PubMed

Molecules. 2023 Jan 11;28(2):715. doi: 10.3390/molecules28020715.ABSTRACTRecently, functional foods have been a subject of great interest in dietetics owing not only to their nutritional value but rather their myriad of health benefits. Moreover, an increase in consumers' demands for such valuable foods warrants the development in not only production but rather tools of quality and nutrient assessment. Bee products, viz., pollen (BP) and bread, are normally harvested from the flowering plants with the aid of bees. BP is further subjected to a fermentation process in bee hives to produce the more valuable and bioavailable BB. Owing to their nutritional and medicinal properties, bee products are considered as an important food supplements rich in macro-, micro-, and phytonutrients. Bee products are rich in carbohydrates, amino acids, vitamins, fatty acids, and minerals in addition to a myriad of phytonutrients such as phenolic compounds, anthocyanins, volatiles, and carotenoids. Moreover, unsaturated fatty acids (USFAs) of improved lipid profile such as linoleic, linolenic, and oleic were identified in BP and BB. This work aims to present a holistic overview of BP and BB in the context of their composition and analysis, and to highlight optimized extraction techniques to maximize their value and future applications in nutraceuticals.PMID:36677772 | DOI:10.3390/molecules28020715

Molecules. 2023 Jan 9;28(2):674. doi: 10.3390/molecules28020674.ABSTRACTCentaurea is a genus compromising over 250 herbaceous flowering species and is used traditionally to treat several ailments. Among the Egyptian Centaurea species, C. lipii was reported to be cytotoxic against multidrug-resistant cancer cells. In this context, we aimed to explore the metabolome of C. lipii and compare it to other members of the genus in pursuance of identifying its bioactive principles. An LC-MS/MS analysis approach synchronized with feature-based molecular networks was adopted to offer a holistic overview of the metabolome diversity of the Egyptian Centaurea species. The studied plants included C. alexandrina, C. calcitrapa, C. eryngioides, C. glomerata, C. lipii, C. pallescens, C. pumilio, and C. scoparia. Their constitutive metabolome showed diverse chemical classes such as cinnamic acids, sesquiterpene lactones, flavonoids, and lignans. Linking the recorded metabolome to the previously reported cytotoxicity identified sesquiterpene lactones as the major contributors to this activity. To confirm our findings, bioassay-guided fractionation of C. lipii was adopted and led to the isolation of the sesquiterpene lactone cynaropicrin with an IC50 of 1.817 µM against the CCRF-CEM leukemia cell line. The adopted methodology highlighted the uniqueness of the constitutive metabolome of C. lipii and determined the sesquiterpene lactones to be the responsible cytotoxic metabolites.PMID:36677732 | DOI:10.3390/molecules28020674

Molecules. 2023 Jan 9;28(2):663. doi: 10.3390/molecules28020663.ABSTRACTEphedrae Herba (Ephedra), known as "MaHuang" in China, is the dried straw stem that is associated with the lung and urinary bladder meridians. At present, more than 60 species of Ephedra plants have been identified, which contain more than 100 compounds, including alkaloids, flavonoids, tannins, sugars, and organic phenolic acids. This herb has long been used to treat asthma, liver disease, skin disease, and other diseases, and has shown unique efficacy in the treatment of COVID-19 infection. Because alkaloids are the main components causing toxicity, the safety of Ephedra must be considered. However, the nonalkaloid components of Ephedra can be effectively used to replace ephedrine extracts to treat some diseases, and reasonable use can ensure the safety of Ephedra. We reviewed the phytochemistry, pharmacology, clinical application, and alkaloid toxicity of Ephedra, and describe prospects for its future development to facilitate the development of Ephedra.PMID:36677722 | DOI:10.3390/molecules28020663

Molecules. 2023 Jan 9;28(2):656. doi: 10.3390/molecules28020656.ABSTRACTBACKGROUND: Homocysteine (Hcy) has been found to be closely related to the occurrence of diabetes mellitus (DM) and is considered as one of the risk factors of DM. However, Hcy alone is not enough as a factor to predict DM, and our study analyzed and determined the relationship between the main metabolites involved in the Hcy metabolic pathway and DM.METHODS: A total of 48 clinical samples were collected, including 18 health control samples and 30 DM samples. All standards and samples were detected by LC-QTOF-MS. Multivariate statistical analysis and k-means cluster analysis were performed to screen and confirm the metabolites significantly correlated with DM.RESULTS: A total of 13 metabolites of the Hcy metabolic pathway were detected in the samples. The content of Hcy, cysteine, taurine, pyridoxamine, methionine, and choline were significantly increased in the DM group (p < 0.05). Hcy, choline, cystathionine, methionine, and taurine contributed significantly to the probabilistic principal component analysis (PPCA) model. The odds ratios (OR) of Hcy, cysteine, taurine, methionine, and choline were all greater than one. K-means cluster analysis showed that the Hcy, taurine, methionine, and choline were significantly correlated with the distribution of glucose values (divided into four levels: 10.5-11.7 mmol/L, 7.7-9.7 mmol/L, 6.0-6.9 mmol/L, and 5.0-5.9 mmol/L, respectively).CONCLUSION: Hcy, taurine, methionine, and choline can be used as risk factors for diabetes diagnosis and are expected to be used for the assessment of diabetes severity.PMID:36677712 | DOI:10.3390/molecules28020656

Molecules. 2023 Jan 9;28(2):653. doi: 10.3390/molecules28020653.ABSTRACTEndometriosis is a common gynecological illness in women of reproductive age that significantly decreases life quality and fertility. Paeonol has been shown to play an important part in endometriosis treatments. Understanding the mechanism is critical for treating endometriosis. In this study, autologous transplantation combined with a 28 day ice water bath was used to create a rat model of endometriosis with cold clotting and blood stagnation. The levels of estradiol and progesterone in plasma were detected by ELISA, and the pathological changes of ectopic endometrial tissue were examined by H&E staining, which proved the efficacy of paeonol. For metabolomic analysis of plasma samples, UPLC-Q/TOF-MS was combined with multivariate statistical analysis to identify the influence of paeonol on small molecule metabolites relevant to endometriosis. Finally, the key targets were screened using a combination of network pharmacology and molecular docking approaches. The results showed that the pathological indexes of rats were improved and returned to normal levels after treatment with paeonol, which was the basis for confirming the efficacy of paeonol. Metabolomics results identified 13 potential biomarkers, and paeonol callbacks 7 of them, involving six metabolic pathways. Finally, four key genes were found for paeonol therapy of endometriosis, and the results of molecular docking revealed a significant interaction between paeonol and the four key genes. This study was successful in establishing a rat model of endometriosis with cold coagulation and blood stagnation. GCH1, RPL8, PKLR, and MAOA were the key targets of paeonol in the treatment of endometriosis. It is also demonstrated that metabolomic techniques give the potential and environment for comprehensively understanding drug onset processes.PMID:36677710 | DOI:10.3390/molecules28020653

Molecules. 2023 Jan 4;28(2):494. doi: 10.3390/molecules28020494.ABSTRACT5-Fluorouracil (5-FU) is a common anti-tumor drug, but there is no effective treatment for its side effect, intestinal mucositis. The inflammatory reaction of macrophages in intestinal mucosa induced by 5-FU is an important cause of intestinal mucositis. In this study, we investigated the anti-inflammatory effects of the three important short-chain fatty acids (SCFAs), including sodium acetate (NaAc), sodium propionate (NaPc), and sodium butyrate (NaB), on human mononuclear macrophage-derived THP-1 cells induced by 5-FU. The expressions of intracellular ROS, pro-inflammatory/anti-inflammatory cytokines, as well as the nuclear factor-κB/NLR family and pyrin domain-containing protein 3 (NF-κB/NLRP3) signaling pathway proteins were determined. Furthermore, the cell metabolites were analyzed by untargeted metabolomics techniques. Our results revealed that the three SCFAs inhibited pro-inflammatory factor expressions, including IL-1β and IL-6, when treated with 5-FU (p < 0.05). The ROS expression and NF-κB activity of 5-FU-treated THP-1 cells were inhibited by the three SCFAs pre-incubated (p < 0.05). Moreover, NLRP3 knockdown abolished 5-FU-induced IL-1β expression (p < 0.05). Further experiments showed that the three SCFAs affected 20 kinds of metabolites that belong to amino acid and phosphatidylcholine metabolism in THP-1 cells. These significantly altered metabolites were involved in amino acid metabolism and glycerolphospholipid and sphingolipid metabolism. It is the first time that three important SCFAs (NaAc, NaPc, and NaB) were identified as inhibiting 5-FU-induced macrophage inflammation through inhibiting ROS/NF-κB/NLRP3 signaling pathways and regulating glycerolphospholipid and sphingolipid metabolism.PMID:36677551 | DOI:10.3390/molecules28020494

Microorganisms. 2023 Jan 5;11(1):135. doi: 10.3390/microorganisms11010135.ABSTRACTMicrobiome-based therapeutics are increasingly evaluated as a strategy to reduce recurrent Clostridioides difficile infection (rCDI), with proposed mechanisms including restoration of the microbiota and microbiota-mediated functions, such as bile acid (BA) metabolism. This study reports a quantitative and sensitive assay for targeted metabolomic assessment, and the application of the assay to profile BA composition in a Phase 2 trial of the investigational microbiota-based live biotherapeutic RBX2660 for reduction of rCDI. A liquid chromatography tandem mass spectrometry method was developed to extract and quantify 35 BAs from 113 participant stool samples from 27 RBX2660-treated rCDI participants in the double-blinded, placebo-controlled clinical trial. The results demonstrate a high-confidence assay as represented by sensitivity, linearity, accuracy, and precision. Furthermore, the assay enabled the observation of primary BAs as the dominant BA species at baseline in stool samples from clinical trial participants, consistent with the expected loss of commensals after broad-spectrum antibiotic treatment. After RBX2660 administration, there was a significant drop in primary BAs concurrent with increased secondary BAs that sustained through 24 months post-RBX2660. Taken together, we describe a robust assay that demonstrates altered BA metabolism in rCDI patients treated with RBX2660 administration.PMID:36677428 | DOI:10.3390/microorganisms11010135

Microorganisms. 2022 Dec 29;11(1):92. doi: 10.3390/microorganisms11010092.ABSTRACTAdaptive laboratory evolution (ALE) is a useful experimental methodology for fundamental scientific research and industrial applications to create microbial cell factories. By using ALE, cells are adapted to the environment that researchers set based on their objectives through the serial transfer of cell populations in batch cultivations or continuous cultures and the fitness of the cells (i.e., cell growth) under such an environment increases. Then, omics analyses of the evolved mutants, including genome sequencing, transcriptome, proteome and metabolome analyses, are performed. It is expected that researchers can understand the evolutionary adaptation processes, and for industrial applications, researchers can create useful microorganisms that exhibit increased carbon source availability, stress tolerance, and production of target compounds based on omics analysis data. In this review article, the methodologies for ALE in microorganisms are introduced. Moreover, the application of ALE for the creation of useful microorganisms as cell factories has also been introduced.PMID:36677384 | DOI:10.3390/microorganisms11010092

Metabolites. 2023 Jan 16;13(1):135. doi: 10.3390/metabo13010135.ABSTRACTEgg 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.PMID:36677059 | DOI:10.3390/metabo13010135

Metabolites. 2023 Jan 15;13(1):131. doi: 10.3390/metabo13010131.ABSTRACTMetabolic 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.PMID:36677056 | DOI:10.3390/metabo13010131

Metabolites. 2023 Jan 14;13(1):129. doi: 10.3390/metabo13010129.ABSTRACTAs 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.PMID:36677054 | DOI:10.3390/metabo13010129

Metabolites. 2023 Jan 13;13(1):127. doi: 10.3390/metabo13010127.ABSTRACTHigh-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.PMID:36677052 | DOI:10.3390/metabo13010127

Metabolites. 2023 Jan 13;13(1):122. doi: 10.3390/metabo13010122.ABSTRACTIdentification 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.PMID:36677046 | DOI:10.3390/metabo13010122

Metabolites. 2023 Jan 11;13(1):117. doi: 10.3390/metabo13010117.ABSTRACTLiver 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.PMID:36677042 | DOI:10.3390/metabo13010117

Metabolites. 2023 Jan 9;13(1):113. doi: 10.3390/metabo13010113.ABSTRACTThe 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.PMID:36677038 | DOI:10.3390/metabo13010113

Metabolites. 2023 Jan 9;13(1):112. doi: 10.3390/metabo13010112.ABSTRACTThe 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.PMID:36677037 | DOI:10.3390/metabo13010112

Metabolites. 2023 Jan 9;13(1):110. doi: 10.3390/metabo13010110.ABSTRACTWe 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 SUVmean and serum metabolites in metastasis. In the metastatic mice, the SUVmean 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 SUVmean 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.PMID:36677035 | DOI:10.3390/metabo13010110

Metabolites. 2023 Jan 9;13(1):107. doi: 10.3390/metabo13010107.ABSTRACTBoth 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.PMID:36677032 | DOI:10.3390/metabo13010107

Metabolites. 2023 Jan 9;13(1):105. doi: 10.3390/metabo13010105.ABSTRACTComputational methods for creating in silico libraries of molecular descriptors (e.g., collision cross sections) are becoming increasingly prevalent due to the limited number of authentic reference materials available for traditional library building. These so-called "reference-free metabolomics" methods require sampling sets of molecular conformers in order to produce high accuracy property predictions. Due to the computational cost of the subsequent calculations for each conformer, there is a need to sample the most relevant subset and avoid repeating calculations on conformers that are nearly identical. The goal of this study is to introduce a heuristic method of finding the most dissimilar conformers from a larger population in order to help speed up reference-free calculation methods and maintain a high property prediction accuracy. Finding the set of the n items most dissimilar from each other out of a larger population becomes increasingly difficult and computationally expensive as either n or the population size grows large. Because there exists a pairwise relationship between each item and all other items in the population, finding the set of the n most dissimilar items is different than simply sorting an array of numbers. For instance, if you have a set of the most dissimilar n = 4 items, one or more of the items from n = 4 might not be in the set n = 5. An exact solution would have to search all possible combinations of size n in the population exhaustively. We present an open-source software called similarity downselection (SDS), written in Python and freely available on GitHub. SDS implements a heuristic algorithm for quickly finding the approximate set(s) of the n most dissimilar items. We benchmark SDS against a Monte Carlo method, which attempts to find the exact solution through repeated random sampling. We show that for SDS to find the set of n most dissimilar conformers, our method is not only orders of magnitude faster, but it is also more accurate than running Monte Carlo for 1,000,000 iterations, each searching for set sizes n = 3-7 out of a population of 50,000. We also benchmark SDS against the exact solution for example small populations, showing that SDS produces a solution close to the exact solution in these instances. Using theoretical approaches, we also demonstrate the constraints of the greedy algorithm and its efficacy as a ratio to the exact solution.PMID:36677030 | DOI:10.3390/metabo13010105

Metabolites. 2023 Jan 8;13(1):103. doi: 10.3390/metabo13010103.ABSTRACTFeeding thermally oxidized lipids to pigs has been shown to compromise growth and health, reduce energy digestibility, and disrupt lipid metabolism. However, the effects of feeding oxidized lipids on amino acid metabolism in pigs have not been well defined even though amino acids are indispensable for the subsistence of energy metabolism, protein synthesis, the antioxidant system, and many other functions essential for pig growth and health. In this study, oxidized corn oil (OCO)-elicited changes in amino acid homeostasis of nursery pigs were examined by metabolomics-based biochemical analysis. The results showed that serum and hepatic free amino acids and metabolites, including tryptophan, threonine, alanine, glutamate, and glutathione, as well as associated metabolic pathways, were selectively altered by feeding OCO, and more importantly, many of these metabolic events possess protective functions. Specifically, OCO activated tryptophan-nicotinamide adenosine dinucleotide (NAD+) synthesis by the transcriptional upregulation of the kynurenine pathway in tryptophan catabolism and promoted adenine nucleotide biosynthesis. Feeding OCO induced oxidative stress, causing decreases in glutathione (GSH)/oxidized glutathione (GSSG) ratio, carnosine, and ascorbic acid in the liver but simultaneously promoted antioxidant responses as shown by the increases in hepatic GSH and GSSG as well as the transcriptional upregulation of GSH metabolism-related enzymes. Moreover, OCO reduced the catabolism of threonine to α-ketobutyrate in the liver by inhibiting the threonine dehydratase (TDH) route. Overall, these protective metabolic events indicate that below a certain threshold of OCO consumption, nursery pigs are capable of overcoming the oxidative stress and metabolic challenges posed by the consumption of oxidized lipids by adjusting antioxidant, nutrient, and energy metabolism, partially through the transcriptional regulation of amino acid metabolism.PMID:36677028 | DOI:10.3390/metabo13010103