PubMed

Food Res Int. 2023 Sep;171:113071. doi: 10.1016/j.foodres.2023.113071. Epub 2023 Jun 5.ABSTRACTBACKGROUND: Food inspection covers a broad range of topics, including nutrient analysis, food pollutants, food auxiliary materials, additives, and food sensory identification. The foundation of diverse subjects like food science, nutrition, health research, and the food industry, as well as the desired reference for drafting trade and food legislation, makes food inspection highly significant. Because of their high efficiency, sensitivity, and accuracy, instrumental analysis methods have gradually replaced conventional analytical methods as the primary means of food hygiene inspection.SCOPE AND APPROACH: Metabolomics-based analysis technology, such as nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and capillary electrophoresis-mass spectrometry (CE-MS), has become a widely used analytics platform. This research provides a bird's eye view of the application and future of metabolomics-related technologies in food inspection.KEY FINDINGS AND CONCLUSIONS: We have provided a summary of the features and the application range of various metabolomics techniques, the strengths and weaknesses of different metabolomics platforms, and their implementation in specific inspection procedures. These procedures encompass the identification of endogenous metabolites, the detection of exogenous toxins and food additives, analysis of metabolite alterations during processing and storage, as well as the recognition of food adulteration. Despite the widespread utilization and significant contributions of metabolomics-based food inspection technologies, numerous challenges persist as the food industry advances and technology continues to improve. Thus, we anticipate addressing these potential issues in the future.PMID:37330829 | DOI:10.1016/j.foodres.2023.113071

Food Res Int. 2023 Sep;171:113069. doi: 10.1016/j.foodres.2023.113069. Epub 2023 Jun 2.ABSTRACTBee pollen (BP) and royal jelly (RJ) have shown therapeutic effects against colitis, but the functional components contained therein remain elusive. Here, we used an integrated microbiomic-metabolomic strategy to clarify the mechanism by which bee pollen lipid extracts (BPL) and royal jelly lipid extracts (RJL) ameliorated dextran sulfate sodium (DSS)-induced colitis in mice. Lipidomic results showed that levels of ceramide (Cer), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) were significantly higher in BPL than in RJL. The anti-inflammatory efficacy of BPL surpassed that of RJL, although both BPL and RJL could attenuate DSS-induced colitis through several mechanisms: reducing the disease activity index (DAI); decreasing histopathological damage; inhibiting the expression of genes encoding proinflammatory cytokines; improving intestinal microbial community structure, and modulating host metabolism. These findings demonstrated that BPL and RJL have great potential as functional ingredients for the production of dietary supplements to prevent early colitis.PMID:37330827 | DOI:10.1016/j.foodres.2023.113069

Food Res Int. 2023 Sep;171:113066. doi: 10.1016/j.foodres.2023.113066. Epub 2023 Jun 2.ABSTRACTBroomcorn millet (BM) is a future smart food. However, no information is available on the metabolism of BM grains under alkaline stress. In this study, the effects of alkaline stress on nonvolatile and volatile metabolites in the BM grains of two varieties (S223 and T289) were investigated through metabolomics approaches. All 933 nonvolatile metabolites and 313 volatile metabolites were identified, with 114 and 89 nonvolatile metabolites and 16 and 20 volatile metabolites accumulating differentially under normal vs. alkaline stresses of S223 and T289, respectively. The results indicated that alkaline stress altered phenylpropanoids, flavonoids, flavone and flavonol, valine, leucine, and isoleucine biosynthesis, as well as arginine, proline, tryptophan, and ascorbate metabolism. The effects of alkaline stress were not identical between the two varieties, which could lead to variations in active substance content. These results provide valuable information for further studies on food chemistry and the functional food development of BM grains.PMID:37330826 | DOI:10.1016/j.foodres.2023.113066

Food Res Int. 2023 Sep;171:113059. doi: 10.1016/j.foodres.2023.113059. Epub 2023 Jun 1.ABSTRACTP. pseudocerasus and P. tomentosa are the two native Chinese cherry species of high economic and ornamental worths. Little is known about the metabolic information of P. pseudocerasus and P. tomentosa. Effective means are lacking for distinguishing these two similar species. In this study, the differences in total phenolic content (TPC), total flavonoid content (TFC), and in vitro antioxidant activities in 21 batches of two species of cherries were compared. A comparative UPLC-QTOF/MS-based metabolomics coupled with three machine learning algorithms was established for differentiating the cherry species. The results demonstrated that P. tomentosa had higher TPC and TFC with average content differences of 12.07 times and 39.30 times, respectively, and depicted better antioxidant activity. Total of 104 differential compounds were identified by UPLC-QTOF/MS metabolomics. The major differential compounds were flavonoids, organooxygen compounds, and cinnamic acids and derivatives. Correlation analysis revealed differences in flavonoids content such as procyanidin B1 or isomer and (Epi)catechin. They could be responsible for differences in antioxidant activities between the two species. Among three machine learning algorithms, the prediction accuracy of support vector machine (SVM) was 85.7%, and those of random forest (RF) and back propagation neural network (BPNN) were 100%. BPNN exhibited better classification performance and higher prediction rate for all testing set samples than those of RF. The study herein found that P. tomentosa had higher nutritional value and biological functions, and thus considered for usage in health products. Machine models based on untargeted metabolomics can be effective tools for distinguishing these two species.PMID:37330825 | DOI:10.1016/j.foodres.2023.113059

Environ Pollut. 2023 Jun 15:122058. doi: 10.1016/j.envpol.2023.122058. Online ahead of print.ABSTRACTFludioxonil (FL) and metalaxyl-M·fludioxonil·azoxystrobin (MFA) are conventional seed coating agents for controlling cotton seedling diseases. However, their effects on seed endophytic and rhizosphere microecology are still poorly understood. This study aimed to assess the effects of FL and MFA on cotton seed endophytes, rhizosphere soil enzymatic activities, microbiome and metabolites. Both seed coating agents significantly changed seed endophytic bacterial and fungal communities. Growing coated seeds in the soils originating from the Alar (AL) and Shihezi (SH) region inhibited soil catalase activity and decreased both bacterial and fungal biomass. Seed coating agents increased rhizosphere bacterial alpha diversity for the first 21 days but decreased fungal alpha diversity after day 21 in the AL soil. Seed coating reduced the abundance of a number of beneficial microorganisms but enriched some potential pollutant-degrading microorganisms. Seed coating agents may have affected the complexity of the co-occurrence network of the microbiome in the AL soil, reducing connectivity, opposite to what was observed in the SH soil. MFA had more pronounced effects on soil metabolic activities than FL. Furthermore, there were strong links between soil microbial communities, metabolites and enzymatic activities. These findings provide valuable information for future research and development on application of seed coatings for disease management.PMID:37330187 | DOI:10.1016/j.envpol.2023.122058

Biol Psychiatry. 2023 Jun 15:S0006-3223(23)01355-0. doi: 10.1016/j.biopsych.2023.05.024. Online ahead of print.ABSTRACTBACKGROUND: The ability to individually predict disease course of major depressive disorder (MDD) is essential for optimal treatment planning. Here, we use a data-driven machine learning approach to assess the predictive value of different sets of biological data (whole-blood proteomics, lipid-metabolomics, transcriptomics, genetics), both separately and added to clinical baseline variables, for the longitudinal prediction of 2-year remission status in MDD at the individual subject level.METHODS: Prediction models were trained and cross-validated in a sample of 643 patients with current MDD (2-year remission n = 325) and subsequently tested for performance in 161 MDD individuals (2-year remission n = 82).RESULTS: Proteomics data showed best unimodal data predictions (AUROC = 0.68). Adding proteomic to clinical data at baseline significantly improved 2-year MDD remission predictions (AUROC = 0.63 vs AUROC = 0.78, p = 0.013), while the addition of other -omics data to clinical data did not yield significantly increased model performance. Feature importance and enrichment analysis revealed proteomic analytes involved in inflammatory response and lipid metabolism, with fibrinogen levels showing the highest variable importance, followed by symptom severity. Machine learning models outperformed psychiatrists' ability to predict two-year remission status (balanced accuracy = 71% vs 55%).CONCLUSION: This study showed the added predictive value of combining proteomic, but not other -omic data, with clinical data for the prediction of 2-year remission status in MDD. Our results reveal a novel multimodal signature of two-year MDD remission status that shows clinical potential for individual MDD disease course predictions from baseline measurements.PMID:37330166 | DOI:10.1016/j.biopsych.2023.05.024

Am J Med Sci. 2023 Jun 15:S0002-9629(23)01226-0. doi: 10.1016/j.amjms.2023.06.010. Online ahead of print.ABSTRACTGlioblastoma (GBM), the most common human brain tumor, has been notoriously resistant to treatment. As a result, the dismal overall survival of GBM patients has not changed over the past three decades. GBM has been stubbornly resistant to checkpoint inhibitor immunotherapies, which have been remarkably effective in the treatment of other tumors. It is clear that GBM resistance to therapy is multifactorial. Although therapeutic transport into brain tumors is inhibited by the blood brain barrier, there is evolving evidence that overcoming this barrier is not the predominant factor. GBMs generally have a low mutation burden, exist in an immunosuppressed environment and they are inherently resistant to immune stimulation, all of which contribute to treatment resistance. In this review, we evaluate the contribution of multi-omic approaches (genomic and metabolomic) along with analyzing immune cell populations and tumor biophysical characteristics to better understand and overcome GBM multifactorial resistance to treatment.PMID:37330006 | DOI:10.1016/j.amjms.2023.06.010

Dev Comp Immunol. 2023 Jun 15:104750. doi: 10.1016/j.dci.2023.104750. Online ahead of print.ABSTRACTThe silkworm (Bombyx mori) is a model species of lepidopteran insect. Microsporidium spp. are obligate intracellular eukaryotic parasites. Infection by the microsporidian Nosema bombycis (Nb) results in an outbreak of Pébrine disease in silkworms and causes substantial losses to the sericulture industry. It has been suggested that Nb depends on nutrients from host cells for spore growth. However, little is known about changes in lipid levels after Nb infection. In this study, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was performed to analyze the effect of Nb infection on lipid metabolism in the midgut of silkworms. A total of 1601 individual lipid molecules were detected in the midgut of silkworms, of which 15 were significantly decreased after Nb challenge. Classification, chain length, and chain saturation analysis revealed that these 15 differential lipids can be classified into different lipid subclasses, of which 13 belong to glycerol phospholipid lipids and two belong to glyceride esters. The results indicated that Nb uses the host lipids to complete its own replication, and the acquisition of host lipid subclasses is selective; not all lipid subclasses are required for microsporidium growth or proliferation. Based on lipid metabolism data, phosphatidylcholine (PC) was found to be an important nutrient for Nb replication. Diet supplementation with lecithin substantially promoted the replication of Nb. Knockdown and overexpression of the key enzyme phosphatidate phosphatase (PAP) and phosphatidylcholine (Bbc) for PC synthesis also confirmed that PC is necessary for Nb replication. Our results showed that most lipids in the host midgut decreased when silkworms were infected with Nb. Reduction of or supplementation with PC may be a strategy to suppress or promote microsporidial replication.PMID:37329996 | DOI:10.1016/j.dci.2023.104750

Sci Total Environ. 2023 Jun 15:164929. doi: 10.1016/j.scitotenv.2023.164929. Online ahead of print.ABSTRACTPyrrolizidine alkaloids (PAs) are a type of plant-derived environmental toxins, which pose a health hazard to human and livestock via contaminating soil, water, plants and food. In this study, we aimed to investigate the effect of lactational retrorsine (RTS, a typical toxic PA) exposure on breastmilk components and glucose-lipid metabolism of offspring rats. Dams were intragastrically administered with 5 mg/(kg·d) RTS during lactation. Metabolomic analyses identified 114 differential constituents of breastmilk after RTS exposure, featured by reduction of lipids and lipid-like molecules while presence of abundant RTS and its derivative. RTS exposure induced liver injury in pups, but the serum leakage of transaminases recovered in adulthood. Serum glucose levels were lower in pups but higher in male adult offspring from RTS group. RTS exposure also induced hypertriglyceridemia, hepatic steatosis and decreased glycogen content in both pups and adult offspring. Additionally, suppression of PPARα-FGF21 axis persisted in offspring liver after RTS exposure. These data indicated that inhibition of PPARα-FGF21 axis induced by deficient breastmilk lipid contents, together with hepatotoxic injury caused by breastmilk RTS, may disrupt glucose and lipid metabolism of pups, and the persistent suppression of PPARα-FGF21 axis may program metabolic disorder of glucose and lipid in adult offspring.PMID:37329908 | DOI:10.1016/j.scitotenv.2023.164929

Food Chem. 2023 Jun 10;426:136601. doi: 10.1016/j.foodchem.2023.136601. Online ahead of print.ABSTRACTMost aged tea has superior sensory qualities and good health benefits. The content of organic acids determines of the quality and biological effects of aged tea, but there are no reports of the effect of storage on the composition and relative proportion of acidic compounds in black tea. This study analyzed and compared the sourness and metabolite profile of black tea produced in 2015, 2017, 2019 and 2021 using pH determination and UPLC-MS/MS. In total, 28 acidic substances were detected, with 17 organic acids predominating. The pH of black tea decreased significantly during storage from pH 4.64 to pH 4.25 with significantly increased in l-ascorbic acid, salicylic acid, benzoic acid and 4-hydroxybenzoic acid. The metabolic pathways ascorbate biosynthesis, salicylate degradation, toluene degradation, etc. were mainly enriched. These findings provide a theoretical basis to regulate the acidity of aged black tea.PMID:37329793 | DOI:10.1016/j.foodchem.2023.136601

Food Chem. 2023 Jun 13;426:136619. doi: 10.1016/j.foodchem.2023.136619. Online ahead of print.ABSTRACTTo insight into the chemical components and their health-promoting function of Camellia drupifera mature-seeds (CMS) in Hainan and Liangguang, UPLC-MS/MS- and HS-SPME/GC-MS-based metabolomic analyses and network pharmacology approaches were combined preformed to Camellia drupifera mature-seeds samples (CMSSs). Totally, 1057 metabolites were identified, of which 76 and 99 metabolites were annotated as key active ingredients in Traditional Chinese Medicines and the active pharmaceutical ingredients for seven human disease-resistance, respectively. Comparative analysis revealed different metabolomic profiles of CMSSs from Hainan and Liangguang. KEGG annotation and enrichment analysis showed secondary metabolic pathways, especially "flavone and flavonol biosynthesis", were played important roles. Finally, 22 metabolites that only detected in CMSSs from Hainan or Liangguang were explored as potential indicators to separate CMS from Hainan out of Liangguang. Our findings enhanced the understanding of chemical compositions of CMS and provided valuable information for the healthy development of oil-tea Camellia industry in Hainan.PMID:37329789 | DOI:10.1016/j.foodchem.2023.136619

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Apr 14;1226:123676. doi: 10.1016/j.jchromb.2023.123676. Online ahead of print.ABSTRACTFunctional dyspepsia (FD) is one of the more common functional disorders, with a prevalence of 20-25 %. It seriously affects the quality life of patients. Xiaopi Hewei Capsule (XPHC) is a classic formula originated from the Chinese Miao minority. Clinical studies have demonstrated that XPHC can effectively alleviate the symptoms of FD, but the molecular mechanism has not been elucidated. The purpose of this work is to investigate the mechanism of XPHC on FD by integrating metabolomics and network pharmacology. The mice models of FD were established, and gastric emptying rate, small intestine propulsion rate, serum level of motilin and gastrin were evaluate to study the interventional effect of XPHC on FD. Next, a metabolomics strategy has been developed to screen differential metabolites and related metabolic pathways induced by XPHC. Then, prediction of active compounds, targets and pathways of XPHC in treating FD were carried out by commonly used network pharmacological method. Finally, two parts of the results were integrated to investigate therapeutic mechanism of XPHC on FD, which were preliminary validated based on molecular docking. Thus, twenty representative different metabolites and thirteen related pathways of XPHC in treating FD were identified. Most of these metabolites were restored using modulation after XPHC treatment. The results of the network pharmacology analysis showed ten crucial compounds and nine hub genes related to the treatment of FD with XPHC. The further integrated analysis focused on four key targets, such as albumin (ALB), epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF) and roto-oncogene tyrosine-protein kinase Src (SRC), and three representative biomarkers such as citric acid, L-leucine and eicosapentaenoic acid. Furthermore, molecular docking results showed that ten bioactive compounds from XPHC have good binding interactions with the four key genes. The functional enrichment analysis indicated that the potential mechanism of XPHC in treating FD was mainly associated with energy metabolism, amino acid metabolism, lipid metabolism, inflammatory reactions and mucosal repair. Our work confirms that network pharmacology-integrated metabolomics strategyis a powerful means to reveal the therapeutic mechanisms of XPHC improves FD, which contribute its further scientific research.PMID:37329776 | DOI:10.1016/j.jchromb.2023.123676

J Proteome Res. 2023 Jun 17. doi: 10.1021/acs.jproteome.3c00007. Online ahead of print.ABSTRACTAs a vision-threatening complication of diabetes mellitus (DM), proliferative diabetic retinopathy (PDR) is associated with sustained metabolic disorders. Herein, we collected the vitreous cavity fluid of 49 patients with PDR and 23 control subjects without DM for metabolomics and lipidomics analyses. Multivariate statistical methods were performed to explore relationships between samples. For each group of metabolites, gene set variation analysis scores were generated, and we constructed a lipid network by using weighted gene co-expression network analysis. The association between lipid co-expression modules and metabolite set scores was investigated using the two-way orthogonal partial least squares (O2PLS) model. A total of 390 lipids and 314 metabolites were identified. Multivariate statistical analysis revealed significant vitreous metabolic and lipid differences between PDR and controls. Pathway analysis showed that 8 metabolic processes might be associated with the development of PDR, and 14 lipid species were found to be altered in PDR patients. Combining metabolomics and lipidomics, we identified fatty acid desaturase 2 (FADS2) as an important potential contributor to the pathogenesis of PDR. Collectively, this study integrates vitreous metabolomics and lipidomics to comprehensively unravel metabolic dysregulation and identifies genetic variants associated with altered lipid species in the mechanistic pathways for PDR.PMID:37329324 | DOI:10.1021/acs.jproteome.3c00007

Cancer Med. 2023 Jun 17. doi: 10.1002/cam4.6248. Online ahead of print.ABSTRACTBACKGROUND: Trials of tyrosine kinase inhibitors (TKI) have not demonstrated dramatic benefits in advanced colorectal cancer (CRC), and this may be a function of poor patient selection. TKI-induced hypertension is reportedly a surrogate marker for treatment benefit for some tumor types. Our objective was to determine whether hypertension was associated with benefit in the context of CRC treatment, and also to gain insight on the pathogenesis of TKI-induced hypertension by monitoring associated changes in the circulating metabolome.PATIENTS AND METHODS: Clinical data were acquired from clinical trial patients with metastatic CRC randomized to cetuximab ± the TKI brivanib (N = 750). Outcomes were evaluated as a function of treatment-induced hypertension. For metabolomic studies, plasma samples were taken at baseline, as well as at 1, 4, and 12 weeks after treatment initiation. Samples were submitted to gas chromatography-mass spectrometry to identify treatment-related metabolomic changes associated with TKI-induced hypertension, compared to pre-treatment baseline. A model based on changes in metabolite concentrations was generated using orthogonal partial least squares discriminant analysis (OPLS-DA).RESULTS: In the brivanib treated group, 95 patients had treatment-related hypertension within 12 weeks of initiating treatment. TKI-induced hypertension was not associated with a significantly higher response rate, nor was it associated with improved progression-free or overall survival. In metabolomic studies, 386 metabolites were identified. There were 29 metabolites that changed with treatment and distinguished patients with and without TKI-induced hypertension. The OPLS-DA model for brivanib-induced hypertension was significant and robust (R2 Y score = 0.89, Q2 Y score = 0.70, CV-ANOVA = 2.01 e-7). Notable metabolomic features previously reported in pre-eclampsia and associated with vasoconstriction were found.CONCLUSION: TKI-induced hypertension was not associated with clinical benefit in metastatic CRC. We have identified changes in the metabolome that are associated with the development of worsening brivanib-induced hypertension that may be useful in future efforts of characterizing this toxicity.PMID:37329221 | DOI:10.1002/cam4.6248

Plant J. 2023 Jun 17. doi: 10.1111/tpj.16357. Online ahead of print.ABSTRACTCassava's storage roots represent one of the most important sources of nutritional carbohydrates worldwide. Particularly, smallholder farmers in Sub-Saharan Africa depend on this crop plant, where resilient and yield-improved varieties are of vital importance to support steadily increasing populations. Aided by a growing understanding of the plant's metabolism and physiology, targeted improvement concepts already led to visible gains in recent years. To expand our knowledge and to contribute to these successes, we investigated storage roots of eight cassava genotypes with differential dry matter content from three successive field trials for their proteomic and metabolic profiles. At large, the metabolic focus in storage roots transitioned from cellular growth processes towards carbohydrate and nitrogen storage with increasing dry matter content. This is reflected in higher abundance of proteins related to nucleotide synthesis, protein turnover and vacuolar energization in low starch genotypes, while proteins involved in sugar conversion and glycolysis were more prevalent in high dry matter genotypes. This shift in metabolic orientation was underlined by a clear transition from oxidative- to substrate-level phosphorylation in high dry matter genotypes. Our analyses highlight metabolic patterns that are consistently and quantitatively associated with high dry matter accumulation in cassava storage roots, providing fundamental understandings of cassava's metabolism as well as a data resource for targeted genetic improvement.PMID:37329210 | DOI:10.1111/tpj.16357

Proteomics Clin Appl. 2023 Jun 17:e2300008. doi: 10.1002/prca.202300008. Online ahead of print.ABSTRACTPURPOSE: Our main goal is to identify the alterations in the amniotic fluid (AF) metabolome in Zika virus (ZIKV)-infected patients and their relation to congenital Zika syndrome (CZS) progression.EXPERIMENTAL DESIGN: We applied an untargeted metabolomics strategy to analyze seven AF of pregnant women: healthy women and ZIKV-infected women bearing non-microcephalic and microcephalic fetuses.RESULTS: Infected patients were characterized by glycerophospholipid metabolism impairment, which is accentuated in microcephalic phenotypes. Glycerophospholipid decreased concentration in AF can be a consequence of intracellular transport of lipids to the placental or fetal tissues under development. The increased intracellular concentration of lipids can lead to mitochondrial dysfunction and neurodegeneration caused by lipid droplet accumulation. Furthermore, the dysregulation of amino acid metabolism was a molecular fingerprint of microcephalic phenotypes, specifically serine, and proline metabolisms. Both amino acid deficiencies were related to neurodegenerative disorders, intrauterine growth retardation, and placental abnormalities.CONCLUSIONS AND CLINICAL RELEVANCE: This study enhances our understanding of the development of CZS pathology and sheds light on dysregulated pathways that could be relevant for future studies.PMID:37329193 | DOI:10.1002/prca.202300008

Cardiovasc Diabetol. 2023 Jun 16;22(1):141. doi: 10.1186/s12933-023-01862-z.ABSTRACTBACKGROUND: Metabolic Syndrome (MetS) is characterized by risk factors such as abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), hypertension, and hyperglycemia, which contribute to the development of cardiovascular disease and type 2 diabetes. Here, we aim to identify candidate metabolite biomarkers of MetS and its associated risk factors to better understand the complex interplay of underlying signaling pathways.METHODS: We quantified serum samples of the KORA F4 study participants (N = 2815) and analyzed 121 metabolites. Multiple regression models adjusted for clinical and lifestyle covariates were used to identify metabolites that were Bonferroni significantly associated with MetS. These findings were replicated in the SHIP-TREND-0 study (N = 988) and further analyzed for the association of replicated metabolites with the five components of MetS. Database-driven networks of the identified metabolites and their interacting enzymes were also constructed.RESULTS: We identified and replicated 56 MetS-specific metabolites: 13 were positively associated (e.g., Val, Leu/Ile, Phe, and Tyr), and 43 were negatively associated (e.g., Gly, Ser, and 40 lipids). Moreover, the majority (89%) and minority (23%) of MetS-specific metabolites were associated with low HDL-C and hypertension, respectively. One lipid, lysoPC a C18:2, was negatively associated with MetS and all of its five components, indicating that individuals with MetS and each of the risk factors had lower concentrations of lysoPC a C18:2 compared to corresponding controls. Our metabolic networks elucidated these observations by revealing impaired catabolism of branched-chain and aromatic amino acids, as well as accelerated Gly catabolism.CONCLUSION: Our identified candidate metabolite biomarkers are associated with the pathophysiology of MetS and its risk factors. They could facilitate the development of therapeutic strategies to prevent type 2 diabetes and cardiovascular disease. For instance, elevated levels of lysoPC a C18:2 may protect MetS and its five risk components. More in-depth studies are necessary to determine the mechanism of key metabolites in the MetS pathophysiology.PMID:37328862 | DOI:10.1186/s12933-023-01862-z

Mol Neurobiol. 2023 Jun 16. doi: 10.1007/s12035-023-03403-x. Online ahead of print.ABSTRACTOptimizing the metabolic phenotype to improve cerebral function is critical for treatment of cerebral ischemia-reperfusion (I/R) injury. Guhong injection (GHI), which comprised safflower extract and aceglutamide, is widely prescribed in Chinese medicine for the treatment of cerebrovascular diseases. In this study, a combination of LC-QQQ-MS and MALDI-MSI were utilized to explore tissue-specific metabolic alterations in the brain of I/R, as well as to evaluate the therapeutic effect of GHI. Pharmacological evaluation demonstrated that GHI can significantly improve infarction rate, neurological deficit, cerebral blood flow, and neuronal damage in I/R rats. Based on LC-QQQ-MS, 23 energy metabolites were found to be significantly altered in the I/R group compared to the sham group (P < 0.05). After GHI treatment, 12 metabolites, including G6P, TPP, NAD, citrate, succinate, malate, ATP, GTP, GDP, ADP, NADP, and FMN showed a significant tendency of returning to baseline values (P < 0.05). Based on MALDI-MSI, 4 metabolites in glycolysis and TCA, 4 metabolites in nucleic acid metabolism, 4 amino acid metabolites, and 6 metabolites were discovered and compared between the different groups in the four special regions of cortex, hippocampus, hypothalamus, and striatum. Parts of these were found to have significant changes after I/R in the special brain region, and were regulated by GHI. The study provides comprehensive and detailed information for specific metabolic reprogramming of brain tissue in rats with I/R, and the therapeutic effect of GHI. Schema describing the discovery strategies of integrated LC-MS and MALDI-MSI to identify cerebral ischemia reperfusion metabolic reprogramming and GHI therapeutic effects.PMID:37328677 | DOI:10.1007/s12035-023-03403-x

Amino Acids. 2023 Jun 17. doi: 10.1007/s00726-023-03293-2. Online ahead of print.ABSTRACTSome individuals are susceptible to accelerated biological ageing, resulting in premature alterations in arterial structure and function. Identifying early-onset vascular ageing characterised by arterial stiffening is vital for intervention and preventive strategies. We stratified and phenotyped healthy children (5-9 yrs) and young adults (20-30 yrs) into their vascular ageing extremes established by carotid-femoral pulse wave velocity (cfPWV) percentiles (i.e., healthy vascular ageing (HVA) and early vascular ageing (EVA)). We compared anthropometric, cardiovascular, and metabolomic profiles and explored associations between cfPWV and urinary metabolites. Children and adults in the EVA groups displayed higher levels of adiposity, cardiovascular, and lifestyle risk factors (adults only) (all p ≤ 0.018). In adults, several urinary metabolites were lower in the EVA group (all q ≤ 0.039) when compared to the HVA group, with no differences observed in children. In multiple regression analysis (adults only), we found inverse associations between cfPWV with histidine (adj. R2 = 0.038; β = -0.192; p = 0.013) and beta-alanine (adj. R2 = 0.034; β = -0.181; p = 0.019) in the EVA group, but with arginine (adj. R2 = 0.021; β = -0.160; p = 0.024) in the HVA group. The inverse associations of beta-alanine and histidine with cfPWV in the EVA group is suggestive that asymptomatic young adults who present with an altered metabolomic and less desired cardiovascular profile in combination with unfavourable lifestyle behaviours may be predisposed to early-onset vascular ageing. Taken together, screening on both a phenotypic and metabolic level may prove important in the early detection, prevention, and intervention of advanced biological ageing.PMID:37328631 | DOI:10.1007/s00726-023-03293-2

Sci Rep. 2023 Jun 16;13(1):9802. doi: 10.1038/s41598-023-36874-y.ABSTRACTBladder cancer (BC) is a common urological malignancy with a high probability of death and recurrence. Cystoscopy is used as a routine examination for diagnosis and following patient monitoring for recurrence. Repeated costly and intrusive treatments may discourage patients from having frequent follow-up screenings. Hence, exploring novel non-invasive ways to help identify recurrent and/or primary BC is critical. In this work, 200 human urine samples were profiled using ultra-high-performance liquid chromatography and ultra-high-resolution mass spectrometry (UHPLC-UHRMS) to uncover molecular markers differentiating BC from non-cancer controls (NCs). Univariate and multivariate statistical analyses with external validation identified metabolites that distinguish BC patients from NCs disease. More detailed divisions for the stage, grade, age, and gender are also discussed. Findings indicate that monitoring urine metabolites may provide a non-invasive and more straightforward diagnostic method for identifying BC and treating recurrent diseases.PMID:37328580 | DOI:10.1038/s41598-023-36874-y