Metabolites

19 pages, 2207 KiB

Open AccessArticle

Anti-Heliobacter pylori and Anti-Inflammatory Potential of Salvia officinalis Metabolites: In Vitro and In Silico Studies

by Hatun A. Alomar, Wafaa M. Elkady, Marwa M. Abdel-Aziz, Taghreed A. Ibrahim and Noha Fathallah

Metabolites 2023, 13(1), 136; https://doi.org/10.3390/metabo13010136 - 16 Jan 2023

Cited by 2 | Viewed by 2333

Abstract

Due to its rising antibiotic resistance and associated inflammations, Helicobacter pylori poses a challenge in modern medicine. Salvia officinalis, a member of the Lamiaceae family, is a promising medicinal herb. In this regard, a phytochemical screening followed by GC-MS and LC-MS was [...] Read more.

Due to its rising antibiotic resistance and associated inflammations, Helicobacter pylori poses a challenge in modern medicine. Salvia officinalis, a member of the Lamiaceae family, is a promising medicinal herb. In this regard, a phytochemical screening followed by GC-MS and LC-MS was done to evaluate the chemical profile of the total ethanolic extract (TES) and the essential oil, respectively. The anti-H. pylori and the anti-inflammatory activities were evaluated by a micro-well dilution technique and COX-2 inhibition assay. Potential anti-H. pylori inhibitors were determined by an in silico study. The results revealed that the main metabolites were flavonoids, sterols, volatile oil, saponins, and carbohydrates. The LC-MS negative ionization mode demonstrated 12 compounds, while GC-MS showed 21 compounds. Carnosic acid (37.66%), epirosmanol (20.65%), carnosol1 (3.3%), and 12-O-methyl carnosol (6.15%) were predominated, while eucalyptol (50.04%) and camphor (17.75%) were dominant in LC-MS and GC-MS, respectively. TES exhibited the strongest anti-H. pylori activity (3.9 µg/mL) asymptotic to clarithromycin (0.43 µg/mL), followed by the oil (15.63 µg/mL). Carnosic acid has the best-fitting energy to inhibit H. pylori (−46.6769 Kcal/mol). TES showed the highest reduction in Cox-2 expression approaching celecoxib with IC₅₀ = 1.7 ± 0.27 µg/mL, followed by the oil with IC₅₀ = 5.3 ± 0.62 µg/mL. Our findings suggest that S. officinalis metabolites with anti-inflammatory capabilities could be useful in H. pylori management. Further in vivo studies are required to evaluate and assess its promising activity. Full article

(This article belongs to the Special Issue Extraction, Characterization, Chemical Composition and Biological Activity of Natural Metabolites)

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22 pages, 2684 KiB

Open AccessEditor’s ChoiceArticle

Integration of LC-MS-Based and GC-MS-Based Metabolic Profiling to Reveal the Effects of Domestication and Boiling on the Composition of Duck Egg Yolks

by Yong Tian, Guoqin Li, Xizhong Du, Tao Zeng, Li Chen, Wenwu Xu, Tiantian Gu, Zhengrong Tao and Lizhi Lu

Metabolites 2023, 13(1), 135; https://doi.org/10.3390/metabo13010135 - 16 Jan 2023

Cited by 2 | Viewed by 1815

Abstract

Egg yolks contain abundant lipids, proteins, and minerals that provide not only essential nutrients for embryonic development but also cheap sources of nutrients for consumers worldwide. Previous composition analyses of egg yolks primarily focused on nutrients such as lipids and minerals. However, few [...] Read more.

Egg yolks contain abundant lipids, proteins, and minerals that provide not only essential nutrients for embryonic development but also cheap sources of nutrients for consumers worldwide. Previous composition analyses of egg yolks primarily focused on nutrients such as lipids and minerals. However, few studies have reported the effects of domestication and heating on yolk composition and characteristics. The objective of this study was to investigate the impact of domestication and boiling on the metabolite contents of egg yolks via untargeted metabolomics using GC-MS and LC-MS. In this study, eggs were collected from Fenghua teals, captive mallards, and Shaoxing ducks. Twelve duck eggs (half raw and half cooked) were randomly selected from each variety, and the egg yolks were separated for metabolic profiling. The analysis identified 1205 compounds in the egg yolks. Domestication generated more differential metabolites than boiling, which indicated that the changes in the metabolome of duck egg yolk caused by domestication were greater than those caused by boiling. In a comparative analysis of domestic and mallard ducks, 48 overlapping differential metabolites were discovered. Among them, nine metabolites were upregulated in domesticated ducks, including monoolein, emodin, daidzein, genistein, and glycitein, which may be involved in lipid metabolism; some of them may also act as phytoestrogens (flavonoids). Another 39 metabolites, including imethylethanolamine, harmalan, mannitol, nornicotine, linoleic acid, diphenylamine, proline betaine, alloxanthin, and resolvin d1, were downregulated by domestication and were linked to immunity, anti-inflammatory, antibacterial, and antioxidant properties. Furthermore, four overlapping differential metabolites that included amino acids and dipeptides were discovered in paired comparisons of the raw and boiled samples. Our findings provided new insights into the molecular response of duck domestication and supported the use of metabolomics to examine the impact of boiling on the composition of egg yolks. Full article

(This article belongs to the Section Nutrition and Metabolism)

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39 pages, 3036 KiB

Open AccessReview

Therapeutic and Toxic Effects of Valproic Acid Metabolites

by Natalia A. Shnayder, Violetta V. Grechkina, Aiperi K. Khasanova, Elena N. Bochanova, Evgenia A. Dontceva, Marina M. Petrova, Azat R. Asadullin, German A. Shipulin, Kuanysh S. Altynbekov, Mustafa Al-Zamil and Regina F. Nasyrova

Metabolites 2023, 13(1), 134; https://doi.org/10.3390/metabo13010134 - 16 Jan 2023

Cited by 15 | Viewed by 3821

Abstract

Valproic acid (VPA) and its salts are psychotropic drugs that are widely used in neurological diseases (epilepsy, neuropathic pain, migraine, etc.) and psychiatric disorders (schizophrenia, bipolar affective disorder, addiction diseases, etc.). In addition, the indications for the appointment of valproate have been expanding [...] Read more.

Valproic acid (VPA) and its salts are psychotropic drugs that are widely used in neurological diseases (epilepsy, neuropathic pain, migraine, etc.) and psychiatric disorders (schizophrenia, bipolar affective disorder, addiction diseases, etc.). In addition, the indications for the appointment of valproate have been expanding in recent years in connection with the study of new mechanisms of action of therapeutic and toxic metabolites of VPA in the human body. Thus, VPA is considered a component of disease-modifying therapy for multiple tumors, neurodegenerative diseases (Huntington’s disease, Parkinson’s disease, Duchenne progressive dystrophy, etc.), and human immunodeficiency syndrome. The metabolism of VPA is complex and continues to be studied. Known pathways of VPA metabolism include: β-oxidation in the tricarboxylic acid cycle (acetylation); oxidation with the participation of cytochrome P-450 isoenzymes (P-oxidation); and glucuronidation. The complex metabolism of VPA explains the diversity of its active and inactive metabolites, which have therapeutic, neutral, or toxic effects. It is known that some active metabolites of VPA may have a stronger clinical effect than VPA itself. These reasons explain the relevance of this narrative review, which summarizes the results of studies of blood (serum, plasma) and urinary metabolites of VPA from the standpoint of the pharmacogenomics and pharmacometabolomics. In addition, a new personalized approach to assessing the cumulative risk of developing VPA-induced adverse reactions is presented and ways for their correction are proposed depending on the patient’s pharmacogenetic profile and the level of therapeutic and toxic VPA metabolites in the human body fluids (blood, urine). Full article

(This article belongs to the Special Issue Urinary Metabolomic Profiling Analysis and Evaluation)

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11 pages, 732 KiB

Open AccessArticle

The Effect of Childhood Obesity or Sarcopenic Obesity on Metabolic Syndrome Risk in Adolescence: The Ewha Birth and Growth Study

by Hyunjin Park, Seunghee Jun, Hye-Ah Lee, Hae Soon Kim, Young Sun Hong and Hyesook Park

Metabolites 2023, 13(1), 133; https://doi.org/10.3390/metabo13010133 - 16 Jan 2023

Cited by 3 | Viewed by 1996

Abstract

The prevalence of obesity and metabolic syndrome (MetS) in the pediatric population has increased globally. We evaluated the impact of childhood obesity and sarcopenic obesity on the risk of MetS in adolescence using the Ewha Birth and Growth Cohort study data. In this [...] Read more.

The prevalence of obesity and metabolic syndrome (MetS) in the pediatric population has increased globally. We evaluated the impact of childhood obesity and sarcopenic obesity on the risk of MetS in adolescence using the Ewha Birth and Growth Cohort study data. In this study, we analyzed data from 227 participants who were followed up at the ages of 7–9 and 13–15 years. Overweight and obesity were defined as a body mass index of the 85th percentile or higher based on national growth charts, and sarcopenic obesity was defined using body composition data. Metabolic diseases in adolescence were identified by calculating the pediatric simple metabolic syndrome score (PsiMS), continuous metabolic syndrome score (cMetS), and single-point insulin sensitivity estimator (SPISE) as MetS indices. The prevalence of overweight was approximately 15% at both 7–9 and 13–15 years old, and that of sarcopenic obesity (7–9 years old) was 19.5%. Boys aged 13–15 years had a significantly larger waist circumference (WC) and higher systolic blood pressure (SBP) than girls. The MetS indices (PsiMS, cMetS, and SPISE) showed no significant differences by gender. Overweight and sarcopenic obese people have a higher overall risk of MetS components than normal people. The overweight group had a significantly higher prevalence of PsiMS and cMetS than the normal group, while the SPISE was significantly lower and the MetS indicator was worse in the overweight group than in the normal group. Similar results were obtained in the group with sarcopenic obesity. Both overweight and sarcopenic obesity remained significantly associated with MetS indicators, even after adjusting for covariates. Furthermore, metabolic health assessed by the cMetS in adolescence was affected not only by childhood overweight but also by adolescence, which showed an interaction effect. The results of this study emphasize the importance and need for early detection of childhood obesity and effective public health interventions. Full article

(This article belongs to the Section Nutrition and Metabolism)

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20 pages, 6733 KiB

Open AccessArticle

Comparison of the Pig Breeds in the Small Intestinal Morphology and Digestive Functions at Different Ages

by Yating Cheng, Sujuan Ding, Md. Abul Kalam Azad, Bo Song and Xiangfeng Kong

Metabolites 2023, 13(1), 132; https://doi.org/10.3390/metabo13010132 - 15 Jan 2023

Cited by 2 | Viewed by 1422

Abstract

The small intestine is the main site for digestion and absorption of nutrients, and the development of the small intestine can be affected by several factors, such as diet composition, age, and genotype. Thus, this study aimed to compare the small intestinal morphology [...] Read more.

The small intestine is the main site for digestion and absorption of nutrients, and the development of the small intestine can be affected by several factors, such as diet composition, age, and genotype. Thus, this study aimed to compare the small intestinal morphology and digestive function differences at different ages of three pig breeds. Thirty litters of newborn Taoyuan black (TB), Xiangcun black (XB), and Duroc (DR) piglets (ten litters per breed) were selected for this study. Ten piglets from each breed were selected and sampled at 1, 10, 21, and 24 days old. The results showed that the TB and XB piglets had lower growth but had higher lactase and maltase activities in the jejunum compared with the DR piglets, while most of the digestive enzyme activities in the ileum were higher in the DR piglets at different ages. The expression levels of nutrient transporters, mainly including amino acids, glucose, and fatty acids transporters, differed in the jejunum at different ages among three pig breeds and were higher in the DR piglets at 1 day old and XB piglets at 24 days old. Collectively, these findings suggest that the phenotypic differences in the growth, intestinal morphology, and digestive function among the three pig breeds mainly resulted from the differences in digestive enzymes and nutrient transporters in the intestine. Full article

(This article belongs to the Section Animal Metabolism)

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16 pages, 2111 KiB

Open AccessArticle

Several Metabolite Families Display Inflexibility during Glucose Challenge in Patients with Type 2 Diabetes: An Untargeted Metabolomics Study

by Giovanni Fanni, Jan W. Eriksson and Maria J. Pereira

Metabolites 2023, 13(1), 131; https://doi.org/10.3390/metabo13010131 - 15 Jan 2023

Viewed by 2318

Abstract

Metabolic inflexibility is a hallmark of insulin resistance and can be extensively explored with high-throughput metabolomics techniques. However, the dynamic regulation of the metabolome during an oral glucose tolerance test (OGTT) in subjects with type 2 diabetes (T2D) is largely unknown. We aimed [...] Read more.

Metabolic inflexibility is a hallmark of insulin resistance and can be extensively explored with high-throughput metabolomics techniques. However, the dynamic regulation of the metabolome during an oral glucose tolerance test (OGTT) in subjects with type 2 diabetes (T2D) is largely unknown. We aimed to identify alterations in metabolite responses to OGTT in subjects with T2D using untargeted metabolomics of both plasma and subcutaneous adipose tissue (SAT) samples. Twenty subjects with T2D and twenty healthy controls matched for sex, age, and body mass index (BMI) were profiled with untargeted metabolomics both in plasma (755 metabolites) and in the SAT (588) during an OGTT. We assessed metabolite concentration changes 90 min after the glucose load, and those responses were compared between patients with T2D and controls. Post-hoc analyses were performed to explore the associations between glucose-induced metabolite responses and markers of obesity and glucose metabolism, sex, and age. During the OGTT, T2D subjects had an impaired reduction in plasma levels of several metabolite families, including acylcarnitines, amino acids, acyl ethanolamines, and fatty acid derivates (p < 0.05), compared to controls. Additionally, patients with T2D had a greater increase in plasma glucose and fructose levels during the OGTT compared to controls (p < 0.05). The plasma concentration change of most metabolites after the glucose load was mainly associated with indices of hyperglycemia rather than insulin resistance, insulin secretion, or BMI. In multiple linear regression analyses, hyperglycemia indices (glucose area under the curve (AUC) during OGTT and glycosylated hemoglobin (HbA1c)) were the strongest predictors of plasma metabolite changes during the OGTT. No differences were found in the adipose tissue metabolome in response to the glucose challenge between T2D and controls. Using a metabolomics approach, we show that T2D patients display attenuated responses in several circulating metabolite families during an OGTT. Besides the well-known increase in monosaccharides, the glucose-induced lowering of amino acids, acylcarnitines, and fatty acid derivatives was attenuated in T2D subjects compared to controls. These data support the hypothesis of inflexibility in several metabolic pathways, which may contribute to dysregulated substrate partitioning and turnover in T2D. These findings are not directly associated with changes in adipose tissue metabolism; therefore, other tissues, such as muscle and liver, are probably of greater importance. Full article

(This article belongs to the Special Issue Insulin Resistance, Adipose Tissue Metabolism and Type 2 Diabetes)

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16 pages, 4112 KiB

Open AccessArticle

Quercetin, a Plant Flavonol Attenuates Diabetic Complications, Renal Tissue Damage, Renal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats

by Arshad Husain Rahmani, Mohammed A. Alsahli, Amjad Ali Khan and Saleh A. Almatroodi

Metabolites 2023, 13(1), 130; https://doi.org/10.3390/metabo13010130 - 15 Jan 2023

Cited by 12 | Viewed by 2312

Abstract

Diabetes mellitus is a metabolic syndrome characterized by increased glucose levels, oxidative stress, hyperlipidemia, and frequently decreased insulin levels. The current research was carried out for eight consecutive weeks to evaluate the possible reno-protective effects of quercetin (50 mg/kg b.w.) on streptozotocin (STZ) [...] Read more.

Diabetes mellitus is a metabolic syndrome characterized by increased glucose levels, oxidative stress, hyperlipidemia, and frequently decreased insulin levels. The current research was carried out for eight consecutive weeks to evaluate the possible reno-protective effects of quercetin (50 mg/kg b.w.) on streptozotocin (STZ) (55 mg/kg b.w.) induced diabetes rat models. Various physiological, biochemical, and histopathological parameters were determined in control, diabetic control, and quercetin-treated diabetic rats. The current findings demonstrated that diabetes control rats showed significantly decreased body weights (198 ± 10 vs. 214 ± 13 g) and insulin levels (0.28 ± 0.04 vs. 1.15 ± 0.05 ng/mL) in comparison to normal control. Besides this, the other parameters showed increased values, such as fasting blood glucose, triglyceride (TG), and total cholesterol levels (99 ± 5 vs. 230 ± 7 mg/dL, 122.9 ± 8.7 vs. 230.7 ± 7.2 mg/dL, 97.34 ± 5.7 vs. 146.3 ± 8 mg/dL) (p < 0.05). In addition, the urea and creatinine levels (39.9 ± 1.8 mg/dL and 102.7 ± 7.8 μmol/L) were also high in diabetes control rats. After 8 weeks of quercetin treatment in STZ-treated animals, body weight, insulin, and fasting blood sugar levels were significantly restored (p < 0.05). The inflammatory markers (TNF-α, IL-6, and IL-1β) were significantly increased (52.64 ± 2, 95.64 ± 3, 23.3 ± 1.2 pg/mL) and antioxidant enzymes levels (SOD, GST, CAT, and GSH) were significantly decreased (40.3 ± 3 U/mg, 81.9 ± 10 mU/mg, 14.2 ± 2 U/mg, 19.9 ± 2 μmol/g) in diabetic rats. All the parameters in diabetic animals treated with quercetin were restored towards their normal values. Histopathological findings revealed that the quercetin-treated group showed kidney architecture maintenance, reduction of fibrosis, and decreased expression of COX-2 protein. These results determined that quercetin has reno-protective effects, and conclude that quercetin possesses a strong antidiabetic potential and might act as a therapeutic agent in the prevention or delay of diabetes-associated kidney dysfunction. Full article

(This article belongs to the Special Issue Research Progress of Plant Compounds for Diabetes and Its Complications)

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33 pages, 1053 KiB

Open AccessReview

The Implication of Mechanistic Approaches and the Role of the Microbiome in Polycystic Ovary Syndrome (PCOS): A Review

by Anirban Goutam Mukherjee, Uddesh Ramesh Wanjari, Sandra Kannampuzha, Reshma Murali, Arunraj Namachivayam, Raja Ganesan, Abhijit Dey, Achsha Babu, Kaviyarasi Renu, Balachandar Vellingiri, Gnanasambandan Ramanathan, George Priya Doss C., Nehal Elsherbiny, Amira M. Elsherbini, Alsamman M. Alsamman, Hatem Zayed and Abilash Valsala Gopalakrishnan

Metabolites 2023, 13(1), 129; https://doi.org/10.3390/metabo13010129 - 14 Jan 2023

Cited by 8 | Viewed by 4527

Abstract

As a complex endocrine and metabolic condition, polycystic ovarian syndrome (PCOS) affects women’s reproductive health. These common symptoms include hirsutism, hyperandrogenism, ovulatory dysfunction, irregular menstruation, and infertility. No one knows what causes it or how to stop it yet. Alterations in gut microbiota [...] Read more.

As a complex endocrine and metabolic condition, polycystic ovarian syndrome (PCOS) affects women’s reproductive health. These common symptoms include hirsutism, hyperandrogenism, ovulatory dysfunction, irregular menstruation, and infertility. No one knows what causes it or how to stop it yet. Alterations in gut microbiota composition and disruptions in secondary bile acid production appear to play a causative role in developing PCOS. PCOS pathophysiology and phenotypes are tightly related to both enteric and vaginal bacteria. Patients with PCOS exhibit changed microbiome compositions and decreased microbial diversity. Intestinal microorganisms also alter PCOS patient phenotypes by upregulating or downregulating hormone release, gut-brain mediators, and metabolite synthesis. The human body’s gut microbiota, also known as the “second genome,” can interact with the environment to improve metabolic and immunological function. Inflammation is connected to PCOS and may be caused by dysbiosis in the gut microbiome. This review sheds light on the recently discovered connections between gut microbiota and insulin resistance (IR) and the potential mechanisms of PCOS. This study also describes metabolomic studies to obtain a clear view of PCOS and ways to tackle it. Full article

(This article belongs to the Special Issue Metabolomics Analysis of the Relationship between Intestinal Microorganisms and Human Diseases)

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20 pages, 2979 KiB

Open AccessArticle

Investigation of Chemical Composition and Biological Activities of Ajuga pyramidalis—Isolation of Iridoids and Phenylethanoid Glycosides

by Anthonin Gori, Benjamin Boucherle, Aurélien Rey, Maxime Rome, Caroline Barette, Emmanuelle Soleilhac, Christian Philouze, Marie-Odile Fauvarque, Nicola Fuzzati and Marine Peuchmaur

Metabolites 2023, 13(1), 128; https://doi.org/10.3390/metabo13010128 - 14 Jan 2023

Cited by 3 | Viewed by 1404

Abstract

Despite several studies on the Ajuga L. genus, the chemical composition of Ajuga pyramidalis, an alpine endemic species, is still largely unknown. The purpose of this study was to therefore deeper describe it, particularly from the phytochemistry and bioactivity perspectives. In that [...] Read more.

Despite several studies on the Ajuga L. genus, the chemical composition of Ajuga pyramidalis, an alpine endemic species, is still largely unknown. The purpose of this study was to therefore deeper describe it, particularly from the phytochemistry and bioactivity perspectives. In that respect, A. pyramidalis was investigated and 95% of the extracted mass of the plant was characterized by chromatography and mass spectrometry. Apart from the already determined chemical compounds, namely, harpagide and 8-O-acetylharpagide, two iridoids, and neoajugapyrin A, a neo-clerodane diterpene, and three polyphenols (echinacoside, verbascoside and teupoloside) were identified for the first time in A. pyramidalis. Incidentally, the first RX structure of a harpagoside derivative is also described in this paper. The extracts and isolated compounds were then evaluated for various biochemical or biological activities; notably a targeted action on the renewal of the epidermis was highlighted with potential applications in the cosmetic field for anti-aging. Full article

(This article belongs to the Special Issue Extraction, Characterization, Chemical Composition and Biological Activity of Natural Metabolites)

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14 pages, 601 KiB

Open AccessArticle

rox: A Statistical Model for Regression with Missing Values

by Mustafa Buyukozkan, Elisa Benedetti and Jan Krumsiek

Metabolites 2023, 13(1), 127; https://doi.org/10.3390/metabo13010127 - 13 Jan 2023

Viewed by 1396

Abstract

High-dimensional omics datasets frequently contain missing data points, which typically occur due to concentrations below the limit of detection (LOD) of the profiling platform. The presence of such missing values significantly limits downstream statistical analysis and result interpretation. Two common techniques to deal [...] Read more.

High-dimensional omics datasets frequently contain missing data points, which typically occur due to concentrations below the limit of detection (LOD) of the profiling platform. The presence of such missing values significantly limits downstream statistical analysis and result interpretation. Two common techniques to deal with this issue include the removal of samples with missing values and imputation approaches that substitute the missing measurements with reasonable estimates. Both approaches, however, suffer from various shortcomings and pitfalls. In this paper, we present “rox”, a novel statistical model for the analysis of omics data with missing values without the need for imputation. The model directly incorporates missing values as “low” concentrations into the calculation. We show the superiority of rox over common approaches on simulated data and on six metabolomics datasets. Fully leveraging the information contained in LOD-based missing values, rox provides a powerful tool for the statistical analysis of omics data. Full article

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

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28 pages, 590 KiB

Open AccessReview

Context-Specific Genome-Scale Metabolic Modelling and Its Application to the Analysis of COVID-19 Metabolic Signatures

by Miha Moškon and Tadeja Režen

Metabolites 2023, 13(1), 126; https://doi.org/10.3390/metabo13010126 - 13 Jan 2023

Cited by 5 | Viewed by 2343

Abstract

Genome-scale metabolic models (GEMs) have found numerous applications in different domains, ranging from biotechnology to systems medicine. Herein, we overview the most popular algorithms for the automated reconstruction of context-specific GEMs using high-throughput experimental data. Moreover, we describe different datasets applied in the [...] Read more.

Genome-scale metabolic models (GEMs) have found numerous applications in different domains, ranging from biotechnology to systems medicine. Herein, we overview the most popular algorithms for the automated reconstruction of context-specific GEMs using high-throughput experimental data. Moreover, we describe different datasets applied in the process, and protocols that can be used to further automate the model reconstruction and validation. Finally, we describe recent COVID-19 applications of context-specific GEMs, focusing on the analysis of metabolic implications, identification of biomarkers and potential drug targets. Full article

(This article belongs to the Special Issue Integration and Analysis of Omics Data Using Genome-Scale Metabolic Models)

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14 pages, 947 KiB

Open AccessReview

MOTS-c Functionally Prevents Metabolic Disorders

by Yue Gao, Xinran Wei, Pingying Wei, Huijie Lu, Luying Zhong, Jie Tan, Hongbo Liu and Zheng Liu

Metabolites 2023, 13(1), 125; https://doi.org/10.3390/metabo13010125 - 13 Jan 2023

Cited by 3 | Viewed by 3537

Abstract

Mitochondrial-derived peptides are a family of peptides encoded by short open reading frames in the mitochondrial genome, which have regulatory effects on mitochondrial functions, gene expression, and metabolic homeostasis of the body. As a new member of the mitochondrial-derived peptide family, mitochondrial open [...] Read more.

Mitochondrial-derived peptides are a family of peptides encoded by short open reading frames in the mitochondrial genome, which have regulatory effects on mitochondrial functions, gene expression, and metabolic homeostasis of the body. As a new member of the mitochondrial-derived peptide family, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is regarding a peptide hormone that could reduce insulin resistance, prevent obesity, improve muscle function, promote bone metabolism, enhance immune regulation, and postpone aging. MOTS-c plays these physiological functions mainly through activating the AICAR-AMPK signaling pathways by disrupting the folate-methionine cycle in cells. Recent studies have shown that the above hormonal effect can be achieved through MOTS-c regulating the expression of genes such as GLUT4, STAT3, and IL-10. However, there is a lack of articles summarizing the genes and pathways involved in the physiological activity of MOTS-c. This article aims to summarize and interpret the interesting and updated findings of MOTS-c-associated genes and pathways involved in pathological metabolic processes. Finally, it is expected to develop novel diagnostic markers and treatment approaches with MOTS-c to prevent and treat metabolic disorders in the future. Full article

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

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26 pages, 2092 KiB

Open AccessReview

Flavonoid Production: Current Trends in Plant Metabolic Engineering and De Novo Microbial Production

by Hasnat Tariq, Saaim Asif, Anisa Andleeb, Christophe Hano and Bilal Haider Abbasi

Metabolites 2023, 13(1), 124; https://doi.org/10.3390/metabo13010124 - 13 Jan 2023

Cited by 10 | Viewed by 4015

Abstract

Flavonoids are secondary metabolites that represent a heterogeneous family of plant polyphenolic compounds. Recent research has determined that the health benefits of fruits and vegetables, as well as the therapeutic potential of medicinal plants, are based on the presence of various bioactive natural [...] Read more.

Flavonoids are secondary metabolites that represent a heterogeneous family of plant polyphenolic compounds. Recent research has determined that the health benefits of fruits and vegetables, as well as the therapeutic potential of medicinal plants, are based on the presence of various bioactive natural products, including a high proportion of flavonoids. With current trends in plant metabolite research, flavonoids have become the center of attention due to their significant bioactivity associated with anti-cancer, antioxidant, anti-inflammatory, and anti-microbial activities. However, the use of traditional approaches, widely associated with the production of flavonoids, including plant extraction and chemical synthesis, has not been able to establish a scalable route for large-scale production on an industrial level. The renovation of biosynthetic pathways in plants and industrially significant microbes using advanced genetic engineering tools offers substantial promise for the exploration and scalable production of flavonoids. Recently, the co-culture engineering approach has emerged to prevail over the constraints and limitations of the conventional monoculture approach by harnessing the power of two or more strains of engineered microbes to reconstruct the target biosynthetic pathway. In this review, current perspectives on the biosynthesis and metabolic engineering of flavonoids in plants have been summarized. Special emphasis is placed on the most recent developments in the microbial production of major classes of flavonoids. Finally, we describe the recent achievements in genetic engineering for the combinatorial biosynthesis of flavonoids by reconstructing synthesis pathways in microorganisms via a co-culture strategy to obtain high amounts of specific bioactive compounds Full article

(This article belongs to the Special Issue Advances in Plant Metabolic Engineering)

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12 pages, 1454 KiB

Open AccessViewpoint

Inflammation Control and Immunotherapeutic Strategies in Comprehensive Cancer Treatment

by Victor Ivanovich Seledtsov, Adas Darinskas, Alexei Von Delwig and Galina Victorovna Seledtsova

Metabolites 2023, 13(1), 123; https://doi.org/10.3390/metabo13010123 - 13 Jan 2023

Viewed by 1576

Abstract

Tumor growth and expansion are determined by the immunological tumor microenvironment (TME). Typically, early tumorigenic stages are characterized by the immune system not responding or weakly responding to the tumor. However, subsequent tumorigenic stages witness the tumor promoting its growth and metastasis by [...] Read more.

Tumor growth and expansion are determined by the immunological tumor microenvironment (TME). Typically, early tumorigenic stages are characterized by the immune system not responding or weakly responding to the tumor. However, subsequent tumorigenic stages witness the tumor promoting its growth and metastasis by stimulating tumor-protective (pro-tumor) inflammation to suppress anti-tumor immune responses. Here, we propose the pivotal role of inflammation control in a successful anti-cancer immunotherapy strategy, implying that available and novel immunotherapeutic modalities such as inflammation modulation, antibody (Ab)-based immunostimulation, drug-mediated immunomodulation, cancer vaccination as well as adoptive cell immunotherapy and donor leucocyte transfusion could be applied in cancer patients in a synergistic manner to amplify each other’s clinical effects and achieve robust anti-tumor immune reactivity. In addition, the anti-tumor effects of immunotherapy could be enhanced by thermal and/or oxygen therapy. Herein, combined immune-based therapy could prove to be beneficial for patients with advanced cancers, as aiming to provide long-term tumor cell/mass dormancy by restraining compensatory proliferation of surviving cancer cells observed after traditional anti-cancer interventions such as surgery, radiotherapy, and metronomic (low-dose) chemotherapy. We propose the Inflammatory Prognostic Score based on the blood levels of C-reactive protein and lactate dehydrogenase as well as the neutrophil-to-lymphocyte ratio to effectively monitor the effectiveness of comprehensive anti-cancer treatment. Full article

(This article belongs to the Special Issue Metabolism of Immune System in Inflammatory and Infectious Diseases)

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18 pages, 4269 KiB

Open AccessArticle

Comprehensive Metabolomic Fingerprinting Combined with Chemometrics Identifies Species- and Variety-Specific Variation of Medicinal Herbs: An Ocimum Study

by Abhishek Kumar Rai, Samreen Khan, Akhilesh Kumar, Basant Kumar Dubey, R. K. Lal, Ashutosh Tiwari, Prabodh Kumar Trivedi, Christopher T. Elliott and Ratnasekhar Ch

Metabolites 2023, 13(1), 122; https://doi.org/10.3390/metabo13010122 - 13 Jan 2023

Cited by 7 | Viewed by 2504

Abstract

Identification of plant species is a crucial process in natural products. Ocimum, often referred to as the queen of herbs, is one of the most versatile and globally used medicinal herbs for various health benefits due to it having a wide variety [...] Read more.

Identification of plant species is a crucial process in natural products. Ocimum, often referred to as the queen of herbs, is one of the most versatile and globally used medicinal herbs for various health benefits due to it having a wide variety of pharmacological activities. Despite there being significant global demand for this medicinal herb, rapid and comprehensive metabolomic fingerprinting approaches for species- and variety-specific classification are limited. In this study, metabolomic fingerprinting of five Ocimum species (Ocimum basilicum L., Ocimum sanctum L., Ocimum africanum Lour., Ocimum kilimandscharicum Gurke., and Hybrid Tulsi) and their varieties was performed using LC-MS, GC-MS, and the rapid fingerprinting approach FT-NIR combined with chemometrics. The aim was to distinguish the species- and variety-specific variation with a view toward developing a quality assessment of Ocimum species. Discrimination of species and varieties was achieved using principal component analysis (PCA), partial least squares discriminate analysis (PLS-DA), data-driven soft independent modelling of class analogy (DD-SIMCA), random forest, and K-nearest neighbours with specificity of 98% and sensitivity of 99%. Phenolics and flavonoids were found to be major contributing markers for species-specific variation. The present study established comprehensive metabolomic fingerprinting consisting of rapid screening and confirmatory approaches as a highly efficient means to identify the species and variety of Ocimum, being able to be applied for the quality assessment of other natural medicinal herbs. Full article

(This article belongs to the Special Issue Natural Products: Chemical Profiling, Computational Studies and Bioactivities)

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32 pages, 317 KiB

Open AccessEditorial

Acknowledgment to the Reviewers of Metabolites in 2022

by Metabolites Editorial Office

Metabolites 2023, 13(1), 121; https://doi.org/10.3390/metabo13010121 - 13 Jan 2023

Viewed by 2097

Abstract

High-quality academic publishing is built on rigorous peer review [...] Full article

14 pages, 1106 KiB

Open AccessArticle

Association of Plasma Irisin Levels with Circulating Endothelial Microparticles (EMPs) and Endothelial Progenitor Cells (EPCs) in Children Born Prematurely

by Panagiota Markopoulou, Arsinoi Koutroumpa, Aimilia Mantzou, Alexandra Margeli, Eleni Papanikolaou and Tania Siahanidou

Metabolites 2023, 13(1), 120; https://doi.org/10.3390/metabo13010120 - 13 Jan 2023

Viewed by 1428

Abstract

Prematurity has been linked with endothelial dysfunction in later life. The purpose of this study was to evaluate the association between plasma irisin, an adipomyokine reported to protect the functional integrity of vascular endothelium, and circulating endothelial microparticles (EMPs) and endothelial progenitor cells [...] Read more.

Prematurity has been linked with endothelial dysfunction in later life. The purpose of this study was to evaluate the association between plasma irisin, an adipomyokine reported to protect the functional integrity of vascular endothelium, and circulating endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs), consisting early biomarkers of endothelial dysfunction, in preterm-born children. We studied 131 prepubertal children; 61 preterm and 70 born at term (controls). Plasma irisin was determined by ELISA. Circulating CD62E(+), CD144(+) and CD31(+)/CD42b(-) EMPs, and CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs, were determined by flow cytometry. Body mass index, waist-to-hip ratio, neck circumference, systolic and diastolic blood pressure, and biochemical parameters (glucose, lipids, insulin, HOMA-IR) were also evaluated. Plasma irisin was significantly lower (p = 0.001), whereas circulating EMPs and EPCs were higher, in children born prematurely compared to controls. Irisin was recognized as independent predictor for CD144(+) and CD31(+)/CD42b(-) EMPs, CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs in the total study population, and for CD31(+)/CD42b(-) EMPs in the preterm group. In conclusion, plasma irisin correlates independently with circulating EMP and EPC subpopulations in prepubertal children and in preterm-born ones. Further studies in children will potentially elucidate the link between irisin and the primary stages of prematurity-related endothelial dysfunction. Full article

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

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11 pages, 2635 KiB

Open AccessArticle

Seasonal Variations of Low-Molecular-Weight Organic Acids in Three Evergreen Broadleaf Rhododendron Forests

by Xiaofei Lv, Jiangtao Hao, Yumeng Zhao, Chaochan Li and Wenxuan Quan

Metabolites 2023, 13(1), 119; https://doi.org/10.3390/metabo13010119 - 12 Jan 2023

Viewed by 1172

Abstract

Low-molecular-weight organic acids (LMWOAs) are widely distributed in forests. Fresh leaves, litter, humus, and the topsoil layer of representative Rhododendron delavayi (RD), Rhododendron agastum (RA), and Rhododendron irroratum (RI) in the Baili Rhododendron National Forest Park were sampled to explore their seasonal changes. [...] Read more.

Low-molecular-weight organic acids (LMWOAs) are widely distributed in forests. Fresh leaves, litter, humus, and the topsoil layer of representative Rhododendron delavayi (RD), Rhododendron agastum (RA), and Rhododendron irroratum (RI) in the Baili Rhododendron National Forest Park were sampled to explore their seasonal changes. The contents of oxalic, tartaric, malic, citric, acetic, lactic, succinic, and formic acids in samples from different seasons were determined by high-performance liquid chromatography. The results showed that the composition and content of the LMWOAs in the fresh leaves, litter, humus, and topsoil layer of the rhododendrons were affected by the tree species, samples, and season. The main LMWOA was oxalic acid (the average content in the samples was 195.31 µg/g), followed by malic acid (the average content in the samples was 68.55 µg/g) and tartaric acid (the average content in the samples was 59.82 µg/g). Succinic acid had the lowest content; the average content in the samples was 18.40 µg/g. The LMWOAs of the RD were the highest (the average content in the samples was 517.42 µg/g), and the LMWOAs of the RI were the lowest (the average content in the samples was 445.18 µg/g). The LMWOAs in the three rhododendron forests were in the order of fresh leaves > litter > humus > soil layers. This study showed the seasonal distribution characteristics of LMWOAs in three evergreen broadleaf rhododendron forests, and the results provide a reference for ecosystem management and the protection of wild rhododendron forests. Full article

(This article belongs to the Section Plant Metabolism)

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10 pages, 256 KiB

Open AccessArticle

Cardiopulmonary Fitness of Preschoolers with Congenital Heart Disease: An Observational Study

by Yen-Yu Chen, Chung-Lan Kao, Sheng-Hui Tuan and Ko-Long Lin

Metabolites 2023, 13(1), 118; https://doi.org/10.3390/metabo13010118 - 11 Jan 2023

Viewed by 1253

Abstract

With advancements in cardiopulmonary rehabilitation over the past few decades, the survival rate of patients with congenital heart disease (CHD) has increased. However, the Cardiopulmonary fitness (CPF) of these patients is poor. Here, we aimed to investigate CPF in preschoolers with CHD (aged [...] Read more.

With advancements in cardiopulmonary rehabilitation over the past few decades, the survival rate of patients with congenital heart disease (CHD) has increased. However, the Cardiopulmonary fitness (CPF) of these patients is poor. Here, we aimed to investigate CPF in preschoolers with CHD (aged 4 to 6 years) using cardiopulmonary exercise testing. We retrospectively compared 102 healthy preschoolers with 80 preschoolers with CHD. The latter had lower peak oxygen consumption, oxygen consumption at anaerobic threshold and metabolic equivalent at anaerobic threshold. The same result was observed in boys with CHD, but not in girls, when sex was sub-analyzed. Considering the body composition, children with CHD had a lower fat-free mass index (FFMI) than their healthy peers. Healthy preschoolers with a normal body mass index (BMI) had higher anaerobic threshold and peak metabolic equivalent values than overweight or underweight children. This was categorized under the BMI reference of the Ministry of Health and Welfare in Taiwan. In conclusion, the CPF difference between the CHD and healthy groups was identified as early as in preschool age, and better CPF in healthy preschoolers within the normal BMI range suggests the importance of weight control in young children. Full article

(This article belongs to the Section Nutrition and Metabolism)

12 pages, 1383 KiB

Open AccessArticle

Elevation of Lipid Metabolites in Deceased Liver Donors Reflects Graft Suffering

by Wei-Chen Lee, Ting-Jung Wu, Chih-Hsien Cheng, Yu-Chao Wang, Hao-Chien Hung, Jin-Chiao Lee, Tsung-Han Wu, Hong-Shiue Chou, Chen-Fang Lee and Kun-Ming Chan

Metabolites 2023, 13(1), 117; https://doi.org/10.3390/metabo13010117 - 11 Jan 2023

Cited by 1 | Viewed by 1127

Abstract

Liver transplantation can be performed with deceased or living donor allografts. Deceased liver grafts are donated from brain- or circulation-death patients, and they have usually suffered from a certain degree of damage. Post-transplant graft function and patient survival are closely related to liver [...] Read more.

Liver transplantation can be performed with deceased or living donor allografts. Deceased liver grafts are donated from brain- or circulation-death patients, and they have usually suffered from a certain degree of damage. Post-transplant graft function and patient survival are closely related to liver allograft recovery. How to define the damage of liver grafts is unclear. A total of 47 liver donors, 23 deceased and 24 living, were enrolled in this study. All deceased donors had suffered from severe brain damage, and six of them had experienced cardio-pulmonary-cerebral resuscitation (CPR). The exploration of liver graft metabolomics was conducted by liquid chromatography coupled with mass spectrometry. Compared with living donor grafts, the deceased liver grafts expressed higher levels of various diacylglycerol, lysophosphatidylcholine, lysophosphatidylethanolamine, oleoylcarnitine and linoleylcarnitine; and lower levels of cardiolipin and phosphatidylcholine. The liver grafts from the donors with CPR had higher levels of cardiolipin, phosphatidic acid, phosphatidylcholine, phatidylethanolamine and amiodarone than the donors without CPR. When focusing on amino acids, the deceased livers had higher levels of histidine, taurine and tryptophan than the living donor livers. In conclusion, the deceased donors had suffered from cardio-circulation instability, and their lipid metabolites were increased. The elevation of lipid metabolites can be employed as an indicator of liver graft suffering. Full article

(This article belongs to the Section Lipid Metabolism)

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8 pages, 1056 KiB

Open AccessBrief Report

New Markers for Cardiovascular Disease in Psoriatic Patients: Preliminary Study on Monocyte Phenotype, ADAMTS7, and mTOR Activity

by Khanty Loyola, Claudio Karsulovic, Raúl Cabrera, Claudio Perez and Lía Hojman

Metabolites 2023, 13(1), 116; https://doi.org/10.3390/metabo13010116 - 11 Jan 2023

Cited by 1 | Viewed by 1253

Abstract

Psoriasis is a skin disease with occasional involvement of non-cutaneous territories. Beyond the usual, cardiovascular events are more frequent in these patients and correlate only partially with disease activity, suggesting the presence of other unknown factors. We selected ten psoriatic patients without treatment [...] Read more.

Psoriasis is a skin disease with occasional involvement of non-cutaneous territories. Beyond the usual, cardiovascular events are more frequent in these patients and correlate only partially with disease activity, suggesting the presence of other unknown factors. We selected ten psoriatic patients without treatment in the last year and matched them for age and gender with eleven healthy subjects. Ficoll-extracted mononuclear cells were analyzed with flow cytometry for monocyte surface phenotype markers, intracellular NFκB/inflammasome-dependent interleukins, and chemotaxis receptor CXCR3. Using ELISA, patient serum was evaluated for ADAMTS7 and CXCL10. Inflammatory M1 monocytes showed higher levels of IL-1β and IL-6 in psoriatic patients. M2 monocytes also showed higher levels of intracellular inflammatory cytokines. Nevertheless, IL-6 values were higher compared to other monocytes and IL-1β. The mTORC activation markers ADAMTS7 and S6Rp were higher in psoriatic patients than in healthy controls. In psoriatic patients, serum levels of ADAMTS7 were elevated, and M2 monocytes showed a distinct inflammatory response with higher relative levels of NFκB-dependent IL-6 and less activity of the CXCR3–CXCL10 chemotactic pathway. These data suggest pathways with potential markers for prediction and early detection of cardiovascular risk in psoriatic patients. Full article

(This article belongs to the Special Issue Psoriasis and Its Related Metabolic Complications)

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13 pages, 1998 KiB

Open AccessArticle

Co-Expression of Lipid Transporters Simultaneously Enhances Oil and Starch Accumulation in the Green Microalga Chlamydomonas reinhardtii under Nitrogen Starvation

by Ru Chen, Yasuyo Yamaoka, Yanbin Feng, Zhanyou Chi, Song Xue and Fantao Kong

Metabolites 2023, 13(1), 115; https://doi.org/10.3390/metabo13010115 - 10 Jan 2023

Cited by 8 | Viewed by 1927

Abstract

Lipid transporters synergistically contribute to oil accumulation under normal conditions in microalgae; however, their effects on lipid metabolism under stress conditions are unknown. Here, we examined the effect of the co-expression of lipid transporters, fatty acid transporters, (FAX1 and FAX2) and ABC transporter [...] Read more.

Lipid transporters synergistically contribute to oil accumulation under normal conditions in microalgae; however, their effects on lipid metabolism under stress conditions are unknown. Here, we examined the effect of the co-expression of lipid transporters, fatty acid transporters, (FAX1 and FAX2) and ABC transporter (ABCA2) on lipid metabolism and physiological changes in the green microalga Chlamydomonas under nitrogen (N) starvation. The results showed that the TAG content in FAX1-FAX2-ABCA2 over-expressor (OE) was 2.4-fold greater than in the parental line. Notably, in FAX1-FAX2-ABCA2-OE, the major membrane lipids and the starch and cellular biomass content also significantly increased compared with the control lines. Moreover, the expression levels of genes directly involved in TAG, fatty acid, and starch biosynthesis were upregulated. FAX1-FAX2-ABCA2-OE showed altered photosynthesis activity and increased ROS levels during nitrogen (N) deprivation. Our results indicated that FAX1-FAX2-ABCA2 overexpression not only enhanced cellular lipids but also improved starch and biomass contents under N starvation through modulation of lipid and starch metabolism and changes in photosynthesis activity. The strategy developed here could also be applied to other microalgae to produce FA-derived energy-rich and value-added compounds. Full article

(This article belongs to the Special Issue Regulation of Plant Lipid Metabolism)

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19 pages, 998 KiB

Open AccessReview

The Role of Quorum Sensing Molecules in Bacterial–Plant Interactions

by Jan Majdura, Urszula Jankiewicz, Agnieszka Gałązka and Sławomir Orzechowski

Metabolites 2023, 13(1), 114; https://doi.org/10.3390/metabo13010114 - 10 Jan 2023

Cited by 12 | Viewed by 3100

Abstract

Quorum sensing (QS) is a system of communication of bacterial cells by means of chemical signals called autoinducers, which modulate the behavior of entire populations of Gram-negative and Gram-positive bacteria. Three classes of signaling molecules have been recognized, Al-1, Al-2, Al-3, whose functions [...] Read more.

Quorum sensing (QS) is a system of communication of bacterial cells by means of chemical signals called autoinducers, which modulate the behavior of entire populations of Gram-negative and Gram-positive bacteria. Three classes of signaling molecules have been recognized, Al-1, Al-2, Al-3, whose functions are slightly different. However, the phenomenon of quorum sensing is not only concerned with the interactions between bacteria, but the whole spectrum of interspecies interactions. A growing number of research results confirm the important role of QS molecules in the growth stimulation and defense responses in plants. Although many of the details concerning the signaling metabolites of the rhizosphere microflora and plant host are still unknown, Al-1 compounds should be considered as important components of bacterial–plant interactions, leading to the stimulation of plant growth and the biological control of phytopathogens. The use of class 1 autoinducers in plants to induce beneficial activity may be a practical solution to improve plant productivity under field conditions. In addition, researchers are also interested in tools that offer the possibility of regulating the activity of autoinducers by means of degrading enzymes or specific inhibitors (QSI). Current knowledge of QS and QSI provides an excellent foundation for the application of research to biopreparations in agriculture, containing a consortia of AHL-producing bacteria and QS inhibitors and limiting the growth of phytopathogenic organisms. Full article

(This article belongs to the Special Issue Bioactive Metabolites from Natural Sources)

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19 pages, 5459 KiB

Open AccessArticle

A Study of the Interaction between Xanthine Oxidase and Its Inhibitors from Chrysanthemum morifolium Using Computational Simulation and Multispectroscopic Methods

by Sze Ping Wee, Khye Er Loh, Kok Wai Lam and Intan Safinar Ismail

Metabolites 2023, 13(1), 113; https://doi.org/10.3390/metabo13010113 - 09 Jan 2023

Cited by 3 | Viewed by 1428

Abstract

The current therapeutic approach for gout is through the inhibition of the xanthine oxidase (XO) enzyme. Allopurinol, a clinically used XO inhibitor, causes many side effects. This study aimed to investigate the interaction between XO and inhibitors identified from Chrysanthemum morifolium by using [...] Read more.

The current therapeutic approach for gout is through the inhibition of the xanthine oxidase (XO) enzyme. Allopurinol, a clinically used XO inhibitor, causes many side effects. This study aimed to investigate the interaction between XO and inhibitors identified from Chrysanthemum morifolium by using computational simulation and multispectroscopic methods. The crude extract, petroleum ether, ethyl acetate (EtOAc), and residual fractions were subjected to an XO inhibitory assay and ¹H NMR analysis. The EtOAc fraction was shown to be strongly correlated to the XO inhibitory activity by using PLS biplot regression analysis. Kaempferol, apigenin, homovanillic acid, and trans-cinnamic acid were suggested to contribute to the XO inhibitory activity. Molecular docking showed that kaempferol and apigenin bound to the active site of XO with their benzopyran moiety sandwiched between Phe914 and Phe1009, interacting with Thr1010 and Arg880 by hydrogen bonding. Kaempferol showed the lowest binding energy in molecular dynamic simulation. The residues that contributed to the binding energy were Glu802, Arg880, Phe 914, and Phe 1009. A fluorescence quenching study showed a combination of static and dynamic quenching for all four inhibitors binding to XO. Circular dichroism spectroscopy revealed that there was no major change in XO conformation after binding with each inhibitor. Full article

(This article belongs to the Special Issue Extraction, Characterization, Chemical Composition and Biological Activity of Natural Metabolites)

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13 pages, 1200 KiB

Open AccessArticle

Mitochondrial and Endoplasmic Reticulum Stress Trigger Triglyceride Accumulation in Models of Parkinson’s Disease Independent of Mutations in MAPT

by Hugo J. R. Fernandes, Josh P. Kent, Michaela Bruntraeger, Andrew R. Bassett, Albert Koulman, Emmanouil Metzakopian and Stuart G. Snowden

Metabolites 2023, 13(1), 112; https://doi.org/10.3390/metabo13010112 - 09 Jan 2023

Cited by 2 | Viewed by 2036

Abstract

The metabolic basis of Parkinson’s disease pathology is poorly understood. However, the involvement of mitochondrial and endoplasmic reticulum stress in dopamine neurons in disease aetiology is well established. We looked at the effect of rotenone- and tunicamycin-induced mitochondrial and ER stress on the [...] Read more.

The metabolic basis of Parkinson’s disease pathology is poorly understood. However, the involvement of mitochondrial and endoplasmic reticulum stress in dopamine neurons in disease aetiology is well established. We looked at the effect of rotenone- and tunicamycin-induced mitochondrial and ER stress on the metabolism of wild type and microtubule-associated protein tau mutant dopamine neurons. Dopamine neurons derived from human isolated iPSCs were subjected to mitochondrial and ER stress using RT and TM, respectively. Comprehensive metabolite profiles were generated using a split phase extraction analysed by reversed phase lipidomics whilst the aqueous phase was measured using HILIC metabolomics. Mitochondrial and ER stress were both shown to cause significant dysregulation of metabolism with RT-induced stress producing a larger shift in the metabolic profile of both wild type and MAPT neurons. Detailed analysis showed that accumulation of triglycerides was a significant driver of metabolic dysregulation in response to both stresses in both genotypes. Whilst the consequence is similar, the mechanisms by which triglyceride accumulation occurs in dopamine neurons in response to mitochondrial and ER stress are very different. Thus, improving our understanding of how these mechanisms drive the observed triglyceride accumulation can potentially open up new therapeutic avenues. Full article

(This article belongs to the Section Cell Metabolism)

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9 pages, 437 KiB

Open AccessArticle

Physical Inactivity, Metabolic Syndrome and Prostate Cancer Diagnosis: Development of a Predicting Nomogram

by Cosimo De Nunzio, Aldo Brassetti, Fabiana Cancrini, Francesco Prata, Luca Cindolo, Petros Sountoulides, Chrysovalantis Toutziaris, Mauro Gacci, Riccardo Lombardo, Antonio Cicione, Giorgia Tema, Luigi Schips, Giuseppe Simone, Sergio Serni and Andrea Tubaro

Metabolites 2023, 13(1), 111; https://doi.org/10.3390/metabo13010111 - 09 Jan 2023

Cited by 3 | Viewed by 1644

Abstract

Insufficient physical activity (PA) may be a shared risk factor for the development of both metabolic syndrome (MetS) and prostate cancer (PCa). To investigate this correlation and to develop a nomogram able to predict tumor diagnosis. Between 2016 and 2018, a consecutive series [...] Read more.

Insufficient physical activity (PA) may be a shared risk factor for the development of both metabolic syndrome (MetS) and prostate cancer (PCa). To investigate this correlation and to develop a nomogram able to predict tumor diagnosis. Between 2016 and 2018, a consecutive series of men who underwent prostate biopsy at three institutions were prospectively enrolled. PA was self-assessed by patients through the Physical Activity Scale for the Elderly (PASE) questionnaire; MetS was assessed according to Adult Treatment Panel III criteria. A logistic regression analyses was used to identify predictors of PCa diagnosis and high-grade disease (defined as International Society of Uro-Pathology grade >2 tumors). A nomogram was then computed to estimate the risk of tumor diagnosis. A total of 291 patients were enrolled; 17.5% of them (n = 51) presented with MetS. PCa was diagnosed in 110 (38%) patients overall while 51 presented high-grade disease. At multivariable analysis, age (OR 1.04; 95%CI: 1.00–1.08; p = 0.048), prostate volume (PV) (OR 0.98; 95%CI: 0.79–0.99; p = 0.004), suspicious digital rectal examination (OR 2.35; 95%CI: 1.11–4.98; p = 0.02), total PSA value (OR 1.12; 95%CI: 1.05–1.2; p < 0.001), and PASE score (OR 0.99; 95%CI: 0.98–0.99; p = 0.01) were independent predictors of tumor diagnosis. The latter two also predicted high-grade PCa. MetS was not associated with PCa diagnosis and aggressiveness. The novel nomogram displayed fair discrimination for PCa diagnosis (AUC = 0.76), adequate calibration (p > 0.05) and provided a net benefit in the range of probabilities between 20% and 90%. reduced PA was associated with an increased risk of PCa diagnosis and high-grade disease. Our nomogram could improve the selection of patients scheduled for prostate biopsy at increased risk of PCa. Full article

(This article belongs to the Special Issue Exercise Training on Metabolic Dysfunctions—Exerkines Are the Missing Link in Preventing Metabolic Complications)

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14 pages, 3285 KiB

Open AccessArticle

Glycolytic Plasticity of Metastatic Lung Cancer Captured by Noninvasive ¹⁸F-FDG PET/CT and Serum ¹H-NMR Analysis: An Orthotopic Murine Model Study

by Yi-Hsiu Chung, Tsai-Hsien Hung, Ching-Fang Yu, Cheng-Kun Tsai, Chi-Chang Weng, Fujie Jhang, Fang-Hsin Chen and Gigin Lin

Metabolites 2023, 13(1), 110; https://doi.org/10.3390/metabo13010110 - 09 Jan 2023

Cited by 3 | Viewed by 2064

Abstract

We aim to establish a noninvasive diagnostic platform to capture early phenotypic transformation for metastasis using ¹⁸F-FDG PET and ¹H-NMR-based serum metabolomics. Mice with implantation of NCI-H460 cells grew only primary lung tumors in the localized group and had both primary [...] Read more.

We aim to establish a noninvasive diagnostic platform to capture early phenotypic transformation for metastasis using ¹⁸F-FDG PET and ¹H-NMR-based serum metabolomics. Mice with implantation of NCI-H460 cells grew only primary lung tumors in the localized group and had both primary and metastatic lung tumors in the metastatic group. The serum metabolites were analyzed using ¹H-NMR at the time of PET/CT scan. The glycolysis status and cell proliferation were validated by Western blotting and staining. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of SUV_mean and serum metabolites in metastasis. In the metastatic mice, the SUV_mean of metastatic tumors was significantly higher than that of primary lung tumors in PET images, which was supported by elevated glycolytic protein expression of HK2 and PKM2. The serum pyruvate level in the metastatic group was significantly lower than that in the localized group, corresponding to increased pyruvate-catalyzed enzyme and proliferation rates in metastatic tumors. In diagnosing localized or metastatic tumors, the areas under the ROC curves of SUV_mean and pyruvate were 0.92 and 0.91, respectively, with p < 0.05. In conclusion, the combination of ¹⁸F-FDG PET and ¹H-NMR-based serum metabolomics demonstrated the feasibility of a glycolytic platform for diagnosing metastatic lung cancers. Full article

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10 pages, 1555 KiB

Open AccessArticle

Appraising the Effects of Metabolic Traits on the Risk of Glaucoma: A Mendelian Randomization Study

by Kai Wang, Fangkun Yang, Xin Liu, Xueqi Lin, Houfa Yin, Qiaomei Tang, Li Jiang and Ke Yao

Metabolites 2023, 13(1), 109; https://doi.org/10.3390/metabo13010109 - 09 Jan 2023

Cited by 1 | Viewed by 2244

Abstract

Metabolic traits are associated with the risk of developing glaucoma in observational studies. To assess whether theses associations reflect causality, we conducted a Mendelian randomization (MR) study. Our study included up to 20,906 glaucoma cases and 438,188 controls. Genetic instruments associated with the [...] Read more.

Metabolic traits are associated with the risk of developing glaucoma in observational studies. To assess whether theses associations reflect causality, we conducted a Mendelian randomization (MR) study. Our study included up to 20,906 glaucoma cases and 438,188 controls. Genetic instruments associated with the concerned 11 exposures at the genome-wide significance level were selected from corresponding genome-wide association studies. Summary-level data for glaucoma were obtained from the UK Biobank, the GERA study, and the FinnGen consortium. Univariable and multivariable MR analyses were conducted separately in two populations. Our results showed that higher genetic liability to type 2 diabetes (T2D) was causally and independently associated with an increased risk of glaucoma (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.06–1.16; p = 4.4 × 10⁻⁶). The association for T2D persisted after multivariable adjustment. In addition, higher genetically predicted systolic blood pressure (SBP), fasting glucose (FG), and HbA1c, were also suggestively associated with glaucoma risk. The OR was 1.08 (95% CI, 1.01–1.16; p = 0.035) for SBP, 1.24 (95% CI, 1.05–1.47; p = 0.011) for FG, and 1.28 (95% CI, 1.01–1.61; p = 0.039) for HbA1c. No evidence was observed to support the causal effects of body mass index and blood lipids for glaucoma. This study suggests a causal role for diabetes, as well as possible roles for higher SBP, FG, and HbA1c in the development of glaucoma. Further validation is needed to assess the potential of these risk factors as pharmacological targets for glaucoma prevention. Full article

(This article belongs to the Special Issue Nutrition and Metabolism in Human Diseases)

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20 pages, 3190 KiB

Open AccessEditor’s ChoiceArticle

Activity of Microbial-Derived Phenolic Acids and Their Conjugates against LPS-Induced Damage in Neuroblastoma Cells and Macrophages

by Dolores González de Llano, Mikel Roldán, Laura Parro, Begoña Bartolomé and M. Victoria Moreno-Arribas

Metabolites 2023, 13(1), 108; https://doi.org/10.3390/metabo13010108 - 09 Jan 2023

Cited by 4 | Viewed by 1721

Abstract

The aim of this study was to investigate whether microbial-derived phenolic acids, 3,4-dihydroxyphenylacetic (DHPA), protocatechuic acid (PCA), and dihydrocaffeic acid (DHCFA) and their conjugated forms (DHCFA 3-O-sulfate and DHCFA 3-O-β-D-glucuronide), exhibit protective effects against neuroinflammation and oxidative stress. Experiments were performed on human [...] Read more.

The aim of this study was to investigate whether microbial-derived phenolic acids, 3,4-dihydroxyphenylacetic (DHPA), protocatechuic acid (PCA), and dihydrocaffeic acid (DHCFA) and their conjugated forms (DHCFA 3-O-sulfate and DHCFA 3-O-β-D-glucuronide), exhibit protective effects against neuroinflammation and oxidative stress. Experiments were performed on human neuronal SH-SY5Y cells stimulated with bacterial lipopolysaccharide (LPS) and tert-butyl hydroperoxide (tBHP). Anti-inflammatory activity in terms of pro-inflammatory cytokine production was also evaluated in LPS-stimulated RAW 264.7 macrophages as a reactive microglial model. Treatment of the SH-SY5Y cells with the free phenolic acids, as well as with the conjugated metabolites, at physiologically concentrations (1, 10 and 50 μM), resulted in increased cell viability of LPS- and tBHP-stimulated cells. Phenolic metabolites and, especially, the conjugated derivatives also protected neuronal cells through significant attenuation of inflammation by decreasing ROS levels. Furthermore, the conjugated and microbial-derived phenolic metabolites significantly inhibited the secretion of proinflammatory cytokines (TNF-α, IL-6, and IL-8) in LPS-stimulated macrophages. Among the phenolic metabolites tested, different efficacies were observed, with the glucuronide form standing out. Overall, these results suggest, for the first time, that conjugated derivatives of phenolic acids seem to be more effective at protecting neurons from inflammation damage and oxidative stress. Further in vivo studies are warranted. Full article

(This article belongs to the Special Issue The Microbiota–Gut–Brain Axis: Role of Metabolism)

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16 pages, 4641 KiB

Open AccessArticle

Metabolite Profiling of Wheat Response to Cultivar Improvement and Nitrogen Fertilizer

by Fulin Zhao, Yifan Wang, Jiayu Hu, Shaolei Shi, Hongyan Zhang, Yang Wang and Youliang Ye

Metabolites 2023, 13(1), 107; https://doi.org/10.3390/metabo13010107 - 09 Jan 2023

Cited by 1 | Viewed by 1494

Abstract

Both genetic improvement and the application of N fertilizer increase the quality and yields of wheat. However, the molecular kinetics that underlies the differences between them are not well understood. In this study, we performed a non-targeted metabolomic analysis on wheat cultivars from [...] Read more.

Both genetic improvement and the application of N fertilizer increase the quality and yields of wheat. However, the molecular kinetics that underlies the differences between them are not well understood. In this study, we performed a non-targeted metabolomic analysis on wheat cultivars from different release years to comprehensively investigate the metabolic differences between cultivar and N treatments. The results revealed that the plant height and tiller number steadily decreased with increased ears numbers, whereas the grain number and weight increased with genetic improvement. Following the addition of N fertilizer, the panicle numbers and grain weights increased in an old cultivar, whereas the panicle number and grain number per panicle increased in a modern cultivar. For the 1950s to 2010s cultivar, the yield increases due to genetic improvements ranged from −1.9% to 96.7%, whereas that of N application ranged from 19.1% to 81.6%. Based on the untargeted metabolomics approach, the findings demonstrated that genetic improvements induced 1.4 to 7.4 times more metabolic alterations than N fertilizer supply. After the addition of N, 69.6%, 29.4%, and 33.3% of the differential metabolites were upregulated in the 1950s, 1980s, and 2010s cultivars, respectively. The results of metabolic pathway analysis of the identified differential metabolites via genetic improvement indicated enrichment in 1-2 KEGG pathways, whereas the application of N fertilizer enriched 2–4 pathways. Our results provide new insights into the molecular mechanisms of wheat quality and grain yield developments. Full article

(This article belongs to the Section Plant Metabolism)

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Metabolites, Volume 13, Issue 1 (January 2023) – 136 articles

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