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Metabolites, Volume 12, Issue 6 (June 2022) – 97 articles

Cover Story (view full-size image): This study examined the longitudinal associations between 104 plasma metabolites and their network-derived clusters, and type 2 diabetes progression in 1221 Puerto Rican middle-aged and older adults from the Boston Puerto Rican Health Study and San Juan Overweight Adult Longitudinal Study, using multivariable Poisson regression models. Combined analyses of two cohorts showed that a cluster of 13 metabolites of branched-chain amino acid and aromatic amino acid metabolism (pooled IRR = 1.87, 95% CI: 1.28; 2.73), and a cell membrane component metabolite cluster (pooled IRR = 1.54, 95% CI: 1.04; 2.27) were associated with a higher risk of incident type 2 diabetes. These findings highlight potential prognostic biomarkers for identifying Puerto Rican adults who may be at high risk for type 2 diabetes. View this paper
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21 pages, 759 KiB  
Article
FADS Polymorphisms Affect the Clinical and Biochemical Phenotypes of Metabolic Syndrome
by Aleš Žák, Marie Jáchymová, Michal Burda, Barbora Staňková, Miroslav Zeman, Adolf Slabý, Marek Vecka and Ondřej Šeda
Metabolites 2022, 12(6), 568; https://doi.org/10.3390/metabo12060568 - 20 Jun 2022
Cited by 1 | Viewed by 1810
Abstract
Long-chain polyunsaturated fatty acids (LC-PUFAs) play important roles in human health, from controlling inflammation to lipid and glucose homeostasis. In our previous study, which employed a cluster analysis of a plasma fatty acid (FA) pattern, we identified two clusters of metabolic syndrome (MetS) [...] Read more.
Long-chain polyunsaturated fatty acids (LC-PUFAs) play important roles in human health, from controlling inflammation to lipid and glucose homeostasis. In our previous study, which employed a cluster analysis of a plasma fatty acid (FA) pattern, we identified two clusters of metabolic syndrome (MetS) independent of clinical and biochemical parameters within the whole study group (controls together with metabolic syndrome (MetS) patients). FA desaturase (FADS) genes are the key regulators of LC-PUFA metabolism. The aim of this study was to analyze associations between FADS polymorphisms and clusters of MetS. The study group consisted of 188 controls and 166 patients with MetS. The first cluster contained 71 controls (CON1) and 109 MetS patients (MetS1). The second cluster consisted of 117 controls (CON2) and 57 MetS patients (MetS2). In comparison with MetS2, cluster MetS1 displayed a more adverse risk profile. Cluster CON1 had, in comparison with CON2, higher body weight and increased triacylglycerol levels (p < 0.05). We found that the FADS rs174537 (p < 0.001), rs174570 (p < 0.01), and rs174602 (p < 0.05) polymorphisms along with two inferred haplotypes had statistically significant genotype associations with the splitting of MetS into MetS1 and MetS2. Conversely, we observed no significant differences in the distribution of FADS polymorphisms between MetS and CON subjects, or between CON1 and CON2. These associations between FADS polymorphisms and two clusters of MetS (differing in waist circumference, HOMA-IR, lipolysis, and oxidative stress) implicate the important influence of genetic factors on the phenotypic manifestation of MetS. Full article
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16 pages, 15208 KiB  
Article
Metabolomic and Transcriptomic Profiling Identified Significant Genes in Thymic Epithelial Tumor
by Enyu Tang, Yang Zhou, Siyang Liu, Zhiming Zhang, Rixin Zhang, Dejing Huang, Tong Gao, Tianze Zhang and Guangquan Xu
Metabolites 2022, 12(6), 567; https://doi.org/10.3390/metabo12060567 - 20 Jun 2022
Cited by 6 | Viewed by 1871
Abstract
Thymomas and thymic carcinomas are malignant thymic epithelial tumors (TETs) with poor outcomes if non-resectable. However, the tumorigenesis, especially the metabolic mechanisms involved, is poorly studied. Untargeted metabolomics analysis was utilized to screen for differential metabolic profiles between thymic cancerous tissues and adjunct [...] Read more.
Thymomas and thymic carcinomas are malignant thymic epithelial tumors (TETs) with poor outcomes if non-resectable. However, the tumorigenesis, especially the metabolic mechanisms involved, is poorly studied. Untargeted metabolomics analysis was utilized to screen for differential metabolic profiles between thymic cancerous tissues and adjunct noncancerous tissues. Combined with transcriptomic data, we comprehensively evaluated the metabolic patterns of TETs. Metabolic scores were constructed to quantify the metabolic patterns of individual tumors. Subsequent investigation of distinct clinical outcomes and the immune landscape associated with the metabolic scores was conducted. Two distinct metabolic patterns and differential metabolic scores were identified between TETs, which were enriched in a variety of biological pathways and correlated with clinical outcomes. In particular, a high metabolic score was highly associated with poorer survival outcomes and immunosuppressive status. More importantly, the expression of two prognostic genes (ASNS and BLVRA) identified from differential metabolism-related genes was significantly associated with patient survival and may play a key role in the tumorigenesis of TETs. Our findings suggest that differential metabolic patterns in TETs are relevant to tumorigenesis and clinical outcome. Specific transcriptomic alterations in differential metabolism-related genes may serve as predictive biomarkers of survival outcomes and potential targets for the treatment of patients with TETs. Full article
(This article belongs to the Topic Cancer Cell Metabolism)
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11 pages, 1515 KiB  
Article
Comparative Metabolomics of Small Molecules Specifically Expressed in the Dorsal or Ventral Marginal Zones in Vertebrate Gastrula
by Yukako Suzuki, Ryosuke Hayasaka, Masako Hasebe, Satsuki Ikeda, Tomoyoshi Soga, Masaru Tomita, Akiyoshi Hirayama and Hiroki Kuroda
Metabolites 2022, 12(6), 566; https://doi.org/10.3390/metabo12060566 - 20 Jun 2022
Cited by 5 | Viewed by 2181
Abstract
Many previous studies have reported the various proteins specifically secreted as inducers in the dorsal or ventral regions in vertebrate gastrula. However, little is known about the effect on cell fate of small molecules below 1000 Da. We therefore tried to identify small [...] Read more.
Many previous studies have reported the various proteins specifically secreted as inducers in the dorsal or ventral regions in vertebrate gastrula. However, little is known about the effect on cell fate of small molecules below 1000 Da. We therefore tried to identify small molecules specifically expressed in the dorsal marginal zone (DMZ) or ventral marginal zone (VMZ) in vertebrate gastrula. Small intracellular and secreted molecules were detected using explants and supernatant samples. Hydrophilic metabolites were analyzed by capillary ion chromatography–mass spectrometry and liquid chromatography–mass spectrometry, and lipids were analyzed by supercritical fluid chromatography–tandem mass spectrometry. In total, 190 hydrophilic metabolites and 396 lipids were identified. The DMZ was found to have high amounts of glycolysis- and glutathione metabolism-related metabolites in explants, and the VMZ was richer in purine metabolism-related metabolites. We also discovered some hydrophilic metabolites and lipids differentially contained in the DMZ or VMZ. Our research would contribute to a deeper understanding of the cellular physiology that regulates early embryogenesis. Full article
(This article belongs to the Special Issue Animal and Cellular Models in Metabolomics Research Volume 2)
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12 pages, 2558 KiB  
Article
NMR-Based Metabolomics Identify Metabolic Change in Spleen of Idiopathic Thrombocytopenic Purpura Patients
by Shi Wen, Zhenzhao Wang, Jianghua Feng, Yuanyuan Yang, Xianchao Lin and Heguang Huang
Metabolites 2022, 12(6), 565; https://doi.org/10.3390/metabo12060565 - 19 Jun 2022
Cited by 1 | Viewed by 1927
Abstract
Idiopathic thrombocytopenic purpura (ITP) is a common hematological disease and the abnormal platelet destruction in the spleen is a critical pathological mechanism for ITP. However, the metabolomic change in the spleen caused by ITP is still unclear. In the present study, the metabolomic [...] Read more.
Idiopathic thrombocytopenic purpura (ITP) is a common hematological disease and the abnormal platelet destruction in the spleen is a critical pathological mechanism for ITP. However, the metabolomic change in the spleen caused by ITP is still unclear. In the present study, the metabolomic information of 18 ITP and 20 normal spleen samples were detected by using 1H high-resolution magic angle spinning NMR spectroscopy (1H MAS NMR). Compared with normal spleen, the concentrations of acetate, alanine, glutamine, glycerol, isoleucine, lysine, valine, phenylalanine, leucine, and methanol in ITP spleen tissue were elevated and 3-hydroxybutyric acid, ascorbate, asparagine, ethanol, glycogen, low-density lipoprotein, malonate, myo-inositol, glycerophosphocholine, pyroglutamate, and taurine were decreased. Amino acids metabolic pathways, such as branched-chain amino acids pathway, were identified as the main involved pathways based on enrichment analysis. The decrease in taurine level in the spleen was the most obvious metabolic signature involving ITP with high sensitivity and specificity to distinguish the spleen of ITP from the normal (CI: 0.825–0.982). Notably, the level of taurine in the spleen was negatively correlated with the efficacy of splenectomy (r = 0.622, p = 0.006). Collectively, the data from our study revealed previously unknown ITP-related metabolomic changes in the spleen and found a potential diagnostic and efficacy-predictive biomarker for ITP treatment. Full article
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19 pages, 2346 KiB  
Review
The Potential Role of Metabolomics in Drug-Induced Liver Injury (DILI) Assessment
by Marta Moreno-Torres, Guillermo Quintás and José V. Castell
Metabolites 2022, 12(6), 564; https://doi.org/10.3390/metabo12060564 - 19 Jun 2022
Cited by 16 | Viewed by 2810
Abstract
Drug-induced liver injury (DILI) is one of the most frequent adverse clinical reactions and a relevant cause of morbidity and mortality. Hepatotoxicity is among the major reasons for drug withdrawal during post-market and late development stages, representing a major concern to the pharmaceutical [...] Read more.
Drug-induced liver injury (DILI) is one of the most frequent adverse clinical reactions and a relevant cause of morbidity and mortality. Hepatotoxicity is among the major reasons for drug withdrawal during post-market and late development stages, representing a major concern to the pharmaceutical industry. The current biochemical parameters for the detection of DILI are based on enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP)) and bilirubin serum levels that are not specific of DILI and therefore there is an increasing interest on novel, specific, DILI biomarkers discovery. Metabolomics has emerged as a tool with a great potential for biomarker discovery, especially in disease diagnosis, and assessment of drug toxicity or efficacy. This review summarizes the multistep approaches in DILI biomarker research and discovery based on metabolomics and the principal outcomes from the research performed in this field. For that purpose, we have reviewed the recent scientific literature from PubMed, Web of Science, EMBASE, and PubTator using the terms “metabolomics”, “DILI”, and “humans”. Despite the undoubted contribution of metabolomics to our understanding of the underlying mechanisms of DILI and the identification of promising novel metabolite biomarkers, there are still some inconsistencies and limitations that hinder the translation of these research findings into general clinical practice, probably due to the variability of the methods used as well to the different mechanisms elicited by the DILI causing agent. Full article
(This article belongs to the Special Issue Advances in Gastroenterology and Metabolism)
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17 pages, 4469 KiB  
Article
Switching to a Standard Chow Diet at Weaning Improves the Effects of Maternal and Postnatal High-Fat and High-Sucrose Diet on Cardiometabolic Health in Adult Male Mouse Offspring
by Andrea Chiñas Merlin, Kassandra Gonzalez, Sarah Mockler, Yessenia Perez, U-Ter Aondo Jia, Adam J. Chicco, Sarah L. Ullevig and Eunhee Chung
Metabolites 2022, 12(6), 563; https://doi.org/10.3390/metabo12060563 - 18 Jun 2022
Cited by 3 | Viewed by 1925
Abstract
Cardiac mitochondrial dysfunction contributes to obesity-associated heart disease. Maternal and postnatal diet plays an important role in cardiac function, yet the impacts of a mismatch between prenatal and postweaning diet on cardiometabolic function are not well understood. We tested the hypothesis that switching [...] Read more.
Cardiac mitochondrial dysfunction contributes to obesity-associated heart disease. Maternal and postnatal diet plays an important role in cardiac function, yet the impacts of a mismatch between prenatal and postweaning diet on cardiometabolic function are not well understood. We tested the hypothesis that switching to a standard chow diet after weaning would attenuate systemic metabolic disorders and cardiac and mitochondrial dysfunction associated with maternal and postnatal high-fat/high-sucrose (HFHS) diet in mice. Six-month-old male CD1 offspring from dams fed a HFHS diet and weaned to the same HFHS diet (HH) or switched to a standard chow diet (HC) were compared to offspring from dams fed a low-fat/low-sucrose diet and maintained on the same diet (LL). HC did not decrease body weight (BW) but normalized glucose tolerance, plasma cholesterol, LDL, and insulin levels compared to the HH. Systolic function indicated by the percent fractional shortening was not altered by diet. In freshly isolated cardiac mitochondria, maximal oxidative phosphorylation-linked respiratory capacity and coupling efficiency were significantly higher in the HC in the presence of fatty acid substrate compared to LL and HH, with modification of genes associated with metabolism and mitochondrial function. Switching to a standard chow diet at weaning can attenuate the deleterious effects of long-term HFHS in adult male mouse offspring. Full article
(This article belongs to the Special Issue Nutrition during Pregnancy and Offspring Growth and Metabolism)
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14 pages, 1545 KiB  
Article
Bee Pollen and Probiotics May Alter Brain Neuropeptide Levels in a Rodent Model of Autism Spectrum Disorders
by Mashael A. Alghamdi, Laila Al-Ayadhi, Wail M. Hassan, Ramesa Shafi Bhat, Mona A. Alonazi and Afaf El-Ansary
Metabolites 2022, 12(6), 562; https://doi.org/10.3390/metabo12060562 - 18 Jun 2022
Cited by 8 | Viewed by 2376
Abstract
Neuropeptides play a major role in maintaining normal brain development in children. Dysfunction of some specific neuropeptides can lead to autism spectrum disorders (ASD) in terms of social interaction and repetitive behavior, but the exact underlying etiological mechanisms are still not clear. In [...] Read more.
Neuropeptides play a major role in maintaining normal brain development in children. Dysfunction of some specific neuropeptides can lead to autism spectrum disorders (ASD) in terms of social interaction and repetitive behavior, but the exact underlying etiological mechanisms are still not clear. In this study, we used an animal model of autism to investigate the role of bee pollen and probiotic in maintaining neuropeptide levels in the brain. We measured the Alpha-melanocyte-stimulating hormone (α-MSH), Beta-endorphin (β-End), neurotensin (NT), and substance P (SP) in brain homogenates of six studied groups of rats. Group I served as control, given only PBS for 30 days; Group II as an autistic model treated with 250 mg PPA/kg BW/day for 3 days after being given PBS for 27 days. Groups III-VI were denoted as intervention groups. G-III was treated with bee pollen (BP) 250 mg/kg body weight/day; G-IV with Lactobacillus paracaseii (LB) (109 CFU/mL) suspended in PBS; G-V with 0.2 g/kg body weight/day Protexin®, a mixture of probiotics (MPB); and G-VI was transplanted with stool from normal animals (FT) for 27 days prior to the induction of PPA neurotoxicity on the last 3 days of study (days 28–30). The obtained data were analyzed through the use of principal component analysis (PCA), discriminant analysis (DA), hierarchical clustering, and receiver operating characteristic (ROC) curves as excellent statistical tools in the field of biomarkers. The obtained data revealed that brain levels of the four measured neuropeptides were significantly reduced in PPA-treated animals compared to healthy control animals. Moreover, the findings demonstrate the ameliorative effects of bee pollen as a prebiotic and of the pure or mixed probiotics. This study proves the protective effects of pre and probiotics against the neurotoxic effects of PPA presented as impaired levels of α-MSH, β-End, NT, and SP. Full article
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21 pages, 1971 KiB  
Review
Lipid Peroxidation Produces a Diverse Mixture of Saturated and Unsaturated Aldehydes in Exhaled Breath That Can Serve as Biomarkers of Lung Cancer—A Review
by Saurin R. Sutaria, Sadakatali S. Gori, James D. Morris, Zhenzhen Xie, Xiao-An Fu and Michael H. Nantz
Metabolites 2022, 12(6), 561; https://doi.org/10.3390/metabo12060561 - 18 Jun 2022
Cited by 22 | Viewed by 3502
Abstract
The peroxidation of unsaturated fatty acids is a widely recognized metabolic process that creates a complex mixture of volatile organic compounds including aldehydes. Elevated levels of reactive oxygen species in cancer cells promote random lipid peroxidation, which leads to a variety of aldehydes. [...] Read more.
The peroxidation of unsaturated fatty acids is a widely recognized metabolic process that creates a complex mixture of volatile organic compounds including aldehydes. Elevated levels of reactive oxygen species in cancer cells promote random lipid peroxidation, which leads to a variety of aldehydes. In the case of lung cancer, many of these volatile aldehydes are exhaled and are of interest as potential markers of the disease. Relevant studies reporting aldehydes in the exhaled breath of lung cancer patients were collected for this review by searching the PubMed and SciFindern databases until 25 May 2022. Information on breath test results, including the biomarker collection, preconcentration, and quantification methods, was extracted and tabulated. Overall, 44 studies were included spanning a period of 34 years. The data show that, as a class, aldehydes are significantly elevated in the breath of lung cancer patients at all stages of the disease relative to healthy control subjects. The type of aldehyde detected and/or deemed to be a biomarker is highly dependent on the method of exhaled breath sampling and analysis. Unsaturated aldehydes, detected primarily when derivatized during preconcentration, are underrepresented as biomarkers given that they are also likely products of lipid peroxidation. Pentanal, hexanal, and heptanal were the most reported aldehydes in studies of exhaled breath from lung cancer patients. Full article
(This article belongs to the Section Lipid Metabolism)
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21 pages, 4029 KiB  
Article
UHPLC-MS Metabolomic Fingerprinting, Antioxidant, and Enzyme Inhibition Activities of Himantormia lugubris from Antarctica
by Carlos Areche, Javier Romero Parra, Beatriz Sepulveda, Olimpo García-Beltrán and Mario J. Simirgiotis
Metabolites 2022, 12(6), 560; https://doi.org/10.3390/metabo12060560 - 18 Jun 2022
Cited by 11 | Viewed by 1914
Abstract
Himantormia lugubris is a Chilean native small lichen shrub growing in the Antarctica region. In this study, the metabolite fingerprinting and the antioxidant and enzyme inhibitory potential from this species and its four major isolated compounds were investigated for the first time. Using [...] Read more.
Himantormia lugubris is a Chilean native small lichen shrub growing in the Antarctica region. In this study, the metabolite fingerprinting and the antioxidant and enzyme inhibitory potential from this species and its four major isolated compounds were investigated for the first time. Using ultra-high performance liquid chromatography coupled to quadrupole-Orbitrap mass spectrometry analysis (UHPLC-Q-Orbitrap-MS), several metabolites were identified including specific compounds as chemotaxonomical markers, while major metabolites were quantified in this species. A good inhibition activity against cholinesterase (acetylcholinesterase (AChE) IC50: 12.38 ± 0.09 µg/mL, butyrylcholinesterase (BChE) IC50: 31.54 ± 0.20 µg/mL) and tyrosinase (22.32 ± 0.21 µg/mL) enzymes of the alcoholic extract and the main compounds (IC50: 28.82 ± 0.10 µg/mL, 36.43 ± 0.08 µg/mL, and 7.25 ± 0.18 µg/mL, respectively, for the most active phenolic atranol) was found. The extract showed a total phenolic content of 47.4 + 0.0 mg of gallic acid equivalents/g. In addition, antioxidant activity was assessed using bleaching of DPPH and ORAC (IC50: 75.3 ± 0.02 µg/mL and 32.7 ± 0.7 μmol Trolox/g lichen, respectively) and FRAP (27.8 ± 0.0 μmol Trolox equivalent/g) experiments. The findings suggest that H. lugubris is a rich source of bioactive compounds with potentiality in the prevention of neurodegenerative or noncommunicable chronic diseases. Full article
(This article belongs to the Section Plant Metabolism)
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16 pages, 829 KiB  
Article
Metabolome Alterations Linking Sugar-Sweetened Beverage Intake with Dyslipidemia in Youth: The Exploring Perinatal Outcomes among CHildren (EPOCH) Study
by Catherine C. Cohen, Dana Dabelea, Gregory Michelotti, Lu Tang, Kartik Shankar, Michael I. Goran and Wei Perng
Metabolites 2022, 12(6), 559; https://doi.org/10.3390/metabo12060559 - 17 Jun 2022
Cited by 1 | Viewed by 1913
Abstract
The objective of this study was to assess intermediary metabolic alterations that link sugar-sweetened beverage (SSB) intake to cardiometabolic (CM) risk factors in youth. A total of 597 participants from the multi-ethnic, longitudinal Exploring Perinatal Outcomes among CHildren (EPOCH) Study were followed in [...] Read more.
The objective of this study was to assess intermediary metabolic alterations that link sugar-sweetened beverage (SSB) intake to cardiometabolic (CM) risk factors in youth. A total of 597 participants from the multi-ethnic, longitudinal Exploring Perinatal Outcomes among CHildren (EPOCH) Study were followed in childhood (median 10 yrs) and adolescence (median 16 yrs). We used a multi-step approach: first, mixed models were used to examine the associations of SSB intake in childhood with CM measures across childhood and adolescence, which revealed a positive association between SSB intake and fasting triglycerides (β (95% CI) for the highest vs. lowest SSB quartile: 8.1 (−0.9,17.0); p-trend = 0.057). Second, least absolute shrinkage and selection operator (LASSO) regression was used to select 180 metabolite features (out of 767 features assessed by untargeted metabolomics) that were associated with SSB intake in childhood. Finally, 13 of these SSB-associated metabolites (from step two) were also prospectively associated with triglycerides across follow-up (from step one) in the same direction as with SSB intake (Bonferroni-adj. p < 0.0003). All annotated compounds were lipids, particularly dicarboxylated fatty acids, mono- and diacylglycerols, and phospholipids. In this diverse cohort, we identified a panel of lipid metabolites that may serve as intermediary biomarkers, linking SSB intake to dyslipidemia risk in youth. Full article
(This article belongs to the Special Issue Determinants, Mechanisms, and Consequences of Childhood Obesity)
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17 pages, 3094 KiB  
Article
Metabolic Profiling of Bladder Cancer Patients’ Serum Reveals Their Sensitivity to Neoadjuvant Chemotherapy
by Juntao Zhuang, Xiao Yang, Qi Zheng, Kai Li, Lingkai Cai, Hao Yu, Jiancheng Lv, Kexin Bai, Qiang Cao, Pengchao Li, Haiwei Yang, Junsong Wang and Qiang Lu
Metabolites 2022, 12(6), 558; https://doi.org/10.3390/metabo12060558 - 17 Jun 2022
Cited by 9 | Viewed by 1979
Abstract
Numerous patients with muscle-invasive bladder cancer develop low responsiveness to cisplatin. Our purpose was to explore differential metabolites derived from serum in bladder cancer patients treated with neoadjuvant chemotherapy (NAC). Data of patients diagnosed with cT2-4aNxM0 was collected. Blood samples were retained prospectively [...] Read more.
Numerous patients with muscle-invasive bladder cancer develop low responsiveness to cisplatin. Our purpose was to explore differential metabolites derived from serum in bladder cancer patients treated with neoadjuvant chemotherapy (NAC). Data of patients diagnosed with cT2-4aNxM0 was collected. Blood samples were retained prospectively before the first chemotherapy for untargeted metabolomics by 1H-NMR and UPLC-MS. To identify characterized metabolites, multivariate statistical analyses were applied, and the intersection of the differential metabolites discovered by the two approaches was used to identify viable biomarkers. A total of 18 patients (6 NAC-sensitive patients and 12 NAC-resistant patients) were enrolled. There were 29 metabolites detected by 1H-NMR and 147 metabolites identified by UPLC-MS. Multivariate statistics demonstrated that in the sensitive group, glutamine and taurine were considerably increased compared to their levels in the resistant group, while glutamate and hypoxanthine were remarkably decreased. Pathway analysis and enrichment analysis showed significant alterations in amino acid pathways, suggesting that response to chemotherapy may be related to amino acid metabolism. In addition, hallmark analysis showed that DNA repair played a regulatory role. Overall, serum metabolic profiles of NAC sensitivity are significantly different in bladder cancer patients. Glycine, hypoxanthine, taurine and glutamine may be the potential biomarkers for clinical treatment. Amino acid metabolism has potential value in enhancing drug efficacy. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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12 pages, 2683 KiB  
Article
Evaluation of Syrosingopine, an MCT Inhibitor, as Potential Modulator of Tumor Metabolism and Extracellular Acidification
by Chloe Buyse, Nicolas Joudiou, Aude Warscotte, Elena Richiardone, Lionel Mignion, Cyril Corbet and Bernard Gallez
Metabolites 2022, 12(6), 557; https://doi.org/10.3390/metabo12060557 - 17 Jun 2022
Cited by 15 | Viewed by 2290
Abstract
Extracellular acidification has been shown to be an important characteristic of invasive tumors, as it promotes invasion and migration but also resistance to treatments. Targeting transporters involved in the regulation of tumor pH constitutes a promising anti-tumor approach, as it would disrupt cellular [...] Read more.
Extracellular acidification has been shown to be an important characteristic of invasive tumors, as it promotes invasion and migration but also resistance to treatments. Targeting transporters involved in the regulation of tumor pH constitutes a promising anti-tumor approach, as it would disrupt cellular pH homeostasis and negatively impact tumor growth. In this study, we evaluated the impact of syrosingopine, an inhibitor of MCT1 and MCT4, as a modulator of tumor metabolism and extracellular acidification in human breast cancer (MDA-MB-231) and pharyngeal squamous cell carcinoma (FaDu) cell models. In both models in vitro, we observed that exposure to syrosingopine led to a decrease in the extracellular acidification rate, intracellular pH, glucose consumption, lactate secretion and tumor cell proliferation with an increase in the number of late apoptotic/necrotic cells. However, in vivo experiments using the MDA-MB-231 model treated with a daily injection of syrosingopine did not reveal any significant change in extracellular pH (pHe) (as measured using CEST-MRI) or primary tumor growth. Overall, our study suggests that targeting MCT could lead to profound changes in tumor cell metabolism and proliferation, and it warrants further research to identify candidates without off-target effects. Full article
(This article belongs to the Special Issue Cancer Associated Changes in Metabolism)
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18 pages, 34537 KiB  
Article
Serum and Soleus Metabolomics Signature of Klf10 Knockout Mice to Identify Potential Biomarkers
by Nadine Baroukh, Nathan Canteleux, Antoine Lefèvre, Camille Dupuy, Cécile Martias, Antoine Presset, Malayannan Subramaniam, John R. Hawse, Patrick Emond, Philippe Pouletaut, Sandrine Morandat, Sabine F. Bensamoun and Lydie Nadal-Desbarats
Metabolites 2022, 12(6), 556; https://doi.org/10.3390/metabo12060556 - 17 Jun 2022
Cited by 6 | Viewed by 2275
Abstract
The transcription factor Krüppel-like factor 10 (Klf10), also known as Tieg1 for TGFβ (Inducible Early Gene-1) is known to control numerous genes in many cell types that are involved in various key biological processes (differentiation, proliferation, apoptosis, inflammation), including cell metabolism [...] Read more.
The transcription factor Krüppel-like factor 10 (Klf10), also known as Tieg1 for TGFβ (Inducible Early Gene-1) is known to control numerous genes in many cell types that are involved in various key biological processes (differentiation, proliferation, apoptosis, inflammation), including cell metabolism and human disease. In skeletal muscle, particularly in the soleus, deletion of the Klf10 gene (Klf10 KO) resulted in ultrastructure fiber disorganization and mitochondrial metabolism deficiencies, characterized by muscular hypertrophy. To determine the metabolic profile related to loss of Klf10 expression, we analyzed blood and soleus tissue using UHPLC-Mass Spectrometry. Metabolomics analyses on both serum and soleus revealed profound differences between wild-type (WT) and KO animals. Klf10 deficient mice exhibited alterations in metabolites associated with energetic metabolism. Additionally, chemical classes of aromatic and amino-acid compounds were disrupted, together with Krebs cycle intermediates, lipids and phospholipids. From variable importance in projection (VIP) analyses, the Warburg effect, citric acid cycle, gluconeogenesis and transfer of acetyl groups into mitochondria appeared to be possible pathways involved in the metabolic alterations observed in Klf10 KO mice. These studies have revealed essential roles for Klf10 in regulating multiple metabolic pathways whose alterations may underlie the observed skeletal muscle defects as well as other diseases. Full article
(This article belongs to the Section Integrative Metabolomics)
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1 pages, 159 KiB  
Correction
Correction: Rigamonti et al. The Role of Aspartate Transaminase to Platelet Ratio Index (APRI) for the Prediction of Non-Alcoholic Fatty Liver Disease (NAFLD) in Severely Obese Children and Adolescents. Metabolites 2022, 12, 155
by Antonello E. Rigamonti, Adele Bondesan, Eugenia Rondinelli, Silvano G. Cella and Alessandro Sartorio
Metabolites 2022, 12(6), 555; https://doi.org/10.3390/metabo12060555 - 17 Jun 2022
Cited by 1 | Viewed by 970
Abstract
In the original publication [...] Full article
(This article belongs to the Special Issue Metabolic Signature of Non-alcoholic Fatty Liver Disease in Children)
19 pages, 18316 KiB  
Article
Lipid Metabolism Is Dysregulated in the Motor Cortex White Matter in Amyotrophic Lateral Sclerosis
by Gemma L. Sadler, Katherine N. Lewis, Vinod K. Narayana, David P. De Souza, Joel Mason, Catriona McLean, David G. Gonsalvez, Bradley J. Turner and Samantha K. Barton
Metabolites 2022, 12(6), 554; https://doi.org/10.3390/metabo12060554 - 17 Jun 2022
Cited by 5 | Viewed by 3085
Abstract
Lipid metabolism is profoundly dysregulated in amyotrophic lateral sclerosis (ALS), yet the lipid composition of the white matter, where the myelinated axons of motor neurons are located, remains uncharacterised. We aimed to comprehensively characterise how myelin is altered in ALS by assessing its [...] Read more.
Lipid metabolism is profoundly dysregulated in amyotrophic lateral sclerosis (ALS), yet the lipid composition of the white matter, where the myelinated axons of motor neurons are located, remains uncharacterised. We aimed to comprehensively characterise how myelin is altered in ALS by assessing its lipid and protein composition. We isolated white matter from the motor cortex from post-mortem tissue of ALS patients (n = 8 sporadic ALS cases and n = 6 familial ALS cases) and age- and sex-matched controls (n = 8) and conducted targeted lipidomic analyses, qPCR for gene expression of relevant lipid metabolising enzymes and Western blotting for myelin proteins. We also quantified myelin density by using spectral confocal reflectance microscopy (SCoRe). Whilst myelin protein composition was similar in ALS and control tissue, both the lipid levels and the expression of their corresponding enzymes were dysregulated, highlighting altered lipid metabolism in the white matter as well as a likely change in myelin composition. Altered myelin composition could contribute to motor neuron dysfunction, and this highlights how oligodendrocytes may play a critical role in ALS pathogenesis. Full article
(This article belongs to the Special Issue Metabolic Dysfunction in Motor Neuron Disease)
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9 pages, 1422 KiB  
Article
Hypouricemic Effect of Submerged Culture of Ganoderma lucidum in Potassium Oxonate-Induced Hyperuricemic Rats
by Chung-Hsiung Huang, Tzu-Yu Chen and Guo-Jane Tsai
Metabolites 2022, 12(6), 553; https://doi.org/10.3390/metabo12060553 - 16 Jun 2022
Cited by 4 | Viewed by 1870
Abstract
Hyperuricemia is a disease caused by a high level of uric acid in the blood. It is an important factor for gout and may be linked to renal and hepatic failure. The objective of this study was to investigate the hypouricemic effects of [...] Read more.
Hyperuricemia is a disease caused by a high level of uric acid in the blood. It is an important factor for gout and may be linked to renal and hepatic failure. The objective of this study was to investigate the hypouricemic effects of submerged culture of Ganoderma lucidum. The lyophilized powder of mycelium (GM) and extracellular polysaccharides (GP) of the G. lucidum submerged culture were prepared. The contents of hypouricemic components, including phenolics and flavonoids, in GM (34.33 ± 0.41 mg/g and 0.32 ± 0.01 mg/g) were higher than that in GP (20.52 ± 1.49 mg/g and not detected). The hypouricemic effect of GM and GP was evaluated in potassium oxonate (PO)-injected rats. The average food intake (23.3 ± 1.2 g/day) and body weight (355.7 ± 28.0 g) were decreased, and the serum level of uric acid (5.56 ± 0.41 mg/dL) was increased in PO-injected rats. However, allopurinol (10 mg/kg b.w.) or GM treatment (200 or 400 mg/kg b.w) improved food intake (26.3 ± 2.7 g/day) and reduced the level of uric acid (4.45 ± 0.46 mg/dL). In parallel, the activity of hepatic xanthine oxidase (XOD) was downregulated from 841.29 ± 299.58 μU/mg protein to 540.80 ± 199.20 μU/mg protein. Moreover, GM and GP (200 or 400 mg/kg b.w) alleviated the level of blood urea nitrogen (BUN) from 30.49 ± 4.71 to 21.16 ± 4.25 mg/dL. GP treatment also diminished the level of alanine transaminase (ALT) from 52.63 ± 18.82 to 27.35 ±6.82 U/L. These results clearly demonstrated the hypouricemic effect of submerged G. lucidum culture and their potential against hyperuricemia-associated renal and hepatic damage. GM was more potent to alleviate hyperuricemia, and GP was more potent to improve renal and hepatic function. Full article
(This article belongs to the Special Issue Functional Foods and Diabetes)
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15 pages, 7093 KiB  
Article
Prognostic Value of Salivary Biochemical Indicators in Primary Resectable Breast Cancer
by Lyudmila V. Bel’skaya and Elena A. Sarf
Metabolites 2022, 12(6), 552; https://doi.org/10.3390/metabo12060552 - 16 Jun 2022
Cited by 2 | Viewed by 1496
Abstract
Despite the fact that breast cancer was detected in the early stages, the prognosis was not always favorable. In this paper, we examined the impact of clinical and pathological characteristics of patients and the composition of saliva before treatment on overall survival and [...] Read more.
Despite the fact that breast cancer was detected in the early stages, the prognosis was not always favorable. In this paper, we examined the impact of clinical and pathological characteristics of patients and the composition of saliva before treatment on overall survival and the risk of recurrence of primary resectable breast cancer. The study included 355 patients of the Omsk Clinical Oncology Center with a diagnosis of primary resectable breast cancer (T1-3N0-1M0). Saliva was analyzed for 42 biochemical indicators before the start of treatment. We have identified two biochemical indicators of saliva that can act as prognostic markers: alkaline phosphatase (ALP) and diene conjugates (DC). Favorable prognostic factors were ALP activity above 71.7 U/L and DC level above 3.93 c.u. Additional accounting for aspartate aminotransferase (AST) activity allows for forming a group with a favorable prognosis, for which the relative risk is reduced by more than 11 times (HR = 11.49, 95% CI 1.43–88.99, p = 0.01591). Salivary AST activity has no independent prognostic value. Multivariate analysis showed that tumor size, lymph nodes metastasis status, malignancy grade, tumor HER2 status, and salivary ALP activity were independent predictors. It was shown that the risk of recurrence decreased with menopause and increased with an increase in the size of the primary tumor and lymph node involvement. Significant risk factors for recurrence were salivary ALP activity below 71.7 U/L and DC levels below 3.93 c.u. before treatment. Thus, the assessment of biochemical indicators of saliva before treatment can provide prognostic information comparable in importance to the clinicopathological characteristics of the tumor and can be used to identify a risk group for recurrence in primary resectable breast cancer. Full article
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17 pages, 4272 KiB  
Article
A Combination of Metabolomics and Machine Learning Results in the Identification of a New Cyst Nematode Hatching Factor
by Lieke E. Vlaar, Benjamin Thiombiano, Davar Abedini, Mario Schilder, Yuting Yang and Lemeng Dong
Metabolites 2022, 12(6), 551; https://doi.org/10.3390/metabo12060551 - 16 Jun 2022
Cited by 4 | Viewed by 2394
Abstract
Potato Cyst Nematodes (PCNs) are an economically important pest for potato growers. A crucial event in the life cycle of the nematode is hatching, after which the juvenile will move toward the host root and infect it. The hatching of PCNs is induced [...] Read more.
Potato Cyst Nematodes (PCNs) are an economically important pest for potato growers. A crucial event in the life cycle of the nematode is hatching, after which the juvenile will move toward the host root and infect it. The hatching of PCNs is induced by known and unknown compounds in the root exudates of host plant species, called hatching factors (HFs, induce hatching independently), such as solanoeclepin A (solA), or hatching stimulants (HSs, enhance hatching activity of HFs). Unraveling the identity of unknown HSs and HFs and their natural variation is important for the selection of cultivars that produce low amounts of HFs and HSs, thus contributing to more sustainable agriculture. In this study, we used a new approach aimed at the identification of new HFs and HSs for PCNs in potato. Hereto, root exudates of a series of different potato cultivars were analyzed for their PCN hatch-inducing activity and their solA content. The exudates were also analyzed using untargeted metabolomics, and subsequently the data were integrated using machine learning, specifically random forest feature selection, and Pearson’s correlation testing. As expected, solA highly correlates with hatching. Furthermore, this resulted in the discovery of a number of metabolite features present in the root exudate that correlate with hatching and solA content, and one of these is a compound of m/z 526.18 that predicts hatching even better than solA with both data methods. This compound’s involvement in hatch stimulation was confirmed by the fractionation of three representative root exudates and hatching assays with the resulting fractions. Moreover, the compound shares mass fragmentation similarity with solA, and we therefore assume it has a similar structure. With this work, we show that potato likely produces a solA analogue, and we contribute to unraveling the hatch-inducing cocktail exuded by plant roots. Full article
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15 pages, 1022 KiB  
Article
A Comprehensive Metabolomics Analysis of Fecal Samples from Advanced Adenoma and Colorectal Cancer Patients
by Oiana Telleria, Oihane E. Alboniga, Marc Clos-Garcia, Beatriz Nafría-Jimenez, Joaquin Cubiella, Luis Bujanda and Juan Manuel Falcón-Pérez
Metabolites 2022, 12(6), 550; https://doi.org/10.3390/metabo12060550 - 15 Jun 2022
Cited by 10 | Viewed by 2598
Abstract
Accurate diagnosis of colorectal cancer (CRC) still relies on invasive colonoscopy. Noninvasive methods are less sensitive in detecting the disease, particularly in the early stage. In the current work, a metabolomics analysis of fecal samples was carried out by ultra-high-performance liquid chromatography–tandem mass [...] Read more.
Accurate diagnosis of colorectal cancer (CRC) still relies on invasive colonoscopy. Noninvasive methods are less sensitive in detecting the disease, particularly in the early stage. In the current work, a metabolomics analysis of fecal samples was carried out by ultra-high-performance liquid chromatography–tandem mass spectroscopy (UPLC-MS/MS). A total of 1380 metabolites were analyzed in a cohort of 120 fecal samples from patients with normal colonoscopy, advanced adenoma (AA) and CRC. Multivariate analysis revealed that metabolic profiles of CRC and AA patients were similar and could be clearly separated from control individuals. Among the 25 significant metabolites, sphingomyelins (SM), lactosylceramides (LacCer), secondary bile acids, polypeptides, formiminoglutamate, heme and cytidine-containing pyrimidines were found to be dysregulated in CRC patients. Supervised random forest (RF) and logistic regression algorithms were employed to build a CRC accurate predicted model consisting of the combination of hemoglobin (Hgb) and bilirubin E,E, lactosyl-N-palmitoyl-sphingosine, glycocholenate sulfate and STLVT with an accuracy, sensitivity and specificity of 91.67% (95% Confidence Interval (CI) 0.7753–0.9825), 0.7 and 1, respectively. Full article
(This article belongs to the Special Issue Advances in Gastroenterology and Metabolism)
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26 pages, 16018 KiB  
Article
Investigating Potential GLP-1 Receptor Agonists in Cyclopeptides from Pseudostellaria heterophylla, Linum usitatissimum, and Drymaria diandra, and Peptides Derived from Heterophyllin B for the Treatment of Type 2 Diabetes: An In Silico Study
by Hui-Jun Liao and Jason T. C. Tzen
Metabolites 2022, 12(6), 549; https://doi.org/10.3390/metabo12060549 - 15 Jun 2022
Cited by 2 | Viewed by 3659
Abstract
GLP-1 receptor agonists stimulate GLP-1R to promote insulin secretion, whereas DPP4 inhibitors slow GLP-1 degradation. Both approaches are incretin-based therapies for T2D. In addition to GLP-1 analogs, small nonpeptide GLP-1RAs such as LY3502970, TT-OAD2, and PF-06882961 have been considered as possible therapeutic alternatives. [...] Read more.
GLP-1 receptor agonists stimulate GLP-1R to promote insulin secretion, whereas DPP4 inhibitors slow GLP-1 degradation. Both approaches are incretin-based therapies for T2D. In addition to GLP-1 analogs, small nonpeptide GLP-1RAs such as LY3502970, TT-OAD2, and PF-06882961 have been considered as possible therapeutic alternatives. Pseudostellaria heterophylla, Linum usitatissimum, and Drymaria diandra are plants rich in cyclopeptides with hypoglycemic effects. Our previous study demonstrated the potential of their cyclopeptides for DPP4 inhibition. Reports of cyclic setmelanotide as an MC4R (GPCR) agonist and cyclic α-conotoxin chimeras as GLP-1RAs led to docking studies of these cyclopeptides with GLP-1R. Heterophyllin B, Pseudostellarin B, Cyclolinopeptide B, Cyclolinopeptide C, Drymarin A, and Diandrine C are abundant in these plants, with binding affinities of −9.5, −10.4, −10.3, −10.6, −11.2, and −11.9 kcal/mol, respectively. The configuration they demonstrated established multiple hydrogen bonds with the transmembrane region of GLP-1R. DdC:(cyclo)-GGPYWP showed the most promising docking score. The results suggest that, in addition to DPP4, GLP-1R may be a hypoglycemic target of these cyclopeptides. This may bring about more discussion of plant cyclopeptides as GLP-1RAs. Moreover, peptides derived from the HB precursor (IFGGLPPP), including IFGGWPPP, IFPGWPPP, IFGGYWPPP, and IFGYGWPPPP, exhibited diverse interactions with GLP-1R and displayed backbones available for further research. Full article
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12 pages, 1387 KiB  
Article
Intrinsic Exercise Capacity Affects Glycine and Angiotensin-Converting Enzyme 2 (ACE2) Levels in Sedentary and Exercise Trained Rats
by Nora Klöting, Michael Schwarzer, Estelle Heyne, Uta Ceglarek, Anne Hoffmann, Knut Krohn, Torsten Doenst and Matthias Blüher
Metabolites 2022, 12(6), 548; https://doi.org/10.3390/metabo12060548 - 15 Jun 2022
Cited by 3 | Viewed by 1741
Abstract
Angiotensin-converting enzyme 2 (ACE2) has been identified as the cellular entry receptor for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High ACE2 tissue expression and low glycine levels were suggested to increase susceptibility for SARS-CoV-2 infection and increasing circulating ACE2 has [...] Read more.
Angiotensin-converting enzyme 2 (ACE2) has been identified as the cellular entry receptor for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High ACE2 tissue expression and low glycine levels were suggested to increase susceptibility for SARS-CoV-2 infection and increasing circulating ACE2 has been proposed as one possible strategy to combat COVID-19. In humans, aerobic physical exercise induces an increase in plasma ACE2 in some individuals. However, it is not clear whether glycine and ACE2 levels depend on intrinsic exercise capacity or on exercise training. We used rats selectively bred for high intrinsic exercise capacity (HCR) or low exercise capacity (LCR) and tested the influence of this genetic predetermination and/or aerobic exercise on metabolites, ACE2 tissue expression and circulating ACE 2. ACE2 expression was measured in different tissues in the sedentary animals and again after 4 weeks of high-intensity aerobic exercise in both LCRs and HCRs. Sedentary HCRs exhibited significantly higher circulating ACE2 concentrations compared to LCRs, but a lower expression of ACE2 in all investigated tissues except for adipose tissue. Body weight was negatively correlated with serum ACE2 and positively correlated with ACE2 expression in the heart. Aerobic exercise caused a significant decrease in ACE2 expression in the lung, heart, muscle, and kidney both in LCRs and HCRs. Our results suggest that ACE2 expression, circulating ACE2 and glycine serum concentration are related to aerobic intrinsic exercise capacity and can be influenced with exercise. These results may support the hypothesis that physically fit individuals have a lower susceptibility for COVID-19 infection. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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10 pages, 257 KiB  
Article
Plasma Metabolite Response to Simple, Refined and Unrefined Carbohydrate-Enriched Diets in Older Adults—Randomized Controlled Crossover Trial
by Neil K. Huang, Nirupa R. Matthan, Gregory Matuszek and Alice H. Lichtenstein
Metabolites 2022, 12(6), 547; https://doi.org/10.3390/metabo12060547 - 15 Jun 2022
Cited by 4 | Viewed by 1516
Abstract
Food intake data collected using subjective tools are prone to inaccuracies and biases. An objective assessment of food intake, such as metabolomic profiling, may offer a more accurate method if unique metabolites can be identified. To explore this option, we used samples generated [...] Read more.
Food intake data collected using subjective tools are prone to inaccuracies and biases. An objective assessment of food intake, such as metabolomic profiling, may offer a more accurate method if unique metabolites can be identified. To explore this option, we used samples generated from a randomized and controlled cross-over trial during which participants (N = 10; 65 ± 8 year, BMI, 29.8 ± 3.2 kg/m2) consumed each of the three diets enriched in different types of carbohydrate. Plasma metabolite concentrations were measured at the end of each diet phase using gas chromatography/time-of-flight mass spectrometry and ultra-high pressure liquid chromatography/quadrupole time-of-flight tandem mass spectrometry. Participants were provided, in random order, with diets enriched in three carbohydrate types (simple carbohydrate (SC), refined carbohydrate (RC) and unrefined carbohydrate (URC)) for 4.5 weeks per phase and separated by two-week washout periods. Data were analyzed using partial least square-discrimination analysis, receiver operating characteristics (ROC curve) and hierarchical analysis. Among the known metabolites, 3-methylhistidine, phenylethylamine, cysteine, betaine and pipecolic acid were identified as biomarkers in the URC diet compared to the RC diet, and the later three metabolites were differentiated and compared to SC diet. Hierarchical analysis indicated that the plasma metabolites at the end of each diet phase were more strongly clustered by the participant than the carbohydrate type. Hence, although differences in plasma metabolite concentrations were observed after participants consumed diets differing in carbohydrate type, individual variation was a stronger predictor of plasma metabolite concentrations than dietary carbohydrate type. These findings limited the potential of metabolic profiling to address this variable. Full article
(This article belongs to the Topic Nutritional and Functional Properties of Cereal Crops)
15 pages, 1470 KiB  
Article
The Impact of Iron Dyshomeostasis and Anaemia on Long-Term Pulmonary Recovery and Persisting Symptom Burden after COVID-19: A Prospective Observational Cohort Study
by Thomas Sonnweber, Philipp Grubwieser, Sabina Sahanic, Anna Katharina Böhm, Alex Pizzini, Anna Luger, Christoph Schwabl, Sabine Koppelstätter, Katharina Kurz, Bernhard Puchner, Barbara Sperner-Unterweger, Katharina Hüfner, Ewald Wöll, Manfred Nairz, Gerlig Widmann, Ivan Tancevski, Judith Löffler-Ragg and Günter Weiss
Metabolites 2022, 12(6), 546; https://doi.org/10.3390/metabo12060546 - 14 Jun 2022
Cited by 11 | Viewed by 3090
Abstract
Coronavirus disease 2019 (COVID-19) is frequently associated with iron dyshomeostasis. The latter is related to acute disease severity and COVID-19 convalescence. We herein describe iron dyshomeostasis at COVID-19 follow-up and its association with long-term pulmonary and symptomatic recovery. The prospective, multicentre, observational cohort [...] Read more.
Coronavirus disease 2019 (COVID-19) is frequently associated with iron dyshomeostasis. The latter is related to acute disease severity and COVID-19 convalescence. We herein describe iron dyshomeostasis at COVID-19 follow-up and its association with long-term pulmonary and symptomatic recovery. The prospective, multicentre, observational cohort study “Development of Interstitial Lung Disease (ILD) in Patients With Severe SARS-CoV-2 Infection (CovILD)” encompasses serial extensive clinical, laboratory, functional and imaging evaluations at 60, 100, 180 and 360 days after COVID-19 onset. We included 108 individuals with mild-to-critical acute COVID-19, whereas 75% presented with severe acute disease. At 60 days post-COVID-19 follow-up, hyperferritinaemia (35% of patients), iron deficiency (24% of the cohort) and anaemia (9% of the patients) were frequently found. Anaemia of inflammation (AI) was the predominant feature at early post-acute follow-up, whereas the anaemia phenotype shifted towards iron deficiency anaemia (IDA) and combinations of IDA and AI until the 360 days follow-up. The prevalence of anaemia significantly decreased over time, but iron dyshomeostasis remained a frequent finding throughout the study. Neither iron dyshomeostasis nor anaemia were related to persisting structural lung impairment, but both were associated with impaired stress resilience at long-term COVID-19 follow-up. To conclude, iron dyshomeostasis and anaemia are frequent findings after COVID-19 and may contribute to its long-term symptomatic outcome. Full article
(This article belongs to the Special Issue Advances in Iron Metabolism and Anemia)
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18 pages, 3044 KiB  
Systematic Review
Changes in Metabolism as a Diagnostic Tool for Lung Cancer: Systematic Review
by Hanne Mariën, Elien Derveaux, Karolien Vanhove, Peter Adriaensens, Michiel Thomeer and Liesbet Mesotten
Metabolites 2022, 12(6), 545; https://doi.org/10.3390/metabo12060545 - 14 Jun 2022
Cited by 4 | Viewed by 1900
Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide, with five-year survival rates varying from 3–62%. Screening aims at early detection, but half of the patients are diagnosed in advanced stages, limiting therapeutic possibilities. Positron emission tomography-computed tomography (PET-CT) is an essential [...] Read more.
Lung cancer is the leading cause of cancer-related mortality worldwide, with five-year survival rates varying from 3–62%. Screening aims at early detection, but half of the patients are diagnosed in advanced stages, limiting therapeutic possibilities. Positron emission tomography-computed tomography (PET-CT) is an essential technique in lung cancer detection and staging, with a sensitivity reaching 96%. However, since elevated 18F-fluorodeoxyglucose (18F-FDG) uptake is not cancer-specific, PET-CT often fails to discriminate between malignant and non-malignant PET-positive hypermetabolic lesions, with a specificity of only 23%. Furthermore, discrimination between lung cancer types is still impossible without invasive procedures. High mortality and morbidity, low survival rates, and difficulties in early detection, staging, and typing of lung cancer motivate the search for biomarkers to improve the diagnostic process and life expectancy. Metabolomics has emerged as a valuable technique for these pitfalls. Over 150 metabolites have been associated with lung cancer, and several are consistent in their findings of alterations in specific metabolite concentrations. However, there is still more variability than consistency due to the lack of standardized patient cohorts and measurement protocols. This review summarizes the identified metabolic biomarkers for early diagnosis, staging, and typing and reinforces the need for biomarkers to predict disease progression and survival and to support treatment follow-up. Full article
(This article belongs to the Special Issue Cancer Associated Changes in Metabolism)
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9 pages, 1443 KiB  
Article
Lipidomic Profiling Identifies a Novel Lipid Signature Associated with Ethnicity-Specific Disparity of Bladder Cancer
by Karthik Reddy Kami Reddy, Danthasinghe Waduge Badrajee Piyarathna, Abu Hena Mostafa Kamal, Vasanta Putluri, Shiva Shankar Ravi, Roni J. Bollag, Martha K. Terris, Yair Lotan and Nagireddy Putluri
Metabolites 2022, 12(6), 544; https://doi.org/10.3390/metabo12060544 - 14 Jun 2022
Cited by 2 | Viewed by 2111
Abstract
Bladder Cancer (BLCA) is the ninth most frequently diagnosed cancer globally and the sixth most common cancer in the US. African Americans (AA) exhibit half the BLCA incidence compared to European Americans (EA), but they have a 70% higher risk of cancer-related death; [...] Read more.
Bladder Cancer (BLCA) is the ninth most frequently diagnosed cancer globally and the sixth most common cancer in the US. African Americans (AA) exhibit half the BLCA incidence compared to European Americans (EA), but they have a 70% higher risk of cancer-related death; unfortunately, this disparity in BLCA mortality remains poorly understood. In this study, we have used an ethnicity-balanced cohort for unbiased lipidomics profiling to study the changes in the lipid fingerprint for AA and EA BLCA tissues collected from similar geographical regions to determine a signature of ethnic-specific alterations. We identified 86 lipids significantly altered between self-reported AA and EA BLCA patients from Augusta University (AU) cohort. The majority of altered lipids belong to phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), ly sophosphatidylcholines (lysoPCs), phosphatidylserines (PSs), and diglycerides (DGs). Interestingly, levels of four lysoPCs (lyso PCs 20:3, lyso PCs 22:1, lyso PCs 22:2, and lyso PCs 26:1) were elevated while, in contrast, the majority of the PCs were reduced in AA BLCA. Significant alterations in long-chain monounsaturated (MonoUN) and polyunsaturated (PolyUN) lipids were also observed between AA and EA BLCA tumor tissues. These first-in-field results implicate ethnic-specific lipid alterations in BLCA. Full article
(This article belongs to the Topic Cancer Cell Metabolism)
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15 pages, 3132 KiB  
Article
The Distribution of Major Brain Metabolites in Normal Adults: Short Echo Time Whole-Brain MR Spectroscopic Imaging Findings
by Xinnan Li, Kagari Abiko, Sulaiman Sheriff, Andrew A. Maudsley, Yuta Urushibata, Sinyeob Ahn and Khin Khin Tha
Metabolites 2022, 12(6), 543; https://doi.org/10.3390/metabo12060543 - 14 Jun 2022
Cited by 6 | Viewed by 1736
Abstract
This prospective study aimed to evaluate the variation in magnetic resonance spectroscopic imaging (MRSI)-observed brain metabolite concentrations according to anatomical location, sex, and age, and the relationships among regional metabolite distributions, using short echo time (TE) whole-brain MRSI (WB-MRSI). Thirty-eight healthy participants underwent [...] Read more.
This prospective study aimed to evaluate the variation in magnetic resonance spectroscopic imaging (MRSI)-observed brain metabolite concentrations according to anatomical location, sex, and age, and the relationships among regional metabolite distributions, using short echo time (TE) whole-brain MRSI (WB-MRSI). Thirty-eight healthy participants underwent short TE WB-MRSI. The major metabolite ratios, i.e., N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, glutamate + glutamine (Glx)/Cr, and myoinositol (mI)/Cr, were calculated voxel-by-voxel. Their variations according to anatomical regions, sex, and age, and their relationship to each other were evaluated by using repeated-measures analysis of variance, t-tests, and Pearson’s product-moment correlation analyses. All four metabolite ratios exhibited widespread regional variation across the cerebral hemispheres (corrected p < 0.05). Laterality between the two sides and sex-related variation were also shown (p < 0.05). In several regions, NAA/Cr and Glx/Cr decreased and mI/Cr increased with age (corrected p < 0.05). There was a moderate positive correlation between NAA/Cr and mI/Cr in the insular lobe and thalamus and between Glx/Cr and mI/Cr in the parietal lobe (r ≥ 0.348, corrected p ≤ 0.025). These observations demand age- and sex- specific regional reference values in interpreting these metabolites, and they may facilitate the understanding of glial-neuronal interactions in maintaining homeostasis. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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13 pages, 3690 KiB  
Review
Research in the Field of Exercise and Metabolomics: A Bibliometric and Visual Analysis
by Zhen Lv, Zhi-Gang Gong and Yong-Jiang Xu
Metabolites 2022, 12(6), 542; https://doi.org/10.3390/metabo12060542 - 14 Jun 2022
Cited by 2 | Viewed by 1916
Abstract
The aim of this article was to conduct a bibliometric analysis of global research trends in the field of exercise and metabolomics between 2005 and 2020. Systematic articles were obtained from the literature in the Web of Science core collection database from 2005 [...] Read more.
The aim of this article was to conduct a bibliometric analysis of global research trends in the field of exercise and metabolomics between 2005 and 2020. Systematic articles were obtained from the literature in the Web of Science core collection database from 2005 to 2020. The relationship between the number of publications, citations, countries, journals, authors, and the evolution of research hotspots was analyzed. A total of 807 studies were included in the analysis. From 2005 to 2020, the number of citations and the number of published articles showed an upward trend. Keyword co-occurrence indicates that research hotspots are focused on exercise, physical activity, metabolomics, obesity, insulin resistance, inflammation, and cardiovascular disease. Keyword clustering indicates that the research frontier is focused on the field of sports medicine, which includes molecular-level studies of exercise interventions in disease and studies of the physiological mechanisms by which exercise alters the body. Overall, this trinity of models, combining chronic disease with exercise interventions and molecular-level studies of metabolomics, has become the forefront of research in the field. This historical review of the field of exercise and metabolomics will further provide a useful basis for hot issues and future development trends. Full article
(This article belongs to the Section Advances in Metabolomics)
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11 pages, 290 KiB  
Review
The Endocannabinoid System: A Potential Therapeutic Target for Coagulopathies
by Wujood Khayat and Christian Lehmann
Metabolites 2022, 12(6), 541; https://doi.org/10.3390/metabo12060541 - 14 Jun 2022
Cited by 3 | Viewed by 1909
Abstract
Abnormal blood coagulation or coagulopathy is a common manifestation of many pathological conditions. It occurs when there is an imbalance between the activities of the coagulation system and the fibrinolytic system, leading to excessive or impaired intravascular blood clot formation, which can disturb [...] Read more.
Abnormal blood coagulation or coagulopathy is a common manifestation of many pathological conditions. It occurs when there is an imbalance between the activities of the coagulation system and the fibrinolytic system, leading to excessive or impaired intravascular blood clot formation, which can disturb blood flow causing ischemia or hemorrhage in the affected tissues. A growing body of evidence has demonstrated blood coagulation abnormalities in association with cannabinoid use, suggesting the involvement of the endogenous cannabinoid system (ECS) in modulating blood coagulation. However, the evidence in the literature has been controversial on whether cannabinoids promote or inhibit blood coagulation. The ECS has been extensively studied in recent years for its potential as a therapeutic target for many diseases. This review provides a brief introduction to the ECS and discusses the reported anticoagulatory and procoagulatory effects of various cannabinoids, highlighting some possible mechanisms that might underlie the observed effects. Understanding the coagulatory effects of cannabinoids and the interaction between the coagulation system and the ECS is vital for developing novel therapeutics for coagulopathies. Full article
19 pages, 1852 KiB  
Review
Poisonous Plants of the Indian Himalaya: An Overview
by Abhishek Jamloki, Vijay Laxmi Trivedi, M. C. Nautiyal, Prabhakar Semwal and Natália Cruz-Martins
Metabolites 2022, 12(6), 540; https://doi.org/10.3390/metabo12060540 - 13 Jun 2022
Cited by 5 | Viewed by 5488
Abstract
Indian Himalayan region (IHR) supports a wide diversity of plants and most of them are known for their medicinal value. Humankind has been using medicinal plants since the inception of civilization. Various types of bioactive compounds are found in plants, which are directly [...] Read more.
Indian Himalayan region (IHR) supports a wide diversity of plants and most of them are known for their medicinal value. Humankind has been using medicinal plants since the inception of civilization. Various types of bioactive compounds are found in plants, which are directly and indirectly beneficial for plants as well as humans. These bioactive compounds are highly useful and being used as a strong source of medicines, pharmaceuticals, agrochemicals, food additives, fragrances, and flavoring agents. Apart from this, several plant species contain some toxic compounds that affect the health of many forms of life as well as cause their death. These plants are known as poisonous plants, because of their toxicity to both humans and animals. Therefore, it is necessary to know in what quantity they should be taken so that it does not have a negative impact on health. Recent studies on poisonous plants have raised awareness among people who are at risk of plant toxicity in different parts of the world. The main aim of this review article is to explore the current knowledge about the poisonous plants of the Indian Himalayas along with the importance of these poisonous plants to treat different ailments. The findings of the present review will be helpful to different pharmaceutical industries, the scientific community and researchers around the world. Full article
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10 pages, 269 KiB  
Article
Serum ANGPTL8 and ANGPTL3 as Predictors of Triglyceride Elevation in Adult Women
by Anna Stefanska, Katarzyna Bergmann, Magdalena Krintus, Magdalena Kuligowska-Prusinska, Karolina Murawska and Grazyna Sypniewska
Metabolites 2022, 12(6), 539; https://doi.org/10.3390/metabo12060539 - 11 Jun 2022
Cited by 6 | Viewed by 1658
Abstract
Angiopoietin-like proteins ANGPTL3 and ANGPTL8 have been shown to inhibit lipoprotein lipase, and thus regulate triglyceride level in the circulation. Whether the regulation of lipid metabolism by ANGPTLs is affected by the menopausal status remains unclear. We aimed to assess the relationships between [...] Read more.
Angiopoietin-like proteins ANGPTL3 and ANGPTL8 have been shown to inhibit lipoprotein lipase, and thus regulate triglyceride level in the circulation. Whether the regulation of lipid metabolism by ANGPTLs is affected by the menopausal status remains unclear. We aimed to assess the relationships between serum ANGPTL3 and ANGPTL8 and atherogenic biomarkers in presumably healthy women during ageing. The study group included 94 women of whom 31 were premenopausal (PRE ≤ 40 years) and 37 were postmenopausal (POST ≥ 52 years). Atherogenic lipid and non-lipid biomarkers and ANGPTLs (ANGPTL3, ANGPTL8) were assayed in serum samples. TG/HDL-C index, non-HDL-cholesterol, remnant cholesterol concentrations, and BMI were calculated. Median levels of ANGPTL3 and concentrations of lipid biomarkers were significantly higher in POST comparing to PRE but ANGPTL8 levels were not different. In PRE, ANGPTL8 levels correlated significantly with TG and TG/HDL-C index while there were no correlations between ANGPTL3 and these biomarkers. In POST both ANGPTLs correlated with TG, sdLDL-C, and TG/HDL-C. ANGPTL8 and sd-LDL-C were the most significant predictors of early triglyceride elevation > 100 mg/dL (1.13 mmol/L) in the whole group and POST whereas the prediction power of ANGPTL3 was negligible in the whole group and non-significant in the subgroups. We demonstrated a significant positive correlation of ANGPTL3 with age category which predisposes to postmenopause. Despite the increase in ANGPTL3 level with ageing the ANGPTL3/ANGPL8 ratio was maintained. In conclusion, ANGPTL8 predicts the early triglyceride elevation better than ANGPTL3, especially in postmenopausal women. The association of ANGPTL3 with triglyceride levels is weaker than ANGPTL8 and depends on menopausal status. We suggest that the choice for the best efficient treatment of dyslipidemia with new inhibitors of angiopoietin-like proteins may depend on the menopausal status. Full article
(This article belongs to the Special Issue Metabolic Disorders in Menopause)
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