PubMed

J Intensive Med. 2024 May 7;5(1):108-110. doi: 10.1016/j.jointm.2024.04.001. eCollection 2025 Jan.NO ABSTRACTPMID:39872829 | PMC:PMC11763573 | DOI:10.1016/j.jointm.2024.04.001

Food Chem X. 2025 Jan 9;25:102168. doi: 10.1016/j.fochx.2025.102168. eCollection 2025 Jan.ABSTRACTTender ginger is often used a fresh vegetable but hard to storage due to the delicate skin, high moisture content and prone to spoilage. In order to develop suitable preservation technology for tender ginger, the effects of vacuum packaging combined with different preservation temperatures (20-25 °C room temperature, 4 °C and 10 °C) on tender ginger shelf life were investigated. The results indicated that vacuum packaging combined with 4 °C (VP4) preservation could easily cause cold damage and postharvest physiological fluctuations. Vacuum packaging combined with 10 °C (VP10) inhibited moisture loss and physiological activities. Metabolomics analysis revealed 169 metabolites significantly differential regulated during VP10 preservation. The characteristic metabolites were primarily associated with amino acid, lipid and nucleotide metabolism. The metabolic pathways mainly involved linoleic acid metabolism; alanine, aspartate and glutamate metabolism; and purine metabolism. The above results indicated that VP10 effectively extended the preservation period of tender ginger with less damage.PMID:39872823 | PMC:PMC11770471 | DOI:10.1016/j.fochx.2025.102168

Bio Protoc. 2025 Jan 20;15(2):e5168. doi: 10.21769/BioProtoc.5168. eCollection 2025 Jan 20.ABSTRACTStable-isotope resolved metabolomics (SIRM) is a powerful approach for characterizing metabolic states in cells and organisms. By incorporating isotopes, such as 13C, into substrates, researchers can trace reaction rates across specific metabolic pathways. Integrating metabolomics data with gene expression profiles further enriches the analysis, as we demonstrated in our prior study on glioblastoma metabolic symbiosis. However, the bioinformatics tools for analyzing tracer metabolomics data have been limited. In this protocol, we encourage the researchers to use SIRM and transcriptomics data and to perform the downstream analysis using our software tool DIMet. Indeed, DIMet is the first comprehensive tool designed for the differential analysis of tracer metabolomics data, alongside its integration with transcriptomics data. DIMet facilitates the analysis of stable-isotope labeling and metabolic abundances, offering a streamlined approach to infer metabolic changes without requiring complex flux analysis. Its pathway-based "metabologram" visualizations effectively integrate metabolomics and transcriptomics data, offering a versatile platform capable of analyzing corrected tracer datasets across diverse systems, organisms, and isotopes. We provide detailed steps for sample preparation and data analysis using DIMet through its intuitive, web-based Galaxy interface. To showcase DIMet's capabilities, we analyzed LDHA/B knockout glioblastoma cell lines compared to controls. Accessible to all researchers through Galaxy, DIMet is free, user-friendly, and open source, making it a valuable resource for advancing metabolic research. Key features • Glioblastoma tumor spheroids in vitro replicate tumors' three-dimensional structure and natural nutrient, metabolite, and gas gradients, providing a more realistic model of tumor biology. • Joint analysis of tracer metabolomics and transcriptomics datasets provides deeper insights into the metabolic states of cells. • DIMet is a web-based tool for differential analysis and seamless integration of metabolomics and transcriptomics data, making it accessible and user-friendly. • DIMet enables researchers to infer metabolic changes, offering intuitive and visually appealing "metabologram" outputs, surpassing conventional visual representations commonly used in the field.PMID:39872723 | PMC:PMC11769753 | DOI:10.21769/BioProtoc.5168

Front Vet Sci. 2025 Jan 13;11:1511311. doi: 10.3389/fvets.2024.1511311. eCollection 2024.ABSTRACTINTRODUCTION: Chinese herbal medicines are relatively inexpensive and have fewer side effects, making them an effective option for improving health and treating diseases. As a result, they have gained more attention in recent years. The weaning period is a critical stage in the life of yaks, often inducing stress in calves. Weaning stress, along with dietary changes, can lead to a decline in physical fitness and immune function, making yaks more susceptible to diarrhea and resulting in high mortality rates during this period. Therefore, our study aimed to address this issue by incorporating traditional Chinese medicine (TCM) formulas into the diet of yaks during the weaning period.METHODS: Following a dialectical analysis, three TCM formulas, mainly composed of Paeonia lactiflora, Coptis chinensis, and Dandelion, were identified for their anti-inflammatory, antioxidant, and immune enhancing potentials. We explored the possible molecular mechanisms of these TCM formulas using network pharmacology analysis and investigated their effects on the physiology of yaks through metabolomics.RESULTS: Network pharmacology analysis revealed several key target proteins in the protein-protein interaction (PPI) network between three formulas and immune-related genes, including PIK3R1, PIK3CA, JAK2, PTK2, and PYPN11. The key target proteins in the PPI network associated with metabolism-related genes included ENPP1, CYP1A1, PTGS1, members of the CYP1 family, and EPHX2. GO analysis of co-targets revealed highly enriched pathways such as protein phosphorylation, plasma membrane, and one-carbon metabolic processes. Metabolomics revealed significant changes in the abundance of metabolites including dimethyl sulfoxide, tyrphostin A25, and thromboxane A2 in the intestines of weaned yaks supplemented with these Chinese herbal compounds. Significant changes were also observed in pathways such as vitamin A metabolism, chloroalkane, and chloroalkene degradation.DISCUSSION: Based on these findings, it can be inferred that TCM formulas improve the physical fitness of weaned yaks by enhancing antioxidant capacity, boosting immunity, and reducing intestinal inflammation. This study preliminarily elucidates the pharmacological mechanisms by which TCM formulas prevent diarrhea and improve physical fitness in weaned yaks through metabolomics and network pharmacology, paving the way for further evaluation of the effectiveness of these three formulas.PMID:39872609 | PMC:PMC11770994 | DOI:10.3389/fvets.2024.1511311

Life Metab. 2024 Apr 26;3(4):loae016. doi: 10.1093/lifemeta/loae016. eCollection 2024 Aug.ABSTRACTBromodomain and extra-terminal domain (BET) proteins, which function partly through MYC proto-oncogene (MYC), are critical epigenetic readers and emerging therapeutic targets in cancer. Whether and how BET inhibition simultaneously induces metabolic remodeling in cancer cells remains unclear. Here we find that even transient BET inhibition by JQ-1 and other pan-BET inhibitors (pan-BETis) blunts liver cancer cell proliferation and tumor growth. BET inhibition decreases glycolytic gene expression but enhances mitochondrial glucose and glutamine oxidative metabolism revealed by metabolomics and isotope labeling analysis. Specifically, BET inhibition downregulates miR-30a to upregulate glutamate dehydrogenase 1 (GDH1) independent of MYC, which produces α-ketoglutarate for mitochondrial oxidative phosphorylation (OXPHOS). Targeting GDH1 or OXPHOS is synthetic lethal to BET inhibition, and combined BET and OXPHOS inhibition therapeutically prevents liver tumor growth in vitro and in vivo. Together, we uncover an important epigenetic-metabolic crosstalk whereby BET inhibition induces MYC-independent and GDH1-dependent glutamine metabolic remodeling that can be exploited for innovative combination therapy of liver cancer.PMID:39872506 | PMC:PMC11749653 | DOI:10.1093/lifemeta/loae016

Life Metab. 2024 Jan 18;3(2):loae004. doi: 10.1093/lifemeta/loae004. eCollection 2024 Apr.ABSTRACTInterorgan lipid transport is crucial for organism development and the maintenance of physiological function. Here, we demonstrate that Drosophila long-chain acyl-CoA synthetase (dAcsl), which catalyzes the conversion of fatty acids into acyl-coenzyme As (acyl-CoAs), plays a critical role in regulating systemic lipid homeostasis. dAcsl deficiency in the fat body led to the ectopic accumulation of neutral lipids in the gut, along with significantly reduced lipoprotein contents in both the fat body and hemolymph. The aberrant phenotypes were rescued by fat body-specific overexpression of apolipophorin. A multi-omics investigation comprising lipidomics, metabolomics, and proteomics in conjunction with genetic screening revealed that glycosylation processes were suppressed in dAcsl knockdown flies. Overexpression of CG9035, human ortholog of which is implicated in the congenital disorder of glycosylation, ameliorated gut lipid accumulation in Drosophila. Aberrant lipoprotein glycosylation led to accelerated proteasome-related degradation and induced ER stress in dAcsl knockdown flies, impairing lipoprotein release into the circulation which compromised interorgan lipid transport between the fat body and the gut. Inhibition of ubiquitin-proteasome-dependent degradation alleviated the phenotype of gut ectopic fat accumulation in dAcsl knockdown flies. Finally, we verified that ACSL4, the human homolog of dAcsl, also regulated lipoprotein levels in HepG2 cells, indicating that the role of dAcsl in modulating lipoprotein secretion and systemic lipid homeostasis is possibly conserved in humans.PMID:39872215 | PMC:PMC11749247 | DOI:10.1093/lifemeta/loae004

Front Plant Sci. 2025 Jan 13;15:1462545. doi: 10.3389/fpls.2024.1462545. eCollection 2024.ABSTRACTThe genetic basis of type 1 red-flesh color development in apple (Malus domestica) depends upon a particular allele of the MdMYB10 gene. Interestingly, type 1 red-flesh apples are fully red after fruit set, but anthocyanin pigmentation in apple fruit cortex may decrease during fruit growth and maturation, leading to variable red patterning and intensities in the mature cortical flesh. We developed a histogram-based color analysis method to quantitatively estimate pigmentation patterns. This methodology was applied to investigate the phenotypic diversity in four hybrid F1 families segregating for red-flesh color. Pigmentation patterns were found to be heritable allowing the identification of a new locus by QTL analysis. To further investigate the mechanisms involved in the spatial deposition of anthocyanin, metabolome, transcriptome and methylome comparisons between white and red flesh areas within the red-flesh genotype cv. 'R201' exhibiting flesh pigmentation patterns, was performed. Wide-targeted analysis showed that white-flesh areas accumulate more dihydrochalcones and hydroxycinnamic acids than red-flesh areas while red-flesh areas accumulate more flavonoids. Anthocyanin biosynthesis genes and anthocyanin positive regulators (MBW complex) were up-regulated in red-flesh areas, while a reduction in anthocyanin storage, transport and stability (increase of pH, down-regulation of MdGSTU22) and an increase in phenolic catabolism were concomitant with color fading process in white-flesh areas. Expression of MdGSTU22 was linked to a differentially methylated region (DMR) suggesting a potential environmental effect on the epigenetic control of gene expression involved in color fading. Altogether, these results provide the first characterization and functional identification of color fading in apple fruit flesh.PMID:39872201 | PMC:PMC11770013 | DOI:10.3389/fpls.2024.1462545

Front Plant Sci. 2025 Jan 13;15:1516990. doi: 10.3389/fpls.2024.1516990. eCollection 2024.ABSTRACTOne significant environmental element influencing the growth and yield of rice (Oryza sativa L.) is high temperature. Nevertheless, the mechanism by which rice responds to high temperature is not fully understood. A rice glycosyltransferase gene, OsDUGT1, was identified as a heat-responsive gene in this investigation. Its function was studied by overexpression and knockout methods. The results showed that under heat stress, OsDUGT1 overexpression lines (OsDUGT1-OE) increased the survival rate of rice, while Osdugt1 knockout lines (Osdugt1-ko) decreased the survival rate compared to wild type (ZH11). In addition to rice, heat stress tolerance was also improved by ectopic expression of OsDUGT1 in transgenic Arabidopsis thaliana plants. We observed that ROS scavenging ability, malondialdehyde accumulation, and the ion leakage are relevant to the expression level of OsDUGT1. Through enzyme activity analysis, we found that OsDUGT1 could glycosylate flavonoid compounds. Correspondingly, the loss of OsDUGT1 function caused a significant decrease in endogenous flavonoid accumulation in rice, which was demonstrated by our metabolomics analysis. Additionally, our transcriptomic analysis of Osdugt1 mutant lines under heat stress condition indicated that mutation of OsDUGT1 can reduce the transcriptional activity of heat response related genes, antioxidant enzyme genes and other genes involved in the flavonoid biosynthetic pathway. In summary, our work revealed that OsDUGT1 plays a crucial role in adjusting and balancing the overall plant metabolism and transcription under heat stress through glycosylation of flavonoids, and offers a key prospect gene for breeding efforts to enhance crop heat tolerance under the trend of climate warming all over the globe.PMID:39872199 | PMC:PMC11769934 | DOI:10.3389/fpls.2024.1516990

Front Mol Biosci. 2025 Jan 13;11:1517289. doi: 10.3389/fmolb.2024.1517289. eCollection 2024.ABSTRACTBACKGROUND: Breast cancer is one of the most prevalent malignancies and a leading cause of death among women worldwide. Among its subtypes, triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive behavior and limited treatment options. This study aimed to investigate the effects of doxorubicin (DOX) and 5-fluorouracil (5-FU) as monotherapies and in combination using an established MDA-MB-231 xenograft model in female BALB/C nude mice employing advanced metabolomics analysis to identify molecular alterations induced by these treatments.METHODS: We conducted comprehensive plasma and tumor tissue sample profiling using ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS).RESULTS: Each treatment group exhibited unique metabolic profiles in plasma and tumor analysis. Univariate and enrichment analyses identified alterations in metabolic pathways. The combination treatment of DOX + 5-FU induced the most extensive metabolic alterations disrupting key pathways including purine, pyrimidine, beta-alanine, and sphingolipid metabolism. It significantly reduced critical metabolites such as guanine, xanthine, inosine, L-fucose, and sphinganine, demonstrating enhanced cytotoxic effects compared to individual treatments. The DOX treatment uniquely increased ornithine levels, while 5-FU altered sphingolipid metabolism, promoting apoptosis.SIGNIFICANCE: This in vivo study highlights TNBC's metabolic alterations to chemotherapeutics, identifying potential biomarkers like L-fucose and beta-alanine, and provides insights for improving treatment strategies.PMID:39872164 | PMC:PMC11769812 | DOI:10.3389/fmolb.2024.1517289

Life Metab. 2024 May 17;3(5):loae018. doi: 10.1093/lifemeta/loae018. eCollection 2024 Oct.ABSTRACTDyslipidemia affects approximately half of all people with gout, and prior Mendelian randomization analysis suggested a causal role for elevated triglycerides in hyperuricemia (HU), but the underlying mechanisms remain elusive. We hypothesize that dyslipidemia promotes hepatic urate biosynthesis in HU and gout and fatty acid (FA) oxidation (FAO) drives this process. Here we developed a targeted metabolomics to quantify major metabolites in purine metabolic pathway in the sera of a human cohort with HU, gout, and normaluricemic controls. We found that the levels of major purine metabolites and multiple FAs were significantly elevated in HU and gout groups compared to normouricemic controls, whereas hypoxathine showed opposite trend. Furthermore, the levels of multiple serum FAs were positively correlated with urate, xanthine, and inosine but negatively with hypoxanthine, which was also observed in a murine model of high-fat diet-induced HU. Using a stable isotope-labeled metabolic flux assay, we discovered that exogenous hypoxanthine plays a key role in urate synthesis. Moreover, FAO-induced hypoxia-inducible factor 1 alpha (HIF-1α) activation upregulated 5'-nucleotidase II (NT5C2) and xanthine dehydrogenase (XDH) levels to facilitate hypoxanthine uptake from the blood to the liver and activation of urate biosynthesis. Our findings were further supported by data in human hepatocytes and 50 paired serum and liver tissues from liver transplant donors. Together, this study uncovers a mechanism by which FAO promotes hepatic urate synthesis by activating HIF-1α-NT5C2/XDH pathways, directly linking lipid metabolism to HU.PMID:39872146 | PMC:PMC11749550 | DOI:10.1093/lifemeta/loae018

Life Metab. 2024 Apr 3;3(5):loae012. doi: 10.1093/lifemeta/loae012. eCollection 2024 Oct.ABSTRACTObesity is considered an epidemic often accompanied by insulin resistance (IR). Heat treatment (HT) has been shown to prevent high-fat diet-induced IR in skeletal muscle, but the underlying mechanisms are poorly understood. In this study, we discovered that high temperature alleviated the hallmarks of obesity by promoting glycogen synthesis and lowering blood glucose levels in skeletal muscle tissue (SMT). Additionally, HT maintained the decay phase of heat shock factor 1 (HSF1), leading to the activation of gene expression of heat shock proteins (HSPs), which contributed to the alleviation of IR in SMT of diet-induced obese (DIO) mice. Metabolomics and lipidomics analyses showed that HT promoted ceramide (Cer) breakdown, resulting in an elevation of both sphingomyelin (SM) and sphingosine, which further contributed to the amelioration of IR in SMT of DIO mice. Importantly, the increase in sphingosine was attributed to the heightened expression of the acid ceramidase N-acylsphingosine amidohydrolase 1 (ASAH1), and the inhibition of ASAH1 attenuated HT-relieved IR in SMT of DIO mice. Surprisingly, high temperature increased the composition of Cer and cholesteryl ester in lipid droplets of skeletal muscle cells. This not only helped alleviate IR but also prevented lipotoxicity in SMT of DIO mice. These findings revealed a previously unknown connection between a high-temperature environment and sphingolipid metabolism in obesity, suggesting that high temperature can improve IR by promoting Cer catabolism in SMT of obese mice.PMID:39872144 | PMC:PMC11749596 | DOI:10.1093/lifemeta/loae012

Front Pharmacol. 2025 Jan 13;15:1370264. doi: 10.3389/fphar.2024.1370264. eCollection 2024.ABSTRACTOBJECTIVE: To elucidate the metabolic mechanisms by which acteoside (ACT) isolated from Cistanche tubulosa alleviates cancer-related fatigue (CRF) in a murine model of colon cancer with cachexia.METHODS: BALB/c mice inoculated with C26 colon cancer cells were treated with paclitaxel (PTX, 10 mg/kg) and ACT (100 mg/kg) alone or in combination for 21 days. Fatigue-associated behaviors, tumor inhibition rate, and skeletal muscle morphology assessed by hematoxylin-eosin (H&E) staining and electron microscopy were evaluated. Finally, liquid chromatography-mass spectrometry (LC/MS) was employed to investigate alterations in the plasma metabolic profile of tumor-bearing mice with CRF in response to ACT treatment, and the affinity between metabolite-associated proteins and ACT was verified by Surface plasmon resonance (SPR) assay.RESULTS: Our study demonstrated the presence of CRF in the colon cancer mouse model, with the severity of fatigue increasing alongside tumor growth. Administration of ACT ameliorated both tumor burden and PTX-induced muscle fatigue-like behavior. LC/MS analysis identified a panel of differentially regulated metabolites, including trans-aconitine, citric acid, 3-coumaric acid, ephedrine, thymine, cytosine, indole-3-acetic acid, and pantothenol-9. These metabolites were primarily enriched in pathways associated with valine biosynthesis, tyrosine metabolism, tryptophan metabolism, and biosynthesis of pyridine alkaloids. Furthermore, several key enzymes, including CYP3A4, CYP19A1, CYP2E1, TNF, BCL-2, RYR2, and ATP2A1, were identified as potential targets underlying the anti-CRF effects of ACT.CONCLUSION: This study suggests that ACT derived from C. tubulosa harbors protective properties against cancer-related fatigue mediated by tumor cells.PMID:39872045 | PMC:PMC11769790 | DOI:10.3389/fphar.2024.1370264

World J Hepatol. 2025 Jan 27;17(1):100377. doi: 10.4254/wjh.v17.i1.100377.ABSTRACTBACKGROUND: The gut microbiome is associated with hepatic encephalopathy (HE), but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are inconsistent.AIM: To study the gut microbiota characteristics of patients with liver cirrhosis with and without HE.METHODS: We searched the PubMed, Web of Science, EMBASE, and Cochrane databases using two keywords, HE, and gut microbiome. According to the inclusion and exclusion criteria, suitable literature was screened to extract data on the diversity and composition of the fecal microbiota in patients with liver cirrhosis with and without HE. The data were analyzed using RevMan and STATA.RESULTS: Seventeen studies were included: (1) A meta-analysis of 7 studies revealed that the Shannon index in liver cirrhosis patients with HE was significantly lower than that in patients without HE [-0.20, 95% confidence interval (CI): -0.28 to -0.13, I2 = 20%]; (2) The relative abundances of Lachnospiraceae (-2.73, 95%CI: -4.58 to -0.87, I2 = 38%) and Ruminococcaceae (-2.93, 95%CI: -4.29 to -1.56, I2 = 0%) in liver cirrhosis patients with HE was significantly lower than those in patients without HE; (3) In patients with HE, Enterococcus, Proteobacteria, Enterococcaceae, and Enterobacteriaceae proportions increased, but Ruminococcaceae, Lachnospiraceae, Prevotellaceae, and Bacteroidetes proportions decreased; (4) Differences in the fecal metabolome between liver cirrhosis patients with and without HE were detected; and (5) Differential gut microbiomes may serve as diagnostic and prognostic tools.CONCLUSION: The gut microbiomes of patients with liver cirrhosis with and without HE differ. Some gut microbiomes may distinguish liver cirrhosis patients with or without HE and determine patient prognosis.PMID:39871903 | PMC:PMC11736471 | DOI:10.4254/wjh.v17.i1.100377

Small. 2025 Jan 28:e2412195. doi: 10.1002/smll.202412195. Online ahead of print.ABSTRACTDiabetic retinopathy (DR) is a microvascular complication of diabetes, affecting 34.6% of diabetes patients worldwide. Early detection and timely treatment can effectively improve the prognosis of DR. Metabolomic analysis provides a powerful tool for studying pathophysiological processes. Conducting metabolomic analyses on DR-related biofluids helps identify differential metabolic expressions during disease progression, thereby discovering potential biomarkers to support clinical diagnosis and treatment. Here, an innovative workflow for vitreous liquid analysis is established, and a machine learning-based DR analysis platform integrating vitreous liquid metabolic fingerprint (VL-MF) and plasma metabolic fingerprint (P-MF) derived via nanoparticle enhanced laser desorption/ionization mass spectrometry is developed. Direct VL-MF and P-MF are obtained with desirable reproducibility (coefficient of variation, CV <5%) and remarkable speed (3 s per sample), and DR patients are distinguished from healthy controls applying dual biofluid-MF with an area under the curve (AUC) of 0.957. Moreover, a biomarker candidate panel from vitreous liquid and plasma with an AUC of 0.945 is constructed and the related metabolic pathways are identified by metabolomics pathway analysis (MetPA). This work offers a powerful multi-biofluid platform that can not only contribute to DR but also provide solid references for other clinical applications.PMID:39871789 | DOI:10.1002/smll.202412195

Food Funct. 2025 Jan 28. doi: 10.1039/d4fo04220d. Online ahead of print.ABSTRACTBioactive peptides rich in branched-chain amino acids (BCAAs) are an effective way to alleviate fatigue conditions, but the deep mechanism remains unclear. This study investigated the anti-fatigue effect of branched-chain amino acid-enriched egg white peptides (BEWPs) through the gut-muscle axis by gut bacteria and untargeted metabolomic analyses. The results demonstrated that BEWPs enhanced exercise endurance and strength by also promoting gastrocnemius development in mice. Furthermore, there was a reduction in oxidative stress, inflammatory response, and the accumulation of unexpected metabolites generated under fatigue conditions. The intake of BEWPs increased the abundances of Lactobacillus, Akkermansia, and unclassified_f_Lachnospiraceae, while decreasing the abundance of Bacteroides. BEWPs also regulated the levels of key metabolites in mouse muscles, including L-glutamic acid by arginine biosynthesis and bile secretion pathways. Notably, Spearman's correlation analysis indicated that there was a significant correlation between these altered metabolites, microbial populations, and indicators of fatigue. In summary, our research demonstrated that BEWPs alleviated fatigue through the gut-muscle axis, which provided new insights into fatigue management and prevention.PMID:39871582 | DOI:10.1039/d4fo04220d

Mol Plant. 2025 Jan 27:S1674-2052(25)00038-3. doi: 10.1016/j.molp.2025.01.017. Online ahead of print.ABSTRACTPotato is the world's most important nongrain crop. Here, we report that 29 genomes from Petota and Etuberosum sections were de novo assembled, and that 248 accessions of wild potatoes, landraces and modern cultivars were re-sequenced at > 25× depth to assess genetic diversity within the Petota section. Subsequently, a graph-based pangenome was constructed by using DM8.1 as the backbone integrated 194,330 nonredundant structural variants. To characterize the metabolome of tubers and illuminate the genomic basis of metabolic traits, LC-MS/MS was employed to obtain the metabolome of 157 accessions, and 9,321 SVs were detected to be significantly associated with 1,258 distinct metabolites via PAV-based metabolomics-GWAS analysis, including metabolites of flavonoids, phenolic acids and phospholipids. To facilitate the utilization of pangenome resources, a comprehensive platform, the potato pangenome database (PPDB, http://101.201.107.228:16666/), was developed for the potato community worldwide. Our study provides a comprehensive genomic resource that enables us to assess the genomic basis of agronomic and metabolic traits, and the genomic dataset resources will accelerate functional genomics studies and genetic improvements in potato.PMID:39871478 | DOI:10.1016/j.molp.2025.01.017

Mol Neurodegener. 2025 Jan 27;20(1):11. doi: 10.1186/s13024-025-00803-6.ABSTRACTAlzheimer's disease (AD) is among the most devastating neurodegenerative disorders with limited treatment options. Emerging evidence points to the involvement of lipid dysregulation in the development of AD. Nevertheless, the precise lipidomic landscape and the mechanistic roles of lipids in disease pathology remain poorly understood. This review aims to highlight the significance of lipidomics and lipid-targeting approaches in the diagnosis and treatment of AD. We summarized the connection between lipid dysregulation in the human brain and AD at both genetic and lipid species levels. We briefly introduced lipidomics technologies and discussed potential challenges and areas of future advancements in the lipidomics field for AD research. To elucidate the central role of lipids in converging multiple pathological aspects of AD, we reviewed the current knowledge on the interplay between lipids and major AD features, including amyloid beta, tau, and neuroinflammation. Finally, we assessed the progresses and obstacles in lipid-based therapeutics and proposed potential strategies for leveraging lipidomics in the treatment of AD.PMID:39871348 | DOI:10.1186/s13024-025-00803-6

J Transl Med. 2025 Jan 27;23(1):119. doi: 10.1186/s12967-025-06148-4.ABSTRACTBACKGROUND: Alzheimer's disease (AD) is the most frequent neurodegenerative disorder worldwide. The great variability in disease evolution and the incomplete understanding of the molecular mechanisms underlying AD make it difficult to predict when a patient will convert from prodromal stage to dementia. We hypothesize that metabolic alterations present at the level of the brain could be reflected at a systemic level in blood serum of patients, and that these alterations could be used as prognostic biomarkers.METHODS: This pilot study proposes a serum investigation via nuclear magnetic resonance (NMR) spectroscopy in a consecutive series of AD patients including 57 patients affected by Alzheimer's disease at dementia stage (AD-dem) and 45 patients with mild cognitive impairment (MCI) due to AD (MCI-AD). As control group, we considered 31 subjects with mild cognitive impairment in whom AD and other neurodegenerative disorders were excluded (MCI). A panel of 26 metabolites and 112 lipoprotein-related parameters was quantified and the logistic LASSO regression algorithm was employed to identify the optimal combination of metabolites-lipoproteins and their ratios to discriminate the groups of interest.RESULTS: In the training set, our model classified AD-dem and MCI with an accuracy of 81.7%. These results were reproduced in the validation set (accuracy 75.0%). Evolution of MCI-AD patients was evaluated over time. Patients who displayed a decrease in MMSE < 1.5 point per year were considered at lower progression rate: we obtained a division in 18 MCI-AD at lower progression rate (MCI-AD LR) and 27 at higher progression rate (MCI-AD HR). The model calculated using 4 metabolic features identified MCI-AD LR and MCI-AD HR with an accuracy of 73.3%.CONCLUSIONS: The identification of potential novel peripheral biomarkers of Alzheimer's disease, as proposed in this study, opens a new prospect for an innovative and minimally invasive method to identify AD in its very early stages. We proposed a novel approach able to sub-stratify MCI-AD patients identifying those associated with a faster rate of clinical progression.PMID:39871333 | DOI:10.1186/s12967-025-06148-4

BMC Med. 2025 Jan 27;23(1):47. doi: 10.1186/s12916-025-03884-8.ABSTRACTBACKGROUND: Mechanisms underlying the association of life-course adiposity with incident hypertension in adulthood have not been comprehensively investigated. In this study, we aimed to investigate the potential biochemical and metabolomic mechanisms underlying the association between adiposity and incident hypertension.METHODS: A total of 180,527 participants from the UK Biobank aged 37 to 73 years were included. Associations of childhood body size or adulthood adiposity status as well as child-adult weight status change with incident adulthood hypertension were estimated by multivariate Cox proportional regression models.RESULTS: Participants with childhood thinner body size and adulthood obesity had the highest risk of incident hypertension (hazard ratio, HR = 3.09, 95% CI = 2.88-3.32) compared with those with "average → normal" pattern, followed by those with "average → obese" pattern (HR = 2.45, 95% CI = 2.31-2.61) and "plumper → obese" pattern (HR = 2.82, 95% CI = 2.62-3.02). Of note, those with "plumper → normal" pattern (HR = 1.11, 95% CI = 1.00-1.23) and "thinner → normal" pattern (HR = 1.17, 95% CI = 1.10-1.24) had the second and third lowest risk of incident hypertension. Adulthood overweight (mediation proportion: 58.7%, 95% CI: 40.4-74.8%) or obesity (mediation proportion = 46.7%, 95% CI: 29.4-64.9%) largely mediated the association between childhood plumper body size and hypertension. The association between adiposity and hypertension was mediated by biochemical indices (e.g., liver function, immunometabolism) and metabolites (e.g., alanine aminotransferase, apolipoprotein A) (mediation proportions ranging from 3.2 to 23.4%).CONCLUSIONS: Thinner or plumper body size in childhood increases the risk of incident adulthood hypertension, and adulthood adiposity partly mediated this association, suggesting the importance of maintaining normal weight across the life course. Several biochemical indices and metabolites mediated these associations providing clues to underlying biological mechanisms.PMID:39871294 | DOI:10.1186/s12916-025-03884-8

BMC Plant Biol. 2025 Jan 28;25(1):119. doi: 10.1186/s12870-025-06097-6.ABSTRACTSelenium is a beneficial element in agriculture, particularly for its potential to improve plant growth and stress tolerance at suitable concentrations. In this study, Phaseolus vulgaris was foliar-sprayed with selenium selenate (Se) or selenium nanoparticles (SeNP) at different concentrations during the vegetative stage; afterward, the seed yield was analyzed for metabolomics using 1H, J-resolved and HSQC NMR data, and NMR databases. A total of 47 metabolites were identified with sugars being the major chemical class. In the control sample, the most abundant sugar was stachyose (14.6 ± 0.8 mM). Among the identified alkaloids, the concentration of trigonelline was the highest (0.6 ± 0.08 mM). Chemometric and cluster analyses distinctly differentiated the control from the Se and SeNP-treated samples. Treatments with SeNP resulted in elevated concentrations of sugars, carboxylic acids, and sulfur-containing amino acids compared to control and Se treated samples. Conversely, betaine levels were higher in Se samples. The presence of Se and SeNP significantly decreased the levels of several aliphatic amino acids, e.g. alanine. The addition of 50 µM SeNP upregulated the levels of trigonelline and syringate by 2-fold and 1.75-fold, respectively, relative to the control. Pathway analysis indicated the most significantly altered pathways due to SeNP addition were arginine biosynthesis and nitrogen metabolism. The pathways influenced by Se addition were glyoxylate and dicarboxylate metabolism as well as glycine-serine and threonine metabolism. This study proved that SeNP are more efficient than Se in enhancing the metabolic profile of Phaseolus vulgaris which will have implications for agricultural practices, focusing on the sustainability and nutritional enhancement of crops.PMID:39871137 | DOI:10.1186/s12870-025-06097-6