PubMed

J Agric Food Chem. 2023 Jun 15. doi: 10.1021/acs.jafc.3c01377. Online ahead of print.ABSTRACTHerbicide-resistant soybeans are among the most widely planted transgenic crops. The in situ evaluation of spatial lipidomics in transgenic and non-transgenic soybeans is important for directly assessing the unintended effects of exogenous gene introduction. In this study, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI)-based non-targeted analytical strategies were used for the first time for in situ detection and imaging of endogenous lipid distributions in transgenic (EPSPS and PAT genes) herbicide-resistant soybean (Glycine max Merrill) (S4003.14) and non-transgenic soybean (JACK) seeds. Statistical analysis revealed significant differences in lipids between S4003.14 and JACK seeds. The variable importance of projection analysis further revealed that 18 identified lipids, including six phosphatidylcholines (PCs), four phosphatidylethanolamines (PEs), five triacylglycerols (TAGs), and three cytidine diphosphate-diacylglycerols (CDP-DAGs), had the strongest differential expression between S4003.14 and JACK seeds. Among those, the upregulated expressions of PC(P-36:1), PC(36:2), PC(P-36:0), PC(37:5), PE(40:2), TAG(52:1), TAG(55:5), and CDP-DAG(37:2) and the downregulated expressions of PC (36:1), TAG(43:0), and three PEs (i.e., PE(P-38:1), PE(P-38:0), and PE(P-40:3)) were successfully found in the S4003.14 seeds, compared to these lipids detected in the JACK seeds. Meanwhile, the lipids of PC (44:8), CDP-DAG(38:0), and CDP-DAG(42:0) were uniquely detected in the S4003.14 soybean seeds, and TAG(45:2) and TAG(57:10) were detected as the unique lipids in the JACK seeds. The heterogeneous distribution of these lipids in the soybean seeds was also clearly visualized using MALDI-MSI. MSI results showed that lipid expression was significantly up/downregulated in S4003.14 seeds, compared to that in JACK seeds. This study improves our understanding of the unintended effects of herbicide-resistant EPSPS and PAT gene transfers on spatial lipidomes in soybean seeds and enables the continued progression of MALDI-MSI as an emerging, reliable, and rapid molecular imaging tool for evaluating unintended effects in transgenic plants.PMID:37318082 | DOI:10.1021/acs.jafc.3c01377

J Exp Bot. 2023 Jun 15:erad230. doi: 10.1093/jxb/erad230. Online ahead of print.ABSTRACTFruit quality traits are determined to a large extent by their metabolome. The metabolite content of climacteric fruit changes drastically during ripening and postharvest storage and has been investigated extensively. However, the spatial distribution of metabolites and how it changes in time has received much less attention as fruit are usually considered as homogenous plant organs. Yet, spatio-temporal changes of starch, which is hydrolysed during ripening, has been used for ages as a ripening index. As vascular transport of water, and, hence, convective transport of metabolites slows down in mature fruit and even stalls after detachment, spatio-temporal changes in their concentration are likely affected by diffusive transport of gaseous molecules that act as substrate (O2), inhibitor (CO2) or regulator (ethylene, NO) of the metabolic pathways that are active during climacteric ripening. In this review we discuss such spatio-temporal changes of the metabolome and how they are affected by transport of metabolic gases and gaseous hormones. As there are currently no measurement techniques available to measure the metabolite distribution repeatedly by nondestructive means, we introduce reaction-diffusion models as an in silico tool to compute it. We show how the different components of such a model can be integrated and used to better understand the role of spatio-temporal changes of the metabolome in ripening and postharvest storage of climacteric fruit that is detached from the plant and discuss future research needs.PMID:37317945 | DOI:10.1093/jxb/erad230

Hosp Pediatr. 2023 Jun 15:e2022007012. doi: 10.1542/hpeds.2022-007012. Online ahead of print.ABSTRACTBiomarkers are commonly used in pediatric medicine to identify disease and guide clinical management for children. Biomarkers can be used to predict risk of disease, provide diagnostic clarification, and offer prognostic expectations. Specimens for biomarker testing might require noninvasive collection (eg, urine, exhaled breath) or invasive procedures (eg, blood, bronchoalveolar lavage) and testing might use various methodologies (eg, genomics, transcriptomics, proteomics, metabolomics). Specimen type and testing methodology depends on the disease of interest, ability to obtain sample, and availability of biomarker testing. To develop a new biomarker, researchers must first identify and validate the target, and then determine the test characteristics of the biomarker. Once it has undergone initial development and testing, a new biomarker is then tested in the clinical setting before being implemented into practice. An ideal biomarker is one that is feasible to obtain, readily quantifiable, and offers meaningful information that impacts care. Learning how to reliably interpret the performance and clinical application of a new biomarker is an important skillset for all pediatricians in the hospital setting. Here we provide a high-level overview of the process from biomarker discovery to application. In addition, we provide an example for the real-world application of biomarkers as an opportunity for clinicians to build on their ability to critically evaluate, interpret, and implement biomarkers in clinical practice.PMID:37317806 | DOI:10.1542/hpeds.2022-007012

Clin Transl Med. 2023 Jun;13(6):e1298. doi: 10.1002/ctm2.1298.ABSTRACTBACKGROUND: Differentiated thyroid cancer (DTC) affects thousands of lives worldwide each year. Typically, DTC is a treatable disease with a good prognosis. Yet, some patients are subjected to partial or total thyroidectomy and radioiodine therapy to prevent local disease recurrence and metastasis. Unfortunately, thyroidectomy and/or radioiodine therapy often worsen(s) quality of life and might be unnecessary in indolent DTC cases. On the other hand, the lack of biomarkers indicating a potential metastatic thyroid cancer imposes an additional challenge to managing and treating patients with this disease.AIM: The presented clinical setting highlights the unmet need for a precise molecular diagnosis of DTC and potential metastatic disease, which should dictate appropriate therapy.MATERIALS AND METHODS: In this article, we present a differential multi-omics model approach, including metabolomics, genomics, and bioinformatic models, to distinguish normal glands from thyroid tumours. Additionally, we are proposing biomarkers that could indicate potential metastatic diseases in papillary thyroid cancer (PTC), a sub-class of DTC.RESULTS: Normal and tumour thyroid tissue from DTC patients had a distinct yet well-defined metabolic profile with high levels of anabolic metabolites and/or other metabolites associated with the energy maintenance of tumour cells. The consistency of the DTC metabolic profile allowed us to build a bioinformatic classification model capable of clearly distinguishing normal from tumor thyroid tissues, which might help diagnose thyroid cancer. Moreover, based on PTC patient samples, our data suggest that elevated nuclear and mitochondrial DNA mutational burden, intra-tumour heterogeneity, shortened telomere length, and altered metabolic profile reflect the potential for metastatic disease.DISCUSSION: Altogether, this work indicates that a differential and integrated multi-omics approach might improve DTC management, perhaps preventing unnecessary thyroid gland removal and/or radioiodine therapy.CONCLUSIONS: Well-designed, prospective translational clinical trials will ultimately show the value of this integrated multi-omics approach and early diagnosis of DTC and potential metastatic PTC.PMID:37317665 | DOI:10.1002/ctm2.1298

J Pineal Res. 2023 Jun 15. doi: 10.1111/jpi.12892. Online ahead of print.ABSTRACTThe accelerated pace of life at the present time has resulted in tremendous alterations in living patterns. Changes in diet and eating patterns, in particular, coupled with irregular light-dark cycles (LD) will further induce circadian misalignment and lead to disease. Emerging data has highlighted the regulatory effects of diet and eating patterns on the host microbe interactions with the circadian clock (CC), immunity, and metabolism. Herein, we studied how LD cycles regulate the homeostatic crosstalk among the gut microbiome (GM), hypothalamic and hepatic CC oscillations, and immunity and metabolism using multi-omics approaches. Our data demonstrated that central CC oscillations lost rhythmicity under irregular LD cycles, but LD cycles had minimal effects on diurnal expression of peripheral CC genes in the liver including Bmal1. We further demonstrated that the GM could regulate hepatic circadian rhythms under irregular LD cycles, the candidate bacteria including Limosilactobacillus, Actinomyces, Veillonella, Prevotella, Campylobacter, Faecalibacterium, Kingella, Clostridia vadinBB60, Veillonella. A comparative transcriptomic study of innate immune genes indicated that different LD cycles had varying effects on immune functions, while irregular LD cycles had greater impacts on hepatic innate immune functions than those in the hypothalamus. Extreme LD cycle alterations (LD0/24 and LD24/0) had worse impacts than slight alterations (LD8/16 and LD16/8), and led to gut dysbiosis in mice receiving antibiotics. Metabolome data also demonstrated that hepatic tryptophan metabolism mediated the homeostatic crosstalk among GM-liver-brain axis in response to different LD cycles. These research findings highlighted that GM could regulate immune and metabolic disorders induced by circadian dysregulation. Further, the data provided potential targets for developing probiotics for individuals with circadian disruption such as shift workers. This article is protected by copyright. All rights reserved.PMID:37317652 | DOI:10.1111/jpi.12892

Microorganisms. 2023 May 17;11(5):1319. doi: 10.3390/microorganisms11051319.ABSTRACTSolid-state fermentation is known to improve plant-based feed nutritional quality; however, the association between microbes and metabolite production in fermented feed remains unclear. We inoculated corn-soybean-wheat bran (CSW) meal feed with Bacillus licheniformis Y5-39, Bacillus subtilis B-1, and lactic acid bacteria RSG-1. Then, 16S rDNA sequencing and untargeted metabolomic profiling were applied to investigate changes in the microflora and metabolites, respectively, and their integrated correlations during fermentation were assessed. The results indicated that trichloroacetic acid soluble protein levels showed a sharp increase, while glycinin and β-conglycinin levels showed a sharp decrease in the fermented feed, as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Pediococcus, Enterococcus, and Lactobacillus were predominant in the fermented feed. Overall, 699 significantly different metabolites were identified before and after fermentation. Arginine and proline, cysteine and methionine, and phenylalanine and tryptophan metabolism were the key pathways, with arginine and proline metabolism being the most important pathway in the fermentation process. By analyzing the correlation between the microbiota and metabolite production, lysyl-valine and lysyl-proline levels were found to be positively correlated with Enterococcus and Lactobacillus abundance. However, Pediococcus was positively correlated with some metabolites contributing to nutritional status and immune function. According to our data, Pediococcus, Enterococcus, and Lactobacillus mainly participate in protein degradation, amino acid metabolism, and lactic acid production in fermented feed. Our results provide new insights into the dynamic changes in metabolism that occurred during the solid-state fermentation of corn-soybean meal feed using compound strains and should facilitate the optimization of fermentation production efficiency and feed quality.PMID:37317292 | DOI:10.3390/microorganisms11051319

Gut Microbes. 2023 Dec 31;15(1):2223330. doi: 10.1080/19490976.2023.2223330.ABSTRACTIndividuals with nonalcoholic fatty liver disease (NAFLD) have an altered gut microbiota composition. Moreover, hepatic DNA methylation may be altered in the state of NAFLD. Using a fecal microbiota transplantation (FMT) intervention, we aimed to investigate whether a change in gut microbiota composition relates to altered liver DNA methylation in NAFLD. Moreover, we assessed whether plasma metabolite profiles altered by FMT relate to changes in liver DNA methylation. Twenty-one individuals with NAFLD underwent three 8-weekly vegan allogenic donor (n = 10) or autologous (n = 11) FMTs. We obtained hepatic DNA methylation profiles from paired liver biopsies of study participants before and after FMTs. We applied a multi-omics machine learning approach to identify changes in the gut microbiome, peripheral blood metabolome and liver DNA methylome, and analyzed cross-omics correlations. Vegan allogenic donor FMT compared to autologous FMT induced distinct differential changes in I) gut microbiota profiles, including increased abundance of Eubacterium siraeum and potential probiotic Blautia wexlerae; II) plasma metabolites, including altered levels of phenylacetylcarnitine (PAC) and phenylacetylglutamine (PAG) both from gut-derived phenylacetic acid, and of several choline-derived long-chain acylcholines; and III) hepatic DNA methylation profiles, most importantly in Threonyl-TRNA Synthetase 1 (TARS) and Zinc finger protein 57 (ZFP57). Multi-omics analysis showed that Gemmiger formicillis and Firmicutes bacterium_CAG_170 positively correlated with both PAC and PAG. E siraeum negatively correlated with DNA methylation of cg16885113 in ZFP57. Alterations in gut microbiota composition by FMT caused widespread changes in plasma metabolites (e.g. PAC, PAG, and choline-derived metabolites) and liver DNA methylation profiles in individuals with NAFLD. These results indicate that FMTs might induce metaorganismal pathway changes, from the gut bacteria to the liver.PMID:37317027 | DOI:10.1080/19490976.2023.2223330

Food Res Int. 2023 Aug;170:112977. doi: 10.1016/j.foodres.2023.112977. Epub 2023 May 22.ABSTRACTPolar lipids play essential biological functions in energy storage, both as structural components of cell membranes and as signaling molecules. In this study, a comprehensive UHPLC-QTRAP-MS-based lipidomic analysis of mature breast milk (BM) and ewe milk (EM) was conducted. Through the analysis, a total of 362 polar lipid species from 14 subclasses were characterized, including 60 phosphatidylethanolamines (PEs), 59 phosphatidylcholines (PCs), 38 phosphatidylinositols (PIs), 35 sphingomyelins (SMs), and 34 ceramides (Cers). Of these, 139 lipid molecules were screened as significantly differentially expressed polar lipids (SDPLs) between the two kinds of milk based on the following criteria: a variable importance in projection (VIP) value > 1.0, a false discovery rate-adjusted P-value < 0.0001, and a fold change (FC) of either > 2.0 or < 0.5; these included 111 upregulated and 28 downregulated SDPLs in EM compared to BM. Among these SDPLs, the content of PE (16:1_18:0) was found to be significantly higher in EM compared to BM (FC = 69.5853, P < 0.0001). Moreover, sphingolipid metabolism and glycerophospholipid metabolism were determined to be vital metabolic pathways. This was derived from the finding that PE, PC, SM, and PI were key lipid metabolites in the two kinds of milk that were related to these two metabolic pathways. This study provides new insights into the characterization of SDPLs in mammalian milk, and also provides a theoretical basis for optimizing infant formula.PMID:37316057 | DOI:10.1016/j.foodres.2023.112977

Food Res Int. 2023 Aug;170:113020. doi: 10.1016/j.foodres.2023.113020. Epub 2023 May 21.ABSTRACTThe production and use of ozone micro-nano bubble water (O3-MNBW) is an innovative technology that prolongs the reactivity of aqueous-phase ozone and maintains the freshness and quality of fruits and vegetables by removing pesticides, mycotoxins, and other contaminants. The quality of parsley treated with different concentrations of O3-MNBW was investigated during storage at 20 ℃ for 5 d, and found that a ten-minute exposure of parsley to 2.5 mg·L-1 O3-MNBW effectively preserved the sensory quality of parsley, and resulted in lower weight loss, respiration rate, ethylene production, MDA levels, and a higher level of firmness, vitamin C, and chlorophyll content, relative to untreated parsley. The O3-MNBW treatment also increased the level of total phenolics and flavonoids, enhanced peroxidase and ascorbate peroxidase activity, and inhibited polyphenol oxidase activity in stored parsley. Five volatile signatures identified using an electronic nose (W1W, sulfur-compounds; W2S, ethanol; W2W, aromatic- and organic- sulfur compounds; W5S, oxynitride; W1S, methane) exhibited a significant decrease in response to the O3-MNBW treatment. A total of 24 major volatiles were identified. A metabolomic analysis identified 365 differentially abundant metabolites (DMs). Among them, 30 and 19 DMs were associated with characteristic volatile flavor substance metabolism in O3-MNBW and control groups, respectively. The O3-MNBW treatment increased the abundance of most DMs related to flavor metabolism and reduced the level of naringin and apigenin. Our results provide insight into the mechanisms that are regulated in response to the exposure of parsley to O3-MNBW, and confirmed the potential use of O3-MNBW as a preservation technology.PMID:37316085 | DOI:10.1016/j.foodres.2023.113020

Food Res Int. 2023 Aug;170:112992. doi: 10.1016/j.foodres.2023.112992. Epub 2023 May 19.ABSTRACTDark tea fermentation involves various fungi, but studies focusing on the mixed fermentation in tea remain limited. This study investigated the influences of single and mixed fermentation on the dynamical alterations of tea metabolites. The differential metabolites between unfermented and fermented teas were determined using untargeted metabolomics. Dynamical changes in metabolites were explored by temporal clustering analysis. Results indicated that Aspergillus cristatus (AC) at 15 days, Aspergillus neoniger (AN) at 15 days, and mixed fungi (MF) at 15 days had respectively 68, 128 and 135 differential metabolites, compared with unfermentation (UF) at 15 days. Most of metabolites in the AN or MF group showed a down-regulated trend in cluster 1 and 2, whereas most of metabolites in the AC group showed an up-regulated trend in cluster 3 to 6. The three key metabolic pathways mainly composed of flavonoids and lipids included flavone and flavonol biosynthesis, glycerophospholipid metabolism and flavonoid biosynthesis. Based on the dynamical changes and metabolic pathways of the differential metabolites, AN showed a predominant status in MF compared with AC. Together, this study will advance the understanding of dynamic changes in tea fermentation and provide valuable insights into the processing and quality control of dark tea.PMID:37316065 | DOI:10.1016/j.foodres.2023.112992

Food Res Int. 2023 Aug;170:112965. doi: 10.1016/j.foodres.2023.112965. Epub 2023 May 14.ABSTRACTThe scandal of detecting 1, 2-propanediol (PL) in milk brought a crisis to the trust of consumers in the dairy industry, and the potential toxicity of PL has aroused the public concern about dietary exposure. A total of 200 pasteurized milk samples were collected from 15 regions, and the quantity of PL ranged between 0 and 0.31 g kg-1. Pseudo-targeted quantitative metabolomics integrated with proteomics demonstrated that PL enhanced the reduction of κ-casein, β-casein, and 107 substances (41 amines and 66 amides) containing amide bonds. Pathway enrichment and topological analysis indicated that PL induced the metabolism of lipids, amino acids, oligosaccharide nucleotides, and alkaloids by accelerating the rate of nucleophilic reaction, and acetylcholinesterase, sarcosine oxidase, and prolyl 4-hydroxylase were determined as the vital enzymes related to the degradation of above nutrients. The results of molecular simulation calculation illustrated that the number of hydrogen bonds between acetylcholinesterase, sarcosine oxidase, and substrate increased to 2 and 3, respectively, while the position of hydrogen bonds between prolyl 4-hydroxylase and proline was shifted, indicating the change of conformation and the enhancement of hydrogen bond force were essential factors for the up-regulation of enzyme activity. This study first revealed the mechanism of deposition and transformation of PL in milk, which contributed to the knowledge of the quality control of milk and provided vital indicators to evaluate the adverse risks of PL in dairy products.PMID:37316053 | DOI:10.1016/j.foodres.2023.112965

Food Res Int. 2023 Aug;170:112963. doi: 10.1016/j.foodres.2023.112963. Epub 2023 May 15.ABSTRACTThe present study attempted for the first time to explore the effects of the daily oral intake of a phenolics-rich extract from chestnut shells (CS) on the metabolomic profiling of rat tissues by liquid chromatography coupled to Orbitrap-mass spectrometry (LC-ESI-LTQ-Orbitrap-MS) targeted to polyphenolics and their metabolites and screen potential oxidative stress biomarkers, validating its use as a promising nutraceutical ingredient with outstanding antioxidant properties for the prevention and co-therapy of lifestyle-related diseases triggered by oxidative stress. The results demonstrated new insights into the metabolomic fingerprinting of polyphenols from CS, confirming their absorption and biotransformation by phase I (hydrogenation) and II (glucuronidation, methylation, and sulfation) enzymes. Phenolic acids were the main polyphenolic class, followed by hydrolyzable tannins, flavanols, and lignans. In contrast to the liver, sulfated conjugates were the principal metabolites reaching the kidneys. The multivariate data analysis predicted an exceptional contribution of polyphenols and their microbial and phase II metabolites to the in-vivo antioxidant response of the CS extract in rats, recommending its use as an appealing source of anti-aging molecules for nutraceuticals. This is the first study that explored the relation between metabolomic profiling of rat tissues and in-vivo antioxidant effects after oral treatment with a phenolics-rich CS extract.PMID:37316050 | DOI:10.1016/j.foodres.2023.112963

Food Res Int. 2023 Aug;170:112953. doi: 10.1016/j.foodres.2023.112953. Epub 2023 May 14.ABSTRACTMany healthy people suffer from milk-related gastrointestinal discomfort (GID) despite not being lactose intolerant; the mechanisms underpinning such condition are unknown. This study aimed to explore milk protein digestion and related physiological responses (primary outcome), gut microbiome and gut permeability in 19 lactose-tolerant healthy nonhabitual milk consumers [NHMCs] reporting GID after consuming cow milk compared to 20 habitual milk consumers [HMCs] without GID. NHMCs and HMCs participated in a milk-load (250 mL) test, underwent blood sample collection at 6 time points over 6 h after milk consumption and collected urine samples and GID self-reports over 24 h. We measured the concentrations of 31 milk-derived bioactive peptides (BAPs), 20 amino acids, 4 hormones, 5 endocannabinoid system mediators, glucose and the dipeptidyl peptidase-IV (DPPIV) activity in blood and indoxyl sulfate in urine samples. Subjects also participated in a gut permeability test and delivered feces sample for gut microbiome analysis. Results showed that, compared to HMCs, milk consumption in NHMCs, along with GID, elicited a slower and lower increase in circulating BAPs, lower responses of ghrelin, insulin, and anandamide, a higher glucose response and serum DPPIV activity. The gut permeability of the two groups was similar, while the habitual diet, which was lower in dairy products and higher in the dietary-fibre-to-protein ratio in NHMCs, possibly shaped the gut microbiome; NHMCs exhibited lower abundance of Bifidobacteria, higher abundance of Prevotella and lower abundance of protease-coding genes, which may have reduced protein digestion, as evidenced by lower urinary excretion of indoxyl sulfate. In conclusion, the findings showed that a less efficient digestion of milk proteins, supported by a lower proteolytic capability of the gut microbiome, may explain GID in healthy people after milk consumption.PMID:37316045 | DOI:10.1016/j.foodres.2023.112953

Food Res Int. 2023 Aug;170:112753. doi: 10.1016/j.foodres.2023.112753. Epub 2023 Apr 7.ABSTRACTIn this study, antioxidant and anti-aging studies were carried out by mannoprotein-rich yeast cell wall enzymatic hydrolysate (MYH) obtained by enzymatic hydrolysis of yeast cell wall through the Caenorhabditis elegans (C. elegans) model. It was found that MYH could improve the lifespan and anti-stress ability of C. elegans by increasing the activity of antioxidant enzymes such as T-SOD, GSH-PX and CAT, and reducing the levels of MDA, ROS and apoptosis. At the same time, through the verification expression of corresponding mRNA, it was found that MYH exerted antioxidant and anti-aging activities by up-regulating the translation of MTL-1, DAF-16, SKN-1 and SOD-3 mRNA, and down-regulating the translation of AGE-1 and DAF-2 mRNA. In addition, it was found that MYH could improve the composition and distribution of the gut microbiota of C. elegans, and significantly improve the level of metabolites through the sequencing of gut microbiota and untargeted metabolomic studies. It has contributed to studying the antioxidant and anti-aging activities of microorganisms such as yeast through the level of gut microbiota and metabolites and the development of related functional foods.PMID:37316035 | DOI:10.1016/j.foodres.2023.112753

Food Res Int. 2023 Aug;170:112997. doi: 10.1016/j.foodres.2023.112997. Epub 2023 May 22.ABSTRACTNot least because it is adaptable to a variety of geographies and climates, potato (Solanum tuberosum L.) is grown across much of the world. Pigmented potato tubers have been found to contain large quantities of flavonoids, which have various functional roles and act as antioxidants in the human diet. However, the effect of altitude on the biosynthesis and accumulation of flavonoids in potato tubers is poorly characterized. Here we carried out an integrated metabolomic and transcriptomic study in order to evaluate how cultivation at low (800 m), moderate (1800 m), and high (3600 m) altitude affects flavonoid biosynthesis in pigmented potato tubers. Both red and purple potato tubers grown at a high altitude contained the highest flavonoid content, and the most highly pigmented flesh, followed by those grown at a low altitude. Co-expression network analysis revealed three modules containing genes which were positively correlated with altitude-responsive flavonoid accumulation. The anthocyanin repressors StMYBATV and StMYB3 exhibited a significant positive relationship with altitude-responsive flavonoid accumulation. The repressive function of StMYB3 was further verified in tobacco flowers and potato tubers. The results presented here add to the growing body of knowledge regarding the response of flavonoid biosynthesis to environmental conditions, and should aid in efforts to develop novel varieties of pigmented potatoes for use across different geographies.PMID:37316022 | DOI:10.1016/j.foodres.2023.112997

Food Res Int. 2023 Aug;170:112934. doi: 10.1016/j.foodres.2023.112934. Epub 2023 May 3.ABSTRACTDuring storage, Aspergillus carbonarius (A. carbonarius) can easily infect grape berries, resulting in a pronounced decline in nutritional value and substantial economic loss for the grape industry. Characterised by broad-spectrum antibacterial activity, eugenol is proven to significantly inhibit A. carbonarius and ochratoxin A (OTA) in vitro. In this study, the potential mechanism of eugenol against A. carbonarius in grapes ('Kyoho') was evaluated using integrative transcriptomic and metabolomics analyses. After eugenol treatment at 50 mM, the inhibition of OTA was reduced by 100%, despite a 56.2% inhibition of A. carbonarius. In the meantime, mycelial growth was completely inhibited by 100 mM eugenol in grape berries. The application of eugenol to grapes stimulated the activity of several enzymes involved in disease resistance, namely catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), chitinase (CHI), β-1,3-glucanase (GLU), cinnamate-4-hydroxylase (C4H), phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL) and glutathione (GSH) content. In addition, the contents of abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA) in eugenol-treated grapes were higher after A. carbonarius inoculation. Combined transcriptomic and metabolomic analysis revealed that in phenylpropane biosynthesis, there were a variety of differentially expressed metabolites (DEMs) and differentially expressed genes (DEGs), and the plant hormone signalling pathway changed significantly. Among these, the levels of 47 polyphenol metabolites significantly increased in eugenol-treated grape berries compared to noneugenol-treated berries. Meanwhile, we investigated the transcript levels of 39 genes in 6 phytohormones signalling in response to eugenol-treated grape berries followed by A. carbonarius inoculation. These results suggest that eugenol positively improved the disease resistance of grapes and might be potentially beneficial for the prevention and treatment of A. carbonarius-caused disease.PMID:37316002 | DOI:10.1016/j.foodres.2023.112934

Metabolism. 2023 Jun 12:155628. doi: 10.1016/j.metabol.2023.155628. Online ahead of print.ABSTRACTBACKGROUND: The Metabolic reprogramming of tumor cells plays a vital role in the progression of hepatocellular carcinoma. Organic cation/carnitine transporter 2 (OCTN2), a sodium-ion dependent carnitine transporter and a sodium-ion independent tetraethylammonium (TEA) transporter, has been reported to contribute tumor malignancies and metabolic dysregulation in renal and esophageal carcinoma. However, the role of lipid metabolism deregulation mediated by OCTN2 in HCC cells has not been clarified.METHODS: Bioinformatics analyses and immunohistochemistry assay were employed to identify OCTN2 expression in HCC tissues. The correlation between OCTN2 expression and prognosis was elucidated through K-M survival analysis. The expression and function of OCTN2 were examined via the assays of western blotting, sphere formation, cell proliferation, migration and invasion. The mechanism of OCTN2-mediated HCC malignancies was investigated through RNA-seq and metabolomic analyses. Furthermore, xenograft tumor models based on HCC cells with different OCTN2 expression levels were conducted to analyze the tumorigenic and targetable role of OCTN2 in vivo.RESULTS: We found that gradually focused OCTN2 was significantly upregulated in HCC and tightly associated with poor prognosis. Additionally, OCTN2 upregulation promoted HCC cells proliferation and migration in vitro and augmented the growth and metastasis of HCC. Moreover, OCTN2 promoted the cancer stem-like properties of HCC by increasing fatty acid oxidation and oxidative phosphorylation. Mechanistically, PGC-1α signaling participated in the HCC cancer stem-like properties mediated by OCTN2 overexpression, which is confirmed by in vitro and in vivo analyses. Furthermore, OCTN2 upregulation may be transcriptionally activated by YY1 in HCC. Particularly, treatment with mildronate, an inhibitor of OCTN2, showed a therapeutic influence on HCC in vitro and in vivo.CONCLUSIONS: Our findings demonstrate that OCTN2 plays a critical metabolic role in HCC cancer stemness maintenance and HCC progression, providing evidence for OCTN2 as a promising target for HCC therapy.PMID:37315888 | DOI:10.1016/j.metabol.2023.155628

Pharmacol Res. 2023 Jun 12:106817. doi: 10.1016/j.phrs.2023.106817. Online ahead of print.ABSTRACTA potential role of berberine, a benzyl isoquinoline alkaloid, in cancer therapy is apparent. Its underlying mechanisms of berberine against breast carcinoma under hypoxia have not been elucidated. We focused on the doubt how berberine restrains breast carcinoma under hypoxia in vitro and in vivo. A molecular analysis of the microbiome via 16S rDNA gene sequencing of DNA from mouse faeces confirmed that the abundances and diversity of gut microbiota were significantly altered in 4T1/Luc mice with higher survival rate following berberine treatment. A metabolome analysis liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS) revealed that berberine regulated various endogenous metabolites, especially L-palmitoylcarnitine. Furthermore, the cytotoxicity of berberine was investigated in MDA-MB-231, MCF-7, and 4T1 cells. In vitro to simulate under hypoxic environment, MTT assay showed that berberine inhibited the proliferation of MDA-MB-231, MCF-7, and 4T1 cells with IC50 values of 4.14 ± 0.35μM, 26.53 ± 3.12μM and 11.62 ± 1.44μM, respectively. Wound healing and trans-well invasion studies revealed that berberine inhibited the invasion and migration of breast cancer cells. RT-qPCR analysis shed light that berberine reduced the expression of hypoxia-inducible factor-1α (HIF-1α) gene. Immunofluorescence and western blot demonstrated that berberine decreased the expression of E-cadherin and HIF-1α protein. Taken together, these results provide evidence that berberine efficiently suppresses breast carcinoma growth and metastasis in a hypoxic microenvironment, highlighting the potential of berberine as a promising anti-neoplastic agent to combat breast carcinoma.PMID:37315824 | DOI:10.1016/j.phrs.2023.106817

J Biol Chem. 2023 Jun 12:104919. doi: 10.1016/j.jbc.2023.104919. Online ahead of print.ABSTRACTCoenzymes are important for all classes of enzymatic reactions and essential for cellular metabolism. Most coenzymes are synthesized from dedicated precursors, also referred to as vitamins, which prototrophic bacteria can either produce themselves from simpler substrates or take up from the environment. The extent to which prototrophs use supplied vitamins and whether externally available vitamins affect the size of intracellular coenzyme pools and control endogenous vitamin synthesis is currently largely unknown. Here, we studied coenzyme pool sizes and vitamin incorporation into coenzymes during growth on different carbon source and vitamin supplementation regimes using metabolomics approaches. We found that the model bacterium Escherichia coli incorporated pyridoxal, niacin, and pantothenate into pyridoxal 5'-phosphate, NAD, and coenzyme A (CoA), respectively. In contrast, riboflavin was not taken up and was produced exclusively endogenously. Coenzyme pools were mostly homeostatic and not affected by externally supplied precursors. Remarkably, we found that pantothenate is not incorporated into CoA as such but is first degraded to pantoate and β-alanine and then rebuilt. This pattern was conserved in various bacterial isolates, suggesting a preference for β-alanine over pantothenate utilization in CoA synthesis. Finally, we found that the endogenous synthesis of coenzyme precursors remains active when vitamins are supplied, which is consistent with described expression data of genes for enzymes involved in coenzyme biosynthesis under these conditions. Continued production of endogenous coenzymes may ensure rapid synthesis of the mature coenzyme under changing environmental conditions, protect against coenzyme limitation, and explain vitamin availability in naturally oligotrophic environments.PMID:37315792 | DOI:10.1016/j.jbc.2023.104919

Clin Chim Acta. 2023 Jun 12:117445. doi: 10.1016/j.cca.2023.117445. Online ahead of print.ABSTRACTOver the last decade, increasing research has focused on urinary exosomes (UEs) in biological fluids and their relationship with physiological and pathological processes. UEs are membranous vesicles with a size of 40-100 nm, containing a number of bioactive molecules such as proteins, lipids, mRNAs, and miRNAs. These vesicles are an inexpensive non-invasive source that can be used in clinical settings to differentiate healthy patients from diseased patients, thereby serving as potential biomarkers for the early identification of disease. Recent studies have reported the isolation of small molecules called exosomal metabolites from individuals' urine with different diseases. These metabolites could utilize for a variety of purposes, such as the discovery of biomarkers, investigation of mechanisms related to disease development, and importantly prediction of cardiovascular diseases (CVDs) risk factors, including thrombosis, inflammation, oxidative stress, hyperlipidemia as well as homocysteine. It has been indicated that alteration in urinary metabolites of N1-methylnicotinamide, 4-aminohippuric acid, and citric acid can be valuable in predicting cardiovascular risk factors, providing a novel approach to evaluating the pathological status of CVDs. Since the UEs metabolome has been clearly and precisely so far unexplored in CVDs, the present study has specifically addressed the role of the mentioned metabolites in the prediction of CVDs risk factors.PMID:37315726 | DOI:10.1016/j.cca.2023.117445