PubMed

Food Chem. 2025 Jan 5;471:142788. doi: 10.1016/j.foodchem.2025.142788. Online ahead of print.ABSTRACTThe study was designed to investigate the mechanism of Riboflavin (RF)-mediated UVA photosensitive oxidation on beef myofibrillar proteins (MP) oxidized at different storage times. To elucidate the direct relationship between RF and protein oxidation, the mechanism of action was analyzed in terms of amino acid and side chain residues, protein structure, and protein oxidative metabolism. Oxidation of MP resulted in significant changes in the levels of carbonyls, sulfhydryls, Lysine, Arginine, Threonin, and Histidine. The oxidized MP secondary structure was changed, fluorescence intensity decreased, and surface hydrophobicity increased. Metabolomics results revealed that RF-mediated UVA photosensitized oxidation is primarily mediated by Riboflavin metabolism and co-regulated with Phenylalanine metabolism. Moreover, with the increase of frozen storage time, Arginine and proline metabolism was inhibited, and the contents of creatine were significantly reduced, which exacerbated MP oxidative damage. The results provide a theoretical basis for unraveling the mechanism of RF-mediated UVA photosensitive oxidation of MP.PMID:39788020 | DOI:10.1016/j.foodchem.2025.142788

Food Chem. 2024 Dec 30;471:142709. doi: 10.1016/j.foodchem.2024.142709. Online ahead of print.ABSTRACTEssential oils (EOs) are gaining popularity due to their potent antibacterial properties, as well as their applications in food preservation and flavor enhancement, offering growth opportunities for the food industry. However, their widespread use as food preservatives is limited by authenticity challenges, primarily stemming from adulteration with cheaper oils. This study investigated a rapid, cost-effective, and non-destructive method for assessing the authenticity of widely used Mentha and Ocimum EOs. The proposed approach integrates Fourier transform near-infrared (FT-NIR) spectroscopy with machine learning to enable rapid metabolic fingerprinting of EOs. Four Mentha species and three Ocimum species were analysed, and the system was tested on market samples adulterated with vegetable oils. The approach achieved exceptional performance, with Q2, R2, and accuracy exceeding 0.98, alongside specificity and sensitivity greater than 98 %. These findings demonstrated that FT-NIR, combined with machine learning, offers a highly efficient solution for addressing authenticity and adulteration issues in EOs.PMID:39788017 | DOI:10.1016/j.foodchem.2024.142709

Food Chem. 2025 Jan 3;471:142761. doi: 10.1016/j.foodchem.2025.142761. Online ahead of print.ABSTRACTPomegranate seeds, a by-product of pomegranate processing, are gaining attention in food industries due to their high antioxidant activity. However, the lack of quality markers reflecting activity and spatial characteristics limits their utilization and product stability. In this research, a selective and sensitive method integrating ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry with feature-based molecular networking, and desorption electrospray ionization-mass spectrometry imaging developed to identify components and locate in-situ images of quality markers via spatial metabolomics analysis. Additionally, molecular docking analyses and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays validated the antioxidant quality markers and elucidated correlations between these markers, regions, and activity. A total of 227 components were identified, and six were selected as quality markers for pomegranate seeds, reflecting their antioxidant activity and spatial characteristics. Consequently, this research provides an efficient method for screening food quality markers based on activity and spatial characteristics, providing insights into food quality evaluation.PMID:39788015 | DOI:10.1016/j.foodchem.2025.142761

Food Chem. 2024 Dec 31;471:142628. doi: 10.1016/j.foodchem.2024.142628. Online ahead of print.ABSTRACTA study of the lipidome and proteome was performed on milk fat globule membranes (MFGM) originating from milk samples from high (HL) and low (LL) lipolysis groups of cows. Combined univariate and multivariate statistical analyses proposed a set of variables highly associated to contrasted samples with regard to milk lipolysis. Milk from HL group were related to 4 phosphatidylinositols, 8 phosphatidylcholines, 1 sphingomyelin and 27 proteins, among them the phosphatidylcholine/phosphatidylethanolamine ratio and ORM1 may contribute to the membrane remodeling of the MFGM. The abundance of CP, CHI3L1, NECTIN2, A2M were strongly positively correlated with HL. Conversely, 3 phosphatidylinositols, 1 phosphatidylcholine and 2 phosphatidylethanolamines were assigned to the LL group. The HL group in cows is associated with a specific MFGM phospholipids and proteins profile, suggesting an impact on membrane fluidity and lipid rafts composition intervening in LPL anchoring and activation, as well as on pro-inflammatory lipids and proteins.PMID:39788004 | DOI:10.1016/j.foodchem.2024.142628

Semin Cell Dev Biol. 2025 Jan 8;167:1-9. doi: 10.1016/j.semcdb.2024.12.006. Online ahead of print.ABSTRACTThe glioblastoma tumour microenvironment is characterised by immense heterogeneity, with malignant and non-malignant cells that interact in a complex ecosystem. Emerging evidence suggests that the tumour microenvironment is key in facilitating rapid proliferation, invasion, migration and cancer cell survival, crucial for treatment resistance. Spatial omics technologies have enabled the molecular characterisation of regions or individual cells within their spatial context, providing previously unattainable insights into the complex organisation of the glioblastoma tumour microenvironment. Understanding this organisation is crucial for the development of new therapeutics and novel diagnostic tools that guide patient care. This review explores spatial omics technologies and how they have contributed to the development of a model outlining the architecture of the glioblastoma tumour microenvironment.PMID:39787997 | DOI:10.1016/j.semcdb.2024.12.006

Mol Genet Metab. 2024 Dec 30;144(3):109009. doi: 10.1016/j.ymgme.2024.109009. Online ahead of print.ABSTRACTThe 3-methylglutaconic aciduria (3-MGA-uria) syndromes comprise a heterogeneous group of inborn errors of metabolism defined biochemically by detectable elevation of 3-methylglutaconic acid (3-MGA) in the urine. In type 1 (or primary) 3-MGA-uria, distal defects in the leucine catabolism pathway directly cause this elevation. Secondary 3-MGA-uria syndromes, however, are unrelated to leucine metabolism-specific defects but share a common biochemical phenotype of elevated 3-MGA. It is currently thought that this accumulation is due to an underlying buildup of acetyl-CoA in the mitochondria from impaired function of the TCA cycle with ensuing formation of trans-3-methylglutaconyl CoA and its subsequent byproducts, including 3-MGA. In these disorders, urine 3-MGA levels are known to be fluctuant and at times undetectable by standard urine organic acid analysis (UOA), thereby reducing the utility of this biochemical screening method. Here, we retrospectively evaluated a cohort of nine patients with confirmed 3-MGA-uria syndromes. It was observed that UOA analysis obtained from three separate patients did not identify detectable 3-MGA levels. This inherent limitation highlights the need for a more sensitive clinical modality. Untargeted metabolomics profiling is a rapidly emerging technology that is being used to detect and characterize biochemical abnormalities in many inborn errors of metabolism. Untargeted metabolomics profiling performed on plasma samples in this cohort identified significant elevations of 3-MGA in all nine individuals. This high degree of clinical sensitivity demonstrates the promising potential for untargeted metabolomics analysis as both an effective biochemical screening tool for 3-MGA-uria syndromes and a functional method to assist with validation of genomic variants of uncertain significance in these disorders.PMID:39787888 | DOI:10.1016/j.ymgme.2024.109009

Int Immunopharmacol. 2025 Jan 8;147:113975. doi: 10.1016/j.intimp.2024.113975. Online ahead of print.ABSTRACTAtopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder characterized by intense pruritus and complex immunopathogenic mechanisms. Recent evidence has highlighted the critical link between dysregulated intestinal microecology and altered immune responses in AD progression. As essential components of the intestinal microenvironment, metabolites play pivotal roles in various physiological processes. Through metabolomic profiling in an AD mouse model, we identified a significant reduction in canthaxanthin (CTX), a bacterial-derived metabolite naturally present in many foods, in AD mice compared to healthy controls. To investigate the therapeutic potential of CTX, we established an AD model by repeatedly applying 2,4-dinitrochlorobenzene (DNCB) to the ears and dorsal skin of mice, successfully inducing AD-like symptoms and lesions. Notably, oral administration of CTX significantly attenuated skin inflammation and reduced serum IgE levels in this DNCB-induced AD model. Both in vivo and in vitro studies demonstrated that CTX treatment effectively suppressed Th2 immune responses. Mechanistically, we found that CTX significantly inhibited the activation of the JAK2-STAT6 signaling pathway in Th2-polarized T cells. Our findings not only demonstrate the therapeutic efficacy of CTX in AD but also elucidate its molecular mechanism in modulating T helper cell subset balance. These insights suggest that CTX could serve as a promising therapeutic agent for AD and potentially other Th2 response-mediated immune disorders.PMID:39787760 | DOI:10.1016/j.intimp.2024.113975

Phytomedicine. 2024 Dec 28;137:156355. doi: 10.1016/j.phymed.2024.156355. Online ahead of print.ABSTRACTBACKGROUND: Metabolic syndrome (MS) refers to a cluster of metabolic disorders characterized by systemic chronic inflammation. Er Miao San (EMS) is a classic traditional Chinese medicine compound containing Phellodendron amurense and Atractylodis rhizome at a ratio of 1:1, proven to be effective against inflammatory diseases in clinical practice. Nevertheless, the precise functions of EMS in treating MS and its underlying mechanism have yet to be elucidated.PURPOSE: This study focuses on the intervention effects of EMS on high humidity exposure and high sugar-fat diet (HHSF)-induced MS in pigs.STUDY DESIGN: Blood biochemical indices and metabolome analysis were employed to confirm the successful establishment of the MS model, and the preliminary evaluation of the intervention effect of EMS was conducted. Subsequently, a parallel microbiota analysis of the tongue and cecum was combined with metabolomic analysis, histopathologic examination, and other molecular biological detection to further assess the administration mechanism of EMS.RESULTS: The results demonstrated that EMS significantly reduced the excessive weight gain rate, fat accumulation, hyperlipidemia, hyperglycemia, and systemic inflammation while improving serum metabolic disorder in MS pigs. Moreover, microbiota analysis indicates that EMS restored the diversity and composition of oral-gut microbiota by increasing the proportions of Lactobacillus (gut), Roseburia (gut), Faecalibacterium (gut), CF231 (gut), Streptococcus (gut), Prevotella (gut), while decreasing those of Chryseobacterium (oral), Corynebacterium (oral), Clostridium (oral), Oscillospira (gut), and Turicibacter (oral, gut). Subsequently, EMS up-regulated the concentrations of acetic acid, butyric acid, propionic acid, while down-regulated isobutyric acid and isovaleric acid. This resulted in a suppression of HDAC3 expression and an increase of SCL16A1 expression in the colon. Notably, the changes in acetic acid and butyric acid showed a strong correlation with gut microbiota. Additionally, EMS reduced the serum level of lipopolysaccharide (LPS) and enhanced epithelial barrier integrity by inhibiting the LPS-TLR4/MyD88/NF-κB pathways.CONCLUSIONS: EMS was found to ameliorate MS by alleviating the dysbiosis of the oral-gut microbiota and serum metabolome, thereby improving gut barrier and reducing systemic inflammation. These findings suggest that EMS holds promise as a therapeutic agent for MS.PMID:39787693 | DOI:10.1016/j.phymed.2024.156355

PLoS One. 2025 Jan 9;20(1):e0314029. doi: 10.1371/journal.pone.0314029. eCollection 2025.ABSTRACTIncreasing evidence suggests that dysbiosis of gut microbiota exacerbates chronic kidney disease (CKD) progression. Curcumin (CUR) has been reported to alleviate renal fibrosis in animal models of CKD. However, the relationship between CUR and gut microbiome in CKD remains unclear. This study aims to investigate the potential anti-renal fibrosis effects of CUR from the gut microbiota perspective. A 5/6 nephrectomy (5/6Nx) rat model was used to explore the therapeutic effect of CUR on renal fibrosis. Tight junction protein expression levels were measured to assess intestinal barrier function. 16S rRNA sequencing was employed to evaluate changes in gut microbiota composition, and metabolomics was utilized to detect alterations in plasma metabolites. The administration of CUR significantly ameliorated renal fibrosis and inhibited inflammation in 5/6Nx rats. Additionally, CUR markedly improved the expression of tight junction proteins and local colon inflammation. CUR also positively reconstructed gut microbiota, significantly increasing the abundance of beneficial bacteria, such as Lachnospiraceae_NK4A136_group, Eubacterium_siraeum_group, and Muribaculaceae was significantly increased. Metabolomics revealed that CUR reduced uremic retention solutes and elevated Vitamin D and short-chain fatty acids (SCFAs). Spearman correlation analysis indicated that gut genera enriched by CUR were positively correlated with Vitamin D and SCFA and negatively correlated with chronic renal injury biomarkers. Mechanistically, we found inhibition of the LPS/TLR4/NF-κB and TGF-β1/Smads pathway in CUR-treated rats. Our study indicates that CUR has the potential to modulate gut microbiota composition, and that this modulation may contribute to the anti-fibrosis effects of CUR.PMID:39787157 | DOI:10.1371/journal.pone.0314029

PLoS One. 2025 Jan 9;20(1):e0313989. doi: 10.1371/journal.pone.0313989. eCollection 2025.ABSTRACTINTRODUCTION: Pulmonary fibrosis (PF) is a chronic and irreversible interstitial lung disease characterized by a lack of effective therapies. Mesenchymal stem cells (MSCs) have garnered significant interest in the realm of lung regeneration due to their abundant availability, ease of isolation, and capacity for expansion. The objective of our study was to investigate the potential therapeutic role of umbilical cord-derived MSCs (UC-MSCs) in the management of PF, with a focus on the alterations in the gut microbiota and its metabolites during the use of UC-MSCs for the treatment of pulmonary fibrosis, as well as the possible mechanisms involved.METHODS: Bleomycin injection was utilized to establish a mouse model of lung fibrosis, followed by the application of 16S rDNA sequencing and LC-MS/MS metabolomics to explore the underlying mechanism of UC-MSC treatment for lung fibrosis. Seventy-five mice were allocated into five groups, namely Control, Model, and low/medium/high dose of UC-MSCs groups, and survival metrics, lung morphology, and the levels of the inflammatory cytokines TNF-α, IL-1β, IL-6, and TGF-β1 were subsequently evaluated. Fecal samples from six mice in each of the Control group, Model group, and UC-MSCs-M groups were collected randomly for 16S rDNA sequencing to analyze the gut microbiota and nontargeted metabolomics.RESULTS: In comparison to IPF model mice, the three treatment groups exhibited increased survival rates, restored alveolar morphology, and reduced levels of the inflammatory cytokines TNF-α, IL-1β, IL-6, and TGF-β1, confirming the anti-inflammatory properties of UC-MSCs in IPF treatment. The findings from the 16S rDNA assay indicate that UC-MSCs treatment effectively lower α-diversity induced such as Chao 1 and ACE, as well as β-diversity, leading to a decrease in microbiota abundance. The findings from the metabolomics analysis revealed that the metabolites exhibiting notable variances were primarily composed of Lipids and lipid-like molecules, Organoheterocyclic compounds, Organic acids and derivatives, and Benzenoids, indicating the potential of UC-MSCs to exert antifibrotic effects via these metabolic pathways.CONCLUSION: Umbilical cord-derived mesenchymal stem cells (UC-MSCs) ameliorate bleomycin-induced pulmonary fibrosis symptoms in mice by exerting anti-inflammatory effects and mitigating pulmonary fibrosis through the modulation of gut microbiota disorders and their metabolism. These findings offer novel insights into the potential mechanisms and clinical utility of stem cell therapy for pulmonary fibrosis.PMID:39787138 | DOI:10.1371/journal.pone.0313989

Radiat Res. 2024 Dec 31. doi: 10.1667/RADE-24-00219.1. Online ahead of print.ABSTRACTBBT-059 is a long-acting PEGylated interleukin-11 analog that has been shown to have hematopoiesis-promoting and anti-apoptotic attributes, and is being studied as a radiation countermeasure for the hematopoietic acute radiation syndrome (H-ARS). This potential countermeasure has been demonstrated to enhance survival in irradiated mice. To investigate the toxicity and safety profile of this agent, 14 nonhuman primates (NHPs, rhesus macaques) were administered two different doses of BBT-059 subcutaneously 24 h after 4 Gy total-body irradiation and were monitored for the next 60 days postirradiation. Blood samples were investigated for the pharmacokinetics and pharmacodynamics of this agent and its effects on complete blood counts, cytokines, vital signs, and for metabolomic studies. No adverse effects were observed in either treatment group. Radiation-induced metabolomic dysregulation was observed in both treatment groups, and BBT-059 afforded some short-term radiomitigation. A few pathways were commonly dysregulated by radiation exposure including the steroid hormone biosynthesis pathway, fatty acid activation, and glycerophospholipid metabolism. Notably, radiation-induced dysregulation to the linoleate metabolism pathway was significantly mitigated by either dose of BBT-059. In brief, this study suggests that BBT-059 has a good safety profile in irradiated NHPs and that its development as a medical countermeasure for U.S. Food and Drug Administration approval for human use should be continued.PMID:39786949 | DOI:10.1667/RADE-24-00219.1

Geroscience. 2025 Jan 9. doi: 10.1007/s11357-024-01490-9. Online ahead of print.ABSTRACTUnintentional weight loss in older populations is linked to greater mortality and morbidity risks. This study aims to understand the metabolic mechanisms of unintentional weight loss and their relationship with body composition changes in older adults. We investigated plasma metabolite associations with weight and body composition changes over 5 years in 1335 participants (mean age 73.4 years at Year 1, 51% women, and 33% Black) from the Health, Aging and Body Composition (Health ABC) study. Multinomial logistic regressions were used to examine associations of the 442 metabolites with weight loss > 5% over 5 years with/without an intention, weight gain > 5%, and fluctuating weight relative to weight stability. Metabolite associations with unintentional weight loss differed from other weight change patterns. Lower levels of essential amino acids, phospholipids, long-chain polyunsaturated triglycerides, cholesterol esters, and uridine were associated with higher odds of unintentional weight loss versus weight stability after adjusting for age, sex, race, and Year 1 BMI categories. Losses in fat mass and muscle mass each attenuated > 20% of the associations between many metabolites, such as phospholipids and essential amino acids, and unintentional weight loss. DXA whole-body fat mass loss (mean 3% annually) further attenuated 9 metabolite associations by > 50% after CT muscle loss (mean 2% annually) adjustment. Lipids and amino acids related to energy and protein balance were associated with unintentional weight loss in older adults. Fat and muscle mass losses partially attenuated these associations, suggesting connections of these metabolic pathways with muscle, and particularly adiposity dynamics.PMID:39786684 | DOI:10.1007/s11357-024-01490-9

Appl Biochem Biotechnol. 2025 Jan 9. doi: 10.1007/s12010-024-05158-0. Online ahead of print.ABSTRACTCaves are a unique ecosystem that harbor diverse microorganisms, and provide a challenging environment to the dwelling microbial communities, which may boost gene expression and can lead to the production of inimitable bioactive natural products. In this study, we obtained 59 actinobacteria from four different caves located in Bahadurkhel, District Karak, Pakistan. On the basis of taxonomic characteristics, 30 isolates were selected and screened for secondary metabolites production and bioactivity profiling. The extracts of all the isolates exhibited promising antibacterial activity against several pathogenic bacteria, with the best outcome seen in the extract of isolate SNK 21. The metabolomic analysis of the extracts by LC-MS/MS-based molecular networking and whole genome sequencing (WGS) followed by antiSMASH analysis revealed the presence of diverse secondary metabolites and biosynthetic gene clusters (BGCs) in SNK 21. Purification of compounds by manual chromatography, HPLC, and characterization by NMR, HR-MS, led to the identification of the active compounds, actinomycin D and its isomer. In addition, metabolomic analysis and genome mining of morphologically distinct isolates, SNK 202 and SNK 329, also showed diverse secondary metabolites and BGCs, underscoring the potential of actinobacteria from undisturbed caves in Pakistan as a new source of bioactive compounds.PMID:39786631 | DOI:10.1007/s12010-024-05158-0

Theor Appl Genet. 2025 Jan 9;138(1):24. doi: 10.1007/s00122-024-04806-7.ABSTRACTGenetic variation for malting quality as well as metabolomic and near-infrared features was identified. However, metabolomic and near-infrared features as additional omics-information did not improve accuracy of predicted breeding values. Significant attention has recently been given to the potential benefits of metabolomics and near-infrared spectroscopy technologies for enhancing genetic evaluation in breeding programs. In this article, we used a commercial barley breeding population phenotyped for grain yield, grain protein content, and five malting quality traits: extract yield, wort viscosity, wort color, filtering speed, and β-glucan, and aimed to: (i) investigate genetic variation and heritability of metabolomic intensities and near-infrared wavelengths originating from leaf tissue and malted grain, respectively; (ii) investigate variance components and heritabilities for genomic models including metabolomics (GOBLUP-MI) or near-infrared wavelengths (GOBLUP-NIR); and (iii) evaluate the developed models for prediction of breeding values for traits of interest. In total, 639 barley lines were genotyped using an iSelect9K-Illumina barley chip and recorded with 30,468 metabolomic intensities and 141 near-infrared wavelengths. First, we found that a significant proportion of metabolomic intensities and near-infrared wavelengths had medium to high additive genetic variances and heritabilities. Second, we observed that both GOBLUP-MI and GOBLUP-NIR, increased the proportion of estimated genetic variance for grain yield, protein, malt extract, and β-glucan compared to a genomic model (GBLUP). Finally, we assessed these models to predict accurate breeding values in fivefold and leave-one-breeding-cycle-out cross-validations, and we generally observed a similar accuracy between GBLUP and GOBLUP-MI, and a worse accuracy for GOBLUP-NIR. Despite this trend, GOBLUP-MI and GOBLUP-NIR enhanced predictive ability compared to GBLUP by 4.6 and 2.4% for grain protein in leave-one-breeding-cycle-out and grain yield in fivefold cross-validations, respectively, but differences were not significant (P-value > 0.01).PMID:39786601 | DOI:10.1007/s00122-024-04806-7

Arch Toxicol. 2025 Jan 9. doi: 10.1007/s00204-024-03944-7. Online ahead of print.ABSTRACTTesting for developmental toxicity is an integral part of chemical regulations. The applied tests are laborious and costly and require a large number of vertebrate test animals. To reduce animal numbers and associated costs, the zebrafish embryo was proposed as an alternative model. In this study, we investigated the potential of transcriptome analysis in the zebrafish embryo model to support the identification of potential biomarkers for key events in developmental toxicity, using the inhibition of angiogenesis as a proof of principle. Therefore, the effects on the zebrafish transcriptome after exposure to the tyrosine kinase inhibitors, sorafenib (1.3 µM and 2.4 µM) and SU4312 (1 µM, 2 µM, and 5 µM), and the putative vascular disruptor compound rotenone (25 nM and 50 nM) were analyzed. An early (2 hpf-hours post fertilization) and a late (24 hpf) exposure start with a time resolved transcriptome analysis was performed to compare the specificity and sensitivity of the responses with respect to anti-angiogenesis. We also showed that toxicodynamic responses were related to the course of the internal concentrations. To identify differentially expressed genes (DEGs) the time series data were compared by applying generalized additive models (GAMs). We observed mainly unspecific developmental toxicity in the early exposure scenario, while a specific repression of vascular related genes was only partially observed. In contrast, differential expression of vascular-related genes could be identified clearly in the late exposure scenario. Rotenone did not show angiogenesis-specific response on a transcriptomic level, indicating that the observed mild phenotype of angiogenesis inhibition may represent a secondary effect.PMID:39786591 | DOI:10.1007/s00204-024-03944-7

J Econ Entomol. 2024 Dec 30:toae303. doi: 10.1093/jee/toae303. Online ahead of print.ABSTRACTPollination by insects is vital for global agriculture, with honey bees (Apis mellifera L.) being the most important pollinators. Honey bees are exposed to numerous stressors, including disease, pesticides, and inadequate nutrition, resulting in significant colony losses. This study investigates the use of drone brood to mitigate these problems. Drone brood, which is normally discarded during varroa mite (Varroa destructor, Anderson and Trueman) management, is rich in proteins, fats, and essential minerals. We compared drone brood with an already suggested pollen supplement (Tenebrio [Tenebrio molitor L.] flour). The results indicate that drone brood flour is a viable source of proteins, fats, and minerals and is potentially antimicrobial due to its high content of elements with known antimicrobial properties. It meets the nutritional needs of honey bees while mitigating the effects of varroa mites. The use of drone brood flour can provide high-quality beeswax, surplus of pollen, and improve bee health, which promotes sustainable beekeeping.PMID:39786553 | DOI:10.1093/jee/toae303

Plant Cell Physiol. 2024 Dec 30:pcae151. doi: 10.1093/pcp/pcae151. Online ahead of print.ABSTRACTSoybean (Glycine max) is a leguminous crop cultivated worldwide that accumulates high levels of isoflavones. Although previous research has often focused on increasing the soybean isoflavone content because of the estrogen-like activity of dietary soy in humans, the rapidly increasing demand for soybean as a plant-based meat substitute has raised concerns about excessive isoflavone intake. Therefore, the production of isoflavone-free soybean has been anticipated. However, there have been no reports of an isoflavone-free soybean until now. Here, 2-hydroxyisoflavanone synthase (IFS), which is essential for isoflavone biosynthesis, was targeted for genome editing in soybean. A novel CRISPR/Cas9 system using Staphylococcus aureus Cas9 instead of the commonly-used Streptococcus pyogenes Cas9 was established and customized. Through Agrobacterium rhizogenes-mediated transformation, IFS-edited hairy roots were generated in which all three IFS genes contained deletion mutations. Metabolome analyses of IFS-edited hairy roots revealed that isoflavone content significantly decreased, whereas levels of flavonoids, including a novel chalcone derivative, increased. A transcriptome analysis revealed changes in the expression levels of a large number of genes, including jasmonic acid-inducible genes. In addition, the functions of selected transcription factor genes (MYB14-L, GmbHLH112, and GmbHLH113), which were dramatically upregulated by IFS editing, were investigated by multi-omics analyses of their over-expressing hairy root lines. They appear to be involved in flavonoid and triterpene saponin biosynthesis, salicylic acid metabolism, and central carbon metabolism. Overall, the results indicated that editing IFS genes caused the redirection of the metabolic flux from isoflavonoid biosynthesis to flavonoid accumulation, as well as dynamic changes in gene regulatory networks.PMID:39786412 | DOI:10.1093/pcp/pcae151

Alzheimers Dement. 2024 Dec;20 Suppl 2:e087895. doi: 10.1002/alz.087895.ABSTRACTBACKGROUND: It is challenging to distinguish which subcortical ischemic vascular disease (SIVD) patients will present with cognitive impairment. A blood-based biomarker to distinguish SIVD patients with cognitive impairment would be superior to neuropsychological measures and neuroimaging measures in terms of cost, time, and feasibility for repeated measures. Metabolomics profiling studies could help identify blood-based biomarkers for SIVD patients with cognitive impairment.METHOD: 100 SIVD patients without cognitive impairment,70 SIVD patients with cognitive impairment, 30 DLB patients and 30 AD patients were recruited from three Chinese research hospitals. 34 SIVD patients without cognitive impairment and 34 SIVD patients were follow-up for 2 years. Patients' serum samples were assessed using non-targeted metabolomics and lipidomics analyses.RESULT: Six metabolites including TG(52:2)-FA18:1, DHCer(d18:0_24:0), ChE(22:4), Cer(d18:1_18:0), SM(d18:1_26:0) and Hex2Cer(d18:1_24:0) were identified as informative biomarkers for cognitive impairment in SIVD patients. The performance was stable after 2 years follow up and in differential diagnosis among AD and DLB patients.CONCLUSION: Our study has developed an accurate and accessible means based on blood samples to identify SIVD patients at high risk of cognitive impairment. Dysregulation of sphingolipid metabolism was involved in the neurobiological pathways that contributed to cognitive impairment in SIVD patients.PMID:39786303 | DOI:10.1002/alz.087895

Alzheimers Dement. 2024 Dec;20 Suppl 2:e088773. doi: 10.1002/alz.088773.ABSTRACTBACKGROUND: The role of circulating metabolome in cognitive impairment is limited and inconclusive. We aimed to identify plasma metabolites associated with cognitive impairment and evaluate the added predictive capacity of metabolite biomarkers on incident cognitive impairment beyond traditional risk factors.METHOD: In the community-based Rugao Longevity and Ageing Study (RuLAS), plasma metabolome was profiled by nuclear magnetic resonance (NMR) spectroscopy. Participants were classified into the cognitively normal, moderately impaired, and severely impaired group according to their performance in two objective cognitive tests. A two-step strategy of cross-sectional discovery followed by prospective validation was applied to identify cognitive impairment-related metabolites. In the discovery stage, we included 1643 participants (age: 78.9 ± 4.5 years) and conducted multinomial logistic regression. In the validation stage, we matched 68 incident cases of cognitive impairment (moderately-to-severely impaired) during the 2-year follow-up to 204 cognitively normal controls by age and sex with a 1:3 ratio and conducted conditional logistic regression. Metabolite set enrichment analysis was performed to identify cognitive impairment-related metabolic pathways. We constructed prediction models for incident cognitive impairment using Lasso regression.RESULT: We identified 28 metabolites cross-sectionally related to severely impaired cognition, among which IDL particle number, ApoB in IDL, leucine, and valine were each prospectively associated with 28%, 28%, 29%, and 33% lower risk of incident cognitive impairment. Based on incident cognitive impairment-related metabolites, three enriched metabolic pathways (valine, leucine, and isoleucine biosynthesis; valine, leucine, and isoleucine degradation; and aminoacyl-tRNA biosynthesis) were found. Incorporating 13 metabolite biomarkers selected by Lasso regression into the traditional risk factors-based prediction model substantially improved the prediction performance on incident cognitive impairment (AUCs: 0.839 vs. 0.703, P <0.001).CONCLUSION: The study identified specific plasma metabolites and potential enriched metabolic pathways related to cognitive impairment. Utilizing the selected metabolites substantially improved the prediction performance for cognitive impairment.PMID:39786116 | DOI:10.1002/alz.088773

Alzheimers Dement. 2024 Dec;20 Suppl 2:e090813. doi: 10.1002/alz.090813.ABSTRACTBACKGROUND: Brain1,2, cerebrospinal fluid (CSF)3,4, and plasma5,6 metabolomics have been informative in identifying disrupted metabolism pathways in Alzheimer's disease (AD). However, many AD-focused metabolomics studies profiled a relatively small number of individuals and metabolites3-6, especially for CSF. In addition, past studies were limited to one or two tissues. Here we present a large-scaled three-tissue metabolomics study for Alzheimer's disease.METHOD: The cohorts of our study include Knight-ADRC, DIAN, ADNI, Barcelona-1, and Fundació ACE. In this study, 362 brain samples (N.ctrl = 27, N.AD = 335), 1,974 CSF samples (N.ctrl = 855, N.AD = 1,119), and 2,369 plasma samples (N.ctrl = 1,274, N.AD = 1,095) were included. The HD4 Metabolon platform was used to measure metabolomics of plasma, CSF, and brain samples. There were 797, 456, and 1,508, metabolites quantified in brain, CSF and plasma tissues. Linear regression model including age, sex, post-mortem interval was used to identify differentially present metabolites. FDR correction was applied to the analyzed metabolites.RESULT: The analyses in brain, CSF, and plasma identified 3, 65, and 553 metabolites differentially presented in AD compared to healthy controls after FDR multiple-test correction. There were 31 metabolites shared between plasma and CSF, in which 28 having consistent direction of effects. Of the 31 CSF-plasma shared metabolites, four metabolites (3-hydroxyisolutyrate, alpha-hydroxyisovalerate, ergothionenine, guaiacol sulfate), belonging to the branched-chain amino acids (BCAAs) or xenobiotics, were nominally significant in brain. The two BCAA-related metabolites, 3-hydroxyisolutyrate and alpha-hydroxyisovalerate, were replicated in another brain study1. Higher 3-hydroxyisolutyrate7 has been associated with obesity, a risk factor for AD. We found that ergothioneine level was low in AD and a recent study showed that this metabolite improved amyloid beta clearance8 in a mouse model. Using metabolites differentially abundant in the plasma tissue, we found BCAA biosynthesis, taurine metabolism, starch and sucrose metabolism, and tryptophan metabolism pathways being altered in AD.CONCLUSION: Our study performed the first multi-tissue metabolomics analyses on Alzheimer's disease. We identified concordant effects across tissues for many differentially abundant metabolites. The shared metabolites throughout tissues were closely linked to the Alzheimer's disease.PMID:39786091 | DOI:10.1002/alz.090813