PubMed

Front Plant Sci. 2022 Nov 3;13:1022961. doi: 10.3389/fpls.2022.1022961. eCollection 2022.ABSTRACTThe gibberellic acid (GA)-stimulated Arabidopsis (GASA) gene family is highly specific to plants and plays crucial roles in plant growth and development. CcGASA4 is a member of the GASA gene family in citrus plants; however, the current understanding of its function in citrus is limited. We used CcGASA4-overexpression transgenic citrus (OEGA) and control (CON) plants to study the role of CcGASA4 in Shatian pomelo. The RNA sequencing (RNA-seq) analysis showed that 3,522 genes, including 1,578 upregulated and 1,944 downregulated genes, were significantly differentially expressed in the CON versus OEGA groups. The Gene Ontology enrichment analysis showed that 178 of the differentially-expressed genes (DEGs) were associated with flowers. A Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEGs were enriched in 134 pathways, including "plant-pathogen interaction", "MAPK signaling pathway-plant", "phenylpropane biosynthesis", "plant hormone signal transduction", "phenylalanine, tyrosine and tryptophan biosynthesis", and "flavonoid and flavonol biosynthesis". The most significantly-enriched pathway was "plant-pathogen interaction", in which 203 DEGs were enriched (126 DEGs were upregulated and 78 were downregulated). The metabolome analysis showed that 644 metabolites were detected in the OEGA and CON samples, including 294 differentially-accumulated metabolites (DAMs; 83 upregulated versus 211 downregulated in OEGA compared to CON). The metabolic pathway analysis showed that these DAMs were mainly involved in the metabolic pathways of secondary metabolites, such as phenylpropanoids, phenylalanine, flavone, and flavonol biosynthesis. Thirteen flavonoids and isoflavones were identified as DAMs in OEGA and CON. We also discovered 25 OEGA-specific accumulated metabolites and found 10 that were associated with disease resistance. CcGASA4 may therefore play a functional role in activating the expression of MAPK signaling transduction pathway and disease resistance genes, inhibiting the expression of auxin- and ethylene-related genes, and activating or inhibiting the expression of brassinosteroid biosynthesis- and abscisic acid-related genes. CcGASA4 may also play a role in regulating the composition and abundance of flavonoids, isoflavones, amino acids, purines, and phenolic compounds. This study provides new insights into the molecular mechanisms of action of CcGASA4 in citrus plants.PMID:36407630 | PMC:PMC9671072 | DOI:10.3389/fpls.2022.1022961

Front Plant Sci. 2022 Nov 3;13:1055779. doi: 10.3389/fpls.2022.1055779. eCollection 2022.ABSTRACTFlesh color is an important target trait in peach [Prunus persica (L.) Batsch] breeding. In this study, two white-fleshed peach cultivars were crossed [Changsong Whitepeach (WP-1) × 'Xiacui'], and their hybrid F1 generation showed color segregation of white flesh (BF1) and yellow flesh (HF1). Metabolome analysis revealed that the flesh color segregation in the hybrid F1 generation was related to the carotenoid content. The decrease in β-carotene and β-cryptoxanthin in BF1 flesh and increase in β-cryptoxanthin oleate, rubixanthin caprate, rubixanthin laurate and zeaxanthin dipalmitate in HF1 flesh contributed to their difference in carotenoid accumulation. Transcriptome analysis demonstrated that compared with BF1, HF1 showed significant up-regulation and down-regulation of ZEP and CCD8 at the core-hardening stage, respectively, while significant down-regulation of NCED in the whole fruit development stage. The down-regulation of NCED might inhibit the breakdown of the violaxanthin and its upstream substances and further promote the accumulation of carotenoids, resulting in yellow flesh. Therefore, NCED may be a key gene controlling the fruit color traits of peach. In this study, targeted metabolomics and transcriptomics were used to jointly explore the mechanism controlling the fruit color of peach, which may help to identify the key genes for the differences in carotenoid accumulation and provide a reference for the breeding of yellow-fleshed peach.PMID:36407629 | PMC:PMC9669654 | DOI:10.3389/fpls.2022.1055779

Front Plant Sci. 2022 Nov 3;13:1024239. doi: 10.3389/fpls.2022.1024239. eCollection 2022.ABSTRACTPholidota chinensis Lindl. is an epiphytic or lithophytic perennial herb of Orchidaceae family used as a garden flower or medicinal plant to treat high blood pressure, dizziness and headache in traditional Chinese medicine. Gastrodin (GAS) is considered as a main bioactive ingredient of this herb but the biosynthetic pathway remains unclear in P. chinensis. To elucidate the GAS biosynthesis and identify the related genes in P. chinensis, a comprehensive analysis of transcriptome and metabolome of roots, rhizomes, pseudobulbs and leaves were performed by using PacBio SMART, Illumina Hiseq and Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). A total of 1,156 metabolites were identified by UPLC-MS/MS, of which 345 differential metabolites were mainly enriched in phenylpropanoid/phenylalanine, flavone and flavonol biosynthesis. The pseudobulbs make up nearly half of the fresh weight of the whole plant, and the GAS content in the pseudobulbs was also the highest in four tissues. Up to 23,105 Unigenes were obtained and 22,029 transcripts were annotated in the transcriptome analysis. Compared to roots, 7,787, 8,376 and 9,146 differentially expressed genes (DEGs) were identified in rhizomes, pseudobulbs and leaves, respectively. And in total, 80 Unigenes encoding eight key enzymes for GAS biosynthesis, were identified. Particularly, glycosyltransferase, the key enzyme of the last step in the GAS biosynthetic pathway had 39 Unigenes candidates, of which, transcript28360/f2p0/1592, was putatively identified as the most likely candidate based on analysis of co-expression, phylogenetic analysis, and homologous searching. The metabolomics and transcriptomics of pseudobulbs versus roots showed that 8,376 DEGs and 345 DEMs had a substantial association based on the Pearson's correlation. This study notably enriched the metabolomic and transcriptomic data of P. chinensis, and it provides valuable information for GAS biosynthesis in the plant.PMID:36407583 | PMC:PMC9673822 | DOI:10.3389/fpls.2022.1024239

Front Nutr. 2022 Nov 3;9:1019205. doi: 10.3389/fnut.2022.1019205. eCollection 2022.ABSTRACTMiao Sour Soup (MSS) is a fermented product from the Qiandongnan region of Guizhou Province, which enrich many beneficial ingredients and is widely consumed in the whole China. Fermented food is beneficial to physical health with the potential positive regulating affection on simple obesity. In this study, we analyzed the mechanism of action of MSS to prevent simple obesity induced by high-fat diet by proteomics and metabolomics. Quantitative proteomics with tandem mass tagging labeling and liquid chromatography-mass spectrometry was used to analyze the changes of liver proteins and metabolites after the MSS intervention. MSS intervention upregulated 33 proteins and 9 metabolites and downregulated 19 proteins and 10 metabolites. Bioinformatics analysis showed that MSS could prevent simple obesity by acting on the PPAR signaling pathway, retinol metabolism, fatty acid β-oxidation, fatty acid degradation, fatty acid biosynthesis, glycine, serine and threonine metabolism, pyruvate metabolism, citrate cycle (TCA cycle) and other signaling pathways. This study provides new insights into the use of MSS to prevent simple obesity caused by high-fat diets and the search for healthy eating patterns with MSS.PMID:36407552 | PMC:PMC9671556 | DOI:10.3389/fnut.2022.1019205

Front Nutr. 2022 Nov 4;9:988653. doi: 10.3389/fnut.2022.988653. eCollection 2022.NO ABSTRACTPMID:36407539 | PMC:PMC9672814 | DOI:10.3389/fnut.2022.988653

Front Nutr. 2022 Nov 3;9:1051964. doi: 10.3389/fnut.2022.1051964. eCollection 2022.ABSTRACTIn the protein nutrition strategy of middle-aged and elderly people, some believe that low protein is good for health, while others believe high protein is good for health. Facing the contradictory situation, the following hypothesis is proposed. There is a process of change from lower to higher ratio of protein nutritional requirements that are good for health in the human body after about 50 years of age, and the age at which the switch occurs is around 65 years of age. Hence, in this study, 50, 25-month-old male rats were randomly divided into five groups: Control (basal diet), LP (low-protein diet with a 30% decrease in protein content compared to the basal diet), HP (high-protein diet with a 30% increase in protein content compared to the basal diet), Model 1 (switched from LP to HP feed at week 4), and Model 2 (switched from LP to HP feed at week 7). After a total of 10 weeks intervention, the liver and serum samples were examined for aging-related indicators, and a newly comprehensive quantitative score was generated using principal component analysis (PCA). The effects of the five protein nutritional modalities were quantified in descending order: Model 1 > HP > LP > Control > Model 2. Furthermore, the differential metabolites in serum and feces were determined by orthogonal partial least squares discriminant analysis, and 15 differential metabolites, significantly associated with protein intake, were identified by Spearman's correlation analysis (p < 0.05). Among the fecal metabolites, 10 were positively correlated and 3 were negatively correlated. In the serum, tyrosine and lactate levels were positively correlated, and acetate levels were negatively correlated. MetaboAnalyst analysis identified that the metabolic pathways influenced by protein intake were mainly related to amino acid and carbohydrate metabolism. The results of metabolomic analysis elucidate the mechanisms underlying the preceding effects to some degree. These efforts not only contribute to a unified protein nutrition strategy but also positively impact the building of a wiser approach to protein nutrition, thereby helping middle-aged and older populations achieve healthy aging.PMID:36407526 | PMC:PMC9673908 | DOI:10.3389/fnut.2022.1051964

Front Cell Dev Biol. 2022 Nov 3;10:977960. doi: 10.3389/fcell.2022.977960. eCollection 2022.ABSTRACTPurpose: Accumulating evidence suggests that solute carrier family 39 member 1 (SLC39A1) conceivably function as a tumor suppressor, but the underlying mechanism in renal cell carcinoma (RCC) is poorly understood. Methods: OSRC-2 renal cancer cells were first transfected with SLC39A1 overexpressed vectors and empty vectors and then used in transcriptomics, proteomics, and metabolomics integrated analyses. Results: SLC39A1 significantly altered several metabolisms at transcriptional, protein and metabolic levels, including purine and pyrimidine metabolism, amino acids and derivatives metabolism, lactose metabolism, and free fatty acid metabolism. Additionally, SLC39A1 could promote ferroptosis, and triggered significant crosstalk in PI3K-AKT signal pathway, cAMP signal pathway, and peroxisome proliferators-activated receptor (PPAR) signal pathway. Conclusion: We found SLC39A1 transfection impaired tumor metabolism and perturbed tumor metabolism-related pathways, which was a likely cause of the alteration in cell proliferation, migration, and cell cycle progression in RCC cells. These multi-omics analyses results provided both a macroscopic picture of molecular perturbation by SLC39A1 and novel insights into RCC tumorigenesis and development.PMID:36407113 | PMC:PMC9669761 | DOI:10.3389/fcell.2022.977960

Int J Endocrinol Metab. 2022 Aug 15;20(3):e120812. doi: 10.5812/ijem-120812. eCollection 2022 Jul.ABSTRACTBACKGROUND: Due to the worldwide spread of COVID-19, various countries have designed scientific studies on different aspects of the disease. Patients with diabetes mellitus (DM) have been proven to be at higher risk of COVID-19-related complications, hospitalization, and death.OBJECTIVES: The aim was to conduct a scientometric analysis of scholarly outputs on diabetes and COVID-19.METHODS: Web of Science was searched for scientific publications on diabetes and COVID-19 by Middle Eastern researchers until September 14, 2021. Collected data were analyzed for document type, subject area, countries, top journals, citation number, and authors' collaboration network using VOS viewer 1.6.15 and bibliometrix R-package 4.1.1.RESULTS: Overall, the characteristics of 603 documents on DM and COVID-19 were analyzed. The top three productive countries in the field were Iran, Turkey, and Saudi Arabia. The top affiliation was from Iran; "Tehran University of Medical Sciences" (n = 168), followed by "Shahid Beheshti University of Medical Sciences" (n = 82). The total citation number was 3704 times. The highest cited paper (348) was a systematic review from Iran, published in arch Acad Emerg Med. The top source was "Diabetes & Metabolic Syndrome: Clinical Research & Reviews," with 26 documents.CONCLUSIONS: The current study provides an overview of the quantity and quality of published scholarly documents on the intersection of DM and COVID-19 in the region. Our findings help scientists find the existing gaps, manage the research budgets, identify active authors and scientific institutes to collaborate with, and use their experience to produce new knowledge in the future.PMID:36407029 | PMC:PMC9661537 | DOI:10.5812/ijem-120812

Front Microbiol. 2022 Nov 3;13:1035167. doi: 10.3389/fmicb.2022.1035167. eCollection 2022.ABSTRACTPlant growth-promoting rhizobacteria (PGPR) are well-acknowledged root endophytic bacteria used for plant growth promotion. However, which metabolites produced by PGPR could promote plant growth remains unclear. Additionally, which genes are responsible for plant growth-promoting traits is also not elucidated. Thus, as comprehensive understanding of the mechanism of endophyte in growth promotion is limited, this study aimed to determine the metabolites and genes involved in plant growth-promotion. We isolated an endophytic Rhizobium sp. WYJ-E13 strain from the roots of Curcuma wenyujin Y.H. Chen et C. Ling, a perennial herb and medicinal plant. The tissue culture experiment showed its plant growth-promoting ability. The bacterium colonization in the root was confirmed by scanning electron microscopy and paraffin sectioning. Furthermore, it was noted that the WYJ-E13 strain produced cytokinin, anthranilic acid, and L-phenylalanine by metabolome analysis. Whole-genome analysis of the strain showed that it consists of a circular chromosome of 4,350,227 bp with an overall GC content of 60.34%, of a 2,149,667 bp plasmid1 with 59.86% GC, and of a 406,180 bp plasmid2 with 58.05% GC. Genome annotation identified 4,349 putative protein-coding genes, 51 tRNAs, and 9 rRNAs. The CDSs number allocated to the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Clusters of Orthologous Genes databases were 2027, 3,175 and 3,849, respectively. Comparative genome analysis displayed that Rhizobium sp. WYJ-E13 possesses the collinear region among three species: Rhizobium acidisoli FH23, Rhizobium gallicum R602 and Rhizobium phaseoli R650. We recognized a total set of genes that are possibly related to plant growth promotion, including genes involved in nitrogen metabolism (nifU, gltA, gltB, gltD, glnA, glnD), hormone production (trp ABCDEFS), sulfur metabolism (cysD, cysE, cysK, cysN), phosphate metabolism (pstA, pstC, phoB, phoH, phoU), and root colonization. Collectively, these findings revealed the roles of WYJ-E13 strain in plant growth-promotion. To the best of our knowledge, this was the first study using whole-genome sequencing for Rhizobium sp. WYJ-E13 associated with C. wenyujin. WYJ-E13 strain has a high potential to be used as Curcuma biofertilizer for sustainable agriculture.PMID:36406393 | PMC:PMC9671153 | DOI:10.3389/fmicb.2022.1035167

Front Mol Biosci. 2022 Nov 3;9:1049016. doi: 10.3389/fmolb.2022.1049016. eCollection 2022.ABSTRACTMetabolomics is a fast-developing technique used in biomedical researches focusing on pathological mechanism illustration or novel biomarker development for diseases. The ability of simultaneously quantifying thousands of metabolites in samples makes metabolomics a promising technique in predictive or personalized medicine-oriented researches and applications. Liquid chromatography-mass spectrometry is the most widely employed analytical strategy for metabolomics. In this current mini-review, we provide a brief update on the recent developments and novel applications of LC-MS based metabolomics in the predictive and personalized medicine sector, such as early diagnosis, molecular phenotyping or prognostic evaluation. COVID-19 related metabolomic studies are also summarized. We also discuss the prospects of metabolomics in precision medicine-oriented researches, as well as critical issues that need to be addressed when employing metabolomic strategy in clinical applications.PMID:36406271 | PMC:PMC9669074 | DOI:10.3389/fmolb.2022.1049016

Front Genet. 2022 Nov 3;13:959170. doi: 10.3389/fgene.2022.959170. eCollection 2022.ABSTRACTPurpose: Increasing evidence has elucidated the significance of lipid metabolism in predicting therapeutic efficacy. Obviously, a systematic analysis of lipid metabolism characterizations of gastric cancer (GC) needs to be reported. Experimental design: Based on two proposed computational algorithms (TCGA-STAD and GSE84437), the lipid metabolism characterization of 367 GC patients and its systematic relationship with genomic characteristics, clinicopathologic features, and clinical outcomes of GC were analyzed in our study. Differentially expressed genes (DEGs) were identified based on the lipid metabolism cluster. At the same time, we applied single-factor Cox regression and random forest to screen signature genes to construct a prognostic model, namely, the lipid metabolism score (LMscore). Next, we deeply explored the predictive value of the LMscore for GC. To verify the specific changes in lipid metabolism, a total of 90 serum, 30 tumor, and non-tumor adjacent tissues from GC patients, were included for pseudotargeted metabolomics analysis via SCIEX triple quad 5500 LC-MS/MS system. Results: Five lipid metabolism signature genes were identified from a total of 3,104 DEGs. The LMscore could be a prognosticator for survival in different clinicopathological GC cohorts. As well, the LMscore was identified as a predictive biomarker for responses to immunotherapy and chemotherapeutic drugs. Additionally, significant changes in sphingolipid metabolism and sphingolipid molecules were discovered in cancer tissue from GC patients by pseudotargeted metabolomics. Conclusion: In conclusion, multivariate analysis revealed that the LMscore was an independent prognostic biomarker of patient survival and therapeutic responses in GC. Depicting a comprehensive landscape of the characteristics of lipid metabolism may help to provide insights into the pathogenesis of GC, interpret the responses of gastric tumors to therapies, and achieve a better outcome in the treatment of GC. In addition, significant alterations of sphingolipid metabolism and increased levels of sphingolipids, in particular, sphingosine (d16:1) and ceramide, were discovered in GC tissue by lipidome pseudotargeted metabolomics, and most of the sphingolipid molecules have the potential to be diagnostic biomarkers for GC.PMID:36406121 | PMC:PMC9669965 | DOI:10.3389/fgene.2022.959170

Front Genet. 2022 Nov 2;13:1042772. doi: 10.3389/fgene.2022.1042772. eCollection 2022.ABSTRACTGene family expansion plays a central role in adaptive divergence and, ultimately, speciation is influenced by phenotypic diversity in different environments. Barley (Hordeum vulgare) is the fourth most important cereal crop in the world and is used for brewing purposes, animal feed, and human food. Systematic characterization of expanded gene families is instrumental in the research of the evolutionary history of barley and understanding of the molecular function of their gene products. A total of 31,750 conserved orthologous groups (OGs) were identified using eight genomes/subgenomes, of which 1,113 and 6,739 were rapidly expanded and contracted OGs in barley, respectively. Five expanded OGs containing 20 barley dirigent genes (HvDIRs) were identified. HvDIRs from the same OG were phylogenetically clustered with similar gene structure and domain organization. In particular, 7 and 5 HvDIRs from OG0000960 and OG0001516, respectively, contributed greatly to the expansion of the DIR-c subfamily. Tandem duplication was the driving force for the expansion of the barley DIR gene family. Nucleotide diversity and haplotype network analysis revealed that the expanded HvDIRs experienced severe bottleneck events during barley domestication, and can thus be considered as potential domestication-related candidate genes. The expression profile and co-expression network analysis revealed the critical roles of the expanded HvDIRs in various biological processes, especially in stress responses. HvDIR18, HvDIR19, and HvDIR63 could serve as excellent candidates for further functional genomics studies to improve the production of barley products. Our study revealed that the HvDIR family was significantly expanded in barley and might be involved in different developmental processes and stress responses. Thus, besides providing a framework for future functional genomics and metabolomics studies, this study also identified HvDIRs as candidates for use in improving barley crop resistance to biotic and abiotic stresses.PMID:36406120 | PMC:PMC9667096 | DOI:10.3389/fgene.2022.1042772

Front Immunol. 2022 Nov 2;13:950441. doi: 10.3389/fimmu.2022.950441. eCollection 2022.ABSTRACTOBJECTIVE: The occurrence of cardiovascular adverse events in the first year after ST-acute myocardial infarction (STEMI) remains high; therefore, identification of patients with poor prognosis is essential for early intervention. This study aimed to evaluate the prognostic value of metabolomics-based biomarkers in STEMI patients and explore their functional mechanisms.METHODS: Metabolite profiling was performed using nuclear magnetic resonance. The plasma concentration of Kynurenine (Kyn) was measured using ultraperformance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry. Major adverse cardiac and cerebral events were assessed for 1 year. A functional metabolomics strategy was proposed for investigating the role of Kyn in both vitro and vivo models.RESULTS: The adjusted hazard ratios in STEMI patients for Kyn in the 4th quartile 7.12(5.71-10.82) was significantly higher than that in the 3rd quartile 3.03(2.62-3.74), 2nd quartile 1.86(1.70-2.03), and 1st quartile 1.20(0.93-1.39).The incidence of MACCE was significantly different among Kyn quartiles and the highest incidence of MACCE was observed in the 4th quartile when compared with the 1st quartile (9.84% vs.2.85%, P<0.001).Immunofluorescence staining indicated that indoleamine-pyrrole 2,3-dioxygenase (IDO1) was located in the CD68 positive staining area of thrombi from STEMI patients and Kyn was induced in the early phase after myocardial infarction. Kyn could trigger inflammation and oxidative stress of macrophage cells by activation of the Sirt3-acSOD2/IL-1β signaling pathway in vitro.CONCLUSIONS: Plasma Kyn levels were positively associated with the occurrence of STEMI. Kyn could induce macrophage cells inflammation and oxidative stress by activating the Sirt3-acSOD2/IL-1β pathway following myocardial ischemia injury. Kyn could be a robust biomarker for STEMI prognosis and reduction of Kyn could be beneficial in STEMI patients.PMID:36405744 | PMC:PMC9667794 | DOI:10.3389/fimmu.2022.950441

Chin Herb Med. 2022 Sep 15;14(4):583-591. doi: 10.1016/j.chmed.2022.01.007. eCollection 2022 Oct.ABSTRACTOBJECTIVE: To elucidate the anti-inflammatory mechanism of Reduning Injection (RDN) by analyzing the potential biomarkers and metabolic pathways of the carrageenan-induced inflammatory model from the overall metabolic level.METHODS: Rat inflammatory model was established by carrageenan. UPLC-Q-TOF/MS was used to detect and analyze changes of endogenous metabolites in the serum and urine of carrageenan-induced inflammatory rats. Combined with multivariate analysis and databases analysis, inflammatory-related potential biomarkers were screened and identified to analyze possible metabolic pathways. The reliability and biological significance of these biomarkers was verified by metabolic network analysis and correlation analysis with pharmacodynamic indicators.RESULTS: A total of 16 potential biomarkers were screened and identified by multivariate analysis and metabolite databases, among which 13 species could be adjusted by RDN. The metabolism pathway analysis revealed that histidine metabolism, sphingolipid metabolism, and tyrosine metabolism were greatly disturbed. Their biomarkers involved urocanic acid, sphingosine, and norepinephrine, all of which showed a callback trend after RDN treatment. The three biomarkers had a certain correlation with some known inflammatory-related small molecules (histamine, arachidonic acid, Leukotriene B4, and PGE2) and pharmacodynamic indicators (IL-6, IL-1β, PGE2 and TNF-α), which indicated that the selected biomarkers had certain reliability and biological significance.CONCLUSION: RDN has a good regulation of the metabolic disorder of endogenous components in carrageenan-induced inflammatory rats. And its anti-inflammatory mechanism is mainly related to the regulation of amino acid and lipid metabolism. This research method is conducive to the interpretation of the overall pharmacological mechanism of Chinese medicine.PMID:36405065 | PMC:PMC9669350 | DOI:10.1016/j.chmed.2022.01.007

Chin Herb Med. 2022 Aug 23;14(4):602-611. doi: 10.1016/j.chmed.2022.07.002. eCollection 2022 Oct.ABSTRACTOBJECTIVE: To establish a metabonomics research technique based on the combination of 1H-NMR and multivariate statistical analysis, so as to explore the metabolic regulation mechanism of Aconiti Radix Cocta extract (ARCE) in rat tissues and serum.METHODS: SD rats were randomly divided into blank group, female group and male group. The 1H-NMR technique was used to collect the information of rat tissues and serum samples in each group. The principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and other methods were used for data pattern recognition, so as to screen out potential differential metabolites and metabolic pathways, and then network analysis and KEGG database were used to analyze the relationship between metabolites, metabolic pathways and diseases.RESULTS: The external features and 1H-NMR analysis showed that the sex of rats had no obvious effect on the drug action. A total of 15 potential differential metabolites and six metabolic pathways were screened out through data pattern recognition. Through network analysis and KEGG pathway analysis, three target diseases closely related to differential metabolites were found, and the metabolic pathway related to lung cancer was the central carbon metabolism of cancer.CONCLUSION: This study shows that Aconiti Radix Cocta (ARC) may regulate the energy metabolism of the body by influencing arginine synthesis, so as to play the roles of anti-inflammation, analgesia, anti-tumor and immune regulation.PMID:36405052 | PMC:PMC9669353 | DOI:10.1016/j.chmed.2022.07.002

iScience. 2022 Nov 3;25(12):105484. doi: 10.1016/j.isci.2022.105484. eCollection 2022 Dec 22.ABSTRACTCadmium (Cd) pollution in soil has become a major environmental issue worldwide. However, the underlying molecular mechanism of low grain-Cd accumulation (GCA) in maize is still largely unknown. Herein, we report the mechanistic basis for low GCA in maize by a multiomics approach. The low GCA genotype L63 showed normal vacuolar formation and a lower capacity of xylem loading of Cd than the high-accumulator L42 under Cd stress. Transcriptomic sequencing identified 84 low-GCA-associated genes which are mainly involved in the S-adenosylmethionine (SAM) cycle, metal transport, and vacuolar sequestration. A metabolome analysis revealed that L63 plants had a more active SAM cycle and a greater capacity for terpenoid synthesis and phenylalanine metabolism than L42. Combining the analysis of transcriptome and metabolome characterized several genes as key genes involved in the determination of Cd accumulation. Our study identifies a mechanistic basis for low Cd accumulation in maize grains and provides candidate genes for genetic improvement of crops.PMID:36404928 | PMC:PMC9672352 | DOI:10.1016/j.isci.2022.105484

J Diabetes Metab Disord. 2022 Jul 6;21(2):2017-2021. doi: 10.1007/s40200-021-00932-x. eCollection 2022 Dec.ABSTRACTBACKGROUND: A considerable amount of research funding goes to diabetes management strategies to improve therapeutic goals and reduce the burden of diabetes. A vast amount of the budget is wasted due to unnecessary studies. A scoping review is a pivotal study to overview the available evidence and avoid research waste. In this review, we will try to find out the scope of available studies on diabetes management interventions, identify associated research gaps, and prioritize future studies.METHOD: We will carry out a study using Arksey and O'Malley's scoping review framework. We will search the Scopus and PubMed databases from 01/01/2015 till 01/01/2020. Only original articles related to pharmacological and non-pharmacological management interventions will be included. These interventional studies should be conducted on the Iranian population. After data extraction, a descriptive data analysis will be used to present information in different charts or tables. We will evaluate related published articles based on their document type, level of evidence, type of diabetes, subject area, interventions types, main findings and outcomes.DISCUSSION: This study represents the first attempt to sum up available studies related to diabetes management interventions performed in Iran. The results of this study will be useful for all the stakeholders and policy-makers involved in diabetes research. It can help clinicians to be informed about studies on management interventions and can guide scientists eager to diabetes research to choose their future research plans based on diabetes research requirements and gaps.PMID:36404829 | PMC:PMC9672267 | DOI:10.1007/s40200-021-00932-x

J Diabetes Metab Disord. 2022 Oct 24;21(2):1975-1989. doi: 10.1007/s40200-022-01139-4. eCollection 2022 Dec.ABSTRACTBACKGROUND: Single nucleotide polymorphisms have been implicated in various diseases, most notably non-communicable diseases (NCDs). The aim of this study was to review available evidence regarding associations between FTO polymorphisms and NCDs in the Iranian population.METHODS: A comprehensive search was conducted through PubMed/Medline and Scopus databases up to December 2021, as well as reference lists of pertinent articles and key journals. All observational studies that examined the association between FTO gene polymorphisms and NCDs in the Iranian population were included. There was no limitation on the publication year. The Newcastle-Ottawa Scale (NOS) was used to assess the study's quality.RESULTS: The initial search yielded 95 studies, of which 30 studies were included in the current systematic review. The underlying disorders were obesity, type 2 diabetes, breast and colorectal cancers, depression, and metabolic syndrome. These studies found an association between FTO gene polymorphisms and obesity in the Iranian population, but the relationship with other NCDs was debatable. Even though, other diseases such as diabetes and metabolic syndrome, which are closely related to obesity, may also be associated with FTO gene polymorphisms.CONCLUSION: FTO gene polymorphism appears to play a role in the occurrence of NCDs. Some of the study results may be misleading due to ethnic differences and the effect of other genetic factors on disease onset, which needs to be investigated further. Finally, FTO gene polymorphisms can be studied as a preventive or therapeutic target.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-022-01139-4.PMID:36404828 | PMC:PMC9672241 | DOI:10.1007/s40200-022-01139-4

Digestion. 2022 Nov 18:1-12. doi: 10.1159/000526864. Online ahead of print.ABSTRACTINTRODUCTION: As the high mortality rate of gastric cancer (GC) is due to delayed diagnosis, early detection is vital for improved patient outcomes. Metabolic deregulation plays an important role in GC. Although various metabolite-level biomarkers for early detection have been assessed, there is still no unified early detection method. We conducted a plasma metabolome study to assess metabolites that may distinguish GC samples from non-GC samples.METHODS: Blood samples were collected from 72 GC patients and 29 control participants (non-GC group) at the Tokyo Medical University Hospital between March 2020 and November 2020. Hydrophilic metabolites were identified and quantified using liquid chromatography-time-of-flight mass spectrometry. Differences in metabolite concentrations between the GC and non-GC groups were evaluated using the Mann-Whitney test. The discrimination ability of each metabolite was evaluated by the area under the receiver operating characteristic curve. A radial basis function (RBF) kernel-based support vector machine (SVM) model was developed to assess the discrimination ability of multiple metabolites. The selection of variables used for the SVM utilized a step-wise regression method.RESULTS: Of the 96 quantified metabolites, 8 were significantly different between the GC and non-GC groups. Of these, N1-acetylspermine, succinate, and histidine were used in the RBF-SVM model to discriminate GC samples from non-GC samples. The area under the curve (AUC) of the RBF-SVM model was higher (0.915; 95% CI: 0.865-0.965, p < 0.0001), indicating good performance of the RBF-SVM model. The application of this RBF-SVM to the validation dataset resulted from the AUC of the RBF-SVM model was (0.885; 95% CI: 0.797-0.973, p < 0.0001), indicating the good performance of the RBF-SVM model. The sensitivity of the RBF-SVM model was better (69.0%) than those of the common tumor markers carcinoembryonic antigen (CEA) (10.5%) and carbohydrate antigen 19-9 (CA19-9) (2.86%). The RBF-SVM showed a low correlation with CEA and CA19-9, indicating its independence.CONCLUSION: We analyzed plasma metabolomics, and a combination of the quantified metabolites showed high sensitivity for the detection of GC. The independence of the RBF-SVM from tumor markers suggested that their complementary use would be helpful for GC screening.PMID:36404717 | DOI:10.1159/000526864

Sci Rep. 2022 Nov 20;12(1):19977. doi: 10.1038/s41598-022-24170-0.ABSTRACTMetabolomic analysis of blood plasma samples from COVID-19 patients is a promising approach allowing for the evaluation of disease progression. We performed the metabolomic analysis of plasma samples of 30 COVID-19 patients and the 19 controls using the high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometric detection (LC-MS/MS). In our analysis, we identified 103 metabolites enriched in KEGG metabolic pathways such as amino acid metabolism and the biosynthesis of aminoacyl-tRNAs, which differed significantly between the COVID-19 patients and the controls. Using ANDSystem software, we performed the reconstruction of gene networks describing the potential genetic regulation of metabolic pathways perturbed in COVID-19 patients by SARS-CoV-2 proteins. The nonstructural proteins of SARS-CoV-2 (orf8 and nsp5) and structural protein E were involved in the greater number of regulatory pathways. The reconstructed gene networks suggest the hypotheses on the molecular mechanisms of virus-host interactions in COVID-19 pathology and provide a basis for the further experimental and computer studies of the regulation of metabolic pathways by SARS-CoV-2 proteins. Our metabolomic analysis suggests the need for nonstructural protein-based vaccines and the control strategy to reduce the disease progression of COVID-19.PMID:36404352 | DOI:10.1038/s41598-022-24170-0