PubMed

Plants (Basel). 2023 May 30;12(11):2172. doi: 10.3390/plants12112172.ABSTRACTChickpea is the second-most-cultivated legume globally, with India and Australia being the two largest producers. In both of these locations, the crop is sown on residual summer soil moisture and left to grow on progressively depleting water content, finally maturing under terminal drought conditions. The metabolic profile of plants is commonly, correlatively associated with performance or stress responses, e.g., the accumulation of osmoprotective metabolites during cold stress. In animals and humans, metabolites are also prognostically used to predict the likelihood of an event (usually a disease) before it occurs, e.g., blood cholesterol and heart disease. We sought to discover metabolic biomarkers in chickpea that could be used to predict grain yield traits under terminal drought, from the leaf tissue of young, watered, healthy plants. The metabolic profile (GC-MS and enzyme assays) of field-grown chickpea leaves was analysed over two growing seasons, and then predictive modelling was applied to associate the most strongly correlated metabolites with the final seed number plant-1. Pinitol (negatively), sucrose (negatively) and GABA (positively) were significantly correlated with seed number in both years of study. The feature selection algorithm of the model selected a larger range of metabolites including carbohydrates, sugar alcohols and GABA. The correlation between the predicted seed number and actual seed number was R2 adj = 0.62, demonstrating that the metabolic profile could be used to predict a complex trait with a high degree of accuracy. A previously unknown association between D-pinitol and hundred-kernel weight was also discovered and may provide a single metabolic marker with which to predict large seeded chickpea varieties from new crosses. The use of metabolic biomarkers could be used by breeders to identify superior-performing genotypes before maturity is reached.PMID:37299151 | DOI:10.3390/plants12112172

Plants (Basel). 2023 May 29;12(11):2144. doi: 10.3390/plants12112144.ABSTRACTThe effects of copper (Cu)-pH interactions on the levels of hormones and related metabolites (HRMs) in Citrus sinensis leaves and roots were investigated. Our findings indicated that increased pH mitigated Cu toxicity-induced alterations of HRMs, and Cu toxicity increased low-pH-induced alterations of HRMs. Increased pH-mediated decreases in ABA, jasmonates, gibberellins, and cytokinins, increases in (±)strigol and 1-aminocyclopropanecarboxylic acid, and efficient maintenance of salicylates and auxins homeostasis in 300 μM Cu-treated roots (RCu300); as well as efficient maintenance of hormone homeostasis in 300 μM Cu-treated leaves (LCu300) might contribute to improved leaf and root growth. The upregulation of auxins (IAA), cytokinins, gibberellins, ABA, and salicylates in pH 3.0 + 300 μM Cu-treated leaves (P3CL) vs. pH 3.0 + 0.5 μM Cu-treated leaves (P3L) and pH 3.0 + 300 μM Cu-treated roots (P3CR) vs. pH 3.0 + 0.5 μM Cu-treated roots (P3R) might be an adaptive response to Cu toxicity, so as to cope with the increased need for reactive oxygen species and Cu detoxification in LCu300 and RCu300. Increased accumulation of stress-related hormones (jasmonates and ABA) in P3CL vs. P3L and P3CR vs. P3R might reduce photosynthesis and accumulation of dry matter, and trigger leaf and root senescence, thereby inhibiting their growth.PMID:37299123 | DOI:10.3390/plants12112144

Plants (Basel). 2023 May 28;12(11):2135. doi: 10.3390/plants12112135.ABSTRACTNitrogen is crucial for plant growth and development, and improving nitrogen use efficiency (NUE) is a viable strategy for reducing dependence on nitrogen inputs and promoting sustainability. While the benefits of heterosis in corn are well known, the physiological mechanisms underlying this phenomenon in popcorn are less understood. We aimed to investigate the effects of heterosis on growth and physiological traits in four popcorn lines and their hybrids under two contrasting nitrogen conditions. We evaluated morpho-agronomic and physiological traits such as leaf pigments, the maximum photochemical efficiency of PSII, and leaf gas exchange. Components associated with NUE were also evaluated. N deprivation caused reductions of up to 65% in terms of plant architecture, 37% in terms of leaf pigments, and 42% in terms of photosynthesis-related traits. Heterosis had significant effects on growth traits, NUE, and foliar pigments, particularly under low soil nitrogen conditions. N-utilization efficiency was found to be the mechanism favoring superior hybrid performance for NUE. Non-additive genetic effects were predominant in controlling the studied traits, indicating that exploring heterosis is the most effective strategy for obtaining superior hybrids to promote NUE. The findings are relevant and beneficial for agro farmers seeking sustainable agricultural practices and improved crop productivity through the optimization of nitrogen utilization.PMID:37299114 | DOI:10.3390/plants12112135

Plants (Basel). 2023 May 24;12(11):2087. doi: 10.3390/plants12112087.ABSTRACTThe texture of fresh jujube fruit is related to its popularity and commercial value. The metabolic networks and essential genes that regulate the texture of jujube (Ziziphus jujuba) fruit are still unknown. In this study, two jujube cultivars with significantly different textures were selected by a texture analyzer. The four developmental stages of the exocarp and mesocarp of jujube fruit were studied separately using metabolomic and transcriptomic analyses. Differentially accumulated metabolites were enriched in several critical pathways related to cell wall substance synthesis and metabolism. Transcriptome analysis confirmed this by finding enriched differential expression genes in these pathways. Combined analysis showed that 'Galactose metabolism' was the most overlapping pathway in two omics. Genes such as β-Gal, MYB and DOF may affect fruit texture by regulating cell wall substances. Overall, this study provides an essential reference for the establishment of texture-related metabolic and gene networks of jujube fruit.PMID:37299066 | DOI:10.3390/plants12112087

Plants (Basel). 2023 May 23;12(11):2078. doi: 10.3390/plants12112078.ABSTRACTUrginea maritima L. (squill) species is widely spread at the Mediterranean region as two main varieties, i.e., white squill (WS) and red squill (RS), that are recognized for several health potentials. The major secondary metabolite classes of the squill are cardiac glycosides, mainly, bufadienolides, flavonoids, and anthocyanins. Herein, a multiplex MS and NMR metabolomics approach targeting secondary and aroma compounds in WS and RS was employed for varieties classification. Solid-phase micro extraction-gas chromatography/mass spectroscopy (SPME-GC/MS), ultra-high-performance liquid chromatography/mass spectrometry (UPLC/MS), as well as nuclear magnetic resonance (NMR) provided fingerprinting and structural confirmation of the major metabolites for both types of the squill. For comparison of the different platforms' classification potential, multivariate data analysis was employed. While Bufadienolides, viz. "hydroxy-scilliglaucosidin-O-rhamnoside, desacetylscillirosidin-O-rhamnoside and bufotalidin-O-hexoside" as well as oxylipids, were enriched in WS, flavonoids, i.e., dihydro-kaempferol-O-hexoside and its aglycon, taxifolin derivative, were predominant in RS. A cytotoxicity screening against three cancer cell lines, including breast adenocarcinoma (MCF-7), lung (A-549), and ovarian (SKOV-3) cell lines was conducted. Results revealed that WS was more effective on A-549 and SKOV-3 cell lines (WS IC50 0.11 and 0.4 µg/mL, respectively) owing to its abundance of bufadienolides, while RS recorded IC50 (MCF7 cell line) 0.17 µg/mL since is is rich inflavonoids.PMID:37299060 | DOI:10.3390/plants12112078

Molecules. 2023 Jun 5;28(11):4555. doi: 10.3390/molecules28114555.ABSTRACTThe composition of bioactive polyphenols from grape canes, an important viticultural byproduct, was shown to be varietal-dependent; however, the influence of soil-related terroir factors remains unexplored. Using spatial metabolomics and correlation-based networks, we investigated how continuous changes in soil features and topography may impact the polyphenol composition in grape canes. Soil properties, topography, and grape cane extracts were analyzed at georeferenced points over 3 consecutive years, followed by UPLC-DAD-MS-based metabolomic analysis targeting 42 metabolites. Principal component analyses on intra-vintage metabolomic data presented a good reproducibility in relation to geographic coordinates. A correlation-driven approach was used to explore the combined influence of soil and topographic variables on metabolomic responses. As a result, a metabolic cluster including flavonoids was correlated with elevation and curvature. Spatial metabolomics driven by correlation-based networks represents a powerful approach to spatialize field-omics data and may serve as new field-phenotyping tool in precision agriculture.PMID:37299031 | DOI:10.3390/molecules28114555

Molecules. 2023 Jun 3;28(11):4535. doi: 10.3390/molecules28114535.ABSTRACTA pipeline for metabolomics, based on UPLC-ESI-MS, was tested on two malignant breast cancer cell lines of the sub-types ER(+), PR(+), and HER2(3+) (MCF-7 and BCC), and one non-malignant epithelial cancer cell line (MCF-10A). This allowed us to quantify 33 internal metabolites, 10 of which showed a concentration profile associated with malignancy. Whole-transcriptome RNA-seq was also carried out for the three mentioned cell lines. An integrated analysis of metabolomics and transcriptomics was carried out using a genome-scale metabolic model. Metabolomics revealed the depletion of several metabolites that have homocysteine as a precursor, which was consistent with the lower activity of the methionine cycle caused by lower expression of the AHCY gene in cancer cell lines. Increased intracellular serine pools in cancer cell lines appeared to result from the over-expression of PHGDH and PSPH, which are involved in intracellular serine biosynthesis. An increased concentration of pyroglutamic acid in malignant cells was linked to the overexpression of the gene CHAC1.PMID:37299011 | DOI:10.3390/molecules28114535

Molecules. 2023 Jun 2;28(11):4522. doi: 10.3390/molecules28114522.ABSTRACTDiet restriction (DR) ameliorates obesity by regulating mitochondrial function. Cardiolipin (CL), a mitochondrial phospholipid, is closely associated with mitochondrial function. This study aimed to evaluate the anti-obesity effects of graded levels of DR based on mitochondrial CL levels in the liver. Obese mice were treated with 0%, 20%, 40%, and 60% reductions in the normal diet compared to normal animals (0 DR, 20 DR, 40 DR, and 60 DR groups, respectively). Biochemical and histopathological analyses were performed to evaluate the ameliorative effects of DR on obese mice. The altered profile of mitochondrial CL in the liver was explored using a targeted metabolomics strategy by ultra-high-pressure liquid chromatography MS/MS coupled with quadrupole time-of-flight mass spectrometry. Finally, gene expression associated with CL biosynthesis and remodeling was quantified. Tissue histopathology and biochemical index evaluations revealed significant improvements in the liver after DR, except for the 60 DR group. The variation in mitochondrial CL distribution and DR levels showed an inverted U-shape, and the CL content in the 40 DR group was the most upregulated. This result is consistent with the results of the target metabolomic analysis, which showed that 40 DR presented more variation. Furthermore, DR led to increased gene expression associated with CL biosynthesis and remodeling. This study provides new insights into the mitochondrial mechanisms underlying DR intervention in obesity.PMID:37298998 | DOI:10.3390/molecules28114522

Molecules. 2023 May 31;28(11):4467. doi: 10.3390/molecules28114467.ABSTRACTColombia is a producer of fine cocoa, according to the International Cocoa Organization; however, most of its exports are in the ordinary cocoa category. To remedy this situation, several national organizations are working to create technological platforms for small producers to certify the quality of their beans. The objective of this study was to identify differential chemical markers in 36 cocoa bean samples from five Colombian departments and associate them with cocoa quality properties. For this purpose, a non-targeted metabolomics approach was performed using UHPLC-HRMS, along with sensory and physicochemical analyses. The 36 samples did not differ in sensory quality, polyphenol content, and theobromine/caffeine ratio. However, the multivariate statistical analysis allowed us to differentiate the samples into four clusters. In addition, a similar grouping of the samples was also observed in the physical analyses. The metabolites responsible for such clustering were investigated with univariate statistical analysis and presumptively identified by comparison of experimental mass spectra with those reported in databases. Alkaloids, flavonoids, terpenoids, peptides, quinolines, and sulfur compounds were identified as discriminants between sample groups. Here, it was presented the metabolic profiles as an important chemical feature for further studies in quality control and more specific characterization of fine cocoa.PMID:37298942 | DOI:10.3390/molecules28114467

Int J Mol Sci. 2023 Jun 4;24(11):9736. doi: 10.3390/ijms24119736.ABSTRACTAlzheimer's disease (AD), a neurodegenerative disorder, is the most common cause of dementia in the elderly population. Since its original description, there has been intense debate regarding the factors that trigger its pathology. It is becoming apparent that AD is more than a brain disease and harms the whole-body metabolism. We analyzed 630 polar and apolar metabolites in the blood of 20 patients with AD and 20 healthy individuals, to determine whether the composition of plasma metabolites could offer additional indicators to evaluate any alterations in the metabolic pathways related to the illness. Multivariate statistical analysis showed that there were at least 25 significantly dysregulated metabolites in patients with AD compared with the controls. Two membrane lipid components, glycerophospholipids and ceramide, were upregulated, whereas glutamic acid, other phospholipids, and sphingolipids were downregulated. The data were analyzed using metabolite set enrichment analysis and pathway analysis using the KEGG library. The results showed that at least five pathways involved in the metabolism of polar compounds were dysregulated in patients with AD. Conversely, the lipid pathways did not show significant alterations. These results support the possibility of using metabolome analysis to understand alterations in the metabolic pathways related to AD pathophysiology.PMID:37298687 | DOI:10.3390/ijms24119736

Int J Mol Sci. 2023 Jun 2;24(11):9692. doi: 10.3390/ijms24119692.ABSTRACTBiologics address a range of unmet clinical needs, but the occurrence of biologics-induced liver injury remains a major challenge. Development of cimaglermin alfa (GGF2) was terminated due to transient elevations in serum aminotransferases and total bilirubin. Tocilizumab has been reported to induce transient aminotransferase elevations, requiring frequent monitoring. To evaluate the clinical risk of biologics-induced liver injury, a novel quantitative systems toxicology modeling platform, BIOLOGXsym™, representing relevant liver biochemistry and the mechanistic effects of biologics on liver pathophysiology, was developed in conjunction with clinically relevant data from a human biomimetic liver microphysiology system. Phenotypic and mechanistic toxicity data and metabolomics analysis from the Liver Acinus Microphysiology System showed that tocilizumab and GGF2 increased high mobility group box 1, indicating hepatic injury and stress. Tocilizumab exposure was associated with increased oxidative stress and extracellular/tissue remodeling, and GGF2 decreased bile acid secretion. BIOLOGXsym simulations, leveraging the in vivo exposure predicted by physiologically-based pharmacokinetic modeling and mechanistic toxicity data from the Liver Acinus Microphysiology System, reproduced the clinically observed liver signals of tocilizumab and GGF2, demonstrating that mechanistic toxicity data from microphysiology systems can be successfully integrated into a quantitative systems toxicology model to identify liabilities of biologics-induced liver injury and provide mechanistic insights into observed liver safety signals.PMID:37298645 | DOI:10.3390/ijms24119692

Int J Mol Sci. 2023 Jun 2;24(11):9657. doi: 10.3390/ijms24119657.ABSTRACTMedium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common inherited mitochondrial metabolic disease of fatty acid β-oxidation, especially in newborns. MCADD is clinically diagnosed using Newborn Bloodspot Screening (NBS) and genetic testing. Still, these methods have limitations, such as false negatives or positives in NBS and the variants of uncertain significance in genetic testing. Thus, complementary diagnostic approaches for MCADD are needed. Recently, untargeted metabolomics has been proposed as a diagnostic approach for inherited metabolic diseases (IMDs) due to its ability to detect a wide range of metabolic alterations. We performed an untargeted metabolic profiling of dried blood spots (DBS) from MCADD newborns (n = 14) and healthy controls (n = 14) to discover potential metabolic biomarkers/pathways associated with MCADD. Extracted metabolites from DBS samples were analyzed using UPLC-QToF-MS for untargeted metabolomics analyses. Multivariate and univariate analyses were used to analyze the metabolomics data, and pathway and biomarker analyses were also performed on the significantly identified endogenous metabolites. The MCADD newborns had 1034 significantly dysregulated metabolites compared to healthy newborns (moderated t-test, no correction, p-value ≤ 0.05, FC 1.5). A total of 23 endogenous metabolites were up-regulated, while 84 endogenous metabolites were down-regulated. Pathway analyses showed phenylalanine, tyrosine, and tryptophan biosynthesis as the most affected pathways. Potential metabolic biomarkers for MCADD were PGP (a21:0/PG/F1alpha) and glutathione, with an area under the curve (AUC) of 0.949 and 0.898, respectively. PGP (a21:0/PG/F1alpha) was the first oxidized lipid in the top 15 biomarker list affected by MCADD. Additionally, glutathione was chosen to indicate oxidative stress events that could happen during fatty acid oxidation defects. Our findings suggest that MCADD newborns may have oxidative stress events as signs of the disease. However, further validations of these biomarkers are needed in future studies to ensure their accuracy and reliability as complementary markers with established MCADD markers for clinical diagnosis.PMID:37298607 | DOI:10.3390/ijms24119657

Int J Mol Sci. 2023 Jun 2;24(11):9650. doi: 10.3390/ijms24119650.ABSTRACTMulberry (Morus alba) is a significant plant with numerous economic benefits; however, its growth and development are affected by nutrient levels. A high level of magnesium (Mg) or magnesium nutrient starvation are two of the significant Mg factors affecting plant growth and development. Nevertheless, M. alba's metabolic response to different Mg concentrations is unclear. In this study, different Mg concentrations, optimal (3 mmol/L), high (6 mmol/L and 9 mmol/L), or low (1 and 2 mmol/L) and deficient (0 mmol/L), were applied to M. alba for three weeks to evaluate their effects via physiological and metabolomics (untargeted; liquid chromatography-mass spectrometry (LC-MS)) studies. Several measured physiological traits revealed that Mg deficiency and excess Mg altered net photosynthesis, chlorophyll content, leaf Mg content and fresh weight, leading to remarkable reductions in the photosynthetic efficiency and biomass of mulberry plants. Our study reveals that an adequate supply of the nutrient Mg promoted the mulberry's physiological response parameters (net photosynthesis, chlorophyll content, leaf and root Mg content and biomass). The metabolomics data show that different Mg concentrations affect several differential metabolite expressions (DEMs), particularly fatty acyls, flavonoids, amino acids, organic acid, organooxygen compounds, prenol lipids, coumarins, steroids and steroid derivatives, cinnamic acids and derivatives. An excessive supply of Mg produced more DEMs, but negatively affected biomass production compared to low and optimum supplies of Mg. The significant DEMs correlated positively with mulberry's net photosynthesis, chlorophyll content, leaf Mg content and fresh weight. The mulberry plant's response to the application of Mg used metabolites, mainly amino acids, organic acids, fatty acyls, flavonoids and prenol lipids, in the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. These classes of compounds were mainly involved in lipid metabolism, amino acid metabolism, energy metabolism, the biosynthesis of other secondary metabolites, the biosynthesis of other amino acids, the metabolism of cofactors and vitamin pathways, indicating that mulberry plants respond to Mg concentrations by producing a divergent metabolism. The supply of Mg nutrition was an important factor influencing the induction of DEMs, and these metabolites were critical in several metabolic pathways related to magnesium nutrition. This study provides a fundamental understanding of DEMs in M. alba's response to Mg nutrition and the metabolic mechanisms involved, which may be critical to the mulberry genetic breeding program.PMID:37298601 | DOI:10.3390/ijms24119650

Int J Mol Sci. 2023 Jun 1;24(11):9614. doi: 10.3390/ijms24119614.ABSTRACTColorectal cancer (CRC) ranks as the third most frequently diagnosed cancer and the second leading cause of cancer-related deaths. The current endoscopic-based or stool-based diagnostic techniques are either highly invasive or lack sufficient sensitivity. Thus, there is a need for less invasive and more sensitive screening approaches. We, therefore, conducted a study on 64 human serum samples representing three different groups (adenocarcinoma, adenoma, and control) using cutting-edge GC×GC-LR/HR-TOFMS (comprehensive two-dimensional gas chromatography coupled with low/high-resolution time-of-flight mass spectrometry). We analyzed samples with two different specifically tailored sample preparation approaches for lipidomics (fatty acids) (25 μL serum) and metabolomics (50 μL serum). In-depth chemometric screening with supervised and unsupervised approaches and metabolic pathway analysis were applied to both datasets. A lipidomics study revealed that specific PUFA (ω-3) molecules are inversely associated with increased odds of CRC, while some PUFA (ω-6) analytes show a positive correlation. The metabolomics approach revealed downregulation of amino acids (alanine, glutamate, methionine, threonine, tyrosine, and valine) and myo-inositol in CRC, while 3-hydroxybutyrate levels were increased. This unique study provides comprehensive insight into molecular-level changes associated with CRC and allows for a comparison of the efficiency of two different analytical approaches for CRC screening using same serum samples and single instrumentation.PMID:37298566 | DOI:10.3390/ijms24119614

Int J Mol Sci. 2023 May 30;24(11):9507. doi: 10.3390/ijms24119507.ABSTRACTSkin diseases such as psoriasis (Ps) and psoriatic arthritis (PsA) are immune-mediated inflammatory diseases. Overlap of autoinflammatory and autoimmune conditions hinders diagnoses and identifying personalized patient treatments due to different psoriasis subtypes and the lack of verified biomarkers. Recently, proteomics and metabolomics have been intensively investigated in a broad range of skin diseases with the main purpose of identifying proteins and small molecules involved in the pathogenesis and development of the disease. This review discusses proteomics and metabolomics strategies and their utility in research and clinical practice in psoriasis and psoriasis arthritis. We summarize the studies, from in vivo models conducted on animals through academic research to clinical trials, and highlight their contribution to the discovery of biomarkers and targets for biological drugs.PMID:37298466 | DOI:10.3390/ijms24119507

Int J Mol Sci. 2023 May 30;24(11):9485. doi: 10.3390/ijms24119485.ABSTRACTThis paper reports on an NMR metabolomics study of lipophilic extracts of Ruditapes philippinarum clams exposed to the hormonal contaminant 17-α-ethinylestradiol (EE2), at 17 °C and 21 °C. The results reveal that exposure at 17 °C triggers a weak response at low EE2 concentrations, suggestive of a slight increase in membrane rigidity, followed by lipid metabolic stability at higher EE2 concentrations. On the other hand, at 21 °C, lipid metabolism begins to respond at 125 ng/L EE2, with antioxidant docosahexaenoic acid (DHA) helping to tackle high-oxidative-stress conditions, in tandem with enhanced storage of triglycerides. Exposure to 625 ng/L EE2 (highest concentration) enhances phosphatidylcholine (PtdCho) and polyunsaturated fatty acid (PUFA) levels, their direct intercorrelation suggesting PUFA incorporation in new membrane phospholipids. This should lead to increased membrane fluidity, probably aided by a decrease in cholesterol. PUFA levels, considered a measure of membrane fluidity, were strongly (and positively) correlated to intracellular glycine levels, thus identifying glycine as the main osmolyte entering the cells under high stress. Membrane fluidity also seems to elicit the loss of taurine. This work contributes to the understanding of the mechanisms of response of R. philippinarum clams to EE2 in tandem with warming while unveiling novel potential markers of stress mitigation, namely high levels of PtdCho, PUFAs (or PtdCho/glycerophosphocholine and PtdCho/acetylcholine ratios) and linoleic acid and low PUFA/glycine ratios.PMID:37298436 | DOI:10.3390/ijms24119485

Int J Mol Sci. 2023 May 30;24(11):9473. doi: 10.3390/ijms24119473.ABSTRACTBlack barley seeds are a health-beneficial diet resource because of their special chemical composition and antioxidant properties. The black lemma and pericarp (BLP) locus was mapped in a genetic interval of 0.807 Mb on chromosome 1H, but its genetic basis remains unknown. In this study, targeted metabolomics and conjunctive analyses of BSA-seq and BSR-seq were used to identify candidate genes of BLP and the precursors of black pigments. The results revealed that five candidate genes, purple acid phosphatase, 3-ketoacyl-CoA synthase 11, coiled-coil domain-containing protein 167, subtilisin-like protease, and caffeic acid-O-methyltransferase, of the BLP locus were identified in the 10.12 Mb location region on the 1H chromosome after differential expression analysis, and 17 differential metabolites, including the precursor and repeating unit of allomelanin, were accumulated in the late mike stage of black barley. Phenol nitrogen-free precursors such as catechol (protocatechuic aldehyde) or catecholic acids (caffeic, protocatechuic, and gallic acids) may promote black pigmentation. BLP can manipulate the accumulation of benzoic acid derivatives (salicylic acid, 2,4-dihydroxybenzoic acid, gallic acid, gentisic acid, protocatechuic acid, syringic acid, vanillic acid, protocatechuic aldehyde, and syringaldehyde) through the shikimate/chorismite pathway other than the phenylalanine pathway and alter the metabolism of the phenylpropanoid-monolignol branch. Collectively, it is reasonable to infer that black pigmentation in barley is due to allomelanin biosynthesis in the lemma and pericarp, and BLP regulates melanogenesis by manipulating the biosynthesis of its precursors.PMID:37298424 | DOI:10.3390/ijms24119473

Int J Mol Sci. 2023 May 29;24(11):9454. doi: 10.3390/ijms24119454.ABSTRACTDevelopmental disabilities are often associated with alterations in metabolism. However, it remains unknown how early these metabolic issues may arise. This study included a subset of children from the Markers of Autism Risks in Babies-Learning Early Signs (MARBLES) prospective cohort study. In this analysis, 109 urine samples collected at 3, 6, and/or 12 months of age from 70 children with a family history of ASD who went on to develop autism spectrum disorder (ASD n = 17), non-typical development (Non-TD n = 11), or typical development (TD n = 42) were investigated by nuclear magnetic resonance (NMR) spectroscopy to measure urinary metabolites. Multivariate principal component analysis and a generalized estimating equation were performed with the objective of exploring the associations between urinary metabolite levels in the first year of life and later adverse neurodevelopment. We found that children who were later diagnosed with ASD tended to have decreased urinary dimethylamine, guanidoacetate, hippurate, and serine, while children who were later diagnosed with Non-TD tended to have elevated urinary ethanolamine and hypoxanthine but lower methionine and homovanillate. Children later diagnosed with ASD or Non-TD both tended to have decreased urinary 3-aminoisobutyrate. Our results suggest subtle alterations in one-carbon metabolism, gut-microbial co-metabolism, and neurotransmitter precursors observed in the first year of life may be associated with later adverse neurodevelopment.PMID:37298406 | DOI:10.3390/ijms24119454

Int J Mol Sci. 2023 May 26;24(11):9311. doi: 10.3390/ijms24119311.ABSTRACTThe origin of life and native tissue development are dependent on the heterogeneity of pluripotent stem cells. Bone marrow mesenchymal stem cells (BMMSCs) are located in a complicated niche with variable matrix stiffnesses, resulting in divergent stem cell fates. However, how stiffness drives stem cell fate remains unknown. For this study, we performed whole-gene transcriptomics and precise untargeted metabolomics sequencing to elucidate the complex interaction network of stem cell transcriptional and metabolic signals in extracellular matrices (ECMs) with different stiffnesses, and we propose a potential mechanism involved in stem cell fate decision. In a stiff (39~45 kPa) ECM, biosynthesis of aminoacyl-tRNA was up-regulated, and increased osteogenesis was also observed. In a soft (7~10 kPa) ECM, biosynthesis of unsaturated fatty acids and deposition of glycosaminoglycans were increased, accompanied by enhanced adipogenic/chondrogenic differentiation of BMMSCs. In addition, a panel of genes responding to the stiffness of the ECM were validated in vitro, mapping out the key signaling network that regulates stem cells' fate decisions. This finding of "stiffness-dependent manipulation of stem cell fate" provides a novel molecular biological basis for development of potential therapeutic targets within tissue engineering, from both a cellular metabolic and a biomechanical perspective.PMID:37298263 | DOI:10.3390/ijms24119311

Int J Mol Sci. 2023 May 25;24(11):9225. doi: 10.3390/ijms24119225.ABSTRACTIn recent decades, vaccines have been extraordinary resources to prevent pathogen diffusion and cancer. Even if they can be formed by a single antigen, the addition of one or more adjuvants represents the key to enhance the response of the immune signal to the antigen, thus accelerating and increasing the duration and the potency of the protective effect. Their use is of particular importance for vulnerable populations, such as the elderly or immunocompromised people. Despite their importance, only in the last forty years has the search for novel adjuvants increased, with the discovery of novel classes of immune potentiators and immunomodulators. Due to the complexity of the cascades involved in immune signal activation, their mechanism of action remains poorly understood, even if significant discovery has been recently made thanks to recombinant technology and metabolomics. This review focuses on the classes of adjuvants under research, recent mechanism of action studies, as well as nanodelivery systems and novel classes of adjuvants that can be chemically manipulated to create novel small molecule adjuvants.PMID:37298177 | DOI:10.3390/ijms24119225