Metabolites

18 pages, 1346 KiB

Open AccessReview

Tryptophan Metabolism and Gut Microbiota: A Novel Regulatory Axis Integrating the Microbiome, Immunity, and Cancer

by Yingjian Hou, Jing Li and Shuhuan Ying

Metabolites 2023, 13(11), 1166; https://doi.org/10.3390/metabo13111166 - 20 Nov 2023

Cited by 22 | Viewed by 7610

Tryptophan metabolism and gut microbiota form an integrated regulatory axis that impacts immunity, metabolism, and cancer. This review consolidated current knowledge on the bidirectional interactions between microbial tryptophan processing and the host. We focused on how the gut microbiome controls tryptophan breakdown via [...] Read more.

Tryptophan metabolism and gut microbiota form an integrated regulatory axis that impacts immunity, metabolism, and cancer. This review consolidated current knowledge on the bidirectional interactions between microbial tryptophan processing and the host. We focused on how the gut microbiome controls tryptophan breakdown via the indole, kynurenine, and serotonin pathways. Dysbiosis of the gut microbiota induces disruptions in tryptophan catabolism which contribute to disorders like inflammatory conditions, neuropsychiatric diseases, metabolic syndromes, and cancer. These disruptions affect immune homeostasis, neurotransmission, and gut-brain communication. Elucidating the mechanisms of microbial tryptophan modulation could enable novel therapeutic approaches like psychobiotics and microbiome-targeted dietary interventions. Overall, further research on the microbiota-tryptophan axis has the potential to revolutionize personalized diagnostics and treatments for improving human health. Full article

(This article belongs to the Special Issue Natural Metabolites on Gut Microbiome Modulation)

► Show Figures

Figure 1

14 pages, 2213 KiB

Open AccessArticle

Metabolomics Assessment of Volume Overload-Induced Heart Failure and Oxidative Stress in the Kidney

by Hsiang-Yu Tang, Jyh-En Huang, Ming-Tong Tsau, Chi-Jen Chang, Ying-Chang Tung, Gigin Lin and Mei-Ling Cheng

Metabolites 2023, 13(11), 1165; https://doi.org/10.3390/metabo13111165 - 20 Nov 2023

Cited by 3 | Viewed by 1896

Abstract

The incidence of heart failure (HF) is increasing and is associated with a poor prognosis. Moreover, HF often coexists with renal dysfunction and is associated with a worsened outcome. In many experimental studies on cardiac dysfunction, the function of other organs was either [...] Read more.

The incidence of heart failure (HF) is increasing and is associated with a poor prognosis. Moreover, HF often coexists with renal dysfunction and is associated with a worsened outcome. In many experimental studies on cardiac dysfunction, the function of other organs was either not addressed or did not show any decline. Until now, the exact mechanisms for initiating and sustaining this interaction are still unknown. The objective of this study is to use volume overload to induce cardiac hypertrophy and HF in aortocaval fistula (ACF) rat models, and to elucidate how volume overload affects metabolic changes in the kidney, even with normal renal function, in HF. The results showed the metabolic changes between control and ACF rats, including taurine metabolism; purine metabolism; glycine, serine, and threonine metabolism; glycerophospholipid metabolism; and histidine metabolism. Increasing the downstream purine metabolism from inosine to uric acid in the kidneys of ACF rats induced oxidative stress through xanthine oxidase. This result was consistent with HK-2 cells treated with xanthine and xanthine oxidase. Under oxidative stress, taurine accumulation was observed in ACF rats, indicating increased activity of the hypotaurine–taurine pathway as a defense mechanism against oxidative stress in the kidney. Another antioxidant, ascorbic acid 2-sulfate, showed lower levels in ACF rats, indicating that the kidneys experience elevated oxidative stress due to volume overload and HF. In summary, metabolic profiles are more sensitive than clinical parameters in reacting to damage to the kidney in HF. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

► Show Figures

Graphical abstract

16 pages, 3324 KiB

Open AccessArticle

Metabolomic Insights into the Mechanisms of Ganoderic Acid: Protection against α-Amanitin-Induced Liver Injury

by Chong Zheng, Shaofang Lv, Jianfang Ye, Lu Zou, Kai Zhu, Haichang Li, Yongxi Dong and Lei Li

Metabolites 2023, 13(11), 1164; https://doi.org/10.3390/metabo13111164 - 20 Nov 2023

Cited by 5 | Viewed by 1597

Abstract

α-Amanitin is a representative toxin found in the Amanita genus of mushrooms, and the consumption of mushrooms containing α-Amanitin can lead to severe liver damage. In this study, we conduct toxicological experiments to validate the protective effects of Ganoderic acid A against α-amanitin-induced [...] Read more.

α-Amanitin is a representative toxin found in the Amanita genus of mushrooms, and the consumption of mushrooms containing α-Amanitin can lead to severe liver damage. In this study, we conduct toxicological experiments to validate the protective effects of Ganoderic acid A against α-amanitin-induced liver damage. By establishing animal models with different durations of Ganoderic acid A treatment and conducting a metabolomic analysis of the serum samples, we further confirmed the differences in serum metabolites between the AMA+GA and AMA groups. The analysis of differential serum metabolites after the Ganoderic acid A intervention suggests that Ganoderic acid A may intervene in α-amanitin-induced liver damage by participating in the regulation of retinol metabolism, tyrosine and tryptophan biosynthesis, fatty acid biosynthesis, sphingosine biosynthesis, spermidine and spermine biosynthesis, and branched-chain amino acid metabolism. This provides initial insights into the protective intervention mechanisms of GA against α-amanitin-induced liver damage and offers new avenues for the development of therapeutic drugs for α-Amanitin poisoning. Full article

(This article belongs to the Special Issue Association between Natural Products and the Metabolism in Humans)

► Show Figures

Figure 1

14 pages, 901 KiB

Open AccessArticle

Associations between Smoking and Smoking Cessation during Pregnancy and Newborn Metabolite Concentrations: Findings from PRAMS and INSPIRE Birth Cohorts

by Brittney M. Snyder, Hui Nian, Angela M. Miller, Kelli K. Ryckman, Yinmei Li, Hilary A. Tindle, Lin Ammar, Abhismitha Ramesh, Zhouwen Liu, Tina V. Hartert and Pingsheng Wu

Metabolites 2023, 13(11), 1163; https://doi.org/10.3390/metabo13111163 - 19 Nov 2023

Viewed by 1626

Abstract

Newborn metabolite perturbations may identify potential biomarkers or mechanisms underlying adverse, smoking-related childhood health outcomes. We assessed associations between third-trimester smoking and newborn metabolite concentrations using the Tennessee Pregnancy Risk Assessment Monitoring System (PRAMS, 2009–2019) as the discovery cohort and INSPIRE (2012–2014) as [...] Read more.

Newborn metabolite perturbations may identify potential biomarkers or mechanisms underlying adverse, smoking-related childhood health outcomes. We assessed associations between third-trimester smoking and newborn metabolite concentrations using the Tennessee Pregnancy Risk Assessment Monitoring System (PRAMS, 2009–2019) as the discovery cohort and INSPIRE (2012–2014) as the replication cohort. Children were linked to newborn screening metabolic data (33 metabolites). Third-trimester smoking was ascertained from birth certificates (PRAMS) and questionnaires (INSPIRE). Among 8600 and 1918 mother–child dyads in PRAMS and INSPIRE cohorts, 14% and 13% of women reported third-trimester smoking, respectively. Third-trimester smoking was associated with higher median concentrations of free carnitine (C0), glycine (GLY), and leucine (LEU) at birth (PRAMS: C0: adjusted fold change 1.11 [95% confidence interval (CI) 1.08, 1.14], GLY: 1.03 [95% CI 1.01, 1.04], LEU: 1.04 [95% CI 1.03, 1.06]; INSPIRE: C0: 1.08 [95% CI 1.02, 1.14], GLY: 1.05 [95% CI 1.01, 1.09], LEU: 1.05 [95% CI 1.01, 1.09]). Smoking cessation (vs. continued smoking) during pregnancy was associated with lower median metabolite concentrations, approaching levels observed in infants of non-smoking women. Findings suggest potential pathways underlying fetal metabolic programming due to in utero smoke exposure and a potential reversible relationship of cessation. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

► Show Figures

Figure 1

15 pages, 2745 KiB

Open AccessArticle

Cobalt and Titanium Alleviate the Methylglyoxal-Induced Oxidative Stress in Pennisetum divisum Seedlings under Saline Conditions

by Bushra Ahmed Alhammad, Khansa Saleem, Muhammad Ahsan Asghar, Ali Raza, Abd Ullah, Taimoor Hassan Farooq, Jean W. H. Yong, Fei Xu, Mahmoud F. Seleiman and Aamir Riaz

Metabolites 2023, 13(11), 1162; https://doi.org/10.3390/metabo13111162 - 19 Nov 2023

Cited by 4 | Viewed by 1727

Abstract

Salinity is considered to be a global problem and a severe danger to modern agriculture since it negatively impacts plants’ growth and development at both cellular- and whole-plant level. However, cobalt (Co) and titanium (Ti), multifunctional non-essential micro-elements, play a crucial role in [...] Read more.

Salinity is considered to be a global problem and a severe danger to modern agriculture since it negatively impacts plants’ growth and development at both cellular- and whole-plant level. However, cobalt (Co) and titanium (Ti), multifunctional non-essential micro-elements, play a crucial role in improving plant growth and development under salinity stress. In the current study, Co and Ti impact on the morphological, biochemical, nutritional, and metabolic profile of Pennisetum divisum plants under three salinity levels which were assessed. Two concentrations of Co (Co-1; 15.0 mg/L and Co-2; 25.0 mg/L), and two concentrations of Ti (Ti-1; 50.0 mg/L and Ti-2; 100.0 mg/L) were applied as foliar application to the P. divisum plants under salinity (S1; 200 mM, S2; 500 mM, and S3; 1000 mM) stress. The results revealed that various morphological, biochemical, and metabolic processes were drastically impacted by the salinity-induced methylglyoxal (MG) stress. The excessive accumulation of salt ions, including Na⁺ (1.24- and 1.21-fold), and Cl⁻ (1.53- and 1.15-fold) in leaves and roots of P. divisum, resulted in the higher production of MG (2.77- and 2.95-fold) in leaves and roots under severe (1000 mM) salinity stress, respectively. However, Ti-treated leaves showed a significant reduction in ionic imbalance and MG concentrations, whereas considerable improvement was shown in K⁺ and Ca²⁺ under salinity stress, and Co treatment showed downregulation of MG content (26, 16, and 14%) and improved the antioxidant activity, such as a reduction in glutathione (GSH), oxidized glutathione (GSSG), Glutathione reductase (GR), Glyoxalase I (Gly I), and Glyoxalase II (Gly II) by up to 1.13-, 1.35-, 3.75-, 2.08-, and 1.68-fold under severe salinity stress in P. divisum roots. Furthermore, MG-induced stress negatively impacted the metabolic profile and antioxidants activity of P. divisum’s root and leaves; however, Co and Ti treatment considerably improved the biochemical processes and metabolic profile in both underground and aerial parts of the studied plants. Collectively, the results depicted that Co treatment showed significant results in roots and Ti treatment presented considerable changes in leaves of P. divism under salinity stress. Full article

(This article belongs to the Special Issue Plant Secondary Metabolites Biosynthesis, Biological Activities and Transcriptional Regulation in Response to Abiotic/Biotic Stresses)

► Show Figures

Graphical abstract

15 pages, 2406 KiB

Open AccessArticle

Assessing the Therapeutic Efficacy of Proton Transport Inhibitors in a Triple-Negative Breast Cancer Murine Model with Magnetic Resonance Imaging—Chemical Exchange Saturation Transfer Tumor pH Imaging

by Chetan Dhakan, Annasofia Anemone, Vittoria Ventura, Antonella Carella, Alessia Corrado, Elisa Pirotta, Daisy Villano, Feriel Romdhane, Francesco Gammaraccio, Silvio Aime and Dario Livio Longo

Metabolites 2023, 13(11), 1161; https://doi.org/10.3390/metabo13111161 - 18 Nov 2023

Cited by 1 | Viewed by 1958

Abstract

Proton transporters play a key role in maintaining the acidic tumor microenvironment; hence, their inhibition has been proposed as a new therapeutic treatment, although few methods can accurately assess their effect in vivo. In this study, we investigated whether MRI-CEST (Magnetic Resonance Imaging—Chemical [...] Read more.

Proton transporters play a key role in maintaining the acidic tumor microenvironment; hence, their inhibition has been proposed as a new therapeutic treatment, although few methods can accurately assess their effect in vivo. In this study, we investigated whether MRI-CEST (Magnetic Resonance Imaging—Chemical Exchange Saturation Transfer) tumor pH imaging can be a useful tool to evaluate in vivo the therapeutic efficacy of several Proton Pump Inhibitors (PPIs) in breast cancer. Cell viability and extracellular pH assays were carried out in breast cancer cells cultured at physiological pH (7.4) or acid-adapted (pH of 6.5 and 6.8) following the exposure to inhibitors of V-ATPase (Lansoprazole, Esomeprazole) or NHE1 (Amiloride, Cariporide) at several concentrations. Next, triple-negative breast cancer 4T1 tumor-bearing mice were treated with Lansoprazole or Amiloride and MRI-CEST tumor pH imaging was utilized to assess the in vivo efficacy. Only Lansoprazole induced, in addition to breast cancer cell toxicity, a significant inhibition of proton extrusion. A significant reduction in tumor volume, prolonged survival, and increase in extracellular tumor pH after 1 and 2 weeks were observed after Lansoprazole treatment, whereas no significant changes were detected upon Amiloride treatment. Our results suggested that MRI-CEST tumor pH imaging can monitor the therapeutic efficacy of PPIs in breast cancer murine models. Full article

(This article belongs to the Special Issue Metabolism and Cancer Biology)

► Show Figures

Graphical abstract

14 pages, 3969 KiB

Open AccessArticle

Identification of Novel Biomarkers for Early Diagnosis of Atherosclerosis Using High-Resolution Metabolomics

by Syed Wasim Sardar, Jeonghun Nam, Tae Eun Kim, Hyunil Kim and Youngja H. Park

Metabolites 2023, 13(11), 1160; https://doi.org/10.3390/metabo13111160 - 18 Nov 2023

Cited by 4 | Viewed by 2344

Abstract

Atherosclerosis (AS) is a metabolic disorder and the pre-stage of several cardiovascular diseases, including myocardial infarction, stroke, and angina pectoris. Early detection of AS can provide the opportunity for effective management and better clinical results, along with the prevention of further progression of [...] Read more.

Atherosclerosis (AS) is a metabolic disorder and the pre-stage of several cardiovascular diseases, including myocardial infarction, stroke, and angina pectoris. Early detection of AS can provide the opportunity for effective management and better clinical results, along with the prevention of further progression of the disease. In the current study, an untargeted and targeted metabolomic approach was used to identify possible metabolic signatures that have altered levels in AS patients. A total of 200 serum samples from individuals with AS and normal were analyzed via liquid chromatography–high-resolution mass spectrometry. Univariate and multivariate analysis approaches were used to identify differential metabolites. A group of metabolites associated with bile acids, amino acids, steroid hormones, and purine metabolism were identified that are capable of distinguishing AS-risk sera from normal. Further, the targeted metabolomics approach confirmed that six metabolites, namely taurocholic acid, cholic acid, cortisol, hypoxanthine, trimethylamine N-oxide (TMAO), and isoleucine, were found to be significantly upregulated, while the concentrations of glycoursodeoxycholic acid, glycocholic acid, testosterone, leucine, methionine, phenylalanine, tyrosine, and valine were found to be significantly downregulated in the AS-risk sera. The receiver operating characteristic curves of three metabolites, including cortisol, hypoxanthine, and isoleucine, showed high sensitivity and specificity. Taken together, these findings suggest cortisol, hypoxanthine, and isoleucine as novel biomarkers for the early and non-invasive detection of AS. Thus, this study provides new insights for further investigations into the prevention and management of AS. Full article

(This article belongs to the Topic Biomarker Development and Application)

► Show Figures

Graphical abstract

15 pages, 3983 KiB

Open AccessArticle

The Dose–Response Effect of Fluoride Exposure on the Gut Microbiome and Its Functional Pathways in Rats

by Zhe Mo, Jian Wang, Xinyue Meng, Ailin Li, Zhe Li, Wenjun Que, Tuo Wang, Korto Fatti Tarnue, Xu Ma, Ying Liu, Shirui Yan, Lei Wu, Rui Zhang, Junrui Pei and Xiaofeng Wang

Metabolites 2023, 13(11), 1159; https://doi.org/10.3390/metabo13111159 - 17 Nov 2023

Cited by 2 | Viewed by 2319

Abstract

Metabolic activities within the gut microbiome are intimately linked to human health and disease, especially within the context of environmental exposure and its potential ramifications. Perturbations within this microbiome, termed “gut microbiome perturbations”, have emerged as plausible intermediaries in the onset or exacerbation [...] Read more.

Metabolic activities within the gut microbiome are intimately linked to human health and disease, especially within the context of environmental exposure and its potential ramifications. Perturbations within this microbiome, termed “gut microbiome perturbations”, have emerged as plausible intermediaries in the onset or exacerbation of diseases following environmental chemical exposures, with fluoride being a compound of particular concern. Despite the well-documented adverse impacts of excessive fluoride on various human physiological systems—ranging from skeletal to neurological—the nuanced dynamics between fluoride exposure, the gut microbiome, and the resulting dose–response relationship remains a scientific enigma. Leveraging the precision of 16S rRNA high-throughput sequencing, this study meticulously examines the ramifications of diverse fluoride concentrations on the gut microbiome’s composition and functional capabilities within Wistar rats. Our findings indicate a profound shift in the intestinal microbial composition following fluoride exposure, marked by a dose-dependent modulation in the abundance of key genera, including Pelagibacterium, Bilophila, Turicibacter, and Roseburia. Moreover, discernible alterations were observed in critical functional and metabolic pathways of the microbiome, such as D-lyxose ketol-isomerase and DNA polymerase III subunit gamma/tau, underscoring the broad-reaching implications of fluoride exposure. Intriguingly, correlation analyses elucidated strong associations between specific bacterial co-abundance groups (CAGs) and these shifted metabolic pathways. In essence, fluoride exposure not only perturbs the compositional equilibrium of the gut microbiota but also instigates profound shifts in its metabolic landscape. These intricate alterations may provide a mechanistic foundation for understanding fluoride’s potential toxicological effects mediated via gut microbiome modulation. Full article

(This article belongs to the Special Issue Effects of Environmental Exposure on Host and Microbial Metabolism)

► Show Figures

Figure 1

3 pages, 835 KiB

Open AccessCorrection

Correction: Nielson et al. Similarity Downselection: Finding the n Most Dissimilar Molecular Conformers for Reference-Free Metabolomics. Metabolites 2023, 13, 105

by Felicity F. Nielson, Bill Kay, Stephen J. Young, Sean M. Colby, Ryan S. Renslow and Thomas O. Metz

Metabolites 2023, 13(11), 1158; https://doi.org/10.3390/metabo13111158 - 17 Nov 2023

Viewed by 980

Abstract

There were missing figures and associated legends for Figure 3 and Figure 4 as published due to a publication error [...] Full article

► Show Figures

Figure 1

16 pages, 713 KiB

Open AccessReview

The Longevity Protein Klotho: A Promising Tool to Monitor Lifestyle Improvements

by Jean-Sébastien Paquette, Caroline Rhéaume, Pierre Cordeau, Julie-Alexandra Moulin, Etienne Audet-Walsh, Virginie Blanchette, Jean-Philippe Drouin-Chartier, Alfred-Kodjo Toi and Angelo Tremblay

Metabolites 2023, 13(11), 1157; https://doi.org/10.3390/metabo13111157 - 16 Nov 2023

Cited by 4 | Viewed by 5048

Abstract

Aging is not a disease; it is a natural evolution of human physiology. Medical advances have extended our life expectancy, but chronic diseases and geriatric syndrome continue to affect the increasingly aging population. Yet modern medicine perpetuates an approach based on treatment rather [...] Read more.

Aging is not a disease; it is a natural evolution of human physiology. Medical advances have extended our life expectancy, but chronic diseases and geriatric syndrome continue to affect the increasingly aging population. Yet modern medicine perpetuates an approach based on treatment rather than prevention and education. In order to help solve this ever-growing problem, a new discipline has emerged: lifestyle medicine. Nutrition, physical activity, stress management, restorative sleep, social connection, and avoidance of risky substances are the pillars on which lifestyle medicine is founded. The aim of this discipline is to increase healthspan and reduce the duration of morbidity by making changes to our lifestyle. In this review, we propose the use of klotho protein as a novel biomarker for lifestyle medicine in order to quantify and monitor the health status of individuals, as no integrative tool currently exists. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

► Show Figures

Figure 1

15 pages, 2307 KiB

Open AccessArticle

Changes in Uterine Metabolome Associated with Metritis Development and Cure in Lactating Holstein Cows

by Eduardo B. de Oliveira, Hugo F. Monteiro, Jessica M. V. Pereira, Deniece R. Williams, Richard V. Pereira, Noelia Silva Del Rio, Paulo R. Menta, Vinicius S. Machado and Fabio S. Lima

Metabolites 2023, 13(11), 1156; https://doi.org/10.3390/metabo13111156 - 16 Nov 2023

Viewed by 2032

Abstract

The objective of this study was to identify alterations in the vaginal discharge (VD) metabolome and potential biomarkers to predict metritis development and a cure in dairy cows. This prospective cohort study was conducted on two dairies located in CA and TX. Vaginal [...] Read more.

The objective of this study was to identify alterations in the vaginal discharge (VD) metabolome and potential biomarkers to predict metritis development and a cure in dairy cows. This prospective cohort study was conducted on two dairies located in CA and TX. Vaginal discharge was evaluated and collected using the Metricheck^® device. Cows were examined for metritis at 4, 7, and 9 days in milk (DIM). Cows with a fetid, watery, and reddish-brown uterine discharge were classified as having metritis and randomized to receive ceftiofur (n = 10) or remain untreated (n = 7). A cure was defined as the absence of a fetid, watery, reddish-brown uterine discharge at 14 d after enrollment. Vaginal discharge samples were collected from 86 cows within 6 h after parturition, at 4 and 7 DIM, at metritis diagnosis, and at 4 and 7 days after metritis diagnosis. Cows with metritis (MET; n = 17) were paired with counterparts without metritis (HTH) of a similar DIM and parity (n = 34). The uterine metabolome was evaluated using untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). Metabolomic data were analyzed using the MetaboAnalyst 5.0. Data were log-transformed and auto-scaled for normalization. Univariate analyses, including the fold-change, were performed to identify the metabolites linked to metritis development and its cure and principal component analysis and partial least squares discriminant analysis were performed to explain metabolite variance between animals developing or not developing metritis and being cured or not being cured of metritis. Comparing HTH with MET cows at calving, 12 metabolites were upregulated, and one was downregulated. At four and seven DIM, 51 and 74 metabolites, respectively, were altered between MET and HTH cows. After metritis development, three and five metabolites were upregulated in cows that were cured and in cows that received treatment and were cured, respectively. In all scenarios, the metabolites lignoceric, malic, and maleic acids, ornithine, and hypotaurine, which are associated with arginine/aminoacyl-tRNA biosynthesis and taurine/purine metabolism, were upregulated in HTH cows. Metritis was associated with changes in the uterine metabolome. Cows not being cured of metritis had changes in the uterus metabolome independent of receiving ceftiofur or remaining untreated. Metabolome analysis may be an important tool to understand the vaginal discharge changes during postpartum and the dynamics of metritis development and cures and help to identify biomarkers to predict metritis being cured. Full article

(This article belongs to the Special Issue The UC Davis West Coast Metabolomics Center Collection: From Compound Identification to Discoveries in Metabolism)

► Show Figures

Figure 1

14 pages, 9717 KiB

Open AccessArticle

Comparative Transcriptome Analysis Reveals the Underlying Response Mechanism to Salt Stress in Maize Seedling Roots

by Chen Zhang, Bin Chen, Ping Zhang, Qinghui Han, Guangwu Zhao and Fucheng Zhao

Metabolites 2023, 13(11), 1155; https://doi.org/10.3390/metabo13111155 - 16 Nov 2023

Cited by 2 | Viewed by 1621

Abstract

Crop growth and development can be impeded by salt stress, leading to a significant decline in crop yield and quality. This investigation performed a comparative analysis of the physiological responses of two maize inbred lines, namely L318 (CML115) and L323 (GEMS58), under salt-stress [...] Read more.

Crop growth and development can be impeded by salt stress, leading to a significant decline in crop yield and quality. This investigation performed a comparative analysis of the physiological responses of two maize inbred lines, namely L318 (CML115) and L323 (GEMS58), under salt-stress conditions. The results elucidated that CML115 exhibited higher salt tolerance compared with GEMS58. Transcriptome analysis of the root system revealed that DEGs shared by the two inbred lines were significantly enriched in the MAPK signaling pathway–plant and plant hormone signal transduction, which wield an instrumental role in orchestrating the maize response to salt-induced stress. Furthermore, the DEGs’ exclusivity to salt-tolerant genotypes was associated with sugar metabolism pathways, and these unique DEGs may account for the disparities in salt tolerance between the two genotypes. Meanwhile, we investigated the dynamic global transcriptome in the root systems of seedlings at five time points after salt treatment and compared transcriptome data from different genotypes to examine the similarities and differences in salt tolerance mechanisms of different germplasms. Full article

(This article belongs to the Special Issue Crop Nutrition Metabolism and Cultivation Physiology)

► Show Figures

Graphical abstract

12 pages, 968 KiB

Open AccessArticle

Assessing the Biological Mechanisms Linking Smoking Behavior and Cognitive Function: A Mediation Analysis of Untargeted Metabolomics

by Jerome J. Choi, Rebecca L. Koscik, Erin M. Jonaitis, Daniel J. Panyard, Autumn R. Morrow, Sterling C. Johnson, Corinne D. Engelman and Lauren L. Schmitz

Metabolites 2023, 13(11), 1154; https://doi.org/10.3390/metabo13111154 - 16 Nov 2023

Viewed by 1875

Abstract

(1) Smoking is the most significant preventable health hazard in the modern world. It increases the risk of vascular problems, which are also risk factors for dementia. In addition, toxins in cigarettes increase oxidative stress and inflammation, which have both been linked to [...] Read more.

(1) Smoking is the most significant preventable health hazard in the modern world. It increases the risk of vascular problems, which are also risk factors for dementia. In addition, toxins in cigarettes increase oxidative stress and inflammation, which have both been linked to the development of Alzheimer’s disease and related dementias (ADRD). This study identified potential mechanisms of the smoking–cognitive function relationship using metabolomics data from the longitudinal Wisconsin Registry for Alzheimer’s Prevention (WRAP). (2) 1266 WRAP participants were included to assess the association between smoking status and four cognitive composite scores. Next, untargeted metabolomic data were used to assess the relationships between smoking and metabolites. Metabolites significantly associated with smoking were then tested for association with cognitive composite scores. Total effect models and mediation models were used to explore the role of metabolites in smoking-cognitive function pathways. (3) Plasma N-acetylneuraminate was associated with smoking status Preclinical Alzheimer Cognitive Composite 3 (PACC3) and Immediate Learning (IMM). N-acetylneuraminate mediated 12% of the smoking-PACC3 relationship and 13% of the smoking-IMM relationship. (4) These findings provide links between previous studies that can enhance our understanding of potential biological pathways between smoking and cognitive function. Full article

(This article belongs to the Special Issue Metabolomics in Neurodegenerative Diseases)

► Show Figures

Figure 1

22 pages, 1081 KiB

Open AccessArticle

Diffuse Optical Monitoring of Cerebral Hemodynamics and Oxygen Metabolism during and after Cardiopulmonary Bypass: Hematocrit Correction and Neurological Vulnerability

by Emilie J. Benson, Danielle I. Aronowitz, Rodrigo M. Forti, Alec Lafontant, Nicolina R. Ranieri, Jonathan P. Starr, Richard W. Melchior, Alistair Lewis, Jharna Jahnavi, Jake Breimann, Bohyun Yun, Gerard H. Laurent, Jennifer M. Lynch, Brian R. White, J. William Gaynor, Daniel J. Licht, Arjun G. Yodh, Todd J. Kilbaugh, Constantine D. Mavroudis, Wesley B. Baker and Tiffany S. Ko Show full author list Hide full author list

Metabolites 2023, 13(11), 1153; https://doi.org/10.3390/metabo13111153 - 16 Nov 2023

Cited by 2 | Viewed by 1816

Abstract

Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical [...] Read more.

Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy to continuously measure CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO₂) in 27 neonatal swine before, during, and up to 24 h after CPB. Concurrently, we sampled cerebral microdialysis biomarkers of metabolic distress (lactate–pyruvate ratio) and injury (glycerol). We applied a novel theoretical approach to correct for hematocrit variation during optical quantification of CBF in vivo. Without correction, a mean (95% CI) +53% (42, 63) increase in hematocrit resulted in a physiologically improbable +58% (27, 90) increase in CMRO₂ relative to baseline at CPB initiation; following correction, CMRO₂ did not differ from baseline at this timepoint. After CPB initiation, OEF increased but CBF and CMRO₂ decreased with CPB time; these temporal trends persisted for 0–8 h following CPB and coincided with a 48% (7, 90) elevation of glycerol. The temporal trends and glycerol elevation resolved by 8–24 h. The hematocrit correction improved quantification of cerebral physiologic trends that precede and coincide with neurological injury following CPB. Full article

(This article belongs to the Special Issue Neurometabolic Monitoring and Imaging in Pediatric Critical Care)

► Show Figures

Figure 1

15 pages, 1052 KiB

Open AccessReview

The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension

by Lan Ye, Bing Wang, Hu Xu and Xiaoyan Zhang

Metabolites 2023, 13(11), 1152; https://doi.org/10.3390/metabo13111152 - 16 Nov 2023

Cited by 4 | Viewed by 2292

Abstract

Mild-to-moderate pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). It is characterized by narrowing and thickening of the pulmonary arteries, resulting in increased pulmonary vascular resistance (PVR) and ultimately leading to right ventricular dysfunction. Pulmonary vascular remodeling in [...] Read more.

Mild-to-moderate pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). It is characterized by narrowing and thickening of the pulmonary arteries, resulting in increased pulmonary vascular resistance (PVR) and ultimately leading to right ventricular dysfunction. Pulmonary vascular remodeling in COPD is the main reason for the increase of pulmonary artery pressure (PAP). The pathogenesis of PH in COPD is complex and multifactorial, involving chronic inflammation, hypoxia, and oxidative stress. To date, prostacyclin and its analogues are widely used to prevent PH progression in clinical. These drugs have potent anti-proliferative, anti-inflammatory, and stimulating endothelial regeneration properties, bringing therapeutic benefits to the slowing, stabilization, and even some reversal of vascular remodeling. As another well-known and extensively researched prostaglandins, prostaglandin E2 (PGE2) and its downstream signaling have been found to play an important role in various biological processes. Emerging evidence has revealed that PGE2 and its receptors (i.e., EP1–4) are involved in the regulation of pulmonary vascular homeostasis and remodeling. This review focuses on the research progress of the PGE2 signaling pathway in PH and discusses the possibility of treating PH based on the PGE2 signaling pathway. Full article

(This article belongs to the Special Issue Metabolic Disorders in Chronic Obstructive Pulmonary Disease and Atherosclerosis)

► Show Figures

Figure 1

15 pages, 5474 KiB

Open AccessArticle

The Mechanism of Mori Folium and Eucommiae Cortex against Cyclophosphamide-Induced Immunosuppression Integrating Network Pharmacology, Molecular Docking, Molecular Dynamics Simulations, and Experimental Validation

by Jinde Liu, Qiao Rong, Chunxiao Zhang, Ali Tariq, Lin Li, Yongning Wu and Feifei Sun

Metabolites 2023, 13(11), 1151; https://doi.org/10.3390/metabo13111151 - 15 Nov 2023

Cited by 2 | Viewed by 2268

Abstract

It has been reported that Mori Folium (MF) and Eucommiae Cortex (EC) exhibit pharmacological effects in the treatment of immunosuppression. However, the mechanism of MF and EC against immunosuppression remains unclear. This study aims to explore the mechanism of action of MF and [...] Read more.

It has been reported that Mori Folium (MF) and Eucommiae Cortex (EC) exhibit pharmacological effects in the treatment of immunosuppression. However, the mechanism of MF and EC against immunosuppression remains unclear. This study aims to explore the mechanism of action of MF and EC for the treatment of immunosuppression through network pharmacology, molecular docking, molecular dynamics simulations and animal experiments. As a result, 11 critical components, 9 hub targets, and related signaling pathways in the treatment of immunosuppression were obtained based on network pharmacology. The molecular docking suggested that 11 critical components exhibited great binding affinity to 9 hub targets of immunosuppression. The molecular dynamics simulations results showed that (-)-tabernemontanine-AR, beta-sitosterol-AR and Dehydrodieugenol-HSP90AA1 complexes are stably bound. Additionally, in the animal experiments, the treated group results compared to the control group suggest that MF and EC have a significant effect on the treatment of immunosuppression. Therefore, MF and EC treatment for immunosuppression may take effects in a multi-component, multi-target, and multi-pathway manner. The results herein may provide novel insights into the treatment of immunosuppression in humans. Full article

(This article belongs to the Section Cell Metabolism)

► Show Figures

Graphical abstract

14 pages, 2398 KiB

Open AccessArticle

Mass Spectrometry Chromatography-Based Metabolomics: The Effect of Long-Term Aerobic Exercise on Learning Ability and the Metabolism of Intestinal Contents in Mice with Alzheimer’s Disease

by Xue Li, Yuanting Zhang, Xianyi Ding, Yu Jin, Changling Wei and Jisheng Xu

Metabolites 2023, 13(11), 1150; https://doi.org/10.3390/metabo13111150 - 14 Nov 2023

Viewed by 1639

Abstract

This study aimed to investigate the effect of long-term aerobic exercise on the metabolism of intestinal contents in APP/PS1 mice was studied using a non-targeted metabolomics technique based on high-performance liquid chromatography-mass spectrometry (HPLC-MS) coupling, providing a theoretical basis for exercise to regulate [...] Read more.

This study aimed to investigate the effect of long-term aerobic exercise on the metabolism of intestinal contents in APP/PS1 mice was studied using a non-targeted metabolomics technique based on high-performance liquid chromatography-mass spectrometry (HPLC-MS) coupling, providing a theoretical basis for exercise to regulate the metabolism of Alzheimer’s disease (AD) organisms. Three-month-old male C57BL/6JNju mice, six wild-type (NC, n = 6); 12 APP/PS1 double transgenic species in total, were randomly divided into AD model (AM, n = 6) and AD model exercise (AE, n = 6) groups. The mice in the NC group were fed naturally, the mice in the AM group were statically placed on a running platform, and the mice in the AE group received a 20-week long-term moderate intensity running platform exercise intervention. Following the exercise intervention, the cecum contents of the mice in each group were collected and analyzed using the HPLC-MS technique, with those meeting both variable important in projection (VIP)> 1.5 and p < 0.05 being screened as differential metabolites. A total of 32 different metabolites were detected between the AM and NC groups, with 19 up-regulated in the AM group such as phosphatidic acid (PA) (18:4(6Z,9Z,12Z,15Z)/21:0) and 13 down-regulated in the AM group, such as 4,8-dimethylnonanoyl, compared to the NC group; 98 different metabolites were found between the AM and AE groups, 41 of which were upregulated such as Lyso phosphatidylcholine (LysoPC) and 57 of which were downregulated compared to the AM group such as Phosphatidylinositol (PI). The regulation of linoleic acid metabolism, glycerophospholipid metabolism, bile secretion, phenylalanine metabolism, and other pathways was predominantly regulated by nine metabolites, which were subsequently identified as indicators of exercise intervention to enhance metabolism in AD mice. The metabolomic technique can identify the metabolic problems of intestinal contents in AD mice and initially screen the biomarkers of exercise to improve the metabolic disorders in AD. These findings can help us better understand the impact of aerobic exercise on AD metabolism. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

► Show Figures

Graphical abstract

15 pages, 4227 KiB

Open AccessArticle

Methionine Promotes Milk Protein Synthesis via the PI3K-mTOR Signaling Pathway in Human Mammary Epithelial Cells

by Peizhi Li, Xibi Fang, Guijie Hao, Xiaohui Li, Yue Cai, Yuhao Yan, Liting Zan, Runjun Yang and Boqun Liu

Metabolites 2023, 13(11), 1149; https://doi.org/10.3390/metabo13111149 - 14 Nov 2023

Viewed by 1962

Abstract

Breast milk is widely considered to be the most natural, safe, and complete food for infants. However, current breastfeeding rates fall short of the recommendations established by the World Health Organization. Despite this, there are few studies that have focused on the promotion [...] Read more.

Breast milk is widely considered to be the most natural, safe, and complete food for infants. However, current breastfeeding rates fall short of the recommendations established by the World Health Organization. Despite this, there are few studies that have focused on the promotion of human lactation through nutrient supplementation. Therefore, the aim of this study was to investigate the effect of methionine on milk synthesis in human mammary epithelial cells (MCF-10A cells) and to explore the underlying mechanisms. To achieve this, MCF-10A cells were cultured with varying concentrations of methionine, ranging from 0 to 1.2 mM. Our results indicated that 0.6 mM of methionine significantly promoted the synthesis of milk protein. An RNA-seq analysis revealed that methionine acted through the PI3K pathway. This finding was validated through real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. In addition, PI3K inhibition assays confirmed that methionine upregulated the expression of both mTOR and p-mTOR through activation of PI3K. Taken together, these findings suggest that methionine positively regulates milk protein synthesis in MCF-10A cells through the PI3K-mTOR signaling pathway. Full article

(This article belongs to the Special Issue Insights into the Metabolic Absorption of Bioactive Peptides Derived from Food Sources)

► Show Figures

Figure 1

26 pages, 6543 KiB

Open AccessArticle

Elicitor-Driven Defense Mechanisms: Shielding Cotton Plants against the Onslaught of Cotton Leaf Curl Multan Virus (CLCuMuV) Disease

by Muhammad Fahad Khan, Ummad Ud Din Umar, Abdulwahed Fahad Alrefaei and Muhammad Junaid Rao

Metabolites 2023, 13(11), 1148; https://doi.org/10.3390/metabo13111148 - 12 Nov 2023

Cited by 1 | Viewed by 1650

Abstract

Salicylic acid (SA), benzothiadiazole (BTH), and methyl jasmonate (MeJA) are potential elicitors found in plants, playing a crucial role against various biotic and abiotic stresses. The systemic acquired resistance (SAR) mechanism was evaluated in cotton plants for the suppression of Cotton leaf curl [...] Read more.

Salicylic acid (SA), benzothiadiazole (BTH), and methyl jasmonate (MeJA) are potential elicitors found in plants, playing a crucial role against various biotic and abiotic stresses. The systemic acquired resistance (SAR) mechanism was evaluated in cotton plants for the suppression of Cotton leaf curl Multan Virus (CLCuMuV) by the exogenous application of different elicitors. Seven different treatments of SA, MeJA, and BTH were applied exogenously at different concentrations and combinations. In response to elicitors treatment, enzymatic activities such as SOD, POD, CAT, PPO, PAL, β–1,3 glucanse, and chitinase as biochemical markers for resistance were determined from virus-inoculated and uninoculated cotton plants of susceptible and tolerant varieties, respectively. CLCuMuV was inoculated on cotton plants by whitefly (Bemesia tabaci biotype Asia II-1) and detected by PCR using specific primers for the coat protein region and the Cotton leaf curl betasatellite (CLCuMuBV)-associated component of CLCuMuV. The development of disease symptoms was observed and recorded on treated and control plants. The results revealed that BTH applied at a concentration of 1.1 mM appeared to be the most effective treatment for suppressing CLCuMuV disease in both varieties. The enzymatic activities in both varieties were not significantly different, and the disease was almost equally suppressed in BTH-treated cotton plants following virus inoculation. The beta satellite and coat protein regions of CLCuMuV were not detected by PCR in the cotton plants treated with BTH at either concentration. Among all elicitors, 1.1 mM BTH was proven to be the best option for inducing resistance after the onset of CLCuMuV infection and hence it could be part of the integrated disease management program against Cotton leaf curl virus. Full article

(This article belongs to the Special Issue Plant Secondary Metabolites Biosynthesis, Biological Activities and Transcriptional Regulation in Response to Abiotic/Biotic Stresses)

► Show Figures

Graphical abstract

13 pages, 2104 KiB

Open AccessArticle

Metabolomic Profiling of Second-Trimester Amniotic Fluid for Predicting Preterm Delivery: Insights from NMR Analysis

by Charalampos Kolvatzis, Paris Christodoulou, Ioannis Kalogiannidis, Konstantinos Tsiantas, Ioannis Tsakiridis, Charikleia Kyrkou, Antigoni Cheilari, Nikolaos S. Thomaidis, Panagiotis Zoumpoulakis, Apostolos Athanasiadis and Alexandra-Maria Michaelidou

Metabolites 2023, 13(11), 1147; https://doi.org/10.3390/metabo13111147 - 12 Nov 2023

Cited by 1 | Viewed by 1798

Abstract

Preterm delivery (PTD) is a notable pregnancy complication, affecting one out of every ten births. This study set out to investigate whether analyzing the metabolic composition of amniotic fluid (AF) collected from pregnant women during the second trimester of pregnancy could offer valuable [...] Read more.

Preterm delivery (PTD) is a notable pregnancy complication, affecting one out of every ten births. This study set out to investigate whether analyzing the metabolic composition of amniotic fluid (AF) collected from pregnant women during the second trimester of pregnancy could offer valuable insights into prematurity. The research employed ¹H–NMR metabolomics to examine AF samples obtained from 17 women who gave birth prematurely (between 29⁺⁰ and 36⁺⁵ weeks of gestation) and 43 women who delivered at full term. The application of multivariate analysis revealed metabolites (dimethylglycine, glucose, myo-inositol, and succinate) that can serve as possible biomarkers for the prognosis and early diagnosis of preterm delivery. Additionally, pathway analysis unveiled the most critical metabolic pathways relevant to our research hypothesis. In summary, these findings suggest that the metabolic composition of AF in the second trimester can be a potential indicator for identifying biomarkers associated with the risk of PTD. Full article

(This article belongs to the Special Issue Preclinical and Clinical Application of Metabolomics in Medicine)

► Show Figures

Figure 1

17 pages, 2119 KiB

Open AccessProtocol

Sphingolipids in Childhood Asthma and Obesity (SOAP Study): A Protocol of a Cross-Sectional Study

by Belavendra Antonisamy, Harshita Shailesh, Yahya Hani, Lina Hayati M. Ahmed, Safa Noor, Salma Yahya Ahmed, Mohamed Alfaki, Abidan Muhayimana, Shana Sunny Jacob, Saroja Kotegar Balayya, Oleksandr Soloviov, Li Liu, Lisa Sara Mathew, Kun Wang, Sara Tomei, Alia Al Massih, Rebecca Mathew, Mohammed Yousuf Karim, Manjunath Ramanjaneya, Stefan Worgall and Ibrahim A. Janahi Show full author list Hide full author list

Metabolites 2023, 13(11), 1146; https://doi.org/10.3390/metabo13111146 - 11 Nov 2023

Viewed by 2026

Abstract

Asthma and obesity are two of the most common chronic conditions in children and adolescents. There is increasing evidence that sphingolipid metabolism is altered in childhood asthma and is linked to airway hyperreactivity. Dysregulated sphingolipid metabolism is also reported in obesity. However, the [...] Read more.

Asthma and obesity are two of the most common chronic conditions in children and adolescents. There is increasing evidence that sphingolipid metabolism is altered in childhood asthma and is linked to airway hyperreactivity. Dysregulated sphingolipid metabolism is also reported in obesity. However, the functional link between sphingolipid metabolism, asthma, and obesity is not completely understood. This paper describes the protocol of an ongoing study on sphingolipids that aims to examine the pathophysiology of sphingolipids in childhood asthma and obesity. In addition, this study aims to explore the novel biomarkers through a comprehensive multi-omics approach including genomics, genome-wide DNA methylation, RNA-Seq, microRNA (miRNA) profiling, lipidomics, metabolomics, and cytokine profiling. This is a cross-sectional study aiming to recruit 440 children from different groups: children with asthma and normal weight (n = 100), asthma with overweight or obesity (n = 100), overweight or obesity (n = 100), normal weight (n = 70), and siblings of asthmatic children with normal weight, overweight, or obesity (n = 70). These participants will be recruited from the pediatric pulmonology, pediatric endocrinology, and general pediatric outpatient clinics at Sidra Medicine, Doha, Qatar. Information will be obtained from self-reported questionnaires on asthma, quality of life, food frequency (FFQ), and a 3-day food diary that are completed by the children and their parents. Clinical measurements will include anthropometry, blood pressure, biochemistry, bioelectrical impedance, and pulmonary function tests. Blood samples will be obtained for sphingolipid analysis, serine palmitoyltransferase (SPT) assay, whole-genome sequencing (WGS), genome-wide DNA methylation study, RNA-Seq, miRNA profiling, metabolomics, lipidomics, and cytokine analysis. Group comparisons of continuous outcome variables will be carried out by a one-way analysis of variance or the Kruskal–Wallis test using an appropriate pairwise multiple comparison test. The chi-squared test or a Fisher’s exact test will be used to test the associations between categorical variables. Finally, multivariate analysis will be carried out to integrate the clinical data with multi-omics data. This study will help us to understand the role of dysregulated sphingolipid metabolism in obesity and asthma. In addition, the multi-omics data from the study will help to identify novel genetic and epigenetic signatures, inflammatory markers, and mechanistic pathways that link asthma and obesity in children. Furthermore, the integration of clinical and multi-omics data will help us to uncover the potential interactions between these diseases and to offer a new paradigm for the treatment of pediatric obesity-associated asthma. Full article

(This article belongs to the Special Issue Advanced Metabolomics and Lipidomics Approaches in Studying Human Diseases)

► Show Figures

Figure 1

14 pages, 789 KiB

Open AccessReview

Modeling Red Blood Cell Metabolism in the Omics Era

by Alicia Key, Zachary Haiman, Bernhard O. Palsson and Angelo D’Alessandro

Metabolites 2023, 13(11), 1145; https://doi.org/10.3390/metabo13111145 - 11 Nov 2023

Cited by 1 | Viewed by 3182

Abstract

Red blood cells (RBCs) are abundant (more than 80% of the total cells in the human body), yet relatively simple, as they lack nuclei and organelles, including mitochondria. Since the earliest days of biochemistry, the accessibility of blood and RBCs made them an [...] Read more.

Red blood cells (RBCs) are abundant (more than 80% of the total cells in the human body), yet relatively simple, as they lack nuclei and organelles, including mitochondria. Since the earliest days of biochemistry, the accessibility of blood and RBCs made them an ideal matrix for the characterization of metabolism. Because of this, investigations into RBC metabolism are of extreme relevance for research and diagnostic purposes in scientific and clinical endeavors. The relative simplicity of RBCs has made them an eligible model for the development of reconstruction maps of eukaryotic cell metabolism since the early days of systems biology. Computational models hold the potential to deepen knowledge of RBC metabolism, but also and foremost to predict in silico RBC metabolic behaviors in response to environmental stimuli. Here, we review now classic concepts on RBC metabolism, prior work in systems biology of unicellular organisms, and how this work paved the way for the development of reconstruction models of RBC metabolism. Translationally, we discuss how the fields of metabolomics and systems biology have generated evidence to advance our understanding of the RBC storage lesion, a process of decline in storage quality that impacts over a hundred million blood units transfused every year. Full article

(This article belongs to the Section Bioinformatics and Data Analysis)

► Show Figures

Figure 1

17 pages, 4925 KiB

Open AccessArticle

Metabolic Features of a Novel Trichoderma asperellum YNQJ1002 with Potent Antagonistic Activity against Fusarium graminearum

by Huimin Ji, Ruohan Yu, Hongyi Liu, Hui Zhang, Xinhua Wang, Jie Chen and Yaqian Li

Metabolites 2023, 13(11), 1144; https://doi.org/10.3390/metabo13111144 - 11 Nov 2023

Viewed by 1679

Abstract

Trichoderma, a well-known and extensively studied fungal genus, has gained significant attention for its remarkable antagonistic abilities against a wide range of plant pathogens. In this study, a total of 108 Trichoderma isolates were screened through in vitro dual antagonistic assays and [...] Read more.

Trichoderma, a well-known and extensively studied fungal genus, has gained significant attention for its remarkable antagonistic abilities against a wide range of plant pathogens. In this study, a total of 108 Trichoderma isolates were screened through in vitro dual antagonistic assays and culture filtrate inhibition against Fusarium graminearum. Of these, the YNQJ1002 displayed noteworthy inhibitory activities along with thermal stability. To validate the metabolic differences between YNQJ1002 and GZLX3001 (with strong and weak antagonism, respectively), UPLC-TOF-MS/MS mass spectrometry was employed to analyze and compare the metabolite profiles. We identified 12 significantly up-regulated metabolites in YNQJ1002, which include compounds like Trigoneoside, Torvoside, trans,trans-hepta-2,4,6-trienoic acid, and Chamazulene. These metabolites are known for their antimicrobial properties or signaling roles as components of cell membranes. Enriched KEGG analysis revealed a significant enrichment in sphingolipid metabolism and linoleic acid metabolism, as well as autophagy. The results demonstrated that YNQJ1002’s abundance of antimicrobial substances, resulting from specific metabolic pathways, enhanced its superior antagonistic activity against F. graminearum. Finally, YNQJ1002 was identified using the ITS, tef1-1α, and rpb2 regions, with MIST system sequence matching confirming its classification within the species. Overall, we have obtained a novel strain, T. asperellum YNQJ1002, which is rich in metabolites and shows potential antagonistic activity against F. graminearum. This study has opened promising prospects for the development of innovative Trichoderma-derived antifungal compounds, featuring a unique mechanism against pathogens. Full article

(This article belongs to the Section Microbiology and Ecological Metabolomics)

► Show Figures

Figure 1

14 pages, 1908 KiB

Open AccessReview

Chikungunya Virus, Metabolism, and Circadian Rhythmicity Interplay in Phagocytic Cells

by Linamary Alvarez-García, F. Javier Sánchez-García, Mauricio Vázquez-Pichardo and M. Maximina Moreno-Altamirano

Metabolites 2023, 13(11), 1143; https://doi.org/10.3390/metabo13111143 - 11 Nov 2023

Viewed by 2159

Abstract

Chikungunya virus (CHIKV) is transmitted to humans by mosquitoes of the genus Aedes, causing the chikungunya fever disease, associated with inflammation and severe articular incapacitating pain. There has been a worldwide reemergence of chikungunya and the number of cases increased to 271,006 [...] Read more.

Chikungunya virus (CHIKV) is transmitted to humans by mosquitoes of the genus Aedes, causing the chikungunya fever disease, associated with inflammation and severe articular incapacitating pain. There has been a worldwide reemergence of chikungunya and the number of cases increased to 271,006 in 2022 in the Americas alone. The replication of CHIKV takes place in several cell types, including phagocytic cells. Monocytes and macrophages are susceptible to infection by CHIKV; at the same time, they provide protection as components of the innate immune system. However, in host–pathogen interactions, CHIKV might have the ability to alter the function of immune cells, partly by rewiring the tricarboxylic acid cycle. Some viral evasion mechanisms depend on the metabolic reprogramming of immune cells, and the cell metabolism is intertwined with circadian rhythmicity; thus, a circadian immunovirometabolism axis may influence viral pathogenicity. Therefore, analyzing the interplay between viral infection, circadian rhythmicity, and cellular metabolic reprogramming in human macrophages could shed some light on the new field of immunovirometabolism and eventually contribute to the development of novel drugs and therapeutic approaches based on circadian rhythmicity and metabolic reprogramming. Full article

(This article belongs to the Special Issue Novel Approaches for Metabolomics in Drugs and Biomarkers Discovery)

► Show Figures

Graphical abstract

15 pages, 3302 KiB

Open AccessArticle

Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study

by Mohammad M. Banoei, Lauralyn A. McIntyre, Duncan J. Stewart, Shirley H. J. Mei, David Courtman, Irene Watpool, John Granton, John Marshall, Claudia dos Santos, Keith R. Walley, Kenny Schlosser, Dean A. Fergusson, Brent W. Winston, on behalf of Canadian Critical Care Trials Group (CCCTG) and on behalf of Canadian Critical Care Translational Biology Group (CCCTBG)

Metabolites 2023, 13(11), 1142; https://doi.org/10.3390/metabo13111142 - 10 Nov 2023

Viewed by 1789

Abstract

Sepsis is the result of an uncontrolled host inflammatory response to infection that may lead to septic shock with multiorgan failure and a high mortality rate. There is an urgent need to improve early diagnosis and to find markers identifying those who will [...] Read more.

Sepsis is the result of an uncontrolled host inflammatory response to infection that may lead to septic shock with multiorgan failure and a high mortality rate. There is an urgent need to improve early diagnosis and to find markers identifying those who will develop septic shock and certainly a need to develop targeted treatments to prevent septic shock and its high mortality. Herein, we explore metabolic alterations due to mesenchymal stromal cell (MSC) treatment of septic shock. The clinical findings for this study were already reported; MSC therapy was well-tolerated and safe in patients in this phase I clinical trial. In this exploratory metabolomics study, 9 out of 30 patients received an escalating dose of MSC treatment, while 21 patients were without MSC treatment. Serum metabolomics profiling was performed to detect and characterize metabolite changes due to MSC treatment and to help determine the sample size needed for a phase II clinical trial and to define a metabolomic response to MSC treatment. Serum metabolites were measured using ¹H-NMR and HILIC-MS at times 0, 24 and 72 h after MSC infusion. The results demonstrated the significant impact of MSC treatment on serum metabolic changes in a dose- and time-dependent manner compared to non-MSC-treated septic shock patients. This study suggests that plasma metabolomics can be used to assess the response to MSC therapy and that treatment-related metabolomics effects can be used to help determine the sample size needed in a phase II trial. As this study was not powered to detect outcome, how the treatment-induced metabolomic changes described in this study of MSC-treated septic shock patients are related to outcomes of septic shock in the short and long term will need to be explored in a larger adequately powered phase II clinical trial. Full article

(This article belongs to the Section Cell Metabolism)

► Show Figures

Figure 1

14 pages, 2506 KiB

Open AccessArticle

PPA1 Deficiency Causes a Deranged Galactose Metabolism Recognizable in Neonatal Screening

by Melanie T. Achleitner, Judith J. M. Jans, Laura Ebner, Johannes Spenger, Vassiliki Konstantopoulou, René G. Feichtinger, Karin Brugger, Doris Mayr, Ron A. Wevers, Christian Thiel, Saskia B. Wortmann and Johannes A. Mayr

Metabolites 2023, 13(11), 1141; https://doi.org/10.3390/metabo13111141 - 10 Nov 2023

Viewed by 1670

Abstract

Two siblings showed increased galactose and galactose-related metabolites in neonatal screening. Diagnostic workup did not reveal abnormalities in any of the known disease-causing enzymes involved in galactose metabolism. Using whole-exome sequencing, we identified a homozygous missense variant in PPA1 encoding the cytosolic pyrophosphatase [...] Read more.

Two siblings showed increased galactose and galactose-related metabolites in neonatal screening. Diagnostic workup did not reveal abnormalities in any of the known disease-causing enzymes involved in galactose metabolism. Using whole-exome sequencing, we identified a homozygous missense variant in PPA1 encoding the cytosolic pyrophosphatase 1 (PPA1), c.557C>T (p.Thr186Ile). The enzyme activity of PPA1 was determined using a colorimetric assay, and the protein content was visualized via western blotting in skin fibroblasts from one of the affected individuals. The galactolytic activity of the affected fibroblasts was determined by measuring extracellular acidification with a Seahorse XFe96 analyzer. PPA1 activity decreased to 22% of that of controls in the cytosolic fraction of homogenates from patient fibroblasts. PPA1 protein content decreased by 50% according to western blot analysis, indicating a reduced stability of the variant protein. The extracellular acidification rate was reduced in patient fibroblasts when galactose was used as a substrate. Untargeted metabolomics of blood samples revealed an elevation of other metabolites related to pyrophosphate metabolism. Besides hyperbilirubinemia in the neonatal period in one child, both children were clinically unremarkable at the ages of 3 and 14 years, respectively. We hypothesize that the observed metabolic derangement is a possible mild manifestation of PPA1 deficiency. Unresolved abnormalities in galactosemia screening might result in the identification of more individuals with PPA1 deficiency, a newly discovered inborn metabolic disorder (IMD). Full article

(This article belongs to the Topic Metabolism and Health)

► Show Figures

Graphical abstract

14 pages, 787 KiB

Open AccessArticle

Cord Blood Metabolite Profiles and Their Association with Autistic Traits in Childhood

by Christin S. Kaupper, Sophia M. Blaauwendraad, Charlotte A. M. Cecil, Rosa H. Mulder, Romy Gaillard, Romy Goncalves, Ingo Borggraefe, Berthold Koletzko and Vincent W. V. Jaddoe

Metabolites 2023, 13(11), 1140; https://doi.org/10.3390/metabo13111140 - 9 Nov 2023

Viewed by 1921

Abstract

Autism Spectrum Disorder (ASD) is a diverse neurodevelopmental condition. Gene–environmental interactions in early stages of life might alter metabolic pathways, possibly contributing to ASD pathophysiology. Metabolomics may serve as a tool to identify underlying metabolic mechanisms contributing to ASD phenotype and could help [...] Read more.

Autism Spectrum Disorder (ASD) is a diverse neurodevelopmental condition. Gene–environmental interactions in early stages of life might alter metabolic pathways, possibly contributing to ASD pathophysiology. Metabolomics may serve as a tool to identify underlying metabolic mechanisms contributing to ASD phenotype and could help to unravel its complex etiology. In a population-based, prospective cohort study among 783 mother–child pairs, cord blood serum concentrations of amino acids, non-esterified fatty acids, phospholipids, and carnitines were obtained using liquid chromatography coupled with tandem mass spectrometry. Autistic traits were measured at the children’s ages of 6 (n = 716) and 13 (n = 648) years using the parent-reported Social Responsiveness Scale. Lower cord blood concentrations of SM.C.39.2 and NEFA16:1/16:0 were associated with higher autistic traits among 6-year-old children, adjusted for sex and age at outcome. After more stringent adjustment for confounders, no significant associations of cord blood metabolites and autistic traits at ages 6 and 13 were detected. Differences in lipid metabolism (SM and NEFA) might be involved in ASD-related pathways and are worth further investigation. Full article

► Show Figures

Figure 1

20 pages, 4078 KiB

Open AccessArticle

Matrix Selection for the Visualization of Small Molecules and Lipids in Brain Tumors Using Untargeted MALDI-TOF Mass Spectrometry Imaging

by Tianyao Lu, Lutz Freytag, Vinod K. Narayana, Zachery Moore, Shannon J. Oliver, Adam Valkovic, Brunda Nijagal, Amanda L. Peterson, David P. de Souza, Malcolm J. McConville, James R. Whittle, Sarah A. Best and Saskia Freytag

Metabolites 2023, 13(11), 1139; https://doi.org/10.3390/metabo13111139 - 9 Nov 2023

Cited by 2 | Viewed by 2515

Abstract

Matrix-assisted laser desorption/ionization mass spectrometry imaging allows for the study of metabolic activity in the tumor microenvironment of brain cancers. The detectable metabolites within these tumors are contingent upon the choice of matrix, deposition technique, and polarity setting. In this study, we compared [...] Read more.

Matrix-assisted laser desorption/ionization mass spectrometry imaging allows for the study of metabolic activity in the tumor microenvironment of brain cancers. The detectable metabolites within these tumors are contingent upon the choice of matrix, deposition technique, and polarity setting. In this study, we compared the performance of three different matrices, two deposition techniques, and the use of positive and negative polarity in two different brain cancer types and across two species. Optimal combinations were confirmed by a comparative analysis of lipid and small-molecule abundance by using liquid chromatography–mass spectrometry and RNA sequencing to assess differential metabolites and enzymes between normal and tumor regions. Our findings indicate that in the tumor-bearing brain, the recrystallized α-cyano-4-hydroxycinnamic acid matrix with positive polarity offered superior performance for both detected metabolites and consistency with other techniques. Beyond these implications for brain cancer, our work establishes a workflow to identify optimal matrices for spatial metabolomics studies. Full article

► Show Figures

Graphical abstract

46 pages, 20973 KiB

Open AccessArticle

The Metabolite Profiling of Aspergillus fumigatus KMM4631 and Its Co-Cultures with Other Marine Fungi

by Anton N. Yurchenko, Liliana E. Nesterenko, Roman S. Popov, Natalya N. Kirichuk, Viktoria E. Chausova, Ekaterina A. Chingizova, Marina P. Isaeva and Ekaterina A. Yurchenko

Metabolites 2023, 13(11), 1138; https://doi.org/10.3390/metabo13111138 - 8 Nov 2023

Cited by 1 | Viewed by 2269

Abstract

An Aspergillus fumigatus KMM 4631 strain was previously isolated from a Pacific soft coral Sinularia sp. sample and was found to be a source of a number of bioactive secondary metabolites. The aims of this work are the confirmation of this strain’ identification [...] Read more.

An Aspergillus fumigatus KMM 4631 strain was previously isolated from a Pacific soft coral Sinularia sp. sample and was found to be a source of a number of bioactive secondary metabolites. The aims of this work are the confirmation of this strain’ identification based on ITS, BenA, CaM, and RPB2 regions/gene sequences and the investigation of secondary metabolite profiles of Aspergillus fumigatus KMM 4631 culture and its co-cultures with Penicillium hispanicum KMM 4689, Amphichorda sp. KMM 4639, Penicillium sp. KMM 4672, and Asteromyces cruciatus KMM 4696 from the Collection of Marine Microorganisms (PIBOC FEB RAS, Vladivostok, Russia). Moreover, the DPPH-radical scavenging activity, urease inhibition, and cytotoxicity of joint fungal cultures’ extracts on HepG2 cells were tested. The detailed UPLC MS qTOF investigation resulted in the identification and annotation of indolediketopiperazine, quinazoline, and tryptoquivaline-related alkaloids as well as a number of polyketides (totally 20 compounds) in the extract of Aspergillus fumigatus KMM 4631. The metabolite profiles of the co-cultures of A. fumigatus with Penicillium hispanicum, Penicillium sp., and Amphichorda sp. were similar to those of Penicillium hispanicum, Penicillium sp., and Amphichorda sp. monocultures. The metabolite profile of the co-culture of A. fumigatus with Asteromyces cruciatus differed from that of each monoculture and may be more promising for the isolation of new compounds. Full article

(This article belongs to the Special Issue Marine Microbes Related Metabolic Studies)

► Show Figures

Graphical abstract

13 pages, 4401 KiB

Open AccessArticle

Depuration and Starvation Regulate Metabolism and Improve Flesh Quality of Yellow Catfish (Pelteobagrus fulvidraco)

by Ya Zhou, Yang Xiong, Xianlin He, Xiaoshu Xue, Guo Tang and Jie Mei

Metabolites 2023, 13(11), 1137; https://doi.org/10.3390/metabo13111137 - 8 Nov 2023

Cited by 1 | Viewed by 2216

Abstract

Fat deposition and off-flavor in the muscle are the main problems affecting flesh quality in aquaculture fish, especially in catfish, leading to low acceptability and reduced market price. Yellow catfish is an important aquaculture fish in China. In this study, 40 days of [...] Read more.

Fat deposition and off-flavor in the muscle are the main problems affecting flesh quality in aquaculture fish, especially in catfish, leading to low acceptability and reduced market price. Yellow catfish is an important aquaculture fish in China. In this study, 40 days of depuration and starvation treatment were explored to improve the muscle quality of aquaculture yellow catfish. After depuration and starvation, the body weight, condition factor (CF) and mesenteric fat index (MFI) were all significantly decreased 20 days after treatment. The metabolomic profiles in muscle were characterized to analyze the muscle quality in yellow catfish. The results showed that the content of ADP, AMP, IMP, glutamic acid and taurine were significantly increased between 20 and 40 days post-treatment in the muscle of yellow catfish during the treatment, which was positively associated with the flesh tenderness and quality. In contrast, aldehydes and ketones associated with off-flavors and corticosterone associated with bitter taste were all decreased at 20 days post-treatment. Considering the balance of body weight loss and flesh quality improvement, depuration and starvation for around 20 days is suitable for aquaculture yellow catfish. Our study not only provides an effective method to improve the flesh quality of aquaculture yellow catfish but also reveals the potential mechanism in this process. Full article

(This article belongs to the Section Food Metabolomics)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Metabolites, Volume 13, Issue 11 (November 2023) – 61 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI