PubMed
FMT intervention decreases urine 5-HIAA levels: a randomized double-blind controlled study
Front Med (Lausanne). 2024 Oct 18;11:1411089. doi: 10.3389/fmed.2024.1411089. eCollection 2024.ABSTRACTBACKGROUND: Autism spectrum disorder (ASD) is often linked to gastrointestinal issues and altered serotonin metabolism. Emerging evidence suggests gut microbiota influence both, with fecal microbiota transplantation (FMT) offering a potential therapeutic approach. However, its impact on serotonin metabolism and ASD symptoms is not well understood. In this study, we aimed to evaluate the clinical effects of FMT and examine changes in specific urinary metabolites in children with ASD.METHODS: A randomized double-blind controlled trial was performed to evaluate the clinical effects of FMT on GI and ASD-related symptoms. Gastrointestinal symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS), and the ASD-related symptoms were assessed using the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and Social Responsiveness Scale (SRS) scores. Urinary metabolites were analyzed by homogeneous enzyme immunoassay using commercially available kits.RESULTS: Significant improvements in GI and core ASD symptoms were observed following FMT intervention. The average GSRS scores decreased from 30.17 (before) to 19 (after; p < 0.0001), CARS scores decreased from 36.22 to 33.33 (p < 0.0001), SRS scores decreased from 151.17 to 137.5 (p = 0.0002), and the ABC scores decreased 76.39 to 53.17 (p < 0.0001) in the FMT group. However, in the placebo group, GSRS, CARS, and SRS scores showed no significant changes, while ABC scores decreased from 72 to 58.75 (p = 0.034). The FMT group also showed a significant reduction in urinary 5-hydroxyindoleacetic acid (5-HIAA) levels from 8.6 to 7.32 mg/L (p = 0.022), while other metabolites showed no significant changes.CONCLUSION: FMT is a safe and effective treatment for improving GI and core symptoms in children with ASD, with 5-HIAA showing potential as a urinary biomarker for treatment response.PMID:39493719 | PMC:PMC11529335 | DOI:10.3389/fmed.2024.1411089
Shorten spreading duration enhance the quality of summer Meitan Cuiya tea
Food Chem X. 2024 Oct 5;24:101878. doi: 10.1016/j.fochx.2024.101878. eCollection 2024 Dec 30.ABSTRACTMeitan Cuiya (MTCY), a representative green tea from Guizhou, China, may exhibit lower quality in summer due to increased bitterness and astringency. Spreading is a common method to enhance tea quality, but its impact on summer MTCY remains unclear. This study combined transcriptomics and volatile metabolomics to investigate the effects of spreading duration on quality of summer fresh tea leaves and MTCY. Results showed that spreading time shortened to 4 h improved the taste of MTCY, due to lower catechins and higher theanine levels. This duration also yielded woody floral scent in MTCY, marked by high levels of trans-Cubebol, linalool, (Z)-linalool oxide. Transcriptomic analysis linked the 4-h spreading to proteasome activities. Aroma formation was related to diterpenoid and flavonoid biosynthesis. Additionally, gibberellins and auxin were associated with quality formation in fresh tea leaves. This research lays a foundation for improving quality of fresh tea leaves and MTCY in summer.PMID:39493592 | PMC:PMC11528227 | DOI:10.1016/j.fochx.2024.101878
A rapid diagnostic technique based on metabolomics to differentiate between preeclampsia (PE) and chronic kidney disease (CKD) using maternal urine
Eur J Obstet Gynecol Reprod Biol X. 2024 Oct 9;24:100348. doi: 10.1016/j.eurox.2024.100348. eCollection 2024 Dec.ABSTRACTSimilar clinical manifestations between preeclampsia and chronic kidney diseases can lead to potential misdiagnosis. Therefore, it is crucial to investigate effective diagnostic approaches that can reduce misdiagnosis and ensure the well-being of pregnant women. In this study, urine samples collected from 44 individuals with preeclampsia, 37 individuals with chronic kidney disease, and 37 healthy pregnant women were analyzed using metabolomic and proteomic strategies to distinguish between these two diseases. A total of 15 small molecules were tentatively identified as biomarkers to differentiate these two diseases, including potential internally exposed drugs and their metabolites like labetalol and SN-38, metabolites of exogenous substances like 3-phenylpropyl glucosinolate, and endogenous substances related to metabolism such as isoglobotriaose and chitobiose. Metabolic differences between preeclampsia from healthy pregnant women, as well as the differences between chronic kidney disease and healthy pregnant women were also investigated. Major mechanistic pathways were investigated based on the combination of metabolomic and proteomic, amino acid metabolisms and folate metabolism play key roles in distinguishing preeclampsia and chronic kidney disease. Two patients who were initially diagnosed with chronic kidney disease were found to have a closer association with preeclampsia following metabolomic analysis. Subsequent clinical symptoms and manifestations further supported the diagnosis of preeclampsia, and one of patient's pregnancy was ultimately terminated due to severe preeclampsia. Results of this study contribute to a better understanding of the pathogenesis and clinical diagnosis of preeclampsia, offering insights that could potentially improve future diagnostic and management approaches.PMID:39493442 | PMC:PMC11530862 | DOI:10.1016/j.eurox.2024.100348
Characterization of <em>O</em>-methyltransferases in the biosynthesis of phenylphenalenone phytoalexins based on the telomere-to-telomere gapless genome of <em>Musella lasiocarpa</em>
Hortic Res. 2024 Mar 8;11(4):uhae042. doi: 10.1093/hr/uhae042. eCollection 2024 Apr.ABSTRACTPhenylphenalenones (PhPNs), phytoalexins in wild bananas (Musaceae), are known to act against various pathogens. However, the abundance of PhPNs in many Musaceae plants of economic importance is low. Knowledge of the biosynthesis of PhPNs and the application of biosynthetic approaches to improve their yield is vital for fighting banana diseases. However, the processes of PhPN biosynthesis, especially those involved in methylation modification, remain unclear. Musella lasiocarpa is a herbaceous plant belonging to Musaceae, and due to the abundant PhPNs, their biosynthesis in M. lasiocarpa has been the subject of much attention. In this study, we assembled a telomere-to-telomere gapless genome of M. lasiocarpa as the reference, and further integrated transcriptomic and metabolomic data to mine the candidate genes involved in PhPN biosynthesis. To elucidate the diversity of PhPNs in M. lasiocarpa, three screened O-methyltransferases (Ml01G0494, Ml04G2958, and Ml08G0855) by phylogenetic and expressional clues were subjected to in vitro enzymatic assays. The results show that the three were all novel O-methyltransferases involved in the biosynthesis of PhPN phytoalexins, among which Ml08G0855 was proved to function as a multifunctional enzyme targeting multiple hydroxyl groups in PhPN structure. Moreover, we tested the antifungal activity of PhPNs against Fusarium oxysporum and found that the methylated modification of PhPNs enhanced their antifungal activity. These findings provide valuable genetic resources in banana breeding and lay a foundation for improving disease resistance through molecular breeding.PMID:39493361 | PMC:PMC11528125 | DOI:10.1093/hr/uhae042
Biomarkers for Early Detection of Stroke: A Systematic Review
Cureus. 2024 Oct 1;16(10):e70624. doi: 10.7759/cureus.70624. eCollection 2024 Oct.ABSTRACTStroke remains a leading cause of mortality and disability worldwide. Identifying reliable biomarkers for stroke diagnosis and risk prediction could significantly improve patient outcomes through earlier intervention and better risk management. The objective of this systematic review is to systematically review recent studies investigating biomarkers for stroke diagnosis and risk prediction and to synthesize the most promising findings. We conducted a systematic review of 10 studies published between 2008 and 2023 that examined various biomarkers in relation to stroke. Studies were evaluated for quality using a simplified version of the Mixed Methods Appraisal Tool. The reviewed studies investigated a diverse array of biomarkers, including lipids, inflammatory markers, hemodynamic markers, microRNAs, metabolites, and neurodegenerative markers. Key findings include the following: (1) non-traditional lipid markers such as triglycerides and non-high-density lipoprotein cholesterol may be more predictive of stroke risk than low-density lipoprotein; (2) inflammatory markers, particularly IL-6, showed strong associations with stroke risk; (3) hemodynamic markers like midregional proatrial natriuretic peptide (MRproANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) demonstrated potential in distinguishing stroke subtypes; (4) specific microRNAs (miR-125a-5p, miR-125b-5p, miR-143-3p) were upregulated in acute ischemic stroke; (5) metabolomic studies identified novel markers such as tetradecanedioate and hexadecanedioate associated with cardioembolic stroke; (6) neurodegenerative markers (total-tau, neurofilament light chain) were linked to increased stroke risk. This review highlights the potential of various biomarkers in improving stroke diagnosis and risk prediction. While individual markers show promise, a multi-marker approach combined with clinical variables appears most likely to yield clinically useful tools. Further large-scale validation studies are needed before these biomarkers can be implemented in routine clinical practice.PMID:39493062 | PMC:PMC11529901 | DOI:10.7759/cureus.70624
Causal Effects of Gut Microbiota on Gout and Hyperuricemia: Insights from Genome-Wide Mendelian Randomization, RNA-Sequencing, 16S rRNA Sequencing, and Metabolomes
Biosci Rep. 2024 Nov 4:BSR20240595. doi: 10.1042/BSR20240595. Online ahead of print.ABSTRACTThis study investigated the causal relationship between gut microbiota (GM), serum metabolome, and host transcriptome in the development of gout and hyperuricemia (HUA) using genome-wide association studies (GWAS) data and HUA mouse model experiments.  Methods: Mendelian randomization (MR) analysis of GWAS summary statistics was performed using an inverse variance weighted (IVW) approach to determine predict the causal role of the gut microbiota on gout. The HUA mouse model was used to characterize changes in the gut microbiome, host metabolome, and host kidney transcriptome by integrating cecal 16S rRNA sequencing, untargeted serum metabolomics, and host mRNA sequencing.</p>  Results: Our analysis demonstrated causal effects of seven gut microbiota taxa on gout, including genera of Ruminococcus, Odoribacter, and Bacteroides. Thirty-eight, immune cell traits were associated with gout. Dysbiosis of Dubosiella, Lactobacillus,Bacteroides, Alloprevotella, and Lachnospiraceae_NK4A136_group genera were associated with changes in the serum metabolites and kidney transcriptome of the HUA model mice. The changes in the gut microbiome of the HUA model mice correlated significantly with alterations in the levels of serum metabolites such as taurodeoxycholic acid, phenylacetylglycine, vanylglycol, methyl hexadecanoic acid, carnosol, 6-aminopenicillanic acid, sphinganine, p-hydroxyphenylacetic acid, pyridoxamine, and de-o-methylsterigmatocystin, and expression of kidney genes such as CNDP2, SELENOP, TTR, CAR3, SLC12A3, SCD1, PIGR, CD74, MFSD4B5, and NAPSA.</p>  Conclusion: Our study demonstrated a causal relationship between GM, immune cells, and gout. HUA development involved alterations in the vitamin B6 metabolism because of gut microbiota dysbiosis that resulted in altered pyridoxamine and pyridoxal levels, dysregulated sphingolipid metabolism, and excessive inflammation.</p>.PMID:39492788 | DOI:10.1042/BSR20240595
Understanding the dynamics of Microcystis bloom: Unraveling the influence of suspended solids through proteomics and metabolomics approaches
Sci Total Environ. 2023 Oct 28:168079. doi: 10.1016/j.scitotenv.2023.168079. Online ahead of print.ABSTRACTLight plays a crucial role in blue-green algae bloom formation in lakes, while suspended solids (SS) influence underwater light intensity. This study investigates the integrated effects of SS concentrations (0-125 mg/L) on Microcystis aeruginosa in natural conditions. Results show that SS inhibits cyanobacterial growth above 100 mg/L, with 25-75 mg/L favoring bloom formation. Proteomic analysis reveals differential protein involvement in ribosomes, ABC transporters, cofactor biosynthesis, and photosynthesis pathways at 25 mg/L SS. SS concentrations within the range of 25-125 mg/L significantly impact the metabolism of algal cells, resulting in an increase in lipid metabolism and a decrease in the biosynthesis of secondary metabolites in cyanobacteria. These coordinated biochemical adaptations play a vital role in the survival of cyanobacteria in challenging environmental conditions. Employing a multi-omics approach enhances our comprehension of how M. aeruginosa responds to SS and the underlying molecular mechanisms, thereby contributing to our understanding of cyanobacteria outbreaks. This underscores the importance of monitoring SS concentrations in lakes as a proactive measure for future control of cyanobacteria dominance.PMID:39492530 | DOI:10.1016/j.scitotenv.2023.168079
Metabolomics reveals that sulfotransferase 1 may regulate colchicine-induced liver injury
Chem Biol Interact. 2023 Oct 28:110776. doi: 10.1016/j.cbi.2023.110776. Online ahead of print.ABSTRACTColchicine is widely used to treat gouty arthritis for years. Previous studies showed that colchicine overdose can cause liver damage, yet the mechanism underlying its hepatotoxicity remains unclear. In this study, hepatotoxicity of colchicine was investigated in vivo. Metabolomic analysis of colchicine metabolites and endogenous metabolites was performed using Ultra High Performance Liquid Chromatography (UHPLC) - mass spectrometry (MS). Seventeen metabolites of colchicine were identified, including 3 novel sulfated metabolites. Meanwhile, endogenous sulfated metabolites were found to be decreased by colchicine. Colchicine might regulate sulfotransferase 1 (SULT1) through perixisome proliferation-activated receptor ɑ (PPARα), and inhibition of SULT1 reduced the levels of sulfated metabolites of colchicine. Inhibition of SULT1 aggravated colchicine-induced liver injury, whereas activation of SULT1 attenuated its liver injury. The supplementation of endogenous sulfated metabolites indoxyl sulfate (IS) or p-cresol sulfate (PCS) alleviated colchicine-induced liver injury through modulation of the CASPASE-1-gasdermin D (GSDMD) pathway. These results indicated that colchicine might cause hepatotoxicity through inhibition of SULT1and decreased production of bioactive sulfated endogenous metabolites IS and PCS. Our results provided evidence for potential therapeutic targets and agents to prevent liver injury caused by colchicine. Targeting the SULT1 enzyme and administration of IS and PCS may be useful in alleviating colchicine hepatotoxicity.PMID:39492502 | DOI:10.1016/j.cbi.2023.110776
Research Note: Comparison of water-soluble metabolites in egg yolk, yolk granules, and yolk plasma based on quantitative metabolomic analysis
Poult Sci. 2023 Oct 6;102(12):103161. doi: 10.1016/j.psj.2023.103161. Online ahead of print.ABSTRACTEgg yolk (EY) can be divided into yolk granules (EYG) and yolk plasma (EYP) after water dilution and centrifugation. EYP had a significantly higher lipid content and is predominantly in the form of low-density lipoprotein (LDL) while EYG has a higher protein content. In order to explore the nutritional differences between EY, EYP and EYG, quantitative metabolomic analysis was carried out by ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). The results showed that a total of 588 small molecule metabolites were identified, mainly glycerol phospholipids (51.59-66.46%), coenzymes, and vitamins (1.21-1.84%). A quantitative comparison showed that amino acids and their metabolites were the most representative metabolites of differential abundance in the contrast of EY and EYG, EYP and EYG. Carbohydrates and their metabolites were the representative metabolites of differential abundance between EY and EYP. The study provided important information for understanding the metabolic composition of EY, EYG, and EYP, as well as providing a reference for utilizing the whole egg.PMID:39492405 | DOI:10.1016/j.psj.2023.103161
Biology of childhood hepatoblastoma and the search for novel treatments
Adv Biol Regul. 2023 Oct 25:100997. doi: 10.1016/j.jbior.2023.100997. Online ahead of print.ABSTRACTOur research laboratory has a longstanding interest in developmental disorders and embryonic tumors, and recent efforts have focused on the pathogenesis of pediatric liver tumors. This review focuses on hepatoblastoma (HB), the most common pediatric liver malignancy. Despite advances in treatment, patients with metastatic HB have a poor prognosis, and survivors often have permanent side effects attributable to chemotherapy. In an effort to improve survival and lessen long-term complications of HB, we have searched for novel molecular vulnerabilities using a combination of patient derived cell lines, metabolomics, and RNA sequencing of human samples at diagnosis and follow-up. These studies have shed light on pathogenesis and identified putative targets for future therapies in children with advanced HB.PMID:39492287 | DOI:10.1016/j.jbior.2023.100997
Recent developments in the analytical approaches of acyl-CoAs to assess their role in mitochondrial fatty acid oxidation disorders
Mol Genet Metab. 2023 Oct 20:107711. doi: 10.1016/j.ymgme.2023.107711. Online ahead of print.ABSTRACTFatty acid oxidation disorders (FAOD) are inborn errors of metabolism that occur due to deficiency of specific enzyme activities and transporter proteins involved in the mitochondrial metabolism of fatty acids, causing a deficiency in ATP production. The identification of suitable biomarkers plays a crucial role in predicting the future risk of disease and monitoring responses to therapies. Acyl-CoAs are directly involved in the steps of fatty acid oxidation and are the primary biomarkers associated with FAOD. However, acyl-CoAs are not used as diagnostic biomarkers in hospitals and clinics as they are present intracellularly with low endogenous levels. Additionally, the analytical method development of acyl-CoAs is quite challenging due to diverse physicochemical properties and instability. Hence, secondary biomarkers such as acylcarnitines are used for the identification of FAOD. In this review, the focus is on the analytical techniques that have evolved over the years for the identification and quantitation of acyl-CoAs. Among these techniques, liquid chromatography-mass spectrometry clearly has an advantage in terms of sensitivity and selectivity. Stable isotope labeling by essential nutrients in cell culture (SILEC) enables the generation of labeled internal standards. Each acyl-CoA species has a distinct pattern of instability and degradation, and the use of appropriately matched internal standards can compensate for such issues. Although significant progress has been made in measuring acyl-CoAs, more efforts are needed for bringing these technical advancements to hospitals and clinics. This review also highlights the difficulties involved in the routine use of acyl-CoAs as a diagnostic biomarker and some of the measures that can be adopted by clinics and hospitals for overcoming these limitations.PMID:39492074 | DOI:10.1016/j.ymgme.2023.107711
Ambient air pollution exposure, plasma metabolomic markers, and risk of type 2 diabetes: A prospective cohort study
J Hazard Mater. 2023 Oct 24;463:132844. doi: 10.1016/j.jhazmat.2023.132844. Online ahead of print.ABSTRACTBACKGROUND: Both air pollution (AP) and impaired lipid metabolism contribute to type 2 diabetes (T2D). However, little is known about the detailed associations of AP to lipidomic markers and the specific lipid metabolomic profile that mediates the impact of AP on incident T2D. We aimed to examine the associations between long-term AP exposure, plasma metabolomic markers, and incident T2D, and subsequently determine the lipid metabolomic profile that mediates the relationship between AP and T2D.METHODS: This prospective study included 82,548 participants from the UK Biobank without a history of T2D at baseline. Baseline plasma samples were analyzed using the nuclear magnetic resonance (NMR) metabolomic platform, which measured 168 metabolomic markers, including lipids, lipoprotein subclasses, and other circulating metabolites. Land Use Regression models were utilized to estimate annual average concentrations of PM2.5 and NO2. The associations among AP, metabolomic markers, and T2D were investigated using multivariable linear regressions and Cox proportional hazards models. Mediation analyses were performed to assess the role of each metabolomic marker in the AP-T2D relationship. Furthermore, principal component (PC) analysis was conducted on 168 metabolomic markers to extract metabolic patterns. These patterns were utilized to determine their associations with AP and T2D, as well as their mediating role in the AP-T2D relationship.RESULTS: We found that long-term AP exposure was associated with some lipid metabolites, including ApoA1, HDL concentration, HDL size, and lipid components within HDL, especially in very large, large, and medium HDL, as well as some other lipids, fatty acids, amino acids, glucose, and glycoprotein acetyls. In pairwise mediation analysis, these metabolites exhibited significant mediation effects in the AP-T2D relationship. We identified six PCS representing distinct metabolic patterns. Long-term exposure to PM2.5 and NO2 showed significantly negative associations with PC2 (characterized by high levels of ApoA1, larger HDL, other lipids, and low levels of larger VLDL). PC2 mediated 12.3% and 10.3% of the associations of PM2.5 and NO2 with incident T2D, respectively.CONCLUSIONS: This study revealed the associations of AP with various lipid metabolites. A lipid metabolomic profile characterized by ApoA1 and larger HDL may mediate the association between AP and incident T2D.PMID:39491993 | DOI:10.1016/j.jhazmat.2023.132844
The Sex Dependent and Independent Effects of Dietary Whey Proteins Are Passed from the Mother to the Offspring
Mol Nutr Food Res. 2024 Nov 3:e2400584. doi: 10.1002/mnfr.202400584. Online ahead of print.ABSTRACTSCOPE: The study assesses the metabolic impact of dietary whey proteins across generations.METHOD AND RESULTS: Virgin females are fed 20% energy whey proteins with 70% energy carbohydrates, which reduces body weight gain and visceral adipose compared to controls fed dietary casein. In contrast, the males are unresponsive. The effect is accentuated in reproductive females that also have reduced plasma levels of glucose. The responsive females have increased cecal levels of pyruvic and lactic acid, suggesting a greater catabolism of carbohydrates in the gut. While the male and female offspring born to mothers on whey proteins continue to reduce body weight gain, the female offspring further decreases the visceral and subcutaneous tissues and increases the gut capacity to breakdown dietary carbohydrates and proteins, whereas the male offspring are able to only decrease the visceral and increase protein catabolism in the gut. The ileum of male mice responded by reducing the gene expression for fibroblast growth factor 15 and increasing the expression of chymotrypsinogen B1.CONCLUSION: The effect of whey proteins on growth can be passed from the mother to the offspring without a sex preference, whereas the transmission of gut activity and adiposity are dependent on the sex of the offspring.PMID:39491812 | DOI:10.1002/mnfr.202400584
The Complement Factor H (Y402H) risk polymorphism for age-related macular degeneration affects metabolism and response to oxidative stress in the retinal pigment epithelium
Free Radic Biol Med. 2024 Nov 2:S0891-5849(24)01015-3. doi: 10.1016/j.freeradbiomed.2024.10.307. Online ahead of print.ABSTRACTAge-related macular degeneration (AMD), the leading cause of central vision loss in the elderly, involves death of the retinal pigment epithelium (RPE) and light-sensing photoreceptors. This multifactorial disease includes contributions from both genetic and environmental risk factors. The current study examined the effect of the Y402H polymorphism of Complement Factor H (CFH, rs1061170) and cigarette smoke, predominant genetic and environmental risk factors associated with AMD. We used targeted and discovery-based approaches to identify genotype-dependent responses to chronic oxidative stress induced by cigarette smoke extract (CSE) in RPE differentiated from induced pluripotent stem cells (iPSC) derived from human donors harboring either the low risk (LR) or high risk (HR) CFH genotype. Chronic CSE altered the metabolic profile in both LR and HR iPSC-RPE and caused a dose-dependent reduction in mitochondrial function despite an increase in mitochondrial content. Notably, cells with the HR CFH SNP showed a greater reduction in maximal respiration and ATP production. Significant genotype-dependent changes in the proteome were observed for HR RPE at baseline (cytoskeleton, MAPK signaling) and after CSE exposure, where a less robust upregulation of the antioxidants and significant downregulation in proteins involved in nucleic acid metabolism and membrane trafficking were noted compared to LR cells. In LR cells, uniquely upregulated proteins were involved in lipid metabolism and chemical detoxification. These genotype-dependent differences at baseline and in response to chronic CSE exposure suggest a broader role for CFH in modulating the response to oxidative stress in RPE and provides insight into the interaction between environmental and genetic factors in AMD pathogenesis.PMID:39491736 | DOI:10.1016/j.freeradbiomed.2024.10.307
Influenza A virus-induced glycolysis facilitates virus replication by activating ROS/HIF-1α pathway
Free Radic Biol Med. 2024 Nov 2:S0891-5849(24)01012-8. doi: 10.1016/j.freeradbiomed.2024.10.304. Online ahead of print.ABSTRACTAs a highly contagious acute respiratory disease, influenza A virus (A/WSN/1933) poses a huge threat to human health and public health. influenza A virus proliferation relies on glucose metabolism in host cells, yet the effects of influenza A virus on glucose metabolism and the underlying molecular mechanisms remain unclear. Here, we created models of WSN virus-infected mice and A549 cells, along with analyzing metabolomics and transcriptomics data, to investigate how WSN virus infection affects host cell glucose metabolism and specific mechanisms. Analysis of metabolites and gene expression showed that WSN virus infection triggers glycolysis in A549 cells, with notable upregulation of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), hypoxia-inducible factor-1 alpha (HIF-1α), and elevated lactate levels. Additionally, it leads to mitochondrial impairment and heightened reactive oxygen species (ROS) generation. Elevated levels of glucose may enhance the replication of WSN virus, whereas inhibitors of glycolysis can reduce it. Enhancement of HIF-1α activation facilitated replication of WSN virus through stimulation of lactate synthesis, with the primary influence of glycolysis on WSN virus replication being mediated by ROS/HIF-1α signaling. Mice given HIF-1α inhibitor PTX-478 or glycolysis inhibitor 2-Deoxyglucose (2-DG) exhibited reduced lactate levels and decreased WSN virus replication, along with mitigated weight loss and lung damage. In summary, WSN virus-induced glycolysis has been demonstrated to enhance virus replication through the activation of the ROS/HIF-1α pathway, suggesting potential new targets for combating the virus.PMID:39491735 | DOI:10.1016/j.freeradbiomed.2024.10.304
(1)H NMR-Based Metabolomic Profiling and Comparison of Human Milk Across Different Lactation Stages in Secretors and Non-Secretors: A Study of Chinese Lactating Women
J Nutr. 2024 Nov 2:S0022-3166(24)01127-1. doi: 10.1016/j.tjnut.2024.10.050. Online ahead of print.ABSTRACTBACKGROUND: Human milk oligosaccharides (HMOs) and other milk-derived metabolites are crucial for infant health, influencing gut microbiota and overall development.OBJECTIVE: This study aims to uncover insights into the variations of HMOs and non-HMO metabolites based on secretor (Se) status, lactation time, mode of delivery, and infant sex.METHODS: An exploratory cross-sectional study was designed to compare the levels of HMOs and non-HMOs metabolites in milk samples from 129 lactating Chinese women within 1 year postpartum. Nuclear magnetic resonance analysis was employed for the identification and quantification of the metabolites. The metabolites measured were grouped into sugars, free amino acids, fatty acids, and metabolites related to energy metabolism. The influence of delivery mode and infant sex on milk metabolite composition were explored.RESULTS: Uniform Manifold Approximation and Projection (UMAP) analysis of HMOs profiles revealed distinct clustering based on Se status, with significant differences in 2'-FL and 3-FL levels observed between Se+ and Se- groups. A decreasing trend for 2'-FL and 6-'SL levels, along with an increase in 3-FL levels, was observed with increasing lactating period within 12 months postpartum. Non-HMOs metabolite analysis indicated that Se status only affected glutamate levels. An increase in glutamine levels was observed 3-9 months postpartum. A continuous increase in o-phosphocholine levels was noted in 12 months postpartum, along with reductions in citrate and sn-glycero-phosphocholine levels. Delivery mode and infant sex did not affect both HMOs and non-HMOs levels.CONCLUSIONS: Metabolomic analysis of human milk reveals significant variation of HMOs, but not in non-HMOs, based on Se status. Changes in certain HMOs and non-HMOs levels were also observed over the one year of lactation. Understanding how these metabolites change over time may influence recommendations for maternal diet, supplementation, and the timing of breastfeeding to ensure optimal nutrient delivery to the infant.PMID:39491676 | DOI:10.1016/j.tjnut.2024.10.050
Maternal Supplementation Spermidine During Gestation Improves Placental Angiogenesis and Reproductive Performance of High Prolific Sows
J Nutr Biochem. 2024 Nov 2:109792. doi: 10.1016/j.jnutbio.2024.109792. Online ahead of print.ABSTRACTSpermidine (SPD) is a widely recognized polyamine compound found in mammalian cells and plays a key role in various cellular processes. We propose that SPD may enhance placental vascular development in pregnant sows, leading to increased birth weight of piglets. Six hundred and nine sows at 60 days of gestation were randomly assigned into a basal diet (CON group), basal diet supplemented 10 mg/kg of SPD (SPD1 group), and basal diet supplemented 20 mg/kg of SPD (SPD2 group), respectively. Compared with the CON, SPD1 significantly increased the average number of healthy piglets per litter and the placental efficiency (P < 0.05), while the average number of mummified fetus per litter and the percentage of weak piglets significantly decreased (P < 0.05). In the plasma metabolomics, SPD content in plasma of sows (P = 0.075) and umbilical cord plasma of piglets (P = 0.078) had an increasing trend in response to SPD1. Furthermore, SPD1 increased the expression of the vascular endothelial cell marker protein, platelet endothelial cell adhesionmolecule-1 (PECAM-1/CD31) and the density of placental stromal vessels (P < 0.05). Moreover, as compared to CON, SPD2 significantly decreased the average number of mummified fetus per litter (P < 0.05), while the placental efficiency and the expression of amino acid transporter solute carrier (SLC) family 7, member7 (SLC7A7) and glucose transporters SLC2A2) and SLC5A4 in placental tissue significantly increased (P < 0.05). These results suggest that maternal supplementation of SPD during pregnancy increased healthy litter number, and promoted placental tissue development. Our findings provide evidence that maternal SPD has the potential to improve the production performance of sows.PMID:39491598 | DOI:10.1016/j.jnutbio.2024.109792
Decabromodiphenyl ethane (DBDPE) inhibited the growth and feeding by disrupting the gut and digestive gland homeostasis in octopus Amphioctopus fangsiao (Mollusca: Cephalopoda)
Sci Total Environ. 2024 Nov 2:177364. doi: 10.1016/j.scitotenv.2024.177364. Online ahead of print.ABSTRACTA novel brominated flame retardant decabromodiphenyl ethane (DBDPE) poses a potential threat to animals, but its effects on cephalopods remain unknown. In this study, Amphioctopus fangsiao, a common octopus in China, was exposed to DBDPE (0, 1, 50, 100, 300 μg/L) for 28 days. Chemical analysis revealed that the digestive gland bore a greater burden of DBDPE compared with other tissues. In addition, accumulated DBDPE could curb the growth and feeding performance of A. fangsiao. The potential effects on the "gut-digestive gland axis" were also elucidated. Specifically, DBDPE in the gut shifted the microorganisms toward a Bacteroidetes-dominated composition, and impaired the intestinal epithelial barrier, thereby triggering oxidative stress and inflammation. Excessive DBDPE also threatens the digestive gland function, including histological damage, immune reaction, oxidative stress, glucolipid metabolism dysfunction, and neurotoxicity. Metabolome plasticity enabled A. fangsiao to develop a DBDPE stress-adaptive metabolic profile via alteration of glucolipid metabolism, immunity, oxidative stress, and signaling molecules. Taken together, we identified a new detoxification mechanism linking the microbiota-gut-digestive gland axis with the growth and food intake of A. fangsiao, which is the first time it has been demonstrated in mollusks. These findings provided important clues for a further mechanism study and risk assessment of DBDPE.PMID:39491558 | DOI:10.1016/j.scitotenv.2024.177364
Microbial ecology and metabolite dynamics of backslopped triticale sourdough productions and the impact of scale
Int J Food Microbiol. 2023 Oct 18;408:110445. doi: 10.1016/j.ijfoodmicro.2023.110445. Online ahead of print.ABSTRACTTriticale (X Triticosecale Wittmack) is a hybrid of wheat (Triticum aestivum L.) and rye (Secale cereale L.), combining the positive attributes of both cereals. However, it has not been exploited for sourdough production yet. Further, the effect of scale on sourdough production has not been investigated systematically up to now. The aims of the present study were to assess the microbial ecology and metabolomic output of eleven spontaneously fermented, backslopped sourdough productions made with triticale flour on a scale of 100, 200, 500, and 1000 g. The acidification profile [pH and total titratable acidity (TTA)], microbial diversity (culture-dependent and culture-independent), metabolite dynamics, and appropriate correlations were determined. After ten fermentation steps, different species of Lactobacillaceae were prevalent in the mature sourdoughs, in particular Latilactobacillus curvatus, Limosilactobacillus fermentum, and Pediococcus pentosaceus. The microbial diversity could be traced back to the grains and was also present in the milling fractions (flour, bran, and shorts). Furthermore, thanks to the use of Illumina-based high-throughput sequencing and an amplicon sequence variant (ASV) approach, the presence of undesirable bacterial groups (bacilli, clostridia, and enterobacteria) during the initial steps of the backslopping cycle was revealed, as well as a finetuned taxonomic diversity of the LAB genera involved. Small sourdough productions (100 and 200 g) selected for a lower species diversity and reached a stable consortium faster than large ones (500 and 1000 g). Although a comparable final pH of 3.6-4.0 was obtained, the TTA of small sourdoughs was lower than that of large ones. Regarding the metabolic output, the simultaneous production of mannitol and erythritol, beyond ethanol and glycerol, could be linked to sourdoughs in which Liml. fermentum was the sole LAB species present. Further, the use of the arginine deiminase pathway by P. pentosaceus and Liml. fermentum was obvious. An appropriate extraction method followed by liquid injection gas chromatography coupled to triple quadrupole tandem mass spectrometry allowed the quantification of interesting volatile organic compounds, such as ethyl lactate. These findings support the inclusion of triticale as a viable alternative to wheat or rye for the production of sourdoughs that can be integrated into bread-making production schemes.PMID:39491387 | DOI:10.1016/j.ijfoodmicro.2023.110445
Insights into major pigment accumulation and (non)enzymatic degradations and conjugations to characterized flavors during intelligent black tea processing
Food Chem. 2023 Oct 27;437(Pt 1):137860. doi: 10.1016/j.foodchem.2023.137860. Online ahead of print.ABSTRACTIntelligently processed black teas (BT) possess premium quality but there is a lack in comprehensive understanding of flavor formation mechanism. In this study, the accumulation of carotenoids, flavonoids, and Maillard products and (non)enzymatic degradations and conjugations to characterized flavors were comprehensively studied. Significant decrease was observed that flava-3-ols were heavily oxidised from > 240 mg·g-1 in fresh leaves (FL) to < 30 mg·g-1, while other 21 flavonoids decreased by < 30% in BT, accompanied by a sweet aftertaste. Carotenes and xanthophylls, significantly accumulated during withering compared to FL (from 641 ± 39.7 μg·g-1 to 728 ± 44.9 μg·g-1) but decreased in BT. Strong correlations were confirmed between the 218 primary metabolites, carotenoids, and flavonoids, and their contributions to BT sweet tastes were elucidated. Furthermore, 45 floral/sweet volatiles with VIP > 1 originating from carotenoids, lipids, and amino acids were screened. An integrated illustration of pigments thermal- and enzymatic-dominated contributions to BT flavour was comprehensively conducted.PMID:39491256 | DOI:10.1016/j.foodchem.2023.137860