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1.
Plasma Metabolomics Profile of "Insulin Sensitive" Male Hypogonadism after Testosterone Replacement Therapy.
Zolla, L, Ceci, M
International journal of molecular sciences. 2022;(3)
Abstract
Male hypogonadism is a disorder characterized by low levels of testosterone, but patients can either show normal insulin (insulin-sensitive (IS)) or over time they can become insulin-resistant (IR). Since the two groups showed different altered metabolisms, testosterone replacement therapy (TRT) could achieve different results. In this paper, we analyzed plasma from 20 IS patients with low testosterone (<8 nmol/L) and HOMAi < 2.5. The samples, pre- and post-treatment with testosterone for 60 days, were analyzed by UHPLC and mass spectrometry. Glycolysis was significantly upregulated, suggesting an improved glucose utilization. Conversely, the pentose phosphate pathway was reduced, while the Krebs cycle was not used. Branched amino acids and carnosine metabolism were positively influenced, while β-oxidation of fatty acids (FFA) was not activated. Cholesterol, HDL, and lipid metabolism did not show any improvements at 60 days but did so later in the experimental period. Finally, both malate and glycerol shuttle were reduced. As a result, both NADH and ATP were significantly lower. Interestingly, a significant production of lactate was observed, which induced the activation of the Cori cycle between the liver and muscles, which became the main source of energy for these patients without involving alanine. Thus, the treatment must be integrated with chemicals which are not restored in order to reactivate energy production.
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2.
Entailing the Next-Generation Sequencing and Metabolome for Sustainable Agriculture by Improving Plant Tolerance.
Ashraf, MF, Hou, D, Hussain, Q, Imran, M, Pei, J, Ali, M, Shehzad, A, Anwar, M, Noman, A, Waseem, M, et al
International journal of molecular sciences. 2022;(2)
Abstract
Crop production is a serious challenge to provide food for the 10 billion individuals forecasted to live across the globe in 2050. The scientists' emphasize establishing an equilibrium among diversity and quality of crops by enhancing yield to fulfill the increasing demand for food supply sustainably. The exploitation of genetic resources using genomics and metabolomics strategies can help generate resilient plants against stressors in the future. The innovation of the next-generation sequencing (NGS) strategies laid the foundation to unveil various plants' genetic potential and help us to understand the domestication process to unmask the genetic potential among wild-type plants to utilize for crop improvement. Nowadays, NGS is generating massive genomic resources using wild-type and domesticated plants grown under normal and harsh environments to explore the stress regulatory factors and determine the key metabolites. Improved food nutritional value is also the key to eradicating malnutrition problems around the globe, which could be attained by employing the knowledge gained through NGS and metabolomics to achieve suitability in crop yield. Advanced technologies can further enhance our understanding in defining the strategy to obtain a specific phenotype of a crop. Integration among bioinformatic tools and molecular techniques, such as marker-assisted, QTLs mapping, creation of reference genome, de novo genome assembly, pan- and/or super-pan-genomes, etc., will boost breeding programs. The current article provides sequential progress in NGS technologies, a broad application of NGS, enhancement of genetic manipulation resources, and understanding the crop response to stress by producing plant metabolites. The NGS and metabolomics utilization in generating stress-tolerant plants/crops without deteriorating a natural ecosystem is considered a sustainable way to improve agriculture production. This highlighted knowledge also provides useful research that explores the suitable resources for agriculture sustainability.
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3.
Characterization of Metabolites in Plasma, Urine and Feces of Healthy Participants after Taking Brahmi Essence for Twelve Weeks Using LC-ESI-QTOF-MS Metabolomic Approach.
Minale, G, Saesong, T, Temkitthawon, P, Waranuch, N, Nuengchamnong, N, Chootip, K, Kamkaew, N, Kongbangkerd, T, Engsuwan, J, Ingkaninan, K
Molecules (Basel, Switzerland). 2021;(10)
Abstract
Brahmi essence, developed from Bacopa monnieri (L.) Wettst. standardized extract and mulberry juice, was proven to improve the memory speed of healthy participants aged 55-80 years old, following a 12-week dietary program. However, the metabolites have not yet been reported. Our objective was to characterize the altered metabolites in the plasma, urine, and feces of healthy volunteers after consumption of Brahmi essence for 12 weeks, using the LC-MS metabolomics approach. The altered metabolites were selected from OPLS-DA S-plots; 15 metabolites in the plasma, 7 in the urine, and 17 in the feces samples were tentatively identified by comparison with an online database and literature. The metabolites in the plasma samples were in the classes of amino acids, acylcarnitine, and phospholipids. Benzeneactamide-4-O-sulphate and 3-hydroxyhippuric acid were found in urine samples. The metabolites in the class of amino acids, together with jujubogenin and pseudojujubogenin, were identified in the fecal samples. The aminoacyl-tRNA, aromatic amino acids, and branched-chain amino acid biosynthetic pathways were mainly related to the identified metabolites in all three samples. It could be implied that those metabolites and their pathways might be linked with the effect of Brahmi essence on memory speed.
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4.
Metformin Treatment or PRODH/POX-Knock out Similarly Induces Apoptosis by Reprograming of Amino Acid Metabolism, TCA, Urea Cycle and Pentose Phosphate Pathway in MCF-7 Breast Cancer Cells.
Huynh, TYL, Oscilowska, I, Sáiz, J, Nizioł, M, Baszanowska, W, Barbas, C, Palka, J
Biomolecules. 2021;(12)
Abstract
It has been considered that proline dehydrogenase/proline oxidase (PRODH/POX) is involved in antineoplastic activity of metformin (MET). The aim of this study is identification of key metabolites of glycolysis, pentose phosphate pathway (PPP), tricarboxylic acids (TCA), urea cycles (UC) and some amino acids in MET-treated MCF-7 cells and PRODH/POX-knocked out MCF-7 (MCF-7crPOX) cells. MCF-7crPOX cells were generated by using CRISPR-Cas9. Targeted metabolomics was performed by LC-MS/MS/QqQ. Expression of pro-apoptotic proteins was evaluated by Western blot. In the absence of glutamine, MET treatment or PRODH/POX-knock out of MCF-7 cells contributed to similar inhibition of glycolysis (drastic increase in intracellular glucose and pyruvate) and increase in the utilization of phospho-enol-pyruvic acid, glucose-6-phosphate and some metabolites of TCA and UC, contributing to apoptosis. However, in the presence of glutamine, MET treatment or PRODH/POX-knock out of MCF-7 cells contributed to utilization of some studied metabolites (except glucose), facilitating pro-survival phenotype of MCF-7 cells in these conditions. It suggests that MET treatment or PRODH/POX-knock out induce similar metabolic effects (glucose starvation) and glycolysis is tightly linked to glutamine metabolism in MCF-7 breast cancer cells. The data provide insight into mechanism of anticancer activity of MET as an approach to further studies on experimental breast cancer therapy.
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5.
Metabolomic Analysis in Inflammatory Bowel Disease: A Systematic Review.
Gallagher, K, Catesson, A, Griffin, JL, Holmes, E, Williams, HRT
Journal of Crohn's & colitis. 2021;(5):813-826
Abstract
BACKGROUND AND AIMS The inflammatory bowel diseases [IBD], Crohn's disease and ulcerative colitis, are chronic, idiopathic gastrointestinal diseases. Although their precise aetiology is unknown, it is thought to involve a complex interaction between genetic predisposition and an abnormal host immune response to environmental exposures, probably microbial. Microbial dysbiosis has frequently been documented in IBD. Metabolomics [the study of small molecular intermediates and end products of metabolism in biological samples] provides a unique opportunity to characterize disease-associated metabolic changes and may be of particular use in quantifying gut microbial metabolism. Numerous metabolomic studies have been undertaken in IBD populations, identifying consistent alterations in a range of molecules across several biological matrices. This systematic review aims to summarize these findings. METHODS A comprehensive, systematic search was carried out using Medline and Embase. All studies were reviewed by two authors independently using predefined exclusion criteria. Sixty-four relevant papers were assessed for quality and included in the review. RESULTS Consistent metabolic perturbations were identified, including increases in levels of branched chain amino acids and lipid classes across stool, serum, plasma and tissue biopsy samples, and reduced levels of microbially modified metabolites in both urine [such as hippurate] and stool [such as secondary bile acids] samples. CONCLUSIONS This review provides a summary of metabolomic research in IBD to date, highlighting underlying themes of perturbed gut microbial metabolism and mammalian-microbial co-metabolism associated with disease status.
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6.
Ionomic Approaches for Discovery of Novel Stress-Resilient Genes in Plants.
Ali, S, Tyagi, A, Bae, H
International journal of molecular sciences. 2021;(13)
Abstract
Plants, being sessile, face an array of biotic and abiotic stresses in their lifespan that endanger their survival. Hence, optimized uptake of mineral nutrients creates potential new routes for enhancing plant health and stress resilience. Recently, minerals (both essential and non-essential) have been identified as key players in plant stress biology, owing to their multifaceted functions. However, a realistic understanding of the relationship between different ions and stresses is lacking. In this context, ionomics will provide new platforms for not only understanding the function of the plant ionome during stresses but also identifying the genes and regulatory pathways related to mineral accumulation, transportation, and involvement in different molecular mechanisms under normal or stress conditions. This article provides a general overview of ionomics and the integration of high-throughput ionomic approaches with other "omics" tools. Integrated omics analysis is highly suitable for identification of the genes for various traits that confer biotic and abiotic stress tolerance. Moreover, ionomics advances being used to identify loci using qualitative trait loci and genome-wide association analysis of element uptake and transport within plant tissues, as well as genetic variation within species, are discussed. Furthermore, recent developments in ionomics for the discovery of stress-tolerant genes in plants have also been addressed; these can be used to produce more robust crops with a high nutritional value for sustainable agriculture.
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7.
Urinary metabolomic profiling reveals difference between two traditional Chinese medicine subtypes of coronary heart disease.
Guo, N, Chen, Y, Yang, X, Yan, H, Fan, B, Quan, J, Wang, M, Yang, H
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2021;:122808
Abstract
The World Health Organization has shown that coronary heart disease (CHD) is a more common cause of death than cancer. In traditional Chinese medicine (TCM), CHD is classified as a form of thoracic obstruction that can be divided in different subtypes including Qi stagnation with blood stasis (QS) and Qi deficiency with blood stasis (QD). Different treatment strategies are used based on this subtyping. Owing to the lack of scientific markers in the diagnosis of these subtypes, subjective judgments made by clinicians have limited the objective manner for utility of TCM in the treatment of CHD. Untargeted (UHPLC-QTOF-MS) and targeted (UHPLC-MS/MS) metabolomics approaches were employed to search significantly different metabolites related to the QS or QD subtypes of CHD with angina pectoris in this study. A total of 42 metabolites were obtained in the untargeted metabolomics analysis and 34 amino acids were detected in the targeted metabolomics analysis. In total, 16 metabolites were found significantly different among different groups. The results showed distinct metabolic profiles of urine samples not only between CHD patients and healthy controls, but also between the two subtypes of CHD. Pathway analysis of the significantly varied metabolites revealed that there were subtype-related differences in the activity of pathways. Therefore, urinary metabolomics can reveal the pathological changes of CHD in different subtypes, make the diagnosis of CHD in different subtypes in an objective manner and comprehensive and contribute to personalized treatment by providing scientific evidence.
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8.
Evaluation of change in metabolome caused by comprehensive diabetes treatment: A prospective observational study of diabetes inpatients with gas chromatography/mass spectrometry-based non-target metabolomic analysis.
Taya, N, Katakami, N, Omori, K, Arakawa, S, Hosoe, S, Watanabe, H, Takahara, M, Miyashita, K, Nishizawa, H, Matsuoka, TA, et al
Journal of diabetes investigation. 2021;(12):2232-2241
Abstract
AIMS/INTRODUCTION Diabetes patients develop a variety of metabolic abnormalities in addition to hyperglycemia. However, details regarding change in various metabolites after comprehensive diabetes treatment remain unknown. This study aimed to identify the short-term change in metabolome in inpatients who were subject to comprehensive diabetes treatment, using gas chromatography/mass spectrometry-based non-target metabolomics techniques. MATERIALS AND METHODS Participants of the present study were randomly recruited from the patients with type 2 diabetes hospitalized due to problems with glycemic control (n = 31) and volunteers without diabetes (n = 30), both of whom were aged between 20 and 75 years. A metabolomic analysis of fasting plasma samples on the 2nd (pre-treatment) and 16th hospital (post-treatment) day with gas chromatography/mass spectrometry using a multiple reaction monitoring mode was carried out. RESULTS A principal component analysis showed that metabolome of fasting plasma was different between individuals with and without diabetes. The metabolome of fasting plasma in diabetes patients after treatment was different from that of pre-treatment, as well as individuals without diabetes. Many amino acids (proline, glycine, serine, threonine, methionine, pyroglutamic acid, glutamine and lysine) were significantly increased by >10% after administering the inpatient diabetes treatment. A hierarchical clustering analysis showed that in the case of patients with markedly decreased monosaccharide levels and increased 1,5-anhydroglucitol, the levels of amino acids increased more significantly. CONCLUSIONS After a 2-week comprehensive treatment, the plasma levels of various amino acids increased in conjunction with the reduction in monosaccharide levels in poorly controlled type 2 diabetes patients.
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9.
Urine and Plasma Metabolome of Healthy Adults Consuming the DASH (Dietary Approaches to Stop Hypertension) Diet: A Randomized Pilot Feeding Study.
Pourafshar, S, Nicchitta, M, Tyson, CC, Svetkey, LP, Corcoran, DL, Bain, JR, Muehlbauer, MJ, Ilkayeva, O, O'Connell, TM, Lin, PH, et al
Nutrients. 2021;(6)
Abstract
We aimed to identify plasma and urine metabolites altered by the Dietary Approaches to Stop Hypertension (DASH) diet in a post-hoc analysis of a pilot feeding trial. Twenty adult participants with un-medicated hypertension consumed a Control diet for one week followed by 2 weeks of random assignment to either Control or DASH diet. Non-missing fasting plasma (n = 56) and 24-h urine (n = 40) were used to profile metabolites using untargeted gas chromatography/mass spectrometry. Linear models were used to compare metabolite levels between the groups. In urine, 19 identifiable untargeted metabolites differed between groups at p < 0.05. These included a variety of phenolic acids and their microbial metabolites that were higher during the DASH diet, with many at false discovery rate (FDR) adjusted p < 0.2. In plasma, eight identifiable untargeted metabolites were different at p < 0.05, but only gamma-tocopherol was significantly lower on DASH at FDR adjusted p < 0.2. The results provide insights into the mechanisms of benefit of the DASH diet.
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10.
The effect of obstructive sleep apnea on peripheral blood amino acid and biogenic amine metabolome at multiple time points overnight.
Kiens, O, Taalberg, E, Ivanova, V, Veeväli, K, Laurits, T, Tamm, R, Ottas, A, Kilk, K, Soomets, U, Altraja, A
Scientific reports. 2021;(1):10811
Abstract
There are no clinical studies that have investigated the differences in blood serum metabolome between obstructive sleep apnea (OSA) patients and controls. In a single-center prospective observational study, we compared metabolomic profiles in the serum of OSA patients with apnea-hypopnea index (AHI) ≥ 15/h and control individuals. Peripheral blood was obtained at 3 different time points overnight: 9:00 p.m.; 5:00 a.m. and 7:00 a.m. We used a targeted approach for detecting amino acids and biogenic amines and analyzed the data with ranked general linear model for repeated measures. We recruited 31 patients with moderate-to-severe OSA and 32 controls. Significant elevations in median concentrations of alanine, proline and kynurenine in OSA patients compared to controls were detected. Significant changes in the overnight dynamics of serum concentrations occurred in OSA: glutamine, serine, threonine, tryptophan, kynurenine and glycine levels increased, whereas a fall occurred in the same biomarker levels in controls. Phenylalanine and proline levels decreased slightly, compared to a steeper fall in controls. The study indicates that serum profiles of amino acid and biogenic amines are significantly altered in patients with OSA referring to vast pathophysiologic shifts reflected in the systemic metabolism.