PubMed

Mol Plant Pathol. 2023 Oct 12. doi: 10.1111/mpp.13396. Online ahead of print.ABSTRACTRoot-knot nematodes (RKNs) inflict extensive damage to global agricultural production. Intercropping has been identified as a viable agricultural tool for combating RKNs, but the mechanisms by which intercropped plants modulate RKN parasitism are still not well understood. Here, we focus on the cucumber-amaranth intercropping system. We used a range of approaches, including the attraction assay, in vitro RNA interference (RNAi), untargeted metabolomics, and hairy root transformation, to unveil the mechanisms by which weak host plants regulate Meloidogyne incognita chemotaxis towards host plants and control infection. Amaranth roots showed a direct repellence to M. incognita through disrupting its chemotaxis. The in vitro RNAi assay demonstrated that the Mi-flp-1 and Mi-flp-18 genes (encoding FMRFamide-like peptides) regulated M. incognita chemotaxis towards cucumber and controlled infection. Moreover, M. incognita infection stimulated cucumber and amaranth to accumulate distinct metabolites in both root tissues and rhizosphere soils. In particular, naringenin and salicin, enriched specifically in amaranth rhizosphere soils, inhibited the expression of Mi-flp-1 and Mi-flp-18. In addition, overexpression of genes involved in the biosynthesis of pantothenic acid and phloretin, both of which were enriched specifically in amaranth root tissues, delayed M. incognita development in cucumber hairy roots. Together, our results reveal that both the distinct host status and disruption of chemotaxis contribute to M. incognita inhibition in intercropping.PMID:37823341 | DOI:10.1111/mpp.13396

New Phytol. 2023 Oct 12. doi: 10.1111/nph.19298. Online ahead of print.ABSTRACTMeloidogyne enterolobii is an emerging root-knot nematode species that overcomes most of the nematode resistance genes in crops. Nematode effector proteins secreted in planta are key elements in the molecular dialogue of parasitism. Here, we show the MeMSP1 effector is secreted into giant cells and promotes M. enterolobii parasitism. Using co-immunoprecipitation and bimolecular fluorescent complementation assays, we identified glutathione-S-transferase phi GSTFs as host targets of the MeMSP1 effector. This protein family plays important roles in plant responses to abiotic and biotic stresses. We demonstrate that MeMSP1 interacts with all Arabidopsis GSTF. Moreover, we confirmed that the N-terminal region of AtGSTF9 is critical for its interaction, and atgstf9 mutant lines are more susceptible to root-knot nematode infection. Combined transcriptome and metabolome analyses showed that MeMSP1 affects the metabolic pathways of Arabidopsis thaliana, resulting in the accumulation of amino acids, nucleic acids, and their metabolites, and organic acids and the downregulation of flavonoids. Our study has shed light on a novel effector mechanism that targets plant metabolism, reducing the production of plant defence-related compounds while favouring the accumulation of metabolites beneficial to the nematode, and thereby promoting parasitism.PMID:37823217 | DOI:10.1111/nph.19298

Food Sci Nutr. 2023 Aug 10;11(10):6271-6287. doi: 10.1002/fsn3.3567. eCollection 2023 Oct.ABSTRACTChinese yam (Dioscorea opposite Thunb.) has been used as food and medicine to treat diarrhea for thousands of years. This article aimed to elucidate the potential mechanism of Dioscoreae Rhizoma starch in alleviating chronic diarrhea induced by rhubarb based on gut microbiotas and fecal metabolome. The administration of the Dioscoreae Rhizoma aqueous extracts, crude polysaccharides, and starch could improve diarrhea and alleviate intestinal injury in chronic diarrhea rats. The Dioscoreae Rhizoma starch displayed the most apparent effect on regulating intestinal microbiotas by increasing the abundance and diversity of microbiotas. At the genus level, there were 17 changed intestinal microbiotas in model rats, and the treatment with Dioscoreae Rhizoma starch regulated 11 microbiotas. Metabolomics analysis revealed that Dioscoreae Rhizoma starch could regulate abnormal fecal metabolites to alleviate diarrhea, and these metabolites are involved in phenylalanine, tyrosine, and tryptophan biosynthesis; tyrosine metabolism; vitamin B6 metabolism; and purine metabolism. This study will contribute to the further research and development of Dioscoreae Rhizoma starch.PMID:37823173 | PMC:PMC10563677 | DOI:10.1002/fsn3.3567

Food Sci Nutr. 2023 Jul 18;11(10):6199-6212. doi: 10.1002/fsn3.3559. eCollection 2023 Oct.ABSTRACTHuman milk oligosaccharides (HMOs) belong to a group of multifunctional glycans that are abundantly present in human breast milk. While health effects of neutral oligosaccharides have been investigated extensively, a lot remains unknown regarding health effects of acidic oligosaccharides, such as the two sialyllactoses (SLs), 3'sialyllactose (3'SL), and 6'sialyllactose (6'SL). We utilized Caenorhabditis elegans (C. elegans) to investigate the effects of SLs on exercise performance. Using swimming as an endurance-type exercise, we found that SLs decrease exhaustion, signifying an increase in endurance that is strongest for 6'SL. Through an unbiased metabolomics approach, we identified changes in energy metabolism that correlated with endurance performance. Further investigation suggested that these metabolic changes were related to adaptations of muscle mitochondria that facilitated a shift from beta oxidation to glycogenolysis during exercise. We found that the effect of SLs on endurance performance required AMPK- (aak-1/aak-2) and adenosine receptor (ador-1) signaling. We propose a model where SLs alter the metabolic status in the gut, causing a signal from the intestine to the nervous system toward muscle cells, where metabolic adaptation increases exercise performance. Together, our results underline the potential of SLs in exercise-associated health and contribute to our understanding of the molecular processes involved in nutritionally-induced health benefits.PMID:37823127 | PMC:PMC10563706 | DOI:10.1002/fsn3.3559

Front Nutr. 2023 Sep 26;10:1242301. doi: 10.3389/fnut.2023.1242301. eCollection 2023.ABSTRACTRuminants' milk is commonly used for supplying nutrients to infants when breast milk is unavailable or limited. Previous studies have highlighted the differences between ruminants' milk composition, digestion, absorption, and fermentation. However, whether consuming different ruminants' milk impact the appearance of the circulatory blood metabolites in the early postnatal life is not well understood. The analysis conducted here aimed to determine the effect of feeding exclusively whole milk from bovine, caprine or ovine species to pigs, approximately 7 days-old for 15 days, on circulatory blood plasma metabolites. Relative intensities of plasma metabolites were detected using a liquid chromatography-mass spectrometry based metabolomic approach. Seven polar and 83 non-polar (lipids) metabolites in plasma were significantly different (false discovery rate < 0.05) between milk treatments. These included polar metabolites involved in amino acid metabolism and lipids belonging to phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, and triglycerides. Compared to the caprine or bovine milk group, the relative intensities of polar metabolites and unsaturated triglycerides were higher in the peripheral circulation of the ovine milk group. In contrast, relative intensities of saturated triglycerides and phosphatidylcholine were higher in the bovine milk group compared to the ovine or caprine milk group. In addition, correlations were identified between amino acid and lipid intake and their appearance in peripheral blood circulation. The results highlighted that consuming different ruminants' milk influences the plasma appearance of metabolites, especially lipids, that may contribute to early postnatal life development in pigs.PMID:37823089 | PMC:PMC10564076 | DOI:10.3389/fnut.2023.1242301

Exposome. 2023 May 26;3(1):osad006. doi: 10.1093/exposome/osad006.ABSTRACTChildhood obesity is an increasingly severe public health problem, with a prospective impact on health. We propose an exposome approach to identify actionable risk factors for this condition. Our assumption is that relationships between external exposures and outcomes such as rapid growth, overweight, or obesity in children can be better understood through a "meet-in-the-middle" model. This is based on a combination of external and internal exposome-based approaches, that is, the study of multiple exposures (in our case, dietary patterns) and molecular pathways (metabolomics and epigenetics). This may strengthen causal reasoning by identifying intermediate markers that are associated with both exposures and outcomes. Our biomarker-based studies in the STOP consortium suggest (in several ways, including mediation analysis) that branched-chain amino acids (BCAAs) could be mediators of the effect of dietary risk factors on childhood overweight/obesity. This is consistent with intervention and animal studies showing that higher intake of BCAAs has a positive impact on body composition, glycemia, and satiety. Concerning food, of particular concern is the trend of increasing intake of ultra-processed food (UPF), including among children. Several mechanisms have been proposed to explain the impact of UPF on obesity and overweight, including nutrient intake (particularly proteins), changes in appetite, or the role of additives. Research from the Avon Longitudinal Study of Parents and Children cohort has shown a relationship between UPF intake and trajectories in childhood adiposity, while UPF was related to lower blood levels of BCAAs. We suggest that an exposome-based approach can help strengthening causal reasoning and support policies. Intake of UPF in children should be restricted to prevent obesity.PMID:37823001 | PMC:PMC7615122 | DOI:10.1093/exposome/osad006

Front Vet Sci. 2023 Sep 26;10:1273944. doi: 10.3389/fvets.2023.1273944. eCollection 2023.ABSTRACTHexavalent chromium Cr (VI) is one of the most hazardous heavy metals in the environment and is toxic to living organisms causing tissue damage, disruption of the intestinal microbiota and cancer. However, there is little information on the relationship between the Cr (VI) and broiler chickens. The current study was performed to investigate the effect of Cr (VI) on growth performance, serum biochemical analysis, histopathological observations, and metabolomics analysis in broilers. Results show that Cr (VI) exposure significantly decreased the body weight (p < 0.01) and caused liver damages in broilers. With the extension of Cr (VI) action time, the liver appeared obvious pathological changes, including hepatic cord disorder, incomplete hepatocyte additionally, decreased serum biochemical indices of calcium (Ca), phosphorus (P), total protein (TP), phosphatase (ALP), and globin (GLB) significantly (p < 0.01). Moreover, metabolomics analysis indicated that 29 differential metabolites were identified, such as phytosphingosine, L-Serine, 12, 13-DHOME, Alpha-dimorphecolic acid, L-Methionine, L-Phenylalanine, 3-Dehydroshikimate, L-Tyrosine, and N-Acetyl-L-phenylalanine were significantly decreased under the action of Cr (VI) (p < 0.05). These 29 differential metabolites are mainly involved in 35 metabolic pathways, such as aminoacyl-tRNA biosynthesis, phenylalanine metabolism, sphingolipid, and linoleic metabolism. The study revealed that exposure to Cr (VI) resulted in a decrease in growth performance and metabolism, with the hazards and toxicity in broiler chicken. The findings provided new insight and a comprehensive understanding of the relationship between Cr (VI) and broiler chickens.PMID:37822955 | PMC:PMC10562699 | DOI:10.3389/fvets.2023.1273944

Front Pharmacol. 2023 Sep 25;14:1215150. doi: 10.3389/fphar.2023.1215150. eCollection 2023.ABSTRACTGlucose metabolic disorders (GMD) can promote insulin resistance (IR) and diabetes, and damage liver and kidney. Gynostemma pentaphyllum is commonly used in the clinical treatment of diabetes, but the research on its main active constituents and GMD has not been reported yet. This study explores the therapeutic potential of gypenosides of heat-processed Gynostemma pentaphyllum (HGyp) on high-fat diet-induced GMD in mice. HGyp was administered at different doses for 12 weeks. The investigation encompassed an array of parameters, including body weight, blood lipids, blood glucose, and liver tissue components. Metabolomic and network analyses were conducted to uncover potential targets and pathways associated with HGyp treatment. The results revealed that HGyp alleviated GMD by reducing body weight, blood glucose, and improving blood lipids levels, while increasing liver glycogen and antioxidant enzyme levels. Additionally, HGyp exhibited protective effects on liver and kidney health by reducing tissue damage. Fourteen blood components were detected by LC-MS. Metabolomic and network analyses indicated the potential engagement of the AGE-RAGE signaling pathway in the therapeutic effects of HGyp.Furthermore, Western blot and ELISA assays confirmed that HGyp upregulated GLO1 and GLUT4 while down-regulating AGEs and RAGE expression in liver tissue. In light of these findings, HGyp demonstrates promise as a potential therapeutic candidate for combating GMD, warranting further exploration in the development of therapeutic strategies or functional products.PMID:37822878 | PMC:PMC10563512 | DOI:10.3389/fphar.2023.1215150

Front Cell Dev Biol. 2023 Sep 26;11:1293677. doi: 10.3389/fcell.2023.1293677. eCollection 2023.NO ABSTRACTPMID:37822867 | PMC:PMC10562682 | DOI:10.3389/fcell.2023.1293677

PNAS Nexus. 2023 Oct 10;2(10):pgad306. doi: 10.1093/pnasnexus/pgad306. eCollection 2023 Oct.ABSTRACTAn acidic tumor microenvironment plays a critical role in tumor progression. However, understanding of metabolic reprogramming of tumors in response to acidic extracellular pH has remained elusive. Using comprehensive metabolomic analyses, we demonstrated that acidic extracellular pH (pH 6.8) leads to the accumulation of N1-acetylspermidine, a protumor metabolite, through up-regulation of the expression of spermidine/spermine acetyltransferase 1 (SAT1). Inhibition of SAT1 expression suppressed the accumulation of intra- and extracellular N1-acetylspermidine at acidic pH. Conversely, overexpression of SAT1 increased intra- and extracellular N1-acetylspermidine levels, supporting the proposal that SAT1 is responsible for accumulation of N1-acetylspermidine. While inhibition of SAT1 expression only had a minor effect on cancer cell growth in vitro, SAT1 knockdown significantly decreased tumor growth in vivo, supporting a contribution of the SAT1-N1-acetylspermidine axis to protumor immunity. Immune cell profiling revealed that inhibition of SAT1 expression decreased neutrophil recruitment to the tumor, resulting in impaired angiogenesis and tumor growth. We showed that antineutrophil-neutralizing antibodies suppressed growth in control tumors to a similar extent to that seen in SAT1 knockdown tumors in vivo. Further, a SAT1 signature was found to be correlated with poor patient prognosis. Our findings demonstrate that extracellular acidity stimulates recruitment of protumor neutrophils via the SAT1-N1-acetylspermidine axis, which may represent a metabolic target for antitumor immune therapy.PMID:37822765 | PMC:PMC10563787 | DOI:10.1093/pnasnexus/pgad306

Front Microbiol. 2023 Sep 25;14:1260120. doi: 10.3389/fmicb.2023.1260120. eCollection 2023.ABSTRACTThe past few decades have been plagued by an increasing number of infections caused by antibiotic resistant bacteria. To mitigate the rise in untreatable infections, we need new antibiotics with novel targets and drug combinations that reduce resistance development. The novel β-clamp targeting antimicrobial peptide BTP-001 was recently shown to have a strong additive effect in combination with the halogenated pyrrolopyrimidine JK-274. In this study, the molecular basis for this effect was examined by a comprehensive proteomic and metabolomic study of the individual and combined effects on Staphylococcus aureus. We found that JK-274 reduced activation of several TCA cycle enzymes, likely via increasing the cellular nitric oxide stress, and BTP-001 induced oxidative stress in addition to inhibiting replication, translation, and DNA repair processes. Analysis indicated that several proteins linked to stress were only activated in the combination and not in the single treatments. These results suggest that the strong additive effect is due to the activation of multiple stress responses that can only be triggered by the combined effect of the individual mechanisms. Importantly, the combination dose required to eradicate S. aureus was well tolerated and did not affect cell viability of immortalized human keratinocyte cells, suggesting a species-specific response. Our findings demonstrate the potential of JK-274 and BTP-001 as antibiotic drug candidates and warrant further studies.PMID:37822747 | PMC:PMC10564113 | DOI:10.3389/fmicb.2023.1260120

Plant Environ Interact. 2023 Sep 15;4(5):229-257. doi: 10.1002/pei3.10121. eCollection 2023 Oct.ABSTRACTRice is more vulnerable to drought than maize, wheat, and sorghum because its water requirements remain high throughout the rice life cycle. The effects of drought vary depending on the timing, intensity, and duration of the events, as well as on the rice genotype and developmental stage. It can affect all levels of organization, from genes to the cells, tissues, and/or organs. In this study, a moderate water deficit was applied to two contrasting rice genotypes, IAC 25 and CIRAD 409, during their reproductive stage. Multi-level transcriptomic, metabolomic, physiological, and morphological analyses were performed to investigate the complex traits involved in their response to drought. Weighted gene network correlation analysis was used to identify the specific molecular mechanisms regulated by each genotype, and the correlations between gene networks and phenotypic traits. A holistic analysis of all the data provided a deeper understanding of the specific mechanisms regulated by each genotype, and enabled the identification of gene markers. Under non-limiting water conditions, CIRAD 409 had a denser shoot, but shoot growth was slower despite better photosynthetic performance. Under water deficit, CIRAD 409 was weakly affected regardless of the plant level analyzed. In contrast, IAC 25 had reduced growth and reproductive development. It regulated transcriptomic and metabolic activities at a high level, and activated a complex gene regulatory network involved in growth-limiting processes. By comparing two contrasting genotypes, the present study identified the regulation of some fundamental processes and gene markers, that drive rice development, and influence its response to water deficit, in particular, the importance of the biosynthetic and regulatory pathways for cell wall metabolism. These key processes determine the biological and mechanical properties of the cell wall and thus influence plant development, organ expansion, and turgor maintenance under water deficit. Our results also question the genericity of the antagonism between morphogenesis and organogenesis observed in the two genotypes.PMID:37822730 | PMC:PMC10564380 | DOI:10.1002/pei3.10121

Plant Environ Interact. 2023 Sep 11;4(5):275-290. doi: 10.1002/pei3.10122. eCollection 2023 Oct.ABSTRACTPlant growth-promoting bacterias (PGPBs) can increase crop output under normal and abiotic conditions. However, the mechanisms underlying the plant salt tolerance-promoting role of PGPBs still remain largely unknown. In this study, we demonstrated that Halomonas ventosae JPT10 promoted the salt tolerance of both dicots and monocots. Physiological analysis revealed that JPT10 reduced reactive oxygen species accumulation by improving the antioxidant capability of foxtail millet seedlings. The metabolomic analysis of JPT10-inoculated foxtail millet seedlings led to the identification of 438 diversely accumulated metabolites, including flavonoids, phenolic acids, lignans, coumarins, sugar, alkaloids, organic acids, and lipids, under salt stress. Exogenous apigenin and chlorogenic acid increased the salt tolerance of foxtail millet seedlings. Simultaneously, JPT10 led to greater amounts of abscisic acid (ABA), indole-3-acetic acid (IAA), salicylic acid (SA), and their derivatives but lower levels of 12-oxo-phytodienoic acid (OPDA), jasmonate (JA), and JA-isoleucine (JA-Ile) under salt stress. Exogenous JA, methyl-JA, and OPDA intensified, whereas ibuprofen or phenitone, two inhibitors of JA and OPDA biosynthesis, partially reversed, the growth inhibition of foxtail millet seedlings caused by salt stress. Our results shed light on the response of foxtail millet seedlings to H. ventosae under salt stress and provide potential compounds to increase salt tolerance in foxtail millet and other crops.PMID:37822729 | PMC:PMC10564379 | DOI:10.1002/pei3.10122

iScience. 2023 Sep 9;26(10):107839. doi: 10.1016/j.isci.2023.107839. eCollection 2023 Oct 20.ABSTRACTIn various cancer models, dietary interventions have been shown to inhibit tumor growth, improve anticancer drug efficacy, and enhance immunity, but no such evidence exists for epithelial ovarian cancer (EOC), the most lethal gynecologic cancer. The anticancer immune responses induced by 16-h intermittent fasting (IF) were studied in mice with EOC. IF consistently reduced metabolic growth factors and cytokines that stimulate tumor growth, creating a tumor-hostile environment. Immune profiling showed that IF dramatically alters anti-cancer immunity by increasing CD4+ and CD8+ cells, Th1 and cytotoxic responses, and metabolic fitness. β-hydroxy butyrate (BHB), a bioactive metabolite produced by IF, partially imitates its anticancer effects by inducing CD8+ effector function. In a direct comparison, IF outperformed exogenous BHB treatment in survival and anti-tumor immune response, probably due to increased ketogenesis. Thus, IF and one of its metabolic mediators BHB suppress EOC growth and sustain a potent anti-tumor T cell response.PMID:37822507 | PMC:PMC10562806 | DOI:10.1016/j.isci.2023.107839

Front Plant Sci. 2023 Sep 26;14:1263354. doi: 10.3389/fpls.2023.1263354. eCollection 2023.ABSTRACTCitrus fruit's appearance is the primary criterion used to assess its quality for the fresh market, hence the rind's condition is a crucial quality trait. Pre-harvest rind disorder is one of the major physiological problems in mandarins. The disorder occurs right before harvest following rain events in some Mandarin varieties. Despite the economic damage caused by this kind of disorder, very limited information is available about the molecular mechanisms underlying the occurrence of this disorder. In the present study, we evaluated the primary metabolites, antioxidants, and hormones associated with the pre-harvest rind disorder in Mandarins. The study was carried out using ten-year-old 'Owari' Satsuma mandarin trees grafted on 'Carrizo' rootstock and grown in a commercial orchard in San Joaquin Valley, California, USA. Samples were collected from healthy tissue of healthy fruit (HF_HT), healthy tissue of damaged fruit (DF_HT), and damaged tissue of damaged fruit (DF_DT). Damaged fruit (DF_HT and DF_DT) showed lower cellulose concentrations than healthy fruit tissues (HF_HT), however, had similar contents of pectin and hemicellulose. The antioxidant activities showed no significant difference in all paired comparisons between samples as expressed in the malondialdehyde (MDA) content. However, DF_DT had a higher H2O2 content compared to HF_HT, but DF_HT had a similar content to that of HF_HT. Furthermore, peroxidase (POD) and polyphenol oxidase (PPO) activities were increased in DF_DT compared to HF_HT (P = 0.0294) and DF_HT (P = 0.0044), respectively. Targeted metabolomics analysis revealed that a total of 76 metabolites were identified in Satsuma rind tissues, and the relative concentrations of 43 metabolites were significantly different across studied samples. The hormonal analysis showed the involvement of jasmonate O-methyltransferase, jasmonic acid-amido synthetase JAR1-like, and JA-isoleucine may key role in causing the rind disorder in mandarins. In addition, the damaged fruit tissues have a higher level of jasmonic acid (JA), 12-oxo-phytodienoic acid, and JA-isoleucine than undamaged tissue.PMID:37822340 | PMC:PMC10562707 | DOI:10.3389/fpls.2023.1263354

Aging Cell. 2023 Oct 12:e13946. doi: 10.1111/acel.13946. Online ahead of print.ABSTRACTAgeing is characterised at the molecular level by six transcriptional 'hallmarks of ageing', that are commonly described as progressively affected as time passes. By contrast, the 'Smurf' assay separates high-and-constant-mortality risk individuals from healthy, zero-mortality risk individuals, based on increased intestinal permeability. Performing whole body total RNA sequencing, we found that Smurfness distinguishes transcriptional changes associated with chronological age from those associated with biological age. We show that transcriptional heterogeneity increases with chronological age in non-Smurf individuals preceding the other five hallmarks of ageing that are specifically associated with the Smurf state. Using this approach, we also devise targeted pro-longevity genetic interventions delaying entry in the Smurf state. We anticipate that increased attention to the evolutionary conserved Smurf phenotype will bring about significant advances in our understanding of the mechanisms of ageing.PMID:37822253 | DOI:10.1111/acel.13946

J Dev Orig Health Dis. 2023 Oct 12:1-12. doi: 10.1017/S2040174423000260. Online ahead of print.ABSTRACTThe maternal metabolic environment can be detrimental to the health of the offspring. In a previous work, we showed that maternal high-fat (HH) feeding in rabbit induced sex-dependent metabolic adaptation in the fetus and led to metabolic syndrome in adult offspring. As early development representing a critical window of susceptibility, in the present work we aimed to explore the effects of the HH diet on the oocyte, preimplantation embryo and its microenvironment. In oocytes from females on HH diet, transcriptomic analysis revealed a weak modification in the content of transcripts mainly involved in meiosis and translational control. The effect of maternal HH diet on the embryonic microenvironment was investigated by identifying the metabolite composition of uterine and embryonic fluids collected in vivo by biomicroscopy. Metabolomic analysis revealed differences in the HH uterine fluid surrounding the embryo, with increased pyruvate concentration. Within the blastocoelic fluid, metabolomic profiles showed decreased glucose and alanine concentrations. In addition, the blastocyst transcriptome showed under-expression of genes and pathways involved in lipid, glucose and amino acid transport and metabolism, most pronounced in female embryos. This work demonstrates that the maternal HH diet disrupts the in vivo composition of the embryonic microenvironment, where the presence of nutrients is increased. In contrast to this nutrient-rich environment, the embryo presents a decrease in nutrient sensing and metabolism suggesting a potential protective process. In addition, this work identifies a very early sex-specific response to the maternal HH diet, from the blastocyst stage.PMID:37822211 | DOI:10.1017/S2040174423000260

J Agric Food Chem. 2023 Oct 11. doi: 10.1021/acs.jafc.3c05501. Online ahead of print.ABSTRACTFumonisin B1 (FB1) is a representative form of fumonisin and is widely present in food and feed. Hydrolyzed fumonisin B1 (HFB1) emerges as a breakdown product of FB1, which is accompanied by FB1 alterations. While previous studies have primarily focused on the liver or kidney toxicity of FB1, with limited studies existing on its neurotoxicity and even fewer on the toxicity of HFB1, this study focuses on the neurotoxicity of FB1 and HFB1 exposure in mice investigated by the open field test, Morris water maze test, histopathological analysis, and nontargeted metabolomics. Further, the levels of oxidative stress-related indices, neurotransmitters, and sphingolipids in the brain were measured to analyze their correlation with behavioral outcomes. The results showed that both FB1 (5 mg/kg) and HFB1 (2.8 mg/kg) reduced autonomous exploratory behavior in mice, impaired spatial learning and memory, and caused mild abnormalities in the brain structure. Quantitative analysis further indicated that exposure to FB1 and HFB1 disrupted neurotransmitter homeostasis, exacerbated oxidative stress, and significantly increased the sphinganine/sphingosine (Sa/So) ratio. Moreover, HFB1 exhibited neurotoxic effects similar to those of FB1, emphasizing the need to pay attention to the neurotoxicity effect of HFB1. These findings underscore the importance of understanding the risks and potential neurological damage associated with FB1 and HFB1 exposure, highlighting the necessity for further research in this crucial field.PMID:37822021 | DOI:10.1021/acs.jafc.3c05501

J Orthop Surg Res. 2023 Oct 11;18(1):769. doi: 10.1186/s13018-023-04240-3.ABSTRACTBACKGROUND: Gout is the most common inflammatory arthritis and closely related to metabolic syndrome, leading to excruciating pain and the decline in quality of patients' life. However, the pathogenesis of gout is still unclear, and novel biomarkers are demanded for the early prediction and diagnosis of gout.OBJECTIVE: This study aimed at profiling the dysregulated metabolic pathways in asymptomatic hyperuricemia (AHU) and gout and elucidating the associations between AHU, gout and metabolomics, which may aid in performing gout screening.METHODS: A total of 300 participants, including 114 healthy controls, 92 patients with AHU, and 94 patients with gout, were analyzed by using a combination of dried blood spot (DBS) sampling and mass spectrometry (MS) technology. Multiple algorithms were applied to characterize altered metabolic profiles in AHU and gout. The mainly altered metabolites were identified by random forest analysis.RESULTS: There were significant differences in AHU and gout compared with control group. The altered metabolites were involved in oxidation of fatty acids, carnitine synthesis, urea cycle, and amino acid metabolism in AHU and gout. Random forest classification of 16 metabolites yielded 3 important features to distinguish gout from AHU.CONCLUSIONS: Distinct metabolomic signatures were observed in AHU and gout. The selected metabolites may have the potential to improve the early detection of gout.PMID:37821971 | DOI:10.1186/s13018-023-04240-3

Cancer Metab. 2023 Oct 11;11(1):16. doi: 10.1186/s40170-023-00317-z.ABSTRACTBACKGROUND: Endometrial cancer (EMC) is the most common female genital tract malignancy with an increasing prevalence in many countries including Japan, a fact that renders early detection and treatment necessary to protect health and fertility. Although early detection and treatment are necessary to further improve the prognosis of women with endometrial cancer, biomarkers that accurately reflect the pathophysiology of EMC patients are still unclear. Therefore, it is clinically critical to identify biomarkers to assess diagnosis and treatment efficacy to facilitate appropriate treatment and development of new therapies for EMC.METHODS: In this study, wide-targeted plasma metabolome analysis was performed to identify biomarkers for EMC diagnosis and the prediction of treatment responses. The absolute quantification of 628 metabolites in plasma samples from 142 patients with EMC was performed using ultra-high-performance liquid chromatography with tandem mass spectrometry.RESULTS: The concentrations of 111 metabolites increased significantly, while the concentrations of 148 metabolites decreased significantly in patients with EMC compared to healthy controls. Specifically, LysoPC and TGs, including unsaturated fatty acids, were reduced in patients with stage IA EMC compared to healthy controls, indicating that these metabolic profiles could be used as early diagnostic markers of EMC. In contrast, blood levels of amino acids such as histidine and tryptophan decreased as the risk of recurrence increased and the stages of EMC advanced. Furthermore, a marked increase in total TG and a decrease in specific TGs and free fatty acids including polyunsaturated fatty acids levels were observed in patients with EMC. These results suggest that the polyunsaturated fatty acids in patients with EMC are crucial for disease progression.CONCLUSIONS: Our data identified specific metabolite profiles that reflect the pathogenesis of EMC and showed that these metabolites correlate with the risk of recurrence and disease stage. Analysis of changes in plasma metabolite profiles could be applied for the early diagnosis and monitoring of the course of treatment of EMC patients.PMID:37821929 | DOI:10.1186/s40170-023-00317-z