PubMed

Front Cell Infect Microbiol. 2022 Dec 22;12:999627. doi: 10.3389/fcimb.2022.999627. eCollection 2022.ABSTRACTIntracerebral hemorrhage (ICH) is the most devastating subtype of stroke, but effective prevention and treatment strategies are lacking. Recently, gut microbiome and its metabolitesis are considered to be an influencing factor of stroke. However, little is known about the effects of the gut microbiome on ICH and host metabolic activity. Therefore, we used 16S sequencing, macrogenomics sequencing and untargeted metabolomics to explore the differences in gut microbial-metabolome interactions between patients with intracerebral hemorrhage and healthy control populations. We found a significant decrease in the phylum of Firmicutes and a significant increase of Bacteroidetes in ICH patients. At the genus level, Streptococcus, Bifidobacterium, Akkermansia, and Lactobacillus were more abundant in ICH patients. Macrogenomic analysis revealed active glycosaminoglycan degradation, heme synthesis, galactose degradation, lipopolysaccharide core region synthesis, and beta-Lactam resistance in ICH patients. Serum untargeted metabolomic analysis combined with ROC curves showed that octanoylcarnitine, decanoylcarnitine, dodecanoylcarnitine, glyceric acid, pyruvic acid, aspartic acid, methylcysteine, pyroglutamic acid, 9E-tetradecenoic acid, N-Acetylneuraminic acid, and aconitic acid were the best markers for the diagnosis of ICH. Correlation analysis showed that microbiome enriched in the gut of ICH patients were significantly correlated with serum metabolites, revealing a close correlation between the gut microbiome of ICH patients and the host metabolome, and significant differences from the healthy population. microbiota-host co-metabolites including pyruvic acid and 9E-tetradecenoic acid is associated with the the National Institutes of Health Stroke Scale (NIHSS) scores. In conclusion, microbiome-related metabolites in ICH patients was associated with the severity of ICH, the microbiota-host co-metabolites may be a potential may be potential therapeutic targets.PMID:36619742 | PMC:PMC9813413 | DOI:10.3389/fcimb.2022.999627

Front Endocrinol (Lausanne). 2022 Dec 22;13:1037289. doi: 10.3389/fendo.2022.1037289. eCollection 2022.ABSTRACTINTRODUCTION: Type 1 diabetes (T1D) is a chronic condition associated with multiple complications that substantially affect both the quality of life and the life-span of children. Untargeted Metabolomics has provided new insights into disease pathogenesis and risk assessment.METHODS: In this study, we characterized the serum metabolic profiles of 76 children with T1D and 65 gender- and age- matched healthy controls using gas chromatography coupled with timeof-flight mass spectrometry. In parallel, we comprehensively evaluated the clinical phenome of T1D patients, including routine blood and urine tests, and concentrations of cytokines, hormones, proteins, and trace elements.RESULTS: A total of 70 differential metabolites covering 11 metabolic pathways associated with T1D were identified, which were mainly carbohydrates, indoles, unsaturated fatty acids, amino acids, and organic acids. Subgroup analysis revealed that the metabolic changes were consistent among pediatric patients at different ages or gender but were closely associated with the duration of the disease.DISCUSSION: Carbohydrate metabolism, unsaturated fatty acid biosynthesis, and gut microbial metabolism were identified as distinct metabolic features of pediatric T1D. These metabolic changes were also associated with T1D, which may provide important insights into the pathogenesis of the complications associated with diabetes.PMID:36619558 | PMC:PMC9813493 | DOI:10.3389/fendo.2022.1037289

Front Endocrinol (Lausanne). 2022 Dec 22;13:1046159. doi: 10.3389/fendo.2022.1046159. eCollection 2022.ABSTRACTBACKGROUND: Hashimoto's thyroiditis, an autoimmune thyroid disease, shows high morbidity worldwide, particularly in female. Patients with Hashimoto's thyroiditis have an increasing risk of hypothyroidism during the occurrence and progression of Hashimoto's thyroiditis. In recent years, metabolomics has been widely applied in autoimmune diseases, especially thyroid disorders. However, metabolites analysis in Hashimoto's thyroiditis is still absent.METHODS: A total of 92 samples were collected, including 35 cases in the control group, 30 cases in the Hashimoto's thyroiditis with euthyroidism group, and 27 cases in the Hashimoto's thyroiditis with subclinical hypothyroidism group. SPSS 25.0 for statistical analysis and ROC curve, SIMCA 14.0, Metaboanalysis for multifactor analysis, and Origin 2021 for correlation analysis.RESULTS: 21 metabolites were identified. 10 metabolites were obtained from control group versus HTE group, 8 serum metabolites were abnormal between control group and HTS group, 3 metabolites were derived from HTE group versus HTS. Kyoto Encyclopedia of Genes and Genomes Enrichment analysis showed that fatty acid degradation, Arginine, and proline metabolism have a significant impact on HTE, while lysine degradation, tyrosine metabolism play an important role HTS group, compared to control group. In the comparison between the HTE and HTS group, Valine, leucine, and isoleucine degradation and Valine, leucine, and isoleucine biosynthesis exists a key role. Correlation analysis shows clinical are not related to metabolites. ROC curve indicates SM, LPC, PC can efficiency in identification patients with HT in different clinical stage from healthy individuals.CONCLUSION: Serum metabolites were changed in HT. Phospholipids such as SM, LPC, PC influence the pathogenesis of Hashimoto's thyroiditis. Fatty acid degradation and lysine degradation pathways have an impact on different clinical stage of HT.PMID:36619550 | PMC:PMC9814722 | DOI:10.3389/fendo.2022.1046159

Int J Med Sci. 2023 Jan 1;20(1):142-150. doi: 10.7150/ijms.77206. eCollection 2023.ABSTRACTMetformin is the most often prescribed drug for people with type 2 diabetes (T2D). More than 120 million patients with T2D use metformin worldwide. However, monotherapy fails to achieve glycemic control in a third of the treated patients. Genetics contribute to some of the inter-individual variations in glycemic response to metformin. Numerous pharmacogenetic studies have demonstrated that variations in genes related to pharmacokinetics and pharmacodynamics of metformin's encoding transporters are mainly associated with metformin response. The goal of this review is to evaluate the current state of metformin pharmacogenetics and metabolomics research, discuss the clinical and scientific issues that need to be resolved in order to increase our knowledge of patient response variability to metformin, and how to improve patient outcomes. Metformin's hydrophilic nature and absorption as well as its action mechanism and effectiveness on T2D initiation are discussed. The impacts of variations associated with various genes are analysed to identify and evaluate the effect of genetic polymorphisms on the therapeutic activity of metformin. The metabolic pattern of T2D and metformin is also indicated. This is to emphasise that studies of pharmacogenetics and metabolomics could expand our knowledge of metformin response in T2D.PMID:36619226 | PMC:PMC9812811 | DOI:10.7150/ijms.77206

Front Mol Biosci. 2022 Dec 21;9:1042231. doi: 10.3389/fmolb.2022.1042231. eCollection 2022.ABSTRACTBackground: Assessing detailed metabolism in exercising persons minute-to-minute has not been possible. We developed a "drop-of-blood" platform to fulfill that need. Our study aimed not only to demonstrate the utility of our methodology, but also to give insights into unknown mechanisms and new directions. Methods: We developed a platform, based on gas chromatography and mass spectrometry, to assess metabolism from a blood-drop. We first observed a single volunteer who ran 13 km in 60 min. We particularly monitored relative perceived exertion (RPE). We observed that 2,3-bisphosphoglycerate peaked at RPE in this subject. We next expanded these findings to women and men volunteers who performed an RPE-based exercise protocol to RPE at Fi O 2 20.9% or Fi O 2 14.5% in random order. Results: At 6 km, our subject reached his maximum relative perceived exertion (RPE); however, he continued running, felt better, and finished his run. Lactate levels had stably increased by 2 km, ketoacids increased gradually until the run's end, while the hypoxia marker, 2,3 bisphosphoglycerate, peaked at maximum relative perceived exertion. In our normal volunteers, the changes in lactate, pyruvate, ß hydroxybutyrate and a hydroxybutyrate were not identical, but similar to our model proband runner. Conclusion: Glucose availability was not the limiting factor, as glucose availability increased towards exercise end in highly exerted subjects. Instead, the tricarboxylic acid→oxphos pathway, lactate clearance, and thus and the oxidative capacity appeared to be the defining elements in confronting maximal exertion. These ideas must be tested further in more definitive studies. Our preliminary work suggests that our single-drop methodology could be of great utility in studying exercise physiology.PMID:36619172 | PMC:PMC9822726 | DOI:10.3389/fmolb.2022.1042231

Front Mol Biosci. 2022 Dec 21;9:1084060. doi: 10.3389/fmolb.2022.1084060. eCollection 2022.ABSTRACTA reliable method for metabolite extraction is central to mass spectrometry-based metabolomics. However, existing methods are lengthy, mostly due to the step of scraping cells from cell culture vessels, which restricts metabolomics in broader application such as lower cell numbers and high-throughput studies. Here, we present a simplified metabolite extraction (SiMeEx) method, to efficiently and quickly extract metabolites from adherent mammalian cells. Our method excludes the cell scraping step and therefore allows for a more efficient extraction of polar metabolites in less than 30 min per 12-well plate. We demonstrate that SiMeEx achieves the same metabolite recovery as using a standard method containing a scraping step, in various immortalized and primary cells. Omitting cell scraping does not compromise the performance of non-targeted and targeted GC-MS analysis, but enables metabolome analysis of cell culture on smaller well sizes down to 96-well plates. Therefore, SiMeEx demonstrates advantages not only on time and resources, but also on the applicability in high-throughput studies.PMID:36619169 | PMC:PMC9812552 | DOI:10.3389/fmolb.2022.1084060

Front Mol Biosci. 2022 Dec 21;9:1074285. doi: 10.3389/fmolb.2022.1074285. eCollection 2022.ABSTRACTAtherosclerosis is a life-threatening disease associated with morbidity and mortality in patients with type 2 diabetes (T2D). This study aimed to characterize a salivary signature of atherosclerosis based on evaluation of carotid intima-media thickness (IMT) to develop a non-invasive predictive tool for diagnosis and disease follow-up. Metabolites in saliva and plasma samples collected at admission and after treatment from 25 T2D patients hospitalized for 2 weeks to undergo medical treatment for diabetes were comprehensively profiled using metabolomic profiling with gas chromatography-mass spectrometry. Orthogonal partial least squares analysis, used to explore the relationships of IMT with clinical markers and plasma and salivary metabolites, showed that the top predictors for IMT included salivary allantoin and 1,5-anhydroglucitol (1,5-AG) at both the baseline examination at admission and after treatment. Furthermore, though treatment induced alterations in salivary levels of allantoin and 1,5-AG, it did not modify the association between IMT and these metabolites (p interaction > 0.05), and models with these metabolites combined yielded satisfactory diagnostic accuracy for the high IMT group even after treatment (area under curve = 0.819). Collectively, this salivary metabolite combination may be useful for non-invasive identification of T2D patients with a higher atherosclerotic burden in clinical settings.PMID:36619162 | PMC:PMC9815705 | DOI:10.3389/fmolb.2022.1074285

Front Pharmacol. 2022 Dec 21;13:1076960. doi: 10.3389/fphar.2022.1076960. eCollection 2022.ABSTRACTIntroduction: Ginkgo biloba L. leaf extract (GBLE) has been reported to be effective for alleviating cognitive and memory impairment in Alzheimer's disease (AD). Nevertheless, the potential mechanism remains unclear. Herein, this study aimed to explore the neuroprotective effects of GBLE on AD and elaborate the underlying therapeutic mechanism. Methods: Donepezil, the most widely prescribed drug for AD, was used as a positive control. An integrated metabolomics and lipidomics approach was adopted to characterize plasma metabolic phenotype of APP/PS1 double transgenic mice and describe the metabolomic and lipidomic fingerprint changes after GBLE intervention. The Morris water maze test and immunohistochemistry were applied to evaluate the efficacy of GBLE. Results: As a result, administration of GBLE significantly improved the cognitive function and alleviated amyloid beta (Aβ) deposition in APP/PS1 mice, showing similar effects to donepezil. Significant alterations were observed in metabolic signatures of APP/PS1 mice compared with wild type (WT) mice by metabolomic analysis. A total of 60 markedly altered differential metabolites were identified, including 28 lipid and lipid-like molecules, 13 organic acids and derivatives, 11 organic nitrogen compounds, and 8 other compounds, indicative of significant changes in lipid metabolism of AD. Further lipidomic profiling showed that the differential expressed lipid metabolites between APP/PS1 and WT mice mainly consisted of phosphatidylcholines, lysophosphatidylcholines, triglycerides, and ceramides. Taking together all the data, the plasma metabolic signature of APP/PS1 mice was primarily characterized by disrupted sphingolipid metabolism, glycerophospholipid metabolism, glycerolipid metabolism, and amino acid metabolism. Most of the disordered metabolites were ameliorated after GBLE treatment, 19 metabolites and 24 lipids of which were significantly reversely regulated (adjusted-p<0.05), which were considered as potential therapeutic targets of GBLE on AD. The response of APP/PS1 mice to GBLE was similar to that of donepezil, which significantly reversed the levels of 23 disturbed metabolites and 30 lipids. Discussion: Our data suggested that lipid metabolism was dramatically perturbed in the plasma of APP/PS1 mice, and GBLE might exert its neuroprotective effects by restoring lipid metabolic balance. This work provided a basis for better understanding the potential pathogenesis of AD and shed new light on the therapeutic mechanism of GBLE in the treatment of AD.PMID:36618950 | PMC:PMC9810818 | DOI:10.3389/fphar.2022.1076960

Front Nutr. 2022 Dec 22;9:1062323. doi: 10.3389/fnut.2022.1062323. eCollection 2022.ABSTRACTFu brick tea (FBT) and its extracts have good lipid-lowering effects and have been used in the treatment of obesity in previous studies. Unfortunately, the therapeutic effect of FBT on non-alcoholic fatty liver disease (NAFLD) has not been thoroughly studied. In this study, we explored the mechanism by which FBT alleviates NAFLD from the perspective of the gut microbiota and liver metabolites. The results showed that FBT could reduce the body weight, liver weight and abdominal fat of NAFLD mice, and improve liver pathological morphology, liver lipid deposition, blood lipids and liver function. Moreover, FBT improved the diversity of the gut microbiota and changed the profile of liver metabolism in NAFLD mice. Further studies showed that FBT could ameliorate the cecum barrier, and regulate the effects of factors related to lipid synthesis in the cecum and liver of NAFLD mice. In conclusion, the present study confirmed that FBT can alleviate high fat induced NAFLD by regulating the homeostasis of the gut microbiota and liver metabolites.PMID:36618677 | PMC:PMC9815510 | DOI:10.3389/fnut.2022.1062323

Front Plant Sci. 2022 Dec 23;13:1069191. doi: 10.3389/fpls.2022.1069191. eCollection 2022.ABSTRACTPhosphorus (P) is an essential macronutrient element for plant growth, and deficiency of inorganic phosphate (Pi) limits plant growth and yield. Elephant grass (Pennisetum purpureum) is an important fodder crop cultivated widely in tropical and subtropical areas throughout the world. However, the mechanisms underlying efficient P use in elephant grass under Pi deficiency remain poorly understood. In this study, the physiological and molecular responses of elephant grass leaves and roots to Pi deficiency were investigated. The results showed that dry weight, total P concentration, and P content decreased in Pi-deprived plants, but that acid phosphatase activity and P utilization efficiency (PUE) were higher than in Pi-sufficient plants. Regarding Pi starvation-responsive (PSR) genes, transcriptomics showed that 59 unigenes involved in Pi acquisition and transport (especially 18 purple acid phosphatase and 27 phosphate transporter 1 unigenes) and 51 phospholipase unigenes involved in phospholipids degradation or Pi-free lipids biosynthesis, as well as 47 core unigenes involved in the synthesis of phenylpropanoids and flavonoids, were significantly up-regulated by Pi deprivation in leaves or roots. Furthermore, 43 unigenes related to Pi-independent- or inorganic pyrophosphate (PPi)-dependent bypass reactions were markedly up-regulated in Pi-deficient leaves, especially five UDP-glucose pyrophosphorylase and 15 phosphoenolpyruvate carboxylase unigenes. Consistent with PSR unigene expression changes, metabolomics revealed that Pi deficiency significantly increased metabolites of Pi-free lipids, phenylpropanoids, and flavonoids in leaves and roots, but decreased phospholipid metabolites. This study reveals the mechanisms underlying the responses to Pi starvation in elephant grass leaves and roots, which provides candidate unigenes involved in efficient P use and theoretical references for the development of P-efficient elephant grass varieties.PMID:36618667 | PMC:PMC9817030 | DOI:10.3389/fpls.2022.1069191

Front Plant Sci. 2022 Dec 22;13:1102044. doi: 10.3389/fpls.2022.1102044. eCollection 2022.ABSTRACTEpitranscriptome constitutes a gene expression checkpoint in all living organisms. Nitrogen is an essential element for plant growth and development that influences gene expression at different levels such as epigenome, transcriptome, proteome, and metabolome. Therefore, our hypothesis is that changes in the epitranscriptome may regulate nitrogen metabolism. In this study, epitranscriptomic modifications caused by ammonium nutrition were monitored in maritime pine roots using Oxford Nanopore Technology. Transcriptomic responses mainly affected transcripts involved in nitrogen and carbon metabolism, defense, hormone synthesis/signaling, and translation. Global detection of epitranscriptomic marks was performed to evaluate this posttranscriptional mechanism in un/treated seedlings. Increased N6-methyladenosine (m6A) deposition in the 3'-UTR was observed in response to ammonium, which seems to be correlated with poly(A) lengths and changes in the relative abundance of the corresponding proteins. The results showed that m6A deposition and its dynamics seem to be important regulators of translation under ammonium nutrition. These findings suggest that protein translation is finely regulated through epitranscriptomic marks likely by changes in mRNA poly(A) length, transcript abundance and ribosome protein composition. An integration of multiomics data suggests that the epitranscriptome modulates responses to nutritional, developmental and environmental changes through buffering, filtering, and focusing the final products of gene expression.PMID:36618661 | PMC:PMC9815506 | DOI:10.3389/fpls.2022.1102044

Front Plant Sci. 2022 Dec 22;13:1102215. doi: 10.3389/fpls.2022.1102215. eCollection 2022.ABSTRACTGreen microalgae can accumulate neutral lipids, as part of a general lipid remodeling mechanism under stress such as nitrogen starvation. Lobosphaera incisa is of special interest because of its unique TAG acyl chain composition, especially 20:4 (n-6) can reach up to 21% of dry weight after nitrogen starvation. In order to identify factors that may influence the accumulation of polyunsaturated fatty acids (PUFAs), we identified recently a linoleate 13-lipoxygenase (LiLOX). It shares highest identity with plastidic enzymes from vascular plants and is induced upon nitrogen starvation. Here, we confirmed the localization of LiLOX in the stroma of plastids via transient expression in epithelial onion cells. In order to further characterize this enzyme, we focused on the identification of the endogenous substrate of LiLOX. In this regard, an ex vivo enzymatic assay, coupled with non-targeted analysis via mass spectrometry allowed the identification of MGDG, DGDG and PC as three substrate candidates, later confirmed via in vitro assays. Further investigation revealed that LiLOX has preferences towards the lipid class MGDG, which seems in agreement with its localization in the galactolipid rich plastid. Altogether, this study shows the first characterization of plastidic LOX from green algae, showing preference for MGDGs. However, lipidomics analysis did neither reveal an endogenous LiLOX product nor the final end product of MGDG oxidation. Nevertheless, the latter is a key to understanding the role of this enzyme and since its expression is highest during the degradation of the plastidic membrane, it is tempting to assume its involvement in this process.PMID:36618660 | PMC:PMC9813749 | DOI:10.3389/fpls.2022.1102215

Front Plant Sci. 2022 Dec 22;13:1076037. doi: 10.3389/fpls.2022.1076037. eCollection 2022.ABSTRACTINTRODUCTION: Camellia is among the most ornamentally valuable flowers and plants worldwide. Flower abscission typically causes significant financial losses by the horticultural landscape. Previous research has revealed that phytohormones, transcription factors, and other genes involved in floral development regulate the maintenance and mortality of flowers.METHODS: In this study, for the first time, the transcriptomes and targeted hormone metabolomics of three developmental stages of the receptacles of two distinct camellia strains (CF: abscission strain, CHF: nonabscission strain) were analyzed to determine their roles in regulating blossom abscission in camellia.RESULTS: ABA content was shown to be considerably upregulated throughout all phases of CF development, as were the genes implicated in the ABA production pathway and their downstream counterparts. Highly expressed genes in CF were involved in galactose metabolism, phenylpropanoid biosynthesis, amino and nucleotide sugar metabolism, pentose and glucuronate interconversions, and MAPK. Among others, highly expressed genes in CHF are associated with fructose and mannose metabolism, alpha-linolenic acid metabolism, biosynthesis of secondary metabolites, starch and sucrose metabolism, and cutin, suberin, and wax biosynthesis. A vast variety of stress response-related pathways and redox-related activities were also shown to be active in CHF. In contrast, CF dramatically activated pathways associated with lignin production, keratinogenesis, cell wall biogenesis, and ABA response. A comparative transcriptomic study of the CF and CHF pathways revealed that the downstream response pathways of hormones, including CTK, BR, IAA, ethylene, and GA, were very active in CF, indicating a significant amount of signal transduction and transcriptional regulation by CF. In addition, members of the transcription factor family, such as MYB, bHLH, MADS, and WD40, may regulate flower abscission.DISCUSSION: A comparative transcriptome analysis of two distinct strains of camellia receptacles elucidates the molecular processes and regulatory characteristics of flower abscission and provides direction for the targeted improvement and breeding of camellia.PMID:36618654 | PMC:PMC9813748 | DOI:10.3389/fpls.2022.1076037

Front Plant Sci. 2022 Dec 21;13:1011026. doi: 10.3389/fpls.2022.1011026. eCollection 2022.ABSTRACTLentil cultivation is often hampered by aphid population outspreads with detrimental impacts to crop development and production, challenging food safety and agriculture sustainability. The pea aphid (Acyrthosiphon pisum) is a significant threat to lentil in the temperate zone rainfed systems. A set of management practices including resilient cultivars and application of insecticides have effectively controlled aphid infestation. However, the plant defense against insect pests is scantily dissected and limited to the individual components including antibiosis, antixenosis and tolerance that constitute a combination of plant stress responses. Utilizing a lentil germplasm collection, we assessed the antixenosis and aphid tolerance mechanisms in association to important morphological parameters. Physiological parameters including relative water content (RWC) measured at 24h and 48h post-aphid infestation revealed genotype-specific responses. The contents of key plant hormones including salicylic acid (SA), jasmonic acid (JA), abscisic acid (ABA) and indoleacetic acid (IAA) implicated in defense signal-transduction pathways were also determined in lentil accessions after aphid herbivory infestation. In parallel, the expression of hallmark defense genes governed by SA- and JA-signaling pathways at 24h and 48h post aphid herbivory revealed significant differentiation patterns among the accessions. An interplay of hormone crosstalk is unveiled that possibly governs defense responses and aphid resistance. Besides the metabolomic profiling of accessions under aphid herbivory indicated the indispensable role of key secondary metabolites accumulation such as flavonoids, alkaloids, phenolics and fatty acids as a front line of plant defense and a potential integration of hormone signaling pathways in metabolome reprogramming. Overall, the study presents a panorama of distinct lentil responses to aphids and a critical view of the molecular mechanisms implicated in lentil insect defense to further our insight and advance crop protection and breeding approaches in a climate changing environment.PMID:36618648 | PMC:PMC9811392 | DOI:10.3389/fpls.2022.1011026

Front Plant Sci. 2022 Dec 22;13:1079212. doi: 10.3389/fpls.2022.1079212. eCollection 2022.ABSTRACTGrain size with high heritability and stability is an important selection target during Tartary buckwheat breeding. However, the mechanisms that regulate Tartary buckwheat grain development are unknown. We generated transcriptome and metabolome sequencing from 10 and 15 days past anthesis (DPA) grains of big grain mutant (bg1) and WT, and identified 4108 differentially expressed genes (DEGs) including 93 significantly up-regulated differential genes and 85 significantly down-regulated genes in both stages, simultaneously. Meanwhile, we identified DEGs involved in ubiquitin-proteasome pathway, HAI-KU (IKU) pathway, mitogen-activated protein kinase (MAPK) signaling pathway, plant hormone (auxin, brassinosteroids and cytokinins) transduction pathway and five transcription factor families, including APETALA (AP2), GROWTH-REGULATING FACTORS (GRF), AUXIN RESPONSE FACTOR (ARF), WRKY and MYB. Weighted gene co-expression network analysis (WGCNA) was performed and obtained 9 core DEGs. Conjoint analyses of transcriptome and metabolome sequencing screened out 394 DEGs. Using a combined comprehensive analysis, we identified 24 potential candidate genes that encode E3 ubiquitin-protein ligase HIP1, EMBRYO-DEFECTIVE (EMB) protein, receptor-like protein kinase FERONIA (FER), kinesin-4 protein SRG1, and so on, which may be associated with the big-grain mutant bg1. Finally, a quantitative real-time Polymerase Chain Reaction (qRT-PCR) assay was conducted to validate the identified DEGs. Our results provide additional knowledge for identification and functions of causal candidate genes responsible for the variation in grain size and will be an invaluable resource for the genetic dissection of Tartary buckwheat high-yield molecular breeding.PMID:36618631 | PMC:PMC9815120 | DOI:10.3389/fpls.2022.1079212

Front Plant Sci. 2022 Dec 21;13:1030578. doi: 10.3389/fpls.2022.1030578. eCollection 2022.ABSTRACTHighland barley is one of the few crops that can be grown at high elevations, making it a key resource within the Tibet Plateau. Weeds are a significant threat to highland barley production, and new herbicides and tolerant barley varieties are needed to control this ever-growing problem. A better understanding of existing herbicide resistance mechanisms is therefore needed. In this study, transcriptomic and metabolomic analyses were used to identify molecular and physiological changes in two highland barley genotypes with differing sensitivities to the herbicide pyroxsulam. We identified several stress-responsive metabolites, including flavonoids and antioxidants, which accumulated to significantly higher levels in the pyroxsulam-resistant genotype. Additionally, we found key genes in both the flavonoid biosynthesis pathway and the antioxidant system that were up-regulated in pyroxsulam-resistant barley. This work significantly expands on the current understanding of the molecular mechanisms underlying differing pyroxsulam tolerance among barley genotypes and provides several new avenues to explore for breeding or engineering tolerant barley.PMID:36618617 | PMC:PMC9812518 | DOI:10.3389/fpls.2022.1030578

Med Res Arch. 2022 Oct 31;10(10). doi: 10.18103/mra.v10i10.3318.ABSTRACTBACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment of recurrent Clostridioides difficile infections (rCDI), but has more limited efficacy in treating either ulcerative colitis (UC) or Crohn's disease (CD), two major forms of inflammatory bowel diseases (IBD). We hypothesize that FMT recipients with rCDI and/or IBD have baseline fecal bile acid (BA) compositions that differ significantly from that of their healthy donors and that FMT will normalize the BA compositions.AIM: To study the effect of single colonoscopic FMT on microbial composition and function in four recipient groups: 1.) rCDI patients without IBD (rCDI-IBD); 2.) rCDI with IBD (rCDI+IBD); 3.) UC patients without rCDI (UC-rCDI); 4.) CD patients without rCDI (CD-rCDI).METHODS: We performed 16S rRNA gene sequence, shotgun DNA sequence and quantitative bile acid metabolomic analyses on stools collected from 55 pairs of subjects and donors enrolled in two prospective single arm FMT clinical trials (Clinical Trials.gov ID NCT03268213, 479696, UC no rCDI ≥ 2x IND 1564 and NCT03267238, IND 16795). Fitted linear mixed models were used to examine the effects of four recipient groups, FMT status (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on microbial diversity and composition, bile acid metabolites and bile acid metabolizing enzyme gene abundance.RESULTS: The pre-FMT stools collected from rCDI ± IBD recipients had reduced α-diversity compared to the healthy donor stools and was restored post-FMT. The α-diversity in the pre-FMT stools collected from UC-rCDI or CD-rCDI recipients did not differ significantly from donor stools. FMT normalized some recipient/donor ratios of genus level taxa abundance in the four groups. Fecal secondary BA levels, including some of the secondary BA epimers that exhibit in vitro immunomodulatory activities, were lower in rCDI±IBD and CD-rCDI but not UC-rCDI recipients compared to donors. FMT restored secondary BA levels. Metagenomic baiE gene and some of the eight bile salt hydrolase (BSH) phylotype abundances were significantly correlated with fecal BA levels.CONCLUSION: Restoration of multiple secondary BA levels, including BA epimers implicated in immunoregulation, are associated with restoration of fecal baiE gene counts, suggesting that the 7-α-dehydroxylation step is rate-limiting.PMID:36618438 | PMC:PMC9817289 | DOI:10.18103/mra.v10i10.3318

Arch Razi Inst. 2022 Jun 30;77(3):1113-1123. doi: 10.22092/ARI.2022.357395.2035. eCollection 2022 Jun.ABSTRACTAcute change in mental state is characterized by an impaired level of consciousness, decreased attention, and cognitive changes, and has a variable course throughout its period. Delirium is common in the elderly and hospitalized patients, especially after major surgeries, and increases mortality and morbidity in patients. This study was designed to investigate the relationship between the incidence of delirium after heart surgery and some intrusive factors during surgery. A total of 263 middle-aged, elderly, and chronic patients with functional class III-IV heart failure were classified based on the New York Heart Association classification and valvular heart disease. Cognitive impairment screening was performed using the Mini-Cog test and clock drawing test in addition to standard general clinical examinations on patients. Cognitive impairment was diagnosed in patients with coronary heart disease preparing for planned surgical treatment, regardless of age, while the results of both tests were significantly worse in elderly patients than in their middle-aged counterparts. In the early postoperative period, both among the middle-aged and elderly patients, there was a significant improvement in the results of the clock drawing test. Middle-aged patients also showed improved results on the Mini-Cog test, while the elderly patients showed an increase in cognitive dysfunction. In the third stage of the examination of cognitive function in the two studied groups of patients with valvular pathology at the first checkpoint, no statistically significant differences were found in the Mini-Mental State Examination (MMSE), Mini-Cog, and clock drawing test. The results of the clock drawing test in the main and control groups were recorded at 8.9±0.4 and 5.8±0.3 points, respectively (P<0.05). The MMSE results were estimated at the points of 27.1±0.1 and 24.1±0.2 in the main and control groups, respectively, while the results of the Mini-Cog test were calculated at 2.2±0.2 and 1.2±0.4 words in the main and control group, respectively (P<0.05). The application of the algorithm for the prevention of cognitive frailty in patients of older age groups after open-heart surgery under cardiopulmonary bypass would possibly lead to a decrease in the number of early and late postoperative complications, which shows the necessity of using it for patients of older age groups in multimodal programs to prepare them for surgical interventions.PMID:36618298 | PMC:PMC9759241 | DOI:10.22092/ARI.2022.357395.2035

Food Funct. 2023 Jan 9. doi: 10.1039/d2fo02964b. Online ahead of print.ABSTRACTAscophyllum nodosum polysaccharide (ANP) can protect against colonic inflammation but the underlying mechanism is still unclear. This study has determined the metabolites of gut microbiota regulated by ANP to reveal the mechanism of the anti-inflammation effect of ANP. Using an in vitro colonic fermentation model, the results indicate that gut microbiota could utilize a proportion of ANP to increase the concentrations of short-chain fatty acids (SCFAs) and decrease ammonia content. Metabolomics revealed that 46 differential metabolites, such as betaine, L-carnitine, and aminoimidazole carboxamide ribonucleotide (AICAR), could be altered by ANP. Metabolic pathway analysis showed that ANP mainly up-regulated the phenylalanine, tyrosine, and tryptophan biosynthesis and aminoacyl-tRNA biosynthesis, which were negatively correlated with inflammation progression. Interestingly, these metabolites associated with inflammation were also up-regulated by ANP in colitis mice, including betaine, L-carnitine, AICAR, N-acetyl-glutamine, tryptophan, and valine, which were mainly associated with amino acid metabolism and aminoacyl-tRNA biosynthesis. Furthermore, the metabolites modulated by ANP were associated with the relative abundances of Akkermansia, Bacteroides, Blautia, Coprobacillus, Enterobacter, and Klebsiella. Additionally, based on VIP values, betaine is a key metabolite after the ANP supplement in vitro and in vivo. As indicated by these findings, ANP can up-regulate the production of SCFAs, betaine, L-carnitine, and AICAR and aminoacyl-tRNA biosynthesis to protect against colonic inflammation and maintain intestinal health.PMID:36617886 | DOI:10.1039/d2fo02964b

J Huntingtons Dis. 2023 Jan 4. doi: 10.3233/JHD-220552. Online ahead of print.ABSTRACTBACKGROUND: Metabolic abnormalities have long been predicted in Huntington's disease (HD) but remain poorly characterized. Chronobiological dysregulation has been described in HD and may include abnormalities in circadian-driven metabolism.OBJECTIVE: Here we investigated metabolite profiles in the transgenic sheep model of HD (OVT73) at presymptomatic ages. Our goal was to understand changes to the metabolome as well as potential metabolite rhythm changes associated with HD.METHODS: We used targeted liquid chromatography mass spectrometry (LC-MS) metabolomics to analyze metabolites in plasma samples taken from female HD transgenic and normal (control) sheep aged 5 and 7 years. Samples were taken hourly across a 27-h period. The resulting dataset was investigated by machine learning and chronobiological analysis.RESULTS: The metabolic profiles of HD and control sheep were separable by machine learning at both ages. We found both absolute and rhythmic differences in metabolites in HD compared to control sheep at 5 years of age. An increase in both the number of disturbed metabolites and the magnitude of change of acrophase (the time at which the rhythms peak) was seen in samples from 7-year-old HD compared to control sheep. There were striking similarities between the dysregulated metabolites identified in HD sheep and human patients (notably of phosphatidylcholines, amino acids, urea, and threonine).CONCLUSION: This work provides the first integrated analysis of changes in metabolism and circadian rhythmicity of metabolites in a large animal model of presymptomatic HD.PMID:36617787 | DOI:10.3233/JHD-220552