PubMed

J Environ Manage. 2025 Jan 6;374:123969. doi: 10.1016/j.jenvman.2024.123969. Online ahead of print.ABSTRACTThe increasing contamination of ecosystems with heavy metals (HMs) due to industrial activities raises significant jeopardies to environmental health and human well-being. Addressing this issue, recent advances in the field of bioremediation have highlighted the potential of plant-associated microbiomes and genetically engineered organisms (GEOs) to mitigate HMs pollution. This review explores recent advancements in bioremediation strategies for HMs detoxification, with particular attention to omics technologies such as metagenomics, metabolomics, and metaproteomics in deepening the understanding of microbial interactions and their potential for neutralizing HMs. Additionally, Emerging strategies and technologies in GEOs and microorganism-aided nanotechnology have proven to be effective bioremediation tools, particularly for alleviating HM contamination. Despite the promising strategies developed in laboratory settings, several challenges impede their practical application, including ecological risks, regulatory limitations, and public concerns regarding the practice of genetically modified organisms. A comprehensive approach that involves interdisciplinary research is essential to enhance the efficacy and safety of bioremediation technologies. This approach should be coupled with robust regulatory frameworks and active public engagement to ensure environmental integrity and societal acceptance. This review underscores the importance of developing sustainable bioremediation strategies that align with ecological conservation goals and public health priorities.PMID:39765072 | DOI:10.1016/j.jenvman.2024.123969

Phytomedicine. 2025 Jan 1;136:156361. doi: 10.1016/j.phymed.2025.156361. Online ahead of print.ABSTRACTBACKGROUND: Artemisia spp. have been used for millennia in traditional medicine to treat a variety of ailments, including malaria. Extracts of Artemisia afra and A. annua remain widely used throughout Africa for healthcare purposes, notably to prevent and/or treat malaria. However, the modes of action of these plant extracts remain unclear, with contradictory reports regarding the presence and role of artemisinin in both plants.PURPOSE: The aim of this study was to identify differences in the antimalarial mode of action of A. afra and A. annua by measuring their phenolic profiles and comparing their effect on parasite metabolism in vitro.METHODS: In this work, we analyzed the phenolic profile of A. afra and A. annua extracts through high-performance liquid chromatography (HPLC), detected and quantified artemisinin through HPLC and mass spectrometry (MS), and performed comparative HPLC-MS metabolomic analysis on in vitro-cultured Plasmodium falciparum trophozoites to elucidate the potential modes of action of these plant extracts.RESULTS: A. afra contained only trace amounts of artemisinin and elicited a different parasite metabolic response compared to A. annua, which contained significantly more artemisinin and correlated closely with the parasite response profile elicited by purified artemisinin. A. annua impacted parasite glutathione metabolism in agreement with the established redox activity of artemisinin, while A. afra had an effect on lipid precursors.CONCLUSIONS: This study reveals that A. afra and A. annua have divergent effects on Plasmodium falciparum metabolism and provides support for ongoing efforts exploring the use of A. afra for the treatment of malaria.PMID:39765035 | DOI:10.1016/j.phymed.2025.156361

Vet Microbiol. 2024 Dec 31;301:110365. doi: 10.1016/j.vetmic.2024.110365. Online ahead of print.ABSTRACTBluetongue (BT) is a viral vector borne disease primarily affecting ruminants such as sheep, cattle, and goats. On 3 September 2023, the Netherlands reported the first case of bluetongue virus serotype 3 (BTV-3/NET2023)), after being BTV free for eleven years. Vaccination with inactivated BT vaccines for serotype 3 has been applied in the Netherlands since May 2024. Nonetheless, in late June/July 2024, BTV-3 re-emerged and spread over large parts of Europe. In October 2024, BTV-12 was identified by follow-up diagnostics after a BTV-3 vaccinated sheep with signs of BT was tested positive for BTV but negative for serotype 3. This marks a significant event, as BTV-12 had never been reported in Europe. Screening of farms in close proximity to the sheep farm and retrospective analysis of samples from clinically affected animals that were panBTV PCR positive resulted in the detection of nine BTV-12 affected farms in total. The emergence of BTV-12 in the Netherlands raises important questions about the route of introduction of BT in the Netherlands and mechanisms of viral spread of this specific serotype. Possible adaptation of new BTV serotypes to the European climatic and husbandry conditions prompts reconsideration of prevention, surveillance, and control strategies in relation to changing ecological conditions and vector dynamics. The initial findings, respective studies as well as the initial attempts to trace the origin of BTV-12/NET2024 are described.PMID:39765008 | DOI:10.1016/j.vetmic.2024.110365

Syst Appl Microbiol. 2025 Jan 3;48(1):126579. doi: 10.1016/j.syapm.2025.126579. Online ahead of print.ABSTRACTSix novel Bifidobacterium strains H1HS16NT, Bin2N, Hma3N, H6bp22N, H1HS10N, and H6bp9N, were isolated from the honey stomach of Apis mellifera. Cells are Gram-positive, non-motile, non-sporulating, facultatively anaerobic, and fructose 6-phosphate phosphoketolase-positive. Optimal growth conditions occur at 37 °C in anaerobiosis in MRS medium added with 2 % fructose and 0.1 % L-cysteine. The 16S rRNA gene sequences analysis revealed clustering with Bifidobacterium species found in honeybees. Strains Hma3N, H6bp22N, and H1HS16NT showed significant similarity to Bifidobacterium polysaccharolyticum JCM 34588T, with an average similarity of 99.63 %. In contrast, strains Bin2N, H1HS10N, and H6bp9N were closely related to Bifidobacterium apousia JCM 34587T, with an average similarity of 99.22 %. Moreover, strains Hma3N and H6bp22N exhibited ANI values of 96.65 % and 96.53 % when compared to Bifidobacterium polysaccharolyticum JCM 34588T, while strains H1HS16NT, Bin2N, H6bp9N, and H1HS10N revealed ANI values of 94.18 %, 94.33 %, 94.22 %, and 95.50 % respectively when compared to B. apousia JCM 34587T. dDDH analysis confirmed that strains Hma3N and H6bp22N belong to B. polysaccharolyticum, whereas strains H1HS16NT, Bin2N, H6bp9N, and H1HS10N represent a novel species. The peptidoglycan of the novel species is of the A4α type (L-Lys-D-Asp). The main cellular fatty acids of the type strain H1HS16NT are C16:0, C14:0, C19:0 cyclo ω9c, and C18:1 ω9c. The DNA G + C content of the type strain is 60.8 mol%. Genome analyses of the strains were also conducted to determine their biosynthesis-related gene clusters, probiotic features, and ecological distribution patterns. Phenotypic and genotypic characterization show that strain H1HS16NT is distinct from the type strains of other recognized Bifidobacterium species. Thus, Bifidobacterium kimbladii sp. nov. (H1HS16NT = DSM 115187T = CCUG 76695T) is proposed as a novel Bifidobacterium species.PMID:39764984 | DOI:10.1016/j.syapm.2025.126579

J Hazard Mater. 2024 Dec 31;486:137066. doi: 10.1016/j.jhazmat.2024.137066. Online ahead of print.ABSTRACTPolylactic acid (PLA) microplastics (MPs) and lead (Pb) co-contamination, an emerging co-contamination, may profoundly impact plant growth. We aimed to evaluate the effects of PLA-MPs and Pb on buckwheat growth and physiology and to elucidate the underlying molecular mechanisms through an integrated transcriptomic and metabolomic approach. PLA-MPs alone reduced buckwheat biomass by 26.0 %, while combined exposure to Pb and PLA-MPs (PLA-Pb) further exacerbated morphological impairments, decreasing biomass by 43.1 % and 50.4 % compared to the control. Antioxidant enzyme activities increased under Pb and PLA-Pb treatments. The analysis revealed 536 differentially expressed metabolites (DEMs) and 3229 differentially expressed genes (DEGs) in PLA-Pb vs. control, 168 DEMs and 1555 DEGs in PLA-Pb vs. PLA, and 196 DEMs and 4057 DEGs in PLA-Pb vs. Pb. Key DEGs involved in lignin biosynthesis, including caffeoyl-CoA-O-methyltransferase, cinnamoyl-CoA reductase, and catechol-O-methyltransferase, were upregulated, suggesting that buckwheat mitigates toxicity by enhancing cell wall modification. Similarly, DEGs and DEMs linked to jasmonate biosynthesis were enriched in the alpha-linolenic acid metabolic pathway, including allene oxide synthase, allene oxide cyclase, and 12-oxophytodienoate reductase, as well as methyl jasmonate. These results suggest that buckwheat counters PLA-MPs-Pb toxicity by enhancing oxidative stress responses and upregulating the synthesis of lignin and unsaturated fatty acids. In conclusion, this study provides novel insights into the molecular mechanisms of plant detoxification under PLA-MPs-Pb co-exposure, highlighting the need for ecological risk assessment of combined microplastic and heavy metal pollution.PMID:39764956 | DOI:10.1016/j.jhazmat.2024.137066

Mult Scler Relat Disord. 2025 Jan 6;94:106250. doi: 10.1016/j.msard.2024.106250. Online ahead of print.ABSTRACTBACKGROUND: Radiologically Isolated Syndrome (RIS) characterized by abnormalities on MRI that do not manifest as clinical symptoms of Multiple Sclerosis (MS) but raise suspicion for MS. Considering that RIS often evolves into MS, various diagnostic criteria have been established, and each suggested biomarker warrants thorough consideration and discussion. In this study, metabolomic profiling of body fluids of patients who were being followed up with a pre-diagnosis of RIS or MS and had not yet received any treatment was conducted. The results were compared internally and with healthy controls to contribute to the early diagnosis of the disease.METHODS: In this study, the body fluids of 63 patients (30 RIS, 33 MS) and 30 healthy controls were used. From the patient group, samples of cerebrospinal fluid (CSF), serum, and urine; from the healthy group, blood and urine were collected. Metabolomic profiles of the body fluids were generated using Nuclear Magnetic Resonance spectroscopy (NMRS). Multivariate statistics were conducted on the NMRS intensity data using the MetaboAnalyst R package after auto-scaling and log-transformation.RESULTS: In CSF levels of lactate, creatine phosphate, and pyruvate; in serum, levels of hydroxyvalerate, xylitol, and agmatine; in urine threonine, creatine, cystine, 2-aminobutyrate, and ascorbic acid were found significantly higher in the MS group compared to RIS (p ≤ 0.05). In Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA), it was observed that there was not enough differentiation between these two groups. Enrichment Analysis was performed on the CSF results of the RIS group, it was highly consistent with MS disease (ratio=∼1.8).CONCLUSION: Literature reveals various results in this regard; however, the findings here emphasize a new distinction. It's important not to expect a single biomarker to stand out in metabolomic profiling methods; instead, the patient's overall results should be collectively evaluated to conduct a comprehensive analysis. The collective findings of RIS patients being consistent with MS indicate the necessity of widespread adoption and utilization of NMRS technique and metabolomic profiling, especially for CSF, in MS diagnostic criteria. Furthermore, this study provides laboratory evidence suggesting that RIS patients constitute a subtype of MS.PMID:39764909 | DOI:10.1016/j.msard.2024.106250

Aquat Toxicol. 2025 Jan 4;279:107236. doi: 10.1016/j.aquatox.2025.107236. Online ahead of print.ABSTRACTSynthetic progestin dydrogesterone is widely used in gynecology and animal husbandry, leading to high environmental detection rates and concentrations. Dydrogesterone influences sex differentiation, gonad development, and spawning in fish. However, its impact on the liver, a vital organ for hormone production and detoxification, remains largely unknown. In this study, zebrafish embryos were exposed to 2.8, 27.6, and 289.8 ng/L of dydrogesterone until they reached sexual maturity. Metabolomics and Fourier transform infrared spectroscopy (FTIR) were employed to investigate alterations in the zebrafish liver. Long-term exposure to dydrogesterone decreased body weight and length in females but increased them in males. The levels of phospholipids, monoglycerides, lysophospholipids, fatty acids, acylcarnitines, acyltaurines, cholesterol, and bile acids increased in the liver of females but decreased in males due to dydrogesterone, making the metabolic pathways the most affected. FTIR analysis revealed a reduction in lipid and protein absorption coupled with an increase in carbohydrate absorption in the liver of exposed males, whereas exposed females exhibited reductions in both lipid and carbohydrate absorption. These findings suggest that long-term exposure to dydrogesterone enhances basic metabolism and physical growth in male zebrafish. To the best of our knowledge, this is the first report on the effects of progestins on body metabolism. Additionally, we find that gender difference is a notable feature of the effects of dydrogesterone on zebrafish.PMID:39764904 | DOI:10.1016/j.aquatox.2025.107236

Food Chem. 2024 Dec 28;470:142574. doi: 10.1016/j.foodchem.2024.142574. Online ahead of print.ABSTRACTThis study aimed to investigate the effects of fermented milk co-fermented with Lactobacillus (L.) helveticus and commercial starter during storage. Thus, systematic analysis revealed the changes with the determination of physicochemical characteristics, functional properties, and metabolome of fermented milk produced by commercial starter Mild 1.0, L. helveticus H11 (H11), and their combination. Co-fermentation with H11 significantly reduced fermentation time and enhanced pH, titratable acidity, viscosity, water-holding capacity, viable counts of H11, sensory attributes, angiotensin-converting enzyme inhibitory activity, valine-proline-proline and isoleucine-proline-proline levels, and storage stability. Additionally, co-fermentation with H11 enriched seven specific flavor compounds (5-tricosyl-1,3-benzenediol, didodecyl thiobispropanoate, glabrone, tuberoside, isomangiferin, indole-5,6-quinone, and luteone 7-glucoside) and five functional metabolites (indolelactic acid, glycine-histidine, stachyose, riboflavin, and asparagusic acid). These findings established H11 as a valuable adjunct culture for the application of commercial starter to produce functional fermented dairy products.PMID:39764886 | DOI:10.1016/j.foodchem.2024.142574

Poult Sci. 2024 Dec 31;104(2):104754. doi: 10.1016/j.psj.2024.104754. Online ahead of print.ABSTRACTThe activity of intestinal stem cells (ISCs) can be modulated by Lactobacillus, which subsequently affects the mucosal absorptive capacity. However, the underlying mechanisms remain unclear. In this study, a total of 189 Hy-Line Brown chickens (Gallus) were randomly assigned to one of seven experimental groups (n = 27 per group). These groups included a control group, a vehicle group (MRS group), a Lactobacillus salivarius group, a L. salivarius supernatant group, and three succinate treatment groups with various dosages. Each group was further subdivided into three replicates, with 9 chickens per replicate. The results indicate that the administration of Lactobacillus salivarius supernatant to laying hens notably increased the mRNA abundance of the amino acid transporters oligopeptide transporter 1 (PepT1) and sodium-dependent neutral amino acid transporter (B0AT). Metabolomic analyses indicated that the supernatant contains a high concentration of organic acids. Among them, succinate could enhance mRNA abundance of PepT1, B0AT and excitatory amino acid transporters 3 (EAAT3) both in vivo and in vitro. Accordingly, succinate could accelerate intestinal epithelial turnover, as indicated by the increased levels of cyclin-dependent kinase 2 (Cdk2) mRNA and proliferating cell nuclear antigen protein (PCNA), as well as ISC differentiation-related protein leucine-rich repeat containing G protein-coupled receptor 5 (LGR5). Furthermore, succinate treatment was shown to elevate the levels of mitochondrial fusion proteins optic atrophy 1 (OPA1) and translocase of outer mitochondrial membrane 20 (TOMM20), resulting in increased local ATP levels. However, pretreatment with NF-56-EJ40, a succinate receptor antagonist, attenuated the effects of succinate on OPA1, TOMM20, and ATP levels, alone with the reducing LGR5 and PCNA levels. Collectively, succinate, a metabolite of L. salivarius, activates the SUCNR1-mitochondria axis in ISCs, facilitating mitochondrial ATP synthesis, promoting ISC activity, and ultimately enhancing mucosal absorptive capacity.PMID:39764876 | DOI:10.1016/j.psj.2024.104754

Genet Epidemiol. 2025 Jan;49(1):e22607. doi: 10.1002/gepi.22607.ABSTRACTLarge-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C). We explored this GxE in the Women's Genome Health Study (WGHS; N = 23,294; the strongest cohort-specific signal in the original meta-analysis), the UK Biobank (UKB; N = 281,380), and the Multi-Ethnic Study of Atherosclerosis (MESA; N = 4587), using self-reported PA (MET-min/wk) and genotypes at rs295849 (nearest gene: LHX1). As originally reported, minor allele carriers of rs295849 in WGHS had a stronger positive association between PA and HDL-C (pint = 0.002). When testing available NMR metabolites to refine the HDL-C outcome, we found a stronger interaction effect on medium-sized HDL particle concentrations (M-HDL-P; pint = 1.0 × 10-4) than HDL-C. Meta-regression revealed a systematically larger interaction effect in cohorts from the original meta-analysis with a greater fraction of women (p = 0.018). In the UKB, GxE effects were stronger in women and using M-HDL-P as the outcome. In MESA, the primary interaction for HDL-C showed nominal significance (pint = 0.013), but without clear sex differences and with a greater magnitude for large HDL-P. Our work provides additional insights into a known gene-PA interaction while illustrating the importance of phenotype and model refinement toward understanding and replicating GxEs.PMID:39764704 | DOI:10.1002/gepi.22607

Front Pharmacol. 2024 Dec 23;15:1481273. doi: 10.3389/fphar.2024.1481273. eCollection 2024.ABSTRACTETHNOPHARMACOLOGICAL IMPORTANCE: Zhili decoction (ZLD) is a traditional Chinese medicine prescription for ulcerative colitis (UC). However, the mechanism by which ZLD exerts its therapeutic effects in the context of UC remains unclear.AIM OF STUDY: The aim of this study was to investigate the effects of ZLD on the gut microbiota and related fecal metabolite levels using a mouse model of UC. In addition, we examined the underlying molecular mechanisms responsible for these effects.MATERIALS AND METHODS: The major components of ZLD were detected by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). An integrated approach employing 16S rRNA and fecal metabolomics was employed to assess the potential impacts of ZLD on gut flora abundance and diversity, fecal metabolite levels, and various metabolic pathways. To further investigate the potential mechanisms of ZLD in treating UC, the expression of genes and proteins were examined by RT-qPCR, immunohistochemical staining and Western blotting.RESULTS: ZLD markedly alleviated symptoms and inflammatory injury in mice with UC. DSS induced notable alterations in the gut microbiome, and ZLD enhanced gut microbial diversity in UC mice by augmenting the abundance of Bacteroidota, Christensenella, Lactobacillus, etc., while reducing the Firmicutes/Bacteroidota ratio. ZLD treatment significantly modified the metabolic profile of mice with UC. It significantly suppressed the arachidonic acid metabolic pathway and promoted the butyrate acid metabolic pathway. ZLD reduced inflammatory factors and inhibited TLR4/NF-κB/NLRP3 pathway expression. In addition, correlation analysis demonstrated a close relationship between gut microbes, fecal metabolites, and inflammatory factors.CONCLUSION: ZLD alleviated UC by regulating gut flora, modulating related metabolite levels, and inhibiting TLR4/NF-κB/NLRP3 pathway.PMID:39764470 | PMC:PMC11701441 | DOI:10.3389/fphar.2024.1481273

Front Vet Sci. 2024 Dec 23;11:1500651. doi: 10.3389/fvets.2024.1500651. eCollection 2024.ABSTRACTBACKGROUND: Recently, environmental pollution has become a significant concern for human, animal, and environmental health, fitting within the "One Health" framework. Among the various environmental contaminants, per- and polyfluoroalkyl substances (PFASs) have gathered substantial attention due to their persistence, bioaccumulation, and adverse health effects. This study aimed to compare the levels of 12 PFASs in the fur, liver, and muscle of wild roe deer to evaluate the feasibility of using fur as a non-invasive biomonitoring matrix.METHODS: A total of 20 male and 20 female roe deer aged between 12 and 24 months were randomly sampled from a hunting area in Northern Italy. Samples of fur, muscle, and liver were collected post-mortem, and PFAS concentrations were measured using a validated UHPLC-HRMS method.RESULTS AND DISCUSSION: The results indicated significant differences in PFAS concentrations among the three matrices. Fur, although easier to sample and store, showed highly variable PFAS levels, with different detection frequencies compared to the muscle and liver. PFASs such as PFHxA were more frequently detected in fur than in the liver and muscle, while compounds such as PFBA, PFPeA, PFHpA, PFDA, PFHxS, 6-2 FTS, and 8-2 FTS were less frequently detected in fur. In conclusion, while fur presents many practical advantages for biomonitoring, such as non-invasive sampling and stability, its use is complicated by varying detection frequencies and concentration levels. These aspects, together with the use of a single sampling technique, can be considered a limitation of the study. Notably, compounds such as PFOA, PFNA, and PFOS showed partially similar detection frequencies across the matrices, suggesting potential interest for further research. This study offers new perspectives on the use of fur for environmental monitoring, highlighting the need for more extensive research to understand the relationship between PFAS concentrations in fur and other biological matrices. Future studies should focus on methodological improvements in extraction and quantification techniques for PFASs in fur to enhance their reliability as a biomonitoring tool.PMID:39764371 | PMC:PMC11701231 | DOI:10.3389/fvets.2024.1500651

Front Plant Sci. 2024 Dec 23;15:1447225. doi: 10.3389/fpls.2024.1447225. eCollection 2024.ABSTRACTINTRODUCTION: Crop rotation of tobacco with other crops could effectively break the negative impact of continuous tobacco cropping, but the mechanisms of intercropping system effects on tobacco, especially on the rhizosphere, are not clear.METHODS: In this study, we investigated the impact of intercropping system on the diversity and function of tobacco metabolites and microorganisms through metabolomic and metagenomic analyses of the tobacco rhizosphere microenvironment intercropped with maize and soybean.RESULTS: The results showed that the contents of huperzine b, chlorobenzene, and P-chlorophenylalanine in tobacco rhizosphere soils differed significantly among soybean-tobacco and maize-tobacco intercropping system. Chlorobenzene and P-chlorophenylalanine had the highest relative abundance under the soybean-tobacco intercropping system, and huperzine b had the highest relative abundance in the maize-tobacco cropping system. At the phylum level, the three most dominant strains were the same across all treatments: Proteobacteria, Actinobacteria, and Acidobacteria, with only minor differences in their abundance, with the fourth most abundant strain in both the tobacco monoculture. KEGG enrichment analysis of the tobacco rhizosphere soil microbiome revealed that intercropping significantly increased the abundance of metabolites in the ABC transporters pathway and up-regulated the LivK, LivH, Livg, LivM, and LivF genes of the branched-chain amino acid pathway.DISCUSSION: Collectively, our results indicate that the intercropping could enhance the activity of Livs to enhance the ABC transport pathway, and thus improve the transmembrane transport ability of tobacco roots, thus reducing the negative impact of continuous tobacco cropping. At the same time, the maize-tobacco intercropping could promote the production and transportation of phenolic acids, flavonoids, and other bioactive substances in the tobacco root system, which could enhance tobacco adaptation capacity to abiotic stress.PMID:39764236 | PMC:PMC11700734 | DOI:10.3389/fpls.2024.1447225

Front Plant Sci. 2024 Dec 23;15:1520786. doi: 10.3389/fpls.2024.1520786. eCollection 2024.ABSTRACTSophora flavescens is a traditional Chinese medicinal herb rich in various bioactive secondary metabolites, such as alkaloids and flavonoids, and exhibits remarkable resistance to abiotic stress. The WRKY transcription factor (TF) family is one of the largest plant-specific TF families and plays a crucial role in plant growth, development, and responses to abiotic stress. However, a comprehensive genome-wide analysis of the WRKY gene family in S. flavescens has not yet been conducted. In this study, we identified 69 SfWRKY genes from the S. flavescens genome and classified them into seven distinct subfamilies based on phylogenetic analysis. Transposed duplications and dispersed duplications were found to be the primary driving forces behind the expansion of the SfWRKY family. Additionally, several cis-acting elements related to the stress response and hormone signaling were discovered within the promoter regions of SfWRKYs. Transcriptomic analyses across five tissues (leaves, flowers, pods, roots, and stems) revealed that genes exhibiting high expression levels in specific tissues generally showed high expression across all the examined tissues. Coexpression network constructed based on metabolomic and transcriptomic analyses of root and pod development indicated that SfWRKY29 may play a significant role in regulating the biosynthesis of secondary metabolites during tissue development. The RT-qPCR results of gene expression analysis revealed that several SfWRKY genes were significantly induced in response to the accumulation of secondary metabolites or salt stress. Our study systematically analyzed WRKY TFs in S. flavescens, which provides valuable reference data for further studies on the key roles of SfWRKY genes in growth development as well as their responses under salt stress conditions.PMID:39764231 | PMC:PMC11700743 | DOI:10.3389/fpls.2024.1520786

Front Mol Biosci. 2024 Dec 23;11:1485587. doi: 10.3389/fmolb.2024.1485587. eCollection 2024.ABSTRACTINTRODUCTION: Gestational Diabetes Mellitus (GDM) is a metabolic disorder marked by Q10 hyperglycemia that can negatively affect both mothers and newborns. The increasing prevalence of GDM and the limitations associated with the standard diagnostic test highlight the urgent need for early screening strategies that promote timely interventions.METHODS: This study aims to investigate the metabolic profile associated with GDM through an untargeted metabolomic analysis using mass spectrometry (MS)- based omics. Serum samples were collected from 40 pregnant women at weeks 24-28 of gestation based on the 2-h 75-g oral glucose tolerance test (OGTT); 50% were diagnosed with GDM (n = 20), and the remaining were considered a control group.RESULTS AND DISCUSSION: The results showed distinct metabolic differences between women with GDM and those without, with 222 significantly dysregulated metabolites, 120 up- and 102 downregulated in GDM compared to the control group. Key metabolic pathways, such as tryptophan, inositol phosphate, phenylalanine, and histidine metabolism, were notably dysregulated in GDM. The study also found that specific metabolites, like N-Acetylproline and Serylmethionine, with area under the curve (AUC) of 0.978 and 0.968, respectively, showed high accuracy in distinguishing between GDM and non-GDM women. This study would enhance our understanding of metabolic alterations in GDM and could contribute to early prediction and management strategies.PMID:39764206 | PMC:PMC11700826 | DOI:10.3389/fmolb.2024.1485587

bioRxiv [Preprint]. 2024 Dec 17:2024.12.16.628663. doi: 10.1101/2024.12.16.628663.ABSTRACTOBJECTIVE: We previously found that per- and polyfluoroalkyl substances (PFAS) mixture exposure is inversely associated with SARS-CoV-2 IgG (IgG) antibody levels in pregnant individuals. Here, we aim to identify metabolites mediating this relationship to elucidate the underlying biological pathways.METHODS: We included 59 pregnant participants from a US-based pregnancy cohort. Untargeted metabolomic profiling was performed using Liquid Chromatography-High Resolution Sass spectrometry (LC-HRMS), and weighted Quantile Sum (WQS) regression was applied to assess the PFAS and metabolites mixture effects on IgG. Metabolite indices positively or negatively associated with IgG levels were constructed separately and their mediation effects were examined independently and jointly.RESULTS: The PFAS-index was negatively associated with IgG levels (beta=-0.273, p=0.002), with PFHpS and PFHxS as major contributors. Two metabolite-indices were constructed, one positively (beta=1.260, p<0.001) and one negatively (beta=-0.997, p<0.001) associated with IgG. Key contributors for these indices included protoporphyrin, 5-hydroxytryptophan, n-acetylproline, and tyrosine. Analysis of single mediator showed that 48.9% (95%CI: 21.9%,125.0%) and 50.1% (95% CI: 8.1%, 90.1%) of the PFAS index-IgG total effect were mediated by the negative and positive metabolite-indices, respectively. Joint analysis of the metabolite-indices indicated a cumulative mediation effect of 73.6% (95%CI: 44.9%, 116.4%). Enriched pathways associated with these metabolites indices were phenylalanine, tyrosine, and tryptophan biosynthesis and arginine metabolism.CONCLUSIONS: We observed significant mediation effects of plasma metabolites on the PFAS-IgG relationship, suggesting that PFAS disrupts the balance of plasma metabolites that contributes to reduced plasma IgG production.PMID:39763891 | PMC:PMC11702545 | DOI:10.1101/2024.12.16.628663

bioRxiv [Preprint]. 2024 Dec 29:2024.12.28.630631. doi: 10.1101/2024.12.28.630631.ABSTRACTPURPOSE: The development of endocrine resistance remains a significant challenge in the clinical management of estrogen receptor-positive ( ER+ ) breast cancer. Metabolic reprogramming is a prominent component of endocrine resistance and a potential therapeutic intervention point. However, a limited understanding of which metabolic changes are conserved across the heterogeneous landscape of ER+ breast cancer or how metabolic changes factor into ER DNA binding patterns hinder our ability to target metabolic adaptation as a treatment strategy. This study uses dimethyl fumarate ( DMF ) to restore tamoxifen ( Tam ) and fulvestrant ( Fulv ) sensitivity in endocrine-resistant cell lines and investigates how metabolic changes influence ER DNA-binding patterns.EXPERIMENTAL DESIGN: To address the challenge of metabolic adaptation in anti-endocrine resistance, we generated Tam and Fulv resistance in six ER+ breast cancer ( BC ) cell lines, representing ductal (MCF7, T47D, ZR75-1, and UCD12), lobular (MDA-MB-134--VI), and HER2 amplified (BT474) BC molecular phenotypes. Metabolomic profiling, RNA sequencing, proteomics, and CUT&RUN assays were completed to characterize metabolic shifts, transcriptional and protein changes, and ER DNA-binding patterns in resistant cells. Dimethyl fumarate was assessed for its ability to reverse Tam and Fulv resistance, restore tricarboxylic acid cycle ( TCA ) cycle function, and restore parental cell (endocrine sensitive) ER DNA binding patterns.RESULTS: Tamoxifen-resistant (TamR) and fulvestrant-resistant (FulvR) cells exhibited disrupted TCA cycle activity, reduced glutathione levels, and altered nucleotide and amino acid metabolism. DMF treatment replenished TCA cycle intermediates and reversed resistance in both TamR and FulvR cells. DMF also increased mevalonate pathway enzyme expression in both TamR and FulvR cells, with TamR cells upregulating enzymes in the cholesterol synthesis phase and FulvR enhancing enzymes in the early part of the pathway. DMF restored ER DNA-binding patterns in TamR cells to resemble parental cells, re-sensitizing them to Tam. In FulvR cells, DMF reversed resistance by modulating ER-cofactor interactions but did not restore parental ER DNA-binding signatures.CONCLUSIONS: Our findings provide new insights into how metabolic reprogramming affects ER DNA-binding activity in endocrine-resistant breast cancer. We demonstrate how altering metabolism can reprogram ER signaling and influence resistance mechanisms by targeting metabolic vulnerabilities, such as TCA cycle disruptions. Additionally, our data provide a comprehensive metabolomic, RNA-seq, and CUT&RUN data set relevant to tumor metabolic adaptation leading to acquired endocrine resistance in highly utilized ER+ breast cancer cell lines. This study improves our understanding of how metabolic states alter ER function in endocrine-resistant breast cancer.PMID:39763830 | PMC:PMC11703175 | DOI:10.1101/2024.12.28.630631

bioRxiv [Preprint]. 2024 Dec 18:2024.12.17.629031. doi: 10.1101/2024.12.17.629031.ABSTRACTGuanosine triphosphate (GTP) is essential for macromolecular biosynthesis, and its intracellular levels are tightly regulated in bacteria. Loss of the alarmone (p)ppGpp disrupts GTP regulation in Bacillus subtilis , causing cell death in the presence of exogenous guanosine and underscoring the critical importance of GTP homeostasis. To investigate the basis of guanosine toxicity, we performed a genetic selection for spontaneous mutations that suppress this effect, uncovering an unexpected link between GTP synthesis and glycolysis. In particular, we identified suppressor mutations in pyk , which encodes pyruvate kinase, a glycolytic enzyme. Metabolomic analysis revealed that inactivating pyruvate kinase prevents guanosine toxicity by reducing GTP levels. Although traditionally associated with ATP generation via substrate-level phosphorylation, B. subtilis pyruvate kinase in vitro was found to produce GTP and UTP approximately ten and three times more efficiently than ATP, respectively. This efficient GTP/UTP synthesis extends to Enterococcus faecalis and Listeria monocytogenes , challenging the conventional understanding of pyruvate kinase's primary role in ATP production. These findings support a model in which glycolysis directly contributes to GTP synthesis, fueling energy-demanding processes such as protein translation. Finally, we observed a synergistic essentiality of the Δ ndk Δ pyk double mutant specifically on glucose, indicating that pyruvate kinase and nucleoside diphosphate kinase are the major contributors of NTP production and complement each other during glycolysis. Our work highlights the critical role of nucleotide selectivity in pyruvate kinase and its broader implications in cellular physiology.IMPORTANCE: In this study, we reveal pyruvate kinase, a key glycolytic enzyme, primarily generates GTP from GDP in Bacillus subtilis , relatively to other trinucleotides such as ATP. This finding, uncovered through genetic selection for mutants that suppress toxic GTP overaccumulation, challenges the conventional understanding that pyruvate kinase predominantly produces ATP via substrate-level phosphorylation. The substantial role of GTP production by pyruvate kinase suggests a model where glycolysis rapidly and directly supplies GTP as the energy currency to power high GTP-demanding processes such as protein synthesis. Our results underscore the importance of nucleotide selectivity (ATP vs. GTP vs UTP) in shaping the physiological state and fate of the cell, prompting further exploration into the mechanisms and broader implications of this selective nucleotide synthesis.PMID:39763737 | PMC:PMC11702619 | DOI:10.1101/2024.12.17.629031

Front Immunol. 2024 Dec 23;15:1514977. doi: 10.3389/fimmu.2024.1514977. eCollection 2024.ABSTRACTIn recent years, tumors have emerged as a major global health threat. An increasing number of studies indicate that the production, development, metastasis, and elimination of tumor cells are closely related to the tumor microenvironment (TME). Advances in artificial intelligence (AI) algorithms, particularly in large language models, have rapidly propelled research in the medical field. This review focuses on the current state and strategies of applying AI algorithms to tumor metabolism studies and explores expression differences between tumor cells and normal cells. The analysis is conducted from the perspectives of metabolomics and interactions within the TME, further examining the roles of various cytokines. This review describes the potential approaches through which AI algorithms can facilitate tumor metabolic studies, which offers a valuable perspective for a deeper understanding of the pathological mechanisms of tumors.PMID:39763649 | PMC:PMC11701166 | DOI:10.3389/fimmu.2024.1514977

Front Oncol. 2024 Dec 23;14:1486310. doi: 10.3389/fonc.2024.1486310. eCollection 2024.ABSTRACTArtificial intelligence (AI) has significantly impacted various fields, including oncology. This comprehensive review examines the current applications and future prospects of AI in lung cancer research and treatment. We critically analyze the latest AI technologies and their applications across multiple domains, including genomics, transcriptomics, proteomics, metabolomics, immunomics, microbiomics, radiomics, and pathomics in lung cancer research. The review elucidates AI's transformative role in enhancing early detection, personalizing treatment strategies, and accelerating therapeutic innovations. We explore AI's impact on precision medicine in lung cancer, encompassing early diagnosis, treatment planning, monitoring, and drug discovery. The potential of AI in analyzing complex datasets, including genetic profiles, imaging data, and clinical records, is discussed, highlighting its capacity to provide more accurate diagnoses and tailored treatment plans. Additionally, we examine AI's potential in predicting patient responses to immunotherapy and forecasting survival rates, particularly in non-small cell lung cancer (NSCLC). The review addresses technical challenges facing AI implementation in lung cancer care, including data quality and quantity issues, model interpretability, and ethical considerations, while discussing potential solutions and emphasizing the importance of rigorous validation. By providing a comprehensive analysis for researchers and clinicians, this review underscores AI's indispensable role in combating lung cancer and its potential to usher in a new era of medical breakthroughs, ultimately aiming to improve patient outcomes and quality of life.PMID:39763611 | PMC:PMC11700796 | DOI:10.3389/fonc.2024.1486310