Non-targeted Metabolomics Analysis Research Articles

Influence of sonication-assisted fermentation on the physicochemical features and antioxidant activities of yogurts fortified by polyphenol-rich pineapple peel powder with varied chemical profiling

This study investigated the effects of pineapple peel powder with varied chemical profiles and sonication-assisted polyphenol biotransformation during fermentation on the quality characteristics of yogurt products. It aimed at exploring the feasibility of sonication-assisted fermentation to enhance the physicochemical properties, control post-acidification, and improve antioxidant activities in yogurts fortified with polyphenol-rich pineapple peel powder. Targeted analysis showed that polyphenol-rich pineapple dietary fiber obtained by ultrasonication-assisted extraction (NPFU) exhibited the slowest rates of acidification, highest antioxidant capacity, and lowest degree of whey separation at 21.67 %. Sonication pretreatments significantly increased transformation of free phenolic acids derived from pineapple peel fiber during fermentation, particularly increasing the accumulation of ferulic acid, caffeic acid and 5-hydroxyflavone, revealing the positive effects of sonication-mediated fermentation in promoting the hydrolysis of conjugated phenolics into free fractions. Yogurts fortified with pineapple peel fiber displayed significantly higher antioxidant activities (p < 0.05) compared to those with pineapple peel whole powder, corresponding with the increased free phenolics. Non-targeted metabolomics analysis was employed to explore the mechanisms underlying the alleviated post-acidification by sonication-assisted fermentation during storage. Metabolomic profiling revealed that the bioactive components from pineapple peel extract significantly influenced the metabolism pathways of lactic acid bacteria particularly involving galactose metabolism, glycerophospholipid metabolism, closely associated with the acid production of the strains and the regulation of the post-acidification rates of yogurt during storage. These results confirmed the potential of ultrasound-assisted fermentation combined with the addition of pineapple dietary fiber to enhance yogurt quality, providing an innovative tool to develop future yogurt products with high marketability.

Mulberry leaf extract ameliorates high-fat diet-induced obesity in mice by regulating the gut microbiota and metabolites

The increasing prevalence of obesity presents a notable challenge to global health. Mulberry leaves enriched with biologically active substances hold promise for alleviating obesity. This research assessed the efficacy of mulberry leaf extract (MLE) in mitigating obesity and metabolic disturbances in mice fed a high-fat diet (HFD). The results demonstrated that MLE, administered at both low (167 mg/kg) and high (333 mg/kg) doses, decreased weight gain and fat accumulation, improved glucose metabolism, enhanced insulin sensitivity, and reduced inflammation. Analysis of fecal samples via 16S rRNA sequencing revealed that MLE corrected the gut microbiota imbalance caused by HFD, lowering the Firmicutes/Bacteroidota ratio as well as increasing the relative abundances of Bifidobacterium, Faecalibaculum, Coriobacteriaceae_UCG-002, and Dubosiella. Additionally, serum non-targeted metabolomics analysis identified 19 key differential metabolites associated with MLE treatment, which were primarily related to glycerophospholipid metabolism and tryptophan metabolism. Correlation analysis revealed negative associations between Dubosiella and Coriobacteriaceae_UCG-002 with specific phospholipids, and positive associations of 5-hydroxyindoleacetate and quinoline-4,8-diol with Bifidobacterium and Coriobacteriaceae_UCG-002. These findings suggest that MLE is effective in treating obesity and underscores its potential as a functional food.

Plasma metabolomic characteristics of atrial fibrillation patients with spontaneous echo contrast.

The spontaneous echo contrast (SEC) in patients with atrial fibrillation (AF) indicates a prethrombic state that ultimately progresses into thrombus formation. A comprehensive understanding of specific plasma metabolomics characteristics may protect AF patients from thrombus, particularly in the early stage. Through the investigation of metabolic pathways, we endeavor to uncover the metabolomic characteristics associated with SEC states, and to examine the differential metabolites by which may exert their influence on thrombotic states. Patients with AF were enrolled, and the participants were divided into three groups based on the results of the echocardiogram: non-SEC, low-SEC and high-SEC group. Samples were collected and subjected to non-targeted metabolomics analysis. The analytical process included data quality control, metabolite difference analysis, component analysis, Kegg cluster analysis, etc. RESULTS: Our metabolic phenotype revealed a clear differential metabolic pattern between the SEC and non-SEC. Specifically, we identified 35 and 142 significantly differential metabolites in venous and atrial plasma, respectively, suggesting that SEC may be involved in pervasive metabolic dysregulation and that the degree of metabolic dysregulation in atrial plasma is more severe than that in venous blood. Patients with SEC have a significantly different metabolic pattern compared to those without SEC. Our work promoted the understanding of mechanism of the occurrence and development of SEC, facilitated the screening of the target metabolites for its therapeutic intervention, and provided evidence for the prevention and treatment of SEC or thrombosis in AF. Our work also provided new directions for subsequent research in related fields. In conclusion, our study not only provides a theoretical basis for understanding the occurrence and development of SEC in AF, but also provides recommendations for the daily diet of AF patients with SEC, such as a balanced intake of essential amino acids, avoiding excessive intake of benzoic acid, and intake of appropriate inositol. Not applicable.

Comparative analysis of oral saliva microbiomes and metabolites in Han population at different altitudes

ObjectiveThis study investigated the differences in oral saliva microbiota composition and metabolic products among Han Chinese populations living at different altitudes, as well as their correlations.MethodThe analysis was conducted using the 16S rRNA gene sequencing method and untargeted metabolomics.Results16S gene sequencing results showed significant differences in bacterial diversity and composition between HH (High altitude Han) group and LH (Low altitude Han) group. LEfSe analysis showed that Selenomonas, Leptotrichia, Veillonella, Prevotella relatively abundant are higher in HH group, Haemophilus, Neisseria, Actinobacillus, Aggregatibacter are higher in LH group (p&amp;lt;0.05). Furthermore, as depicted in the phylogenetic tree, there are differences observed between the two groups at all taxonomic levels: 4 phyla, 6 classes, 6 orders, 9 families, 9 genera and 8 species (p&amp;lt;0.05). After conducting PICRUSt functional prediction analysis, we identified 11 significantly different KEGG categories (level 2) between the two groups. These categories primarily encompass energy metabolism, amino acid metabolism, and carbohydrate metabolism. Furthermore, non-targeted metabolomics analysis revealed a total of 997 distinct metabolites in the two groups. These differentiated metabolites can be classified into 13 Class I categories including amino acids and their metabolites, benzene and its derivatives, organic acids and their derivatives, heterocyclic compounds, aldehydes, ketones and esters, nucleotides and their metabolites among others. Additionally, fatty acyl compounds, alcohols and amines as well as glycerophospholipids are present along with carbohydrates and other physiologically active components such as hormones. Finally, Pearson correlation analysis of the top 20 differential metabolites with microorganisms demonstrated an interaction between them; however further experimental verification is required to elucidate the specific mechanism of action.ConclusionTherefore, this study revealed the effect of altitude on oral saliva microbes and metabolites, as well as their correlations.

Loureirin B Ameliorates Glycolipid Metabolism Disorders in Ob/ob Mice by Regulating Bile Acid Levels and Modulating Gut Microbiota Composition.

Loureirin B (LB), an active component of Resina Draconis, exhibits hypoglycemic and hypolipidemic effects; however, its mode of action remains unclear. Here, ob/ob mice were utilized to investigate the effects of LB on the regulation of glucolipid metabolism disorders. Non-targeted metabolomics and 16S rDNA sequencing were performed to elucidate the potential mechanisms involved. Results indicated that LB treatment (45 mg/kg) significantly improved glucose intolerance and insulin resistance, reduced lipid levels, and alleviated hepatic steatosis. Non-targeted metabolomics analysis revealed that LB treatment regulated bile acid levels. Quantification of liver bile acids demonstrated that LB treatment significantly decreased the ratio of 12α-OH to non-12α-OH bile acids in the liver. 16S rDNA sequencing results showed that LB treatment increased the abundance of short-chain fatty acid-producing microbiota while decreasing the abundance of bile salt hydrolase (BSH) enzyme-producing microbiota. In conclusion, LB ameliorates glucolipid metabolism disorders by regulating liver bile acid levels and modulating the composition of the gut microbiota.

Profiling of Metabolome in the Plasma Following a circH19 Knockdown Intervention in Diet-Induced Obese Mice

The circular RNA circH19 has been implicated in the regulation of gene expression and various biological processes, including obesity. Objectives: This study aimed to elucidate the metabolic changes in plasma after circH19 knockdown in a diet-induced obese (DIO) mouse model. Methods: Plasma samples were collected following the intervention and subjected to non-targeted metabolomics analysis using liquid chromatography–mass spectrometry (LC-MS). Metabolic profiling was performed to identify and quantify metabolites, followed by multivariate statistical analysis to discern differential metabolic signatures. Results: A total of 1250 features were quantified, resulting in the upregulation of 564 metabolites and the downregulation of 686 metabolites in the circH19 knockdown group compared to the control mice. Metabolic pathway analysis revealed disruptions in lipid metabolism, amino acid turnover, and energy production pathways. Notably, the intervention led to a substantial decrease in circulating lipids and alterations in the plasma amino acid profile, indicative of an impact on protein catabolism and anabolic processes. The observed shifts in lipid and amino acid metabolism suggest potential therapeutic avenues for obesity and related metabolic disorders. Conclusions: The circH19 knockdown in DIO mice led to significant alterations in plasma metabolites, highlighting its potential role in the regulation of obesity and metabolic disorders.

Tetrandrine Alleviates Pulmonary Fibrosis by Modulating Lung Microbiota-Derived Metabolism and Ameliorating Alveolar Epithelial Cell Senescence.

Tetrandrine (TET) is a minimally toxic drug extracted from the root of Stephania tetrandra. We previously demonstrated that TET could ameliorate pulmonary fibrosis (PF) by modulating autophagy. However, the mechanism behind TET's protective effects on PF remains unclear. In this study, we utilized 16S rRNA gene sequencing, nontargeted metabolomic analysis, and network pharmacology to identify changes in lung microbiota and metabolites that mediate alveolar epithelial cell senescence in bleomycin (BLM)-induced PF in mice. Additionally, we employed Western blot analysis, RT-PCR, and immunofluorescence staining to investigate the invitro and invivo effects of TET and its influential bacterial metabolites on PF. The TET intervention alleviated PF by regulating the compositions of lung microbial communities (Streptococcus, Micrococcus, Acinetobacter, Altererythrobacter, Atopostipes, Candidatus Cloacimonas, Clostridium sensu stricto 1, Sphingomonas, Listeria, Blautia, and Pseudomonas) and metabolites (3,4-dihydroxyphenylpropionic acid (3,4-DHPPA), 6-Aminonicotinamide, N-acetyl-5-methoxykynuramine, and resiniferatoxin). Through network pharmacological analysis, it was determined that 3,4-DHPPA played a crucial role in alleviating PF by further inhibiting the senescence of alveolar epithelial cells, a finding further validated in exvivo experiments. TET mitigated BLM-induced PF in murine models through the modulation of lung microbiota composition and metabolism. Specifically, TET augmented the level of the microbiota-derived metabolite, 3,4-DHPPA, which in turn attenuated alveolar epithelial cell senescence.

The involvement and possible targeting of cardiolipins degradation and disturbed linoleic acid metabolism in cardiac atrophy under cancer cachexia

Cardiac atrophy is one of the critical characteristics of cancer cachexia though its mechanisms had not been fully clarified. In the present study, to study the mechanisms of cardiac atrophy in cancer cachexia and search for possible drug targets, cancer cachexia mice bearing C26 colon tumor cells and cultured H9c2 cardiomyocytes induced with simulated cancer cachexia injuries were used as in vivo and in vitro model, respectively. Results of both spatial metabolomics and LC-MS non-targeted metabolomics analysis of heart tissues suggested the disturbance of glycerophospholipid and fatty acid metabolism in the cancer cachexia hearts. Results of lipidomic analysis confirmed that the fatty acid composition of glycerophospholipids changed and the levels of linoleic acid (LA)-rich cardiolipins (CLs) significantly decreased. GC-MS analysis of fatty acids profile confirmed that the level of LA significantly increased and the ratio value of ω-6/ω-3 polyunsaturated fatty acids (PUFA) also increased in the cancer cachexia hearts. In H9c2 cardiomyocytes induced by simulated cancer cachexia injuries, degradation of CLs were also observed. Furthermore, SS-31, a tetrapeptide targeting CLs, could protect the H9c2 cardiomyocytes under simulated cancer cachexia injury by ameliorating the degradation of CLs, inhibiting apoptosis and attenuating the decrease in cell size. Collectively, these results have provided new insights into the cardiac atrophy in cancer cachexia, in which degradation of glycerophospholipids such as CLs and increase in LA and AA-related oxylipins might be important contributing factors and possible therapy targets.

Effect of fermentation temperature on the non-volatile components and in vitro hypoglycemic activity of Jinxuan black tea.

Fermentation significantly influences the chemical composition of black tea, yet the effects of different fermentation temperatures on non-volatile components and their in vitro hypoglycemic activity are insufficiently studied. This research investigates how varying temperatures (20, 25, and 30°C) affect the bioactive profile and the inhibitory activity of Jinxuan black tea against α-glucosidase and α-amylase. Our results show that lower fermentation temperatures (20°C) lead to elevated levels of key bioactive compounds, including tea polyphenols (9.24%), soluble sugars (8.24%), thearubigins (7.17%), and theasinesin A (0.15%). These compounds correlate strongly with enhanced α-glucosidase inhibition (R = 0.76-0.97). Non-targeted metabolomic analysis revealed that 36 differential metabolites, including catechins, exhibited altered levels with increasing fermentation temperature. Notably, tea fermented at 20°C exhibited superior hypoglycemic activity, with α-glucosidase inhibition (IC50 = 14.00 ± 1.00 μg/ml) significantly outperforming α-amylase inhibition (IC50 = 2.48 ± 0.28 mg/ml). The findings of this research underscore the importance of fermentation temperature in optimizing the bioactive profile of black tea. It is proposed that recommendations for future processing or formulation should emphasize the use of lower fermentation temperatures, aimed at augmenting the health benefits linked to higher polyphenol content and stronger hypoglycemic activity.

Identification of potential key metabolites in synbiotic yoghurt made with probiotic Saccharomyces cerevisiae var. boulardii CNCM I-745 and prebiotic inulin by non-targeted metabolomics analysis

Probiotic yeasts are attracting widespread attention due to their unique therapeutic properties and benefits to human health, but how they function in food system has been much less studied. Here, yoghurt was prepared using probiotic Saccharomyces cerevisiae var. boulardii CNCM I-745 with and without addition of prebiotic inulin, and the metabolic changes in yoghurt during 28 days of storage at 4 °C were analyzed by non-targeted metabolomics method. Potential functional metabolites that were differentially expressed in the synbiotic yoghurt added with inulin were identified, including hydroxyisocaproic acid, indolelactic acid, α-lactose, pelargonic acid, trehalose, 2-isopropylmalic acid, maltitol, D-glucuronic acid, raffinose, uric acid, and maltohexaose. These differential metabolites might play an important role in improving probiotic yeast survival and synbiotic yoghurt functionality through relevant metabolic pathways. This study promotes comprehension on the metabolic properties of the probiotic yeast in yoghurt with significance in exploring its applications in synbiotic dairy products.

Using metabolomics to explore the effects of epigenetic-modification strategies on the metabolites of Acanthus ilicifolius L. endophytic fungi against ovarian cancer

Ovarian cancer is a serious threat to women's health and safety. So far, people have discovered more than 130 small molecule compounds of natural origin for anti-tumor, of which approximately 50% are of microbial origin. The Acanthus ilicifolius L. species is primarily distributed in the Guangdong, Hainan, and Guangxi regions of China and grows in tidally accessible coastal areas. Recent studies have revealed that Acanthus ilicifolius L. extracts are endowed with a range of pharmacological properties, including anti-inflammatory, hepatoprotective, antioxidant, and antitumor activities. Endophytic fungi are commonly found in the healthy tissue and organs of medicinal plants. These fungi and the plants they inhabit form mutually beneficial symbiotic relationships. Endophytic fungi produce a series of secondary metabolites, with active substances having shown great economic value and applications prospects in drug research and development as well as for the biological control of plant diseases. Secondary metabolites production by endophytic fungi is regulated by specific gene clusters, and several techniques have been used to stimulate the secondary metabolic processes of fungi, including epigenetic-modification and OSMAC (one strain many compounds) strategies, co-culturing, and gene modification. Among these, epigenetic modification has been shown to be effective; this strategy involves the addition of small-molecule epigenetic modifiers to the culture medium, thereby activating silenced biosynthetic gene clusters without altering the DNA sequences of the fungi. This approach facilitates the expression of silenced genes in endophytic fungi, thereby increasing the number and diversity of secondary metabolites. Furthermore, it assists in overcoming the inhibition of microbial secondary-metabolite synthesis under laboratory conditions, and enhances silenced-gene expressions. The advent of novel analytical techniques and bioinformatics has provided a comprehensive, multifaceted, and holistic understanding of fungal metabolism through the development of metabolomics as a research platform. However, few studies have combined anti-ovarian cancer-activity screening with metabolomic approaches in the search for activity-differentiating metabolites from endophytic fungi under the intervention of epigenetic modifiers. Herein, we investigated the impact of epigenetic modifiers on the secondary metabolites of the endophytic Diaporthe goulteri fungus from Acanthus ilicifolius L. to determine their potential anti-ovarian cancer activities. Crude extracts were obtained by controlling three variables: the number of fermentation days, the type of epigenetic modifier, and its concentration, with activities screened using the CCK-8 (cell counting kit-8) method. Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was subsequently employed for non-targeted metabolomic analysis. A multivariate statistical analysis model was constructed using principal component analysis and orthogonal partial least squares-discriminant analysis, which combines model and variable importance projection, with qualitative screening performed and significant changes (variable importance in the projection (VIP)≥1; P<0. 05) determined. Fifteen differential metabolites were identified in the fungal and epigenetic modification group, primarily comprising polyketides, amino acids, derivatives, alkaloids, and organic acids, including prenderol, glycine, valine, 2-ethylcaproic acid, rubratoxin B, finasteride, 6-silaspiro[5.5]undecane, 1-(2-nitrophenoxy)octane, heptadecene, 1-pentadecene, 11-ketoetiocholanolone, 3-(1-ethyl-1,3,3-trimethyl-2,3-dihydro-1H-inden-5-yl)butanal, N2-benzoylarginine, tabutrex, (3aR,6S,6aS)-6-(4-hydroxy-2-methoxy-2-butanyl)-4,4-dimethylhexahydro-1(2H)-pentalenone, and 8-aminoquinoline. The expressions of prenderol, 1-(2-nitrophenoxy)octane, 3-(1-ethyl-1,3,3-trimethyl-2,3-dihydro-1H-inden-5-yl)butanal, N2-benzoylarginine, and 8-aminoquinoline were downregulated, whereas the expressions of the remaining 10 substances were upregulated. Polyketides were the main components that exhibited higher expressions. This study showed that latent active differential metabolites can be searched by combining anti-ovarian cancer-activity screening with metabolomics analysis, thereby providing a reference for the further development of Acanthus ilicifolius L. resources and the subsequent targeted isolation of active compounds.

Revealing the dynamic changes of metabolites and molecular mechanisms of chlorogenic acid accumulation during the leaf development of Vaccinium dunalianum based on multi-omic analyses.

Vaccinium dunalianum, a medicinal plant, is utilized for Quezui Tea production from its leaf buds and young leaves. Despite prior research on V. dunalianum revealing several medicinal compounds, the comprehensive variations in metabolites during its growth and development, along with the molecular mechanisms underlying high chlorogenic acid (CGA) yield, remain unclear. Through a joint analysis of transcriptomics and proteomics, our study first identified 15 key structural genes and 3 transcription factors influencing CGA biosynthesis in V. dunalianum, offering new evidence to understand its regulatory network. Furthermore, non-targeted metabolomics analysis provides the first extensive report on the metabolic profile of V. dunalianum, furnishing a valuable dataset for deeper exploration of its nutritional and medicinal value, and the development of a quality evaluation system for its product Quezui Tea. This study offers the most comprehensive molecular information on V. dunalianum, marking a significant step toward understanding and enhancing the plant's potential for medicinal and nutritional applications. Additionally, this study also reveals V. dunalianum holds promise as a natural antioxidant source for functional foods, providing data support for network pharmacology.

Dielectric Barrier Discharge Cold Plasma Improves Storage Stability in Paddy Rice by Activating the Phenylpropanoid Biosynthesis Pathway.

A nonthermal pretreatment using dielectric barrier discharge cold plasma (DBD-CP) was developed to improve the stress resistance of paddy rice during postharvest storage. The physicochemical properties, bioactive characteristics, and secondary metabolites of paddy rice were assessed after applying an optimized DBD-CP procedure, with enzyme activities and gene expression monitored over a 60 day storage period at 35 °C. A 17.06% reduction in the total color change index was noted in the DBD-CP group. Bioactive compounds, particularly gallic acid, were significantly increased, enhancing the defense mechanisms against high-temperature stress. Nontargeted metabolomics analysis indicated an upregulation of phenylpropanoid metabolism in DBD-CP-treated rice compared to controls, with notable increases in secondary metabolites such as coumaric acid, caffeic acid, and sinapic acid, suggesting potential biomarkers for stress resistance. Further verification showed significant enhancements in key enzymes of phenylpropanoid metabolism, including phenylalanine ammonia lyase (PAL), cinnamic acid-4-hydroxylase (C4H), plant coumaric acid-3-hydroxylase (C3H), and cinnamyl alcohol dehydrogenase (CAD), with increases ranging from 1.71 to 2.28 times. Gene expression levels of OsPAL7, OsC4H4, and OsCAD2 aligned with these enzymatic changes post-DBD-CP treatment. In conclusion, DBD-CP treatment can modulate phenylpropanoid metabolism in paddy rice, thereby enhancing bioactive compound levels to reduce stress damage during high-temperature storage.

Effects of MDA-19 on Zebrafish Larval Behavior: Perspectives From Neurodevelopment, Oxidative Stress, and Metabolomics.

As global regulations on synthetic cannabinoids tighten, illicit vendors increasingly turn to new structures of synthetic cannabinoids to evade legal scrutiny. MDA-19, a novel synthetic cannabinoid, exhibited significant agonistic effects on type 2 cannabinoid receptors invivo and showed emerging trends of abuse in illicit markets. However, research on the toxicological effects of MDA-19 remains scarce. In this study, we examined the effects of MDA-19 on neurodevelopment, behavior, oxidative stress, and metabolomics by exposing zebrafish embryos to MDA-19 solutions with concentrations of 1, 10, and 20 mg/L over 5 days. Results revealed that exposure to 10 and 20 mg/L of MDA-19 accelerated hatching in zebrafish embryos but led to reduced body length without affecting mortality or malformation. Furthermore, exposure to all concentrations of MDA-19 resulted in diminished swimming ability and reduced activity time in zebrafish. Transgenic zebrafish (hb9-GFP) exposed to MDA-19 exhibited impaired development of spinal motor neurons. Notably, exposure to 20 mg/L MDA-19 increased the levels of reactive oxygen species (ROS) in zebrafish and elevated the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), while the levels of the lipid oxidation product malondialdehyde (MDA) remained unaffected. Nontargeted metabolomics analyses showed that MDA-19 interfered with multiple metabolic pathways affecting energy metabolism, such as alanine, aspartate, and glutamate metabolism; the citric acid cycle (TCA cycle), pantothenate, and coenzyme A biosynthesis; and purine metabolism. In conclusion, the present study provided the essential evidence for the neurotoxic effects of MDA-19, which was associated with impaired neurodevelopment, dysregulation of oxidative stress homeostasis, and altered energy metabolism.

Comparative Metabolomics to Unravel the Biochemical Mechanism Associated with Rancidity in Pearl Millet (Pennisetum glaucum L.).

Despite being a highly nutritious and resilient cereal, pearl millet is not popular among consumers and food industries due to the short shelf-life of flour attributed to rapid rancidity development. The biochemical mechanism underlying rancidity, a complex and quantitative trait, needs to be better understood. The present study aims to elucidate the differential accumulation of metabolites in pearl millet that impact the rancidity process. Metabolite profiling was conducted on ten pearl millet genotypes with varying levels of rancidity-comprising high, low, and medium rancid genotypes-utilizing liquid chromatography and high-resolution mass spectrometry (LC-HRMS) at different accelerated ageing conditions. Through non-targeted metabolomic analysis, crucial metabolites associated with rancidity were identified across various biochemical pathways, including fatty acids, glycerophospholipids, sphingolipids, glycerol lipids, flavonoids, alkaloids, and terpenoids. Notably, metabolites such as fatty aldehydes, fatty alcohols, fatty esters, fatty acyls, fatty esters, and fatty amides were significantly elevated in high rancid genotypes, indicating their involvement in the rancidity process. These fatty acids-related metabolites further break down into saturated and unsaturated fatty acids. Four key fatty acids-stearic, palmitic, linoleic and linolenic acid-were quantified in the ten pearl millet genotypes, confirming their role in rancidity development. This investigation promises novel insights into utilizing metabolomics to understand the biochemical processes and facilitate precision breeding for developing low-rancidity pearl millet lines.

Fermentative Characteristics and Metabolic Profiles of Japanese Apricot Juice Fermented with Lactobacillus acidophilus and Torulaspora delbrueckii.

Functional fermented fruit juices produced using a combination of non-Saccharomyces yeast and lactic acid bacteria (LAB) are relatively unexplored. The effects of three inoculation protocols, single inoculation with Lactobacillus acidophilus (La), single inoculation with Torulaspora delbrueckii (Td), and co-culture of both La + Td, on the physicochemical, microbiological, sensory properties, and metabolic profile of fermented JA juices after 24 h at 30 °C were investigated. Uninoculated (UI) Japanese apricot (JA) juice was used as a control. The results show significant increases in the color intensity of the fermented-JA juices, whereas an enhancement of total phenolic contents is observed in the fermented JA-juices acquired through the use of La for both single and co-culture inoculations. The colony counts of LAB and yeast in the inoculated JA juices increased by approximately 2.0 and 1.7 log CFU/mL at 24 h, respectively. The antibacterial activity of JA juices against four pathogenic bacteria was detected. All JA juices exhibited antimicrobial activity against the tested pathogenic strains, with strong antibacterial properties of La-fermented juice being recorded against Bacillus cereus at the lowest MIC of 124 µL/mL. Additionally, La + Td-fermented and UI-JA juices demonstrated comparable anticancer activity against HT-29 cells with IC50 values of 823.37 and 754.87 µg/mL, respectively. Furthermore, a total of 995 compounds was identified as differential fermentation metabolites through non-targeted metabolome analysis across different fermentation groups. These findings illustrate the significant potential of using JA juice for La and Td fermentation to develop functional juices.

METTL3 confers oxaliplatin resistance through the activation of G6PD-enhanced pentose phosphate pathway in hepatocellular carcinoma.

Oxaliplatin-based therapeutics is a widely used treatment approach for hepatocellular carcinoma (HCC) patients; however, drug resistance poses a significant clinical challenge. Epigenetic modifications have been implicated in the development of drug resistance. In our study, employing siRNA library screening, we identified that silencing the m6A writer METTL3 significantly enhanced the sensitivity to oxaliplatin in both in vivo and in vitro HCC models. Further investigations through combined RNA-seq and non-targeted metabolomics analysis revealed that silencing METTL3 impeded the pentose phosphate pathway (PPP), leading to a reduction in NADPH and nucleotide precursors. This disruption induced DNA damage, decreased DNA synthesis, and ultimately resulted in cell cycle arrest. Mechanistically, METTL3 was found to modify E3 ligase TRIM21 near the 3'UTR with N6-methyladenosine, leading to reduced RNA stability upon recognition by YTHDF2. TRIM21, in turn, facilitated the degradation of the rate-limiting enzyme of PPP, G6PD, through the ubiquitination-proteasome pathway. Importantly, high expression of METTL3 was significantly associated with adverse prognosis and oxaliplatin resistance in HCC patients. Notably, treatment with the specific METTL3 inhibitor, STM2457, significantly improved the efficacy of oxaliplatin. These findings underscore the critical role of the METTL3/TRIM21/G6PD axis in driving oxaliplatin resistance and present a promising strategy to overcome chemoresistance in HCC.

Distinct accumulation patterns, translocation efficiencies, and impacts of nano-fertilizer and nano-pesticide in wheat through foliar versus soil application

The use of nano-chemicals in agriculture has been shown to enhance crop production through soil additions or foliar sprays. However, the accumulation pattern, translocation efficiency, mode of action of nanomaterials (NMs) via different application methods remain unclear. In this study, wheat was treated with CuO-NPs/CeO2-NPs (50 and 100 nm) for 21 days using soil and foliar application separately. Foliar spray resulted in higher accumulation and more efficient translocation of NMs compared to soil addition. Smaller NMs exhibited higher accumulation and transfer capabilities under the same application method. The accumulation of CuO-NPs was approximately 20 times greater than that of CeO2-NPs, particularly under the soil addition treatment. Scanning electron microscopy analysis demonstrated that NMs could directly enter wheat leaves via stomata during foliar application. Wheat growth was inhibited by roughly 15 % following CuO-NPs exposure, whereas no significant effects on growth were observed with CeO2-NPs. By integrating nontargeted metabolomics analysis with targeted physiological characteristics assessments, it was revealed that CuO-NPs mainly disturbed nitrogen metabolism pathways and induced oxidative damage. In contrast, CeO2-NPs enhanced carbohydrates related biological processes such as starch and sucrose metabolism, glycolysis, and TCA cycle, which are crucial for carbon metabolism. These findings suggest that the type of nanomaterial is a crucial factor to consider when evaluating their foliar or soil application in agriculture.

Systematic evaluation of Rutongshu oral liquid based on chromatographic fingerprinting and nontargeted metabolomic analysis

AbstractBased on chromatographic fingerprinting combined with quantitative analysis on characteristic chemical constituents as well as hierarchical cluster analysis, an easy and sensitive approach utilizing high performance liquid chromatography (HPLC) was developed for the identification and quality evaluation of Rutongshu oral liquid (ROL). What is more, nontargeted metabolomic analysis was conducted to gain a global view in terms of its chemical profile. In this study, 16 peaks from different batches (S1–S10) of ROL samples produced by Taihe Hospital of Chinese Medicine were selected as common peaks for the evaluation of their similarity whose values of all tested 10 batches exceeded 0.90 when compared with the control fingerprints. Meanwhile, simultaneous quantification of five markers in the oral solution, including albiflorin, paeoniflorin, chlorogenic acid, quercetin and ferulic acid was performed, and standard curves established for respective reference substances showed good regression in the linear range (r2 &gt; 0.999) with recoveries in the range of 98.96–102.35%. The ultra-high performance liquid chromatography (UHPLC) combined with Orbitrap Exploris 120 mass spectrometer resulted in 88 identified compounds. The results of validation showed that the established method was reproducible, precise and stable. This study offers an effective, dependable and useful approach for the systematic evaluation of the hospital formulation ROL.

Angiotensin-(1-7) improves intestinal microbiota disturbances and modulates fecal metabolic aberrations in acute pancreatitis.

Acute pancreatitis (AP) is a serious health problem that dysregulates intestinal microbiota. Angiotensin (Ang)-(1-7) plays a protective role in the intestinal barrier in AP, but its effect on intestinal microbiota remains clear. To investigate the impact of Ang-(1-7) on AP-induced intestinal microbiota disorder and metabolites. We collected blood and fecal samples from 31 AP patients within 48 h after admission to the hospital, including 11 with mild AP (MAP), 14 with moderately severe AP (MSAP), six with severe AP (SAP). Mice were divided into four groups: control, AP, AP + Ang-(1-7) via tail vein injection, and AP + Ang-(1-7) via oral administration. The samples of mice were collected 12 h after AP. Pancreatic and intestinal histopathology scores were analyzed using the Schmidt and Chiu scores. Fecal microbiota and metabolites analysis was performed via 16S rDNA sequencing and nontargeted metabolomics analysis, respectively. In patients, the abundance of beneficial bacteria (Negativicutes) decreased and pathogenic bacteria (Clostridium bolteae and Ruminococcus gnavus) increased in SAP compared with MAP. Ang-(1-7) levels were associated with changes in the microbiota. There were differences in the intestinal microbiota between control and AP mice. Ang-(1-7) attenuated intestinal microbiota dysbiosis in AP mice, reflecting in the increase in beneficial bacteria (Odoribacter and Butyricimonas) than AP, as well as pancreatic and intestinal injuries. Oral administration of Ang-(1-7) reversing AP-induced decreases in metabolisms: secondary bile acids, emodin, and naringenin. Ang-(1-7) may improve intestinal microbiota dysbiosis and modulate fecal metabolites in AP, thereby reducing the damage of AP.