PubMed

Reprod Sci. 2025 Jan 30. doi: 10.1007/s43032-024-01779-2. Online ahead of print.ABSTRACTThe metabolomic approach has recently been used in the assessment of semen quality and male fertility. Additionally, the crucial roles of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) in metabolic syndrome (MetS) were reported. However, little information exists about the association between BCAAs and AAAs with semen parameters, particularly in men with and without MetS. Our objective was to explore the association between BCAAs and AAAs in blood and seminal plasma and sperm parameters in men with MetS (MetS +) and without MetS (MetS-). In a cross-sectional study between January-July 2022, we investigated 98 men (age: 25-42 years; MetS + : n = 28 and MetS-: n = 70) at Royan Institute, Tehran, Iran. All participants underwent anthropometric indices measurements using standard protocols. From each participant, a single fasting blood sample was collected on the same day that the semen sample was collected. The BCAAs and AAAs in blood and seminal plasma were measured using high-performance liquid chromatography (HPLC). The aromatase activity (total testosterone/ estradiol ratio) was significantly lower in MetS + (0.16) than MetS- (0.35) (p = 0.016). Semen parameters were similar between the MetS + and the MetS- groups. All BCAA and AAA family members, except tryptophan, were higher in the blood plasma of men with metabolic syndrome. Meanwhile, the seminal plasma of BCAA and AAAs were similar. Intriguingly, Valine in blood (r = -0.329; p < 0.001) and seminal (r = -0.237; p < 0.05) plasma were correlated with abnormal sperm morphology in patients without metabolic syndrome (MetS-). Further research is necessary to validate these findings and to explore the underlying mechanisms and interactions between the plasma BCAAs and AAAs and sperm parameters.PMID:39885000 | DOI:10.1007/s43032-024-01779-2

Toxicol Appl Pharmacol. 2025 Jan 28:117247. doi: 10.1016/j.taap.2025.117247. Online ahead of print.ABSTRACTOBJECTIVES: Investigating the effect of melatonin (MLT) on the pharmacokinetics and related neurotransmitter and amino acid metabolism of vigabatrin (VGB) in epileptic rats in vivo.METHODS: High performance liquid chromatography was used to examine the pharmacokinetics and tissue distribution of VGB after intragastric administration dosing (50，100，200) mg/kg singly or in combination with melatonin (20 mg/kg) in rats. The single-compartment model of first-order elimination was fitted with the nonlinear mixed-effect model of first-order estimation. Targeting metabolomics were used to measure and analyze the amino acid levels in the hippocampus of kainic acid (KA)-induced epileptic rats treated with VGB alone or coupled melatonin.RESULTS: Melatonin significantly alters the pharmacokinetics of VGB, primarily by lengthening the elimination t1/2, Tmax, MRT and Vz/F, and decreasing the Cmax of both vigabatrin R(-) enantiomer (R-VGB) and vigabatrin S(+) enantiomer (S-VGB). Moreover, the concentrations of R-VGB and S-VGB were increased significantly in the lung and spleen of VGB + MLT group at 15 min compared with that of the VGB group. At 1 h, S-VGB levels increased significantly in spleen. At 4 h, the levels of S-VGB in the hippocampus and R-VGB in the prefrontal cortex increased significantly. Results of targeted metabolomics experiment showed that compared with control group, the level of aminobutyric acid/glutamate (GABA/Glu) in hippocampus of KA-induced epileptic rats was decreased, while glutamate/glutamine (Glu/Gln), tyrosine, dopamine, 3-methoxytyramine, tryptophan, 5-hydroxytryptamine, arginine and phenylalanine were significantly increased. These elevated levels of neurotransmitters and amino acids were decreased in VGB- and VGB + MLT treated group.CONCLUSIONS: MLT affected the pharmacokinetics and tissue distribution of VGB in rats, prolonging its elimination time and improving the tissue distribution. Moreover, it might help VGB improve the imbalance of neurotransmitters and amino acids in the hippocampus of epileptic rats.PMID:39884559 | DOI:10.1016/j.taap.2025.117247

J Ethnopharmacol. 2025 Jan 28:119413. doi: 10.1016/j.jep.2025.119413. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The pathogenesis of alcoholic gastric injury has long been a significant topic in the medical field. Dan-Shen-Yin (DSY), a classic traditional Chinese medicine formula, has been shown to alleviate gastric mucosal injury and to treat stomachaches in clinical settings. However, the mechanism by which DSY against alcoholic gastric injury requires further investigation.AIM OF THE STUDY: This study aimed to explore the effect and mechanism of DSY in preventing alcohol-induced gastric mucosal injury.MATERIALS AND METHODS: The Rat model of alcohol-induced gastric injury (AIGI) was established by gavage with 56% ethanol for 1 month. The protective effect of DSY against AIGI was confirmed. Serum non-targeted metabolomics and gastric tissue transcriptomics were employed to explore the potential mechanisms of DSY in treating alcoholic gastric injury, followed by further verification via Western blotting (WB), Histopathological and Immunohistochemical etc. Additionally, an ionomycin-induced calcium overload model and an ethanol-induced injury model in gastric epithelial cells (GES-1) were established for in vitro experiments. The active ingredients of DSY were screened using flow cytometry, laser confocal microscopy, and molecular docking techniques.RESULTS: Transcriptome analysis indicated that elevated calcium levels were a key pathological change in the gastric tissue of AIGI rats. DSY was found to inhibit the activation of the phosphatidylinositol signaling pathway and reduce calcium levels in serum and gastric tissue. Inositol trisphosphate receptor (IP3R) was identified as a significant potential target of DSY in AIGI rats, where IP3R was activated. Both in vivo(AIGI rats) and in vitro experiments(GES-1 Cell) demonstrated that DSY effectively inhibited the activation of IP3R-mediated calcium signaling pathway (downregulated IP3R, Grp75, VDAC1) and alleviated apoptosis (downregulated Caspase 9, Caspase 3, Cytc, Bax and upregulated Bcl-XL, Bcl-2) caused by elevated calcium levels. Furthermore, compounds including salvianolic acid A, salvianolic acid B, lithospermic acid, and isoorientin from DSY were successfully identified as possessing anti-apoptotic activity and inhibiting IP3R expression.CONCLUSION: This study suggested that calcium levels were a key pathological change in AIGI rats. DSY could inhibit the activation of the phosphatidylinositol signaling pathway, reduce calcium levels, and inhibit IP3R to repair mitochondrial apoptosis. Salvianolic acid a, salvianolic acid b, lithospermic acid, and isoorientin were potential active ingredients for the treatment of alcoholic gastric injury.PMID:39884485 | DOI:10.1016/j.jep.2025.119413

J Ethnopharmacol. 2025 Jan 28:119417. doi: 10.1016/j.jep.2025.119417. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Inonotus obliquus has also been used as a traditional folk medicine in Europe and Northeastern China to treat metabolic diseases. Betulinic acid (BA) is a major ingredient with anti-diabetic property derived from I. obliquus, however, its bioavailability is limited. Whether the beneficial effects of BA on type 2 diabetic mellitus (T2DM) referring to modulation of gut microbiota and associated metabolites remain unclear.AIM OF THE STUDY: This work aims to investigate the alleviating effect of BA on T2DM in db/db mice and elucidate the mechanism from perspective of network pharmacology, gut microbiome and fecal metabolome.MATERIALS AND METHODS: BA was orally administered to db/db mice for 45 days, and the related biochemical parameters were evaluated. The associated mechanism was explored using network pharmacology analysis, 16S rRNA sequencing and UHPLC-MS metabolomics comprehensively. Additionally, Spearman analysis was performed to assess the correlation between gut microbes, metabolites, and T2DM-related biochemical parameters.RESULTS: BA ameliorated T2DM symptoms by reducing body weight gain, regulating serum glucose and lipid levels, and mitigating T2DM-associated liver injury in db/db mice. Network pharmacology analysis indicated the ameliorative effect was via targeting at PPAR activity. BA intervention increased the relative abundance of short-chain fatty acids (SCFAs) producing bacteria including Lactobacillus and Eubacterium_xylanophilum group, and enhanced the production of SCFAs. Moreover, BA primarily regulates arginine and proline metabolism, D-glutamine and D-glutamate metabolism, and alanine, aspartate and glutamate metabolism. Spearman analysis indicated a negative correlation between SCFAs-producing bacteria and amino acids, as well as serum glucose and lipid levels.CONCLUSION: Apart from PPAR signaling pathway, BA modulated gut microbiota composition and associated metabolites in db/db mice. This study provided novel insights into the therapeutic potential of BA for alleviating T2DM symptoms.PMID:39884483 | DOI:10.1016/j.jep.2025.119417

Food Chem. 2025 Jan 27;473:142988. doi: 10.1016/j.foodchem.2025.142988. Online ahead of print.ABSTRACTThis study evaluated the in vitro antioxidant activity and bioactive compound content of mixed-strain lactic acid bacteria-fermented black mulberry juice (FBMJ) and its protective effects against oxidative stress using physicochemical experiments and a cellular oxidative stress model. We also performed preliminary analyses of polysaccharide structures in FBMJ and identified the dynamic changes in the phenolic profiles of FBMJ during the fermentation process. The results indicated that FBMJ polyphenols can improve cell vitality and prevent H2O2-induced oxidative stress by reducing intracellular reactive oxygen species concentrations and regulating mitochondrial membrane potential. Metabolomic analysis proposed transformation pathways for FBMJ polyphenols, including the biotransformation of specific phenolic acids, such as hydroxycinnamic and hydroxybenzoic acids, and the degradation of rutin and anthocyanins. These findings will help explain why fermentation enhances the bioactivity of black mulberry juice by elucidating the biotransformation of polyphenolic compounds during fermentation.PMID:39884228 | DOI:10.1016/j.foodchem.2025.142988

Lung Cancer. 2025 Jan 8;200:108082. doi: 10.1016/j.lungcan.2025.108082. Online ahead of print.ABSTRACTBACKGROUND: Lung cancer is the deadliest disease globally, with more than 120,000 diagnosed cases and more than 75,000 deaths annually in Japan. Several treatment options for advanced lung cancer are available, and the discovery of biomarkers will be useful for personalized medicine. Using metabolome analysis, we aimed to identify biomarkers for diagnosis and treatment response by examining the changes in metabolites associated with lung cancer progression.METHODS: Plasma samples from patients with recurrent or metastatic non-small cell lung carcinomas diagnosed at Tohoku University Hospital between 2019 and 2024 were used in this study. Metabolomic analysis was performed using the Biocrates Life Sciences MxP Quant 500 kit. Multivariate, principal component, and orthogonal partial least squares discriminant analyses were performed.RESULTS: The triglyceride and phosphatidylcholine concentrations were higher in the patients with early than in those with advanced lung adenocarcinomas. However, the cholesterol ester concentrations were higher for the patients with advanced lung cancer. The concentrations of hexosylceramide were higher in patients with early lung adenocarcinoma than in those with squamous cell carcinoma. Relative to epidermal growth factor receptor (EGFR)-mutation negative cases, the EGFR-mutation positive cases showed marked differences between the ceramide and triglyceride concentrations. For the best therapeutic effect of EGFR-TKI treatment, the hexosylceramide (HexCer) (d18:1/24:0), ceramide (Cer) (d18:2/22:0), and ceramide (Cer) (d18:2/24:0) concentrations were higher for the stable and progressive disease groups. The concentrations of phosphatidylcholine (PC) ae C42:2, sphingomyelin (SM) C24:1, and lysophosphatidylcholine (lysoPC) a C18:2 were higher in the partial response group treated with immune checkpoint inhibitors and chemotherapy.CONCLUSION: Metabolomic analysis may be useful for the diagnosis and treatment of lung cancer and may provide clues for new therapeutic strategies. PC ae C42:2, SM C24:1, and lysoPC a C18:2 can serve as predictive biomarkers for monitoring the therapeutic effects of the combination of immune checkpoint inhibitors and chemotherapy.PMID:39884221 | DOI:10.1016/j.lungcan.2025.108082

Chemosphere. 2025 Jan 29;373:144160. doi: 10.1016/j.chemosphere.2025.144160. Online ahead of print.ABSTRACTThe universe of possible chloro-paraffin (CP) structures is a complex one. Even the world of short-chain CPs (SCCPs) is large, containing thousands of constitutional isomers and stereoisomers. We investigated a technical SCCP mixture (Hordalub 80, Vantage Leuna, mCl = 56%) and found 33 CP-homologues in this material with carbon- (nC) and chlorine-numbers (nCl) varying from 10 to 13 and 4-12, respectively. In addition, 27 chloro-olefins (COs) and 18 chloro-diolefins (CdiOs) could be detected with high-resolution mass spectrometry (HRMS, R > 100'000). Respective mass spectra were processed with the R-based automated spectra evaluation routine (RASER). The SCCP mixture was then exposed to Sphingobium chinhatense IP26, which have been isolated and cultivated from a strain found in a chemical dumpsite in Chinhat, Lucknow, India. After exposure for 6 days, additional signals corresponding to hydroxylated and olefinic metabolites were observed in respective mass spectra. RASER was adapted to identify and read-out these metabolite signals too. S. chinhatense expressed the enzymes LinA and LinB. LinA, a dehydrohalogenase (17.3 kDa), is catalyzing the elimination of HCl, converting paraffinic to olefinic material (C(H)-C(X) to CC). LinB, a dehalohydroxylase (32 kDa), transforms halides to alcohols (C-X to C-OH). Both enzymes were active and we identified 9 different metabolite classes. We found mono- (CP-ols), di- (CP-diols), tri- (CP-triols) and some tetra-hydroxylated CPs (CP-tetraols). In addition to the chloro-olefins and chloro-diolefins, we also observed mono- (CO-ols) and di-hydroxylated olefins (CO-diols) and hydroxylated diolefins (CdiO-ols). In other words, the exposure of 33 SCCP homologues to S. chinhatense resulted in a metabolome with 176 metabolites including 27 COs, 18 CdiOs, 72 mono-to tetra-hydroxylated CPs, 23 CO-ols and 19 CO-diols and 17 CdiO-ols. The qualitative characterization based on HR-MS and chromatographic retention times confirmed the formation of these phase-I metabolites, which can now be searched for in other materials and environmental samples.PMID:39884139 | DOI:10.1016/j.chemosphere.2025.144160

J Hazard Mater. 2025 Jan 27;488:137386. doi: 10.1016/j.jhazmat.2025.137386. Online ahead of print.ABSTRACTMicroplastic pollution has emerged as a significant environmental concern at the global level, potentially threatening biodiversity conservation and human wellbeing. As an important biological group with a wide global distribution, migratory shorebirds face considerable stress due to plastic and microplastic pollution. However, few studies have explored the ecotoxic impact of microplastic pollution on migratory shorebirds. To investigate the physiological effects of microplastic pollution on migratory shorebirds, this study obtained the morphological data of 79 dunlins at a key stopover site at the midpoint of the East Asian-Australasian Flyway in 2023 autumn. Meanwhile, fecal and blood samples were collected to examine the microplastic abundance accumulated in the body and metabolic levels. Microplastics were detected in 100 % of dunlins, comprising 12 distinct polymer types. The average abundance of microplastics ingested by dunlins was 134.50 items/g, which was higher than the reported abundance of environmental sediment. The present study confirmed that individuals with longer bills ingested more microplastics, resulting in significantly decreased body mass for the same shorebird. Compared to the low contamination group, metabolomic analysis also revealed that dunlins with elevated microplastic contamination exhibited the down-regulation of 10 metabolic pathways, including pyrimidine metabolism, beta-alanine metabolism, and vitamin C metabolism. The findings of this study underscore the potential threat microplastics pose to the health of migratory shorebirds. It is recommended that synergies be developed between microplastic management and biodiversity conservation at global and regional scales, with migratory birds serving as pivotal indicator species.PMID:39884043 | DOI:10.1016/j.jhazmat.2025.137386

J Hazard Mater. 2025 Jan 25;488:137358. doi: 10.1016/j.jhazmat.2025.137358. Online ahead of print.ABSTRACTThe prevalence and persistence of phthalate esters (PAEs) in agricultural soils has garnered global attention. Assessing their potential impacts on crop yield and quality necessitates a thorough understanding of their risks. In this study, we elucidated the carbon flow-dependent mechanisms of the decreased grain quality upon exposure to PAEs through a soil-based rice cultivation experiment. Combining metabolomics and transcriptomics methods, our findings revealed that the glycolytic intermediates derived from sucrose breakdown preferentially flowed towards amino acid synthesis, rather than starch and fatty acid synthesis under exposure to dibutyl phthalate (DBP) or di(2-ethylhexyl) phthalate (DEHP). This redirection led to decreased levels of starch (by 14-23 %) and fatty acids (by 10-40 %) in the grains. Notably, the increased amino acids primarily served as antioxidants to mitigate DBP and DEHP stresses, rather than enhancing protein quality. Consequently, a reduction in protein levels by 5.7-38 % was observed. Moreover, our study pinpointed glucose-6-phosphate, a common precursor for amino acids, fatty acids, and starch synthesis, as the crucial branching node in glycolysis that redirected this carbon flow. This study offers a new perspective for evaluating the ecological risks associated with PAEs, paving the way for future research and interventions to mitigate their adverse effects on crops.PMID:39884038 | DOI:10.1016/j.jhazmat.2025.137358

Forensic Sci Int Genet. 2025 Jan 27;76:103231. doi: 10.1016/j.fsigen.2025.103231. Online ahead of print.ABSTRACTThe personal identification of monozygotic (MZ) twins is of great importance in forensic medicine. Due to the extreme similarity in genetic between MZ twins, it is challenging to differentiate them using autosomal STR genotyping. Forensic experts are striving to explore available genetic markers that can differentiate between MZ twins. With the advent of next-generation sequence (NGS), an increasing number of genetic markers have been demonstrated to effectively differentiate between MZ twins. Here, we summarized for the relevant studies on MZ twins' differentiation and discussed the limitations of the underlying markers. In details, single-nucleotide variants (SNVs), copy number variation (CNV), mitochondrial DNA (mtDNA), DNA methylation, and non-coding RNA have been demonstrated considerable value. Furthermore, the utilization of proteomics, metabolomics, and microbiomics has shed light on MZ twin differentiation. Additionally, we introduce the methodologies for MZ differentiation based on external morphological variations observed in the human body. Looking to the future, the process of aging may represent a novel avenue for the differentiation of MZ twins.PMID:39883969 | DOI:10.1016/j.fsigen.2025.103231

J Pharm Biomed Anal. 2025 Jan 25;256:116701. doi: 10.1016/j.jpba.2025.116701. Online ahead of print.ABSTRACTPreeclampsia, a life-threatening pregnancy complication, remains a major global health concern. Understanding the complex molecular mechanisms underlying this disorder is crucial for improving both diagnostics and therapeutic strategies. In this study, a multi-omics approach based on NMR metabolomics and RNA-seq transcriptomics analyses was conducted to analyze placental tissue samples obtained from patients with preeclampsia and healthy controls. Metabolomics data analysis results indicated alterations in several metabolite levels including lactate, myo-inositol, glutamate, glutamine, valine, leucine, isoleucine, creatinine, alanine, taurine, choline, phosphocholine, glycerophosphocholine, ethanolamine, and dihydroxyacetone. These alterations cause significant disruptions in the Krebs cycle, energy, lipid, and amino acid metabolisms. Concurrently, transcriptomics data analysis identified 10 upregulated and 37 downregulated genes (|log2FC= > 1 and padj < 0.05) in preeclampsia patients. Identified genes were linked to critical roles such as vasoconstriction, angiogenesis, inflammation, hormonal balance, oxidative stress, and collagen integrity. Multi-omics data analysis revealed the association of certain metabolites with several other genes. A gene interaction network formed by these genes resulted in a lower protein-protein interaction enrichment value (p-value < 1e-16) compared to the network formed with the differentially expressed genes (p-value = 0.0183) which suggests the importance of considering multiple omics levels for a comprehensive understanding of the disease.PMID:39883963 | DOI:10.1016/j.jpba.2025.116701

Proc Natl Acad Sci U S A. 2025 Feb 4;122(5):e2417529122. doi: 10.1073/pnas.2417529122. Epub 2025 Jan 30.ABSTRACTChromobox 2 (CBX2), a crucial component of the polycomb repressive complex (PRC), has been implicated in the development of various human cancers. However, its role in the regulation of tumor immunogenicity and immune evasion remains inadequately understood. In this study, we found that ablation of CBX2 led to tumor growth inhibition, activation of the tumor immune microenvironment, and enhanced therapeutic efficacy of anti-PD1 or adoptive T cell therapies by using murine syngeneic tumor models. By analysis of the CBX2-regulated transcriptional program coupled with mass spectrometry screening of CBX2-interacting proteins, we found that CBX2 suppresses interferon signaling independent of its function in the canonical PRC. Mechanistically, CBX2 directly interacts with RACK1 and facilitates the recruitment of HDAC1, which attenuates the H3K27ac modification on the promoter regions of interferon-stimulated genes, thereby suppressing interferon signaling. Consequently, CBX2 reduces tumor immunogenicity and enables immune evasion. Moreover, a high expression level of CBX2 is associated with immune suppressive tumor microenvironment and reduced efficacy of immunotherapy across various human cancer types. Our study identifies a noncanonical CBX2-RACK1-HDAC1 corepressor complex in suppression of tumor immunogenicity, thereby presenting a potential target and biomarker for tumor immunotherapy.PMID:39883845 | DOI:10.1073/pnas.2417529122

PLoS One. 2025 Jan 30;20(1):e0313159. doi: 10.1371/journal.pone.0313159. eCollection 2025.ABSTRACTAflatoxin B1 (AFB1) is a class 1 carcinogen and mycotoxin known to contribute to the development of hepatocellular carcinoma (HCC), growth impairment, altered immune system modulation, and malnutrition. AFB1 is synthesized by Aspergillus flavus and is known to widely contaminate foodstuffs, particularly maize, wheat, and groundnuts. The mechanism in which AFB1 causes genetic mutations has been well studied, however its metabolomic effects remained largely unknown. A better understanding of how AFB1 disrupts metabolism would provide insight into how this mycotoxin leads to carcinogenesis, growth impairment, and/or immunomodulation, and may reveal potential targets for pharmacological or nutritional interventions to protect against these effects. The current study evaluated the metabolomic effects of various doses (2.5 μM, 5 μM, 10uM) of AFB1 treatment to HepG2 (liver), MDA-MB-231 (breast), and A549 (lung) cells. Treated and control cells' metabolomic profiles were evaluated via ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Univariate and multivariate analyses revealed significant alterations in metabolite concentrations from each dose of AFB1 treatment in each cell type. Pathway analysis was then used to understand broader biochemical functions affected by AFB1 treatment in each cell type. HepG2 cell pathway analyses revealed significant pathway perturbations in lipid metabolism, carnitine synthesis, catecholamine biosynthesis, purine metabolism, and spermidine and spermine biosynthesis. Analysis of A549 cells found a greater emphasis of perturbations on various amino acids along with lipid synthesis-related pathways, and catecholamine biosynthesis. Finally, analysis of treated MDA-MB-231 cells found spermidine and spermine biosynthesis, carnitine synthesis, plasma membrane-related pathways (phosphatidylcholine synthesis and alpha linolenic acid and linoleic acid metabolism), and various amino acid metabolism pathways to be most affected. These highlighted pathways should be targeted in future investigations to evaluate their potential in mitigating or preventing the development of negative health effects associated with AFB1 exposure.PMID:39883710 | DOI:10.1371/journal.pone.0313159

J Nat Prod. 2025 Jan 30. doi: 10.1021/acs.jnatprod.4c01105. Online ahead of print.ABSTRACTA marine-derived Pleosporales fungus, Uzbekistanica storfjordensis, was isolated from driftwood and described as a new species. The fungus was cultivated in liquid media and a molecular networking-driven approach was used to identify potential new secondary metabolites. The targeted compounds were isolated using preparative HPLC-MS, and through extensive spectroscopic analysis, eight new ophiobolin-type sesterterpenes, bipolarolides H-O (1-8), were identified. The absolute configurations of the compounds were determined by ECD assessment. Bipolarolide L (5), M (6), and O (8) exhibited inhibitory activity against Streptococcus agalactiae with MIC values of 86, 66, and 64 μM, respectively.PMID:39883606 | DOI:10.1021/acs.jnatprod.4c01105

Adv Biotechnol (Singap). 2024 Jul 16;2(3):25. doi: 10.1007/s44307-024-00032-w.ABSTRACTMilitarine is a monomer molecule with abundant and distinctive biological properties, also the lead member of secondary metabolites in Bletilla striata, while its biosynthesis mechanism is still unknown. To improve the production efficiency of militarine, sodium acetate and salicylic acid (SA) were introduced as elicitors into the suspension-cultured callus of B. striata. Subsequently, samples were taken from callus at different culturing stages to investigate the synthesis mechanisms of militarine in B. striata through integrated metabolomics and transcriptomics. Metabolomics analysis revealed that acetate ions promoted militarine synthesis, while SA had an inhibitory effect. Additionally, regulators such as ferulic acid, 2-hydroxy-3-phenylpropionic acid, and cis-beta-D-Glucosyl-2-hydroxycinnamate were identified as influencing militarine synthesis. Transcriptomics analysis indicated that the expression levels of genes involved in phenylalanine metabolism, phenylpropanoid biosynthesis, and tyrosine metabolism were correlated with militarine content. This study sheds light on the regulatory mechanism of militarine biosynthesis in plants. The results suggested that acetate ions and SA impact militarine synthesis through specific metabolic pathways and gene expression changes. This knowledge serves as a foundation for future research on militarine biosynthesis and its industrial production.PMID:39883253 | DOI:10.1007/s44307-024-00032-w

Adv Biotechnol (Singap). 2024 Aug 5;2(3):26. doi: 10.1007/s44307-024-00034-8.ABSTRACTExtreme environments such as hyperarid, hypersaline, hyperthermal environments, and the deep sea harbor diverse microbial communities, which are specially adapted to extreme conditions and are known as extremophiles. These extremophilic organisms have developed unique survival strategies, making them ideal models for studying microbial diversity, evolution, and adaptation to adversity. They also play critical roles in biogeochemical cycles. Additionally, extremophiles often produce novel bioactive compounds in response to corresponding challenging environments. Recent advances in technologies, including genomic sequencing and untargeted metabolomic analysis, have significantly enhanced our understanding of microbial diversity, ecology, evolution, and the genetic and physiological characteristics in extremophiles. The integration of advanced multi-omics technologies into culture-dependent research has notably improved the efficiency, providing valuable insights into the physiological functions and biosynthetic capacities of extremophiles. The vast untapped microbial resources in extreme environments present substantial opportunities for discovering novel natural products and advancing our knowledge of microbial ecology and evolution. This review highlights the current research status on extremophilic microbiomes, focusing on microbial diversity, ecological roles, isolation and cultivation strategies, and the exploration of their biosynthetic potential. Moreover, we emphasize the importance and potential of discovering more strain resources and metabolites, which would be boosted greatly by harnessing the power of multi-omics data.PMID:39883228 | DOI:10.1007/s44307-024-00034-8

Anal Chem. 2025 Jan 30. doi: 10.1021/acs.analchem.4c03222. Online ahead of print.ABSTRACTSample pretreatment for mass spectrometry (MS)-based metabolomics and lipidomics is normally conducted independently with two sample aliquots and separate matrix cleanup procedures, making the two-step process sample-intensive and time-consuming. Herein, we introduce a high-throughput pretreatment workflow for integrated nontargeted metabolomics and lipidomics leveraging the enhanced matrix removal (EMR)-lipid microelution 96-well plates. The EMR-lipid technique was innovatively employed to effectively separate and isolate non-lipid small metabolites and lipids in sequence using significantly reduced sample amounts and organic solvents. Our proposed methodology enables parallel profiling of metabolome and lipidome within a single sample aliquot using ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Following method development and optimization with representative metabolites at levels comparable to those detected in human blood, the optimized workflow was applied to prepare metabolome-lipidome from maternal and umbilical cord-blood sera prior to comprehensive profiling using three different UHPLC columns. Results indicate that, compared with conventional two-step metabolomics-lipidomics sample pretreatment workflow, this new approach substantially reduces sample amount and processing time, while still preserving metabolite profiles and revealing additional MS features. Over 2500 metabolites were annotated in human sera with >1000 shared across maternal and cord blood. The shared metabolites are closely linked to various physiological functions, including nutrient transfer, hormonal regulation, waste product clearance, and metabolic programming, underscoring the significant impact of maternal metabolic activities on neonatal metabolic health. In summary, the proposed workflow enables efficient sample pretreatment for nontargeted metabolomics-lipidomics using one single sample while achieving broad metabolite coverage, highlighting its remarkable applicability in clinical and preclinical research.PMID:39883156 | DOI:10.1021/acs.analchem.4c03222

Cancer Epidemiol Biomarkers Prev. 2025 Jan 30. doi: 10.1158/1055-9965.EPI-24-1390. Online ahead of print.ABSTRACTBACKGROUND: Current evidence suggests higher physical activity (PA) levels are associated with a reduced risk of colorectal cancer (CRC). However, the mediating role of the circulating metabolome in this relationship remains unclear.METHODS: Targeted metabolomics data from 6,055 participants in the EPIC cohort were used to identify metabolites associated with PA and derive a metabolomic signature of PA levels. PA levels were estimated using the validated Cambridge PA index based on baseline questionnaires. Mediation analyses were conducted in a nested case-control study (1,585 cases, 1,585 controls) to examine whether individual metabolites and the metabolomic signature mediated the PA-CRC association.RESULTS: PA was inversely associated with CRC risk (odds ratio [OR] per category change: 0.90, 95% confidence intervals [CI]: 0.83, 0.97; p-value = 0.009). PA levels were associated with 24 circulating metabolites after false discovery rate correction (FDR), with the strongest associations observed for phosphatidylcholine acyl-alkyl (PC ae) C34:3 (FDR-adjusted p-value = 1.18 × 10⁻¹⁰) and lysophosphatidylcholine acyl (lysoPC a) C18:2 (FDR-adjusted p-value = 1.35 × 10⁻⁶). PC ae C34:3 partially mediated the PA-CRC association (natural indirect effect: 0.991, 95% CI: 0.982, 0.999; p-value = 0.04), explaining 7.4% of the association. No mediation effects were observed for the remaining metabolites or the overall PA metabolite signature.CONCLUSIONS: PC ae C34:3 mediates part of the PA-CRC inverse association, but further studies with improved PA measures and extended metabolomic panels are needed.IMPACT: These findings provide insights into PA-related biological mechanisms influencing CRC risk and suggest potential targets for cancer prevention interventions.PMID:39883068 | DOI:10.1158/1055-9965.EPI-24-1390

J Tissue Eng. 2025 Jan 28;16:20417314241295928. doi: 10.1177/20417314241295928. eCollection 2025 Jan-Dec.ABSTRACTGrowing evidence indicates that type 2 diabetes (T2D) is associated with an increased risk of developing Parkinson's disease (PD) through shared disease mechanisms. Studies show that insulin resistance, which is the driving pathophysiological mechanism of T2D plays a major role in neurodegeneration by impairing neuronal functionality, metabolism and survival. To investigate insulin resistance caused pathological changes in the human midbrain, which could predispose a healthy midbrain to PD development, we exposed iPSC-derived human midbrain organoids from healthy individuals to either high insulin concentration, promoting insulin resistance, or to more physiological insulin concentration restoring insulin signalling function. We combined experimental methods with metabolic modelling to identify the most insulin resistance-dependent pathogenic processes. We demonstrate that insulin resistance compromises organoid metabolic efficiency, leading to increased levels of oxidative stress. Additionally, insulin-resistant midbrain organoids showed decreased neuronal activity and reduced amount of dopaminergic neurons, highlighting insulin resistance as a significant target in PD prevention.PMID:39882547 | PMC:PMC11775974 | DOI:10.1177/20417314241295928

Front Med (Lausanne). 2025 Jan 15;11:1538373. doi: 10.3389/fmed.2024.1538373. eCollection 2024.ABSTRACTAcne vulgaris (AV) is a common inflammatory disorder involving the pilosebaceous unit. Many studies have reported that people with AV have higher levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) compared to healthy controls. Hence, they concluded that an unhealthy lipid profile is an independent risk factor for AV. Recent research in metabolomics and lipidomics has been propelled by rapid advancements in technologies including computational methods and mass spectrometry. Using metabolomics and lipidomics approach, a broad range of structurally diverse lipid species were detected and important lipid biomarkers were identified that are vital to the pathogenesis of AV. In this review, we will describe the recent progress in dyslipidemia of AV using metabolomics and lipidomics advances. We will begin with a literature overview of dyslipidemia of AV, followed by a short introduction of metabolomics and lipidomics. Finally, we will focus on applying metabolomics and lipidomics in dyslipidemia of AV.PMID:39882523 | PMC:PMC11774704 | DOI:10.3389/fmed.2024.1538373