PubMed

Plant Physiol Biochem. 2024 Nov 7;217:109262. doi: 10.1016/j.plaphy.2024.109262. Online ahead of print.ABSTRACTAdaptation of crops to recurrent drought stress is crucial for maintaining agricultural productivity and achieving food security under changing climate. Guard cells, pivotal regulators of plant water usage and assimilation, are central to this adaptation process. However, the metabolic dynamics of guard cells under drought stress remain poorly understood, particularly in grapevine, a prominent crop grown in arid regions, and maize, a staple crop with substantial water requirements. In this study, differences in guard cells metabolism during drought stress of grapevine and maize were investigated by performing physiological and metabolomic analyses. Metabolomic analysis highlighted differential responses in amino acids and sugars, with grapevine guard cells displaying greater stability in amino acid and sugar signatures, while maize showed marked increases in sugar levels. These findings suggest two distinct adaptive strategies, a vigorous acclimation of guard cells, as observed in maize, and an attenuated acclimation of guard cells, shown in grapevine. Understanding these metabolic adjustments is helpful for enhancing drought resilience in agricultural systems.PMID:39546948 | DOI:10.1016/j.plaphy.2024.109262

Comp Biochem Physiol Part D Genomics Proteomics. 2024 Nov 12;52:101359. doi: 10.1016/j.cbd.2024.101359. Online ahead of print.ABSTRACTNitrite contamination and stress on aquatic organisms are increasingly emphasized in freshwater ecosystems. Freshwater bivalves exhibit high tolerance to nitrite; however, the underlying mechanism is unknown. Accordingly, this study investigated the tolerance mechanism of the globally occurring freshwater bivalve Anodonta woodiana. A. woodiana were exposed to nominal concentrations of 0, 250, 500, 1000, 2000, and 4000 mg/L nitrite for 96 h to calculate the 96-h median lethal concentration (96-h LC50). A combined transcriptome and metabolome analysis of the hemolymph (the most vital component of the bivalve immune system) was performed after exposing A. woodiana to 300 mg/L nitrite (approximately half the 96-h LC50) for 96 h. The 96-h LC50 of nitrite in A. woodiana was 618.7 mg/L. Transcriptome analysis identified 5600 differentially expressed genes (DEGs) primarily related to ribosomes, lysosomes, DNA replication, and nucleotide excision repair. Metabolome analysis identified 216 differentially expressed metabolites (DEMs) primarily involved in biosynthesis of amino acids, 2-oxocarboxylic acid metabolism, protein digestion and absorption, aminoacyl-tRNA biosynthesis, nucleotide metabolism, ABC transporters, and valine, leucine and isoleucine degradation. Combined transcriptome and metabolome analysis revealed that DEGs and DEMs were primarily associated with nucleotide (purine and pyrimidine) and amino acid metabolism (including aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism, arginine and proline metabolism, and valine, leucine and isoleucine degradation) as well as the immune system (necroptosis and glutathione metabolism). This study is the first to describe the high tolerance of A. woodiana to nitrite and elucidate the molecular mechanisms underlying high nitrite tolerance in mussels.PMID:39546928 | DOI:10.1016/j.cbd.2024.101359

Int J Food Microbiol. 2024 Nov 9;427:110974. doi: 10.1016/j.ijfoodmicro.2024.110974. Online ahead of print.ABSTRACTSecondary metabolites are a group of invaluable phytochemicals in raspberries. Fermentation process leads to changes in the phytochemical composition of fruits. This study aimed to investigate the influence of Lacticaseibacillus paracasei subsp. paracasei FBKL1.0328 and Lactiplantibacillus plantarum subsp. plantarum FBKL1.0310 on the secondary metabolites of red raspberry juice (CR) and uncover their conversion pathways via metabolomics based on ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). A total of 695 secondary metabolites in the unfermented and fermented samples were identified. There were 90, 83 and 52 differential secondary metabolites identified in LCR (L. paracasei FBKL1.0328 fermented raspberry juice) vs. CR, LPR (L. plantarum FBKL1.0310 fermented raspberry juice) vs. CR, and LCR vs. LPR, respectively. Certain phenolic acids (e.g. 3-phenyllacitc acid), flavonoids (e.g. galangin-7-glucoside), alkaloids (e.g. indole-3-lactic acid), and terpenoids (e.g. glucosyl 7-methyl-3-methyleneoctane-1,2,6,7-tetraol) were selected as the crucial differential metabolites. These two lactobacilli utilized distinct metabolic pathways for processing secondary metabolites. L. paracasei FBKL1.0328 primarily transformed flavonoids through the "Flavone and flavonol biosynthesis" pathway. L. plantarum FBKL1.0310 mainly converted phenolic acids via the "Tyrosine metabolism" pathway and the "Aminobenzoate degradation" pathway. Interestingly, L. plantarum FBKL1.0310 outperformed L. paracasei FBKL1.0328 in upregulating certain valuable bioactive compounds such as indole-3-lactic acid and 3-phenyllacitc acid, underscoring its potential as a promising strain for developing health-beneficial fermented fruit juices. These findings provide insights to how different lactobacilli modify secondary metabolite composition in red raspberry juice and offer valuable information for the industrial application of lactobacilli in fruit processing.PMID:39546897 | DOI:10.1016/j.ijfoodmicro.2024.110974

Comput Biol Med. 2024 Nov 14;184:109414. doi: 10.1016/j.compbiomed.2024.109414. Online ahead of print.ABSTRACTUntargeted metabolomics is an extremely useful approach for the discrimination of biological systems and biomarker identification. However, data analysis workflows are complex and face many challenges. Two of these challenges are the demand of high sample size and the possibility of severe class imbalance, which is particularly common in clinical studies. The latter can make statistical models less generalizable, increase the risk of overfitting and skew the analysis in favour of the majority class. One possible approach to mitigate this problem is data augmentation. However, the use of artificial data requires adequate data augmentation methods and criteria for assessing the quality of the generated data. In this work, we used Conditional Wasserstein Generative Adversarial Networks with Gradient Penalty (CWGAN-GPs) for data augmentation of metabolomics data. Using a set of benchmark datasets, we applied several criteria for the evaluation of the quality of generated data and assessed the performance of supervised predictive models trained with datasets that included such data. CWGAN-GP models generated realistic data with identical characteristics to real samples, mostly avoiding mode collapse. Furthermore, in cases of class imbalance, the performance of predictive models improved by supplementing the minority class with generated samples. This is evident for high quality datasets with well separated classes. Conversely, model improvements were quite modest for high class overlap datasets. This trend was confirmed by using synthetic datasets with different class separation levels. Data augmentation is a viable procedure to alleviate class imbalance problems but is not universally beneficial in metabolomics.PMID:39546879 | DOI:10.1016/j.compbiomed.2024.109414

Talanta. 2024 Nov 6;283:127144. doi: 10.1016/j.talanta.2024.127144. Online ahead of print.ABSTRACTExosomes, emerging as ideal non-invasive biomarkers for disease diagnosis and monitoring, have seldom been explored based on metabolite levels. In this study, we designed and synthesized a pH-responsive phase-transition bifunctional affinity nanopolymer (pH-BiAN) that could efficiently and homogeneously separate exosomes from urine. Specifically, poly-4-vinylpyridine (P4VP) was chosen as the pH-responsive polymer and simultaneously modified with two exosome-affinity components CD63 aptamer and distearoyl phosphoethanolamine (DSPE) through a one-step amide reaction at room temperature. By utilizing two distinct but synergistic affinity mechanisms-the immune affinity between CD63 aptamer and exosomal CD63 proteins, and hydrophobic interactions between the DSPE and the exosomal lipids-pH-BiAN can enable efficient and specific exosome separation. Moreover, during the urine exosome capture procedure, the pH-BiAN outperforms conventional solid exosome separation materials by remaining soluble in the urine sample, significantly enhancing mass transfer and contact efficiency. After exosome capture, pH-BiAN can quickly aggregate and convert to solid upon pH adjustment, allowing for easy centrifugation separation. Afterwards, multiple machine learning models were established by combining liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) untargeted metabolomics for isolated exosomes, and the clinical accuracy of the training and test sets was more than 0.919, which could well distinguish early osteoarthritis patients from healthy people.PMID:39546833 | DOI:10.1016/j.talanta.2024.127144

Methods Mol Biol. 2025;2878:273-291. doi: 10.1007/978-1-0716-4264-1_15.ABSTRACTTo be able to understand how spaceflight can affect human biology, there is a need for maximizing the amount of information that can be obtained from experiments flown to space. Recently there has been an influx of data obtained from astronauts through multi-omics approaches based on both governmental and commercial spaceflight missions. In addition to data from humans, mitochondrial specific data is gathered for other experiments from rodents and other organisms that are flown in space. This data has started to universally demonstrate that mitochondrial dysfunction is the key regulator associated with increasing health risks associated with spaceflight. This mitochondrial dysfunction can have influence downstream on immune suppression, inflammation, circadian rhythm issues, and more. Due to the space environment, standard methodologies have to be altered for performing mitochondrial specific analysis and in general sample collection for omics. To perform mitochondrial specific analysis and data collection from samples flown to space we will outline the current sample collection methods, processing of the samples, and specific analysis. Specifically we will highlight the different mitochondrial methodologies and challenges involved with research associated with spaceflight.PMID:39546268 | DOI:10.1007/978-1-0716-4264-1_15

Br J Pharmacol. 2024 Nov 15. doi: 10.1111/bph.17390. Online ahead of print.ABSTRACTBACKGROUND AND PURPOSE: Pneumoconiosis, especially silicosis, is a prevalent occupational disease with substantial global economic implications and lacks a definitive cure. Both pneumoconiosis and idiopathic pulmonary fibrosis (IPF) are interstitial lung diseases, which share many common physiological characteristics. Because pirfenidone and nintedanib are approved to treat IPF, their potential efficacy as antifibrotic agents in advanced silicosis deserves further exploration. Thus, we aimed to evaluate the individual and combined effects of pirfenidone and nintedanib in treating advanced silicosis mice and elucidate the underlying mechanisms of their therapeutic actions via multiomics.EXPERIMENTAL APPROACH: We administered monotherapy or combined therapy of pirfenidone and nintedanib, with low and high doses, in silicosis established after 6 weeks and evaluated lung function, inflammatory responses and fibrotic status. Additionally, we employed transcriptomic and metabolomic analyses to uncover the mechanisms underlying different therapeutic strategies.KEY RESULTS: Both pirfenidone and nintedanib were effective in treating advanced silicosis, with superior outcomes observed in combination therapy. Transcriptomic and metabolomic analyses revealed that pirfenidone and nintedanib primarily exerted their therapeutic effects by modulating immune responses, signalling cascades and metabolic processes involving lipids, nucleotides and carbohydrates. Furthermore, we experimentally validated both monotherapy and combined therapy yielded therapeutic benefits through two common signalling pathways: steroid biosynthesis and purine metabolism.CONCLUSION AND IMPLICATIONS: In conclusion, pirfenidone and nintedanib, either individually or in combination, demonstrate substantial potential in advanced silicosis. Furthermore, combined therapy outperformed monotherapy, even at low doses. These therapeutic benefits are attributed to their influence on diverse signalling pathways and metabolic processes.PMID:39546810 | DOI:10.1111/bph.17390

Proc Natl Acad Sci U S A. 2024 Nov 19;121(47):e2417232121. doi: 10.1073/pnas.2417232121. Epub 2024 Nov 15.ABSTRACTThe gut microbiota produces high concentrations of antimicrobial short-chain fatty acids (SCFAs) that restrict the growth of invading microorganisms. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium triggers inflammation in the large intestine to ultimately reduce microbiota density and bloom, but it is unclear how the pathogen gains a foothold in the homeostatic gut when SCFA-producing commensals are abundant. Here, we show that S. Typhimurium invasion of the ileal mucosa triggers malabsorption of dietary amino acids to produce downstream changes in nutrient availability in the large intestine. In gnotobiotic mice engrafted with a community of 17 human Clostridia isolates, S. Typhimurium virulence factors triggered marked changes in the cecal metabolome, including an elevated abundance of amino acids. In an ex vivo fecal culture model, we found that two of these amino acids, lysine and ornithine, countered SCFA-mediated growth inhibition by restoring S. Typhimurium pH homeostasis through the inducible amino acid decarboxylases CadA and SpeF, respectively. In a mouse model of gastrointestinal infection, S. Typhimurium CadA activity depleted dietary lysine to promote cecal ecosystem invasion in the presence of an intact microbiota. From these findings, we conclude that virulence factor-induced malabsorption of dietary amino acids in the small intestine changes the nutritional environment of the large intestine to provide S. Typhimurium with resources needed to counter growth inhibition by microbiota-derived SCFAs.PMID:39546570 | DOI:10.1073/pnas.2417232121

JMIR Res Protoc. 2024 Nov 15;13:e63562. doi: 10.2196/63562.ABSTRACTBACKGROUND: Research in the developmental origins of health and disease provides compelling evidence that adverse events during the first 1000 days of life from conception can impact life course health. Despite many decades of research, we still lack a complete understanding of the mechanisms underlying some of these associations. The Newcastle 1000 Study (NEW1000) is a comprehensive, prospective population-based pregnancy cohort study based in Newcastle, New South Wales, Australia, that will recruit pregnant women and their partners at 11-14 weeks' gestation, with assessments at 20, 28, and 36 weeks; birth; 6 weeks; and 6 months, in order to provide detailed data about the first 1000 days of life to investigate the developmental origins of noncommunicable diseases.OBJECTIVE: The study aims to provide a longitudinal multisystem approach to phenotyping, supported by robust clinical data and collection of biological samples in NEW1000.METHODS: This manuscript describes in detail the large variety of samples collected in the study and the method of collection, storage, and utility of the samples in the biobank, with a particular focus on incorporation of the samples into emerging and novel large-scale "-omics" platforms, including the genome, microbiome, epigenome, transcriptome, fragmentome, metabolome, proteome, exposome, and cell-free DNA and RNA. Specifically, this manuscript details the methods used to collect, process, and store biological samples, including maternal, paternal, and fetal blood, microbiome (stool, skin, vaginal, oral), urine, saliva, hair, toenail, placenta, colostrum, and breastmilk.RESULTS: Recruitment for the study began in March 2021. As of July 2024, 1040 women and 684 partners were enrolled, with 922 infants born. The NEW1000 biobank contains 24,357 plasma aliquots from ethylenediaminetetraacetic acid (EDTA) tubes, 5284 buffy coat aliquots, 4000 plasma aliquots from lithium heparin tubes, 15,884 blood serum aliquots, 2977 PAX RNA tubes, 26,595 urine sample aliquots, 2280 fecal swabs, 17,687 microbiome swabs, 2356 saliva sample aliquots, 1195 breastmilk sample aliquots, 4007 placental tissue aliquots, 2680 hair samples, and 2193 nail samples.CONCLUSIONS: NEW1000 will generate a multigenerational, deeply phenotyped cohort with a comprehensive biobank of samples relevant to a large variety of analyses, including multiple -omics platforms.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/63562.PMID:39546349 | DOI:10.2196/63562

J Am Soc Mass Spectrom. 2024 Nov 15. doi: 10.1021/jasms.4c00408. Online ahead of print.ABSTRACTThe matrix effect limits the accuracy of quantitation of the otherwise popular metabolomics technique liquid chromatography coupled to mass spectrometry (LC-MS). The gold standard to correct for this phenomenon, whereby compounds coeluting with the analyte of interest cause ionization enhancement or suppression, is to quantify an analyte based on the peak area ratio with an isotopologue added to the sample as an internal standard. However, these stable isotopes are expensive and sometimes unavailable. Here, we describe an alternative approach: matrix effect correction and quantifying analytes using a signal ratio with a postcolumn infused standard (PCIS). Using an LC-MS/MS method for eight endocannabinoids and related metabolites in plasma, we provide strategies to select, optimize, and evaluate PCIS candidates. Based on seven characteristics, the structural endocannabinoid analogue arachidonoyl-2'-fluoroethylamide was selected as a PCIS. Three methods to evaluate the PCIS correction vs no correction showed that PCIS correction improved values for the matrix effect, precision, and dilutional linearity of at least six of the analytes to within acceptable ranges. PCIS correction also resulted in parallelization of calibration curves in plasma and neat solution, for six of eight analytes even with higher accuracy than peak area ratio correction with their stable isotope labeled internal standard, i.e., the gold standard. This enables quantification based on neat solutions, which is a significant step toward absolute quantification. We conclude that PCIS has great, but so far underappreciated, potential in accurate LC-MS quantification.PMID:39546343 | DOI:10.1021/jasms.4c00408

Anal Chem. 2024 Nov 15. doi: 10.1021/acs.analchem.4c01939. Online ahead of print.ABSTRACTThe change of metabolic pathways is recognized as the key to disease discovery prompting the development of ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)-based quantitative platforms to explore the dynamic metabolite profiles of organisms. In this study, a liquid chromatography method based on cyanopropyl (CN) was developed. By adjusting the pH environment of the column, we achieved the elution of 51 metabolites spanning the most comprehensive set of biological pathways currently known. Offering rapid chromatography, efficient separation, and green chemistry benefits, the method encompasses nucleosides and nucleotides, the oxidative-redox metabolome, the glycolysis pathway, the pentose phosphate pathway, the purine de novo pathway, amino acids, and neurological disorder-related metabolites. The mass spectrometry was equipped with electrospray ionization in both positive and negative modes with scheduled multiple reactions monitoring. The validation of the method involved a comprehensive assessment of linearity, accuracy, precision, and matrix effect. The linear range was from 1.0 to 2000 ng mL-1 with a high correlation coefficient (r > 0.99). The LOD ranged from 0.1 to 10 ng mL-1, and the LOQ ranged from 0.1 to 25 ng mL-1. The overall recovery ranged from 81.3% to 117.8%, with RSD < 15.1%. Subsequently, an analysis of metabolites was conducted in dSH-SY5Y neuroblastoma cells with 6-hydroxydopamine, a commonly used neurotoxin in neurodegenerative diseases. The results demonstrate that neurotoxin-induced mitochondrial damage significantly altered related analytes, corroborating previous estimates and validating the feasibility and reliability of the bioanalytical platform.PMID:39546327 | DOI:10.1021/acs.analchem.4c01939

Methods Mol Biol. 2025;2878:163-199. doi: 10.1007/978-1-0716-4264-1_9.ABSTRACTIn vitro and ex vivo studies are crucial for mitochondrial research, offering valuable insights into cellular mechanisms and aiding in diagnostic and therapeutic strategies. Accurate in vitro models rely on adequate cell culture conditions, such as the composition of culture media and oxygenation levels. These conditions can influence energy metabolism and mitochondrial activities, thus impacting studies involving mitochondrial components, such as the effectiveness of anticancer drugs. This chapter focuses on practical guidance for creating setups that replicate in vivo microenvironments, capturing the original metabolic context of cells. We explore protocols to better mimic the physiological cell environment, promote cellular reconfiguration, and prime cells according to the modeled context. The first part is dedicated to the use of human dermal fibroblasts, which are a promising model for pre-clinical mitochondrial research due to their adaptability and relevance to human mitochondrial physiology. We present an optimized protocol for gradually adjusting extracellular glucose levels, which demonstrated significant mitochondrial, metabolic, and redox remodeling in normal adult dermal fibroblasts. The second part is dedicated to replication of tumor microenvironments, which are relevant for studies targeting cellular energy metabolism to inhibit tumor growth. Currently available physiological media can mimic blood plasma metabolome but not the specific tumor microenvironment. To address this, we describe optimized media formulation and oxygenation protocols, which can simulate the tumor microenvironment in cell culture experiments. Replicating in vivo microenvironments in in vitro and ex vivo studies can enhance our understanding of cellular processes, facilitate drug development, and advance personalized therapeutics in mitochondrial medicine.PMID:39546262 | DOI:10.1007/978-1-0716-4264-1_9

Planta. 2024 Nov 15;260(6):138. doi: 10.1007/s00425-024-04571-3.ABSTRACTThe metabolomic of the Italian endemic species Stachys italica was investigated and potential positive metabolites for human's health were detected, quantified and discussed in relation to its synecology. Stachys italica is a species endemic to central-southern Italy, traditionally used for human consumption. The present research reports the results of a phytosociological study of this species in two southern regions of Italy (Apulia and Calabria). The collected plant material was used to make two types of extracts: hot water infusion to evaluate the use of this plant as tea and hydroalcoholic extraction to evaluate the use of it in herbal liqueur preparation. The extracts obtained by the hot water infusion had a values of total polyphenols and antioxidant capacity similar to values found in black tea. The analysis of non-volatiles compounds revealed the presence of biologically active substances like lavandulifolioside, verbascoside, and methoxyflavones. The analysis of volatiles fraction of metabolites demonstrated fifty-three volatiles compounds in the plant aerial part, 19 of which belonging to monoterpenoids, and 17 to the class of sesquiterpenoids. Among them, α-pinene, β-pinene, cis-ocimene, limonene and t-caryophyllene, were the most abundant compounds. The results were compared with already published results and referred to other similar species (such as Sideritis syriaca) which represent herbal mixtures usually collected and used as "mountain tea" in the Balkans and Eastern European countries.PMID:39545970 | DOI:10.1007/s00425-024-04571-3

Mol Microbiol. 2024 Nov 15. doi: 10.1111/mmi.15329. Online ahead of print.ABSTRACTIn Pseudomonas donghuensis SVBP6, isolated from an agricultural field, the well-conserved Gac-Rsm pathway upregulates biosynthesis of the antifungal compound 7-hydroxytropolone (7-HT). However, 7-HT does not fully explain the strain's Gac-Rsm-dependent antimicrobial activity. Here, we combined comparative transcriptomic, proteomic, and metabolomic approaches to identify novel GacS-dependent biosynthetic gene clusters (BGC) and/or extracellular specialized metabolites. Our data revealed a broad impact of GacS on gene expression and extracellular metabolite profile of SVBP6. At both the mRNA and polypeptide levels, specialized metabolism was the main affected functional category in the gacS mutant. The major extracellular MS/MS spectral families promoted by GacS were fatty acid amides, fatty acids, and alkaloids. GacS was required for the production of the antimicrobial compound pseudoiodinine and to activate expression of the corresponding BGC. We also detected GacS-dependent production of 2,3,4-trihydro-β-carboline-1-one, which may add to the antimicrobial arsenal of SVBP6. Furthermore, transcriptomics and proteomics pinpointed several GacS-activated BGCs that had escaped in silico genome mining tools. Altogether, comparative multi-omics analyses of gacS loss-of-function mutants in Pseudomonas isolates are a promising strategy to uncover bioactive metabolites and/or their BGCs. Discovery of novel natural products is important for harnessing the potential of microbiota to improve crop plant growth and health.PMID:39545927 | DOI:10.1111/mmi.15329

Mol Oncol. 2024 Nov 15. doi: 10.1002/1878-0261.13759. Online ahead of print.ABSTRACTNeoadjuvant chemotherapy (NAT) is increasingly used for the treatment of non-metastatic pancreatic ductal adenocarcinoma (PDAC) and is established as a standard of care for borderline resectable and locally advanced PDAC. However, full exploitation of its clinical benefits is limited by the lack of biomarkers that assess treatment response. To address this unmet need, global metabolomic profiling was performed on tumor tissue and paired serum samples from patients with treatment-naïve (TN; n = 18) and neoadjuvant leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride and oxaliplatin (FOLFIRINOX)-treated (NAT; n = 17) PDAC using liquid chromatography mass spectrometry. Differentially abundant metabolites (DAMs) in TN versus NAT groups were identified and their correlation with various clinical parameters was assessed. Metabolomics profiling identified 40 tissue and five serum DAMs in TN versus NAT PDAC. In general, DAMs associated with amino acid and nucleotide metabolism were lower in NAT compared to TN. Four DAMs-3-hydroxybutyric acid (BHB), 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), glycochenodeoxycholate and citrulline-were common to both tissue and serum and showed a similar pattern of differential abundance in both groups. A strong positive correlation was observed between serum carbohydrate 19-9 antigen (CA 19-9) and tissue carnitines (C12, C18, C18:2) and N8-acetylspermidine. The reduction in CA 19-9 following NAT correlated negatively with serum deoxycholate levels, and the latter correlated positively with survival. This study revealed neoadjuvant-chemotherapy-induced changes in metabolic pathways in PDAC, mainly amino acid and nucleotide metabolism, and these correlated with reduced CA 19-9 following neoadjuvant FOLFIRINOX treatment.PMID:39545923 | DOI:10.1002/1878-0261.13759

J Agric Food Chem. 2024 Nov 15. doi: 10.1021/acs.jafc.4c06019. Online ahead of print.ABSTRACTThe gut microbiota contribute significantly to the immune system. Low-medium polarity ginsenosides from wild ginseng (LWG) have potential immunomodulatory effects. However, how the LWG regulates gut microbiota to enhance immunity remains unclear. To explore the interaction between gut microbes and metabolites mediating LWG's immunomodulatory effects, this study examined LWG's impact on splenocytes and CTX-induced immunosuppressed mice. Metabolomic and metagenomic analyses were conducted in vivo to explore the mechanism by which LWG regulates gut microbiota to enhance immunity. In vitro data suggest that LWG at 4 μg/mL enhances the splenocyte activity. Furthermore, LWG effectively reduces symptoms in immunocompromised mice, including weight loss and intestinal mucosal damage. LWG alleviated gut microbiota disturbance, restored tryptophan metabolites (IA, IAA, and IPA), and significantly increased JNK, ERK, and p38MAPK protein levels, which were downstream of AhR. Our study demonstrated that LWG improves the immunity by reshaping gut microbiota, restoring intestinal mucosa, and boosting the gut microbiota-related metabolism of tryptophan to activate the AhR/MAPK pathway. This research offers new insights into the mechanism by which LWG regulates immune function.PMID:39545702 | DOI:10.1021/acs.jafc.4c06019

West Afr J Med. 2024 Nov 10;41(11 Suppl 1):S57.ABSTRACTINTRODUCTION: Severe acute symptomatic hypocalcemia, requiring emergency medical intervention, is a significant but poorly understood condition with high morbidity. In our setting, patients present to emergency rooms with painful carpo-pedal spasms that last for several hours, sometimes mimicking seizure disorders. Metabolomics and genetic profiling are innovative approaches that pinpoint molecular and genetic determinants of hypocalcemia risk which can be adopted to guide treatment in our population.OBJECTIVE: To determine the prevalence of hypocalcemia in urban Kano as a preliminary step towards identifying key risk factors.METHODS: We obtained retrospective data from patients who presented to a tertiary hospital between January and December 2023. Serum calcium levels were measured on Abbott Architect c4000 autoanalyzer. We analyzed data using R statistical software (version 4.3.2). Chi-square tests were used to assess significant differences (p < 0.05).RESULTS: A total of 1,270 samples were analyzed, consisting of 59.3% (n = 753) males, their mean age was 36.2 ± 4 years. Mean serum calcium levels were 2.05 ± 0.34 mmol/L to 2.11 ± 1.00 mmol/L. Overall prevalence of hypocalcemia (serum calcium < 2.2 mmol/L) was 52.2%. Females exhibited a significantly higher prevalence (58.8%) compared to males (p = 0.03). The highest prevalence was observed in the 40-59-year age group (p < 0.01).CONCLUSION: Hypocalcemia is highly prevalent in our population emphasizing the need for innovative approaches to better understand the genetic predictors, enable early intervention and prevent the long-term complications. These findings also provide a foundation for future multicenter studies and could inform public health policies targeting at risk groups. Keywords: Hypocalcaemia, Risk prediction,Metabolomics, Genetic markers.PMID:39545459

Plant Cell Environ. 2024 Nov 15. doi: 10.1111/pce.15282. Online ahead of print.ABSTRACTThe availability of nitrogen (N) can dramatically influence crops resistance to herbivorous insects. However, the interaction between N fertilization and crop resistance to insects is not well understood. In this study, the effects of N fertilization on the grain aphid (Sitobion miscanthi) were investigated using three wheat (Triticum aestivum) cultivars with different aphid resistances. We measured aphid life cycle parameters, fecundity, survival rate, weight and feeding behavior, in conjunction with wheat metabolomics, transcriptomics and alien introgression analysis. Our results demonstrated that higher N application benefits aphid feeding across all three wheat cultivars. We also reveal that the highly resistant cultivar (ZM9) can only exert its resistance-advantage under low N fertilization, losing its advantage compared to moderately resistant cultivar YN19 and susceptible cultivar YN23 under higher N fertilization. The effects of N fertilization on wheat-aphid interactions were due to changes in the regulation of carbon and nitrogen metabolism. Integration of multi-omics highlighted specific aphid-induced differentially expressed genes (DEGs, e.g., TUB6, Tubulin 6; ENODL20, Early nodulin-like protein 20; ACT7 Actin 7; Prx47, Peroxidase 47) and significantly different metabolites (SDMs, e.g., crotonoside, guanine, 2'-O-methyladenosine, ferulic acid) in ZM9. Additionally, we report the unique SDMs-DEGs interactions, associated with introgression during wheat domestication, may help infer aphid resistance. In summary, this study provides new insights into the relationships between N fertilization practices, defense responses and integrated pest management for sustainable wheat production.PMID:39545337 | DOI:10.1111/pce.15282

Food Funct. 2024 Nov 15. doi: 10.1039/d4fo02309a. Online ahead of print.ABSTRACTVanillic acid (VA) is a natural phenolic acid compound that is widely found in various foods and medicinal plants, with a remarkable antifibrotic effect observed in animal studies, but its exact antifibrotic mechanism remains unclear. Herein, hepatic function, fibrotic index, and histopathological, microbiome, and metabolomic methods were used to investigate the potential mechanisms behind the improvement effect of vanillic acid against thioacetamide (TAA)-induced liver fibrosis in mice. Our results showed that VA reversed TAA-induced liver fibrosis manifested a decrease in collagen fiber deposition, serum transaminase, serum hepatic fibrotic index, and liver inflammation indicator levels. When analyzed, TAA injection mainly increased the abundance of Akkermansia and Roseburia and significantly reduced the abundance of Anaerotruncus. VA reversed these changes back to normal levels to varying degrees. Metabolomic profiling demonstrated that VA treatment was efficacious in modulating several key liver metabolites involved in neuroactive ligand-receptor interaction, prolactin signaling pathway, estrogen signaling pathway, and glutathione metabolism. Conclusively, VA may ameliorate liver damage and suppress the fibrogenesis caused by thioacetamide by correcting intestinal microbiota disorders and promoting normal hepatic metabolism. This research provides a novel perspective on vanillic acid as a dietary supplement for hepatic fibrosis improvement.PMID:39545308 | DOI:10.1039/d4fo02309a

Front Microbiol. 2024 Oct 31;15:1487978. doi: 10.3389/fmicb.2024.1487978. eCollection 2024.ABSTRACTOBJECTIVE: The purpose of this study was to explore the potential mechanism of Helicobacter pylori (Hp) eradication by probiotic therapy through 16S rRNA gene sequencing technology and untargeted metabolomics.METHODS: Twenty four Hp-infected children were recruited from the Shanxi Bethune Hospital, and 24 healthy children were recruited as a blank control group. Group A: fecal samples from 24 healthy children. Group B: fecal samples of 24 children with Hp infection. Group B1 (n = 15): fecal samples of group B treated with probiotic therapy for 2 weeks. Group B2 (n = 19): fecal samples of group B treated with probiotic therapy for 4 weeks. The above fecal samples were analyzed by 16S rRNA gene sequencing technology and untargeted metabolomics.RESULTS: There was no significant difference in alpha diversity and beta diversity among the four groups, but many bacteria with statistical difference were found in each group at the bacterial genus level and phylum level. LEfSe results showed that in group B, Porphyromonadaceae, Shigella and other microorganisms related to intestinal microecological dysbiosis were enriched. And in group B2, abundant characteristic microorganisms were found, namely Bacillales and Prevotella. KEGG metabolic pathway enrichment analysis showed that groups B1 and B2 were involved in 10 metabolic pathways potentially related to probiotic treatment: purine metabolism, nitrogen metabolism, arginine biosynthesis, alanine, aspartic acid and glutamate metabolism, glyoxylic acid and dicarboxylic acid metabolism, unsaturated fatty acid biosynthesis, fatty acid extension, fatty acid degradation, pyrimidine metabolism, fatty acid biosynthesis.CONCLUSION: Probiotic therapy can inhibit Hp to some extent and can relieve gastrointestinal symptoms, making it a preferred therapy for children with Hp infection and functional abdominal pain. Hp infection can reduce the diversity of intestinal microbes, resulting in the disturbance of intestinal microbiota and changes in the relative abundance of microbiota in children, while probiotic therapy can restore the diversity of intestinal microbes and intestinal microecological balance.PMID:39545236 | PMC:PMC11560915 | DOI:10.3389/fmicb.2024.1487978