PubMed

Phytomedicine. 2023 May 29;116:154910. doi: 10.1016/j.phymed.2023.154910. Online ahead of print.ABSTRACTBACKGROUND: Sepsis is one of the major threats to human health with high mortality. Simiao Yong'an decoction (SMYAD) has the efficacy of anti-inflammation, improving coagulation and microcirculation, which is applicable for the clinical assistance treatment of sepsis. Yet, its material basis and relevant mechanisms are still vague.PURPOSE: Explore the quality markers (Q-markers), biomarkers and potential mechanisms of SMYAD combined with imipenem/cilastatin sodium for anti-sepsis.METHODS: Linear-Trap-LC/MSn was employed to profile the compounds in the extract and medicated serum of SMYAD. Then, the components and targets obtained from databases were applied to network pharmacology. Q-markers' range was narrowed via the affinity of three times docking and determined as per its screening criteria. Also, the content of them was detected by HPLC. Next, cecal ligation and puncture (CLP) model was reproduced to observe the effect of SMYAD united antibiotic by survival rate, histopathology score, ELISA, western blot and qPCR. Finally, metabolomics based upon GC-MS was exerted to discover the differential endogenous metabolites, metabolic pathway and joint pathway of SMYAD combined with antibiotic for sepsis.RESULTS: The 25 serum migrant ingredients derived from 113 chemical compounds of SMYAD were identified for the first time, and 6 components were determined as the Q-markers of SMYAD. The enrichment analysis indicated that the potential mechanism was mainly associated with the IL-17 signaling pathway, complement-coagulation cascades signaling pathway and VEGF signaling pathway. Then, SMYAD united antibiotic declined the mortality of septic rats, restored cytokine levels, ameliorated histopathological lesions and decreased the mRNA and protein expression of target proteins in a dose-dependent way. Furthermore, 8 differential metabolites were regarded as latent biomarkers related to the antiseptic effect of SMYAD united antibiotic, which were mainly involved in the Citrate cycle (TCA cycle) metabolic pathway.CONCLUSIONS: Different skeletons of compounds, including iridoids, phenylpropanoids, organic acids, triterpenes and others, were the main compositions of SMYAD. Among them, 6 components were determined as the Q-markers, which provided a basis for the construction of quality standards for this ancient classic formula. The combination therapy of SMYAD and antibiotic obviously ameliorated inflammatory reaction, coagulation dysfunction and microcirculation abnormalities for sepsis by inhibiting IL-17 signaling pathway, complement-coagulation cascades signaling pathway and VEGF signaling pathway.PMID:37267690 | DOI:10.1016/j.phymed.2023.154910

Food Chem. 2023 May 20;424:136377. doi: 10.1016/j.foodchem.2023.136377. Online ahead of print.ABSTRACTPecan nuts are highly enriched in phenolic compounds, which contribute to the health benefits of pecans. Phenolic compounds represent the main oxidation reaction substrates, thus leading to quality deterioration, namely pellicle browning or a decrease in beneficial effects during pecan storage. Hence, four different storage conditions were performed for 180 d to simulate real production situations. Targeted metabolomics was chosen to identify the specific phenolic compounds involved in quality deterioration under different storage conditions in 0, 90, and 180 d samples. A total of 118 phenolic compounds were detected, nine of which were identified for the first time in pecan. The total phenolic content (TPC) and antioxidant capacities initially demonstrated high scores, after which they tended to decrease during the storage process. The significantly modified phenolic compounds during storage were selected as the metabolite markers of pecan quality deterioration, including catechin, procyanidin (PA) trimer, PA tetramer, trigalloyl hexahydroxydiphenoyl (HHDP) glucose, and tetragalloyl hexoside. Fresh pecan kernels resulted in more pronounced changes in hydrolysable tannins (HTs), whereas dry kernels resulted in the most accentuated changes in condensed tannins (CTs). To the best of our knowledge, this is the first attempt to study individual phenolic changes during storage of pecan in such massive amounts. The results can offer a valuable theoretical basis for future control of pecan quality deterioration through phenolics during storage.PMID:37267651 | DOI:10.1016/j.foodchem.2023.136377

Poult Sci. 2023 May 23;102(8):102753. doi: 10.1016/j.psj.2023.102753. Online ahead of print.ABSTRACTHere, we examined the effects of crossbreeding and sex on growth performance, slaughter performance, and meat quality in Xingguo gray (XG) goose, using transcriptomic and metabolomic techniques. The experiment was conducted using 400 goslings (1-day old) of 2 genotypes: the XG breed and its ternary hybrids [F2 geese; (XG Goose♂ × Yangzhou Goose♀)♀ × Shitou Goose♂]. The goslings were divided into 4 groups: female XG, male XG, female F2 geese, and male F2 geese, and growth parameters were examined at 70 d of age, using 30 birds from each group. Following slaughter, samples of breast and thigh muscles were collected from each group for chemical, metabolome, and transcriptome analyses. Growth rate, live body and slaughter weights, meat chemical composition, and muscle fiber diameter were affected by crossbreeding and sex. Crossbreeding significantly improved the dressing percentage, semieviscerated rate, eviscerated yield, and abdominal fat yield of XG geese. To clarify the potential regulatory network affected by crossbreeding and sex, we used RNA-seq and nontargeted metabolomics to detect changes in male and female goose breast muscle. The transcriptome results showed that there were 534, 323, 297, and 492 differently expressed genes (DEGs) among the 4 comparison groups (XG-Female vs. F2-Female, XG-Male vs. F2-Male, F2-Male vs. F2-Female, and XG-Male vs. XG-Female, respectively) that were mainly related to muscle growth and development and fatty acid metabolism pathways. A total of 141 significantly differentially accumulated metabolites (DAMs) were enriched in serine and threonine, propionate, and pyruvate metabolism. Finally, we comprehensively analyzed the metabolome and transcriptome data and found that many DEGs and DAMs played crucial roles in lipid metabolism and muscle growth and development. In summary, crossbreeding can improve XG goose production performance and affect breast muscle gene expression and metabolites in both female and male geese.PMID:37267641 | DOI:10.1016/j.psj.2023.102753

PLoS One. 2023 Jun 2;18(6):e0286692. doi: 10.1371/journal.pone.0286692. eCollection 2023.ABSTRACTFlavin-containing monooxygenase 5 (FMO5) is a member of the FMO family of proteins, best known for their roles in the detoxification of foreign chemicals and, more recently, in endogenous metabolism. We have previously shown that Fmo5-/- mice display an age-related lean phenotype, with much reduced weight gain from 20 weeks of age. The phenotype is characterized by decreased fat deposition, lower plasma concentrations of glucose, insulin and cholesterol, higher glucose tolerance and insulin sensitivity, and resistance to diet-induced obesity. In the present study we report the use of metabolomic and transcriptomic analyses of livers of Fmo5-/- and wild-type mice to identify factors underlying the lean phenotype of Fmo5-/- mice and gain insights into the function of FMO5. Metabolomics was performed by the Metabolon platform, utilising ultrahigh performance liquid chromatography-tandem mass spectroscopy. Transcriptomics was performed by RNA-Seq and results analysed by DESeq2. Disruption of the Fmo5 gene has wide-ranging effects on the abundance of metabolites and expression of genes in the liver. Metabolites whose concentration differed between Fmo5-/- and wild-type mice include several saturated and monounsaturated fatty acids, complex lipids, amino acids, one-carbon intermediates and ADP-ribose. Among the genes most significantly and/or highly differentially expressed are Apoa4, Cd36, Fitm1, Hspa5, Hyou1, Ide, Me1 and Mme. The results reveal that FMO5 is involved in upregulating the NRF2-mediated oxidative stress response, the unfolded protein response and response to hypoxia and cellular stress, indicating a role for the enzyme in adaptation to oxidative and metabolic stress. FMO5 also plays a role in stimulating a wide range of metabolic pathways and processes, particularly ones involved in lipid homeostasis, the uptake and metabolism of glucose, the generation of cytosolic NADPH, and in one-carbon metabolism. The results predict that FMO5 acts by stimulating the NRF2, XBP1, PPARA and PPARG regulatory pathways, while inhibiting STAT1 and IRF7 pathways.PMID:37267233 | DOI:10.1371/journal.pone.0286692

J Ocul Pharmacol Ther. 2023 Jun 2. doi: 10.1089/jop.2023.0006. Online ahead of print.ABSTRACTBackground: Prostaglandin (PG) receptor agonists are the first-line eyedrop medication treatment for glaucoma. The pathophysiology of this disease is not completely known, and elevated intraocular pressure (IOP) is the key risk factor. The membranes of the axons (of the retinal ganglion cells) passing through the optic nerve (ON) head experience significant damage. Lipids are an essential component of the cell's membranes, and their profile changes owing to neurodegeneration. In this investigation, three agonists for distinct PG receptors were used to lower IOP and to determine their effect on the ON lipids. We utilized DBA/2J mice as a model of progressive IOP increase and C57BL/6J mice as a model of ON crush. Methods: DBA/2J and C57BL/6J mice were treated daily for 2 weeks with Latanoprost, PF-04217329, or Rivenprost. The IOP was measured every 2 days and pattern electroretinogram was conducted for DBA/2J throughout the study. Lipidomics of ONs were performed for each model and treatment group. Results: Of the tested compounds, Latanoprost and Rivenprost were the most effective agents decreasing IOP in DBA/2J mice. Triglyceride levels increased in the ONs of DBA/2J mouse model, but phosphatidylethanolamine levels underwent highest level changes in the C57BL/6J mouse model when treated with Latanoprost. Conclusions: Topical ocular FP- and EP4-receptor agonists appreciably lowered IOP in the DBA/2J mice representing pigmentary glaucoma. The observed changes in ON lipidomics in the different models of neurodegeneration suggest possible use of such measures in the development of more effective medicines for both IOP reduction and ON protection.PMID:37267222 | DOI:10.1089/jop.2023.0006

Toxicol Sci. 2023 Jun 2:kfad056. doi: 10.1093/toxsci/kfad056. Online ahead of print.ABSTRACTDevelopmental exposure to the persistent environmental pollutant, polybrominated diphenyl ethers (PBDEs), is associated with increased diabetes prevalence. The microbial tryptophan metabolite, indole 3-propionic acid (IPA), is associated with reduced risk of type-2 diabetes and lower-grade inflammation and is a PXR activator. To explore the role of IPA in modifying the PBDE developmental toxicity, we orally exposed humanized PXR-transgenic (hPXR-TG) mouse dams to vehicle, 0.1 mg/kg/day DE-71 (an industrial PBDE mixture), DE-71+IPA (20 mg/kg/day), or IPA, from 4-weeks preconception to the end of lactation. Pups were weaned at 21-days of age and IPA supplementation continued in the corresponding treatment groups. Tissues were collected at various ages until 6 months of age (n = 5 per group). In general, the effect of maternal DE-71 exposure on the gut microbiome of pups was amplified over time. The regulation of hepatic cytokines and prototypical xenobiotic-sensing transcription factor target genes by DE-71 and IPA was age- and sex-dependent, where DE-71-mediated mRNA increased selected cytokines (Il10, Il12p40, Il1β [both sexes], and [males]). The hepatic mRNA of the AhR target gene Cyp1a2 was increased by maternal DE-71 and DE-71+IPA exposure at PND21 but intestinal Cyp1a1 was not altered by any of the exposures and ages. Maternal DE-71 exposure persistently increased serum indole, a known AhR ligand, in age- and sex-dependent manner. In conclusion, maternal DE-71 exposure produced a pro-inflammatory signature along the gut-liver axis, including gut dysbiosis, dysregulated tryptophan microbial metabolism, attenuated PXR signaling, and elevated AhR signaling in post-weaned hPXR-TG pups over time, which was partially corrected by IPA supplementation.PMID:37267213 | DOI:10.1093/toxsci/kfad056

Bioinformatics. 2023 Jun 2:btad358. doi: 10.1093/bioinformatics/btad358. Online ahead of print.ABSTRACTSUMMARY: mpwR is an R package for a standardized comparison of mass spectrometry (MS)-based proteomic label-free workflows recorded by data-dependent or data-independent spectral acquisition. The user-friendly design allows easy access to compare the influence of sample preparation procedures, combinations of liquid chromatography (LC)-MS setups, as well as intra- and inter-software differences on critical performance measures across an unlimited number of analyses. mpwR supports outputs of commonly used software for bottom-up proteomics, such as ProteomeDiscoverer, Spectronaut, MaxQuant and DIA-NN.AVAILABILITY: mpwR is available as an open-source R package. Release versions can be accessed on CRAN (https://CRAN.R-project.org/package=mpwR) for all major operating systems. The development version is maintained on GitHub (https://github.com/okdll/mpwR) and full documentation with examples and workflow templates is provided via the package website (https://okdll.github.io/mpwR/).PMID:37267150 | DOI:10.1093/bioinformatics/btad358

Forensic Sci Med Pathol. 2023 Jun 2. doi: 10.1007/s12024-023-00643-0. Online ahead of print.ABSTRACTEstimation of the postmortem interval (PMI), especially the early PMI, plays a key role in forensic practice. Although several studies based on metabolomics approaches have presented significant findings for PMI estimation, most did not examine the effects of ambient temperature. In this study, gas chromatography-mass spectrometry (GC‒MS)‒based metabolomics was adopted to explore the changes in metabolites in the cardiac blood of suffocated rats at various ambient temperatures (5 °C, 15 °C, 25 °C, and 35 °C) from 0 to 24 h after death. Isoleucine, alanine, proline, valine, glycerol, glycerol phosphate, xanthine, and hypoxanthine were found to contribute to PMI in all temperature groups. Hypoxanthine and isoleucine were chosen to establish estimation models (equations) with an interpolation function using PMI as the dependent variable (f(x, y)), relative intensity as the independent variable x, and temperature as the independent variable y. Thereafter, these two models were validated with predictive samples and shown to have potential predictive ability. The findings indicate that isoleucine, alanine, proline, valine, glycerol, glycerol phosphate, xanthine, and hypoxanthine may be significant for PMI estimation at various ambient temperatures. Furthermore, a method to determine PMI based on ambient temperature and PMI-related metabolites was explored, which may provide a basis for future studies and practical applications.PMID:37266864 | DOI:10.1007/s12024-023-00643-0

J Comp Physiol B. 2023 Jun 2. doi: 10.1007/s00360-023-01500-w. Online ahead of print.ABSTRACTSeveral earthworm species are known to be able to withstand freezing. At the biochemical level, this ability is based on cryoprotectant accumulation as well as several other mechanisms. In this study, we used 1H NMR to investigate metabolomic changes in two freeze-tolerant earthworm taxa, Dendrobaena octaedra and one of the genetic lineages of Eisenia sp. aff. nordenskioldi f. pallida. A total of 45 metabolites were quantified. High concentrations of glucose were present in frozen tissues of both taxa. No other putative cryoprotectants were found. We detected high levels of glycolysis end products and succinate in frozen animals, indicating the activation of glycolysis. Concentrations of many other substances also significantly increased. On the whole, metabolic change in response to freezing was much more pronounced in the specimens of Eisenia sp. aff. nordenskioldi f. pallida, including signs of nucleotide degradation.PMID:37266592 | DOI:10.1007/s00360-023-01500-w

Eur J Nutr. 2023 Jun 2. doi: 10.1007/s00394-023-03182-0. Online ahead of print.ABSTRACTBACKGROUND: The skeletal muscle mass decreases with age and the responsiveness of aging muscles' protein synthesis rate (MPS) to protein intake seems to deteriorate.OBJECTIVE: This study investigated the impact of 12 months of protein supplementation with or without physical exercise training on the basal and postprandial MPS and the skeletal muscle metabolome of healthy older Danes (> 65 years, 29 females/37 males).METHODS: Subjects were randomized to follow one of five intervention groups: (1) carbohydrate, (2) collagen protein, (3) whey protein, (4) home-based light resistance training with whey protein, and (5) center-based heavy-load resistance training with whey protein. Before and after the intervention, a tracer infusion trial was conducted to measure basal and postprandial MPS in response to intake of a cocktail consisting of 20 g whey hydrolysate + 10 g glucose. In addition, the skeletal muscle metabolome was measured using gas chromatography-mass spectrometry (GC-MS) at basal state and 4 h after the intake of the cocktail.RESULTS: One year of daily protein or carbohydrate supplementation did not alter the basal and protein-stimulated postprandial muscle protein synthesis rate or the muscle metabolome of healthy older Danes. Basal MPS (%/h) at baseline for all subjects were 0.0034 ± 0,011 (mean ± SD). In contrast to previous studies, no difference was observed in basal MPS between males and females (p = 0.75). With the developed untargeted GC-MS methodology, it was possible to detect and tentatively annotate > 70 metabolites from the human skeletal muscle samples.CONCLUSION: One year of protein supplementation in comparison to an isocaloric-control supplement seems to affect neither the MPS at basal or postprandial state nor the skeletal muscle metabolome.CLINICAL TRIAL REGISTRY: Number: NCT02115698, clinicaltrials.gov/ct2/show/NCT02115698.PMID:37266586 | DOI:10.1007/s00394-023-03182-0

Front Immunol. 2023 May 17;14:1128239. doi: 10.3389/fimmu.2023.1128239. eCollection 2023.ABSTRACTINTRODUCTION: Interstitial lung disease (ILD) is a heterogenous group of lung disorders where destruction and incomplete regeneration of the lung parenchyma often results in persistent architectural distortion of the pulmonary scaffold. Continuous mesenchyme-centered, disease-relevant signaling likely initiates and perpetuates the fibrotic remodeling process, specifically targeting the epithelial cell compartment, thereby destroying the gas exchange area.METHODS: With the aim of identifying functional mediators of the lung mesenchymal-epithelial crosstalk with potential as new targets for therapeutic strategies, we developed a 3D organoid co-culture model based on human induced pluripotent stem cell-derived alveolar epithelial type 2 cells that form alveolar organoids in presence of lung fibroblasts from fibrotic-ILD patients, in our study referring to cases of pulmonary fibrosis, as well as control cell line (IMR-90).RESULTS: While organoid formation capacity and size was comparable in the presence of fibrotic-ILD or control lung fibroblasts, metabolic activity was significantly increased in fibrotic-ILD co-cultures. Alveolar organoids cultured with fibrotic-ILD fibroblasts further demonstrated reduced stem cell function as reflected by reduced Surfactant Protein C gene expression together with an aberrant basaloid-prone differentiation program indicated by elevated Cadherin 2, Bone Morphogenic Protein 4 and Vimentin transcription. To screen for key mediators of the misguided mesenchymal-to-epithelial crosstalk with a focus on disease-relevant inflammatory processes, we used mass spectrometry and characterized the secretome of end stage fibrotic-ILD lung fibroblasts in comparison to non-chronic lung disease (CLD) patient fibroblasts. Out of the over 2000 proteins detected by this experimental approach, 47 proteins were differentially abundant comparing fibrotic-ILD and non-CLD fibroblast secretome. The fibrotic-ILD secretome profile was dominated by chemokines, including CXCL1, CXCL3, and CXCL8, interfering with growth factor signaling orchestrated by Interleukin 11 (IL11), steering fibrogenic cell-cell communication, and proteins regulating extracellular matrix remodeling including epithelial-to-mesenchymal transition. When in turn treating alveolar organoids with IL11, we recapitulated the co-culture results obtained with primary fibrotic-ILD fibroblasts including changes in metabolic activity.CONCLUSION: We identified mediators likely contributing to the disease-perpetuating mesenchymal-to-epithelial crosstalk in ILD. In our alveolar organoid co-cultures, we were able to highlight the importance of fibroblast-initiated aberrant epithelial differentiation and confirmed IL11 as a key player in fibrotic-ILD pathogenesis by unbiased fibroblast secretome analysis.PMID:37266432 | PMC:PMC10230276 | DOI:10.3389/fimmu.2023.1128239

Front Pharmacol. 2023 May 17;14:1189971. doi: 10.3389/fphar.2023.1189971. eCollection 2023.ABSTRACTIntroduction: Aconite is a form of traditional Chinese medicine (TCM) that has been widely used to treat diarrhea for thousands of years. However, it is not clear whether the anti-diarrhea role of aconite aqueous extract (AA) is associated with regulation of the gut microbiota or with bile acid (BA) metabolism. This study aimed to confirm whether AA exerts its anti-diarrhea effects by regulating the gut microbiota and BA metabolism. Methods: The therapeutic effect of AA in a mouse model of diarrhea was measured based on analysis of body weight, fecal water content, diarrhea scores, intestinal propulsion rate, colonic pathology, and colonic immunohistochemistry. In addition, 16S rRNA high-throughput sequencing was conducted to analyze the effect of AA on the gut microbiota, and targeted metabolomics was employed to analyze the effect of AA on metabolism of BAs. Results: The results showed that treatment with AA reduced fecal water content and diarrhea scores, inhibited intestinal propulsion rate and pathological changes in the colon, and increased AQP3 and AQP4 content in the colon. In addition, AA was found to be capable of regulating the gut microbiota. Effects included increasing its richness (according to the ACE and Chao1 indices); altering the gut microbiota community structure (PCA, PCoA, and NMDS); increasing the relative abundance of norank_f_Muribaculaceae, Ruminococcus, Lachnospiraceae_NK4A136_group, Prevotellaceae_UCG-001, and norank_f_norank_o_Clostridia_UCG-014; and decreasing the relative abundance of Escherichia-Shigella, unclassified_f_Ruminococcaceae, Ruminococcus_torques_group, and Parasutterella. More importantly, AA significantly increased fecal TCA (a primary BA) and DCA, LCA, GDCA, dehydro-LCA, and 12-keto-LCA (secondary BAs), thus restoring BA homeostasis. Moreover, AA increased the ratios of DCA/CA, DCA/TCA, and LCA/CDCA and decreased the ratios of TLCA/LCA, GLCA/LCA, and TUDCA/UDCA. Conclusion: The anti-diarrhea effect of AA was associated with restoration of the gut microbiota and BA metabolism-related homeostasis. The results of this study provide insights into the application of AA and the treatment of diarrhea.PMID:37266146 | PMC:PMC10229775 | DOI:10.3389/fphar.2023.1189971

Front Bioeng Biotechnol. 2023 May 15;11:1167892. doi: 10.3389/fbioe.2023.1167892. eCollection 2023.ABSTRACTGas fermentation has emerged as a sustainable route to produce fuels and chemicals by recycling inexpensive one-carbon (C1) feedstocks from gaseous and solid waste using gas-fermenting microbes. Currently, acetogens that utilise the Wood-Ljungdahl pathway to convert carbon oxides (CO and CO2) into valuable products are the most advanced biocatalysts for gas fermentation. However, our understanding of the functionalities of the genes involved in the C1-fixing gene cluster and its closely-linked genes is incomplete. Here, we investigate the role of two genes with unclear functions-hypothetical protein (hp; LABRINI_07945) and CooT nickel binding protein (nbp; LABRINI_07950)-directly adjacent and expressed at similar levels to the C1-fixing gene cluster in the gas-fermenting model-acetogen Clostridium autoethanogenum. Targeted deletion of either the hp or nbp gene using CRISPR/nCas9, and phenotypic characterisation in heterotrophic and autotrophic batch and autotrophic bioreactor continuous cultures revealed significant growth defects and altered by-product profiles for both ∆hp and ∆nbp strains. Variable effects of gene deletion on autotrophic batch growth on rich or minimal media suggest that both genes affect the utilisation of complex nutrients. Autotrophic chemostat cultures showed lower acetate and ethanol production rates and higher carbon flux to CO2 and biomass for both deletion strains. Additionally, proteome analysis revealed that disruption of either gene affects the expression of proteins of the C1-fixing gene cluster and ethanol synthesis pathways. Our work contributes to a better understanding of genotype-phenotype relationships in acetogens and offers engineering targets to improve carbon fixation efficiency in gas fermentation.PMID:37265994 | PMC:PMC10230548 | DOI:10.3389/fbioe.2023.1167892

MedComm (2020). 2023 May 30;4(3):e302. doi: 10.1002/mco2.302. eCollection 2023 Jun.ABSTRACTEndometriosis is a common, estrogen-dependent chronic gynecological disease that endangers the reproductive system and systemic metabolism of patients. We aimed to investigate the differences in metabolic profiles in the follicular fluid between infertile patients with endometriosis and controls. A total of 25 infertile patients with endometriosis and 25 infertile controls who were similar in age, BMI, fertilization method and ovulation induction treatment were recruited in this study. Metabolomics analysis of follicular fluid was performed by two methods of high-performance liquid chromatography tandem mass spectrometry. There were 36 upregulated and 17 downregulated metabolites in the follicular fluid of patients in the endometriosis group. KEGG pathway analysis revealed that these metabolites were enriched in phenylalanine, tyrosine and tryptophan biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine metabolism and pyrimidine metabolism pathways. A biomarker panel consisting of 20 metabolites was constructed by random forest, with an accuracy of 0.946 and an AUC of 0.988. This study characterizes differences in follicular fluid metabolites and associated pathway profiles in infertile patients with endometriosis. These findings can provide a better comprehensive understanding of the disease and a new direction for the study of oocyte quality, as well as potential metabolic markers for the prognosis of endometriosis.PMID:37265938 | PMC:PMC10229744 | DOI:10.1002/mco2.302

Hum Reprod Open. 2023 May 5;2023(2):hoad013. doi: 10.1093/hropen/hoad013. eCollection 2023.ABSTRACTSTUDY QUESTIONS: The primary objective of this study is to determine what parental factors or specific ART may influence the risk for adverse cardiometabolic outcomes among children so conceived and their parents. The secondary objective of this study is to prospectively examine the effects of infertility or ART on the intrauterine environment, obstetric and neonatal outcomes.WHAT IS KNOWN ALREADY: Pregnancies conceived with ART are at an increased risk of being affected by adverse obstetric and neonatal outcomes when compared to spontaneously conceived (SC) pregnancies among fertile women. Small cohort studies have suggested ART-conceived children may have a higher risk of long-term cardiometabolic disturbances as well. Currently, few studies have compared long-term cardiometabolic outcomes among ART-conceived children and non-IVF treated (NIFT) children, to children conceived spontaneously to parents with infertility (subfertile parents).STUDY DESIGN SIZE DURATION: The Developmental Epidemiological Study of Children born through Reproductive Technologies (DESCRT) is a prospective cohort study that aims to: establish a biobank and epidemiological cohort of children born to subfertile or infertile parents who either conceived spontaneously (without assistance) or used reproductive technologies to conceive (all offspring were from couples assessed and/or treated in the same institute); prospectively examine the effects of infertility or ART on the intrauterine environment, obstetric and neonatal outcomes; and determine what parental factors or ART may influence the cardiometabolic risk of children so conceived. Pregnancies and resultant children will be compared by mode of conception, namely offspring that were conceived without medical assistance or SC or following NIFT, IVF with fresh embryo transfer or frozen embryo transfer (FET), and by fertilization method (conventional versus ICSI). DESCRT has a Child group evaluating long-term outcomes of children as well as a Pregnancy group that will compare obstetric and neonatal outcomes of children conceived since the commencement of the study. Recruitment started in May of 2017 and is ongoing. When the study began, we estimated that ∼4000 children would be eligible for enrollment.PARTICIPANTS/MATERIALS SETTING METHODS: Eligible participants are first-trimester pregnancies (Pregnancy group) or children (Child group) born to parents who were evaluated at an infertility center in the University of California, San Francisco, CA, USA who were SC or conceived after reproductive treatments (NIFT, IVF ± ICSI, FET). Children in the Child group were conceived at UCSF and born from 2001 onwards. In the Pregnancy group, enrollment began in November of 2017.The primary outcome is the cardiometabolic health of offspring in the Child group, as measured by blood pressure and laboratory data (homeostatic model assessment for insulin resistance (HOMA-IR), oral glucose disposition). There are several secondary outcome measures, including: outcomes from parental survey response (assessing parent/child medical history since delivery-incidence of cardiometabolic adverse events), anthropomorphic measurements (BMI, waist circumference, skinfold thickness), and laboratory data (liver enzymes, lipid panel, metabolomic profiles). In the Pregnancy group, outcomes include laboratory assessments (bhCG, maternal serum analytes, soluble fms-like tyrosine kinase-1 (sFLT-1), and placental growth factor (PlGF)) and placental assessments (placental volume in the second and third trimester and placental weight at delivery). Importantly, aliquots of blood and urine are stored from parents and offspring as part of a biobank. The DESCRT cohort is unique in two ways. First, there is an extensive amount of clinical and laboratory treatment data: parental medical history and physical examination at the time of treatment, along with ovarian reserve and infertility diagnosis; and treatment specifics: for example, fertilization method, culture O2 status, embryo quality linked to each participant. These reproductive data will aid in identifying explanatory variables that may influence the primary cardiometabolic outcomes of the offspring-and their parents. Second, the DESCRT control group includes pregnancies and children SC from parents with subfertility, which may help to assess when infertility, as opposed to reproductive treatments, may be affecting offspring cardiometabolic health.STUDY FUNDING/COMPETING INTERESTS: This study is funded by the National Institutes of Health NICHD (1R01HD084380-01A1). A.J.A. is a shareholder in Carrot and consultant for Flo Health. The other authors have no conflicts of interest.TRIAL REGISTRATION NUMBER: NCT03799107.TRIAL REGISTRATION DATE: 10 January 2019.DATE OF FIRST PATIENT’S ENROLLMENT: 10 May 2017.PMID:37265937 | PMC:PMC10229433 | DOI:10.1093/hropen/hoad013

Front Oncol. 2023 May 17;13:1163289. doi: 10.3389/fonc.2023.1163289. eCollection 2023.ABSTRACTGlioma is one of the most common malignant primary brain tumours in adults, of which, glioblastoma is the most prevalent and malignant entity. Glioma is often diagnosed at a later stage of disease progression, which means it is associated with significant mortality and morbidity. Therefore, there is a need for earlier diagnosis of these tumours, which would require sensitive and specific biomarkers. These biomarkers could better predict glioma onset to improve diagnosis and therapeutic options for patients. While liquid biopsies could provide a cheap and non-invasive test to improve the earlier detection of glioma, there is little known on pre-diagnostic biomarkers which predate disease detection. In this review, we examine the evidence in the literature for pre-diagnostic biomarkers in glioma, including metabolomics and proteomics. We also consider the limitations of these approaches and future research directions of pre-diagnostic biomarkers for glioma.PMID:37265788 | PMC:PMC10229864 | DOI:10.3389/fonc.2023.1163289

Chin Herb Med. 2023 Feb 16;15(2):310-316. doi: 10.1016/j.chmed.2022.06.013. eCollection 2023 Apr.ABSTRACTOBJECTIVE: The barks, leaves, and branches of Cinnamomum cassia have been historically used as a traditional Chinese medicine, spice, and food preservative, in which phenylpropanoids are responsible compounds. However phenylpropanoid biosynthesis pathways are not clear in C. cassia. We elucidated the pathways by descriptive analyses of differentially expressed genes related to phenylpropanoid biosynthesis as well as to identify various phenylpropanoid metabolites.METHODS: Chemical analysis, metabolome sequencing, and transcriptome sequencing were performed to investigate the molecular mechanisms underlying the difference of active components content in the barks, branches and leaves of C. cassia.RESULTS: Metabolomic analysis revealed that small amounts of flavonoids, coumarine, and cinnamaldehyde accumulated in both leaves and branches. Transcriptome analysis showed that genes associated with phenylpropanoid and flavonoid biosynthesis were downregulated in the leaves and branches relative to the barks. The observed differences in essential oil content among the three tissues may be attributable to the differential expression of genes involved in the phenylpropanoid and flavonoid metabolic pathways.CONCLUSION: This study identified the key genes in the phenylpropanoid pathway controling the flavonoid, coumarine, and cinnamaldehyde contents in the barks, branches and leaves by comparing the transcriptome and metabolome. These findings may be valuable in assessing phenylpropanoid and flavonoid metabolites and identifying specific candidate genes that are related to the synthesis of phenylpropanoids and flavonoids in C. cassia.PMID:37265774 | PMC:PMC10230625 | DOI:10.1016/j.chmed.2022.06.013

Chin Herb Med. 2022 Nov 21;15(2):298-309. doi: 10.1016/j.chmed.2022.11.002. eCollection 2023 Apr.ABSTRACTOBJECTIVE: Diterpenoids with a wide variety of biological activities from Anoectochilus roxburghii, a precious medicinal plant, are important active components. However, due to the lack of genetic information on the metabolic process of diterpenoids in A. roxburghii, the genes involved in the molecular regulation mechanism of diterpenoid metabolism are still unclear. This study revealed the complex metabolic genes for diterpenoids biosynthesis in different organs of A. roxburghii by combining analysis of transcriptomics and metabolomics.METHODS: The differences in diterpenoid accumulation in roots, stems and leaves of A. roxburghii were analyzed by metabonomic analysis, and its metabolic gene information was obtained by transcriptome sequencing. Then, the molecular mechanism of differential diterpenoid accumulation in different organs of A. roxburghii was analyzed from the perspective of gene expression patterns.RESULTS: A total of 296 terpenoid metabolites were identified in the five terpenoid metabolic pathways in A. roxburghii. There were 38, 34, and 18 diterpenoids with different contents between roots and leaves, between leaves and stems, and between roots and stems, respectively. Twenty-nine metabolic enzyme genes with 883 unigenes in the diterpenoid synthesis process were identified, and the DXS and FDPS in the terpenoid backbone biosynthesis stage and CPA, GA20ox, GA3ox, GA2ox, and MAS in the diterpenoid biosynthesis stage were predicted to be the key metabolic enzymes for the accumulation of diterpenoids. In addition, 14 key transcription factor coding genes were predicted to be involved in the regulation of the diterpenoid biosynthesis. The expression of genes such as GA2ox, MAS, CPA, GA20ox and GA3ox might be activated by some of the 14 transcription factors. The transcription factor NTF-Y and PRE6 were predicted to be the most important transcription factors.CONCLUSION: This study determined 29 metabolic enzyme genes and predicted 14 transcription factors involved in the molecular regulation mechanism of diterpenoid metabolism in A. roxburghii, which provided a reference for the further study of the molecular regulation mechanism of the accumulation of diterpenoids in different organs of A. roxburghii.PMID:37265764 | PMC:PMC10230631 | DOI:10.1016/j.chmed.2022.11.002

Front Plant Sci. 2023 May 17;14:1179553. doi: 10.3389/fpls.2023.1179553. eCollection 2023.ABSTRACTMaking tea from jujube leaves changed the chemical composition and aroma composition of jujube leaves. Here, Through LC-MS, GC-IMS, and GC-MS technology, we have revealed the effect of jujube leaf processing changes on metabolites. LC-MS identified 468 non-volatile metabolites, while GC-IMS and GC-MS detected 52 and 24 volatile metabolites, respectively. 109 non-volatile metabolites exhibiting more pronounced differences were screened. Most lipids and lipid-like molecules, organic acids, amino acids, and flavonoids increased significantly after processing. GC-IMS and GC-MS analysis revealed that the contents of aldehydes and ketones were significantly increased, while esters and partial alcohols were decreased after processing into jujube leaf tea. The main flavor substances of fresh jujube leaf and jujube leaf tea were eugenol and (E) - 2-Hexenal, respectively. Furthermore, amino acids and lipids were closely linked to the formation of volatile metabolites. Our study provided new insights into the changes in metabolites of jujube leaves processed into jujube leaf tea, and had great potential for industrial application. It laid a foundation for further research on fruit tree leaf tea.PMID:37265633 | PMC:PMC10231682 | DOI:10.3389/fpls.2023.1179553

Front Plant Sci. 2023 May 17;14:1125560. doi: 10.3389/fpls.2023.1125560. eCollection 2023.ABSTRACTClimate change is a major concern in agriculture; in grapevine production, climate change can affect yield and wine quality as they depend on the complex interactions between weather, plant material, and viticultural techniques. Wine characteristics are strongly influenced by microclimate of the canopy affecting primary and secondary metabolites of the grapevine. Air temperature and water availability can influence sugar and acid concentration in grapes and relative wines, and their content of volatile compounds such as norisoprenoids. This becomes relevant in sparkling wine production where grapes are generally harvested at a relatively low pH, high acidity, and low sugar content and where the norisoprenoids significantly contributes to the final aroma of the wine. The effect of climate change on grapevine and wine, therefore, calls for the implementation of on-field adaptation strategies. Among them canopy management through leaf removal and shading have been largely investigated in the wine growing sector. The present study, conducted over 4 years (2010-2013) aims at investigating how leaf removal and artificial shading strategies affect grape maturation, must quality and the production of norisoprenoids, analyzed using an untargeted approach, in sparkling wine. Specifically, this paper investigates the effect of meteorological conditions (i.e., water availability and temperatures) and the effect of leaf removal and shading on Vitis vinifera L. cv. Chardonnay and Pinot noir, which are suitable to produce sparkling wine in the DOCG Franciacorta wine growing area (Lombardy, Italy). The effect of leaf removal and shading practices on norisoprenoids has been the focus of the study. No defoliation and artificial shading treatments play an important role in the preservation of the acidity in warm seasons and this suggests calibrating defoliation activities in relation to the meteorological trend without standardized procedures. This is particularly relevant in the case of sparkling wine, where the acidity is essential to determine wine quality. The enhanced norisoprenoid aromas obtained with a total defoliation represent a further element to direct defoliation and shading strategies. The obtained results increase knowledge about the effect of different defoliation and artificial shading applications in relation to meteorological condition supporting the management decision-making in the Franciacorta wine growing area.PMID:37265632 | PMC:PMC10229778 | DOI:10.3389/fpls.2023.1125560