Next Issue
Volume 13, March
Previous Issue
Volume 13, January
 
 

Metabolites, Volume 13, Issue 2 (February 2023) – 176 articles

Cover Story (view full-size image): The severity of the symptoms associated with COVID-19 is highly variable and has been associated with circulating amino acids. We studied a sample of 736 participants from the Biobanque Québécoise COVID-19, with symptoms classified as mild, moderate or severe. We assessed the association between circulating amino acids and the odds of presenting mild vs severe symptoms as well as their accuracy to predict adverse outcomes. Out of 20 amino acids tested, 16 were significantly associated with disease severity. Phenylalanine had a fair ability to predict the occurrence of adverse outcomes, similar to traditionally measured laboratory variables. Overall, severe COVID-19 symptoms are associated with altered levels of many circulating amino acids hinting at global changes in nitrogen metabolism.  View this paper
  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Select all
Export citation of selected articles as:
12 pages, 1308 KiB  
Article
Concentrations of Plasma Amino Acids and Neurotransmitters in Participants with Functional Gut Disorders and Healthy Controls
Metabolites 2023, 13(2), 313; https://doi.org/10.3390/metabo13020313 - 20 Feb 2023
Cited by 2 | Viewed by 1383
Abstract
Amino acids are important in several biochemical pathways as precursors to neurotransmitters which impact biological processes previously linked to functional gastrointestinal disorders (FGIDs). Dietary protein consumption, metabolic host processes, and the gut microbiome can influence the plasma concentration of amino acids and neurotransmitters, [...] Read more.
Amino acids are important in several biochemical pathways as precursors to neurotransmitters which impact biological processes previously linked to functional gastrointestinal disorders (FGIDs). Dietary protein consumption, metabolic host processes, and the gut microbiome can influence the plasma concentration of amino acids and neurotransmitters, and their uptake by tissues. The aim of this analysis was to quantify 19 proteogenic and 4 non-proteogenic amino acids and 19 neurotransmitters (including precursors and catabolites, herein referred to as neurotransmitters) to ascertain if their circulating concentrations differed between healthy participants and those with FGIDs. Plasma proteogenic and non-proteogenic amino acids and neurotransmitters were measured using ultra-performance liquid chromatography and liquid chromatography–mass spectrometry, respectively, from 165 participants (Rome IV: irritable bowel syndrome (IBS-constipation, IBS-diarrhea), functional constipation, functional diarrhea, and healthy controls). There were significant differences (p < 0.05) in pairwise comparisons between healthy controls and specific FGID groups for branched-chain amino acids (BCAAs), ornithine, and alpha-aminobutyric acid. No other significant differences were observed for the neurotransmitters or any other amino acids analyzed. Multivariate and bivariate correlation analyses between proteogenic and non-proteogenic amino acids and neurotransmitters for constipation (constipation (IBS-C and functional constipation) and phenotypes diarrhea (IBS-D and functional diarrhea)) and healthy controls suggested that associations between BCAAs, 5-hydroxytryptophan, and kynurenine in combination with tyrosine, 3,4-dihydroxyphenylalanine, and 3,4-dihydroxyphenylacetic acid and associations with gamma-aminobutyric acid, glutamate, asparagine, and serine are likely disrupted in FGID phenotypes. In conclusion, although correlations were evident between some proteogenic and non-proteogenic amino acids and neurotransmitters, the results showed minor concentration differences in plasma proteogenic and non-proteogenic amino acids, amino acid-derived metabolites, and neurotransmitters between FGID phenotypes and healthy controls. Full article
(This article belongs to the Section Nutrition and Metabolism)
Show Figures

Figure 1

10 pages, 971 KiB  
Article
Glucose-6-Phosphate Dehydrogenase Activity in Milk May Serve as a Non-Invasive Metabolic Biomarker of Energy Balance in Postpartum Dairy Cows
Metabolites 2023, 13(2), 312; https://doi.org/10.3390/metabo13020312 - 20 Feb 2023
Viewed by 1283
Abstract
Negative energy balance (EB) postpartum is associated with adverse outcomes in dairy cows; therefore, non-invasive biomarkers to measure EB are of particular interest. We determined whether specific metabolites, oxidative stress indicators, enzyme activity, and fatty acid (FA) profiles in milk can serve as [...] Read more.
Negative energy balance (EB) postpartum is associated with adverse outcomes in dairy cows; therefore, non-invasive biomarkers to measure EB are of particular interest. We determined whether specific metabolites, oxidative stress indicators, enzyme activity, and fatty acid (FA) profiles in milk can serve as indicators of negative EB. Forty-two multiparous Holstein dairy cows were divided at calving into 2 groups: one was milked 3 times daily and the other, twice a day for the first 30 d in milk (DIM). Cows were classified retrospectively as being in either negative EB (NEB, n = 19; the mean EB during the first 21 DIM were less than the overall median of −2.8 Mcal/d), or in positive EB (PEB, n = 21; the mean EB was ≥−2.8 Mcal/d). The daily milk yield, feed intake, and body weight were recorded individually. Blood samples were analyzed for metabolites and stress biomarkers. Milk samples were taken twice weekly from 5 to 45 DIM to analyze the milk solids, the FA profile, glucose, glucose-6-P (G6P), G6P-dehydrogenase (G6PDH) activity, malic and lactic acids, malondialdehyde (MDA), and oxygen radical antioxidant capacity (ORAC). The NEB cows produced 10.5% more milk, and consumed 7.6% less dry matter than the PEB cows. The plasma glucose concentration was greater and β-hydroxybutyrate was lower in the PEB vs. the NEB cows. The average concentrations of milk glucose, G6P, malic and lactic acids, and MDA did not differ between groups; however, the G6PDH activity was higher and ORAC tended to be higher in the milk of NEB vs. the PEB cows. The correlation between milk G6PDH activity and EB was significant (r = −0.39). The percentages of oleic acid and total unsaturated FA in milk were higher for the NEB vs. the PEB cows. These findings indicate that G6PDH activity in milk is associated with NEB and that it can serve as a non-invasive candidate biomarker of NEB in postpartum cows, that should be validated in future studies. Full article
(This article belongs to the Topic Biomarker Development and Application)
Show Figures

Figure 1

12 pages, 939 KiB  
Article
Prenatal SSRI Exposure Increases the Risk of Autism in Rodents via Aggravated Oxidative Stress and Neurochemical Changes in the Brain
Metabolites 2023, 13(2), 310; https://doi.org/10.3390/metabo13020310 - 20 Feb 2023
Cited by 1 | Viewed by 1606
Abstract
The mechanisms underlying selective serotonin reuptake inhibitor (SSRI) use during pregnancy as a major autism risk factor are unclear. Here, brain neurochemical changes following fluoxetine exposure and in an autism model were compared to determine the effects on autism risk. The study was [...] Read more.
The mechanisms underlying selective serotonin reuptake inhibitor (SSRI) use during pregnancy as a major autism risk factor are unclear. Here, brain neurochemical changes following fluoxetine exposure and in an autism model were compared to determine the effects on autism risk. The study was performed on neonatal male western albino rats which were divided into Groups one (control), two (propionic acid [PPA]-induced autism model), and three (prenatal SSRI-exposed newborn rats whose mothers were exposed to 5 mg/kg of fluoxetine over gestation days 10–20). SSRI (fluoxetine) induced significant neurochemical abnormalities in the rat brain by increasing lipid peroxide (MDA), Interferon-gamma (IFN-γ), and caspase-3 levels and by depleting Glutathione (GSH), Glutathione S-transferases (GST), Catalase, potassium (K+), and Creatine kinase (CK) levels, similarly to what has been discovered in the PPA model of autism when compared with control. Prenatal fluoxetine exposure plays a significant role in asset brain damage in newborns; further investigation of fluoxetine as an autism risk factor is thus warranted. Full article
(This article belongs to the Special Issue Complementary and Alternative Medicine in Autism Spectrum Disorders)
Show Figures

Graphical abstract

18 pages, 1884 KiB  
Review
Molnupiravir: A Versatile Prodrug against SARS-CoV-2 Variants
Metabolites 2023, 13(2), 309; https://doi.org/10.3390/metabo13020309 - 20 Feb 2023
Cited by 10 | Viewed by 3150
Abstract
The nucleoside analog β-D-N4-hydroxycytidine is the active metabolite of the prodrug molnupiravir and is accepted as an efficient drug against COVID-19. Molnupiravir targets the RNA-dependent RNA polymerase (RdRp) enzyme, which is responsible for replicating the viral genome during the replication process [...] Read more.
The nucleoside analog β-D-N4-hydroxycytidine is the active metabolite of the prodrug molnupiravir and is accepted as an efficient drug against COVID-19. Molnupiravir targets the RNA-dependent RNA polymerase (RdRp) enzyme, which is responsible for replicating the viral genome during the replication process of certain types of viruses. It works by disrupting the normal function of the RdRp enzyme, causing it to make mistakes during the replication of the viral genome. These mistakes can prevent the viral RNA from being transcribed, converted into a complementary DNA template, translated, or converted into a functional protein. By disrupting these crucial steps in the viral replication process, molnupiravir can effectively inhibit the replication of the virus and reduce its ability to cause disease. This review article sheds light on the impact of molnupiravir and its metabolite on SARS-CoV-2 variants of concern, such as delta, omicron, and hybrid/recombinant variants. The detailed mechanism and molecular interactions using molecular docking and dynamics have also been covered. The safety and tolerability of molnupiravir in patients with comorbidities have also been emphasized. Full article
(This article belongs to the Section Pharmacology and Drug Metabolism)
Show Figures

Figure 1

12 pages, 2141 KiB  
Article
Divergent Thyroid Hormone Levels in Plasma and Left Ventricle of the Heart in Compensated and Decompensated Cardiac Hypertrophy Induced by Chronic Adrenergic Stimulation in Mice
Metabolites 2023, 13(2), 308; https://doi.org/10.3390/metabo13020308 - 20 Feb 2023
Cited by 2 | Viewed by 1254
Abstract
Chronic hemodynamic overload of the heart induces ventricular hypertrophy that may be either compensatory or progress to decompensation and heart failure. The gradual impairment of ventricular function is, at least in part, the result of a reduction of cardiac thyroid-hormone (TH) action. Here, [...] Read more.
Chronic hemodynamic overload of the heart induces ventricular hypertrophy that may be either compensatory or progress to decompensation and heart failure. The gradual impairment of ventricular function is, at least in part, the result of a reduction of cardiac thyroid-hormone (TH) action. Here, we examined the proposed roles of increased cardiac expression of the TH-inactivating enzyme deiodinase type 3 (D3) and reduced plasma TH levels in diminishing cardiac TH levels. Using minipumps, mice were infused for one and two weeks with isoproterenol (ISO) alone or in combination with phenylephrine (PE). Remodeling of the heart induced by these adrenergic agonists was assessed by echocardiography. Left ventricular (LV) tissue and plasma TH levels (T4 and T3) were determined using liquid chromatography-tandem mass spectrometry. LV D3 activity was determined by conversion of radiolabeled substrate and quantification following HPLC. The results show that ISO induced compensated LV hypertrophy with maintained cardiac output. Plasma levels of T4 and T3 remained normal, but LV hormone levels were reduced by approximately 30% after two weeks, while LV D3 activity was not significantly increased. ISO + PE induced decompensated LV hypertrophy with diminished cardiac output. Plasma levels of T4 and T3 were substantially reduced after one and two weeks, together with a more than 50% reduction of hormone levels in the LV. D3 activity was increased after one week and returned to control levels after two weeks. These data show for the first time that relative to controls, decompensated LV hypertrophy with diminished cardiac output is associated with a greater reduction of cardiac TH levels than compensated hypertrophy with maintained cardiac output. LV D3 activity is unlikely to account for these reductions after two weeks in either condition. Whereas the mechanism of the mild reduction in compensated hypertrophy is unclear, changes in systemic TH homeostasis appear to determine the marked drop in LV TH levels and associated impairment of ventricular function in decompensated hypertrophy. Full article
(This article belongs to the Special Issue Metabolic Effects of the Intracellular Regulation of Thyroid Hormone)
Show Figures

Figure 1

18 pages, 3022 KiB  
Article
Expression Silencing of Mitogen-Activated Protein Kinase 8 Interacting Protein-1 Conferred Its Role in Pancreatic β-Cell Physiology and Insulin Secretion
Metabolites 2023, 13(2), 307; https://doi.org/10.3390/metabo13020307 - 20 Feb 2023
Cited by 1 | Viewed by 1535
Abstract
Mitogen-activated protein kinase 8 interacting protein-1 (MAPK8IP1) gene has been recognized as a susceptibility gene for diabetes. However, its action in the physiology of pancreatic β-cells is not fully understood. Herein, bioinformatics and genetic analyses on the publicly available database were performed to [...] Read more.
Mitogen-activated protein kinase 8 interacting protein-1 (MAPK8IP1) gene has been recognized as a susceptibility gene for diabetes. However, its action in the physiology of pancreatic β-cells is not fully understood. Herein, bioinformatics and genetic analyses on the publicly available database were performed to map the expression of the MAPK8IP1 gene in human pancreatic islets and to explore whether this gene contains any genetic variants associated with type 2 diabetes (T2D). Moreover, a series of functional experiments were executed in a rat insulinoma cell line (INS-1 832/13) to investigate the role of the Mapk8ip1 gene in β-cell function. Metabolic engineering using RNA-sequencing (RNA-seq) data confirmed higher expression levels of MAPK8IP1 in human islets compared to other metabolic tissues. Additionally, comparable expression of MAPK8IP1 expression was detected in sorted human endocrine cells. However, β-cells exhibited higher expression of MAPK8IP1 than ductal and PSC cells. Notably, MAPK8IP1 expression was reduced in diabetic islets, and the expression was positively correlated with insulin and the β-cell transcription factor PDX1 and MAFA. Using the TIGER portal, we found that one genetic variant, “rs7115753,” in the proximity of MAPK8IP1, passes the genome-wide significance for the association with T2D. Expression silencing of Mapk8ip1 by small interfering RNA (siRNA) in INS-1 cells reduced insulin secretion, glucose uptake rate, and reactive oxygen species (ROS) production. In contrast, insulin content, cell viability, and apoptosis without cytokines were unaffected. However, silencing of Mapk8ip1 reduced cytokines-induced apoptosis and downregulated the expression of several pancreatic β-cell functional markers including, Ins1, Ins2, Pdx1, MafA, Glut2, Gck, Insr, Vamp2, Syt5, and Cacna1a at mRNA and/or protein levels. Finally, we reported that siRNA silencing of Pdx1 resulted in the downregulation of MAPK8IP1 expression in INS-1 cells. In conclusion, our findings confirmed that MAPK8IP1 is an important component of pancreatic β-cell physiology and insulin secretion. Full article
Show Figures

Figure 1

16 pages, 1271 KiB  
Review
Hypomagnesemia as a Risk Factor and Accelerator for Vascular Aging in Diabetes Mellitus and Chronic Kidney Disease
Metabolites 2023, 13(2), 306; https://doi.org/10.3390/metabo13020306 - 19 Feb 2023
Cited by 2 | Viewed by 1871
Abstract
The age-old axiom that one is as old as his or her vessels are, calls for ongoing critical re-examination of modifiable risk factors of accelerated vascular ageing in chronic kidney diseases. Attempts to modulate vascular risk with cholesterol-lowering agents have largely failed in [...] Read more.
The age-old axiom that one is as old as his or her vessels are, calls for ongoing critical re-examination of modifiable risk factors of accelerated vascular ageing in chronic kidney diseases. Attempts to modulate vascular risk with cholesterol-lowering agents have largely failed in advanced chronic kidney disease (CKD). In addition to nitrogen waste products, many pathological biochemical processes also play a role in vascular calcification in chronic kidney damage. Magnesium, a cation vital for the body, may substantially reduce cardiovascular diseases’ risk and progression. This narrative review aimed to address the relationship between hypomagnesemia and vascular calcification, which promotes further cardiovascular complications in diabetes, aging, and CKD. Articles with predefined keywords were searched for in the PubMed and Google Scholar databases with specific inclusion and exclusion criteria. We hypothesized that a decrease in serum magnesium levels contributes to increased vascular calcification and thereby increases cardiovascular mortality. In summary, based on existing evidence in the literature, it appears that simple and inexpensive oral magnesium supplementation may reduce the cardiovascular mortality of patients who are already severely affected by such diseases; in this context, the concept of ‘normal’ vs. ‘ideal’ serum magnesium levels should be carefully re-examined. Full article
Show Figures

Figure 1

14 pages, 4278 KiB  
Article
Effects of Dietary Steroid Saponins on Growth Performance, Serum and Liver Glucose, Lipid Metabolism and Immune Molecules of Hybrid Groupers (♀Epinephelus fuscoguttatus × ♂Epinephelus lanceolatu) Fed High-Lipid Diets
Metabolites 2023, 13(2), 305; https://doi.org/10.3390/metabo13020305 - 19 Feb 2023
Cited by 2 | Viewed by 1390
Abstract
High-lipid diets are attributed to excessive lipid deposition and metabolic disturbances in fish. The aim of this experiment was to investigate the effects of steroidal saponins on growth performance, immune molecules and metabolism of glucose and lipids in hybrid groupers (initial weight 22.71 [...] Read more.
High-lipid diets are attributed to excessive lipid deposition and metabolic disturbances in fish. The aim of this experiment was to investigate the effects of steroidal saponins on growth performance, immune molecules and metabolism of glucose and lipids in hybrid groupers (initial weight 22.71 ± 0.12 g) fed high-lipid diets. steroidal saponins (0%, 0.1% and 0.2%) were added to the basal diet (crude lipid, 14%) to produce three experimental diets, designated S0, S0.1 and S0.2, respectively. After an 8-week feeding trial, no significant differences were found between the S0 and S0.1 groups in percent weight gain, specific growth rate, feed conversion ratio, protein efficiency ratio and protein deposition rate (p > 0.05). All those in the S0.2 group were significantly decreased (p < 0.05). Compared to the S0 group, fish in the S0.1 group had lower contents of serum triglyceride and low-density lipoprotein cholesterol and higher high-density lipoprotein cholesterol and glucose (p < 0.05). The activities of superoxide dismutase, catalase and glutathione peroxidase were significantly higher, and malondialdehyde contents were significantly lower in the S0.1 group than in the S0 group (p < 0.05). Hepatic triglyceride, total cholesterol and glycogen were significantly lower in the S0.1 group than in the S0 group (p < 0.05). Activities of lipoprotein lipase, total lipase, glucokinase and pyruvate kinase, and gene expression of lipoprotein lipase, triglyceride lipase and glucokinase, were significantly higher in the S0.1 group than in the S0 group. Interleukin-10 mRNA expression in the S0.1 group was significantly higher than that in the S0 group, while the expression of interleukin-6 and tumor necrosis factor-α genes were significantly lower than those in the S0 group. In summary, adding 0.1% steroidal saponins to a high-lipid diet not only promoted lipolysis in fish livers, but also activated glycolysis pathways, thus enhancing the utilization of the dietary energy of the groupers, as well as supporting the fish’s nonspecial immune-defense mechanism. Full article
Show Figures

Figure 1

18 pages, 1684 KiB  
Article
Machine Learning Methods Improve Specificity in Newborn Screening for Isovaleric Aciduria
Metabolites 2023, 13(2), 304; https://doi.org/10.3390/metabo13020304 - 18 Feb 2023
Cited by 3 | Viewed by 1424
Abstract
Isovaleric aciduria (IVA) is a rare disorder of leucine metabolism and part of newborn screening (NBS) programs worldwide. However, NBS for IVA is hampered by, first, the increased birth prevalence due to the identification of individuals with an attenuated disease variant (so-called “mild” [...] Read more.
Isovaleric aciduria (IVA) is a rare disorder of leucine metabolism and part of newborn screening (NBS) programs worldwide. However, NBS for IVA is hampered by, first, the increased birth prevalence due to the identification of individuals with an attenuated disease variant (so-called “mild” IVA) and, second, an increasing number of false positive screening results due to the use of pivmecillinam contained in the medication. Recently, machine learning (ML) methods have been analyzed, analogous to new biomarkers or second-tier methods, in the context of NBS. In this study, we investigated the application of machine learning classification methods to improve IVA classification using an NBS data set containing 2,106,090 newborns screened in Heidelberg, Germany. Therefore, we propose to combine two methods, linear discriminant analysis, and ridge logistic regression as an additional step, a digital-tier, to traditional NBS. Our results show that this reduces the false positive rate by 69.9% from 103 to 31 while maintaining 100% sensitivity in cross-validation. The ML methods were able to classify mild and classic IVA from normal newborns solely based on the NBS data and revealed that besides isovalerylcarnitine (C5), the metabolite concentration of tryptophan (Trp) is important for improved classification. Overall, applying ML methods to improve the specificity of IVA could have a major impact on newborns, as it could reduce the newborns’ and families’ burden of false positives or over-treatment. Full article
Show Figures

Figure 1

15 pages, 617 KiB  
Article
Association of Red Blood Cell Distribution Width and Neutrophil-to-Lymphocyte Ratio with Calcification and Cardiovascular Markers in Chronic Kidney Disease
Metabolites 2023, 13(2), 303; https://doi.org/10.3390/metabo13020303 - 17 Feb 2023
Cited by 2 | Viewed by 1428
Abstract
We aimed to investigate the association between Red Blood Cell Distribution Width (RDW) and Neutrophil-to-Lymphocyte Ratio (NLR), simple, rapidly assessed markers from the complete blood count with vascular calcification (VC)/stiffness and cardiovascular disease (CVD) in chronic kidney disease (CKD). Dephosphorylated, uncarboxylated matrix Gla-protein [...] Read more.
We aimed to investigate the association between Red Blood Cell Distribution Width (RDW) and Neutrophil-to-Lymphocyte Ratio (NLR), simple, rapidly assessed markers from the complete blood count with vascular calcification (VC)/stiffness and cardiovascular disease (CVD) in chronic kidney disease (CKD). Dephosphorylated, uncarboxylated matrix Gla-protein (dp-ucMGP), and central/peripheral hemodynamics’ parameters were measured in 158 CKD patients, including Hemodialysis and Peritoneal Dialysis. Spearman’s rho analysis showed that RDW correlated with C-reactive protein (CRP) (r = 0.29, p < 0.001), dp-ucMGP (r = 0.43, p = < 0.0001), central diastolic blood pressure (DBP) (r = −0.19, p = 0.02), and albuminuria (r = −0.17, p = 0.03). NLR correlated with the duration of CVD (r = 0.32, p < 0.001), CRP (r = 0.27, p = 0.01), dp-ucMGP (r = 0.43, p < 0.0001), central DBP (r = −0.32, p < 0.0001) and eGFR (r = −0.25, p = 0.04). In multiple regression models, circulating dp-ucMGP was an independent predictor of RDW (β = 0.001, p = 0.001) and NLR (β = 0.002, p = 0.002). In CKD patients, RDW and NLR are associated with traditional and novel markers of VC and CVD. Full article
(This article belongs to the Special Issue Metabolism of Red Blood Cells in Chronic Renal Failure)
Show Figures

Graphical abstract

10 pages, 266 KiB  
Article
Metabolic Deregulations in Patients with Polycystic Ovary Syndrome
Metabolites 2023, 13(2), 302; https://doi.org/10.3390/metabo13020302 - 17 Feb 2023
Cited by 1 | Viewed by 2270
Abstract
Polycystic ovary syndrome (PCOS) contributes to endocrine and metabolic complications for women worldwide. The aim of this study was to establish the usefulness of new anthropometric indices and atherogenic indices in the evaluation of metabolic disorders, in particular, glucose and insulin abnormalities in [...] Read more.
Polycystic ovary syndrome (PCOS) contributes to endocrine and metabolic complications for women worldwide. The aim of this study was to establish the usefulness of new anthropometric indices and atherogenic indices in the evaluation of metabolic disorders, in particular, glucose and insulin abnormalities in the profiles of women with polycystic ovary syndrome (PCOS). In the study, a total of 49 women with PCOS aged between 18 and 39 years were recruited. All patients were tested for fasting glucose and insulin, lipid parameters, oral-glucose administration, and biochemical parameters. All of them underwent anthropometric measurements, such as BMI (body mass index), WHR (waist-to-hip ratio), WHtR (waist-to-height ratio), BAI (body adiposity index), VAI (visceral adiposity index), LAP (lipid accumulation product), BRI (body roundness index), ABSI (A body shape index), AIP (atherogenic risk of plasma), AC (atherogenic coefficient), Castelli risk index-I, Castelli risk index-II and (LCI) lipoprotein combine index, TG/HDL-C ratio, METS-IR (The metabolic score of insulin resistance), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and triglyceride glucose-waist circumference index (TyG-WC index) were calculated. The analyzed anthropometric measurements/indices and atherogenic indices demonstrated significant correlations in PCOS women. T A strong relationship was found between fasting glucose, fasting insulin, glucose after 60 min, HOMA-IR index in the patients with PCOS. There was no significant relationship between HbA1c and other analyzed parameters and indices. Most of the analyzed anthropometric and atherogenic indices may be useful tools in evaluating metabolic disorders, and, in particular, glucose and insulin abnormalities in PCOS women. Full article
16 pages, 2398 KiB  
Article
Machine Learning-Based Integration of Metabolomics Characterisation Predicts Progression of Myopic Retinopathy in Children and Adolescents
Metabolites 2023, 13(2), 301; https://doi.org/10.3390/metabo13020301 - 17 Feb 2023
Cited by 5 | Viewed by 1406
Abstract
Myopic retinopathy is an important cause of irreversible vision loss and blindness. As metabolomics has recently been successfully applied in myopia research, this study sought to characterize the serum metabolic profile of myopic retinopathy in children and adolescents (4–18 years) and to develop [...] Read more.
Myopic retinopathy is an important cause of irreversible vision loss and blindness. As metabolomics has recently been successfully applied in myopia research, this study sought to characterize the serum metabolic profile of myopic retinopathy in children and adolescents (4–18 years) and to develop a diagnostic model that combines clinical and metabolic features. We selected clinical and serum metabolic data from children and adolescents at different time points as the training set (n = 516) and the validation set (n = 60). All participants underwent an ophthalmologic examination. Untargeted metabolomics analysis of serum was performed. Three machine learning (ML) models were trained by combining metabolic features and conventional clinical factors that were screened for significance in discrimination. The better-performing model was validated in an independent point-in-time cohort and risk nomograms were developed. Retinopathy was present in 34.2% of participants (n = 185) in the training set, including 109 (28.61%) with mild to moderate myopia. A total of 27 metabolites showed significant variation between groups. After combining Lasso and random forest (RF), 12 modelled metabolites (mainly those involved in energy metabolism) were screened. Both the logistic regression and extreme Gradient Boosting (XGBoost) algorithms showed good discriminatory ability. In the time-validation cohort, logistic regression (AUC 0.842, 95% CI 0.724–0.96) and XGBoost (AUC 0.897, 95% CI 0.807–0.986) also showed good prediction accuracy and had well-fitted calibration curves. Three clinical characteristic coefficients remained significant in the multivariate joint model (p < 0.05), as did 8/12 metabolic characteristic coefficients. Myopic retinopathy may have abnormal energy metabolism. Machine learning models based on metabolic profiles and clinical data demonstrate good predictive performance and facilitate the development of individual interventions for myopia in children and adolescents. Full article
(This article belongs to the Special Issue Metabolic Studies in Ophthalmology and Visual Science)
Show Figures

Figure 1

16 pages, 3954 KiB  
Article
Metabolite Changes in Indonesian Tempe Production from Raw Soybeans to Over-Fermented Tempe
Metabolites 2023, 13(2), 300; https://doi.org/10.3390/metabo13020300 - 17 Feb 2023
Cited by 2 | Viewed by 1890
Abstract
Tempe is fermented soybean from Java, Indonesia, that can serve as a functional food due to its high nutritional content and positive impact on health. Although the tempe fermentation process is known to affect its nutrient content, changes in the metabolite profile during [...] Read more.
Tempe is fermented soybean from Java, Indonesia, that can serve as a functional food due to its high nutritional content and positive impact on health. Although the tempe fermentation process is known to affect its nutrient content, changes in the metabolite profile during tempe production have not been comprehensively examined. Thus, this research applied a metabolomics approach to investigate the metabolite profile in each step of tempe production, from soybean soaking to over-fermentation. Fourteen samples of raw soybeans, i.e., soaked soybeans (24 h), steamed soybeans, fungal fermented soybeans, and over-fermented soybeans (up to 72 h), were collected. Untargeted metabolomics by gas chromatography/mass spectrometry (GC–MS) was used to determine soybean transformations from various fermentation times and identify disparity-related metabolites. The results showed that soybeans samples clustered together on the basis of the different fermentation steps. The results also showed that sugar, sugar alcohol, organic acids, and amino acids, as well as fermentation time, contributed to the soybean metabolite profile transformations. During the fermentation of tempe, sugars and sugar alcohols accumulated at the beginning of the process before gradually decreasing as fermentation progressed. Specifically, at the beginning of the fermentation, gentiobiose, galactinol, and glucarate were accumulated, and several metabolites such as glutamine, 4-hydroxyphenylacetic acid, and homocysteine increased along with the progression of fermentation. In addition, notable isoflavones daidzein and genistein increased from 24 h of fermentation until 72 h. This is the first report that provides a complete description of the metabolic profile of the tempe production from soybean soaking to over-fermentation. Through this study, the dynamic changes at each step of tempe production were revealed. This information can be beneficial to the tempe industry for the improvement of product quality based on metabolite profiling. Full article
(This article belongs to the Special Issue Omics Technologies in Fermentation Science 2.0)
Show Figures

Graphical abstract

13 pages, 1329 KiB  
Article
Application of Machine Learning to Metabolomic Profile Characterization in Glioblastoma Patients Undergoing Concurrent Chemoradiation
Metabolites 2023, 13(2), 299; https://doi.org/10.3390/metabo13020299 - 17 Feb 2023
Cited by 4 | Viewed by 1455
Abstract
We here characterize changes in metabolite patterns in glioblastoma patients undergoing surgery and concurrent chemoradiation using machine learning (ML) algorithms to characterize metabolic changes during different stages of the treatment protocol. We examined 105 plasma specimens (before surgery, 2 days after surgical resection, [...] Read more.
We here characterize changes in metabolite patterns in glioblastoma patients undergoing surgery and concurrent chemoradiation using machine learning (ML) algorithms to characterize metabolic changes during different stages of the treatment protocol. We examined 105 plasma specimens (before surgery, 2 days after surgical resection, before starting concurrent chemoradiation, and immediately after chemoradiation) from 36 patients with isocitrate dehydrogenase (IDH) wildtype glioblastoma. Untargeted GC-TOF mass spectrometry-based metabolomics was used given its superiority in identifying and quantitating small metabolites; this yielded 157 structurally identified metabolites. Using Multinomial Logistic Regression (MLR) and GradientBoostingClassifier (GB Classifier), ML models classified specimens based on metabolic changes. The classification performance of these models was evaluated using performance metrics and area under the curve (AUC) scores. Comparing post-radiation to pre-radiation showed increased levels of 15 metabolites: glycine, serine, threonine, oxoproline, 6-deoxyglucose, gluconic acid, glycerol-alpha-phosphate, ethanolamine, propyleneglycol, triethanolamine, xylitol, succinic acid, arachidonic acid, linoleic acid, and fumaric acid. After chemoradiation, a significant decrease was detected in 3-aminopiperidine 2,6-dione. An MLR classification of the treatment phases was performed with 78% accuracy and 75% precision (AUC = 0.89). The alternative GB Classifier algorithm achieved 75% accuracy and 77% precision (AUC = 0.91). Finally, we investigated specific patterns for metabolite changes in highly correlated metabolites. We identified metabolites with characteristic changing patterns between pre-surgery and post-surgery and post-radiation samples. To the best of our knowledge, this is the first study to describe blood metabolic signatures using ML algorithms during different treatment phases in patients with glioblastoma. A larger study is needed to validate the results and the potential application of this algorithm for the characterization of treatment responses. Full article
(This article belongs to the Special Issue Artificial Intelligence in Cancer Metabolism and Metabolomics)
Show Figures

Figure 1

11 pages, 941 KiB  
Article
Constituents of the Stem Bark of Trichilia monadelpha (Thonn.) J. J. De Wilde (Meliaceae) and Their Antibacterial and Antiplasmodial Activities
Metabolites 2023, 13(2), 298; https://doi.org/10.3390/metabo13020298 - 17 Feb 2023
Cited by 3 | Viewed by 1459
Abstract
The chemical investigation of the EtOH extract from the stem bark of Trichilia monadelpha (Thonn.) J. J. De Wilde afforded two new limonoids (1 and 2): 24-acetoxy-21,25-dihydroxy-21,23-epoxytirucall-7-en-3-one (1) and (6R)-1-O-deacetylkhayanolide E (2), together [...] Read more.
The chemical investigation of the EtOH extract from the stem bark of Trichilia monadelpha (Thonn.) J. J. De Wilde afforded two new limonoids (1 and 2): 24-acetoxy-21,25-dihydroxy-21,23-epoxytirucall-7-en-3-one (1) and (6R)-1-O-deacetylkhayanolide E (2), together with eleven known compounds (313), including additional limonoids, flavonoids, triterpenoids, steroids, and fatty acid. Their structures were determined using 1D- and 2D-NMR experiments, ESI mass spectrometry, and single crystal X-ray diffraction analysis. The antibacterial and antiplasmodial activities of the extracts, sub-extracts, fractions, and some of the isolated compounds were evaluated in known pathogenic strains, including Staphylococcus aureus and Plasmodium falciparum. Fraction E (n-Hex/EtOAc 30:70, v/v) showed significant activity against S. aureus ATCC 25923 with a MIC value of 3.90 µg/mL, while one of its constituents (epicatechin (9)) exhibited significant activity with MIC values of 7.80 µg/mL. Interestingly, grandifotane A (6) (IC50 = 1.37 µM) and khayanolide D (5) (IC50 = 1.68 µM) were highly active against the chloroquine-sensitive/sulfadoxine-resistant plasmodium falciparum 3D7 strain, unlike their corresponding plant extract and fractions. Full article
Show Figures

Figure 1

12 pages, 1369 KiB  
Review
Energy System Contributions during Olympic Combat Sports: A Narrative Review
Metabolites 2023, 13(2), 297; https://doi.org/10.3390/metabo13020297 - 17 Feb 2023
Cited by 7 | Viewed by 3637
Abstract
This narrative review focuses on the studies that estimate the energy systems’ contributions during match simulations of striking (boxing, karate, and taekwondo), grappling (judo), and weapon-based (fencing) Olympic combat sports. The purpose is to provide insights into the metabolism of these athletes. In [...] Read more.
This narrative review focuses on the studies that estimate the energy systems’ contributions during match simulations of striking (boxing, karate, and taekwondo), grappling (judo), and weapon-based (fencing) Olympic combat sports. The purpose is to provide insights into the metabolism of these athletes. In striking Olympic combat sports, the oxidative contribution varied from 62% (in karate and taekwondo) to 86% (in boxing), the ATP-PCr system contribution varied from 10% (in boxing) to 31% (in taekwondo), and the glycolytic contribution was between 3% (in the third round of taekwondo) and 21% (in karate). In grappling combat sports, only judo was studied, and for a 4 min match, the oxidative contribution was 79%, followed by 14% ATP-PCr system contribution and 7% contribution from the glycolytic system. In fencing, the only weapon-based Olympic combat sport, the oxidative contribution varied from 81% (in the first bout) to 90% (in the second bout), followed by 9% (bout 2) to 12% (bout 1) contribution from the ATP-PCr system, and 0.6% to 7% contribution from the glycolytic system during 3 × 3 min bouts of épée match simulation. Hence, Olympic combat sports are primarily powered by the oxidative system, but the key scoring actions are likely fueled by anaerobic pathways. Full article
(This article belongs to the Special Issue Metabolic Flexibility in Exercise Performances and Metabolic Diseases)
Show Figures

Figure 1

13 pages, 4343 KiB  
Article
Exploration of Blood Metabolite Signatures of Colorectal Cancer and Polyposis through Integrated Statistical and Network Analysis
Metabolites 2023, 13(2), 296; https://doi.org/10.3390/metabo13020296 - 17 Feb 2023
Viewed by 1565
Abstract
Colorectal cancer (CRC), one of the most prevalent and deadly cancers worldwide, generally evolves from adenomatous polyps. The understanding of the molecular mechanisms underlying this pathological evolution is crucial for diagnostic and prognostic purposes. Integrative systems biology approaches offer an optimal point of [...] Read more.
Colorectal cancer (CRC), one of the most prevalent and deadly cancers worldwide, generally evolves from adenomatous polyps. The understanding of the molecular mechanisms underlying this pathological evolution is crucial for diagnostic and prognostic purposes. Integrative systems biology approaches offer an optimal point of view to analyze CRC and patients with polyposis. The present study analyzed the association networks constructed from a publicly available array of 113 serum metabolites measured on a cohort of 234 subjects from three groups (66 CRC patients, 76 patients with polyposis, and 92 healthy controls), which concentrations were obtained via targeted liquid chromatography-tandem mass spectrometry. In terms of architecture, topology, and connectivity, the metabolite-metabolite association network of CRC patients appears to be completely different with respect to patients with polyposis and healthy controls. The most relevant nodes in the CRC network are those related to energy metabolism. Interestingly, phenylalanine, tyrosine, and tryptophan metabolism are found to be involved in both CRC and polyposis. Our results demonstrate that the characterization of metabolite–metabolite association networks is a promising and powerful tool to investigate molecular aspects of CRC. Full article
(This article belongs to the Special Issue Cancer Metabolomics 2023)
Show Figures

Figure 1

17 pages, 661 KiB  
Review
Metabolic Impact of Frailty Changes Diabetes Trajectory
Metabolites 2023, 13(2), 295; https://doi.org/10.3390/metabo13020295 - 16 Feb 2023
Cited by 8 | Viewed by 1966
Abstract
Diabetes mellitus prevalence increases with increasing age. In older people with diabetes, frailty is a newly emerging and significant complication. Frailty induces body composition changes that influence the metabolic state and affect diabetes trajectory. Frailty appears to have a wide metabolic spectrum, which [...] Read more.
Diabetes mellitus prevalence increases with increasing age. In older people with diabetes, frailty is a newly emerging and significant complication. Frailty induces body composition changes that influence the metabolic state and affect diabetes trajectory. Frailty appears to have a wide metabolic spectrum, which can present with an anorexic malnourished phenotype and a sarcopenic obese phenotype. The sarcopenic obese phenotype individuals have significant loss of muscle mass and increased visceral fat. This phenotype is characterised by increased insulin resistance and a synergistic increase in the cardiovascular risk more than that induced by obesity or sarcopenia alone. Therefore, in this phenotype, the trajectory of diabetes is accelerated, which needs further intensification of hypoglycaemic therapy and a focus on cardiovascular risk reduction. Anorexic malnourished individuals have significant weight loss and reduced insulin resistance. In this phenotype, the trajectory of diabetes is decelerated, which needs deintensification of hypoglycaemic therapy and a focus on symptom control and quality of life. In the sarcopenic obese phenotype, the early use of sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists is reasonable due to their weight loss and cardio–renal protection properties. In the malnourished anorexic phenotype, the early use of long-acting insulin analogues is reasonable due to their weight gain and anabolic properties, regimen simplicity and the convenience of once-daily administration. Full article
(This article belongs to the Special Issue Glycometabolic Control in Older Patients with Type 2 Diabetes)
Show Figures

Figure 1

19 pages, 15482 KiB  
Article
A Comprehensive Analysis to Elucidate the Effects of Spraying Mineral Elements on the Accumulation of Flavonoids in Epimedium sagittatum during the Harvesting Period
Metabolites 2023, 13(2), 294; https://doi.org/10.3390/metabo13020294 - 16 Feb 2023
Viewed by 1153
Abstract
The harvesting period is a critical period for the accumulation of flavonoids in the leaves of the important medicinal plant Epimedium sagittatum. In this study, we conducted an experiment on E. sagittatum leaves sprayed with mineral elements with the aim of improving [...] Read more.
The harvesting period is a critical period for the accumulation of flavonoids in the leaves of the important medicinal plant Epimedium sagittatum. In this study, we conducted an experiment on E. sagittatum leaves sprayed with mineral elements with the aim of improving the quality of the herbal leafage during the harvesting period. We elucidated the changes in flavonoids (icariin, epimedin A, epimedin B, and epimedin C) in E. sagittatum leaves. The sum of main flavonoids content reached a maximum (11.74%) at 20 days after the high-concentration Fe2+ (2500 mg·L−1) treatment. We analyzed the FT-IR spectra characteristics of E. sagittatum leaf samples using the FT-IR technique, and constructed an OPLS-DA model and identified characteristic peaks to achieve differentiated identification of E. sagittatum. Further, widely untargeted metabolomic analysis identified different classes of metabolites. As the most important characteristic flavonoids, the relative contents of icariin, icaritin, icariside I, and icariside II were found to be up-regulated by high-Fe2+ treatment. Our experimental results demonstrate that high-concentration Fe2+ treatment is an effective measure to increase the flavonoids content in E. sagittatum leaves during the harvesting period, which can provide a scientific basis for the improvement of E. sagittatum leaf cultivation agronomic measures. Full article
(This article belongs to the Special Issue Secondary Metabolites from Plant Sources)
Show Figures

Graphical abstract

13 pages, 317 KiB  
Article
Comparison of Diagnostic Models to Estimate the Risk of Metabolic Syndrome in a Chilean Pediatric Population: A Cross-Sectional Study
Metabolites 2023, 13(2), 293; https://doi.org/10.3390/metabo13020293 - 16 Feb 2023
Cited by 1 | Viewed by 1066
Abstract
The pediatric population has various criteria for measuring metabolic syndrome (MetS). The diversity of consensus for diagnosis has led to different non-comparable reported prevalence. Given the increase in its prevalence in pediatric ages, it is necessary to develop efficient methods to encourage early [...] Read more.
The pediatric population has various criteria for measuring metabolic syndrome (MetS). The diversity of consensus for diagnosis has led to different non-comparable reported prevalence. Given the increase in its prevalence in pediatric ages, it is necessary to develop efficient methods to encourage early detection. Consequently, early screening for the risk of MetS could favor timely action in preventing associated comorbidities in adulthood. This study aimed to establish the diagnostic capacity of models that use non-invasive (anthropometric) and invasive (serum biomarkers) variables for the early detection of MetS in Chilean children. A cross-sectional study was carried out on 220 children aged 6 to 11. Multivariate logistic regressions and discriminant analyses were applied to determine the diagnostic capacity of invasive and non-invasive variables. Based on these results, four diagnostic models were created and compared: (i) anthropometric, (ii) hormonal (insulin, leptin, and adiponectin), (iii) Lipid A (high-density cholesterol lipoprotein [HDL-c] and triglycerides [TG]) and (iv) Lipid B (TG/HDL-c). The prevalence of MetS was 26.8%. Lipid biomarkers (HDL-c and TG) and their ratio (TG/HDL-c) presented higher diagnostic capacity, above 80%, followed by body mass index (BMI, 0.71–0.88) and waist-to-height ratio (WHtR, 0.70–0.87). The lipid model A was the most accurate (sensitivity [S] = 62.7%, specificity [E] = 96.9%, validity index 87.7%), followed by the anthropometric model (S = 69.5%, E = 88.8% and validity index = 83.6%). In conclusion, detecting MetS was possible through invasive and non-invasive methods tested in overweight and obese children. The proposed models based on anthropometric variables, or serum biomarkers of the lipid model A, presented acceptable validity indices. Moreover, they were higher than those that measured adipokines, leptin, and adiponectin. The anthropometric model was the most cost-effective and easy to apply in different environments. Full article
(This article belongs to the Section Integrative Metabolomics)
11 pages, 794 KiB  
Article
Influence of Flavonoid-Rich Fraction of Monodora tenuifolia Seed Extract on Blood Biochemical Parameters in Streptozotocin-Induced Diabetes Mellitus in Male Wistar Rats
Metabolites 2023, 13(2), 292; https://doi.org/10.3390/metabo13020292 - 16 Feb 2023
Cited by 3 | Viewed by 1276
Abstract
Diabetes mellitus is a metabolic disorder caused by either the total destruction of the pancreatic beta cells that secrete insulin for the uptake of glucose from the circulation or as a result of the inability of body cells to respond to the presence [...] Read more.
Diabetes mellitus is a metabolic disorder caused by either the total destruction of the pancreatic beta cells that secrete insulin for the uptake of glucose from the circulation or as a result of the inability of body cells to respond to the presence of insulin in the blood. The present study investigated the effect of a flavonoid-rich fraction of Monodora tenuifolia seed extract (FFMTSE) on blood parameters in streptozotocin (STZ)-induced diabetic male Wistar rats. The rats were divided into seven groups (n = 6). Group 1: normal control rats, Group 2: rats + FFMTSE (25 mg/kgbwt), Group 3: rats + FFMTSE (50 mg/kgbwt), Group 4: diabetic control rats, Group 5: diabetic rats + FFMTSE (25 mg/kgbwt), Group 6: diabetic rats + FFMTSE (50 mg/kgbwt), and Group 7: diabetic rats + Metformin. The assessment of the lipid profile, kidney functions (urea and creatinine), and cardiac biomarkers (LDH and CK-MB) were carried out in the plasma using established protocols. The results showed a significant increase in the concentrations of triacylglycerol, cholesterol, LDL-cholesterol, VLDL-cholesterol, urea, and creatinine, as well as in cardiac enzyme activities in diabetic rats. However, the administration of the FFMTSE significantly improved the observed biochemical parameters. In addition, an increased concentration of HDL-cholesterol concentration was observed in the diabetic rats upon treatment with FFMTSE. These findings indicate that FFMTSE could be a potent anti-nephropathy and anti-cardiomyopathy agent in diabetic conditions. Full article
Show Figures

Figure 1

16 pages, 1679 KiB  
Review
Abnormalities of Sphingolipids Metabolic Pathways in the Pathogenesis of Psoriasis
Metabolites 2023, 13(2), 291; https://doi.org/10.3390/metabo13020291 - 16 Feb 2023
Cited by 5 | Viewed by 1837
Abstract
Psoriasis is immune-mediated skin disorder affecting thousands of people. Sphingolipids (SLs) are bioactive molecules present in the epidermis, involved in the following cellular processes: proliferation, differentiation, and apoptosis of keratinocytes. Alterations in SLs synthesis have been observed in psoriatic skin. To investigate if [...] Read more.
Psoriasis is immune-mediated skin disorder affecting thousands of people. Sphingolipids (SLs) are bioactive molecules present in the epidermis, involved in the following cellular processes: proliferation, differentiation, and apoptosis of keratinocytes. Alterations in SLs synthesis have been observed in psoriatic skin. To investigate if the imbalance in lipid skin metabolism could be related to psoriasis, we analyzed the gene expression in non-lesioned and lesioned skin of patients with psoriasis available in two datasets (GSE161683 and GSE136757) obtained from National Center for Biotechnology Information (NCBI). The differentially expressed genes (DEGs) were searched for using NCBI analysis, and Gene Ontology (GO) biological process analyses were performed using the Database of Annotation, Visualization, and Integrated Discovery (DAVID) platform. Venn diagrams were done with InteractiVenn tool and heatmaps were constructed using Morpheus software. We observed that the gene expression of cytoplasmic phospholipase A2 (PLA2G4D), glycerophosphodiester phosphodiesterase domain containing 3 (GDP3), arachidonate 12-lipoxygenase R type (ALOX12B), phospholipase B-like 1 (PLBD1), sphingomyelin phosphodiesterase 3 (SMPD3), ganglioside GM2 activator (GM2A), and serine palmitoyltransferase long chain subunit 2 (SPTLC2) was up-regulated in lesioned skin psoriasis when compared with the non-lesioned skin. These genes are related to lipid metabolism and more specifically to sphingolipids. So, in the present study, the role of sphingolipids in psoriasis pathogenesis is summarized. These genes could be used as prognostic biomarkers of psoriasis and could be targets for the treatment of patients who suffer from the disease. Full article
(This article belongs to the Special Issue Skin Metabolism and Cutaneous Disorders)
Show Figures

Figure 1

11 pages, 928 KiB  
Article
Impact of the Extraction Method on the Chemical Composition and Antioxidant Potency of Rosmarinus officinalis L. Extracts
Metabolites 2023, 13(2), 290; https://doi.org/10.3390/metabo13020290 - 16 Feb 2023
Cited by 1 | Viewed by 1564
Abstract
Rosmarinus officinalis L. is a dietary source that produces polyphenols as secondary metabolites. These natural compounds with potent antioxidant abilities are increasingly recommended as a supplement to inhibit oxidative stress. In the current work, we evaluated the impact of the extraction method on [...] Read more.
Rosmarinus officinalis L. is a dietary source that produces polyphenols as secondary metabolites. These natural compounds with potent antioxidant abilities are increasingly recommended as a supplement to inhibit oxidative stress. In the current work, we evaluated the impact of the extraction method on the chemical composition of R. officinalis extract, especially on the content of carnosic (CA) and rosmarinic (RA) acids using UPLC-MS-DAD as well as on their antioxidant potency. Four extracts of Tunisian rosemary were obtained from non-conventional extraction techniques:ultrasound-assisted extraction (UAE),supercritical extraction (SFE) and UAE and SFE combined ((UAE-SFE(I), UAE-SFE(II)). The UAE exhibited the best total phenolic compounds (i.e., 85.27 mg GAEg−1), the highest content of CAand RA and the strongest antioxidant abilities (i.e., IC50 = 0.13 mg/mL and EC50 = 0.93 mg/mL for DPPH scavenging test and iron reducing power ability assay). The evaluation of antioxidant activity of UAE inhuman skin fibroblast (HS-68) cell line was carried out after the induction of oxidative stress. The results determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed a strong protective effect against H2O2oxidative stress induction in cells pretreated with UAE. The obtained results allow us to give new insight about the effect of the extraction method on the chemical composition and biological activities of the extract and the importance of the choice of the most appropriate processing technique to prepare rosemary extract with a high antioxidant potency and protective effect against oxidative stress. Full article
(This article belongs to the Special Issue Effect of Diet on Gut Microbiota and Host Metabolism)
Show Figures

Graphical abstract

13 pages, 2690 KiB  
Article
Short-Term Estivation and Hibernation Induce Changes in the Blood and Circulating Hemocytes of the Apple Snail Pomacea canaliculata
Metabolites 2023, 13(2), 289; https://doi.org/10.3390/metabo13020289 - 16 Feb 2023
Cited by 5 | Viewed by 1519
Abstract
States of natural dormancy include estivation and hibernation. Ampullariids are exemplary because they undergo estivation when deprived of water or hibernation when exposed to very low temperatures. Regardless of the condition, ampullariids show increased endogenous antioxidant defenses, anticipating the expected respiratory burst during [...] Read more.
States of natural dormancy include estivation and hibernation. Ampullariids are exemplary because they undergo estivation when deprived of water or hibernation when exposed to very low temperatures. Regardless of the condition, ampullariids show increased endogenous antioxidant defenses, anticipating the expected respiratory burst during reoxygenation after reactivation, known as “Preparation for Oxidative Stress (POS)”. In this work, we tested the POS hypothesis for changes in the blood and hemocytes of the bimodal breather Pomacea canaliculata (Ampullariidae) induced at experimental estivation and hibernation. We described respiratory (hemocyanin, proteins, lactate), antioxidant (GSH, uric acid, SOD, CAT, GST), and immunological (hemocyte levels, ROS production) parameters. We showed that, although the protein level remains unchanged in all experimental groups, hemocyanin increases in response to estivation. Furthermore, lactate remains unchanged in challenged snails, suggesting an aerobic metabolism during short-term challenges. Blood uric acid increases during estivation and arousal from estivation or hibernation, supporting the previously proposed antioxidant role. Regarding hemocytes, we showed that the total population increases with all challenges, and granulocytes increase during hibernation. We further showed that hibernation affects ROS production by hemocytes, possibly through mitochondrial inhibition. This study contributed to the knowledge of the adaptive strategies of ampullariids to tolerate adverse environmental conditions. Full article
(This article belongs to the Special Issue Response to Oxidative Stress as a Welfare Parameter)
Show Figures

Graphical abstract

15 pages, 2702 KiB  
Article
Widely Targeted Metabolomics Reveals Metabolite Diversity in Jalapeño and Serrano Chile Peppers (Capsicum annuum L.)
Metabolites 2023, 13(2), 288; https://doi.org/10.3390/metabo13020288 - 16 Feb 2023
Cited by 3 | Viewed by 1719
Abstract
Chile peppers (Capsicum annuum L.) are good sources of vitamins and minerals that can be included in the diet to mitigate nutritional deficiencies. Metabolomics examines the metabolites involved in biological pathways to understand the genes related to complex phenotypes such as the [...] Read more.
Chile peppers (Capsicum annuum L.) are good sources of vitamins and minerals that can be included in the diet to mitigate nutritional deficiencies. Metabolomics examines the metabolites involved in biological pathways to understand the genes related to complex phenotypes such as the nutritional quality traits. The current study surveys the different metabolites present in jalapeño (‘NuMex Pumpkin Spice’) and serrano (‘NuMex LotaLutein’) type chile peppers grown in New Mexico using a widely targeted metabolomics approach, with the ‘NuMex LotaLutein’ as control. A total of 1088 different metabolites were detected, where 345 metabolites were differentially expressed; 203 (59%) were downregulated and 142 (41%) were upregulated (i.e., relative metabolite content is higher in ‘NuMex Pumpkin Spice’). The upregulated metabolites comprised mostly of phenolic acids (42), flavonoids (22), and organic acids (13). Analyses of principal component (PC) and orthogonal partial least squares demonstrated clustering based on cultivars, where at least 60% of variation was attributed to the first two PCs. Pathway annotation identified 89 metabolites which are involved in metabolic pathways and the biosynthesis of secondary metabolites. Altogether, metabolomics provided insights into the different metabolites present which can be targeted for breeding and selection towards the improvement of nutritional quality traits in Capsicum. Full article
Show Figures

Figure 1

13 pages, 2240 KiB  
Article
Effects of APOE Genotype and Western Diet on Metabolic Phenotypes in Female Mice
Metabolites 2023, 13(2), 287; https://doi.org/10.3390/metabo13020287 - 16 Feb 2023
Cited by 1 | Viewed by 1406
Abstract
Western diets high in sugars and saturated fats have been reported to induce metabolic and inflammatory impairments that are associated with several age-related disorders, including Alzheimer’s disease (AD) and type 2 diabetes (T2D). The apolipoprotein E (APOE) genotype is associated with [...] Read more.
Western diets high in sugars and saturated fats have been reported to induce metabolic and inflammatory impairments that are associated with several age-related disorders, including Alzheimer’s disease (AD) and type 2 diabetes (T2D). The apolipoprotein E (APOE) genotype is associated with metabolic and inflammatory outcomes that contribute to risks for AD and T2D, with the APOE4 genotype increasing risks relative to the more common APOE3 allele. In this study, we investigated the impacts of the APOE genotype on systemic and neural effects of the Western diet. Female mice with knock-in of human APOE3 or APOE4 were exposed to control or Western diet for 13 weeks. In the control diet, we observed that APOE4 mice presented with impaired metabolic phenotypes, exhibiting greater adiposity, higher plasma leptin and insulin levels, and poorer glucose clearance than APOE3 mice. Behaviorally, APOE4 mice exhibited worse performance in a hippocampal-dependent learning task. In visceral adipose tissue, APOE4 mice exhibited generally higher expression levels of macrophage- and inflammation-related genes. The cerebral cortex showed a similar pattern, with higher expression of macrophage- and inflammation-related genes in APOE4 than APOE3 mice. Exposure to the Western diet yielded modest, statistically non-significant effects on most metabolic, behavioral, and gene expression measures in both APOE genotypes. Interestingly, the Western diet resulted in reduced gene expression of a few macrophage markers, specifically in APOE4 mice. The observed relative resistance to the Western diet suggests protective roles of both female sex and young adult age. Further, the data demonstrate that APOE4 is associated with deleterious systemic and neural phenotypes and an altered response to a metabolic stressor, findings relevant to the understanding of interactions between the APOE genotype and risks for metabolic disorders. Full article
Show Figures

Figure 1

12 pages, 2751 KiB  
Article
Disequilibrium in the Thioredoxin Reductase-1/Thioredoxin-1 Redox Couple Is Associated with Increased T-Cell Apoptosis in Children with Autism
Metabolites 2023, 13(2), 286; https://doi.org/10.3390/metabo13020286 - 16 Feb 2023
Cited by 2 | Viewed by 1187
Abstract
Autism spectrum disorder (ASD) is a neuropsychiatric childhood disorder that affects social skill and language development, and is characterized by persistent stereotypic behaviors, restricted social interests, and impaired language/social skills. ASD subjects have dysregulated immune responses due to impairment in inflammatory and antioxidant [...] Read more.
Autism spectrum disorder (ASD) is a neuropsychiatric childhood disorder that affects social skill and language development, and is characterized by persistent stereotypic behaviors, restricted social interests, and impaired language/social skills. ASD subjects have dysregulated immune responses due to impairment in inflammatory and antioxidant signaling in immune cells, such as T cells. Thioredoxin reductase-1 (TrxR1) and thioredoxin-1 (Trx1) play a crucial role in the maintenance of redox equilibrium in several immune cells, including T cells. T-cell apoptosis plays a crucial role in the pathogenesis of several inflammatory diseases. However, it remains to be explored how the TrxR1/Trx1 redox couple affects T-cells apoptosis in ASD and typically developing control (TDC) groups. Therefore, this single-center cross-sectional study explored the expression/activity of TrxR1/Trx1, and Bcl2, 7-AAD/annexin V immunostaining in T cells of ASD (n = 25) and TDC (n = 22) groups. Further, effects of the LPS were determined on apoptosis in TDC and ASD T cells. Our data show that T cells have increased TrxR1 expression, while having decreased Trx1 expression in the ASD group. Further, TrxR enzymatic activity was also elevated in T cells of the ASD group. Furthermore, T cells of the ASD group had a decreased Bcl2 expression and an increased % of annexin V immunostaining. Treatment of T cells with LPS caused greater apoptosis in the ASD group than the TDC group, with same treatment. These data reveal that the redox couple TrxR1/Trx1 is dysregulated in T cells of ASD subjects, which is associated with decreased Bcl2 expression and increased apoptosis. This may lead to decreased survival of T cells in ASD subjects during chronic inflammation. Future studies should investigate environmental factors, such as gut dysbiosis and pollutants, that may cause abnormal immune responses in the T cells of ASD subjects due to chronic inflammation. Full article
(This article belongs to the Special Issue Metabolism of Immune System in Inflammatory and Infectious Diseases)
Show Figures

Figure 1

16 pages, 1861 KiB  
Article
Chemical Characterization and Leishmanicidal Activity In Vitro and In Silico of Natural Products Obtained from Leaves of Vernonanthura brasiliana (L.) H. Rob (Asteraceae)
Metabolites 2023, 13(2), 285; https://doi.org/10.3390/metabo13020285 - 16 Feb 2023
Cited by 1 | Viewed by 1322
Abstract
Vernonanthura brasiliana (L.) H. Rob is a medicinal plant used for the treatment of several infections. This study aimed to evaluate the antileishmanial activity of V. brasiliana leaves using in vitro and in silico approaches. The chemical composition of V. brasiliana leaf extract was determined [...] Read more.
Vernonanthura brasiliana (L.) H. Rob is a medicinal plant used for the treatment of several infections. This study aimed to evaluate the antileishmanial activity of V. brasiliana leaves using in vitro and in silico approaches. The chemical composition of V. brasiliana leaf extract was determined through liquid chromatography-mass spectrometry (LC-MS). The inhibitory activity against Leishmania amazonensis promastigote was evaluated by the MTT method. In silico analysis was performed using Lanosterol 14alpha-demethylase (CYP51) as the target. The toxicity analysis was performed in RAW 264.7 cells and Tenebrio molitor larvae. LC-MS revealed the presence of 14 compounds in V. brasiliana crude extract, including flavonoids, flavones, sesquiterpene lactones, and quinic acids. Eriodictol (ΔGbind = −9.0), luteolin (ΔGbind = −8.7), and apigenin (ΔGbind = −8.6) obtained greater strength of molecular interaction with lanosterol demethylase in the molecular docking study. The hexane fraction of V. brasiliana showed the best leishmanicidal activity against L. amazonensis in vitro (IC50 12.44 ± 0.875 µg·mL−1) and low cytotoxicity in RAW 264.7 cells (CC50 314.89 µg·mL−1, SI = 25.30) and T. molitor larvae. However, the hexane fraction and Amphotericin-B had antagonistic interaction (FICI index ≥ 4.0). This study revealed that V. brasiliana and its metabolites are potential sources of lead compounds for drugs for leishmaniasis treatment. Full article
(This article belongs to the Special Issue The Natural Products in the Treatment and Prevention of Diseases)
Show Figures

Figure 1

15 pages, 2001 KiB  
Article
Serum Androgen Metabolites Correlate with Clinical Variables in African and European American Men with Localized, Therapy Naïve Prostate Cancer
Metabolites 2023, 13(2), 284; https://doi.org/10.3390/metabo13020284 - 16 Feb 2023
Viewed by 1418
Abstract
Dihydrotestosterone (DHT) and testosterone (T), which mediate androgen receptor nuclear translocation and target gene transcription, are crucial androgens and essential molecular triggers required for the proliferation and survival of prostate cancer cells. Therefore, androgen metabolism is commonly targeted in the treatment of prostate [...] Read more.
Dihydrotestosterone (DHT) and testosterone (T), which mediate androgen receptor nuclear translocation and target gene transcription, are crucial androgens and essential molecular triggers required for the proliferation and survival of prostate cancer cells. Therefore, androgen metabolism is commonly targeted in the treatment of prostate cancer. Using a high-pressure liquid chromatographic assay with tandem mass spectral detection, we determined the serum levels of metabolites produced during DHT/T biosynthesis in African American (AA) and European American (EA) men with localized, therapy naïve prostate cancer. Serum progesterone and related metabolites were significantly lower in AA men than in EA men, and these differences were associated with rapid disease progression. Multivariate analysis revealed significant differences between a subset of intermediate androgen metabolites between AA and EA men and between men with <=3 + 4 and >=4 + 3 Gleason score disease. AA men have a significantly higher frequency of single nucleotide polymorphisms in CYP11B1 and CYP11B2, enzymes that regulate corticosterone-aldosterone conversion. Finally, higher levels of T and pregnenolone were associated with a lower risk of progression-free survival only in AA men. This work provides new insight into androgen metabolism and racial disparities in prostate cancer by presenting evidence of dysregulated androgen biosynthesis in therapy naïve disease that correlates with clinical variables. Full article
Show Figures

Graphical abstract

12 pages, 4272 KiB  
Article
Sensitivity Intensified Ninhydrin-Based Chromogenic System by Ethanol-Ethyl Acetate: Application to Relative Quantitation of GABA
Metabolites 2023, 13(2), 283; https://doi.org/10.3390/metabo13020283 - 16 Feb 2023
Cited by 3 | Viewed by 1429
Abstract
Gamma-aminobutyric acid (GABA) is a functional metabolite in various organisms. Herein, a sensitivity intensified ninhydrin-based chromogenic system (SINICS), achieved by ethanol and ethyl acetate, is described for the reliable relative quantitation of GABA. A 2.9 mL SINICS kit comprises 1% ninhydrin, 40% ethanol, [...] Read more.
Gamma-aminobutyric acid (GABA) is a functional metabolite in various organisms. Herein, a sensitivity intensified ninhydrin-based chromogenic system (SINICS), achieved by ethanol and ethyl acetate, is described for the reliable relative quantitation of GABA. A 2.9 mL SINICS kit comprises 1% ninhydrin, 40% ethanol, 25% ethyl acetate, and 35 μL 0.2 M sodium acetate buffer (pH 5.0). In practice, following the addition of a 0.1 mL sample to the kit, the chromogenic reaction is completed by heating at 70 °C for 30 min. The kit increased the color development sensitivity of L-glutamic acid and GABA, with the detection limits being reduced from 20 mM and 200 mM to 5 mM and 20 mM, respectively. The chromophore was stable for at least 2 h at room temperature, which was sufficient for a routine colorimetric analysis. The absorbance at 570 nm with the deduction of background directly represents the content of amino acid. For a proof-of-concept, the SINICS was adopted to optimize the GABA fermentation process of Levilactobacillus brevis CD0817. The results demonstrated that SINICS is an attractive alternative to the available ninhydrin-based colorimetric methods. Full article
Show Figures

Figure 1

Previous Issue
Next Issue
Back to TopTop