PubMed

Front Plant Sci. 2023 Feb 9;14:1129515. doi: 10.3389/fpls.2023.1129515. eCollection 2023.ABSTRACTAlternaria alternata is a necrotrophic fungal pathogen with a broad host range that causes widespread and devastating disease in sweet cherry (Prunus avium). We selected a resistant cultivar (RC) and a susceptible cultivar (SC) of cherry and used a combined physiological, transcriptomic, and metabolomic approach to investigate the molecular mechanisms underlying the plant's resistance to A. alternata, of which little is known. We found that A. alternata infection stimulated the outbreak of reactive oxygen species (ROS) in cherry. The responses of the antioxidant enzymes and chitinase to disease were observed earlier in the RC than in the SC. Moreover, cell wall defense ability was stronger in the RC. Differential genes and metabolites involved in defense responses and secondary metabolism were primarily enriched in the biosynthesis of phenylpropanoids, tropane, piperidine and pyridine alkaloids, flavonoids, amino acids, and α-linolenic acid. Reprogramming the phenylpropanoid pathway and the α-linolenic acid metabolic pathway led to lignin accumulation and early induction of jasmonic acid signaling, respectively, in the RC, which consequently enhanced antifungal and ROS scavenging activity. The RC contained a high level of coumarin, and in vitro tests showed that coumarin significantly inhibited A. alternata growth and development and had antifungal effect on cherry leaves. In addition, differentially expressed genes encoding transcription factors from the MYB, NAC, WRKY, ERF, and bHLH families were highly expressed, they could be the key responsive factor in the response of cherry to infection by A. alternata. Overall, this study provides molecular clues and a multifaceted understanding of the specific response of cherry to A. alternata.PMID:36844070 | PMC:PMC9947566 | DOI:10.3389/fpls.2023.1129515

Front Plant Sci. 2023 Feb 9;14:1030236. doi: 10.3389/fpls.2023.1030236. eCollection 2023.ABSTRACTINTRODUCTION: Sweet potato is an important staple food crop in the world and contains abundant secondary metabolites in its underground tuberous roots. The large accumulation of several categories of secondary metabolites result in colorful pigmentation of the roots. Anthocyanin, is a typical flavonoid compound present in purple sweet potatoes and it contributes to the antioxidant activity.METHODS: In this study, we developed joint omics research via by combing the transcriptomic and metabolomic analysis to explore the molecular mechanisms underlying the anthocyanin biosynthesis in purple sweet potato. Four experimental materials with different pigmentation phenotypes, 1143-1 (white root flesh), HS (orange root flesh), Dianziganshu No.88 (DZ88, purple root flesh), and Dianziganshu No.54 (DZ54, dark purple root flesh) were comparably studied.RESULTS AND DISCUSSION: We identified 38 differentially accumulated pigment metabolites and 1214 differentially expressed genes from a total of 418 metabolites and 50893 genes detected. There were 14 kinds of anthocyanin detected in DZ88 and DZ54, with glycosylated cyanidin and peonidin as the major components. The significantly enhanced expression levels of multiple structural genes involved in the central anthocyanin metabolic network, such as chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), dihydroflavonol 4-reductase (DFR), anthocyanidin synthase/leucocyanidin oxygenase (ANS), and glutathione S-transferase (GST) were manifested to be the primary reason why the purple sweet potatoes had a much higher accumulation of anthocyanin. Moreover, the competition or redistribution of the intermediate substrates (i.e. dihydrokaempferol and dihydroquercetin) between the downstream production of anthocyanin products and the flavonoid derivatization (i.e. quercetin and kaempferol) under the regulation of the flavonol synthesis (FLS) gene, might play a crucial role in the metabolite flux repartitioning, which further led to the discrepant pigmentary performances in the purple and non-purple materials. Furthermore, the substantial production of chlorogenic acid, another prominent high-value antioxidant, in DZ88 and DZ54 seemed to be an interrelated but independent pathway differentiated from the anthocyanin biosynthesis. Collectively, these data from the transcriptomic and metabolomic analysis of four kinds of sweet potatoes provide insight to understand the molecular mechanisms of the coloring mechanism in purple sweet potatoes.PMID:36844045 | PMC:PMC9951203 | DOI:10.3389/fpls.2023.1030236

Exp Dermatol. 2023 Feb 26. doi: 10.1111/exd.14780. Online ahead of print.ABSTRACTSebum is a lipid-rich mixture secreted by the sebaceous gland (SG) onto the skin surface. By penetrating through the epidermis, sebum may be involved in the regulation of epidermal and dermal cells in both healthy and diseased skin conditions. Saturated and monounsaturated fatty acids (FAs), found as free FAs (FFAs) and in bound form in neutral lipids, are essential constituents of sebum and key players of the inflammatory processes occurring in the pilosebaceous unit in acne-prone skin. Little is known on the interplay among uptake of saturated FFAs, their biotransformation, and induction of proinflammatory cytokines in sebocytes. In the human SG, palmitate (C16:0) is the precursor of sapienate (C16:1n-10) formed by insertion of a double bond (DB) at the Δ6 position catalysed by the fatty acid desaturase 2 (FADS2) enzyme. Conversely, palmitoleate (C16:1n-7) is formed by insertion of a DB at the Δ9 position catalysed by the stearoyl coenzyme A desaturase 1 (SCD1) enzyme. Other FFAs processed in the SG, also undergo these main desaturation pathways. We investigated lipogenesis and release of IL-6 and IL-8 pro-inflammatory cytokines in SZ95 sebocytes in vitro after treatment with saturated FFAs, i.e. C16:0, margarate (C17:0), and stearate (C18:0) with or without specific inhibitors of SCD1 and FADS2, and a drug with mixed inhibitory effects on FADS1 and FADS2 desaturase enzymes. C16:0 underwent extended desaturation through both SCD1 and FADS2 catalysed pathways and displayed the strongest lipoinflammatory effects. Inhibition of desaturation pathways proved to enhance lipoinflammation induced by SFAs in SZ95 sebocytes.PMID:36843338 | DOI:10.1111/exd.14780

Int J Cancer. 2023 Feb 26. doi: 10.1002/ijc.34487. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS) are highly persistent endocrine-disrupting chemicals that may contribute to breast cancer development; however, epidemiologic evidence is limited. We investigated associations between prediagnostic serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and postmenopausal breast cancer risk, overall and by hormone receptor status, in a nested case-control study of 621 cases and 621 matched controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. PFOS and PFOA levels were determined based on serum metabolomic profiling performed using ultra-performance liquid chromatography-tandem mass spectrometry. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each PFAS and breast cancer risk, overall, by estrogen receptor (ER) or progesterone receptor (PR) status, and by joint ER/PR status. We found little evidence of association between PFOS or PFOA and breast cancer risk overall. However, in subtype-specific analyses, we observed statistically significant increased risks of ER+, PR+, and ER+/PR+ tumors for the third vs. lowest quartile of serum PFOS (ORs [95% CIs]=1.59 [1.01-2.50], 2.34 [1.29-4.23], and 2.19 [1.21-3.98], respectively) and elevated but non-statistically significant ORs for the fourth quartile. Conversely, for PFOA, modest positive associations with ER-, PR-, ER+/PR-, and ER-/PR- tumors were generally seen in the upper quartiles. Our findings contribute evidence supporting positive associations between serum PFOS and hormone receptor-positive tumors, and possibly between PFOA and receptor-negative tumors. Future prospective studies incorporating tumor hormone receptor status are needed to better understand the role of PFAS in breast cancer etiology. This article is protected by copyright. All rights reserved.PMID:36843273 | DOI:10.1002/ijc.34487

New Phytol. 2023 Feb 26. doi: 10.1111/nph.18840. Online ahead of print.ABSTRACTKiwifruit (Actinidia chinensis) is one of the popular fruits worldwide, and its quality is mainly determined by key metabolites (sugars, flavonoids and vitamins). Previous works on kiwifruit are mostly done via a single omics approach or involve only limited metabolites. Consequently, the dynamic metabolomes during kiwifruit development and ripening and the underlying regulatory mechanisms are poorly understood. In this study, using high-resolution metabolomic and transcriptomic analyses, we investigated kiwifruit metabolic landscapes at 11 different developmental and ripening stages and revealed a parallel classification of 515 metabolites and their co-expressed genes into 10 distinct metabolic vs gene modules (MM vs GM). Through integrative bioinformatics coupled with functional genomic assays, we constructed a global map and uncovered essential transcriptomic and transcriptional regulatory networks for all major metabolic changes that occurred throughout the kiwifruit growth cycle. Apart from known MM vs GM for metabolites such as soluble sugars, we identified novel transcription factors that regulate the accumulation of procyanidins, vitamin C and other important metabolites. Our findings thus shed light on the kiwifruit metabolic regulatory network and provide a valuable resource for the designed improvement of kiwifruit quality.PMID:36843264 | DOI:10.1111/nph.18840

Gut Microbes. 2023 Jan-Dec;15(1):2183690. doi: 10.1080/19490976.2023.2183690.ABSTRACTCholestasis refers to impaired bile flow from the liver to the intestine. In neonates, cholestasis causes poor growth and may progress to liver failure and death. Normal bile flow requires an intact liver-gut-microbiome axis, whereby liver-derived primary bile acids are transformed into secondary bile acids. Microbial bile salt hydrolase (BSH) enzymes are responsible for the first step, deconjugating glycine- and taurine-conjugated primary bile acids. Cholestatic neonates often are treated with the potent choleretic bile acid ursodeoxycholic acid (UDCA), although interactions between UDCA, gut microbes, and other bile acids are poorly understood. To gain insight into how the liver-gut-microbiome axis develops in extreme prematurity and how cholestasis alters this maturation, we conducted a nested case-control study collecting 124 stool samples longitudinally from 24 preterm infants born at mean 27.2 ± 1.8 weeks gestation and 946 ± 249.6 g, half of whom developed physiologic cholestasis. Samples were analyzed by whole metagenomic sequencing, in vitro BSH enzyme activity assays optimized for low biomass fecal samples, and quantitative mass spectrometry to measure the bile acid metabolome. In extremely preterm neonates, acquisition of the secondary bile acid biosynthesis pathway and BSH genes carried by Clostridium perfringens are the most prominent features of early microbiome development. Cholestasis interrupts this developmental pattern. BSH gene abundance and enzyme activity are profoundly reduced in cholestatic neonates, resulting in decreased quantities of unconjugated bile acids. UDCA restores total fecal bile acid levels in cholestatic neonates, but this is due to a 522-fold increase in fecal UDCA. A majority of bile acids in early development are atypical positional and stereo-isomers of bile acids. We report novel associations linking isomeric bile acids and BSH activity to neonatal growth trajectories. These data highlight deconjugation of bile acids as a key microbial function that is acquired in early neonatal development and impaired by cholestasis.PMID:36843227 | DOI:10.1080/19490976.2023.2183690

Clin Endocrinol (Oxf). 2023 Feb 26. doi: 10.1111/cen.14899. Online ahead of print.ABSTRACTOBJECTIVE: Polycystic ovary syndrome (PCOS) is a pathophysiological disease affecting reproductive and metabolic indicators. Research has shown that kisspeptin might be involved in the regulation of pituitary hormone secretion and energy metabolism. The aim of this study was to investigate the relationship between serum kisspeptin levels and abnormal metabolism in PCOS.METHODS: Fifty patients with PCOS and 50 control patients were recruited for this study. Serum kisspeptin levels were measured via ELISA. HPLC-MS/MS metabolomics was used to study the changes in serum metabolism between the PCOS and control groups.RESULTS: Serum kisspeptin levels were significantly elevated in individuals with PCOS compared with those in healthy controls (P=0.011) and positively correlated with LH, T, FFA, BA, and LEP levels (P<0.05). Significantly dysregulated expression of several metabolites was observed in the intergroup comparisons of the high-kisspeptin PCOS, low-kisspeptin PCOS, and healthy control groups. These primarily consisted of lipid, amino acid, and carbohydrate metabolites, among which palmitic acid and N-formylkynurenine levels were lower in the high-kisspeptin group than in controls. Metabolite set enrichment analysis was also performed based on metabolites in the KEGG database. The results showed that owing to the differences in kisspeptin concentrations in individuals with PCOS, there was a significant difference in amino acid and pyruvate metabolism.CONCLUSIONS: Kisspeptin could be a potential biomarker for the diagnosis of PCOS and plays an important role in metabolic regulation in individuals with PCOS. In addition, metabolomics provides a promising method for the study of metabolic abnormalities in individuals with PCOS, which might contribute to our understanding of its mechanisms. This article is protected by copyright. All rights reserved.PMID:36843187 | DOI:10.1111/cen.14899

Phytochem Anal. 2023 Feb 26. doi: 10.1002/pca.3212. Online ahead of print.ABSTRACTBACKGROUND: Semen Aesculi, a traditional Chinese herbal medicine, has a long history of use for treating chest and abdominal pain with distension. In addition, the horse chestnut (Aesculus hippocastanum L.) is another species of Aesculus in Europe and has notable clinical significance in alleviating chronic venous insufficiency, hemorrhoids, and postoperative edema. Thus, highlighting the comparative study of Semen Aesculi and horse chestnut may broaden clinical applications.OBJECTIVES: To conduct a comprehensive comparative analysis on the chemical profiling of these two varieties and determine whether they have equivalent clinical efficacy by integrating plant metabolomics and multivariate statistical methods.METHODS: Initially, a comprehensive characterisation was performed using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) platform, and in total 44 active ingredients were identified. Then, untargeted metabolomics combined with principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) was applied for the discrimination of a German species and three official Chinese species. Next, 24 marker compounds responsible for the discrimination of different species were screened out and used to predict the species of unknown samples by genetic algorithm-optimised support vector machine (GA-SVM) with a high prediction accuracy. Finally, a heatmap visualisation was employed for clarifying the distribution of the identified active ingredients.RESULTS: The three species of Chinese Semen Aesculi showed distinct separation from each other, while European horse chestnut and Aesculus chinensis Bunge were similar in chemical composition.CONCLUSIONS: This work provided experimental evidence for further expanding the clinical application of Chinese Semen Aesculi and promoted the species identification and quality control of Semen Aesculi.PMID:36843182 | DOI:10.1002/pca.3212

Respir Res. 2023 Feb 26;24(1):63. doi: 10.1186/s12931-023-02368-8.ABSTRACTBACKGROUND: Asthma is a heterogeneous disease with high morbidity. Advancement in high-throughput multi-omics approaches has enabled the collection of molecular assessments at different layers, providing a complementary perspective of complex diseases. Numerous computational methods have been developed for the omics-based patient classification or disease outcome prediction. Yet, a systematic benchmarking of those methods using various combinations of omics data for the prediction of asthma development is still lacking.OBJECTIVE: We aimed to investigate the computational methods in disease status prediction using multi-omics data.METHOD: We systematically benchmarked 18 computational methods using all the 63 combinations of six omics data (GWAS, miRNA, mRNA, microbiome, metabolome, DNA methylation) collected in The Vitamin D Antenatal Asthma Reduction Trial (VDAART) cohort. We evaluated each method using standard performance metrics for each of the 63 omics combinations.RESULTS: Our results indicate that overall Logistic Regression, Multi-Layer Perceptron, and MOGONET display superior performance, and the combination of transcriptional, genomic and microbiome data achieves the best prediction. Moreover, we find that including the clinical data can further improve the prediction performance for some but not all the omics combinations.CONCLUSIONS: Specific omics combinations can reach the optimal prediction of asthma development in children. And certain computational methods showed superior performance than other methods.PMID:36842969 | DOI:10.1186/s12931-023-02368-8

Am J Mens Health. 2023 Jan-Feb;17(1):15579883231153018. doi: 10.1177/15579883231153018.ABSTRACTBirthplace, as a proxy for environmental exposures (e.g., diet), may influence metabolomic profiles and influence risk of cancer. This secondary analysis investigated metabolomic profile differences between foreign and U.S.-born Mexican-origin (MO) Hispanic men to shed light on potential mechanisms through which foreign- and U.S.-born individuals experience differences in cancer risk and risk factors. Plasma samples from MO Hispanic men (N = 42) who participated in a previous lifestyle intervention were collected pre-and post-intervention. Metabolomic profiles were characterized from samples using ultra performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-QTOF). Models were visualized using supervised orthogonal projections to latent structures-discriminant analysis (OPLS-DA). Progenesis QI was used for peak integration and metabolite identification. Plasma metabolomic profiles differed between foreign- and U.S.-born pre-intervention (R2 = .65) and post-intervention (R2 = .62). Metabolomic profiles differed pre- versus post-intervention (R2 = .35 and R2 = .65) for the foreign- and U.S.-born group, respectively. Both endogenous metabolites and dietary components characterized differences between foreign- and U.S.-born participants pre- and post-intervention. Plasma metabolomic profiles from MO Hispanic men differed by birthplace. These results advance our understanding of relevant exposures that may affect cancer risk among MO Hispanic men born abroad or in the United States.PMID:36842961 | DOI:10.1177/15579883231153018

J Ethnopharmacol. 2023 Feb 24:116301. doi: 10.1016/j.jep.2023.116301. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Yiyi Fuzi Baijiang formula (YFB) is a traditional Chinese medicine prescription composed of Coix seed, Radix Aconiti Lateralis and Patrinia villosa, which has been used to treat ulcerative colitis (UC) for thousands of years.AIM OF THE STUDY: To investigate the therapeutic effect and metabolic analysis of YFB formula on UC in rats induced by 2,4,6-trinitro-benzene sulfonic acid (TNBS).MATERIALS AND METHODS: Six main alkaloids in the YFB formula were determined by UPLC‒MS/MS. The rat UC model was induced by TNBS, and the therapeutic effect of YFB formula on UC was evaluated by disease activity index (DAI) score and hematoxylin-eosin (HE) staining. UPLC-QTRAP-MS metabolomics technology was used to screen potential biomarkers for YFB treatment of UC in combination with multivariate data statistics and further analyze related metabolic pathways. Western blotting was used to detect the protein levels of NLRP1, NLRP3, NLRC4, ASC, pro-caspase1 and Caspase-1 in rat liver tissues. ELISA and immunohistochemistry were used to detect the contents of interleukin (IL)-17A, IL-21, IL-22, IL-6, TNF-α, IL-1β and IL-18 in rat serum and liver tissues.RESULTS: The DAI scores of the YFB groups were significantly reduced, and colon tissue injury was significantly improved (p < 0.01). The results of metabolomics analysis revealed 29 potential biomarkers in serum and 27 potential biomarkers in liver. YFB formula can treat UC by affecting glycerophospholipid metabolism, primary bile acid biosynthesis, glyoxylic acid and dicarboxylic acid metabolism, and arginine and proline metabolism. Compared with the model group, the contents of IL-17A, IL-21, IL-22, IL-6, TNF-α, IL-1β and IL-18 in the YFB groups were decreased in a dose-dependent manner (p < 0.01). Compared with those in the model group, the protein levels of NLRP1, NLRP3, NLRC4, ASC, pro-caspase1 and Caspase-1 in the YFB groups were significantly decreased in a dose-dependent manner (p < 0.01).CONCLUSIONS: The therapeutic effect of YFB formula on UC rats was dose dependent, and the effect of the YFB (2.046 g/kg) group was close to that of the positive group. YFB formula has an anti-inflammatory effect on UC by regulating the balance of Th17/Treg cells in rats.PMID:36842724 | DOI:10.1016/j.jep.2023.116301

Gastroenterology. 2023 Feb 24:S0016-5085(23)00164-6. doi: 10.1053/j.gastro.2023.02.025. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Although small patient subsets benefit from current targeted strategies or immunotherapy, gemcitabine remains the first-line drug for pancreatic cancer (PC) treatment. However, gemcitabine resistance is widespread and compromises long-term survival. Here, we identified ubiquitin-conjugating enzyme E2T (UBE2T) as a potential therapeutic target to combat gemcitabine resistance in PC.METHODS: Proteomics and metabolomics were combined to examine the effect of UBE2T on pyrimidine metabolism remodeling. Spontaneous PC mice (LSL-KrasG12D/+, LSL-Trp53R172H/+, Pdx1-Cre; KPC) with Ube2t-conditional knockout, organoids, and large-scale clinical samples were used to determine the effect of UBE2T on gemcitabine efficacy. Organoids, patient-derived xenografts (PDX), and KPC mice were used to examine the efficacy of the combination of a UBE2T inhibitor and gemcitabine.RESULTS: Spontaneous PC mice with Ube2t deletion had a marked survival advantage following gemcitabine treatment, and UBE2T levels were positively correlated with gemcitabine resistance in clinical patients. Mechanistically, UBE2T catalyzes RING1-mediated ubiquitination of p53 and relieves the transcriptional repression of RRM1 and RRM2, resulting in unrestrained pyrimidine biosynthesis and alleviation of replication stress. Additionally, high-throughput compound library screening using organoids identified pentagalloylglucose (PGG) as a potent UBE2T inhibitor and gemcitabine sensitizer. The combination of gemcitabine and PGG diminished tumor growth in PDX models and prolonged long-term survival in spontaneous PC mice.CONCLUSIONS: Collectively, UBE2T-mediated p53 degradation confers PC gemcitabine resistance by promoting pyrimidine biosynthesis and alleviating replication stress. This study offers an opportunity to improve PC survival by targeting UBE2T and develop a promising gemcitabine sensitizer in clinical translation setting.PMID:36842710 | DOI:10.1053/j.gastro.2023.02.025

J Magn Reson. 2023 Feb 21;349:107405. doi: 10.1016/j.jmr.2023.107405. Online ahead of print.ABSTRACTIn this work we demonstrate the use of microfluidic NMR for in situ culture and quantitative analysis of metabolism in hepatocellular carcinoma (HCC) cell lines. A hydrothermal heating system is used to enable continuous in situ NMR observation of HCC cell culture over a 24 h incubation period. This technique is nondestructive, non-invasive and can measure millimolar concentrations at microlitre volumes, within a few minutes and in precisely controlled culture conditions. This is sufficient to observe changes in primary energy metabolism, using around 500-3500 cells per device, and with a time resolution of 17 min. The ability to observe intracellular responses in a time-resolved manner provides a more detailed view of a biological system and how it reacts to stimuli. This capability will allow detailed metabolomic studies of cell-culture based cancer models, enabling quantification of metabolic reporgramming, the metabolic tumor microenvironment, and the metabolic interplay between cancer- and immune cells.PMID:36842430 | DOI:10.1016/j.jmr.2023.107405

Environ Int. 2023 Feb 13;173:107819. doi: 10.1016/j.envint.2023.107819. Online ahead of print.ABSTRACTAgriculture-related manufactured nano-objects (MNOs) can revolutionize the crop production and help to achieve sustainable development goals. MNOs with diverse physico-chemical properties and ability to encapsulate and deliver active ingredients in controlled, targeted and stimuli responsive manner can enhance the efficiency while minimizing collateral damage to non-target organisms and environment. Application of MNOs in the form of nanopesticides and nanofertilizers is known to affect soil microbial communities both positively and negatively, but detailed studies with varying dose, type and environmental conditions are scarce. Therefore, it is imperative to understand the complex mechanisms and factors which shape the MNOs-microbial interactions through integrating state of the art technologies including omics (transcriptomics, metabolomics, and proteomics), artificial intelligence, and statistical frameworks. Lastly, we propose the idea of MNOs-mediated manipulation of soil microbiome to modify the soil microbial communities for improved microbial services. These microbial services, if harnessed appropriately, can revolutionize modern agriculture and help in achieving sustainable development goals.PMID:36842382 | DOI:10.1016/j.envint.2023.107819

J Pharm Biomed Anal. 2023 Feb 13;228:115295. doi: 10.1016/j.jpba.2023.115295. Online ahead of print.ABSTRACTAconiti Lateralis Radix Praeparata is one of the most famous traditional Chinese medicines possessing a variety of pharmacological activities on top of the toxicities. Due to the heterogeneity and non-standardization of the processing procedures, the subtypes and contents of the differential compounds between different processed products still remained indistinct, causing great risk in their proper use. In order to achieve the comparison and quality evaluation of different processed products of Aconiti Lateralis Radix Praeparata and develop new processed products with less toxicity, a quantification and pseudotargeted metabolomics method was developed based on the dynamic MRM mode of triple quadrupole (QqQ) mass spectrometry, and multivariate statistical analysis methods were applied to compare different processed products. Method validation results indicated good specificity, linearity, repeatability, precision, stability and recovery of the established quantification method and good linearity, precision and stability of the pseudotargeted metabolomics method. Differential compounds of different processed products were screened out and further confirmed by the quantification results. At last, the processing procedures were optimized to obtain new processed products of "Heishunpian" (black slices) with less toxicity, in which the contents of the toxic diester-type diterpenoid alkaloids were reduced from 106.98 μg/g to 0.85-12.96 μg/g. This study provided a valuable reference for the establishment of comprehensive quality evaluation methods of herbal medicines and a scientific basis for the optimization of processing procedures of Aconiti Lateralis Radix Praeparata.PMID:36842334 | DOI:10.1016/j.jpba.2023.115295

Ultrason Sonochem. 2023 Feb 21;94:106339. doi: 10.1016/j.ultsonch.2023.106339. Online ahead of print.ABSTRACTThe current work combines headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC/MS) with multivariate analysis fusion metabonomics for examining metabolite profile changes. The correlation with metabolic pathways during the fermentation of kombucha tea were comprehensively explored. For optimizing the fermentation process, ultrasound-assisted factors were explored. A total of 132 metabolites released by fermented kombucha were detected by HS-SPME-GC/MS. We employed the principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) to present the relationship between aroma components and fermentation time, of which the first two principal components respectively accounted for 60.3% and 6.5% of the total variance. Multivariate statistical analysis showed that during the fermentation of kombucha tea, there were significant differences in the phenotypes of metabolites in the samples, and 25 characteristic metabolites were selected as biomarkers. Leaf alcohol was first proposed as the characteristic volatile in the fermentation process of kombucha. Furthermore, we addressed the generation pathways of characteristic volatiles, their formation mechanisms, and the transformational correlation among them. Our findings provide a roadmap for future kombucha fermentation processing to enhance kombucha flavor and aroma.PMID:36842214 | DOI:10.1016/j.ultsonch.2023.106339

Andrology. 2023 Feb 26. doi: 10.1111/andr.13412. Online ahead of print.ABSTRACTBACKGROUND: Asthenozoospermia is one of the essential causes of male infertility, and its incidence is significantly higher in obese men. Due to its complex etiology and unknown pathomechanism, the diagnosis and treatment of obesity-induced asthenozoospermia is a prevalent problem in reproductive medicine.OBJECTIVE: To explore major differential metabolites and metabolic pathways in seminal plasma and pathological mechanisms for obesity-induced asthenozoospermia.MATERIALS AND METHODS: We performed nontarget metabolomic studies on the seminal plasma of healthy with normal semen parameters men (HN group, n = 20), obese with normal semen parameters men (ON group, n = 20) and obesity-induced asthenozoospermia men (OA group, n = 20) based on gas chromatography-mass spectrometry (GC-MS). Metabolic profilings and related pathway analyses were conducted to discriminate differential metabolites and metabolic pathways.RESULTS: A total of 20 differential metabolites including fructose, succinic acid, aconitic acid, methylmaleic acid, glucopyranose, serine, valine, leucine, phenylalanine, glycine, glutamic acid, alanine, proline and threonine were identified in HN group and ON group, 24 differential metabolites including glucose, fructose, pyruvic acid, citric acid, succinic acid, aconitic acid, glucopyranose, glutamic acid, valine, leucine, glycine, phenylalanine, lysine, citrulline, proline and alanine were produced in OA group and ON group, and 28 differential metabolites including glucose, fructose, citric acid, succinic acid, glucopyranose, valine, glycine, serine, leucine, phenylalanine, alanine, threonine, proline, glutamic acid, citrulline, lysine and tyrosine were produced in OA group and HN group. In addition, abnormal energy metabolism including carbohydrate metabolism (TCA cycle, glycolysis/gluconeogenesis and pyruvate metabolism) and amino acid metabolism (phenylalanine, tyrosine and tryptophan biosynthesis, D-glutamine and D-glutamate metabolism; phenylalanine metabolism, etc.) were found in ON group and OA group.CONCLUSION: Obesity could affect the metabolite composition in seminal plasma and abnormal energy metabolism in seminal plasma mainly including carbohydrate metabolism and amino acid metabolism was closely related to obesity-induced asthenozoospermia. This article is protected by copyright. All rights reserved.PMID:36841993 | DOI:10.1111/andr.13412

J Sep Sci. 2023 Feb 26:e2201004. doi: 10.1002/jssc.202201004. Online ahead of print.ABSTRACTEpilepsy is a complex neurological disease characterized by spontaneous recurrent seizures that affects around 1% of the global population. Despite the significant progress in the mechanisms of epileptogenesis, there is still about 60% of cases in which the cause is unknown. Thus, revealing the molecular mechanisms of epileptogenesis will greatly improve the development of epilepsy treatment. Since comprehensive characterization of amino acids and water-soluble vitamins is important in understanding the underlying mechanisms of epilepsy or seizures, we developed two liquid chromatography-tandem mass spectrometry methods to quantify 17 water-soluble vitamins and 46 amino acids and applied them to our pentylenetetrazole-induced kindling rat model. All water-soluble vitamins were detected with a linearity of r > 0.992 and limits of quantitation between 0.1 and 5 ng/ml except for nicotinic acid. For amino acids, the linearities obtained were good with correlation coefficients higher than 0.99, and matrix effects were between 85.3 and 110%. To handle the multidimensional data more effectively, multivariate statistical analysis approaches used in non-targeted metabolomics were creatively exploited in the visualization, interpretation, and exploration of the results. This article is protected by copyright. All rights reserved.PMID:36841992 | DOI:10.1002/jssc.202201004

Eye (Lond). 2023 Feb 25. doi: 10.1038/s41433-023-02457-4. Online ahead of print.ABSTRACTBACKGROUND: Pathological myopia (PM) is closely associated with blinding ocular morbidities. Identifying biomarkers can provide clues on pathogeneses. This study aimed to identify metabolic biomarkers and underlying mechanisms in the vitreous humour (VH) of PM patients with complications.METHODS: VH samples were collected from 39 PM patients with rhegmatogenous retinal detachment (RRD) (n = 23) or macular hole (MH)/myopic retinoschisis (MRS) (n = 16) and 23 controls (MH with axial length < 26 mm) who underwent surgical treatment. VH metabolomic profiles were investigated using ultra-performance liquid chromatography‒mass spectrometry. The area under the receiver operating characteristic curve (AUC) was computed to identify potential biomarkers for PM diagnosis.RESULTS: Bioinformatics analysis identified nineteen and four metabolites altered in positive and negative modes, respectively, and these metabolites were involved in tryptophan metabolism. Receiver operating characteristic analysis showed that seventeen metabolites (AUC > 0.6) in the positive mode and uric acid in the negative mode represent potential biomarkers for PM with complications (AUC = 0.894). Pairwise and pathway analyses among the RRD-PM, MH/MRS-PM and control groups showed that tryptophan metabolism and uric acid were closely correlated with PM. Altered metabolites and pathways in our study were characterized by increased oxidative stress and altered energy metabolism. These results contribute to a better understanding of myopia progression with or without related complications.CONCLUSIONS: Our study provides metabolomic signatures and related immunopathological features in the VH of PM patients, revealing new insight into the prevention and treatment of PM and related complications.PMID:36841867 | DOI:10.1038/s41433-023-02457-4

Sci Rep. 2023 Feb 25;13(1):3296. doi: 10.1038/s41598-023-30231-9.ABSTRACTMetabolomics-derived metabolites (henceforth metabolites) may mediate the relationship between modifiable risk factors and clinical biomarkers of metabolic health (henceforth clinical biomarkers). We set out to study the associations of metabolites with clinical biomarkers and a potential mediation effect in a population of young adults. First, we conducted a systematic literature review searching for metabolites associated with 11 clinical biomarkers (inflammation markers, glucose, blood pressure or blood lipids). Second, we replicated the identified associations in a study population of n = 218 (88 males and 130 females, average age of 18 years) participants of the DONALD Study. Sex-stratified linear regression models adjusted for age and BMI and corrected for multiple testing were calculated. Third, we investigated our previously reported metabolites associated with anthropometric and dietary factors mediators in sex-stratified causal mediation analysis. For all steps, both urine and blood metabolites were considered. We found 41 metabolites in the literature associated with clinical biomarkers meeting our inclusion criteria. We were able to replicate an inverse association of betaine with CRP in women, between body mass index and C-reactive protein (CRP) and between body fat and leptin. There was no evidence of mediation by lifestyle-related metabolites after correction for multiple testing. We were only able to partially replicate previous findings in our age group and did not find evidence of mediation. The complex interactions between lifestyle factors, the metabolome, and clinical biomarkers warrant further investigation.PMID:36841863 | DOI:10.1038/s41598-023-30231-9