PubMed

Toxicol Appl Pharmacol. 2024 Dec 17:117203. doi: 10.1016/j.taap.2024.117203. Online ahead of print.ABSTRACTCadmium (Cd) is among the top seven most hazardous environmental contaminants. Minimal risk levels for daily exposure have been established, such as no observable adverse effect level (NOAEL) and lowest observable adverse effect level (LOAEL). Chronic exposure to Cd, at both NOAEL and LOAEL doses, causes toxicity in diverse tissues. However, Cd toxicity in adipose tissue, an endocrine and metabolic organ, remains relatively understudied. We aimed to investigate the potentially toxic effects of chronic Cd exposure (at NOAEL and LOAEL doses) on epidydimal adipose tissue of adult male Wistar rats. Ninety male Wistar rats were divided into three groups (n = 30): Control Cd-free, NOAEL, and LOAEL that received CdCl2 in drinking water for 15 days to 5 months. We evaluated over time zoometry, serum and adipose Cd concentration, redox balance, GLUT4 and Nrf2 expression, histology, leptin, adiponectin, adipose insulin resistance index, free fatty acids, and glucose tolerance. The higher dose group showed a more pronounced and sustained increase in serum and adipose tissue of Cd concentration. Zoometry was similarly affected in both Cd-exposed groups with adipocyte hypertrophy. The redox balance was maintained due to the augmenting of Nrf2 expression. Leptin concentration augmented, while adiponectin diminished. Adipose insulin resistance increased simultaneously to lipolysis and glucose intolerance despite high GLUT4 expression. In conclusion, this study provides strong evidence that chronic Cd exposure, even at minimal risk levels (LOAEL and NOAEL doses), has toxic effects, disrupting the function of epididymal adipose tissue and contributing to metabolic disorders.PMID:39701214 | DOI:10.1016/j.taap.2024.117203

Prog Neuropsychopharmacol Biol Psychiatry. 2024 Dec 17:111223. doi: 10.1016/j.pnpbp.2024.111223. Online ahead of print.ABSTRACT3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a widely abused recreational drug that has also gained interest for potential clinical applications in mental health. With the growing recognition of gut microbiota's role in mental health, this study examined whether repeated oral MDMA administration could affect gut microbiota in the small intestine, cecum, and colon of male rats. Repeated oral MDMA administration (10 mg/kg/day for 14 days) caused significant changes in the gut microbiota across these regions, with distinct effects observed in each. PICRUSt2 analysis revealed significant alterations in several metabolic pathways in these regions, indicating potential shifts in microbial functional capabilities associated with MDMA treatment. Untargeted metabolomics analysis revealed that MDMA significantly altered levels of two metabolites-ferulic acid and methylmalonic acid-in the colon, without changes in the blood, small intestine, or cecum. Notably, methylmalonic acid levels in the colon positively correlated with Lawsonibacter and Oscillibacter. These findings suggest that repeated oral MDMA treatment can alter gut microbiota composition across intestinal regions, potentially contributing to its pharmacological effects.PMID:39701173 | DOI:10.1016/j.pnpbp.2024.111223

NMR Biomed. 2025 Jan;38(1):e5299. doi: 10.1002/nbm.5299.ABSTRACTTo improve reliability of metabolite quantification at both, 3 T and 7 T, we propose a novel parametrized macromolecules quantification model (PRaMM) for brain 1H MRS, in which the ratios of macromolecule peak intensities are used as soft constraints. Full- and metabolite-nulled spectra were acquired in three different brain regions with different ratios of grey and white matter from six healthy volunteers, at both 3 T and 7 T. Metabolite-nulled spectra were used to identify highly correlated macromolecular signal contributions and estimate the ratios of their intensities. These ratios were then used as soft constraints in the proposed PRaMM model for quantification of full spectra. The PRaMM model was validated by comparison with a single-component macromolecule model and a macromolecule subtraction technique. Moreover, the influence of the PRaMM model on the repeatability and reproducibility compared with those other methods was investigated. The developed PRaMM model performed better than the two other approaches in all three investigated brain regions. Several estimates of metabolite concentration and their Cramér-Rao lower bounds were affected by the PRaMM model reproducibility, and repeatability of the achieved concentrations were tested by evaluating the method on a second repeated acquisitions dataset. Although the observed effects on both metrics were not significant, the fit quality metrics were improved for the PRaMM method (p ≤ 0.0001). Minimally detectable changes are in the range 0.5-1.9 mM, and the percentage coefficients of variations are lower than 10% for almost all the clinically relevant metabolites. Furthermore, potential overparameterization was ruled out. Here, the PRaMM model, a method for an improved quantification of metabolites, was developed, and a method to investigate the role of the MM background and its individual components from a clinical perspective is proposed.PMID:39701127 | DOI:10.1002/nbm.5299

J Pharm Biomed Anal. 2024 Dec 16;255:116638. doi: 10.1016/j.jpba.2024.116638. Online ahead of print.ABSTRACTUnderstanding the pharmacodynamics of ritonavir through metabolomics offers insights into its side effects and helps in the development of safer therapies. This study aimed to investigate the effects of ritonavir treatment on the metabolic profiles of rabbits via a metabolomics approach, with the objective of elucidating its impact on various biochemical pathways and identifying relevant biomarkers. The rabbits were divided into control and ritonavir-treated groups, and their plasma samples were analyzed via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF/MS/MS). Metabolites were identified on the basis of the masscharge ratio (m/z) and validated via XCMS software. Metabolites with a fold change ≥ 1.5 and P ≤ 0.01 were analyzed via principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) to distinguish between the groups. MetaboAnalyst 6.0 was used for pathway analysis to identify metabolic pathways affected by ritonavir. The PCA and OPLS-DA models revealed clear separation between the control and ritonavir-treated groups, with high R² and Q² values indicating robust model performance. Pathway analysis revealed that ritonavir treatment significantly affected several metabolic pathways, including those related to ether lipid, phenylalanine, sphingolipid, and glycerophospholipid metabolism. Particularly significant changes were observed in metabolites related to lipid metabolism, oxidative stress responses and cellular signaling. Ritonavir significantly impacts metabolic pathways, particularly those involved in lipid metabolism, and oxidative stress responses, which may influence immune responses and drug interactions. This study also highlights the potential of integrating metabolomics with personalized medicine approaches to optimize ritonavir treatment strategies and reduce adverse effects. These findings indicate that ritonavir significantly influences cellular homeostasis and metabolic processes in addition to its antiviral properties. This highlights the necessity of comprehending the metabolic effects of ritonavir to enhance its clinical application, especially in the management of COVID-19. Further research is warranted to explore these alterations and their implications for therapeutic strategies.PMID:39700866 | DOI:10.1016/j.jpba.2024.116638

Food Chem. 2024 Dec 14;468:142492. doi: 10.1016/j.foodchem.2024.142492. Online ahead of print.ABSTRACTAstragali radix (HQ) is a herb with rich medicinal and edible value. Wild-simulated HQ (FYS) and Transplanted HQ (PZ) are its currently two primary forms available in the market. Metabolomics was employed to investigate their intricate metabolic variations under various cultivation methods and growth years. Notable similarities were observed in their metabolic changes across various growth years. Specifically, saponins was higher in the early growth phase, while flavonoids increased in the later. Additionally, comparative analysis of HQ samples from different cultivation methods indicated that FYS generally exhibited different chemical characteristics compared to PZ within the same market circulation period, and Calycosin-7-O-Glc-6"-O-acetate and Cycloastragenol-H2O might be used to discriminant them (the content of Calycosin-7-O-Glc-6"-O-acetate and Cycloastragenol-H2O was higher in FYS than in PZ). This approach elucidates the dynamic change pattern of characteristic metabolites and pinpoints potential biomarkers for both FYS and PZ, thereby enhancing our understanding of these medicinal materials.PMID:39700793 | DOI:10.1016/j.foodchem.2024.142492

Comp Biochem Physiol Part D Genomics Proteomics. 2024 Dec 13;54:101401. doi: 10.1016/j.cbd.2024.101401. Online ahead of print.ABSTRACTHypoxia disrupts multiple physiological processes, including metabolism, immunity, and reproduction in teleosts. The brain plays a critical role in adapting to environmental changes, regulating the endocrine system, and controlling reproduction. The present study investigated the sex-specific cerebral responses to chronic hypoxia through an integrated analysis of the transcriptome, proteome, and metabolome of yellow catfish. Common cerebral responses in both females and males included activation of the HIF signaling pathway, angiogenesis, and improved oxygen delivery by red blood cells. Reproductive defects were indicated by the downregulation of gh1, cga, and tshb in both sexes. Thyroid hormone homeostasis was more severely disrupted by hypoxia in females than in males, accompanied by a significant decrease in the level of VTG in the female brain. Damaged brain function was evidenced by the highly enriched pathways of "cytokine-cytokine receptor interaction" and "ECM-receptor interaction," and the blood-brain barrier (BBB) also appeared to be disrupted in female fish. In the male brain, reproductive-related genes or proteins, including prl, lepr, and AVP, were specifically decreased. Dysfunction in the male brain was also indicated by the enrichment of pathways such as "cytokine-cytokine receptor interaction" and "neuroactive ligand-receptor interaction," based on differentially expressed genes (DEGs) and proteins (DEPs). Additionally, chronic hypoxia appeared to inhibit cerebral amino acid metabolism in males. In summary, our results offer insight into understanding the sex-specific cerebral responses induced by chronic hypoxia in teleosts.PMID:39700741 | DOI:10.1016/j.cbd.2024.101401

Environ Int. 2024 Dec 11;195:109180. doi: 10.1016/j.envint.2024.109180. Online ahead of print.ABSTRACTOrganic fertilizer application promotes the prevalence of antibiotic resistance genes (ARGs), yet the factors driving temporal differences in ARG abundance under long-term organic fertilizer application remain unclear. This study investigated the temporal dynamics of ARG diversity and abundance in both bulk and rhizosphere soils over 17 years (2003-2019), and explored microbial evolution strategies, ARG hosts succession and the influence of root exudates on ARGs regulation. The results showed that the ARGs abundance in rhizosphere soil was lower than that in bulk soil under long-term fertilization, and ARGs abundance exhibited a decrease and then remained stable in rhizosphere soil over time. There was a strong association between host bacteria and dominant ARGs (p < 0.05). Structural equations demonstrated that bacterial community had a most pronounced influence on ARGs (p < 0.05), and metabolites exhibited an important mediation effect on bacterial community (p < 0.05), thereby impacting ARGs. The metabolome analysis evidenced that significant correlations were found between defensive root exudates and most ARGs abundance (p < 0.05), like, luteolin-7-glucoside was negatively correlated with tetA(58). These findings provide deeper insights into the dynamics of soil ARGs under long-term fertilization, and identify critical factors that influence ARGs colonization in soils, providing support for controlling the spread of ARGs in agriculture soils.PMID:39700687 | DOI:10.1016/j.envint.2024.109180

Poult Sci. 2024 Nov 10;104(1):104506. doi: 10.1016/j.psj.2024.104506. Online ahead of print.ABSTRACTThe use of bio-enzyme as feed additives holds significant potential. This study aimed to evaluate the impact of a kind of compound bio-enzyme supplementation (the main functional components are probiotics and astragalus polysaccharides) on the production performance, serum immunity, and intestinal health of Pekin ducks. A total of 126 male Pekin ducks were randomly assigned to three groups: a control group (CG, no additive), a low-dose group (LG, 0.1 % bio-enzyme), and a high-dose group (HG, 0.2 % bio-enzyme), with 6 replicates per group. Ducks were raised until 35 days of age, with weekly measurements of growth performance. At day 35, serum immunoglobulins were measured, carcass traits were recorded, and cecal contents were analyzed using 16S rRNA sequencing and metabolomics. Results indicated a significant increase in ADG (P = 0.049) and a decrease in feed-to-gain ratio (F:G) (P = 0.020) in LG and HG compared to CG during rearing. The HG showed a notable improvement in half eviscerated yield (HEY) (P = 0.023) and full eviscerated yield (FEY) (P = 0.008). No substantial changes were observed in immunological parameters (P > 0.05). The jejunal villus height to crypt depth ratio (VH/CD) significantly increased (P < 0.001) in LG, with notable improvements in duodenal (P = 0.001) and jejunal (P < 0.001) VH/CD in HG. The Shannon index (P = 0.042) and Pielou index (P = 0.038) of cecal microbiota were markedly lower in HG. Notable changes in the relative abundance of Firmicutes and Bacteroidota were observed in LG and HG. Differential bacteria and metabolites among the treatments were identified, and their correlations were analyzed. KEGG enrichment pathways of the metabolites were also identified. In conclusion, this bio-enzyme can improve production performance, intestinal wall structure, and microbiota in Pekin ducks. A 0.1 % concentration of this bio-enzyme is optimal for Pekin duck production.PMID:39700598 | DOI:10.1016/j.psj.2024.104506

J Exp Bot. 2024 Dec 19:erae506. doi: 10.1093/jxb/erae506. Online ahead of print.ABSTRACTUnderstanding how crop varieties acclimate to elevated temperatures is key to priming them for future climates. Here, we exposed two genotypes of Sorghum bicolor (one sensitive to heat shock (Sen) and one tolerant (Tol)) from multiple growth temperatures to a six-day heat shock (reaching 45°C), carrying out a suite of measurements before and during heat shock. Sen consistently reduced photosynthetic functioning during heat shock, while Tol increased its photosynthetic rate. Higher abundance of heat shock protein transcripts and metabolites related to heat tolerance were noted for Tol when compared to Sen both before and during heat shock, which can be attributed to constitutive and inducible responses to elevated temperatures. In addition, important changes in metabolic pathways were clearly identified for Tol during heat shock (including upregulation of raffinose family oligosaccharides and downregulation of the GABA catalytic pathway), even as the concentration of hexose sugars became depleted. We infer Tol was able to tolerate elevated temperatures due to an upregulation of osmoprotectants, chaperones and reactive oxygen species scavengers and by the suppression of SnRK1 via transcripts and metabolites during heat shock. Our results highlight potential targets for attributes of high temperature tolerance which can be utilised in future breeding trials.PMID:39700407 | DOI:10.1093/jxb/erae506

PLoS One. 2024 Dec 19;19(12):e0315330. doi: 10.1371/journal.pone.0315330. eCollection 2024.ABSTRACTMembrane transporters are responsible for moving a wide variety of molecules across biological membranes, making them integral to key biological pathways in all organisms. Identifying all membrane transporters within a (meta-)proteome, along with their specific substrates, provides important information for various research fields, including biotechnology, pharmacology, and metabolomics. Protein datasets are frequently annotated with thousands of molecular functions that form complex networks, often with partial or full redundancy and hierarchical relationships. This complexity, along with the low sample count for more specific functions, makes them unsuitable as classes for supervised learning methods, meaning that the creation of an optimal subset of annotations is required. However, selection of this subset requires extensive manual effort, along with knowledge about the biology behind the respective functions. Here, we present an automated pipeline to address this problem. Unlike previous approaches for reducing redundancy in GO datasets, we employ machine learning to identify a subset of functional annotations in a training dataset. Classes in the resulting predictive model meet four essential criteria: sufficient sample size for training predictive models, minimal redundancy, strong class separability, and relevance to substrate transport. Furthermore, we implemented a pipeline for creating training datasets of transmembrane transporters that cover a wide range of organisms, including plants, bacteria, mammals, and single-cell eukaryotes. For a dataset containing 98.1% of transporters from S. cerevisiae, the pipeline automatically reduced the number of functional annotations from 287 to 11 GO terms that could be classified with a median pairwise F1 score of 0.87±0.16. For a meta-organism dataset containing 96% of all transport proteins from S. cerevisiae, A. thaliana, E. coli and human, the number of classes was reduced from 695 to 49, with a median F1 score of 0.92±0.10 between pairs of GO terms. When lowering the percentage of covered proteins down to 67%, the pipeline found a subset of 30 GO terms with a median F1 score of 0.95±0.06.PMID:39700222 | DOI:10.1371/journal.pone.0315330

J Cell Mol Med. 2024 Dec;28(24):e70277. doi: 10.1111/jcmm.70277.ABSTRACTLipid reprogramming in carcinoma is reported to have a role in carcinogenesis, prognosis and therapy response. The lipid reprogramming could be contributed by either autonomous or nonautonomous resources. Since the nonautonomous lipid resources contributed by lipoproteins and their receptors have been reported in epithelial ovarian cancer (EOC), the impact of autonomous lipid metabolites was unknown. This report revealed a unique lipid class, ether-linked phosphatidyl-ethanolamine (PE O-), which enhances chemo-insensitivity and progression in EOC and potentially cross carcinomas. Analysis of CCLEC/GDSCC database and in-house cell line lipidomes identified PE O- as the major lipid associated with cisplatin/paclitaxel sensitivity. In the testing of PE O- effect on cancer phenotypes, it enhanced cell growth, migratory activities and promoted cisplatin/paclitaxel insensitivity. In addition, treating AGPS inhibitor-sensitised chemo-cytotoxic upon cisplatin/paclitaxel treatments. Treating PE O- could reverse AGPS inhibitor chemosensitisation effect on EOC cells. At last, using TCGA-EOC transcriptome database, the PE O- related gene expressions were positive correlated with patient prognosis in general, or in whom were treated with platin- or taxel-based chemotherapies. The expressions of genes for the synthesis of PE O- aggravates therapy response in EOC patients. PE O- facilitates human carcinoma cell line growth, mobility and chemo-insensitivity.PMID:39700026 | DOI:10.1111/jcmm.70277

Anal Chem. 2024 Dec 19. doi: 10.1021/acs.analchem.4c04060. Online ahead of print.ABSTRACTMethods for assessing compound identification confidence in metabolomics and related studies have been debated and actively researched for the past two decades. The earliest effort in 2007 focused primarily on mass spectrometry and nuclear magnetic resonance spectroscopy and resulted in four recommended levels of metabolite identification confidence─the Metabolite Standards Initiative (MSI) Levels. In 2014, the original MSI Levels were expanded to five levels (including two sublevels) to facilitate communication of compound identification confidence in high resolution mass spectrometry studies. Further refinement in identification levels have occurred, for example to accommodate use of ion mobility spectrometry in metabolomics workflows, and alternate approaches to communicate compound identification confidence also have been developed based on identification points schema. However, neither qualitative levels of identification confidence nor quantitative scoring systems address the degree of ambiguity in compound identifications in the context of the chemical space being considered. Neither are they easily automated nor transferable between analytical platforms. In this perspective, we propose that the metabolomics and related communities consider identification probability as an approach for automated and transferable assessment of compound identification and ambiguity in metabolomics and related studies. Identification probability is defined simply as 1/N, where N is the number of compounds in a database that matches an experimentally measured molecule within user-defined measurement precision(s), for example mass measurement or retention time accuracy, etc. We demonstrate the utility of identification probability in an in silico analysis of multiproperty reference libraries constructed from a subset of the Human Metabolome Database and computational property predictions, provide guidance to the community in transparent implementation of the concept, and invite the community to further evaluate this concept in parallel with their current preferred methods for assessing metabolite identification confidence.PMID:39699939 | DOI:10.1021/acs.analchem.4c04060

Nat Prod Res. 2024 Dec 19:1-6. doi: 10.1080/14786419.2024.2443490. Online ahead of print.ABSTRACTPhanera vahlii (Wight & Arn.) Benth., leaves are used traditionally in variety of diseases. Chemical examination of the leaves yielded Davinvolunol B (1) and Quercetin-3-O-rhamnoside (2). Compared with the other extracts, the aqueous methanol extract significantly inhibited Streptococcus aureus with an IC50 of 8 µg/mL. In the anticancer activity assay, the ethyl acetate extract was effective against HeLa cells (IC50 19 µg/mL), the methanol extract was effective against A549 cells (IC50 of 19 µg/mL), the aqueous methanol extract was effective against PANC-1 cells (IC50 of 17 µg/mL) and the chloroform extract was effective against HT1080 cells (IC50 of 19 µg/mL). The polar extracts which showed good antioxidant activity exhibited strong bioactivity. This finding was supported by untargeted phytometabolite profiling of extracts using UPLC-ESI-Q-TOF-MSE. The PCA score plot and the Ven diagram revealed that the extracts had a distinctive and adequate number of polar molecules that likely contributed to their observed inhibitory activity.PMID:39699566 | DOI:10.1080/14786419.2024.2443490

Food Funct. 2024 Dec 19. doi: 10.1039/d4fo04301d. Online ahead of print.ABSTRACTObesity-related metabolic syndrome is intimately associated with infiltrated adipose tissue macrophages (ATMs), gut microbiota, and metabolic disorders. Pediococcus acidilactici holds the potential to mitigate obesity; however, there exist strain-specific functionalities and diverse mechanisms, which deserve extensive exploration. This study aims to explore the potential of P. acidilactici Y01, isolated from traditional sour whey, in alleviating HFD-induced metabolic syndrome in mice and elucidating its underlying mechanism. The results showed that P. acidilactici Y01 could inhibit the increase of body weight gain, the deposition of fat, lipid disorders and chronic low-grade inflammation, improve glucose tolerance and insulin resistance, and could reduce adipose tissue inflammation by decreasing M1-type ATMs and increasing M2-type ATMs. Meanwhile, P. acidilactici Y01 significantly increased the abundance of potentially beneficial intestinal bacteria, such as Akkermansia, Alistipes, Bifidobacterium, Lachnospiraceae_NK4A136_group, Lactobacillus, norank_f__Muribaculaceae, and Parabacteroides, and partially restored the levels of metabolites, such as phosphatidylcholines, glycerophosphocholines, sphingolipids and unsaturated fatty acids. The fecal microbiota transplantation experiment demonstrated that P. acidilactici Y01 ameliorated obesity-related metabolic syndrome by modulating the polarization of M1/M2 ATMs mediated by gut microbiota. Overall, as a dietary supplement, P. acidilactici Y01 has good potential in the prevention and treatment of obesity.PMID:39699275 | DOI:10.1039/d4fo04301d

Microbiol Spectr. 2024 Dec 19:e0136824. doi: 10.1128/spectrum.01368-24. Online ahead of print.ABSTRACTMicrobiota-released extracellular vesicles (MEVs) have emerged as a key player in intercellular signaling. However, their involvement in the gut-brain axis has been poorly investigated. We hypothesize that MEVs cross host cellular barriers and deliver their cargoes of bioactive compounds to the brain. In this study, we aimed to investigate the cargo capacity of MEVs for bioactive metabolites and their interactions with the host cellular barriers. First, we conducted a multi-omics profiling of MEVs' contents from ex vivo and stool samples. Metabolomics analysis identified various neuro-related compounds encapsulated within MEVs, such as arachidonyl-dopamine, gabapentin, glutamate, and N-acylethanolamines. Metaproteomics unveiled an enrichment of enzymes involved in neuronal metabolism, primarily in the glutamine/glutamate/gamma-aminobutyric acid (GABA) pathway. These neuro-related proteins and metabolites were correlated with Bacteroides spp. We isolated 18 Bacteroides strains and assessed their GABA production capacity in extracellular vesicles (EVs) and culture supernatant. A GABA-producing Bacteroides finegoldii, released EVs with a high GABA content (4 µM) compared to Phocaeicola massiliensis. Upon testing the capacity of MEVs to cross host barriers, MEVs exhibited a dose-dependent paracellular transport and were endocytosed by Caco-2 and hCMEC/D3 cells. Exposure of Caco-2 cells to MEVs did not alter expression of genes related to intestinal barrier integrity, while affected immune pathways and cell apoptosis process as revealed by RNA-seq analyses. In vivo, MEVs biodistributed across mice organs, including the brain, liver, stomach, and spleen. Our results highlight the ability of MEVs to cross the intestinal and blood-brain barriers to deliver their cargoes to distant organs, with potential implication for the gut-brain axis.IMPORTANCE: Microbiota-released extracellular vesicles (MEVs) have emerged as a key player in intercellular signaling. In this study, a multi-level analysis revealed presence of a diverse array of biologically active molecules encapsulated within MEVs, including neuroactive metabolites, such as arachidonyl-dopamine, gabapentin, glutamate, and N-acylethanolamines, and gamma-aminobutyric acid (GABA). Metaproteomics also unveiled an enrichment of neural-related proteins, mainly the glutamine/glutamate/GABA pathway. MEVs were able to cross epithelial and blood-brain barriers in vitro. RNA-seq analyses showed that MEVs stimulate several immune pathways while suppressing cell apoptosis process. Furthermore, MEVs were able to traverse the intestinal barriers and reach distal organs, including the brain, thereby potentially influencing brain functionality and contributing to mental and behavior.PMID:39699251 | DOI:10.1128/spectrum.01368-24

Tree Physiol. 2024 Dec 19:tpae166. doi: 10.1093/treephys/tpae166. Online ahead of print.ABSTRACTIron plaques on the root surface can promote or inhibit the absorption and accumulation of heavy metals by plants. However, the mechanism by which iron regulates the response of Robinia pseudoacacia to mercury (Hg) have not been elucidated which hinders its application in divalent Hg (Hg2+) removal from Hg-contaminated soil. In this study, association analyses between transcriptome and metabolome were used to investigate effects of iron on the rhizosphere microenvironment and performance of R. pseudoacacia to assess its potential for Hg2+ removal. The results showed that the addition of 10 mg kg-1 iron significantly increased the development of iron plaques on root surface, and reduced the secretion of low-molecular-weight organic acids by roots, thereby changing rhizosphere soil characteristics and decreasing total Hg in roots. In addition, the secretion of choline supported signal transduction and enhanced the interaction between R. pseudoacacia and rhizobia, thereby inducing resistance to Hg2+. Anti-oxidative enzyme activities were increased and Hg2+ exposure of plants was reduced. Enhanced Hg2+ resistance was indicated by improved photosynthesis and growth despite promoted xylem loading and transport of Hg2+, resulting in its accumulation in aboveground tissues that is essential for Hg2+ removal. These results indicate that iron addition has a great potential to improve the growth of R. pseudoacacia in Hg-contaminated soil and promote the accumulation of Hg2+ in aboveground tissues for phytoremediation approaches.PMID:39699123 | DOI:10.1093/treephys/tpae166

Curr Opin Pediatr. 2025 Feb 1;37(1):59-66. doi: 10.1097/MOP.0000000000001419. Epub 2024 Dec 2.ABSTRACTPURPOSE OF REVIEW: We provide an overview of the etiology of childhood cancer, the state of the literature, and highlight some opportunities for future research, including technological advancements that could be applied to etiologic studies of childhood cancer to accelerate our understanding.RECENT FINDINGS: Risk factors of childhood cancer were summarized based on demographics and perinatal factors, environmental risk factors, and genetic risk factors. Overall, demographics and perinatal factors are the most well studied in relation to childhood cancer. While environmental risk factors have been implicated, more work is needed to pinpoint specific exposures, identify window(s) of susceptibility, and understand mechanisms. With genome-wide association studies (GWAS), genetic risk factors of eight childhood cancers have emerged, and opportunities remain to conduct GWAS for other cancer types and determine whether risk variants are inherited or de novo. Technological advancements that can shed light into the susceptibility of childhood cancer include metabolomics, using primary teeth as an exposure matrix, and long-read sequencing.SUMMARY: The development of childhood cancer remains largely not well understood. Collaboration to increase sample size to conduct analyses by histology and/or molecular subtype and application of novel technologies will accelerate our understanding of childhood cancer.PMID:39699102 | DOI:10.1097/MOP.0000000000001419

Plant Cell Physiol. 2024 Dec 19:pcae149. doi: 10.1093/pcp/pcae149. Online ahead of print.ABSTRACTTrees in the genus Populus synthesize sticky and fragrant resins to protect dormant leaf buds during winter. These resins contain diverse phenolic metabolites, in particular hydroxycinnamate esters and methylated flavonoids. P. trichocarpa leaf bud resin is characterized by methylated dihydrochalcone aglycones. To determine how the resin profile is influenced by seasonal changes, P. trichocarpa lateral leaf bud extracts and secreted surface resin were collected monthly over a one-year cycle. The dihydrochalcones in both sets of extracts were quantified using ultrahigh pressure liquid chromatography - mass spectrometry (UPLC-MS) and other chemical changes monitored using non-targeted metabolomics by ultrahigh pressure liquid chromatography - high resolution mass spectrometry (UPLC-HRMS). The results indicate that the dihydrochalcone content changes over the seasons and that biosynthesis occurs concomitant with bud development in the summer months. Non-targeted metabolomics data confirmed a pattern of dramatic changes in the summer, and further suggested additional periods of substantive biochemical change in the resin. While overall patterns of surface-extracted resin matched that of whole bud extracts, some of the dynamics were shifted in the surface resin samples. This study provides the basis for the use of dihydrochalcones and other identified resin components as metabolic markers for more detailed investigations of resin biosynthesis, secretion and movement to the bud surface.PMID:39699046 | DOI:10.1093/pcp/pcae149

Mov Disord. 2024 Dec 19. doi: 10.1002/mds.30083. Online ahead of print.ABSTRACTBACKGROUND: Recent studies have reported that expanded GCA repeats in the GLS gene can cause glutaminase deficiency with ataxia phenotype. However, to data, no studies have investigated the distribution and role of GCA repeats in the GLS gene of Chinese individuals.OBJECTIVE: The aim was to investigate the distribution of GCA repeats in Chinese individuals, including undiagnosed ataxia patients for identifying causal factors, healthy controls for determining the normal range, and ATX-ATXN3 (spinocerebellar ataxia type 3, SCA3) patients for exploring genetic modifiers.METHODS: We combined whole-genome sequencing (WGS), repeat-primed polymerase chain reaction, capillary electrophoresis (RP-PCR/CE), and ExpansionHunter to screen the GCA repeats in the GLS gene of 349 undiagnosed ataxia individuals, 1505 healthy controls, and 1236 ATX-ATXN3 (SCA3) patients from mainland China.RESULTS: No expanded GCA repeats in the GLS gene were detected across any of the samples. The average number of GCA repeats was 11 (range: 8-31), 12 (range: 6-33), and 11 (range: 6-33) for undiagnosed ataxia patients, healthy controls, and SCA3 patients, respectively. The intermediate repeat size (9 < repeat size ≤ 13) of the nonexpanded GCA allele in the GLS gene was associated with later disease onset in ATX-ATXN3 (SCA3) patients.CONCLUSIONS: Abnormal expansions of GLS GCA repeats are rare in the Chinese population. However, intermediate-length normal GCA repeat sizes may influence the age at onset (AAO) in ATX-ATXN3 (SCA3) patients. © 2024 International Parkinson and Movement Disorder Society.PMID:39699045 | DOI:10.1002/mds.30083

J Proteome Res. 2024 Dec 19. doi: 10.1021/acs.jproteome.4c00902. Online ahead of print.ABSTRACTThe prevalence rate of colorectal cancer (CRC) has dramatically increased in recent decades. However, robust CRC biomarkers with therapeutic value for early diagnosis are still lacking. To comprehensively reveal the molecular characteristics of CRC development, we employed a multiomics strategy to investigate eight different types of CRC samples. Proteomic analysis revealed 2022 and 599 differentially expressed tissue proteins between CRC and control groups in CRC patients and CRC mice, respectively. In patients with colorectal precancerous lesions, 25 and 34 significantly changed proteins were found between patients and healthy controls in plasma and white blood cells, respectively. Notably, vesicle-associated membrane protein-associated protein A (VAPA) was found to be consistently and significantly decreased in most types of CRC samples, and its level was also significantly correlated with increased overall survival of CRC patients. Furthermore, 37 significantly enriched pathways in CRC were further validated via metabolomics analysis. Ten VAPA-related pathways were found to be significantly enriched in CRC samples, among which PI3K-Akt signaling, central carbon metabolism in cancer, cholesterol metabolism, and ABC transporter pathways were also enriched in the premalignant stage. Our study identified VAPA and its associated pathways as key regulators, suggesting their potential applications in the early diagnosis and prognosis of CRC.PMID:39699012 | DOI:10.1021/acs.jproteome.4c00902