PubMed

J Agric Food Chem. 2023 May 8. doi: 10.1021/acs.jafc.2c08372. Online ahead of print.ABSTRACTIn China, the endemic species Garcinia yunnanensis and native Garcinia xanthochymus are known as edible and medicinal plants. However, a systematic metabolomic and bioactivity evaluation of different plant parts from both species is lacking. In this study, comprehensive investigations of 11 plant parts of G. yunnanensis and 10 of G. xanthochymus employing UPLC-ESI-QTOF-MSE-based metabolomic analysis in conjunction with three bioactivity assays were undertaken. A customized chemotaxonomic-based in-house library containing 6456 compounds was constructed and coupled to the Progenesis QI informatic platform for metabolite annotations. From these two species, a total of 235 constituents were characterized using multiple criteria. Differences in metabolite profiles between the plant parts within each species were uncovered using multivariate analysis. Based on orthogonal partial least-squares discriminant analysis (OPLS-DA), 23 markers were identified as highly differential metabolites from G. xanthochymus and 20 from G. yunnanensis. Comparative assessment of the biological assays revealed the activity variations among different plant parts. The seeds of both species and G. yunnanensis latex exhibited excellent cytotoxic and antibacterial activities, while G. xanthochymus roots and G. yunnanensis arils showed strong anti-inflammatory effects. S-plot analysis identified 26 potential biomarkers for the observed activities, including the known cytotoxic agent cycloxanthochymol and the anti-inflammatory compound garcimultiflorone B, which likely explains some of the potent observed bioactivity.PMID:37154236 | DOI:10.1021/acs.jafc.2c08372

Theranostics. 2023 Apr 1;13(7):2088-2113. doi: 10.7150/thno.81488. eCollection 2023.ABSTRACTTuberculosis is an airborne disease caused by Mycobacterium tuberculosis (Mtb) and can manifest both pulmonary and extrapulmonary disease, including ocular tuberculosis (OTB). Accurate diagnosis and swift optimal treatment initiation for OTB is faced by many challenges combined with the lack of standardized treatment regimens this results in uncertain OTB outcomes. The purpose of this study is to summarize existing diagnostic approaches and recently discovered biomarkers that may contribute to establishing OTB diagnosis, choice of anti-tubercular therapy (ATT) regimen, and treatment monitoring. The keywords ocular tuberculosis, tuberculosis, Mycobacterium, biomarkers, molecular diagnosis, multi-omics, proteomics, genomics, transcriptomics, metabolomics, T-lymphocytes profiling were searched on PubMed and MEDLINE databases. Articles and books published with at least one of the keywords were included and screened for relevance. There was no time limit for study inclusion. More emphasis was placed on recent publications that contributed new information about the pathogenesis, diagnosis, or treatment of OTB. We excluded abstracts and articles that were not written in the English language. References cited within the identified articles were used to further supplement the search. We found 10 studies evaluating the sensitivity and specificity of interferon-gamma release assay (IGRA), and 6 studies evaluating that of tuberculin skin test (TST) in OTB patients. IGRA (Sp = 71-100%, Se = 36-100%) achieves overall better sensitivity and specificity than TST (Sp = 51.1-85.7%; Se = 70.9-98.5%). For nuclear acid amplification tests (NAAT), we found 7 studies on uniplex polymerase chain reaction (PCR) with different Mtb targets, 7 studies on DNA-based multiplex PCR, 1 study on mRNA-based multiplex PCR, 4 studies on loop-mediated isothermal amplification (LAMP) assay with different Mtb targets, 3 studies on GeneXpert assay, 1 study on GeneXpert Ultra assay and 1 study for MTBDRplus assay for OTB. Specificity is overall improved but sensitivity is highly variable for NAATs (excluding uniplex PCR, Sp = 50-100%; Se = 10.5-98%) as compared to IGRA. We also found 3 transcriptomic studies, 6 proteomic studies, 2 studies on stimulation assays, 1 study on intraocular protein analysis and 1 study on T-lymphocyte profiling in OTB patients. All except 1 study evaluated novel, previously undiscovered biomarkers. Only 1 study has been externally validated by a large independent cohort. Future theranostic marker discovery by a multi-omics approach is essential to deepen pathophysiological understanding of OTB. Combined these might result in swift, optimal and personalized treatment regimens to modulate the heterogeneous mechanisms of OTB. Eventually, these studies could improve the current cumbersome diagnosis and management of OTB.PMID:37153734 | PMC:PMC10157737 | DOI:10.7150/thno.81488

Front Neurol. 2023 Apr 20;14:1036453. doi: 10.3389/fneur.2023.1036453. eCollection 2023.ABSTRACTBACKGROUND: Qihuang needle therapy is a newly developed acupuncture therapy to treat tic disorders in clinical practice. However, the mechanism to reduce tic severity remains unknown. Changes in intestinal flora and circulation metabolites are perhaps the potential pathogenesis of tic disorders. As a result, we present a protocol for a controlled clinical trial using multi-omics analysis to probe the mechanism of the Qihuang needle in managing tic disorders.METHODS: This is a matched-pairs design, controlled, clinical trial for patients with tic disorders. Participants will be allocated to either an experimental group or a healthy control group. The main acupoints are Baihui (GV20), Yintang (EX-HN3), and Jueyinshu (BL14). The experimental group will receive Qihuang needle therapy for a month, while the control group will receive no interventions.EXPECTED OUTCOMES: The change in the severity of the tic disorder is set as the main outcome. Secondary outcomes include gastrointestinal severity index and recurrence rate, which will be calculated after a 12-week follow-up. Gut microbiota, measured by 16S rRNA gene sequencing; serum metabolomics, assessed via LC/MS; and serum zonulin, assessed by enzyme-linked immunosorbent assay (ELISA), will be used as biological specimen analysis outcomes. The present study will investigate the possible interactions between intestinal flora and serum metabolites and the improvement of clinical profiles, which may elucidate the mechanism of Qihuang needle therapy for tic disorders.TRIAL REGISTRATION: This trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/). Registration number: ChiCTR2200057723, Date: 2022-04-14.PMID:37153669 | PMC:PMC10157291 | DOI:10.3389/fneur.2023.1036453

Therap Adv Gastroenterol. 2023 May 2;16:17562848231168199. doi: 10.1177/17562848231168199. eCollection 2023.ABSTRACTBACKGROUND: Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported.OBJECTIVE: Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment.DESIGN: Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients (n = 116).METHODS: Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model.RESULTS: Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers.CONCLUSION: Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment.PMID:37153496 | PMC:PMC10161336 | DOI:10.1177/17562848231168199

Front Med (Lausanne). 2023 Apr 20;10:1153360. doi: 10.3389/fmed.2023.1153360. eCollection 2023.ABSTRACTBACKGROUND: ErXian decoction is a Chinese herbal compound that can prevent and control the course of osteoarthritis (OA) and osteoporosis (OP). OP and OA are two age-related diseases that often coexist in elderly individuals, and both are associated with dysregulation of the gut microbiome. In the initial study, Palmatine (PAL) was obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and network pharmacological screening techniques, followed by 16S rRNA sequencing and serum metabolomics of intestinal contents, to explore the mechanism of PAL in the treatment of OA and OP.METHODS: The rats selected for this study were randomly divided into three groups: a sham group, an OA-OP group and a PAL group. The sham group was intragastrically administered normal saline solution, and the PLA group was treated with PAL for 56 days. Through microcomputed tomography (micro-CT), ELISA, 16S rRNA gene sequencing and non-targeted metabonomics research, we explored the potential mechanism of intestinal microbiota and serum metabolites in PAL treatment of OA-OP rats.RESULTS: Palmatine significantly repair bone microarchitecture of rat femur in OA-OP rats and improved cartilage damage. The analysis of intestinal microflora showed that PAL could also improve the intestinal microflora disorder of OA-OP rats. For example, the abundance of Firmicutes, Bacteroidota, Actinobacteria, Lactobacillus, unclassified_f_Lachnospiraceae, norank_f_Muribaculaceae, Lactobacillaceae, Lachnospiraceae and Muribaculaceae increased after PAL intervention. In addition, the results of metabolomics data analysis showed that PAL also change the metabolic status of OA-OP rats. After PAL intervention, metabolites such as 5-methoxytryptophol, 2-methoxy acetaminophen sulfate, beta-tyrosine, indole-3-carboxylic acid-O-sulfate and cyclodopa glucoside increased. Association analysis of metabolomics and gut microbiota (GM) showed that the communication of multiple flora and different metabolites played an important role in OP and OA.CONCLUSION: Palmatine can improve cartilage degeneration and bone loss in OA-OP rats. The evidence we provided supports the idea that PAL improves OA-OP by altering GM and serum metabolites. In addition, the application of GM and serum metabolomics correlation analysis provides a new strategy for uncovering the mechanism of herbal treatment for bone diseases.PMID:37153081 | PMC:PMC10159182 | DOI:10.3389/fmed.2023.1153360

Front Endocrinol (Lausanne). 2023 Apr 20;14:1084858. doi: 10.3389/fendo.2023.1084858. eCollection 2023.ABSTRACTHypertensive cerebral microbleeds (HCMB) may be the early stage of hypertensive intracerebral hemorrhage (HICH), which is a serious threat to health due to its high mortality and disability rates. The early clinical symptoms of HCMB may not be significant. Moreover, it is difficult to achieve early diagnosis and intervention for targeted prevention of HICH. Although hypertension (HTN) is a predisposition for HCMB, it remains unclear whether there is any difference between hypertensive patients with or without HCMB. Therefore, we carried out liquid chromatography-mass spectrometry (LC-MS) to analyze early biomarkers for HCMB in mice with hypertension and to lay the foundation for early prevention of HICH in hypertensive patients. In total, 18 C57 male mice were randomly divided into the HCMB (n = 6), HTN (n = 6), and control groups (CON, n = 6). Hematoxylin-eosin and diaminobenzidine staining were used to assess the reliability of the model. The metabolite expression level and sample category stability were tested using the displacement test of orthogonal partial least squares discriminant analysis (OPLS-DA). Significant differences in metabolites were screened out using variable importance in the projection (VIP > 1), which were determined using the OPLS-DA model and the P-value of the t-test (P < 0.05) combined with the nonparametric rank-sum test. With an area under the curve (AUC) > 0.85 and a P-value of 0.05, the receiver operating characteristic curve (ROC) was used to further screen the distinct metabolites of HCMB. Compared with the HTN and CON groups, the HCMB group had significantly higher blood pressure and lower average body weight (P < 0.05). Through untargeted LC-MS analysis, 93 distinct metabolites were identified in the HCMB (P < 0.05, VIP > 1) group. Among these potential biomarkers, six significantly decreased and eight significantly increased differential metabolites were found. Meanwhile, we found that the HCMB group had statistically distinct arginine and purine metabolism pathways (P < 0.05), and citrulline may be the most significant possible biomarker of HCMB (AUC > 0.85, P < 0.05). All of these potential biomarkers may serve as early biomarkers for HICH in hypertension.PMID:37152968 | PMC:PMC10159181 | DOI:10.3389/fendo.2023.1084858

Front Endocrinol (Lausanne). 2023 Apr 19;14:1120988. doi: 10.3389/fendo.2023.1120988. eCollection 2023.ABSTRACTINTRODUCTION: Several metabolite classes have been identified in human endometrium, including lipids, nucleotides, amino acids, organic acids, and sugars. The first studies suggest the importance of metabolites in endometrial functions, as imbalance in uterine metabolites has been associated with low implantation rate and endometriosis. Nevertheless, most of studies have put emphasis on specific metabolite classes, and we lack the knowledge of the whole metabolome composition in human uterus. Further, a healthy dietary pattern has been shown to potentially protect against different endometrial dysfunctions and is a potential modulator of metabolomic composition and, consequently, the intrauterine microenvironment. The Mediterranean Diet (MD), characterized by a high intake of fruits, vegetables, cereals, nuts, legumes, fish, and olive oil, and a low consumption of meat, dairy products, and processed foods, has been associated with a wide range of benefits for health. Indeed, the MD pattern has displayed a beneficial role in endometriosis management and fertility; however, the relationship between the MD and the endometrial metabolome is still unknown. In our study, we set out to analyze receptive-phase endometrial metabolome profiles among women with infertility and their associations with MD.METHODS: The study included women with male factor infertility (n=8), unexplained infertility (n=10), recurrent implantation failure (n=14), and endometriosis (n=13). The endometrial metabolome was analyzed with ultrahigh-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS). The MD adherence of the participants was assessed using the 14-point MEDAS questionnaire of adherence to the MD.RESULTS: We provide the whole metabolome profile of the endometrium, where 925 different metabolites were identified. Among these metabolites, lipids comprised the largest part, where polyunsaturated fatty acids (PUFAs) prevailed. Women with endometriosis and recurrent implantation failure were found to have lower levels of PUFAs compared to women with male factor and unexplained infertility (i.e., no clear endometrial alterations), identifying a metabolome profile associated with infertility diagnoses where altered endometrial functions are suspected. Moreover, MD adherence seemed to be associated with the endometrial metabolomic profile in a manner dependent on the health status of the uterus.CONCLUSION: The study findings provide insight into the molecular background of female infertility and lead to identification of potential molecular biomarkers and possibilities for modulating the endometrial microenvironment and, thereby, endometrial functions involved in embryo implantation and infertility.PMID:37152925 | PMC:PMC10155813 | DOI:10.3389/fendo.2023.1120988

Front Mol Biosci. 2023 Apr 21;10:1169449. doi: 10.3389/fmolb.2023.1169449. eCollection 2023.NO ABSTRACTPMID:37152901 | PMC:PMC10160367 | DOI:10.3389/fmolb.2023.1169449

Front Mol Biosci. 2023 Apr 19;10:1171366. doi: 10.3389/fmolb.2023.1171366. eCollection 2023.ABSTRACTHigh-frequency hearing is regarded as one of the most functionally important traits in laryngeally echolocating bats. Abundant candidate hearing-related genes have been identified to be the important genetic bases underlying high-frequency hearing for laryngeally echolocating bats, however, extensive metabolites presented in the cochleae have not been studied. In this study, we identified 4,717 annotated metabolites in the cochleae of two typical laryngeally echolocating bats using the liquid chromatography-mass spectroscopy technology, metabolites classified as amino acids, peptides, and fatty acid esters were identified as the most abundant in the cochleae of these two echolocating bat species, Rhinolophus sinicus and Vespertilio sinensis. Furthermore, 357 metabolites were identified as significant differentially accumulated (adjusted p-value <0.05) in the cochleae of these two bat species with distinct echolocating dominant frequencies. Downstream KEGG enrichment analyses indicated that multiple biological processes, including signaling pathways, nervous system, and metabolic process, were putatively different in the cochleae of R. sinicus and V. sinensis. For the first time, this study investigated the extensive metabolites and associated biological pathways in the cochleae of two laryngeal echolocating bats and expanded our knowledge of the metabolic molecular bases underlying high-frequency hearing in the cochleae of echolocating bats.PMID:37152899 | PMC:PMC10154556 | DOI:10.3389/fmolb.2023.1171366

Acta Endocrinol (Buchar). 2022 Oct-Dec;18(4):494-501. doi: 10.4183/aeb.2022.494.ABSTRACTCONTEXT: Accumulating data supports the key role of disrupted amino acids (AAs) metabolism in diabetes. Conflicting data regarding the relevance of serum AAs in diabetes and hypertension suggest that their relationship needs further investigation.OBJECTIVE: To investigate serum AAs as biomarkers of increased BP variability evaluated during 24-hour ambulatory BP monitoring in the presence of type 2 diabetes.DESIGN: Cross-sectional.SUBJECTS AND METHODS: We analyzed serum AAs using targeted metabolomics (ultrahigh-performance liquid chromatography/mass spectrometry) in patients with type 2 diabetes (n=80). BP variability was assessed using 24-hour ambulatory BP monitoring. Participants were divided into two groups based on the 24-hour diastolic BP variability median value.RESULTS: Aspartic acid, isoleucine, leucine, and phenylalanine were significantly lower, while glutamine was significantly higher in the group with higher diastolic BP variability (p-value <0.05 and variable importance in the projection >1). Corresponding pathways identified as disrupted in patients with diabetes and a higher 24-hour diastolic BP variability were phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and alanine, aspartate, and glutamate metabolism (pathway impact value >0).CONCLUSIONS: We identified specific changes in serum AAs and target AAs pathways in relation to increased 24-hour diastolic BP variability in patients with type 2 diabetes.PMID:37152871 | PMC:PMC10162828 | DOI:10.4183/aeb.2022.494

Front Microbiol. 2023 Apr 20;14:1159653. doi: 10.3389/fmicb.2023.1159653. eCollection 2023.ABSTRACTINTRODUCTION: Hybridization has been widely used among Chinese wild boars to improve their growth performance and maintain meat quality. Most studies have focused on the genetic basis for such variation. However, the differences in the gut environment between hybrid and purebred boars, which can have significant impacts on their health and productivity, have been poorly understood.METHODS: In the current study, metagenomics was used to detect the gut microbial diversity and composition in hybrid Batun (BT, Berkshire × Tunchang) pigs and purebred Tunchang (TC) pigs. Additionally, untargeted metabolomic analysis was used to detect differences in gut metabolic pathways. Furthermore, multiple molecular experiments were conducted to demonstrate differences in intestinal functions.RESULTS: As a result of hybridization in TC pigs, a microbial change was observed, especially in Prevotella and Lactobacillus. Significant differences were found in gut metabolites, including fatty acyls, steroids, and steroid derivatives. Furthermore, the function of the intestinal barrier was decreased by hybridization, while the function of nutrient metabolism was increased.DISCUSSION: Evidences were shown that hybridization changed the gut microbiome, gut metabolome, and intestinal functions of TC pigs. These findings supported our hypothesis that hybridization altered the gut microbial composition, thereby modifying the intestinal functions, even the host phenotypes. Overall, our study highlights the importance of considering the gut microbiome as a key factor in the evaluation of animal health and productivity, particularly in the context of genetic selection and breeding programs.PMID:37152756 | PMC:PMC10157192 | DOI:10.3389/fmicb.2023.1159653

Front Mol Neurosci. 2023 Apr 20;16:1155620. doi: 10.3389/fnmol.2023.1155620. eCollection 2023.ABSTRACTINTRODUCTION: The microbiota plays a critical role in modulating various aspects of host physiology, particularly through the microbiota-gut-brain (MGB) axis. However, the mechanisms that transduce and affect gut-to-brain communication are still not well understood. Recent studies have demonstrated that dysbiosis of the microbiome is associated with anxiety and depressive symptoms, which are common complications of metabolic syndrome. Germ-free (GF) animal models offer a valuable tool for studying the causal effects of microbiota on the host.METHODS: We employed gene expression and nuclear magnetic resonance (NMR)-based metabolomic techniques to investigate the relationships between brain plasticity and immune gene expression, peripheral immunity, and cerebral and liver metabolism in GF and specific pathogen-free (SPF) mice.RESULTS: Our principal findings revealed that brain acetate (p = 0.012) was significantly reduced in GF relative to SPF mice, whereas glutamate (p = 0.0013), glutamine (p = 0.0006), and N-acetyl aspartate (p = 0.0046) metabolites were increased. Notably, cFOS mRNA expression, which was significantly decreased in the prefrontal cortex of GF mice relative to SPF mice (p = 0.044), correlated with the abundance of a number of key brain metabolites altered by the GF phenotype, including glutamate and glutamine.DISCUSSION: These results highlight the connection between the GF phenotype, altered brain metabolism, and immediate-early gene expression. The study provides insight into potential mechanisms by which microbiota can regulate neurotransmission through modulation of the host's brain and liver metabolome, which may have implications for stress-related psychiatric disorders such as anxiety.PMID:37152431 | PMC:PMC10157641 | DOI:10.3389/fnmol.2023.1155620

Mayo Clin Proc Innov Qual Outcomes. 2023 Apr 22;7(3):153-164. doi: 10.1016/j.mayocpiqo.2023.03.002. eCollection 2023 Jun.ABSTRACTOBJECTIVE: To describe and compare the determinants of 1-year mortality after premature vs non-premature acute coronary syndrome (ACS).PATIENTS AND METHODS: Participants presenting with ACS were enrolled in a prospective registry of 29 hospitals in 4 countries, from January 22, 2012 to January 22, 2013, with 1-year of follow-up data. The primary outcome was all-cause 1-year mortality after premature ACS (men aged <55 years and women aged <65 years) and non-premature ACS (men aged ≥55 years and women aged ≥65 years). The associations between the baseline patient characteristics and 1-year mortality were analyzed in models adjusting for the Global Registry of Acute Coronary Events (GRACE) score and reported as adjusted odds ratio (aOR) (95% CI).RESULTS: Of the 3868 patients, 43.3% presented with premature ACS that was associated with lower 1-year mortality (5.7%) than those with non-premature ACS. In adjusted models, women experienced higher mortality than men after premature (aOR, 2.14 [1.37-3.41]) vs non-premature ACS (aOR, 1.28 [0.99-1.65]) (P interaction=.047). Patients lacking formal education vs any education had higher mortality after both premature (aOR, 2.92 [1.87-4.61]) and non-premature ACS (aOR, 1.78 [1.36-2.34]) (P interaction=.06). Lack of employment vs any employment was associated with approximately 3-fold higher mortality after premature and non-premature ACS (P interaction=.72). Using stepwise logistic regression to predict 1-year mortality, a model with GRACE risk score and 4 characteristics (education, employment, body mass index [kg/m2], and statin use within 24 hours after admission) had higher discrimination than the GRACE risk score alone (area under the curve, 0.800 vs 0.773; P comparison=.003).CONCLUSION: In this study, women, compared with men, had higher 1-year mortality after premature ACS. The social determinants of health (no formal education or employment) were strongly associated with higher 1-year mortality after premature and non-premature ACS, improved mortality prediction, and should be routinely considered in risk assessment after ACS.PMID:37152409 | PMC:PMC10160579 | DOI:10.1016/j.mayocpiqo.2023.03.002

Front Plant Sci. 2023 Apr 19;14:1108351. doi: 10.3389/fpls.2023.1108351. eCollection 2023.ABSTRACTCompositional traits in potato [Solanum tuberosum L.] are economically important but genetically complex, often controlled by many loci of small effect; new methods need to be developed to accelerate analysis and improvement of such traits, like chip quality. In this study, we used network analysis to organize hundreds of metabolic features detected by mass spectrometry into groups, as a precursor to genetic analysis. 981 features were condensed into 44 modules; module eigenvalues were used for genetic mapping and correlation analysis with phenotype data collected by the Solanaceae Coordinated Agricultural Project. Half of the modules were associated with at least one SNP according to GWAS; 11 of those modules were also significantly correlated with chip color. Within those modules features associated with chipping provide potential targets for selection in addition to selection for reduced glucose. Loci associated with module eigenvalues were not evenly distributed throughout the genome but were instead clustered on chromosomes 3, 7, and 8. Comparison of GWAS on single features and modules of clustered features often identified the same SNPs. However, features with related chemistries (for example, glycoalkaloids with precursor/product relationships) were not found to be near neighbors in the network analysis and did not share common SNPs from GWAS. Instead, the features within modules were often structurally disparate, suggesting that linkage disequilibrium complicates network analyses in potato. This result is consistent with recent genomic studies of potato showing that chromosomal rearrangements that create barriers to recombination are common in cultivated germplasm.PMID:37152172 | PMC:PMC10154602 | DOI:10.3389/fpls.2023.1108351

Front Plant Sci. 2023 Apr 20;14:1082245. doi: 10.3389/fpls.2023.1082245. eCollection 2023.ABSTRACTAs a highly economic small fruit crop, blueberry is enjoyed by most people in terms of color, taste, and rich nutrition. To better understand its coloring mechanism on the process of ripening, an integrative analysis of the metabolome and transcriptome profiles was performed in three blueberry varieties at three developmental stages. In this study, 41 flavonoid metabolites closely related to the coloring in blueberry samples were analyzed. It turned out that the most differential metabolites in the ripening processes were delphinidin-3-O-arabinoside (dpara), peonidin-3-O-glucoside (pnglu), and delphinidin-3-O-galactoside (dpgal), while the most differential metabolites among different varieties were flavonols. Furthermore, to obtain more accurate and comprehensive transcripts of blueberry during the developmental stages, PacBio and Illumina sequencing technology were combined to obtain the transcriptome of the blueberry variety Misty, for the very first time. Finally, by applying the gene coexpression network analysis, the darkviolet and bisque4 modules related to flavonoid synthesis were determined, and the key genes related to two flavonoid 3', 5'-hydroxylase (F3'5'H) genes in the darkviolet module and one bHLH transcription factor in the bisque4 module were predicted. It is believed that our findings could provide valuable information for the future study on the molecular mechanism of flavonoid metabolites and flavonoid synthesis pathways in blueberries.PMID:37152168 | PMC:PMC10157174 | DOI:10.3389/fpls.2023.1082245

Front Plant Sci. 2023 Apr 21;14:1172228. doi: 10.3389/fpls.2023.1172228. eCollection 2023.NO ABSTRACTPMID:37152147 | PMC:PMC10161898 | DOI:10.3389/fpls.2023.1172228

Front Plant Sci. 2023 Apr 20;14:1150046. doi: 10.3389/fpls.2023.1150046. eCollection 2023.ABSTRACTThe low temperature normally applied to prevent fruit decay during the storage of apples, can also triggers the onset of a chilling injury disorder known as superficial scald. In this work, the etiology of this disorder and the mechanism of action of two preventing strategies, such as the application of 1-MCP (1-methylcyclopropene) and storage at low oxygen concentration in 'Granny Smith' and 'Ladina' apple cultivars were investigated. The metabolite assessment highlighted a reorganization of specific metabolites, in particular flavan-3-ols and unsaturated fatty acids, while the genome-wide transcriptomic analysis grouped the DEGs into four functional clusters. The KEGG pathway and GO enrichment analysis, together with the gene-metabolite interactome, showed that the treatment with 1-MCP prevented the development of superficial scald by actively promoting the production of unsaturated fatty acids, especially in 'Granny Smith'. 'Ladina', more susceptible to superficial scald and less responsive to the preventing strategies, was instead characterized by a higher accumulation of very long chain fatty acids. Storage at low oxygen concentration stimulated a higher accumulation of ethanol and acetaldehyde together with the expression of genes involved in anaerobic respiration, such as malate, alcohol dehydrogenase and pyruvate decarboxylase in both cultivars. Low oxygen concentration, likewise 1-MCP, through a direct control on ethylene prevented the onset of superficial scald repressing the expression of PPO, a gene encoding for the polyphenol oxidase enzyme responsible of the oxidation of chlorogenic acid. Moreover, in 'Granny Smith' apple, the expression of three members of the VII subgroups of ERF genes, encoding for elements coordinating the acclimation process to hypoxia in plants was observed. The global RNA-Seq pattern also elucidated a specific transcriptomic signature between the two cultivars, disclosing the effect of the different genetic background in the control of this disorder.PMID:37152125 | PMC:PMC10157158 | DOI:10.3389/fpls.2023.1150046

Front Plant Sci. 2023 Apr 19;14:1175878. doi: 10.3389/fpls.2023.1175878. eCollection 2023.ABSTRACTPanax notoginseng saponins (PNSs) are used as industrial raw materials to produce many drugs to treat cardio-cerebrovascular diseases. However, it is a heat-sensitive plant, and its large-scale artificial cultivation is impeded by high temperature stress, leading to decreases in productivity and PNSs yield. Here, we examined exogenous foliar leucine to alleviate heat stress and explored the underlying mechanism using metabolomics. The results indicated that 3 and 5 mM exogenous foliar leucine significantly alleviated heat stress in one-year- and two-year-old P. notoginseng in pots and field trials. Exogenous foliar leucine enhanced the antioxidant capacity by increasing the activities of antioxidant enzymes (POD, SOD) and the contents of antioxidant metabolites (amino acids). Moreover, exogenous foliar leucine enhanced carbohydrate metabolism, including sugars (sucrose, maltose) and TCA cycle metabolites (citric acid, aconitic acid, succinic acid and fumaric acid), in P. notoginseng leaves, stems, and fibrous roots to improve the energy supply of plants and further alleviate heat stress. Field experiments further verified that exogenous foliar leucine increased the productivity and PNSs accumulation in P. notoginseng. These results suggest that leucine application is beneficial for improving the growth and quality of P. notoginseng under heat stress. It is therefore possible to develop plant growth regulators based on leucine to improve the heat resistance of P. notoginseng and other crops.PMID:37152124 | PMC:PMC10154563 | DOI:10.3389/fpls.2023.1175878

Front Plant Sci. 2023 Apr 21;14:1194937. doi: 10.3389/fpls.2023.1194937. eCollection 2023.NO ABSTRACTPMID:37152123 | PMC:PMC10161930 | DOI:10.3389/fpls.2023.1194937

Int J Biol Sci. 2023 Apr 9;19(7):2097-2113. doi: 10.7150/ijbs.81824. eCollection 2023.ABSTRACTDietary fat intake is positively associated with elevated risk of colorectal cancer (CRC). Currently, clinical treatments remian inadequate bacause of the complex pathogenesis of CRC induced by a high-fat diet (HFD). Mechanistically, imbalances in gut microbiota are associated with HFD-associated colorectal tumourigenesis. Therefore, we investigated the anti-tumor activity of berberine (BBR) in modulating the dysregulated gut microbiota and related metabolites by preforming 16S rDNA sequencing and liquid chromatography/mass spectrometry. As expected, BBR treatment significantly decreased the number of colonic polyps, ameliorated gut barrier disruption, and inhibited colon inflammation and related oncogenic pathways in AOM/DSS-induced CRC model mice fed with an HFD. Furthermore, BBR alleviated gut microbiota dysbiosis and increased the abundance of beneficial gut microorganisms, including Akkermansia and Parabacteroides, in HFD-fed CRC mice. In addition, metabolomics analysis demonstrated significantly altered the glycerophospholipid metabolism during the progression of HFD-associated CRC in mice, whereas BBR treatment reverted these changes in glycerophospholipid metabolites, particularly lysophosphatidylcholine (LPC), which was confirmed to promote CRC cell proliferation and ameliorate cell junction impairment. Notably, BBR had no clear anti-tumor effects on HFD-fed CRC model mice with gut microbiota depletion, whereas transplantation of BBR-treated gut microbiota to gut microbiota-depleted CRC mice recapitulated the inhibitory effects of BBR on colorectal tumourigenesis and LPC levels. This study demonstrated that BBR inhibited HFD-associated CRC directly through modulating gut microbiota-regulated LPC levels, thereby providing a promising microbiota-modulating therapeutic strategy for the clinical prevention and treatment of Western diet-associated CRC.PMID:37151876 | PMC:PMC10158016 | DOI:10.7150/ijbs.81824