016/j.ecoenv.2023.115832. Online ahead of print.ABSTRACTAgricultural productivity is constantly being forced to maintain yield stability to feed the enormously growing world population. However, shrinking arable and nutrient-deprived soil and abiotic and biotic stressor (s) in different magnitudes put additional challenges to achieving global food security. Though well-defined, the concept of macro, micronutrients, and beneficial elements is from a plant nutritional perspective. Among various micronutrients, selenium (Se) is essential in small amounts for the life cycle of organisms, including crops. Selenium has the potential to improve soil health, leading to the improvement of productivity and crop quality. However, Se possesses an immense encouraging phenomenon when supplied within the threshold limit, also having wide variations. The supplementation of Se has exhibited promising outcomes in lessening biotic and abiotic stress in various crops. Besides, bulk form, nano-Se, and biogenic-Se also revealed some merits and limitations. Literature suggests that the possibilities of biogenic-Se in stress alleviation and fortifying foods are encouraging. In this article, apart from adopting a combination of a conventional extensive review of the literature and bibliometric analysis, the authors have assessed the journey of Se in the "soil to spoon" perspective in a diverse agroecosystem to highlight the research gap area. There is no doubt that the time has come to seriously consider the tag of beneficial elements associated with Se, especially in the drastic global climate change era.PMID:38141336 | DOI:10.1016/j.ecoenv.2023.115832

J Hazard Mater. 2023 Dec 19;465:133279. doi: 10.1016/j.jhazmat.2023.133279. Online ahead of print.ABSTRACTIn recent years, plastic pollution has become a global environmental problem, posing a potential threat to agricultural ecosystems and human health, and may further exacerbate global food security problems. Studies have revealed that exposure to micro/nano-plastics (MPs/NPs) might cause various aspects of physiological toxicities, including plant biomass reduction, intracellular oxidative stress burst, photosynthesis inhibition, water and nutrient absorption reduction, cellular and genotoxicity, seed germination retardation, and that the effects were closely related to MP/NP properties (type, particle size, functional groups), exposure concentration, exposure duration and plant characteristics (species, tissue, growth stage). Based on a brief review of the physiological toxicity of MPs/NPs to plant growth, this paper comprehensively reviews the potential molecular mechanism of MPs/NPs on plant growth from perspectives of multi-omics, including transcriptome, metabolome, proteome and microbiome, thus to reveal the role of MPs/NPs in plant transcriptional regulation, metabolic pathway reprogramming, protein translational and post-translational modification, as well as rhizosphere microbial remodeling at multiple levels. Meanwhile, this paper also provides prospects for future research, and clarifies the future research directions and the technologies adopted.PMID:38141304 | DOI:10.1016/j.jhazmat.2023.133279

J Hazard Mater. 2023 Dec 19;465:133300. doi: 10.1016/j.jhazmat.2023.133300. Online ahead of print.ABSTRACTBisphenol F (BPF) has evoked global attentions due to its ubiquity and detrimental effects. Herein, a flexible molecularly imprinted fiber library was firstly proposed for the metabolic analysis of BPF in aquatic ecosystems. The library includes flexible single fibers and fiber arrays to precisely identify BPF and its metabolites with a wide range of polarities. Compared to commercial polyacrylate, the performance increased 11.56-570.98-fold. The adsorption capacity and the LogKow value were positively related. These arrays were used for the acquisition of environmental metabolomics data from aquatic ecosystems. In-depth data analysis showed that risk quotient was lower than 0.76, and bioaccumulation factor was lower than 2000 L/kg. Distribution concentration of BPF and its metabolites changed seasonally, and accumulation in sediment was much larger than that in surface water and hydrobionts. The risk is gradually increasing in sediment, but it does not reach high risk. The likelihood of bioaccumulation of parent compounds was greater than its metabolites. The library can be used in the metabolic diagnosis of pollutants with a broad range of polarities, providing a new method to acquire data for further ecological risk assessment, and offering a revolutionary strategy for environmental metabolomics investigation in aquatic ecosystems.PMID:38141296 | DOI:10.1016/j.jhazmat.2023.133300

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Dec 18;1232:123976. doi: 10.1016/j.jchromb.2023.123976. Online ahead of print.ABSTRACTExposure to polychlorinated biphenyls (PCBs) has been linked to dyslipidemia. Under acute exposure to PCBs, it has been observed that the secretion of bile acids (BAs) can be impacted, limiting (indirectly) lipid absorption in the gut. In this context, two non-targeted metabolomics studies on pig serum have recently suggested that BA concentrations may fluctuate under exposure to current non-dioxin-like (NDL)-PCB levels in food, reflecting the acute effects of such chronic exposure. The objective of this research is to implement a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for BA analysis in order to validate the findings of previous metabolomics studies, in which BA levels in serum samples from pigs exposed to environmental doses of NDL-PCBs were highlighted to be affected. The proposed LC-MS method involves the use of a C18-pentafluorophenyl LC column, which is not usually selected for the separation of BAs, but shows better performance for the separation of isomers than typical C18 columns. This LC-MS method shows excellent analytical performance such as low limits of detection (LODs) (≤1 ng/mL for most BAs) and good linearity (R2 > 0.994), while no matrix effect was observed. A total of 13 BAs have been quantified, while further BA isomers could be detected and semi-quantified. The application of this targeted LC-MS method confirmed previous findings, suggesting that exposure to low doses of NDL-PCBs decreases the concentration of BAs (i.e., glycochenodeoxycholic acid, hyodeoxycholic acid and taurochenodeoxycholic acid) while the effect on the precursors (cholic acid and chenodeoxycholic acid) is less pronounced.PMID:38141289 | DOI:10.1016/j.jchromb.2023.123976

Metabolomics. 2023 Dec 23;20(1):10. doi: 10.1007/s11306-023-02071-1.ABSTRACTINTRODUCTION: Regular physical activity and dietary variety are modifiable and influential factors of health outcomes. However, the cumulative effects of these behaviors are not well understood. Metabolomics may have a promising research potential to extend our knowledge and use it in the attempts to find a long-term and sustainable personalized approach in exercise and diet recommendations.OBJECTIVE: The main aim was to investigate the effect of the 12 week very low carbohydrate high fat (VLCHF) diet and high-intensity interval training (HIIT) on lipidomic and metabolomic profiles in individuals with overweight and obesity.METHODS: The participants (N = 91) were randomly allocated to HIIT (N = 22), VLCHF (N = 25), VLCHF + HIIT (N = 25) or control (N = 19) groups for 12 weeks. Fasting plasma samples were collected before the intervention and after 4, 8 and 12 weeks. The samples were then subjected to untargeted lipidomic and metabolomic analyses using reversed phase ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry.RESULTS: The VLCHF diet affected plasma lipids considerably while the effect of HIIT was unremarkable. Already after 4 weeks of intervention substantial changes of plasma lipids were found in both VLCHF diet groups. The changes persisted throughout the entire 12 weeks of the VLCHF diet. Specifically, acyl carnitines, plasmalogens, fatty acyl esters of hydroxy fatty acid, sphingomyelin, ceramides, cholesterol esters, fatty acids and 4-hydroxybutyric were identified as lipid families that increased in the VLCHF diet groups whereas lipid families of triglycerides and glycerophospholipids decreased. Additionally, metabolomic analysis showed a decrease of theobromine.CONCLUSIONS: This study deciphers the specific responses to a VLCHF diet, HIIT and their combination by analysing untargeted lipidomic and metabolomic profile. VLCHF diet caused divergent changes of plasma lipids and other metabolites when compared to the exercise and control group which may contribute to a better understanding of metabolic changes and the appraisal of VLCHF diet benefits and harms.CLINICAL TRIAL REGISTRY NUMBER: NCT03934476, registered 1st May 2019 https://clinicaltrials.gov/ct2/show/NCT03934476?term=NCT03934476&draw=2&rank=1 .PMID:38141101 | DOI:10.1007/s11306-023-02071-1

Metabolomics. 2023 Dec 23;20(1):11. doi: 10.1007/s11306-023-02073-z.ABSTRACTINTRODUCTION: The Automated Quantification Algorithm (AQuA) is a rapid and efficient method for targeted NMR-based metabolomics, currently optimised for blood plasma. AQuA quantifies metabolites from 1D-1H NMR spectra based on the height of only one signal per metabolite, which minimises the computational time and workload of the method without compromising the quantification accuracy.OBJECTIVES: To develop a fast and computationally efficient extension of AQuA for quantification of selected metabolites in highly complex samples, with minimal prior sample preparation. In particular, the method should be capable of handling interferences caused by broad background signals.METHODS: An automatic baseline correction function was combined with AQuA into an automated workflow, the extended AQuA, for quantification of metabolites in plant root exudate NMR spectra that contained broad background signals and baseline distortions. The approach was evaluated using simulations as well as a spike-in experiment in which known metabolite amounts were added to a complex sample matrix.RESULTS: The extended AQuA enables accurate quantification of metabolites in 1D-1H NMR spectra with varying complexity. The method is very fast (< 1 s per spectrum) and can be fully automated.CONCLUSIONS: The extended AQuA is an automated quantification method intended for 1D-1H NMR spectra containing broad background signals and baseline distortions. Although the method was developed for plant root exudates, it should be readily applicable to any NMR spectra displaying similar issues as it is purely computational and applied to NMR spectra post-acquisition.PMID:38141081 | DOI:10.1007/s11306-023-02073-z