PubMed

Adv Sci (Weinh). 2025 Jan 14:e2409105. doi: 10.1002/advs.202409105. Online ahead of print.ABSTRACTHyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathological characteristics of AD, as confirmed by measuring mannose levels in the brains and serum of AD mice, as well as in the serum of AD patients. AD mice are given mannose by intra-cerebroventricular injection (ICV) or in drinking water to investigate the effects of mannose on cognition and AD pathological progression. Chronic mannose overload increases β-amyloid (Aβ) burdens and exacerbates cognitive impairments, which are reversed by a mannose-free diet or mannose transporter antagonists. Mechanistically, single-cell RNA sequencing and metabolomics suggested that mannose-mediated N-glycosylation of BACE1 and Nicastrin enhances their protein stability, promoting Aβ production. Additionally, reduced mannose intake decreased BACE1 and Nicastrin stability, ultimately lowering Aβ production and mitigating AD pathology. this results highlight that high-dose mannose consumption may exacerbate AD pathogenesis. Restricting dietary mannose may have therapeutic benefits.PMID:39807036 | DOI:10.1002/advs.202409105

Adv Sci (Weinh). 2025 Jan 14:e2413296. doi: 10.1002/advs.202413296. Online ahead of print.ABSTRACTLarge-scale studies indicate a strong relationship between the gut microbiome, type 2 diabetes mellitus (T2DM), and atherosclerotic cardiovascular disease (ASCVD). Here, a higher abundance of the type III secretion system (T3SS) virulence factors of Enterobacteriaceae/Escherichia-Shigella in patients with T2DM-related-ASCVD, which correlates with their atherosclerotic stenosis is reported. Overexpression of T3SS via Citrobacter rodentium (CR) infection in Apoe-/- T2DM mice exacerbated atherosclerotic lesion formation and increased gut permeability. Non-targeted metabolomic and proteomic analysis of mouse serum showed that T3SS caused abnormal glycerophospholipid metabolism in mice. Proteomics, RNA sequencing, and functional analyses showed that T3SS induced ferroptosis in intestinal epithelial cells, partly due to increased expression of ferritin heavy chains (FTH1). This findings first demonstrated that T3SS increases ferroptosis in intestinal epithelial cells, via disrupting the intestinal barrier and upregulation of phosphatidylcholine, thereby exacerbating T2DM-related ASCVD.PMID:39807021 | DOI:10.1002/advs.202413296

Cancer Metab. 2025 Jan 14;13(1):1. doi: 10.1186/s40170-024-00372-0.ABSTRACTInvasiveness of pituitary adenoma is the main cause of its poor prognosis, mechanism of which remains largely unknown. In this study, the differential proteins between invasive and non-invasive pituitary tumors (IPA and NIPA) were identified by TMT labeled quantitative proteomics. The differential metabolites in venous bloods from patients with IPA and NIPA were analyzed by untargeted metabolomics. Proteomic data showed that the top five up-regulated proteins were AD021, C2orf15, PLCXD3, HIST3H2BB and POU1F1, and the top five down-regulated proteins were AIPL1, CALB2, GLUD2, SLC4A10 and GTF2I. Metabolomic data showed that phosphatidylinositol (PI) was most remarkably up-regulated and melibiose was most obviously down-regulated. Further investigation demonstrated that PI stimulation increased the expression of PITPNM1, POU1F1, C2orf15 and LDHA as well as the phosphorylation of AKT and ERK, and promoted the proliferation, migration and invasion of GH3 cells, which were blocked by PITPNM1knockdown. Inhibiting AKT phosphorylation reduced the expression of POU1F1, C2orf15 and LDHA in PI-stimulated cells while activating AKT increased their expression in PITPNM1-silencing cells, which was similar to the function of ERK. POU1F1 silence suppressed the expression of LDHA and C2orf15. Luciferase report assay and ChIP assay demonstrated that POU1F1 positively regulated the transcription of LDHA and C2orf15. In addition, PI propelled the metastasis of GH3 cells in vivo, and elevated the expression of PITPNM1, POU1F1, C2orf15 and LDHA. These results suggested that elevated serum PI might contribute to the proliferation and invasion of pituitary adenoma by regulating the expression of PITPNM1/AKT/ERK/POU1F1 axis.PMID:39806458 | DOI:10.1186/s40170-024-00372-0

Orphanet J Rare Dis. 2025 Jan 13;20(1):21. doi: 10.1186/s13023-024-03484-4.ABSTRACTBACKGROUND: Intestinal Behçet's syndrome (IBS) has high morbidity and mortality rates with serious complications. However, there are few specific biomarkers for IBS. The purposes of this study were to investigate the distinctive metabolic changes in plasma samples between IBS patients and healthy people, active IBS and inactive IBS patients, and to identify candidate metabolic biomarkers which would be useful for diagnosing and predicting IBS.METHODS: In this study, we performed a global untargeted metabolomics approach in plasma samples from 30 IBS patients and 20 healthy subjects. P value < 0.05 and variable importance projection (VIP) values > 1 were considered to be statistically significant metabolites. Univariate receiver operating characteristic (ROC) curve analysis was plotted as a measure for assessing the clinical performance of metabolites, and area under curve (AUC) were assessed.RESULTS: A total of 147 differentially abundant metabolites (DAMs) were identified between IBS patients and normal control (NC) group. The potential pathways involved in the pathogenesis of IBS include linoleic acid metabolism; GABAergic synapse; biosynthesis of unsaturated fatty acids; valine, leucine and isoleucine biosynthesis; ovarian steroidogenesis; and others. In addition, a total of 103 significant metabolites were selected to distinguish active IBS from inactive IBS patients. Tyrosine metabolism, dopaminergic synapse and neuroactive ligand-receptor interaction were found to be closely related to the disease activity of IBS. Furthermore, three potential metabolites including quinate, stearidonic acid (SDA) and capric acid (CA) could significantly differ IBS patients from NC group. On the other hand, 1-methyladenosine (m1A), genipin, methylmalonic acid (MMA) and ascorbate could significantly differentiated active IBS from inactive IBS patients.CONCLUSION: In conclusion, this study demonstrated the characteristic plasma metabolic profiles between IBS group and NC group, as well as between active and inactive IBS patients by using an untargeted LC/MS metabolomics profiling approach. In this study, quinate, SDA and CA were identified as potential diagnostic biomarkers for IBS. Additionally, m1A, genipin, MMA and ascorbate could serve as potential biomarkers for evaluating IBS activity. These findings might provide potential valuable insights for developing therapeutic strategies to manage IBS in the future.PMID:39806438 | DOI:10.1186/s13023-024-03484-4

Cardiovasc Diabetol. 2025 Jan 13;24(1):18. doi: 10.1186/s12933-025-02581-3.ABSTRACTBACKGROUND: Existing cardiovascular risk prediction models still have room for improvement in patients with type 2 diabetes who represent a high-risk population. This study evaluated whether adding metabolomic biomarkers could enhance the 10-year prediction of major adverse cardiovascular events (MACE) in these patients.METHODS: Data from 10,257 to 1,039 patients with type 2 diabetes from the UK Biobank (UKB) and the German ESTHER cohort, respectively, were used for model derivation, internal and external validation. A total of 249 metabolites were measured with nuclear magnetic resonance (NMR) spectroscopy. Sex-specific LASSO regression with bootstrapping identified significant metabolites. The enhanced model's predictive performance was evaluated using Harrell's C-index.RESULTS: Seven metabolomic biomarkers were selected by LASSO regression for enhanced MACE risk prediction (three for both sexes, three male- and one female-specific metabolite(s)). Especially albumin and the omega-3-fatty-acids-to-total-fatty-acids-percentage among males and lactate among females improved the C-index. In internal validation with 30% of the UKB, adding the selected metabolites to the SCORE2-Diabetes model increased the C-index statistically significantly (P = 0.037) from 0.660 to 0.678 in the total sample. In external validation with ESTHER, the C-index increase was higher (+ 0.043) and remained statistically significant (P = 0.011).CONCLUSIONS: Incorporating seven metabolomic biomarkers in the SCORE2-Diabetes model enhanced its ability to predict MACE in patients with type 2 diabetes. Given the latest cost reduction and standardization efforts, NMR metabolomics has the potential for translation into the clinical routine.PMID:39806417 | DOI:10.1186/s12933-025-02581-3

BMC Genomics. 2025 Jan 13;26(1):30. doi: 10.1186/s12864-025-11208-6.ABSTRACTBACKGROUND: Megalobrama amblycephala presents unsynchronized growth, which affects its productivity and profitability. The liver is essential for substance exchange and energy metabolism, significantly influencing the growth of fish.RESULTS: To investigate the differential metabolites and genes governing growth, and understand the mechanism underlying their unsynchronized growth, we conducted comprehensive transcriptomic and metabolomic analyses of liver from fast-growing (FG) and slow-growing (SG) M. amblycephala individuals. A total of 2,097 differentially expressed genes (DEGs) were identified between FG and SG, with 830 genes exhibiting significantly higher expression level in FG. KEGG and GO enrichment analysis indicated that the DEGs with higher expression level were significantly correlated with insulin signaling pathway, steroid hormone and lipid metabolism related pathway (PPAR signaling pathway and fatty acid degradation). In the metabolomic analysis, 224 differentially expressed metabolites (DEMs) were detected, of which 128 were significantly more abundant in FG. These more abundant DEMs were prominently enriched in pathways associated with cell proliferation and energy metabolism (Oxidative phosphorylation, mTOR signaling pathway and FoxO signaling pathway). In addition, DEGs and DEMs in adenosine diphosphate (ATP) hydrolysis activity and associate with fatty acid metabolism, glucose metabolism, and amino acid metabolism pathways were both found in the transcriptomic and metabolomic integrated data. These findings suggest that the large amounts of energy generated by fatty acid, glucose metabolism and other energy metabolism pathway promote the rapid growth of FG.CONCLUSIONS: This research is the first to integrate metabolomic and transcriptomic analyses of liver to identify key genes, metabolites, and pathways to uncover the molecular and metabolic mechanisms of unsynchronized growth in M. amblycephala. The identified metabolic and genes can be potential targets for selective breeding programs to improve growth performance in aquaculture.PMID:39806290 | DOI:10.1186/s12864-025-11208-6

BMC Genom Data. 2025 Jan 13;26(1):3. doi: 10.1186/s12863-024-01294-y.ABSTRACTBACKGROUND: Wheat seeds display different colors due to the types and contents of anthocyanins, which is closely related to anthocyanin metabolism. In this study, a transcriptomic and metabolomic analysis between white and purple color wheat pericarp aimed to explore some key genes and metabolites involved in anthocyanin metabolism.RESULTS: Two wheat cultivars, a white seed cultivar Shiluan02-1 and purple seed cultivar Hengzi151 were used to identify the variations in differentially expressed genes (DEGs) and differentially accumulated flavonoids (DAFs). Based on metabolomic data, 314 metabolites and 191 DAFs were identified. Chalcone, flavonol, pro-anthocyanidin and anthocyanidin were the most differentially accumulated flavonoid compounds in Hengzi151. 2610 up-regulated and 2668 down-regulated DEGs were identified according to transcriptomic data. The results showed that some structural genes in anthocyanin synthesis pathway were prominently activated in Hengzi151, such as PAL, CAD, CHS and so on. Transcription factors (TFs) of MYB, bHLH, WD40 and some other TFs probably involved in regulating anthocyanin biosynthesis were identified. Some genes from hormone synthetic and signaling pathways that may participate in regulating anthocyanin biosynthesis also have been identified.CONCLUSIONS: Our results provide valuable information on the candidate genes and metabolites involved in the anthocyanin metabolism in wheat pericarp.PMID:39806276 | DOI:10.1186/s12863-024-01294-y

Plant Cell Rep. 2025 Jan 13;44(2):30. doi: 10.1007/s00299-024-03410-9.ABSTRACTCannabis trichome development progresses in distinct phases that underpin the dynamic biosynthesis of cannabinoids and terpenes. This study investigates the molecular mechanisms underlying cannabinoid and terpenoid biosynthesis in glandular trichomes of Cannabis sativa (CsGTs) throughout their development. Female Cannabis sativa c. Hindu Kush were cultivated under controlled conditions, and trichome development was analysed from week 3 to week 8 of the flowering period. We employed light microscopy, quantitative metabolomics and proteomics to analyse morphological changes in trichome secretory cell development, and temporal changes in metabolite accumulation and protein abundance. Our findings identified three distinct developmental phases: pre-secretory (T3), secretory (T6), and post-secretory (T8), the first time the three phases of trichome development have been identified and investigated in CsGTs. The pre-secretory phase was characterized by smaller secretory cells, limited metabolite accumulation and elevated levels of proteins involved in protein biosynthesis and cellular development. The secretory phase exhibited the highest biosynthetic activity, marked by larger secretory cells, increased plastidal activity, central carbon metabolism, and significant accumulation of cannabinoids and terpenoids. The post-secretory phase showed a decrease in secretory cell size, reduced metabolic activity, and a decrease in the abundance of primary and secondary metabolism enzymes, although THCA continued to accumulate. Key enzymes showed dynamic changes correlating with the stages of trichome development. This study provides a comprehensive understanding of the molecular mechanisms regulating cannabinoid and terpenoid biosynthesis in CsGTs, offering insights for enhancing the production of these valuable compounds through targeted breeding and biotechnological approaches.PMID:39806251 | DOI:10.1007/s00299-024-03410-9

EMBO J. 2025 Jan 13. doi: 10.1038/s44318-024-00339-3. Online ahead of print.ABSTRACTPolyglucosans are glycogen molecules with overlong chains, which are hyperphosphorylated in the neurodegenerative Lafora disease (LD). Brain polyglucosan bodies (PBs) cause fatal neurodegenerative diseases including Lafora disease and adult polyglucosan body disease (ABPD), for which treatments, biomarkers, and good understanding of their pathogenesis are currently missing. Mutations in the genes for the phosphatase laforin or the E3 ubiquitin ligase malin can cause LD. By depleting PTG, an activator of the glycogen chain-elongating enzyme glycogen synthase (GYS1), in laforin- and malin-deficient LD mice, we show that abnormal glycogen chain lengths and not hyperphosphorylation underlie polyglucosan formation, and that polyglucosan bodies induce neuroinflammation. We provide evidence indicating that a small pool of overactive GYS1 contributes to glycogen insolubility in LD and APBD. In contrast to previous findings, metabolomics experiments using in situ-fixed brains reveal only modest metabolic changes in laforin-deficient mice. These changes are not replicated in malin-deficient or APBD mice, and are not normalized in rescued LD mice. Finally, we identify a pool of metabolically volatile malto-oligoglucans as a polyglucosan body- and neuroinflammation-associated brain energy source, and promising candidate biomarkers for LD and APBD, including malto-oligoglucans and the neurodegeneration marker CHI3L1/YKL40.PMID:39806098 | DOI:10.1038/s44318-024-00339-3

Sci Rep. 2025 Jan 13;15(1):1796. doi: 10.1038/s41598-025-86083-y.ABSTRACTSweet corn is highly susceptible to water deprivation, making it crucial to identify effective strategies for enhancing its tolerance to water deficit conditions. This study investigates the novel application of Spermine as a bio-stimulant to improve sweet corn (Zea mays L. var. saccharata) resilience under hydroponic water deficit conditions. Four genotypes (Dessert, Messenger, Tyson, and Royalty) were treated with Spermine (0.2 mM foliar application), polyethylene glycol 6000 (8% and 12%), and their combinations. The impacts on growth parameters, photosynthetic performance, and oxidative stress markers were evaluated. Spermine significantly enhanced biomass parameters, counteracting the severe reductions caused by PEG-induced water deprivation. In the Dessert and Tyson genotypes, total biomass increased by 145%, while it increased by 118% in Messenger and 110% in Royalty when treated with Spermine under severe water deprivation. However, Spermine treatment application did not recorded higher differences compared to control under non water deficit conditions. In the Dessert genotype, root length increased by 36.6% under combined treatment compared to 12% PEG alone. Spermine also mitigated reductions in shoot length, improved by 90.6% and specific leaf area, with a notable 272.6% increase in Tyson under severe water deficit. Photosynthetic performance, including chlorophyll and carotenoid levels, was enhanced, with a 103.1% increase in relative chlorophyll content in Dessert under severe water deprivation. Spermine also reduced oxidative damage, as indicated by a 48.7% decrease in malondialdehyde levels in Tyson, and increased peroxidase activity, enhancing antioxidant defense in Messenger under severe water deprivation. The quantum efficiency of Photosystem II, which was significantly reduced by water deficit, showed substantial improvement with Spermine treatment, with increases of 107.2% in Tyson and 99.4% in Royalty under moderate water deprivation. These results highlight the potential of Spermine as an effective strategy to improve sweet corn resilience under water-limited conditions, offering a novel approach for sustainable crop management.PMID:39806014 | DOI:10.1038/s41598-025-86083-y

Sci Rep. 2025 Jan 13;15(1):1812. doi: 10.1038/s41598-025-86310-6.ABSTRACTOcean surface temperatures and the frequency and intensity of marine heatwaves are increasing worldwide. Understanding how marine organisms respond and adapt to heat pulses and the rapidly changing climate is crucial for predicting responses of valued species and ecosystems to global warming. Here, we carried out an in situ experiment to investigate sublethal responses to heat spikes of a functionally important intertidal bivalve, the venerid clam Austrovenus stutchburyi. We describe changes in metabolic responses under two warming scenarios (five days and seven days) at two sites (muddy and sandy). Tidal flat warming during every low tide for five days affected the abundance of multiple functional metabolites within this species. The metabolic response was related to pathways such as metabolic energetics, amino acid and lipid metabolism, and accumulation of stress-related metabolites. There was some recovery after cooler weather during the final two days of the experiment. The degree of change was greater in muddy versus sandy sediments. Our findings provide new evidence of the metabolomic response of these important bivalve to heat stress, which could be used for resource managers when implementing strategies to mitigate the impacts of climate change on valuable marine resources.PMID:39805974 | DOI:10.1038/s41598-025-86310-6

Zhongguo Zhong Yao Za Zhi. 2024 Dec;49(23):6468-6480. doi: 10.19540/j.cnki.cjcmm.20240912.501.ABSTRACTThis article aims to analyze the therapeutic effect and probe into the mechanism of Sanhuang Hushen Fangshuai Decoction in treating chronic kidney disease(CKD) based on metabolomics and bioinformatics. The patients with stage 3-4 CKD diagnosed and treated in the Changzhou Hospital of Traditional Chinese Medicine from June 2023 to March 2024 were enrolled in this study. The patients were treated with Sanhuang Hushen Fangshuai Decoction, and the therapeutic effect was evaluated. The serum samples were collected before and after treatment. Ultra-performance liquid chromatography was employed to detect metabolites in the serum, and multivariate statistical analysis was performed. Bioinformatics was employed to screen the active components and targets of the decoction and the potential targets of CKD. The protein-protein interaction(PPI) network of the common targets shared by the decoction and CKD and the drug-component-target network were constructed. The core components and targets were screened according to the correlation degree of the network. The binding between core components and targets was verified by molecular docking. The results showed that Sanhuang Hushen Fangshuai Decoction improved the renal function and reduced proteinuria. Compared with the healthy population, the post-treatment population showed recovery of 54 up-regulated metabolites and 43 down-regulated metabolites. Enrichment analysis results showed that the key pathways included adenosine triphosphate binding cassette(ABC) transport, tryptophan metabolism, and tyrosine metabolism. The results of bioinformatics analysis showed that the core components of Sanhuang Hushen Fangshuai Decoction in treating CKD included kaempferol, β-sitosterol, luteolin, 7-O-methylisolingol, and tanshinone Ⅱ_A. The core targets included TP53, PTGS2, JUN, AKT1, and TNF. Molecular docking results showed that the core components bound well to the target genes. The results of joint pathway analysis suggested that both differential metabolites and key targets were involved in galactose metabolism, nicotinamide metabolism, and other pathways. This study suggests that Sanhuang Hushen Fangshuai Decoction is effective for CKD, and it can regulate multiple abnormal metabolites and participates in multiple metabolic pathways involving amino acids and sugars. The active components such as kaempferol in the decoction may regulate related targets such as TP53 and PTGS2. This study provides a basis for the prevention and treatment of CKD with traditional Chinese medicine.PMID:39805793 | DOI:10.19540/j.cnki.cjcmm.20240912.501

Zhongguo Zhong Yao Za Zhi. 2024 Dec;49(23):6417-6428. doi: 10.19540/j.cnki.cjcmm.20240802.701.ABSTRACTIn order to elucidate the therapeutic effect and mechanism of action of Zhengqing Fengtongning Sustained-release Tablets on knee osteoarthritis, this study created a knee osteoarthritis model using 0.2 mL 40 g·L~(-1) papain and randomly divided the rats into the model group, high-dose and low-dose groups of Zhengqing Fengtongning Sustained-release Tablets, and celecoxib group. All groups were given the drug for four weeks, with the diameter of their knee joint being measured during this period. Hematoxylin-eosin staining and Senna solid green staining were utilized to observe the pathology of knee joint tissue in SD rats. The initial therapeutic impact of Zhengqing Fengtongning Sustained-release Tablets on knee osteoarthritis in rats was assessed by monitoring the levels of interleukin-1β(IL-1β) and interleukin-6(IL-6) in the plasma. Using a combination of non-targeted metabolomics and 16S rRNA techniques, researchers determined the variations in endogenous molecules and intestinal flora in rats and identified potential biomarkers. The results showed that Zhengqing Fengtongning Sustained-release Tablets improved the diameter of knee joint swelling, ameliorated the pathological damage of cartilage tissue, and reduced the plasma levels of IL-1β and IL-6 in rats with knee osteoarthritis. Metabolomics analysis identified 22 potential biomarkers associated with the modulatory effects of Zhengqing Fengtongning Sustained-release Tablets, including 5-hydroxytryptamine, corticosterone, methylmalonic acid, and other biomarkers, which were mainly involved in eight metabolic pathways, including tryptophan metabolism, vitamin K metabolism, steroid synthesis, and so on. The results of intestinal flora showed a decrease in the diversity of intestinal flora in the model group, an increase in the diversity of intestinal flora, and an improvement in the microecology of intestinal flora. Significant differences were found in Lachnospiraceae＿NK4A136＿group, Helicobacter, Lactobacillus, Bacteroides, and Parabacteroides. Finally, the results of the combined analysis showed that 22 biomarkers were correlated with five genera. The above results indicate that Zhengqing Fengtongning Sustained-release Tablets can improve the tissue morphology and structure of knee joints, reduce the level of plasma inflammatory factors, regulate the diversity of intestinal flora, and balance the metabolic pathways of steroid synthesis, vitamin K metabolism, and tryptophan metabolism to exert a therapeutic effect on knee osteoarthritis.PMID:39805788 | DOI:10.19540/j.cnki.cjcmm.20240802.701

Zhongguo Zhong Yao Za Zhi. 2024 Dec;49(24):6773-6783. doi: 10.19540/j.cnki.cjcmm.20240712.709.ABSTRACTThis paper explored the protective effect and potential mechanism of Shouhui Tongbian Capsules(SHTB) on cerebral ischemia-reperfusion rat models. Rats were randomly divided into sham surgery group, model group, low-dose SHTB group(0.2 g·kg~(-1)·d~(-1)), high-dose SHTB group(SHTB g·kg~(-1)·d~(-1)), and an edaravone positive drug group(5.4 mg·kg~(-1)·d~(-1)), with 12 rats in each group. Rats were given continuous intragastric administration seven days before surgery, and the suture method was used to establish the cerebral ischemia-reperfusion injury(CIRI) rat model. Zea-Longa rating scale for neurological functions was used to assess the degree of neurological function impairment in rats; hematoxylin-eosin(HE) staining was used to observe the pathological damage of rats' brain tissue; TTC staining was used to measure the area of cerebral infarction in rats; enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in each group. Western blot was used to detect the level of tight junction protein associated with the blood-brain barrier and intestinal barrier, as well as the protein expression of the TLR4/MyD88/NF-κB pathway in brain tissue. Changes in rats' brain tissue and metabolites in serum were detected by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), so as to explore the potential mechanism of SHTB treatment for CIRI in rats. Compared with the model group, SHTB could significantly alleviate the pathological damage to the brain of CIRI rats, reduce the volume of cerebral infarction, and lower the level of inflammation in the serum; Western blot results showed that SHTB could regulate the expression of tight junction proteins related to the blood-brain barrier and intestinal barrier in CIRI rats and downregulate the expression of TLR4, NF-κB, and MyD88 proteins in brain tissue. The UPLC-MS/MS results indicated that SHTB could significantly regulate the content of potential differential metabolites such as fatty acids, and serum and brain tissue are involved in pathways such as unsaturated fatty acid biosynthesis. SHTB could repair intestinal barrier function, reduce inflammation levels in the body, and improve the damaged blood-brain barrier, exerting a protective effect on brain nerves. Its mechanism may be achieved by balancing fatty acid metabolism and regulating the expression of TLR4/MyD88/NF-κB signaling pathway proteins.PMID:39805766 | DOI:10.19540/j.cnki.cjcmm.20240712.709

Zhongguo Zhong Yao Za Zhi. 2024 Dec;49(24):6735-6745. doi: 10.19540/j.cnki.cjcmm.20240621.401.ABSTRACTThis study aims to investigate the protective effect and potential mechanism of Jingfang Granules(JF) on the mouse model of chronic fatigue syndrome(CFS). Mice were randomized into normal, model, and low-, medium-, and high-dose(0.9, 1.8, and 3.6 g·kg~(-1)·d~(-1), respectively) JF groups according to the body weight. In addition to the normal group, other groups of mice received exhaustive swimming training and tail suspension training every day for the modeling of CFS. The mice in each administration group were administrated with JF at the corresponding dose by gavage, and those in the other groups were administrated with an equal amount of purified water. The exhaustive swimming and tail suspension tests were conducted in each group. The UV-glutamate dehydrogenase method was used to determine the serum level of urea nitrogen(UREA), and the lactate dehydrogenase(LDH) assay kit was used to determine the LDH level. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in the serum, muscle tissue, and brain tissue of mice in each group. Western blot was employed to determine the expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), nuclear factor-kappa B(NF-κB) and their phosphorylated proteins in the muscle tissue of mice. The 16S rDNA sequencing and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) were adopted to detect the changes of intestinal flora and intestinal metabolites in mice. Compared with the model group, JF significantly prolonged the swimming exhaustion time and shortened the tail suspension time of the model mice, lowered the levels of LDH and UREA in the serum as well as the levels of IL-6 and TNF-α in the serum, muscle tissue, and brain tissue of CFS mice. In addition, JF down-regulated the expression of TLR4, MyD88, and p-NF-κB/NF-κB in the muscle tissue of CFS mice compared with the model group. The results of 16S rDNA sequencing demonstrated that JF ameliorated the intestinal flora disorder of CFS mice. The results of UPLC-MS/MS revealed that JF significantly affected the histidine metabolism pathway in the intestinal tract of CFS mice. Spearman analysis displayed that histamine, a metabolite involved in histidine metabolism, was negatively correlated with the abundance of Clostridia＿UCG-014, Dubosiella, and RF39 and positively correlated with the abundance of Coriobacteriaceae＿UCG-002. The metabolite imidazole-4-acetaldehyde was negatively correlated with the abundance of Clostridia＿UCG-014, Dubosiella, and RF39 and positively correlated with the abundance of Coriobacteriaceae＿UCG-002. In conclusion, JF can increase the swimming exhaustion time, reduce the immobility time of tail suspension, lower serum LDH and UREA levels, and alleviate inflammation response. It may exert the therapeutic effect by improving intestinal flora homeostasis and inhibiting histidine metabolism by down-regulating the expression of proteins in the TLR4/MyD88/NF-κB signaling pathway, thereby relieving the symptoms of CFS in mice.PMID:39805762 | DOI:10.19540/j.cnki.cjcmm.20240621.401

Am J Clin Nutr. 2025 Jan 11:S0002-9165(25)00013-9. doi: 10.1016/j.ajcnut.2025.01.013. Online ahead of print.ABSTRACTBACKGROUND: A proinflammatory diet has been linked to an increased risk of breast cancer. However, the underlying metabolic roles remain to be elucidated.OBJECTIVE: To investigate the metabolic mechanism between proinflammatory diet and breast cancer risk.METHODS: This prospective study included 273,324 females from the UK Biobank. The dietary inflammatory potential was assessed via an energy-adjusted dietary inflammatory index (E-DII) based on a 24-hour recall questionnaire. The plasma metabolome was profiled via high-throughput nuclear magnetic resonance spectroscopy (NMR). A metabolic signature was constructed by summing selected metabolite concentrations weighted by the coefficients via absolute shrinkage and selection operator (LASSO) analysis. Multivariate Cox regression was applied to assess the associations of the E-DII and metabolic signature with breast cancer risk.RESULTS: We constructed a metabolic signature comprising 26 metabolites associated with a proinflammatory diet. These metabolites primarily included lipoproteins, amino acids, fatty acids, and ketone bodies. Both the E-DII and metabolic signature were positively associated with breast cancer risk (hazard ratio [HR] comparing the highest quintile to the lowest quintile = 1.17, 95% confidence interval [CI] = (1.04, 1.32); and 1.21, 95% CI = (1.01, 1.46), respectively). Furthermore, we found that saturated fatty acids to total fatty acids percentage and acetone concentration were positively associated (HR = 1.20, 95% CI = (1.04, 1.37); 1.15, 95% CI = (1.01, 1.32), respectively), while the degree of unsaturation was inversely associated with breast cancer risk (HR = 0.86; 95% CI = 0.75, 0.99).CONCLUSION: We identified a metabolic signature that reflects a proinflammatory diet and is associated with an increased risk of breast cancer.PMID:39805559 | DOI:10.1016/j.ajcnut.2025.01.013

Environ Pollut. 2025 Jan 11:125664. doi: 10.1016/j.envpol.2025.125664. Online ahead of print.ABSTRACTThis study aims to investigate the physiological changes in growth and metabolic response mechanisms of highland barley under different concentrations of cadmium. To achieve this, cadmium stress was applied to green barley at levels of 20, 40, and 80 mg/L. The results revealed that, under Cd(II) stress, the chlorophyll content and photosynthesis in leaves of highland barley seedlings were inhibited to some extent. Additionally, the malondialdehyde (MDA) content and superoxide dismutase activity increased significantly, indicating that the seedlings were affected by oxidative stress. In addition, Cd(II) stress also significantly affected the accumulation of metabolites in highland barley seedlings, resulting in an increase in lipids and lipid molecules, organic heterocyclic compounds, and phenylpropanoids. Cd(II) stress also significantly interfered with phenylalanine metabolism, fructose and mannose metabolism, amino acid, sugar, and nucleotide sugar metabolism, and biosynthetic metabolic pathways of isoquinoline alkaloids. The increase in Cd(II) stress also resulted in elevated levels of soluble sugars, soluble proteins, and proline as defense mechanisms against the stress. Overall, barley has a very good ability to resist adversity, and the mechanism of barley's resistance to adversity has not been deeply investigated. Therefore, in this paper, we systematically investigated the stress resistance mechanism of barley to cadmium stress and found that the growth physiology and metabolism of barley seedlings were significantly affected by cadmium stress. Differential changes in metabolites and enrichment of metabolic pathways may be the main mechanisms for barley seedlings to cope with Cd(II) stress . This provides direction for selecting better varieties of barley.PMID:39805469 | DOI:10.1016/j.envpol.2025.125664

Environ Pollut. 2025 Jan 11:125677. doi: 10.1016/j.envpol.2025.125677. Online ahead of print.ABSTRACTLead (Pb), one of the most ubiquitous and harmful contaminants of farmland, seriously threatens soil health and food security. Silicon nanoparticles (SiNPs) have potential applications in soil remediation and phytoremediation. Yet, how SiNPs influence plant growth under Pb stress remains poorly understood. In this study, the candidate Pb-hyperaccumulator Lolium multiflorum was selected to investigate the toxicity of Pb and the mitigation of Pb stress by SiNPs. The application of SiNPs was able to enhance Pb enrichment and maintain proper photosynthesis and root growth of L. multiflorum. Transcriptomic and metabolomic analyses indicated that Pb exposure interfered with nitrogen metabolism and alanine, aspartate and glutamate metabolism pathways in roots, which changed the root exudate composition. Besides, SiNPs altered both the accumulation of metabolites and correlated gene expression in roots, further affecting root exudates and stimulating the defense system, consequently increasing Pb tolerance. Our findings both demonstrated that co-application of L. multiflorum with SiNPs has potential for phytoremediation of Pb-polluted soil and revealed the contributions of SiNP amendment to mitigating Pb toxicity, and provided a new strategy for phytoremediation of farmland ecosystems.PMID:39805468 | DOI:10.1016/j.envpol.2025.125677

Aquat Toxicol. 2025 Jan 12;279:107217. doi: 10.1016/j.aquatox.2024.107217. Online ahead of print.ABSTRACTImproving the understanding of how chemicals affect on organisms and assessing the associated environmental risks is of major interest in environmental studies. This can be achieved by using complementary approaches based on the study of the molecular responses of organisms. Because of the known chemical pressures on the environment, regulations on the content of some chemicals, such as cadmium, have been mostly completed. In contrast, the environmental toxicity of rare earth elements (REEs), which are widely used in industry, has only recently begun to receive attention. Here, we investigated the effects of cadmium, and two REEs, samarium and gadolinium, on marine mussels under laboratory exposures. We found that after an 8-day exposure at 500 µg/L, the metals were bioaccumulated by the mussels. Furthermore, samarium and gadolinium affected two oxidative stress biomarkers, GST and SOD. Lipidomic analysis showed that lipid content was modulated by the REEs, but not by cadmium. Interestingly, several compounds belonging to the phosphoinositide metabolism were more abundant, suggesting a pro-mitotic or cell survival response, while a higher abundance of cardiolipins after samarium exposure suggested an alteration of mitochondrial activity. Moreover, depending on the tissue and the metal considered, transcriptional analyses revealed an effect on metallothionein, hsp70/90, energy metabolism enzymes, as well as pro-mitotic transcript accumulation. Thus, this study sheds a new light on metal toxicity and in particularl REEs by highlighting the accumulation and toxicity of cadmium, samarium and gadolinium at 500 µg/L at different molecular levels, from gene expression to the lipidome of blue mussels.PMID:39805254 | DOI:10.1016/j.aquatox.2024.107217

Talanta. 2025 Jan 10;286:127460. doi: 10.1016/j.talanta.2024.127460. Online ahead of print.ABSTRACTSpatial metabolomics offers the combination of molecular identification and localization. As a tool for spatial metabolomics, mass spectrometry imaging (MSI) can provide detailed information on localization. However, molecular annotation with MSI is challenging due to the lack of separation prior to mass spectrometric analysis. Contrarily, surface sampling capillary electrophoresis mass spectrometry (SS-CE-MS) provides detailed molecular information, although the size of the sampling sites is modest. Here, we describe a platform for spatial metabolomics where MSI using pneumatically assisted nanospray desorption electrospray ionization (PA-nano-DESI) is combined with SS-CE-MS to gain both in-depth chemical information and spatial localization from thin tissue sections. We present the workflow, including the user-friendly setup and switching between the techniques, compare the obtained data, and demonstrate a quantitative approach when using the platform for spatial metabolomics of ischemic stroke.PMID:39805200 | DOI:10.1016/j.talanta.2024.127460