PubMed

Heliyon. 2023 May 19;9(6):e16138. doi: 10.1016/j.heliyon.2023.e16138. eCollection 2023 Jun.ABSTRACTBenzylisoquinoline alkaloids in lotus (Nelumbo nucifera) seed plumules and leaves exhibit significant tissue specificity for their pharmacological effects and potential nutritional properties. Herein, 46 benzylisoquinoline alkaloids were identified via UPLC-QTOF-HRMS, of which 9 were annotated as glycosylated monobenzylisoquinoline alkaloids concentrated in the seed plumules. The spatial distribution of targeted benzylisoquinoline alkaloids in leaves, seed plumules, and milky sap was determined via MALDI-MSI. Furthermore, 37 Nelumbo cultivars were investigated using targeted metabolomics to provide insights into functional tea development. While aporphine alkaloids comprised the main compounds present in lotus leaves, bisbenzylisoquinoline alkaloids were the main compounds in lotus plumules, where glycosylation primarily occurs. These findings can help understand the distribution of benzylisoquinoline alkaloids in lotus tissue and the directional breeding of varieties enriched with specific chemical functional groups for nutritional and pharmacological applications.PMID:37251486 | PMC:PMC10220311 | DOI:10.1016/j.heliyon.2023.e16138

Heliyon. 2023 May 19;9(6):e16417. doi: 10.1016/j.heliyon.2023.e16417. eCollection 2023 Jun.ABSTRACTWith the progress of society, the health problems of pets have attracted more and more attention. Recent studies have shown that intestinal microflora and related fecal metabolites play a crucial role in the healthy growth of cats. However, the potential role and related metabolic characteristics of gut microbiota in different age groups of pet cats need to be further clarified. 16S rRNA gene sequencing was used to analyze the intestinal microbial composition of young and old cats. LC-MS metabonomic analysis is used to characterize the changes in the metabolic spectrum in feces. The potential relationship between intestinal microorganisms and metabolites, as well as the differences in different age groups, were studied. The species composition of intestinal microflora in the young group and old group is significantly different, T-test algorithm shows 36 different ASVs and 8 different genuses, while the Wilcoxon algorithm shows 81 different ASVs and 17 different genuses. The metabolomics analysis identified 537 kinds of fecal metabolites, which are rich in differences between young and old cats, and may be potential biomarkers indicating the health of cats. 16S rRNA analysis showed significant differences in fructose and mannose metabolism, while metabonomics KEGG analysis showed significant difference in choline metabolism in cancer. Our study compared the differences between the intestinal microbiome and fecal metabolites in young and old cats. This difference provides a new direction for further exploring the relationship between the composition and metabolism of intestinal microbiota in cats of different age groups. It also provides a reference for cat health research.PMID:37251444 | PMC:PMC10220381 | DOI:10.1016/j.heliyon.2023.e16417

Front Immunol. 2023 May 12;14:1117638. doi: 10.3389/fimmu.2023.1117638. eCollection 2023.ABSTRACTInflammation is thought to be a key cause of many chronic diseases and cancer. However, current therapeutic agents to control inflammation have limited long-term use potential due to various side-effects. This study aimed to examine the preventive effects of norbergenin, a constituent of traditional anti-inflammatory recipes, on LPS-induced proinflammatory signaling in macrophages and elucidate the underlying mechanisms by integrative metabolomics and shotgun label-free quantitative proteomics platforms. Using high-resolution mass spectrometry, we identified and quantified nearly 3000 proteins across all samples in each dataset. To interpret these datasets, we exploited the differentially expressed proteins and conducted statistical analyses. Accordingly, we found that LPS-induced production of NO, IL1β, TNFα, IL6 and iNOS in macrophages was alleviated by norbergenin via suppressed activation of TLR2 mediated NFκB, MAPKs and STAT3 signaling pathways. In addition, norbergenin was capable of overcoming LPS-triggered metabolic reprogramming in macrophages and restrained the facilitated glycolysis, promoted OXPHOS, and restored the aberrant metabolites within the TCA cycle. This is linked to its modulation of metabolic enzymes to support its anti-inflammatory activity. Thus, our results uncover that norbergenin regulates inflammatory signaling cascades and metabolic reprogramming in LPS stimulated macrophages to exert its anti-inflammatory potential.PMID:37251401 | PMC:PMC10213229 | DOI:10.3389/fimmu.2023.1117638

ACS Omega. 2023 May 8;8(20):18128-18139. doi: 10.1021/acsomega.3c01441. eCollection 2023 May 23.ABSTRACTDoxorubicin (DOX) is a broad-spectrum chemotherapeutic drug used in clinical treatment of malignant tumors. It has a high anticancer activity but also high cardiotoxicity. The aim of this study was to explore the mechanism of Tongmai Yangxin pills (TMYXPs) in ameliorating DOX-induced cardiotoxicity through integrated metabolomics and network pharmacology. In this study, first, an ultrahigh-performance liquid chromatography-quadrupole-time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) metabonomics strategy was established to obtain metabolite information and potential biomarkers were determined after data processing. Second, network pharmacological analysis was used to evaluate the active components, drug-disease targets, and key pathways of TMYXPs to alleviate DOX-induced cardiotoxicity. Targets from the network pharmacology analysis and metabolites from plasma metabolomics were jointly analyzed to select crucial metabolic pathways. Finally, the related proteins were verified by integrating the above results and the possible mechanism of TMYXPs to alleviate DOX-induced cardiotoxicity was studied. After metabolomics data processing, 17 different metabolites were screened, and it was found that TMYXPs played a role in myocardial protection mainly by affecting the tricarboxylic acid (TCA) cycle of myocardial cells. A total of 71 targets and 20 related pathways were screened out with network pharmacological analysis. Based on the combined analysis of 71 targets and different metabolites, TMYXPs probably played a role in myocardial protection through regulating upstream proteins of the insulin signaling pathway, MAPK signaling pathway, and p53 signaling pathway, as well as the regulation of metabolites related to energy metabolism. They then further affected the downstream Bax/Bcl-2-Cyt c-caspase-9 axis, inhibiting the myocardial cell apoptosis signaling pathway. The results of this study may contribute to the clinical application of TMYXPs in DOX-induced cardiotoxicity.PMID:37251132 | PMC:PMC10210219 | DOI:10.1021/acsomega.3c01441

Bio Protoc. 2023 May 20;13(10):e4673. doi: 10.21769/BioProtoc.4673. eCollection 2023 May 20.ABSTRACTHere, we present an in vivo drug screening protocol using a zebrafish model of metastasis for the identification of anti-metastatic drugs. A tamoxifen-controllable Twist1a-ERT2 transgenic zebrafish line was established to serve as a platform for the identification. By crossing Twist1a-ERT2 with xmrk (a homolog of hyperactive form of the epidermal growth factor receptor) transgenic zebrafish, which develop hepatocellular carcinoma, approximately 80% of the double transgenic zebrafish show spontaneous cell dissemination of mCherry-labeled hepatocytes from the liver to the entire abdomen and tail regions in five days, through induction of epithelial to mesenchymal transition (EMT). This rapid and high-frequency induction of cell dissemination makes it possible to perform an in vivo drug screen for the identification of anti-metastatic drugs targeting metastatic dissemination of cancer cells. The protocol evaluates the suppressor effect of a test drug on metastasis in five days, by comparing the frequencies of the fish showing abdominal and distant dissemination patterns in the test drug-treated group with those in the vehicle-treated group. Our study previously identified that adrenosterone, an inhibitor for hydroxysteroid (11-beta) dehydrogenase 1 (HSD11β1), has a suppressor effect on cell dissemination in the model. Furthermore, we validated that a pharmacologic and genetic inhibition of HSD11β1 suppressed metastatic dissemination of highly metastatic human cell lines in a zebrafish xenotransplantation model. Taken together, this protocol opens new routes for the identification of anti-metastatic drugs. Graphical overview Timing Day 0: Zebrafish spawning Day 8: Primary tumor induction Day 11: Chemical treatment Day 11.5: Metastatic dissemination induction in the presence of a test chemical Day 16: Data analysis.PMID:37251091 | PMC:PMC10213071 | DOI:10.21769/BioProtoc.4673

Front Mol Biosci. 2023 May 11;10:1178269. doi: 10.3389/fmolb.2023.1178269. eCollection 2023.ABSTRACTHypoxia in disease describes persistent low oxygen conditions, observed in a range of pathologies, including cancer. In the discovery of biomarkers in biological models, pathophysiological traits present a source of translatable metabolic products for the diagnosis of disease in humans. Part of the metabolome is represented by its volatile, gaseous fraction; the volatilome. Human volatile profiles, such as those found in breath, are able to diagnose disease, however accurate volatile biomarker discovery is required to target reliable biomarkers to develop new diagnostic tools. Using custom chambers to control oxygen levels and facilitate headspace sampling, the MDA-MB-231 breast cancer cell line was exposed to hypoxia (1% oxygen) for 24 h. The maintenance of hypoxic conditions in the system was successfully validated over this time period. Targeted and untargeted gas chromatography mass spectrometry approaches revealed four significantly altered volatile organic compounds when compared to control cells. Three compounds were actively consumed by cells: methyl chloride, acetone and n-Hexane. Cells under hypoxia also produced significant amounts of styrene. This work presents a novel methodology for identification of volatile metabolisms under controlled gas conditions with novel observations of volatile metabolisms by breast cancer cells.PMID:37251079 | PMC:PMC10210155 | DOI:10.3389/fmolb.2023.1178269

iScience. 2023 May 9;26(6):106827. doi: 10.1016/j.isci.2023.106827. eCollection 2023 Jun 16.ABSTRACTCancer cells often acquire resistance to cell death programs induced by loss of integrin-mediated attachment to extracellular matrix (ECM). Given that adaptation to ECM-detached conditions can facilitate tumor progression and metastasis, there is significant interest in effective elimination of ECM-detached cancer cells. Here, we find that ECM-detached cells are remarkably resistant to the induction of ferroptosis. Although alterations in membrane lipid content are observed during ECM detachment, it is instead fundamental changes in iron metabolism that underlie resistance of ECM-detached cells to ferroptosis. More specifically, our data demonstrate that levels of free iron are low during ECM detachment because of changes in both iron uptake and iron storage. In addition, we establish that lowering the levels of ferritin sensitizes ECM-detached cells to death by ferroptosis. Taken together, our data suggest that therapeutics designed to kill cancer cells by ferroptosis may be hindered by lack of efficacy toward ECM-detached cells.PMID:37250802 | PMC:PMC10209538 | DOI:10.1016/j.isci.2023.106827

JHEP Rep. 2023 Apr 5;5(7):100749. doi: 10.1016/j.jhepr.2023.100749. eCollection 2023 Jul.ABSTRACTStandard of care for the treatment of ascites in cirrhosis is to administer a sodium-restricted diet and diuretic therapy. The progression of cirrhosis will eventually lead to the development of refractory ascites, at which point diuretics will no longer be able to control the ascites. Second-line therapies such as a transjugular intrahepatic portosystemic shunt (TIPS) placement or repeat large volume paracentesis are then required. There is some evidence that regular infusions of albumin may delay the onset of refractoriness and improve survival, especially if given at an early stage in the natural history of ascites and for a long enough duration. The use of TIPS can eliminate ascites, but its insertion is associated with complications, especially cardiac decompensation and worsening of hepatic encephalopathy. New information is now available regarding how to best select patients for TIPS, what type of cardiac investigations are needed and how under-dilating the TIPS at the time of insertion may help. The use of a non-absorbable antibiotics, such as rifaximin, starting in the pre-TIPS period may also reduce the likelihood of post-TIPS hepatic encephalopathy. In patients who are not suitable for TIPS, the use of an alfapump to remove the ascites via the bladder can improve quality of life without significantly altering survival. In the future it may be possible to use metabolomics to help refine the management of patients with ascites, e.g. to assess their response to non-selective beta-blockers or to predict the development of other complications such as acute kidney injury.PMID:37250493 | PMC:PMC10220491 | DOI:10.1016/j.jhepr.2023.100749

iScience. 2023 Apr 28;26(5):106772. doi: 10.1016/j.isci.2023.106772. eCollection 2023 May 19.ABSTRACTApocynum species have great application prospects in textile and phytoremediation of saline soil, are rich in flavonoids, and possess medicinal significance. Here, we report the draft genomes of Apocynum venetum and Apocynum hendersonii, and elucidate their evolutionary relationship. The high synteny and collinearity between the two suggested that they have experienced the same WGD event. Comparative analysis revealed that flavone 3-hydroxylase (ApF3H) and differentially evolved flavonoid 3-O-glucosyl transferase (ApUFGT) genes are critical for determining natural variation in flavonoid biosynthesis between the species. Overexpression of ApF3H-1 enhanced the total flavonoid content and promoted the antioxidant capacity of transformed plants compared to the wild-type. ApUFGT5 and 6 explained the diversification of flavonoids or their derivatives. These data provide biochemical insight and knowledge on the genetic regulation of flavonoid biosynthesis, supporting the adoption of these genes in breeding programs aimed at the multipurpose utilization of the plants.PMID:37250304 | PMC:PMC10214733 | DOI:10.1016/j.isci.2023.106772

Front Microbiol. 2023 May 12;14:1125195. doi: 10.3389/fmicb.2023.1125195. eCollection 2023.ABSTRACTINTRODUCTION: Pollutant gas emissions in the current production system of the livestock industry have negative influences on environment as well as the health of farm staffs and animals. Although ammonia (NH3) is considered as the primary and harmful gas pollutant in the rabbit farm, less investigation has performed to determine the toxic effects of house ammonia exposure on rabbit in the commercial confined barn.METHODS: In this study, we performed multi-omics analysis on rabbits exposed to high and low concentration of house ammonia under similar environmental conditions to unravel the alterations in nasal and colonic microbiota, pulmonary and colonic gene expression, and muscular metabolic profile.RESULTS AND DISCUSSION: The results showed that house ammonia exposure notably affected microbial structure, composition, and functional capacity in both nasal and colon, which may impact on local immune responses and inflammatory processes. Transcriptome analysis indicated that genes related to cell death (MCL1, TMBIM6, HSPB1, and CD74) and immune response (CDC42, LAMTOR5, VAMP8, and CTSB) were differentially expressed in the lung, and colonic genes associated with redox state (CAT, SELENBP1, GLUD1, and ALDH1A1) were significantly up-regulated. Several key differentially abundant metabolites such as L-glutamic acid, L-glutamine, L-ornithine, oxoglutaric acid, and isocitric acid were identified in muscle metabolome, which could denote house ammonia exposure perturbed amino acids, nucleotides, and energy metabolism. In addition, the widespread and strong inter-system interplay were uncovered in the integrative correlation network, and central features were confirmed by in vitro experiments. Our findings disclose the comprehensive evidence for the deleterious effects of house ammonia exposure on rabbit and provide valuable information for understanding the underlying impairment mechanisms.PMID:37250049 | PMC:PMC10213413 | DOI:10.3389/fmicb.2023.1125195

Front Microbiol. 2023 May 12;14:1186841. doi: 10.3389/fmicb.2023.1186841. eCollection 2023.ABSTRACTINTRODUCTION: The overuse of antibiotics has made public health and safety face a serious cisis. It is urgent to develop new clinical treatment methods to combat drug resistant bacteria to alleviate the health crisis. The efficiency of antibiotics is closely related to the metabolic state of bacteria. However, studies on fluoroquinolone resistant Salmonella are relatively rare.METHODS: CICC21484 were passaged in medium with and without sarafloxacin and obtain sarafloxacin- susceptible Salmonella Typhimurium (SAR-S) and sarafloxacin resistant Salmonella Typhimurium (SAR-R), respectively. Non-targeted metabolomics was used to analyze the metabolic difference between SAR-S and SAR-R. Then we verified that exogenous L-leucine promoted the killing effect of sarafloxacin in vitro, and measured the intracellular ATP, NADH and reactive oxygen species levels of bacteria. Gene expression was determined using Real Time quantitative PCR.RESULTS: We confirmed that exogenous L-leucine increased the killing effect of sarafloxacin on SAR-R and other clinically resistant Salmonella serotypes. Exogenous L-leucine stimulated the metabolic state of bacteria, especially the TCA cycle, which increased the working efficiency of the electron transfer chain and increased the intracellular NADH, ATP concentration, and reactive oxygen species level. Our results suggest that when the metabolism of drug-resistant bacteria is reprogrammed, the bactericidal effect of antibiotics improves.DISCUSSION: This study further enhances research in the anti-drug resistance field at the metabolic level and provides theoretical support for solving the current problem of sarafloxacin drug resistance, a unique fluoroquinolone drug for animals and indicating the potential of L-leucine as a new antibiotic adjuvant.PMID:37250042 | PMC:PMC10213264 | DOI:10.3389/fmicb.2023.1186841

Front Microbiol. 2023 May 12;14:1138914. doi: 10.3389/fmicb.2023.1138914. eCollection 2023.ABSTRACTINTRODUCTION: Residual feed intake (RFI) is a indicator to evaluate animal feed. This experiment was explored to study the relationship between intestinal microbiome and metabolome of ducks with different residual feed intake during laying period.METHODS: A total of 300 Shaoxing ducks aged 42 weeks were randomly selected and fed a diet of 60 d. At the end of the trial, 20 samples were selected according to the phenotype of RFI and divided into two groups (HRFI and LRFI). The cecal microbiota composition was explored by 16S ribosomal RNA gene sequencing and rectal metabolomics uses liquid chromatography-mass spectrometry (LC-MS) to identify the composition of metabolites in a non-targeted manner.RESULTS: Results show feed intake and feed conversion ratio in the group HRFI were significantly higher than those in the group LRFI (p < 0.05). Chao1 indices were higher in the group LRFI than in the HRFI (p < 0.05), Shannon and Simpson indices were higher in the group LRFI than in the HRFI (p < 0.01). After linear discriminant analysis effect size (p < 0.05, LDA score > 3), Rikenellaceae, Rikenellaceae_RC9_gut_group, Lactobacillales and Ruminococcus_2, etc. were significantly enriched in the group LRFI at the genus level, while Prevotellaceae_NK3B31_group and Bacteria were significantly enriched in the group HRFI. After LC-MS analysis we found 338 metabolic difference products and 10 metabolic pathways, including the ABC transporter system, cysteine and methionine metabolism, arginine and proline metabolism, and vitamin B6 metabolism, were identified to be associated with the significantly differentially expressed between the groups LRFI and HRFI (p < 0.05). We hypothesize that the difference between ducks with different RFIs is mainly due to the fact that ducks with LRFI have more SCFAs-producing bacteria in their gut microorganisms, which regulate the RFI of animals. This process we found that Phascolarctobaterium and Anaerobiospirillum may provide energy for ABC transporter system by producing SCFAs, and regulate RFI to improve feed utilization efficiency.DISCUSSION: These results revealed the relationship between microbiome and metabonomics in laying ducks with different RFI, and provided theoretical basis for further study on the relationship between them.PMID:37250027 | PMC:PMC10213451 | DOI:10.3389/fmicb.2023.1138914

Metabolomics. 2023 May 30;19(6):52. doi: 10.1007/s11306-023-02014-w.ABSTRACTINTRODUCTION: Faba bean (Vicia faba L.) flowers are edible and used as garnishes because of their aroma, sweet flavor and attractive colors. Anthocyanins are the common plant pigments that give flowers their vivid colors, whereas non-anthocyanin flavonoids can serve as co-pigments that can modify the color intensity of flowers.OBJECTIVES: To explore the polyphenol diversity and differences in standard and wing petals of faba bean flowers; and identify glycosylated flavonoids that contribute to flower color.METHODS: Flower standard and wing petals from 30 faba bean genotypes (eight color groups with a total of 60 samples) were used for polyphenol extraction. Samples were analyzed using a targeted method and a semi-untargeted analysis using liquid chromatography-high resolution mass spectrometry (LC-HRMS) combined with photodiode array (PDA) detection. Compound Discoverer software was used for polyphenol identification and multivariate analysis.RESULTS: The semi-untargeted analysis guided by the PDA detected 90 flavonoid metabolites present in faba bean flower petals. Ten anthocyanins largely influenced the flower colors, but other flavonoids (63 flavonols and 12 flavones) found with variable levels in different flower color groups appeared to also influence color, especially in mixed colors.CONCLUSION: Analysis of the different colored faba bean flowers confirmed that the color variation between the flowers was mainly controlled by anthocyanins in brown, red and purple-red flowers. Of the other flavonoids, multiglycosylated kaempferols were abundant in white and brown flowers, monoglycosylated kaempferols were common in red and purple-red flowers, and quercetin and apigenin glycosides were abundant co-pigments in purple-red flowers.PMID:37249718 | DOI:10.1007/s11306-023-02014-w

Environ Monit Assess. 2023 May 30;195(6):759. doi: 10.1007/s10661-023-11380-w.ABSTRACTInvasive plants can change the soil ecological environment in the invasion area to adapt to their growth and reproduction through root exudates. Root exudates are the most direct manifestation of plant responses to external environmental changes, but there is a lack of studies on root exudates of invasive plants in the context of inevitable global warming and nitrogen deposition. In this research, we used widely targeted metabolomics to investigate Ambrosia trifida root exudates during seedling and maturity under warming and nitrogen deposition to reveal the possible mechanisms of A. trifida adaptation to climate change. The results showed that the organic acids increased under warming condition but decreased after nitrogen addition in the seedling stage. Phenolic acids increased greatly after nitrogen addition in the mature stage. Most phenolic acids were annotated in the phenylpropane metabolic pathway and tyrosine metabolism. Therefore, nitrogen deposition may increase the adaptability of A. trifida through root exudates, making it more invasive under global warming. The results provide new ideas for preventing and controlling the invasion of A. trifida under climate change.PMID:37249649 | DOI:10.1007/s10661-023-11380-w

J Trauma Acute Care Surg. 2023 May 29. doi: 10.1097/TA.0000000000003987. Online ahead of print.ABSTRACTBACKGROUND: Cardiac Dysfunction (CD) has emerged as a key contributor to delayed organ failure and late mortality in patients surviving the initial traumatic haemorrhagic response. Inflammatory processes are implicated in the initial stages of this CD, however downstream pathways leading to a characteristic rapid fall in SV and CO are not yet fully defined. Currently, no cardioprotective treatments are available. We investigated the role of myocardial oxidative stress in the pathogenesis of CD associated to traumatic haemorrhagic injury, and its related metabolomic profile.METHODS: Ex vivo tissue from a 3-hour murine model of pressure-controlled trauma haemorrhagic shock (THS) was analyzed. Animals were randomized to echocardiography-guided crystalloid fluid resuscitation or a control group (sham: cannulation and anaesthesia only, or naïve: no intervention). THS and naïve samples were assessed by immunohistochemistry for nuclear 8-OHdG expression as a marker of oxidative stress. Metabolomic analysis of THS and sham group tissue was performed by LC-MS.RESULTS: 8-OHdG expression across the myocardium was significantly higher following THS injury compared to naïve group (33.01 ± 14.40% vs. 15.08 ± 3.96%, p < 0.05). THS injury significantly increased lysine (p = 0.022), and decreased aconitate (p = 0.016) and glutamate (p = 0.047) in the myocardium, indicating activation of a catabolic metabolism and oxidative stress response.CONCLUSION: We confirm the acute development of oxidative stress lesions and altered cardiac energy metabolism following traumatic haemorrhage injury, providing insight into the relationship between inflammatory damage and impaired cardiac contractility. These findings may provide targets for development of novel cardioprotective therapeutics aiming to decrease late mortality from trauma.LEVEL OF EVIDENCE: Original Research (Basic Science), N/A.PMID:37249511 | DOI:10.1097/TA.0000000000003987

Mol Omics. 2023 May 30. doi: 10.1039/d3mo00033h. Online ahead of print.ABSTRACTBackground: The DNA damage repair enzyme, poly(ADP-ribose) polymerase 1 (PARP1), is crucial for lipid and glucose metabolism. However, no evidence has been presented on the relationship between liver lipid accumulation and the PARP1 inhibitor, 3-aminobenzamide (3-AB), in atherosclerosis. Methods: ApoE-/- mice were used to explore the effect of 3-AB on atherosclerotic liver lipid accumulation, and the experiment of Sprague Dawley (SD) rats was designed to determine if the lowering of liver lipid levels by 3-AB was linked to gut bacteria. The levels of bile acid metabolism-related targets were assessed by ELISA, western blotting, and RT-qPCR. The relative abundances of gut microbes and biomarkers were determined using 16S rRNA sequencing analysis. Bile acid levels in the liver and ileum were examined by ultra-performance liquid chromatography-tandem mass spectrometry. The relationship between gut microbes and bile acids was assessed by Spearman's correlation analysis. Results: 3-AB significantly reduced the formation of aortic plaques in apoE-/- mice, according to gross oil red staining. H & E and Oil Red O staining revealed that 3-AB significantly reduced the hepatic lipid droplet area in ApoE-/- mice and SD rats. Compared with the atherosclerosis (ATH) group, 3-AB dramatically decreased the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) in the serum of SD rats and apoE-/- mice, and the levels of TC, TG, and LDL-C in the serum and liver of apoE-/- mice. Furthermore, in apoE-/- mice and SD rats, 3-AB increased the mRNA and protein levels of farnesoid X receptor (FXR) and bile salt export pump (BSEP) in the liver, while inhibiting the mRNA and protein levels of FXR and fibroblast growth factor 15 (FGF15) in the ileum, respectively. 3-AB clearly inhibited the mRNA and protein levels of PARP1 in the liver and ileum of apoE-/- mice and rats. Following treatment with 3-AB, the levels of conjugated bile acids decreased in the liver of apoE-/- mice and increased in the ileum of SD rats, according to targeted metabolomic analysis. Microbiome sequencing analysis revealed that 3-AB reduced the relative abundance of Lactobacillus, Bifidobacterium, Listeria, Clostridium, Bacillus, and Staphylococcus in the feces of apoE-/- mice, and the relative abundance of Blautia, Clostridium, and Listeria in the feces of SD rats, eventually decreasing the total abundance of 10 bile salt hydrolase-associated gut microbes. According to the correlation analysis, 3-AB regulates bile acid metabolism, which is primarily related to Bifidobacterium. Conclusion: 3-AB alleviated atherosclerosis by modulating the bile acid metabolism and bile salt hydrolase-related gut microbes.PMID:37249474 | DOI:10.1039/d3mo00033h

Cancer Biomark. 2023 May 11. doi: 10.3233/CBM-220250. Online ahead of print.ABSTRACTBACKGROUND: Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies. The poor prognosis of EOC is mainly due to its asymptomatic early stage, lack of effective screening methods, and a late diagnosis in the advanced stages of the disease.OBJECTIVE: This study investigated metabolomic abnormalities in epithelial ovarian cancers.METHODS: Our study developed a novel strategy to rapidly identify the metabolic biomarkers in the plasma of the EOC patients using Internal Extraction Electrospray Ionization Mass Spectrometry (IEESI-MS) and Liquid Chromatography-mass Spectrometry (HPLC-MS), which could distinguish the differential metabolites in between plasma samples collected from 98 patients with epithelial ovarian cancer, including 78 cases with original (P), and 20 cases with self-configuration (ZP), as well as 60 healthy subjects, including 30 cases in the original sample (H), 30 cases in self-configuration (ZH), and 6 cases in a blind sample (B).RESULTS: Our study detected 880 metabolites based on criteria variable importance in projection (VIP) > 1, among which 26 metabolites were selected for further identification. They are mainly metabolism-related lipids, amino acids, nucleic acids, and others. The metabolic pathways associated with the differential metabolites were explored by the KEGG analysis, a comprehensive database that integrates genome, chemistry, and system function information. The abnormal metabolites of EOC patients identified by IEESI-MS and HPLC-MS included Lysophosphatidylcholine (16:0) [Lyso PC (16:0)], L-Phenylalanine, L-Leucine, Phenylpyruvic acid, L-Tryptophan, and L-Histidine.CONCLUSIONS: Identifying the abnormal metabolites of EOC patients through metabolomics analyses could provide a new strategy to identify valuable potential biomarkers for the screening and early diagnosis of EOC.PMID:37248885 | DOI:10.3233/CBM-220250

IET Nanobiotechnol. 2023 May 29. doi: 10.1049/nbt2.12141. Online ahead of print.ABSTRACTMetabolomics, an emerging omics technology developed in the post-gene age, is an important part of systems biology. It interprets the pathophysiological state of the subject by quantitatively describing the dynamic changes of metabolites through analytical methods, mainly mass spectrometry (MS) and nuclear magnetic resonance (NMR). Assisted reproductive technology (ART) is a method used to manipulate sperm, oocytes, and embryos to achieve conception. Recently, several studies have reported that metabolomics methods can be used to measure metabolites in ART samples; these metabolites can be used to evaluate the quality of gametes and embryos. This article reviews the progress of research on metabolomics and the application of this technology in the field of ART, thus providing a reference for research and development directions in the future.PMID:37248807 | DOI:10.1049/nbt2.12141

Plant J. 2023 May 29. doi: 10.1111/tpj.16332. Online ahead of print.ABSTRACTField-grown crops rarely experience growth conditions in which yield can be maximized. Environmental stresses occur in combination, with advancements in crop tolerance further complicated by its polygenic nature. Strategic targeting of causal genes is required to realize future crop production needs. Here, we employed a systems biology approach in wheat to investigate physio-metabolic adjustments and transcriptome reprogramming involved in acclimations to heat, drought, salinity and all combinations therein. A significant shift in magnitude and complexity of plant response was evident across stress scenarios based on the agronomic losses, increased proline concentrations and 8.7-fold increase in unique differentially expressed transcripts (DETs) observed under the triple stress condition. Transcriptome data from all stress treatments were assembled into an online, open-access eFP browser for visualizing gene expression during abiotic stress. Weighted gene co-expression network analysis revealed 152 hub genes of which 32 % contained the transcriptional repression EAR (ethylene-responsive element binding factor-associated amphiphilic repression) motif. Cross-referencing against the 31 DETs common to all stress treatments isolated TaWRKY33 as a leading candidate for greater plant tolerance to combinatorial stresses. Integration of our findings with available literature on gene functional characterization allowed us to further suggest flexible gene combinations for future adaptive gene stacking in wheat. Our approach demonstrates the strength of robust multi-omics-based data resources for gene discovery in complex environmental conditions. Accessibility of such datasets will promote cross-validation of candidate genes across studies and aid in accelerating causal gene validation for crop resiliency.PMID:37248640 | DOI:10.1111/tpj.16332

Pestic Biochem Physiol. 2023 Jun;193:105452. doi: 10.1016/j.pestbp.2023.105452. Epub 2023 May 9.ABSTRACTProthioconazole (PTC), as a popular triazole fungicide, with its main metabolite prothioconazole desthio (PTC-d), have attracted widespread concern due to their widely use and toxicological effects on non-target organisms. However, toxic effects of study analyzed PTC and PTC-d on the hepatic metabolism of mammalian still remains unclear. In this study, we conducted the study of the C57BL/6 mice which oral exposure to 30 mg/kg PTC and PTC-d via metabolomic analysis. In the liver, the metabolomics profile unveiled that exposure to 30 mg/kg PTC and PTC-d led to significantly altered 13 and 28 metabolites respectively, with 6 metabolites in common including significant decreased d-Fructose, Glutathione, showing the change of carbohydrate, lipid and amino acid metabolism. Via the further exploration of genes related to hepatic glycolipid metabolism and the biomarkers of oxidative stress, we found that liver was potentially damaged after exposure to 5 and 30 mg/kg PTC and PTC-d. Particularly, it was proved that PTC-d caused more adverse effect than its parent compound PTC on hepatotoxicity, and high concentration PTC or PTC-d exposure is more harmful than low concentration exposure.PMID:37248020 | DOI:10.1016/j.pestbp.2023.105452