PubMed

Gene. 2023 Sep 1:147752. doi: 10.1016/j.gene.2023.147752. Online ahead of print.ABSTRACTIsatis indigotica Fortune is a plant species containing lignan compounds of significant economic value. Its root plays a crucial role in treating viruses and exhibits antitumor, anti-inflammatory, antibacterial, and other biological activities. Now, I. indigotica has been included in Isatis tinctoria Linnaeus. In this study, the roots of diploid I. indigotica, tetraploid I. indigotica, and Isatis tinctoria Linnaeus were analyzed using metabolome and transcriptome analysis. The metabolomic analysis detected 48 lignan metabolites, including Lirioresinol A, Vladinol A, Syringaresinol, Arctigenin, Acanthoside B, and Sesamin as characteristic compounds, without significant variations among the remaining metabolites. The transcriptomic analysis identified 41 differentially expressed phenylpropanoid synthase genes, which were further analyzed for variations in lignan transcriptome profiles across different samples. RT-qPCR analysis also revealed differential genes expression related to lignan biosynthesis pathway among the three sample groups. The analysis of transcription factors showed that the AP2-EREBP family (Iin24319), MYB family (Iin24843), and WRKY family (Iin08158) displayed expression patterns similar to Iin14549. Phylogenetic analyses also indicate that Iin14549 may play a role in lignan synthesis. These transcription factor families exhibited high expression in tetraploid I. indigotica, moderate expression in diploid I. indigotica, and low expression in I. tinctoria. The findings of this study can serve as a reference for improving the quality of I. indigotica and developing germplasms with high lignan content. Additionally, these results lay a foundation for the functional characterization of UGTs in lignan biosynthesis pathway.PMID:37661029 | DOI:10.1016/j.gene.2023.147752

J Nutr. 2023 Sep 1:S0022-3166(23)72560-1. doi: 10.1016/j.tjnut.2023.08.032. Online ahead of print.ABSTRACTBACKGROUND: Maternal vitamin B12 (B12) deficiency plays a vital role in fetal programming, as corroborated by previous studies on murine models and longitudinal human cohorts.OBJECTIVE: This study assessed the effects of diet-induced maternal B12 deficiency on F1 offspring in terms of cardiometabolic health and normalization of these effects by maternal peri-conceptional B12 supplementation.METHODS: A diet-induced maternal B12 deficient Wistar rat model was generated where female rats were either fed a control AIN-76A diet (with 0.01 g/Kg B12) or same diet with B12 removed. Females from B12 deficient group were mated with males on control diet. A subset of B12 deficient females was repleted with B12 on day 1 of conception. The offspring in F1 generation were assessed for changes in body composition, plasma biochemical and molecular changes in the liver. A multi-omics approach was used to get a mechanistic insight into the changes in the offspring liver.RESULTS: We show that a 36% reduction in plasma B12 levels during pregnancy in F0 females can lead to continued B12 deficiency (60-70% compared to control) in the F1 offspring and program them for cardio-metabolic adversities. These adversities like high triglycerides and low HDL were seen only among F1 males but not females. DNA methylome analysis in the liver of F1 3-month-old offspring highlights sexual dimorphism in the alteration of methylation status of genes critical to signaling processes. Proteomics and targeted metabolomics analysis confirm that this sex-specific alterations occur through modulations in PPAR signaling and steroid hormone biosynthesis pathway. Repletion of deficient mothers with B12 at conception normalizes most of the molecular and biochemical changes.CONCLUSIONS: Maternal B12 deficiency has a programming effect on the next generation and increases the risk for cardio-metabolic syndrome in a sex-specific manner. Normalization of the molecular risk markers on B12 supplementation indicates a causal role.PMID:37660953 | DOI:10.1016/j.tjnut.2023.08.032

Am J Clin Nutr. 2023 Sep 1:S0002-9165(23)66116-7. doi: 10.1016/j.ajcnut.2023.08.018. Online ahead of print.ABSTRACTBACKGROUND: Whether red meat consumption is associated with higher inflammation, or confounded by increased adiposity, remains unclear. Plasma metabolites both capture the effects of diet after food is processed, digested, and absorbed, and correlate with markers of inflammation, so can help clarify diet-health relationships.OBJECTIVE: To identify whether any metabolites associated with red meat intake are also associated with inflammation.DESIGN: A cross-sectional analysis of observational data from older adults (52.84% female, mean age 63±0.3 years), participating in the Multi-Ethnic Study of Atherosclerosis (MESA). Dietary intake was assessed by food frequency questionnaire, alongside C-reactive protein (CRP), interleukin-2, interleukin-6, fibrinogen, homocysteine, and tumor necrosis factor alpha, and untargeted proton nuclear magnetic resonance 1H NMR metabolomic features. Associations between these variables were examined using linear regression models, adjusted for demographic factors lifestyle behaviors, and BMI.RESULTS: Neither processed not unprocessed forms of red meat were associated with any markers of inflammation (all P>.01). However, again in analyses which adjust for BMI, unprocessed red meat was inversely associated with inversely associated with spectral features representing the metabolite glutamine (sentinel hit: β=-0.09 ± 0.02, P=2.0*10-5), an amino acid which was also inversely associated with CRP level (β=-0.11 ± 0.01, P=3.3*10-10).CONCLUSIONS: Our analyses were unable to support a relationship between either processed or unprocessed red meat and inflammation, over and above any confounding by BMI. Glutamine, a plasma correlate of lower unprocessed red meat intake, was associated with lower CRP levels. The differences in diet-inflammation associations vs. diet metabolite-inflammation associations warrants further investigation to understand the extent that these arise from (1) a reduction in measurement error with metabolite measures; (2) the extent that factors other than unprocessed red meat intake contribute to glutamine levels; (3) the ability of plasma metabolites to capture individual differences in how food intake is metabolized.PMID:37660929 | DOI:10.1016/j.ajcnut.2023.08.018

Sci Total Environ. 2023 Sep 1:166697. doi: 10.1016/j.scitotenv.2023.166697. Online ahead of print.ABSTRACTThe drifting process of U. prolifera were simulated in a large-volume flowing water system with conditions similar to the field in the Yellow Sea. Biomass and chl-a content per unit of U. prolifera were monitored in the flowing water system by simulating nutrients and temperature variations of seawaters from starting place to terminus of U. prolifera in the South Yellow Sea. According to the variations of nutrients during the drifting process, the floating process can be divided into three stages. Differentially expressed genes and differential metabolites in the three stages of U. prolifera drifting process were identified, which are mainly related to glycometabolism, nitrogen metabolism, and selenium compound metabolism. The process from Stage I to Stage II are mainly related to the translation and molecular function of biological processes, and the main differential metabolites are primary metabolites, whereas, from Stage II to Stage III, secondary metabolites start to increase, indicating that U. prolifera resisted environmental stress by increasing lipids and producing secondary metabolites. It will provide some guidance for the comprehensive interpretation of the biological basis and ecological mechanisms of the large-scale U. prolifera green tides in the Yellow Sea.PMID:37660825 | DOI:10.1016/j.scitotenv.2023.166697

Sci Total Environ. 2023 Sep 1:166765. doi: 10.1016/j.scitotenv.2023.166765. Online ahead of print.ABSTRACTSilver nanoparticles (AgNPs) are widely present in aquatic and soil environment, raising significant concerns about their impacts on creatures in ecosystem. While the toxicity of AgNPs on microorganisms has been reported, their effects on biogeochemical processes and specific functional microorganisms remain relatively unexplored. In this study, a 28-day microcosmic experiment was conducted to investigate the dose-dependent effects of AgNPs (10 mg and 100 mg Ag kg-1 soil) on nitrogen transformation and functional microorganisms in agricultural soils. The molecular mechanisms were uncovered by examining change in functional microorganisms and metabolic pathways. To enable comparison, the toxicity of positive control with an equivalent Ag+ dose from CH3COOAg was also included. The results indicated that both AgNPs and CH3COOAg enhanced nitrogen fixation and nitrification, corresponding to increased relative abundances of associated functional genes. However, they inhibited denitrification via downregulating nirS, nirK, and nosZ genes as well as reducing nitrate and nitrite reductase activities. In contrast to high dose of AgNPs, low levels increased bacterial diversity. AgNPs and CH3COOAg altered the activities of associated metabolic pathways, resulting in the enrichment of specific taxa that demonstrated tolerance to Ag. At genus level, AgNPs increased the relative abundances of nitrogen-fixing Microvirga and Bacillus by 0.02 %-629.39 % and 14.44 %-30.10 %, respectively, compared with control group (CK). The abundances of denitrifying bacteria, such as Rhodoplanes, Pseudomonas, and Micromonospora, decreased by 19.03 % to 32.55 %, 24.73 % to 50.05 %, and 15.66 % to 76.06 %, respectively, compared to CK. CH3COOAg reduced bacterial network complexity, diminished the symbiosis mode compared to AgNPs. The prediction of genes involved in metabolic pathways related to membrane transporter and cell motility showed sensitive to AgNPs exposure in the soil. Further studies involving metabolomics are necessary to reveal the essential effects of AgNPs and CH3COOAg on biogeochemical cycle of elements in agricultural soil.PMID:37660816 | DOI:10.1016/j.scitotenv.2023.166765

Chemosphere. 2023 Sep 1:140048. doi: 10.1016/j.chemosphere.2023.140048. Online ahead of print.ABSTRACTPolychlorinated biphenyls (PCBs) are a class of contaminants of great concern, linked to the development of many chronic diseases. Adverse effects of PCBs have been documented in humans after accidental and massive exposure. However, little is known about the effect of chronic exposure to low-dose PCBs mixtures, and studies regarding scattered lifetime exposures to non-dioxin-like (NDL)-PCBs are especially missing. In this work, serum samples from pigs chronically exposed through their diet during 22 days to Aroclor 1260 (i.e. a commercially available mixture of NDL-PCBs) underwent a metabolomics analysis using gas chromatography-high resolution mass spectrometry (GC-HRMS), with the objective to investigate the effect of exposure to low doses of NDL-PCBs (few ng/kg body weight (b.w.) per day). The study showed that the serum profiles of 84 metabolites are significantly altered by the administration of Aroclor 1260, of which 40 could be identified at least at level 2. The aggregate interpretation of the results of this study, together with the outcome of a previous one involving LC-HRMS profiling, provided a substantial and concise overview of the effect of low dose exposure to NDL-PCBs, reflecting the hepatotoxic and neurotoxic effects already reported in literature at higher and longer exposures. These results are intended to contribute to the debate on the current toxicological reference values for these substances.PMID:37660801 | DOI:10.1016/j.chemosphere.2023.140048

Prog Neuropsychopharmacol Biol Psychiatry. 2023 Sep 1:110858. doi: 10.1016/j.pnpbp.2023.110858. Online ahead of print.ABSTRACTRestricted and repetitive behaviors (RRBs) are one of the characteristics of various neuropsychiatric disorders with complex and diverse molecular mechanisms. Repetitive self-grooming behavior is one of the manifestations of RRBs in humans and rodents. Research on the neural mechanism of repetitive self-grooming behavior is expected to reveal the underlying logic of the occurrence of RRBs. Pax2 is an important member of the paired-box transcription factor family. It is expressed in different regions of the developing central nervous system. Our previous study showed that Pax2 heterozygous gene knockout mice (Pax2+/- KO mice) exhibit significantly increased self-grooming, which suggests that the Pax2 gene is involved in the control of self-grooming behavior, but the molecular mechanism is still unclear. In this study, we further constructed the Pax2 neuron-specific deletion mice (Nestin-Pax2 mice). Targeted metabolomics and transcriptomics techniques was used to analyze. The results showed that there is an excitatory/inhibitory imbalance of the neurotransmitter system and the Arc gene was significantly up-regulated in the prefrontal cortex (PFC) of Nestin-Pax2 mice. This study suggests that the potential regulatory mechanism of the increased repetitive self-grooming behavior in Pax2 gene deletion mice is that the deletion of the Pax2 gene affects the expression of Arc in the PFC, leading to impaired synaptic plasticity and excitatory/inhibitory imbalance, and participating in the occurrence of repetitive self-grooming behavior.PMID:37660748 | DOI:10.1016/j.pnpbp.2023.110858

Aquat Toxicol. 2023 Aug 19;263:106666. doi: 10.1016/j.aquatox.2023.106666. Online ahead of print.ABSTRACTUnder high-density culture, cannibalism occurs frequently during the molting of the Chinese mitten crabs Eriocheir sinensis, resulting in a large reduction in production. We found that the leakage of molting fluid from sexually immature crabs informs conspecifics that they are in a molting process. This hypothesis was verified through metabolomics analyses combined with behavioral experiments. The GlcNAc-6-P was identified as a molting biomarker from the differential metabolites by non-targeted metabolomics. In addition, we found that the concentration of GlcNAc-6-P in the molting fluid was significantly higher than other molting metabolites at different molting stages, reaching 5.84 μmol L-1, indicating that the molting fluid was the source of GlcNAc-6-P. Moreover, the behavioral experiments showed that crabs were actively approached to high concentrations of GlcNAc-6-P (1 μmol L-1), but had no obvious choice tendency at different concentrations of UTP, 20-HE and low concentrations of GlcNAc-6-P (0.1 μmol L-1, 0.01 μmol L-1) compared with the control groups. In conclusion, that E. sinensis by sensing the concentration change of GlcNAc-6-P can locate the source of GlcNAc-6-P release and actively approach the high concentration GlcNAc-6-P area and attack the molting crab, causing cannibalism. Blocking the reception pathway of molting chemical cues in E. sinensis, thereby preventing the perception of signals originating from conspecifics' molting in the vicinity, could lead to a reduction in cannibalistic behavior and an increase in overall production. Additionally, this method presents a prospective solution for addressing cannibalism in other crustacean species where such behavior is prevalent.PMID:37660581 | DOI:10.1016/j.aquatox.2023.106666

Mol Genet Metab. 2023 Aug 25;140(3):107689. doi: 10.1016/j.ymgme.2023.107689. Online ahead of print.ABSTRACTTriheptanoin (triheptanoylglycerol) has shown value as anaplerotic therapy for patients with long chain fatty acid oxidation disorders but is contraindicated in medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. In search for anaplerotic therapy for patients with MCAD deficiency, fibroblasts from three patients homozygous for the most common mutation, ACADMG985A/G985A, were treated with fatty acids hypothesized not to require MCAD for their metabolism, including heptanoic (C7; the active component of triheptanoin), 2,6-dimethylheptanoic (dMC7), 6-amino-2,4-dimethylheptanoic (AdMC7), or 4,8-dimethylnonanoic (dMC9) acids. Their effectiveness as anaplerotic fatty acids was assessed in live cells by monitoring changes in cellular oxygen consumption rate (OCR) and mitochondrial protein lysine succinylation, which reflects cellular succinyl-CoA levels, using immunofluorescence (IF) staining. Krebs cycle intermediates were also quantitated in these cells using targeted metabolomics. The four fatty acids induced positive changes in OCR parameters, consistent with their oxidative catalysis and utilization. Increases in cellular IF staining of succinylated lysines were observed, indicating that the fatty acids were effective sources of succinyl-CoA in the absence of media glucose, pyruvate, and lipids. The ability of MCAD deficient cells to metabolize C7 was confirmed by the ability of extracts to enzymatically utilize C7-CoA as substrate but not C8-CoA. To evaluate C7 therapeutic potential in vivo, Acadm-/- mice were treated with triheptanoin for seven days. Dose dependent increase in plasma levels of heptanoyl-, valeryl-, and propionylcarnitine indicated efficient metabolism of the medication. The pattern of the acylcarnitine profile paralleled resolution of liver pathology including reversing hepatic steatosis, increasing hepatic glycogen content, and increasing hepatocyte protein succinylation, all indicating improved energy homeostasis in the treated mice. These results provide the impetus to evaluate triheptanoin and the medium branched chain fatty acids as potential therapeutic agents for patients with MCAD deficiency.PMID:37660571 | DOI:10.1016/j.ymgme.2023.107689

Ecotoxicol Environ Saf. 2023 Sep 1;264:115411. doi: 10.1016/j.ecoenv.2023.115411. Online ahead of print.ABSTRACTCadmium (Cd) is a ubiquitous heavy metal with neurotoxicity. Our previous study reported that Cd could inhibit the proliferation of mouse neural stem cells (mNSCs). However, the underlying mechanisms are obscure. In recent years, the rapid growth of multi-omics techniques enables us to explore the cellular responses that occurred after toxicant exposure at the molecular level. In this study, we used a combination of metabolomics and transcriptomics approaches to investigate the effects of exposure to Cd on mNSCs. After treatment with Cd, the metabolites and transcripts in mNSCs changed significantly with 110 differentially expressed metabolites and 2135 differentially expressed genes identified, respectively. The altered metabolites were mainly involved in glycerophospholipid metabolism, arginine and proline metabolism, arginine biosynthesis, glyoxylate and dicarboxylate metabolism. Meanwhile, the transcriptomic data demonstrated perturbed membrane function and signal transduction. Furthermore, integrated analysis of metabolomic and transcriptomic data suggested that glycerophospholipid metabolism might be the major metabolic pathway affected by Cd in mNSCs. More interestingly, the supplementation of lysophosphatidylethanolamine (LPE) attenuated Cd-induced mitochondrial impairment and the inhibition of cell proliferation and differentiation in mNSCs, further supporting our analysis. Overall, the study provides new insights into the mechanisms of Cd-induced neurotoxicity.PMID:37660531 | DOI:10.1016/j.ecoenv.2023.115411

Reprod Biol. 2023 Sep 1;23(4):100811. doi: 10.1016/j.repbio.2023.100811. Online ahead of print.ABSTRACTType 2 diabetes mellitus (T2DM) can cause prostate damage and affect male reproductive function, but the underlying mechanisms are not completely understood. In this study, we used liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics to identify endogenous metabolites in the prostate of a T2DM mouse model. The selected endogenous metabolites were then subjected to bioinformatics analysis and metabolic pathway studies to understand their role in the development of T2DM-induced prostate damage. We used male homozygous BTBR ob/ob mice (n = 12) and BTBR WT mice (n = 11) in this study. We monitored changes in blood glucose, body weight, prostate weight, and prostate index, as well as performed hematoxylin and eosin (H&E) staining and observed that the prostate of the BTBR ob/ob was damaged. We then used ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) for metabolomics analysis. The stability of the model was validated using principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). Using variable importance in projection (VIP) > 1, false discovery rate (FDR) < 0.05, and coefficient of variation (CV) < 30 as criteria, a total of 149 differential metabolites (62 upregulated and 87 downregulated) were identified between the prostates of the two groups of mice. Topological pathway analysis showed that these differential metabolites were mainly involved in sphingolipid (SP) and glycerophospholipid (GP) metabolism. In conclusion, our study not only emphasizes the damage caused by T2DM to the prostate but also provides new insights into the potential mechanisms of T2DM-induced male reproductive dysfunction.PMID:37660522 | DOI:10.1016/j.repbio.2023.100811

World J Microbiol Biotechnol. 2023 Sep 4;39(11):298. doi: 10.1007/s11274-023-03736-8.ABSTRACTSaccharomyces cerevisiae is a health microorganism closely related to human life, especially in food and pharmaceutical industries. S. cerevisiae W303a and CEN.PK2-1C are two commonly used strains for synthetic biology-based natural product production. Yet, the metabolomic and transcriptomic differences between these two strains have not been compared. In this study, metabolomics and transcriptomics were applied to analyze the differential metabolites and differential expression genes (DEGs) between W303a and CEN.PK2-1C cultured in YPD and SD media. The growth rate of W303a in YPD medium was the lowest compared with other groups. When cultured in YPD medium, CEN.PK2-1C produced more phenylalanine than W303a; when cultured in SD medium, W303a produced more phospholipids than CEN.PK2-1C. Transcriptomic analysis revealed that 19 out of 22 genes in glycolysis pathway were expressed at higher levels in CEN.PK2-1C than that in W303a no matter which media were used, and three key genes related to phenylalanine biosynthesis including ARO9, ARO7 and PHA2 were up-regulated in CEN.PK2-1C compared with W303a when cultured in YPD medium, whereas seven DEGs associated with phospholipid biosynthesis were up-regulated in W303a compared with CEN.PK2-1C when cultured in SD medium. The high phenylalanine produced by CEN.PK2-1C and high phospholipids produced by W303a indicated that CEN.PK2-1C may be more suitable for synthesis of natural products with phenylalanine as precursor, whereas W303a may be more appropriate for synthesis of phospholipid metabolites. This finding provides primary information for strain selection between W303a and CEN.PK2-1C for synthetic biology-based natural product production.PMID:37661201 | DOI:10.1007/s11274-023-03736-8

Plant J. 2023 Sep 2. doi: 10.1111/tpj.16450. Online ahead of print.ABSTRACTIn the marine environment, distance signaling based on water-borne cues occurs during interactions between macroalgae and herbivores. In the brown alga Laminaria digitata from North-Atlantic Brittany, oligoalginates elicitation or grazing was shown to induce chemical and transcriptomic regulations, as well as emission of a wide range of volatile aldehydes, but their biological roles as potential defense or warning signals in response to herbivores remain unknown. In this context, bioassays using the limpet Patella pellucida and L. digitata were carried out for determining the effects of algal transient incubation with 4-hydroxyhexenal (4-HHE), 4-hydroxynonenal (4-HNE) and dodecadienal on algal consumption by grazers. Simultaneously, we have developed metabolomic and transcriptomic approaches to study algal molecular responses after treatments of L. digitata with these chemical compounds. The results indicated that, unlike the treatment of the plantlets with 4-HNE or dodecadienal, treatment with 4-HHE decreases algal consumption by herbivores at 100 ng.ml-1 . Moreover, we showed that algal metabolome was significantly modified according to the type of aldehydes, and more specifically the metabolite pathways linked to fatty acid degradation. RNAseq analysis further showed that 4-HHE at 100 ng.ml-1 can activate the regulation of genes related to oxylipin signaling pathways and specific responses, compared to oligoalginates elicitation. As kelp beds constitute complex ecosystems consisting of habitat and food source for marine herbivores, the algal perception of specific aldehydes leading to targeted molecular regulations could have an important biological role on kelps/grazers interactions.PMID:37658798 | DOI:10.1111/tpj.16450

Clin Exp Med. 2023 Sep 2. doi: 10.1007/s10238-023-01170-6. Online ahead of print.ABSTRACTThe primary objective of the RisCoin study was to investigate the interplay of genetic, metabolic, and lifestyle factors as well as stress levels on influencing the humoral immune response after at least two COVID-19 vaccinations, primarily with mRNAs, and the risk of SARS-CoV-2 breakthrough infections during follow-up. Here, we describe the study design, procedures, and study population. RisCoin is a prospective, monocentric, longitudinal, observational cohort study. Between October and December 2021, 4515 participants with at least two COVID-19 vaccinations, primarily BNT162b2 and mRNA-1273, were enrolled at the LMU University Hospital of Munich, thereof > 4000 healthcare workers (HCW), 180 patients with inflammatory bowel disease under immunosuppression, and 119 patients with mental disorders. At enrollment, blood and saliva samples were collected to measure anti-SARS-CoV-2 antibodies, their neutralizing capacity against Omicron-BA.1, stress markers, metabolomics, and genetics. To ensure the confidential handling of sensitive data of study participants, we developed a data protection concept and a mobile application for two-way communication. The application allowed continuous data reporting, including breakthrough infections by the participants, despite irreversible anonymization. Up to 1500 participants attended follow-up visits every two to six months after enrollment. The study gathered comprehensive data and bio-samples of a large representative HCW cohort and two patient groups allowing analyses of complex interactions. Our data protection concept combined with the mobile application proves the feasibility of longitudinal assessment of anonymized participants. Our concept may serve as a blueprint for other studies handling sensitive data on HCW.PMID:37659994 | DOI:10.1007/s10238-023-01170-6

Zhonghua Kou Qiang Yi Xue Za Zhi. 2023 Sep 2;58(9):938-943. doi: 10.3760/cma.j.cn112144-20230627-00254. Online ahead of print.ABSTRACTObjective: To investigate the metabolic disorders in placental tissues of dexamethasone induced cleft palate mode. Methods: Twelve pregnant rabbits were randomly divided into dexamethasone group (experimental group, 8) and saline control group (4), and a certain amount of dexamethasone and saline were administered intramuscularly to the experimental and control groups respectively from embryonic days (ED) 13 to 16, and placental tissue samples were collected on day 21 of gestation. The corresponding profiles of the embryonic placental tissue samples were obtained by liquid chromatography-triple tandem quadrupole(LC-MS), and the metabolites of the embryonic placental tissues were characterized by principal component analysis among the dexamethasone-treated group with cleft palate (D-CP group), the dexamethasone-treated group without cleft palate (D-NCP group) and the control group. Results: There were significant metabolic differences among the D-CP group, D-NCP group and control group, with a total of 133 differential metabolites (VIP>1, P<0.05) involving in important metabolic pathways including vitamin B6 metabolism, lysine metabolism, arginine anabolic metabolism, and galactose metabolism. The four metabolites, vitamin B6, galactose, lysine and urea, differed among the three groups (P<0.05). There were significant differences in vitamin B6 (0.960±0.249, 0.856±0.368, 1.319±0.322), galactose (0.888±0.171, 1.033±0.182, 1.127±0.127), lysine (1.551±0.924, 1.789±1.435, 0.541±0.424) and urea (0.743±0.142, 1.137±0.301, 1.171±0.457, respectively) levels among control group, D-NCP group and D-CP group (F=5.90, P=0.008; F=5.59, P=0.009; F=4.26, P=0.025; F=5.29, P=0.012). Conclusions: The results indicated that dexamethasone induced cleft palate may be highly correlated with metabolic disorders including vitamin B6 metabolism, lysine metabolism, arginine anabolic metabolism and galactose metabolism.PMID:37659853 | DOI:10.3760/cma.j.cn112144-20230627-00254

J Ethnopharmacol. 2023 Aug 31:117115. doi: 10.1016/j.jep.2023.117115. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The utilization of plants with therapeutic properties in traditional medicine has a longstanding practice. Among them, the well-known Allium cepa L. commonly known as onion has been valued for its anti-inflammatory and antioxidant potential in the treatment of various ailments, including gastric ulcers.AIM OF THE STUDY: This study investigated the gastroprotective potential of red onion peel extract and its fractions in a rat model of ethanol-induced gastric ulcer. Moreover, their phytochemical profiles were compared to identify the active metabolites.MATERIALS AND METHODS: Mass spectrometry-based metabolomics and chemometrics were performed for phytochemical analysis. Ethanol-induced gastric ulcer model was used to assess the gastroprotective activity. Nine groups of rats were allocated as follows: Group 1 was the normal control; Group 2 rats were used as a positive control (1 mL of absolute ethanol); and Group 3 rats were treated with famotidine at a dose of 20 mg/kg orally. Group 4 and 5 rats were treated with total acidified ethanolic extract (T1, T2). Group 6 and 7 rats were treated with anthocyanins-rich fractions (P1, P2). Groups 8 and 9 were the flavonoids-rich fraction (S1, S2) treatment. Prior to scarification, the ulcer index in mm was obtained from gastric tissues photographed beside a ruler with further analysis using ImageJ software.RESULTS: Seventy key major and discriminatory metabolites were identified including flavonoids, anthocyanins, phenolic acids, and miscellaneous compounds. The examined extract and its fractions significantly reduced the ulcer index and inflammatory cytokines via downregulating HMGB-1/NF-κB. Also, they augmented the expression of Nrf2/HO-1 and reduced NOX1/4 mRNA expression. Moreover, there was a significant reduction in the oxidative stress and apoptotic biomarkers as well as a noticeable enhancement in histopathological changes of the stomach tissues.CONCLUSION: Red onion peels have a promising dose dependent gastroprotective potential in alcohol-induced ulcers via modulating Nrf2/HO-1 and HMGB-1/NF-κB trajectories. This highlights the potential of red onion peels in treating gastric ulcers.PMID:37659760 | DOI:10.1016/j.jep.2023.117115

J Stomatol Oral Maxillofac Surg. 2023 Aug 31:101618. doi: 10.1016/j.jormas.2023.101618. Online ahead of print.ABSTRACTPURPOSE: Oral leukoplakia (OL) is a common potentially malignant oral disorder. Therefore, there is a need for simple screening methods for OL before its transformation into oral cancer. Furthermore, because invasive open biopsy is the sole method to determine if an OL lesion is dysplastic, there is also a clinical need for non-invasive methods to differentiate dysplastic OL from non-dysplastic OL. This study aimed to identify salivary metabolites that can help differentiate patients with OL from healthy controls (HC) and also dysplastic OL from non-dysplastic OL.MATERIAL & METHODS: Whole unstimulated saliva samples were collected from patients with OL (n = 30) and HCs (n = 29). The OL group included nine patients with dysplastic OL and 20 with non-dysplastic OL. Hydrophilic metabolites in the saliva samples were comprehensively analyzed through capillary electrophoresis mass spectrometry. To evaluate the discrimination ability of a combination of multiple markers, a multiple logistic regression (MLR) model was developed to differentiate patients OL from HCs and dysplastic OL from non-dysplastic OL.RESULTS: Twenty-eight metabolites were evidently different between patients with OL and HCs. Finally, three metabolites (guanine, carnitine, and N-acetylputrescine) were selected to develop the MLR model, which resulted in a high area under curve (AUC) of the receiver operating characteristic (ROC) to differentiate patients with OL from HCs (AUC = 0.946, p < 0.001, 95% confidential interval [CI] = 0.889- 1.000). Similarly, two metabolites were evidently different between patients with dysplastic and non-dysplastic OL. Finally, only one metabolite (7-methylguanine) was selected in the MLR model, which revealed a moderate discrimination ability for dysplastic and non-dysplastic OL (AUC = 0761, p = 0.027, 95% CI = 0.551-0.972).CONCLUSION: Our candidate salivary metabolites showed potential not only to discriminate OL from HC, but also to discriminate dysplastic OL from non-dysplastic OL.PMID:37659754 | DOI:10.1016/j.jormas.2023.101618

Plant Sci. 2023 Aug 31:111852. doi: 10.1016/j.plantsci.2023.111852. Online ahead of print.ABSTRACTWith the increasing population, there lies a pressing demand for food, feed and fibre, while the changing climatic conditions pose severe challenges for agricultural production worldwide. Water is the lifeline for crop production; thus, enhancing crop water-use efficiency (WUE) and improving drought resistance in crop varieties are crucial for overcoming these challenges. Genetically-driven improvements in yield, WUE and drought tolerance traits can buffer the worst effects of climate change on crop production in dry areas. While traditional crop breeding approaches have delivered impressive results in increasing yield, the methods remain time-consuming and are often limited by the existing allelic variation present in the germplasm. Significant advances in breeding and high-throughput omics technologies in parallel with smart agriculture practices have created avenues to dramatically speed up the process of trait improvement by leveraging the vast volumes of genomic and phenotypic data. For example, individual genome and pan-genome assemblies, along with transcriptomic, metabolomic and proteomic data from germplasm collections, characterised at phenotypic levels, could be utilised to identify marker-trait associations and superior haplotypes for crop genetic improvement. In addition, these omics approaches enable the identification of genes involved in pathways leading to the expression of a trait, thereby providing an understanding of the genetic, physiological and biochemical basis of trait variation. These data-driven gene discoveries and validation approaches are essential for crop improvement pipelines, including genomic breeding, speed breeding and gene editing. Herein, we provide an overview of prospects presented using big data-driven approaches (including artificial intelligence and machine learning) to harness new genetic gains for breeding programs and develop drought-tolerant crop varieties with favourable WUE and high-yield potential traits.PMID:37659733 | DOI:10.1016/j.plantsci.2023.111852

Plant Sci. 2023 Aug 31:111853. doi: 10.1016/j.plantsci.2023.111853. Online ahead of print.ABSTRACTThe squash gain-of-function mutant etr2b disrupts the ethylene-binding domain of ethylene receptor CpETR2B, conferring partial ethylene insensitivity, changes in flower and fruit development, and enhanced salt tolerance. In this paper, we found that etr2b also confers a growth advantage as well as a physiological and metabolomic response that make the mutant better adapted to drought. Mutant plants had a higher root and leaf biomass than WT under both well-watered and drought conditions, but the reduction in growth parameters in response to drought was similar in WT and etr2b. Water deficit reduced all gas-exchange parameters in both WT and etr2b, but under moderate drought the mutant increased photosynthesis rate in comparison with control conditions, and showed a higher leaf CO2 concentration, transpiration rate, and stomata conductance than WT. The response of etr2b to drought indicates that ethylene is a negative regulator of plant growth under both control and drought. Since etr2b increased ABA content in well-watered plant, but prevented the induction of ABA production in response to drought, it is likely that the etr2b response under drought is not mediated by ABA. A 1H NMR metabolomic analysis revealed that etr2b enhances the accumulation of osmolytes (soluble sugars and trigonelline), unsaturated and polyunsaturated fatty acids, and phenolic compounds under drought, concomitantly with a reduction of malic- and fumaric-acid. The role of CpETR2B and ethylene in the regulation of these drought-protective metabolites is discussed.PMID:37659732 | DOI:10.1016/j.plantsci.2023.111853

Prog Neuropsychopharmacol Biol Psychiatry. 2023 Aug 31:110849. doi: 10.1016/j.pnpbp.2023.110849. Online ahead of print.ABSTRACTOBJECTIVES: Approximately one-third of major depressive disorder (MDD) patients do not respond to standard antidepressants and develop treatment-resistant depression (TRD). We aimed to reveal metabolic differences and discover promising potential biomarkers in TRD.METHODS: Our study recruited 108 participants including healthy controls (n = 40) and patients with TRD (n = 35) and first-episode drug-naive MDD (DN-MDD) (n = 33). Plasma samples were presented to ultra performance liquid chromatography-tandem mass spectrometry. Then, a machine-learning algorithm was conducted to facilitate the selection of potential biomarkers.RESULTS: TRD appeared to be a distinct metabolic disorder from DN-MDD and healthy controls (HCs). Compared to HCs, 199 and 176 differentially expressed metabolites were identified in TRD and DN-MDD, respectively. Of all the metabolites that were identified, spermine, spermidine, and carnosine were considered the most promising biomarkers for diagnosing TRD and DN-MDD patients, with the resulting area under the ROC curve of 0.99, 0.99, and 0.93, respectively. Metabolic pathway analysis yielded compelling evidence of marked changes or imbalances in both polyamine metabolism and energy metabolism, which could potentially represent the primary altered pathways associated with MDD. Additionally, l-glutamine, Beta-alanine, and spermine were correlated with HAMD score.CONCLUSIONS: A more disordered metabolism structure is found in TRD than in DN-MDD and HCs. Future investigations should prioritize the comprehensive analysis of potential roles played by these differential metabolites and disturbances in polyamine pathways in the pathophysiology of TRD and depression.PMID:37659714 | DOI:10.1016/j.pnpbp.2023.110849