PubMed

Chem Biol Interact. 2025 Feb 28:111449. doi: 10.1016/j.cbi.2025.111449. Online ahead of print.NO ABSTRACTPMID:40024497 | DOI:10.1016/j.cbi.2025.111449

Mol Cells. 2025 Feb 28:100200. doi: 10.1016/j.mocell.2025.100200. Online ahead of print.ABSTRACTColorectal cancer (CRC) continues to rank among the deadliest and most prevalent cancers worldwide, necessitating an innovative and comprehensive approach that addresses this serious health challenge at various stages, from screening and diagnosis to treatment and prognosis. As CRC research progresses, the adoption of an omics-centered approach holds transformative potential to revolutionize the management of this disease. Advances in omics technologies encompassing genomics, transcriptomics, proteomics, metabolomics, and epigenomics allow to unravel the oncogenic alterations at these levels elucidating the intricacies and the heterogeneous nature of CRC. By providing a comprehensive molecular landscape of CRC, omics technologies enable the discovery of potential biomarkers for early non-invasive detection of CRC, definition of CRC subtypes, prediction of its staging, prognosis, and overall survival of CRC patients. They also allow the identification of potential therapeutic targets, prediction of drug response, tracking treatment efficacy, detection of residual disease and cancer relapse, and deciphering the mechanisms of drug resistance. Moreover, they allow the distinction of non-metastatic CRC patients from the metastatic ones as well as the stratification of metastatic risk. Importantly, omics technologies open up new opportunities to establish molecular-based criteria to guide selection of effective treatment paving the way for the personalization of therapy for CRC patients. This review consolidates current knowledge on the omics-based preclinical discoveries in CRC research emphasizing the significant potential of these technologies to improve CRC screening, diagnosis, prognosis and promote the implementation of personalized medicine to ultimately reduce CRC prevalence and mortality.PMID:40024318 | DOI:10.1016/j.mocell.2025.100200

Int Immunopharmacol. 2025 Mar 1;151:114364. doi: 10.1016/j.intimp.2025.114364. Online ahead of print.ABSTRACTOver the past decade, research has increasingly demonstrated that oligomeric α-synuclein (O-αS) plays a pivotal role in the pathogenesis of Parkinson's disease (PD), particularly in mediating dopaminergic neuron injury and neuroinflammation. In this study, we investigated the anti-inflammatory effects of tanshinone I (Tan I), an active component of the traditional Chinese medicine Danshen, on O-αS-induced inflammation in primary mouse astrocytes. Using metabolomics analysis, we identified key pathways regulated by Tan I. Our results showed that Tan I significantly suppressed O-αS-induced mRNA expression of pro-inflammatory cytokines, including interleukin-1β, IL-6, tumor necrosis factor-α and cyclooxygenase-2. Metabolomic profiling revealed that Tan I enhanced NAD+ metabolism, leading to activation of the NAD+-Sirt1 pathway and subsequent inhibition of nuclear factor-κB activity. Together, these findings suggest that Tan I attenuates neuroinflammatory response in astrocytes by modulating NAD+-dependent signaling mechanisms.PMID:40024217 | DOI:10.1016/j.intimp.2025.114364

Bioorg Med Chem. 2025 Feb 24;121:118128. doi: 10.1016/j.bmc.2025.118128. Online ahead of print.ABSTRACTSwertiamarin, a predominant component in many traditional Chinese swertia herbs, shows significant anti-HBV activity clinically. (R)-gentiandiol and (S)-gentiandiol are the metabolites of swertiamarin in vivo. In this study, HBsAg, HBeAg and HBV-DNA were determined in liver tissue of HBV-transgenic C57BL/6NCrl mice to analyze anti-HBV activities of swertiamarin, (R)-gentiandiol and (S)-gentiandiol. It was found that HBsAg, HBeAg and HBV-DNA levels were significantly reduced in a dose-dependent manner when (R)-gentiandiol was administered at 1.5, 3 and 6 mg/kg. However, (S)-gentiandiol showed no anti-HBV activity at all. In addition, we also performed untargeted metabolomics to discover biomarkers and metabolic pathways of swertiamarin and (R)-gentiandiol in HBV-transgenic C57BL/6NCrl mice. A total of 15 candidate biomarkers were obtained. Meanwhile, the metabolic disorders including 8 metabolic pathways, such as taurine and hypotaurine metabolism were explored. Taurine and hypotaurine metabolism was the primary pathway for (R)-gentiandiol to regulate HBV-transgenic C57BL/6NCrl mice. It is the first time to clarify real active anti-HBV metabolites of swertiamarin, which can offer more insights into anti-HBV activities of swertia herbs, and bring novel ideas for new drug development in anti-HBV herbs.PMID:40024145 | DOI:10.1016/j.bmc.2025.118128

J Pharm Biomed Anal. 2025 Feb 19;259:116761. doi: 10.1016/j.jpba.2025.116761. Online ahead of print.ABSTRACTArsenic (As)-induced hypertension is a significant public health concern, highlighting the need for early risk prediction. This study aimed to develop a predictive model for occupational As exposure and hypertension using metabolomics and machine learning. A total of 365 male smelting workers from southern regions were selected. Forty workers from high and low urinary arsenic (U-As) exposure groups were chosen for non-targeted metabolomics analysis. Univariate analysis revealed that U-As is a risk factor for blood pressure and hypertension (P < 0.05). Restricted cubic spline (RCS) analysis showed that both systolic and diastolic blood pressure, as well as hypertension risks, increased with U-As, with a threshold at 32 µg/L. Of 1145 metabolites, 383 differentially expressed metabolites (382 upregulated, 1 downregulated) were identified. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a predictive model for occupational hypertension, with N-hexosyl leucine, myristic acid, gamma-glutamylvaline, and pregnanediol disulfate as predictors. The area under the curve (AUC) of the receiver operating characteristic (ROC) for the predictive model was 0.917, indicating strong predictability and accuracy. This model, based on metabolomics and machine learning, provides an effective tool for early identification and intervention for occupational populations at high risk of hypertension due to As exposure.PMID:40024027 | DOI:10.1016/j.jpba.2025.116761

Poult Sci. 2025 Feb 17;104(4):104916. doi: 10.1016/j.psj.2025.104916. Online ahead of print.ABSTRACTThis study investigated the impact of light duration on Testosterone secretion in Chahua No.2 roosters, utilizing combined Transcriptome and Metabolome analyses to uncover critical genes, Metabolites, and signaling pathways. We randomly selected 240 Chahua No.2 roosters at 42 days old and divided them into four groups: simulated natural light (Ⅰ), 12L:12D (Ⅱ), 16L:8D (Ⅲ), and 20L:4D (Ⅳ), each group has 6 replicates, with 10 chickens per replicate. Blood samples were collected at 91 and 140 days post-hatch to measure Testosterone levels. Results showed that at 91 days, group Ⅳ had significantly higher Testosterone levels than groups Ⅰ, Ⅱ, and Ⅲ (P < 0.01), with group Ⅲ also higher than groups Ⅰ (P < 0.01) and Ⅱ (P < 0.05). By 140 days, group Ⅳ maintained significantly higher Testosterone than groups Ⅰ and Ⅱ (P < 0.01) and higher than group Ⅲ (P < 0.05), while group Ⅲ was also elevated compared to groups Ⅰ and Ⅱ (P < 0.05). Testicles Transcriptomics analysis revealed 891 differentially expressed genes, including 479 down-regulated and 412 up-regulated genes. Key signaling pathways identified included Steroid Hormone Biosynthesis, Cytochrome P450, and retinol metabolism. Testicles Metabolomics analysis identified 174 differential Metabolites, with 91 up-regulated and 83 down-regulated, focusing on pathways like Amino Sugar Metabolism and Tryptophan Metabolism. Integrated analysis pinpointed 19 common signaling pathways, with the top ten including Cytochrome P450, tyrosine metabolism, and amino acid biosynthesis. Our findings indicate that extending light duration enhances Testosterone secretion in roosters. Through comprehensive transcriptomic and metabolomic analyses, we established that pathways associated with steroid hormone synthesis and Cytochrome P450 play a crucial role in light duration-regulated Testosterone secretion, highlighting key genes such as CYP11A1, CYP17A1, and HSD3B1, alongside Metabolites like ergosterol-5,7,22,24(28)-tetraene-3beta-alcohol.PMID:40024014 | DOI:10.1016/j.psj.2025.104916

Ecotoxicol Environ Saf. 2025 Mar 1;292:117974. doi: 10.1016/j.ecoenv.2025.117974. Online ahead of print.ABSTRACTCottonseed meal is widely used as an alternative source of protein in the animal feed industry. However, the presence of toxic gossypol limits its use in livestock production. In order to reduce gossypol toxicity, microbial degradation is generally considered to be an environmentally friendly and cost-effective strategy. Candida tropicalis ZD-3 has demonstrated the ability to degrade gossypol. Nevertheless, the genome of gossypol-induced C. tropicalis ZD-3 has not been fully sequenced, and its comprehensive metabolic profile remains unexplored. In this study, the degradation rate of gossypol by ZD-3 reached 88.5 %, as determined by high performance liquid chromatography (HPLC). The characteristic peaks of amides were changed after gossypol treatment by Fourier transform infrared spectroscopy (FTIR) analysis. Genomic correlation results showed that gene function annotation revealed 64 protein-coding genes potentially involved in gossypol catabolism, primarily encoding aldehyde dehydrogenase, aldehyde reductase, and glutathione peroxidase. Metabolomic analysis indicated that gossypol activated ABC transporters and amino acid synthesis pathways, such as histidine, lysine, and arginine biosynthesis. These pathways provided substantial energy for C. tropicalis ZD-3 cells to cope with external stress, promoted the tricarboxylic acid (TCA) cycle, and formed a complex regulatory network for gossypol tolerance and degradation. This study marks the first revelation of gossypol metabolism in C. tropicalis, laying a foundation for further research on gossypol degradation and detoxification.PMID:40023996 | DOI:10.1016/j.ecoenv.2025.117974

Phytomedicine. 2025 Feb 24;140:156553. doi: 10.1016/j.phymed.2025.156553. Online ahead of print.ABSTRACTBACKGROUND: Parkinson's disease (PD) is a complex and multifactorial disorder of the nervous system. Tianma Gouteng Decoction (TGD) is a clinical prescription of traditional Chinese medicine for PD, but its neuroprotective effects and mechanisms for PD are poorly understood.PURPOSE: The aim of this study was to explore the mechanism of TGD in the treatment of PD.STUDY DESIGN: Serum pharmacochemistry, single cell sequencing, network pharmacology, and validation experiment were combined to study the effect of TGD in PD model.METHODS: TGD water extract and its distribution in serum of PD mice were analyzed by secondary metabolomics. The crossing blood-brain barrier components and targets were preliminarily identified. Target cells and pathways of TGD were analyzed by network pharmacology and single cell sequencing.RESULTS: TGD treatment improved the movement disorders in MPTP-induced PD mice, restoring dopaminergic neurons in the substantia nigra region and suppressing the expression of α-synuclein. We identified 1272 components in TGD, among which 73 were distributed in the serum of PD mice after oral administration. Network pharmacological analysis demonstrated that these components were involved in the regulation of apoptosis, and 15 of them could across the blood-brain barrier and bind to PD pathological proteins. Single nucleus RNA sequencing analysis identified 18 cell subpopulations, and TGD treatment restored the neuron-oligodendrocyte crosstalk. Neurons were identified as the most widely responding target cells, while oligodendrocytes were the core response target cells to TGD therapy. After treatment, the apoptosis of oligodendrocytes was inhibited, and the secretion of trophic factor was enhanced, facilitating the improvement of neuronal synaptic plasticity and neuroinflammation.CONCLUSION: This study systematically elucidates the molecular mechanism of TGD improving movement disorders, which is helpful to provide new ideas for drug development of PD.PMID:40023970 | DOI:10.1016/j.phymed.2025.156553

J Trace Elem Med Biol. 2025 Feb 27;88:127625. doi: 10.1016/j.jtemb.2025.127625. Online ahead of print.ABSTRACTThe outbreak of COVID-19 pandemic has caused substantial health loss worldwide, and the long-term sequelae of COVID, resulting from repeated coronavirus infection, have emerged as a new public health concern. We report the widespread presence of abnormal metallomic profiles in the sera of patients who have recovered from SARS-CoV-2 coronavirus infection, even after 6 months post-discharge from hospital. We measured the concentrations of Fe, Cu, Zn, Se, Cr, Mn, Ba, Ni, Pb, Ag, As, Cd, Co, and V in the sera of 25 recovered participants and 38 healthy controls in the cross-sectional study. Higher concentrations of Cu, Ag, As, Ba, Cd, Ni, Pb, Cr and V were observed in the recovered participants, whereas lower concentrations of Fe and Se were obtained in these participants. Except for Zn, Mn, and Co, all other elements showed significant differences (p < 0.05) between the two groups, with variations dependent on age and gender. Further correlation analysis between metallome and metabolome indicated that SARS-CoV-2 infection continues to disrupt metallic homeostasis and affect metabolic processes, such as lipid metabolism and cell respiration, as well as the functions of certain organs (e.g., liver, kidney, and heart), even after 6 months recovery. Our findings provide novel insights into the potential long-term effect of COVID-19 on the human body from a new perspective of metallomics.PMID:40023939 | DOI:10.1016/j.jtemb.2025.127625

J Pharmacol Exp Ther. 2025 Feb;392(2):100059. doi: 10.1016/j.jpet.2024.100059. Epub 2024 Dec 10.ABSTRACTChronic intestinal inflammation significantly contributes to the development of colorectal cancer and remains a pertinent clinical challenge, necessitating novel therapeutic approaches. Indole-based microbial metabolite mimics Felix Kopp Kortagere 6 (FKK6), which is a ligand and agonist of the pregnane X receptor (PXR), was recently demonstrated to have PXR-dependent anti-inflammatory and protective effects in a mouse model of dextran sodium sulfate (DSS)-induced acute colitis. Here, we examined the therapeutic potential of FKK6 in a mouse model (C57BL/6 FVB humanized PXR mice) of colitis-associated colon cancer (CAC) induced by azoxymethane and DSS. FKK6 (2 mg/kg) displayed substantial antitumor activity, as revealed by reduced size and number of colon tumors, improved colon histopathology, and decreased expression of tumor markers (c-MYC, β-catenin, Ki-67, and cyclin D) in the colon. In addition, we carried out a chronic toxicity (30 days) assessment of FKK6 (1 mg/kg and 2 mg/kg) in C57BL/6 mice. Histological examination of tissues, biochemical blood analyses, and immunohistochemical staining for Ki-67 and γ-H2AX showed no difference between FKK6-treated and control mice. Comparative metabolomic analyses in mice exposed for 5 days to DSS and administered with FKK6 (0.4 mg/kg) revealed no significant effects on several classes of metabolites in the mouse fecal metabolome. Ames and micronucleus tests showed no genotoxic and mutagenic potential of FKK6 in vitro. In conclusion, anticancer effects of FKK6 in azoxymethane/DSS-induced CAC, together with FKK6 safety data from in vitro tests and in vivo chronic toxicity study, and comparative metabolomic study, are supportive of the potential therapeutic use of FKK6 in the treatment of CAC. SIGNIFICANCE STATEMENT: Microbial metabolite mimicry proposes that chemical mimics of microbial metabolites that serve to protect hosts against aberrant inflammation in the gut could serve as a new paradigm for the development of drugs targeting inflammatory bowel disease if, like the parent metabolite, is devoid of toxicity but more potent against the microbial metabolite receptor. We identified a chemical mimic of Felix Kopp Kortagere 6, and we propose that Felix Kopp Kortagere 6 is devoid of toxicity yet significantly reduces tumor formation in an azoxymethane-dextran sodium sulfate model of murine colitis-induced colon cancer.PMID:40023602 | DOI:10.1016/j.jpet.2024.100059

Adv Food Nutr Res. 2025;113:423-474. doi: 10.1016/bs.afnr.2024.09.007. Epub 2024 Oct 11.ABSTRACTThis chapter explores the application of omics technologies in food mycology, emphasizing the significant impact of filamentous fungi on agriculture, medicine, biotechnology and the food industry. The chapter delves into the importance of understanding fungal secondary metabolism due to its implications for human health and industrial use. Several omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, are reviewed for their role in studying the genetic potential and metabolic capabilities of food-related fungi. The potential of CRISPR/Cas9 in fungal research is highlighted, showing its ability to unlock the full genetic potential of these organisms. The chapter also addresses the challenges posed by Big Data research in Omics and the need for advanced data processing methods. Through these discussions, the chapter highlights the future benefits and challenges of omics-based research in food mycology and its potential to revolutionize our understanding and utilization of fungi in various domains.PMID:40023565 | DOI:10.1016/bs.afnr.2024.09.007

Adv Food Nutr Res. 2025;113:383-422. doi: 10.1016/bs.afnr.2024.09.013. Epub 2024 Oct 18.ABSTRACTEnteric pathogens, particularly bacterial pathogens, are associated with millions of cases of foodborne illness in the U.S. and worldwide, necessitating the identification and development of methods to control and minimize their impact on public health. Predictive modeling and quantitative microbial risk assessment are two such methods that analyze data on microbial behavior, particularly as a response to changes in the food matrix, to predict and control the presence and prevalence of these pathogens in food. However, a number of these bacterial enteric pathogens, including Escherichia coli, Listeria monocytogenes, and Salmonella enterica, have inherent genetic and phenotypic differences among their subtypes and variants. This has led to an increasing reliance on "omics" technologies, including genomics, proteomics, transcriptomics, and metabolomics, to identify and characterize pathogenic microorganisms and their behavior in food systems. With this exponential increase in available data on these enteric pathogens, comes a need for the development of novel strategies to analyze this data. Advanced data analysis/analytics is a means to extract value from these large data sources, and is considered the core of data processing. In the past few years, advanced data analytics methods such as machine learning and artificial intelligence have been increasingly used to extract meaningful, actionable knowledge from these data sources to help mitigate food safety issues caused by enteric pathogens. This chapter reviews the latest in research into the use of advanced data analytics, particularly machine learning, to analyze "omics" data of enteric bacterial pathogens, and identifies potential future uses of these techniques in mitigating the risk of these pathogens on public health.PMID:40023564 | DOI:10.1016/bs.afnr.2024.09.013

Mol Pharmacol. 2025 Feb;107(2):100007. doi: 10.1016/j.molpha.2024.100007. Epub 2024 Dec 12.ABSTRACTOrganic anion transporting polypeptide (OATP) 1B1 is crucial for hepatic uptake of many drugs and endogenous substrates. The clinically relevant OATP1B1 c.521 T>C (V174A) polymorphism exhibits reduced transport activity in vitro and in vivo in humans. Previously, we reported increased total phosphorylation of V174A-OATP1B1 compared to wild-type (WT)-OATP1B1, although the differentially phosphorylated sites remain to be identified. Lysine-acetylation, a key posttranslational modification (PTM), has not been investigated in OATP1B1. This study aimed to identify differential PTMs of WT-OATP1B1 and V174A-OATP1B1 by quantitatively comparing the relative abundance of modified peptides using liquid chromatography-tandem mass spectrometry-based proteomics and to assess the impact of these PTMs on OATP1B1 transport function using [3H]-estradiol-17-β-D-glucuronide as substrate in transporter-expressing human embryonic kidney 293 cells. We discovered that OATP1B1 is lysine-acetylated at 13 residues. Compared to WT-OATP1B1, V174A-OATP1B1 has increased concurrent phosphorylation at S659 and S663 and concurrent phosphorylation (at S659 and S663) and lysine-acetylation (at K650) (P < .05). Variants mimicking concurrent phosphorylation (S659E-S663E-OATP1B1) and concurrent phosphorylation and acetylation (K650Q-659E-S663E-OATP1B1) both demonstrated reduced substrate transport by 0.86 ± 0.055-fold and 0.65 ± 0.047-fold of WT-OATP1B1 (both P < .05), respectively. Single-site mimics of phosphorylation or lysine-acetylation at K650, S659, and S663 did not affect OATP1B1 transport function, indicating cooperative effects on OATP1B1 by concurrent PTMs. All variants and WT-OATP1B1 were primarily localized to the plasma membrane and colocalized with plasma membrane protein Na/K-ATPase as determined by immunofluorescent staining and confocal microscopy. The current study elucidates a novel mechanism in which concurrent serine-phosphorylation and lysine-acetylation impair OATP1B1-mediated transport, suggesting potential interplay between these PTMs in regulating OATP1B1. SIGNIFICANCE STATEMENT: Understanding organic anion transporting polypeptide (OATP1B1) regulation is key to predicting altered drug disposition. The Val174Ala-OATP1B1 polymorphism exhibits reduced transport activity and is the most effective predictor of statin-induced myopathy. Val174Ala-OATP1B1 was found to be associated with increased serine-phosphorylation at Ser659 and Ser663 and lysine-acetylation at Lys650; concurrent PTMs at these sites reduce OATP1B1 function. These findings revealed a novel mechanism involved in transporter regulation, suggesting potential interplay between these PTMs in governing hepatic drug transport and response.PMID:40023514 | DOI:10.1016/j.molpha.2024.100007

Int J Biol Macromol. 2025 Feb 27:141573. doi: 10.1016/j.ijbiomac.2025.141573. Online ahead of print.ABSTRACTPolygonum multiflorum Thunb (PM) is known for its potential to extend lifespan. Although the polysaccharides, the primary constituents of PM, remain largely unexplored in terms of their anti-aging effects and underlying mechanisms, this study investigates them in detail. The anti-aging effects of two purified polysaccharides from PM were evaluated: neutral polysaccharide (RPMP-N, weight average molecular weight 245.30 kDa) and acidic polysaccharide (RPMP-A, weight average molecular weight 28.45 kDa), using a D-Galactose-induced (D-Gal) aging mouse model. In the experimental group, RPMP-N and RPMP-A were administered at doses of 50 (low) and 150 mg/kg/day (high). The activity of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX), which are essential for scavenging free radicals and form a key part of the body's antioxidant defense system, was measured in aging mice. The results showed significant improvements following treatment with RPMP-N and RPMP-A. Additionally, both polysaccharides demonstrated the ability to repair and protect against liver and brain injuries. The expression of P16, P21, and P53 proteins, which regulate cellular senescence through distinct mechanisms, was significantly reduced in liver and brain tissues after treatment. Notably, untargeted metabolomics revealed that RPMP-N and RPMP-A exerted significant anti-aging effects in the D-Gal aging mouse model, primarily influencing metabolism pathways related to lysine, sphingolipids, cysteine, and methionine. In conclusion, these findings provide important insights into the anti-aging mechanisms of PM polysaccharides, supporting their potential for clinical applications, drug development, and regulatory science.PMID:40023426 | DOI:10.1016/j.ijbiomac.2025.141573

J Ethnopharmacol. 2025 Feb 27:119571. doi: 10.1016/j.jep.2025.119571. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Sanghuangporus, the dried fruiting body of Sanghuangporus vaninii (Ljub) L.W.Zhou et Y.C.Dai. As the main species of Sanghuang, it has been well-known and used commonly as a traditional medicinal and edible macrofungi for thousands of years in many countries, including China, Korea and Japan. Although it has good hepatoprotective activity, its potential efficacy and mechanism on liver fibrosis remain elusive.AIM OF THE STUDY: Total Sanghuangporus vaninii extract (TSH) was prepared by ethanol extraction to investigate its chemical components and to conduct an initial assessment of its efficacy and underlying mechanism in a murine model of liver fibrosis.MATERIALS AND METHODS: The chemical components of TSH were initially analyzed by UHPLC-Q-Orbitrap HRMS. To elucidate the effects of TSH, an in vivo model of fibrosis was established in mice using carbon tetrachloride (CCl4), followed by assessments of serum liver function and histopathological analysis. Besides, indicators related to liver fibrosis, hepatic stellate cells (HSCs) activation, inflammation response and ferroptosis related indicators were detected by western blotting, immunohistochemistry and real-time quantitative PCR (RT-qPCR) analysis. Additionally, the 16S rDNA sequencing and untargeted metabolomics analysis of intestinal microbiota were employed to investigating the role of TSH in gut microbiome. In vitro, the human hepatocyte line L02 was stimulated with erastin and treated with or without TSH to elucidate its underlying mechanism.RESULTS: The administration of TSH significantly improved serum indicators of liver injury in CCl4-induced fibrosis mice, reduced HSCs activation and collagen deposition, while inhibiting the expressions of transforming growth factor-β1(TGF-β1)/Smad signaling pathway. Notably, TSH treatment attenuated hepatocyte ferroptosis and lipid peroxidation both in vivo and in vitro, as evidenced by a marked decrease in liver iron and malondialdehyde (MDA) contents. In particular, TSH was demonstrated to activate the nuclear factor erythroid 2-related factor 2 (Nrf2)-glutathione peroxidase 4 (GPX4) signaling pathway, thereby protecting hepatocytes from ferroptosis with a particular enhancement of Nrf2 nuclear transcription. Furthermore, TSH influenced gut microbiota composition and ameliorated intestinal metabolic disorders. The increased abundance of Parasutterella and Olsenellas due to TSH treatment was significantly positively correlated with elevated phosphatidylcholines involved in linoleic acid metabolism, and negatively correlated with the reduction of fatty acyls. And the enrichment of intestinal linoleic acid metabolism presented a negative correlation in the reduction of liver fibrosis biomarkers.CONCLUSIONS: Our findings indicate that the TSH treatment exerts a significantly protective effect on CCl4-induced mice by ameliorating hepatic injury and ferroptosis damage, inhibiting HSCs activation and collagen deposition, and remodeling gut microbiota homeostasis and metabolic imbalance. Notably, TSH attenuated hepatocyte ferroptosis in liver fibrosis and exhibited upregulation of the Nrf2-GPX4 signaling pathway. Furthermore, TSH could enrich the abundance of Parasutterella and Olsenellas, which may contribute to intestinal linoleic acid metabolism, thereby contributing to the reduction of liver fibrosis damage. Our study provides more effective and unreported evidence of TSH in anti-fibrosis activity.PMID:40023344 | DOI:10.1016/j.jep.2025.119571

Gene. 2025 Feb 27:149371. doi: 10.1016/j.gene.2025.149371. Online ahead of print.ABSTRACTThe ornamental crabapple Malus (M.) 'Lollipop' is renowned for its compact growth and fragrant flowers. This study aims to elucidate the biosynthesis molecular mechanism of volatile organic compounds (VOCs) across four developmental stages of the M. 'Lollipop' flowers using metabolomics and transcriptomics analyses. Gas chromatography-mass spectrometry (GC-MS) identified 29 VOCs (aliphatic derivatives, benzenes, and alkanes) in M. 'Lollipop' flowers. Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) analysis highlights 14 key differential aromatic compounds (VIP≥1), featuring (Z)-3-hexen-1-yl acetate in stage 1, methyl benzoate in stage 2, benzyl alcohol and linalool in stage 3, and camphene and (Z)-3-hexen-1-ol in stage 4. (Z)-3-hexen-1-yl acetate was identified as a co-primary constituent in the four flowering stages, designated as a key and floral contributing metabolite (variable importance in projection (VIP) ≥ 1& odor activity value (OAV) ≥ 1). RNA sequencing revealed key genes including CAT, DXS, MVD, HMGCR, FDPS, and TPSc in camphene and linalool synthesis, aroA, ADT, PDT, PAL, BEBT1, SDR, 4CL, CNL, and BALDH for benzyl alcohol, benzaldehyde, and methyl benzoate production. And PLA2G, SPLA2, TGL4, LOX2S and ADH1 in (Z)-3-hexen-1-yl acetate and (Z)-3-hexen-1-ol synthesis. 24 transcription factors (TFs) were predicted to be closely linked to genes involved in VOC synthesis. The findings above deepen our comprehension of the floral scent in crabapple, laying a foundation for further investigations into their functions and potential industrial applications.PMID:40023340 | DOI:10.1016/j.gene.2025.149371

Bioresour Technol. 2025 Feb 27:132309. doi: 10.1016/j.biortech.2025.132309. Online ahead of print.ABSTRACTRecovering the nitrogen-rich biopolymer cyanophycin [(β-Asp-Arg)n] from algal-bacterial consortia enhances the reclamation of value-added chemicals from wastewater. However, the modulation of light/dark conditions on cyanophycin accumulation remain unknown. In this study, the trends and mechanisms of cyanophycin synthesis in algal-bacterial consortia under light/dark conditions were investigated. The results showed that cyanophycin production during the dark periods ranged from 137-150 mg/g MLSS (mixed liquid suspended solids), which was 32 %-38 % higher than those during the light period (p < 0.001). Metatranscriptomics results demonstrated that 50 metagenome-assembled genomes contribute to cyanophycin production, with the Planktothrix genus being the dominant contributor. Metabolomics findings suggested that algal-bacterial consortia produce higher level of arginine for cyanophycin synthesis under light conditions. This study demonstrates the feasibility of increasing cyanophycin production by merging light/dark cycles, and offers a novel strategy for high yield of valuable biopolymers from wastewater substrate.PMID:40023333 | DOI:10.1016/j.biortech.2025.132309

Brain Behav Immun. 2025 Feb 27:S0889-1591(25)00070-4. doi: 10.1016/j.bbi.2025.02.030. Online ahead of print.ABSTRACTAutism Spectrum Disorder (ASD) is a highly prevalent neurodevelopmental condition characterized by social communication deficits and repetitive/restricted behaviors. Several studies showed that oxidative stress and inflammation may contribute to ASD. Indeed, increased levels of oxygen radicals and pro-inflammatory molecules were described in the brain and peripheral blood of persons with ASD and mouse models. Despite this, a potential direct connection between oxidative stress and inflammation within specific brain areas and ASD-related behaviors has not been investigated in detail yet. Here, we used RT-qPCR, RNA sequencing, metabolomics, immunohistochemistry, and flow cytometry to show that pro-inflammatory molecules were increased in the cerebellum and periphery of mice lacking Cntnap2, a robust model of ASD. In parallel, oxidative stress was present in the cerebellum of mutant animals. Systemic treatment with N-acetyl-cysteine (NAC) rescued cerebellar oxidative stress, inflammation, as well as motor and social impairments in Cntnap2-/- mice, concomitant with enhanced function of microglia cells in NAC-treated mutants. Intriguingly, social deficits, cerebellar inflammation, and microglia dysfunction were induced by NAC in Cntnap2+/+ animals. Our findings suggest that the interplay between oxidative stress and inflammation accompanied by genetic vulnerability may underlie ASD-related behaviors in Cntnap2 mutant mice.PMID:40023202 | DOI:10.1016/j.bbi.2025.02.030

Talanta. 2025 Feb 23;291:127812. doi: 10.1016/j.talanta.2025.127812. Online ahead of print.ABSTRACTBreast cancer (BC) is the primary cause of cancer-related deaths in women. Currently, the discovery of biomarkers primarily relies on single platform, which might overlook other potential biomarkers and lead to inaccurate diagnoses. This study aims to: (1) expand the detection range of biomarkers through multiple analytical techniques, thereby improving the accuracy of BC diagnosis, and (2) analyze the metabolic pathways of the biomarkers to explore the metabolic mechanisms underlying BC. Urine samples from BC patients and healthy controls were analyzed using two techniques: Ultra-high performance liquid chromatography combined with Quadrupole-Exactive-Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS), and headspace solid-phase microextraction combined with gas chromatography-high resolution mass spectrometry (HS-SPME/GC-HRMS). Data from each platform was analyzed independently using both univariate and multivariate statistical approaches to identify candidate biomarkers. Subsequently, a mid-level data fusion approach was applied to integrate the candidate biomarkers identified by each platform. The fused data were used to construct orthogonal partial least squares discriminant analysis (OPLS-DA) models and random forest (RF) models, which were then compared against models based on individual platform. The fused RF and OPLS-DA models demonstrated enhanced diagnostic accuracy compared to the individual model. Integrating GC-HRMS and UPLC-Q-Exactive Orbitrap-MS achieved the best performance, with an AUC value of 0.967, sensitivity of 86.37 %, and specificity of 89.19 %. Metabolic pathway analysis revealed that 10 metabolic pathways exert an impact on BC. Four pathways-pyruvate metabolism, sulfur metabolism, taurine and hypotaurine metabolism, and tyrosine metabolism-were found to be associated with BC in both metabolomics and volatolomics studies, indicating that these pathways play pivotal roles in BC. This study confirmed the potential of merging multi-platforms to enhance the accuracy of BC diagnosis, offering new avenues for understanding the metabolic mechanisms of BC.PMID:40023122 | DOI:10.1016/j.talanta.2025.127812

Phytomedicine. 2025 Feb 20;139:156537. doi: 10.1016/j.phymed.2025.156537. Online ahead of print.ABSTRACTBACKGROUND: Hyperlipidemia is a lipid metabolism disorder that, in severe cases, can lead to conditions such as hypertension, coronary heart disease, and cirrhosis. Previous studies have identified Ilicis Rotundae Cortex (IRC) crude extract as having the potential to regulate blood lipids. However, whether the triterpenoids therein are the principal agents responsible for hypolipidemic effects and their specific mechanisms of action remain unexplored. This study aimed to investigate the effects of total triterpenoids (TT) extract derived from IRC on hyperlipidemia and to elucidate their potential mechanisms.METHODS: TT extract was first prepared and characterized to assess their hypolipidemic activity in cell models. A hyperlipidemia mouse model was established by using C57BL/6 J mice fed a high-fat, high-sugar, and high-cholesterol diet for 8 weeks. TT extract was administered as a prophylactic intervention for 4 weeks to evaluate its impact on blood lipid levels, liver lipid metabolism, and liver function. Based on progressive analysis, this study integrated serum non-targeted metabolomics analysis strategy and bile acids-targeted metabolomics analysis strategy. It was combined with modern molecular biology techniques to reveal the mechanism by which TT extract ameliorated the symptoms of hyperlipidemia through a cascade approach.RESULTS: TT extract treatment significantly reduced lipid levels in hyperlipidemic mice. Notably, TT extract down-regulated bile acid levels, particularly bile acids as FXR antagonists such as T-β-MCA, β-MCA, TUDCA, and UDCA. This effect is likely mediated through alterations in the hepatic FXR-SHP and ileal FXR-FGF15 signaling pathways. TT extract administration led to decreased expression of CYP7A1 and CYP7B1, resulting in reduced bile acid levels in vivo. Additionally, FXR expression was upregulated in both the liver and ileum, potentially activating FGF15 in the ileum, which in turn transmits signals to the liver and modulates SHP and BSEP expression. These changes contribute to the regulation of bile acid synthesis, metabolism, and excretion. In vitro experiments also demonstrated that TT extract influenced the protein expression of FXR and FGF19.CONCLUSION: Our findings demonstrate that TT extract from IRC has hypolipidemic effects. This study is the first to reveal the mechanism by which TT extract improves hyperlipidemia from the perspective of the hepatic-intestinal axis and bile acid metabolism. Its underlying mechanism is related to activating the intestinal FXR-FGF15/19 signaling pathway, which transmits signals to the liver, thereby affecting the hepatic FXR-SHP signaling pathway. This results in improved bile acid metabolism, ultimately reducing hepatic injury and ileal inflammation to exert hypolipidemic effects.PMID:40023069 | DOI:10.1016/j.phymed.2025.156537