PubMed

Inflammation. 2025 Feb 27. doi: 10.1007/s10753-025-02260-1. Online ahead of print.ABSTRACTPeriodontitis is a chronic inflammatory disease characterized by inflammation of the periodontal soft tissues and loss of alveolar bone. In the oral environment, subgingival microorganisms and salivary metabolites reflect the host's health status. This study aimed to understand periodontitis severity and progression rate by analyzing subgingival microflora and salivary metabolites to identify potential biomarkers. Fifty-three volunteers with stage II periodontitis were graded using the bone loss (%)/age index into two grades: 33 in grade A (< 0.25) and 20 in grade B (0.25-1.00). Using a case-control study, simultaneously analyzed biomarkers associated with the severity and rate of progression of periodontitis. The red complex, the orange complex, Campylobacter spp., uncultured Candidatus Saccharibacteria and metabolites such as 5-Aminovaleric acid, N1-Acetylspermine showed a significant positive correlation with periodontal clinical parameters. Furthermore, we identified four of the salivary differential metabolites (DL-Leucineamide, Dodecanedioic acid, L-Tyrosine methyl ester and Phenylpyruvic acid) that may serve as potential biomarkers for predicting the rate of periodontitis progression. These results showed that the red complex significantly correlated with periodontitis severity and influenced changes in salivary metabolites. Additionally, biomarkers indicating the progression rate were predominantly amino acid derivatives, confirming that interactions between microorganisms and metabolites may exacerbate periodontitis development.PMID:40011293 | DOI:10.1007/s10753-025-02260-1

Int J Biol Macromol. 2025 Feb 24:141467. doi: 10.1016/j.ijbiomac.2025.141467. Online ahead of print.ABSTRACTThe purpose of this study is to investigate the effects and mechanisms of Acanthopanax senticosus polysaccharides (ASPS) on lipopolysaccharide (LPS)-induced intestinal injury and growth performance in piglets. Our results indicated that ASPS improved the growth performance in LPS-challenged piglets, including the increase in average daily gain (ADG), average daily feed intake (ADFI), and the feed to gain ratio (F/G). ASPS alleviated LPS-induced intestinal inflammation in piglets, accompanied by the increase in the villus height to crypt depth ratio (VCR) and the decreased in the expression levels of IL-1β, IL-6, and TNF-α. 16S rRNA sequencing results showed that ASPS improved gut microbiota dysbiosis and increased Lactobacillus_sp._L_YJ abundance. The combined analysis of untargeted metabolomics of intestinal contents and serum showed that ASPS significantly increased the levels of hyodeoxycholic acid (HDCA), DHA ethyl ester, and alanylalanine, and the level of HDCA is the highest among all metabolites, suggesting that ASPS regulated the metabolites of intestinal contents and serum to alleviate LPS-induced intestinal inflammation in piglets, and HDCA might play a significant role during this process. Furthermore, we investigated the effects of HDCA on growth performance and intestinal inflammation in LPS-challenged piglets. The results indicated that HDCA alleviated LPS-induced intestinal inflammation and improved the growth performance in piglets. In conclusion, ASPS could alleviate LPS-induced intestinal inflammation in piglets by gut microbiota and hyodeoxycholic acid regulation. These findings might provide strong evidence for ASPS as a feed additive to improve piglet diarrhea, and reveal the therapeutic potential of hyodeoxycholic acid in preventing intestinal inflammation in piglets.PMID:40010458 | DOI:10.1016/j.ijbiomac.2025.141467

Int J Sport Nutr Exerc Metab. 2025 Feb 25:1-18. doi: 10.1123/ijsnem.2024-0127. Online ahead of print.ABSTRACTExercise perturbs various aspects of gastrointestinal integrity and function, which may lead to performance impeding gastrointestinal symptoms (GIS) and/or precipitate clinical issues warranting medical management. This study aimed to determine the impact of prebiotic supplementation on gastrointestinal integrity and functional status in response to exertional heat stress (EHS). Sixteen endurance athletes completed two trials of 3-hr running at 60% V˙O2max in 30 °C at baseline (T1) and following an 8-week supplementation period (T2), with 16 g/day prebiotic (PREBIOTIC) or matched placebo (PLACEBO). Blood samples were collected pre-EHS and post-EHS and in recovery for determination of stress response (cortisol), intestinal epithelial injury (intestinal fatty acid binding protein), bacterial endotoxemia (sCD14), and systemic inflammation (C-reactive protein). GIS and feeding tolerance variables were assessed throughout the EHS. Orocecal transit time was determined via a lactulose challenge given at 2.5 hr into EHS. Plasma cortisol (combined mean: +252 ng/ml), intestinal fatty acid binding protein (+800 pg/ml), and sCD14 (+487 ng/ml) concentrations increased in response to EHS in T1 (p ≤ .05), but not for C-reactive protein (+0.8 μg/ml; p > .05), in both PREBIOTIC and PLACEBO. PREBIOTIC supplementation resulted in a blunted intestinal fatty acid binding protein response on T2 (+316 pg/ml) compared with an increase (+1,001 ng/ml) in PLACEBO (p = .005). Lower sCD14 was observed at T2 (2,799 ng/ml) versus T1 (3,246 ng/ml) in PREBIOTIC only (p = .039). No intervention effects were observed for C-reactive protein. No difference within or between PREBIOTIC and PLACEBO at T1 and T2 was observed for orocecal transit time, GIS, and feeding tolerance. In conclusion, 8 weeks of prebiotic supplementation modestly attenuates EHS associated perturbations to intestinal integrity, but does not further impair gastrointestinal transit and/or exacerbate EHS associated GIS or feeding tolerance.PMID:40010361 | DOI:10.1123/ijsnem.2024-0127

Plant Physiol Biochem. 2025 Feb 18;222:109664. doi: 10.1016/j.plaphy.2025.109664. Online ahead of print.ABSTRACTSoil waterlogging is a major abiotic stress that severely impairs maize growth and development by inducing hypoxic conditions that disrupt essential physiological processes. Transcription factors (TFs) play crucial roles in modulating plant responses to waterlogging stress by regulating the expression of stress-related genes that enhance or diminish stress tolerance. In this study, we conducted an association analysis to identify 11 TFs closely associated with waterlogging stress in maize. Notably, the PLATZ family emerged as a novel and significant contributor to waterlogging stress. Overexpression of ZmPLATZ15 resulted in increased sensitivity to waterlogging at maize seedlings. Conversely, ZmEREB200, a member of the maize Group VII ERF (ZmERFVII) family, was significantly downregulated in the ZmPLATZ15 overexpression lines under waterlogging stress. Promoter analysis revealed that ZmPLATZ15 regulates ZmEREB200 by binding to the A/T-rich motifs in the ZmEREB200 promoter. Interestingly, overexpression of ZmEREB200 was found to enhance waterlogging tolerance at maize seedlings. To further elucidate their roles, we analyzed the transcriptomic profiles of ZmPLATZ15 and ZmEREB200 overexpression lines under waterlogging stress. The overlapping differentially expressed genes in both ZmPLATZ15 and ZmEREB200 overexpression lines were significantly enriched in pathways associated with redox balance and salicylic acid metabolism, both of which are crucial for modulating waterlogging tolerance at maize seedlings. Metabolomic analysis revealed that antioxidant enzyme activity, salicylic acid, and glutathione levels were decreased in OE-ZmPLATZ15, while these metabolites were significantly increased in OE-ZmEREB200. These contrasting metabolic responses in overexpression lines may underlie their different tolerances to waterlogging stress. Our findings provide valuable insights into the regulatory mechanisms underlying maize's response to waterlogging stress and highlight the potential of TFs as tools for developing maize varieties with enhanced waterlogging tolerance.PMID:40010256 | DOI:10.1016/j.plaphy.2025.109664

Tissue Cell. 2025 Feb 22;94:102808. doi: 10.1016/j.tice.2025.102808. Online ahead of print.ABSTRACTSea urchins are widely distributed in waters worldwide. The present study carried out the in vitro metabolomic bioactivity profiling using UPLCMS/MS of Paracentrotus lividus spines extract. Investigations were also conducted on molecular anticancer, anti-inflammatory, antidiabetic, antioxidant, and antibacterial properties. A comprehensive untargeted metabolic profiling of P. lividus spines extract resulted in the classification of more than 13 metabolites. Their metabolomic quantitative evaluations were assumed by measuring total phenolic, flavonoids, dihydroflavonol, sugar, and protein contents. The P. lividus spines extract exhibited powerful antioxidant capacity using DPPH*, ABTS+, reducing power, and phosphomolybdate assays. Moreover, P. lividus spines extract highly elucidated antidiabetic and anti-inflammatory activity by inhibiting α-amylase enzyme and protein denaturation. Further, the spines of the P. lividus exhibited significant antibacterial effects. Besides, extract from P. lividus spines showed a strong cytotoxic impact against a variety of HepG-2 and MCF-7 cancer cell lines. It was discovered that the P. lividus spines extract triggered cell cycle arrest in the sub-G0/G1 phase and suppressed the growth of cancer cells via suppressing mRNA of Akt/MAPK/Bcl-2/c-myc and protein expression of β-Catenin/ki-67. Conclusively, the extract derived from the spines of the sea urchin species P. lividus demonstrates significant potential for utilization in various pharmaceutical industries.PMID:40010182 | DOI:10.1016/j.tice.2025.102808

Comp Biochem Physiol Part D Genomics Proteomics. 2025 Feb 19;55:101451. doi: 10.1016/j.cbd.2025.101451. Online ahead of print.ABSTRACTThe present study utilized non-targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate the metabolomic responses of sea cucumber (Apostichopus japonicus) juveniles under predation stress induced by sea stars (Asterina pectinifera) at various time points (3 h, 12 h, 72 h, and 96 h). The findings revealed significant temporal changes in the metabolic profiles of the sea cucumber juveniles under predation stress, with 25, 72, 55, and 53 metabolic products exhibiting significantly different expression levels at each time point (positive ion mode, P < 0.05), respectively. Notably, the impact of predation stress was most pronounced at the 12-h mark. Multivariate statistical methods, including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), further confirmed distinct clustering of the experimental group away from the control group at each time point, with the most pronounced separation occurring at 12 h, indicating a significant and time-dependent metabolic response to predation stress. Key metabolic pathways associated with predation stress were identified, such as carbon metabolism, pentose phosphate pathway, purine metabolism, riboflavin metabolism, longevity regulation, and antifolate resistance pathways, by integrating variable importance in the projection (VIP), fold change (FC), and P-value. KEGG enrichment analysis highlighted significant expression changes of key metabolites like carbamoyl phosphate, gluconolactone, inosine, 2'-deoxyguanosine, and adenylate in response to predation stress, potentially related to energy metabolism, antioxidant defense, signal transduction, and cellular stress responses. The study provides novel insights into the metabolic adaptability of sea cucumber juveniles to predation stress.PMID:40010144 | DOI:10.1016/j.cbd.2025.101451

Biochem Biophys Res Commun. 2025 Feb 19;754:151513. doi: 10.1016/j.bbrc.2025.151513. Online ahead of print.ABSTRACTVascular aging contributes to the morbidity and mortality in older individuals, closely linked to an imbalance between energy consumption and production. Despite its importance, our understanding of how aging affects vascular metabolism and leads to vascular diseases remains limited. In this study, we explored the metabolomic characteristics of vascular aging by analyzing aortic tissues from young and old mice through untargeted metabolomic analysis using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). We identified 85 differential metabolites, with 37 up-regulated and 48 down-regulated, primarily consisting of lipids and lipid-like molecules, based on the criteria of variable importance in projection (VIP) > 1 and P < 0.05. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed significant involvement of these metabolites in six metabolic pathways (P < 0.05), particularly in glycerophospholipid metabolism. Receiver operating characteristic (ROC) curve analysis highlighted eight altered metabolites in glycerophospholipid metabolism, such as phosphatidylcholine (PC) (17:0/22:6) and lysophosphatidylcholine (LPC) (18:2), which demonstrated strong discriminatory ability for vascular aging with an area under the curve (AUC) exceeding 0.85. This study provides novel insights into metabolomic signature of vascular aging, offering important clues for future treatments of age-related vascular disorders.PMID:40010140 | DOI:10.1016/j.bbrc.2025.151513

Talanta. 2025 Feb 18;290:127770. doi: 10.1016/j.talanta.2025.127770. Online ahead of print.ABSTRACTGut microbiota produces a wide range of microbial metabolites with potential neuroactive properties. Among these, p-cresol, a by-product of tyrosine breakdown, has gained significant attention in various neuropsychiatric disorders, including autism spectrum disorder. However, current methods fail to detect p-cresol at trace levels in both the systemic circulation and brain, limiting the study of its role in neuropsychiatric disorders. There, the precise and accurate determination of p-cresol at low picogram levels is an unmet analytical need. To address this gap, we developed a highly-sensitive, validated method for quantifying p-cresol at low picogram levels in urine, plasma, and brain using chemical derivatization and liquid chromatography-tandem mass spectrometry (LC-MS/MS). We found that derivatization with 1,2-dimethylimidazole-5-sulfonyl chloride (5-DMIS-Cl or 5-DMISC) increased up to 40-fold the sensitivity compared to traditional dansyl derivatization. Therefore, a method based on 5-DMISC derivatization and sum of transitions was selected for validation. The method was accurate (recoveries 91-100 %) and precise (RSD <15 %) in all tested matrices, enabling detection down to100 pg/mL for urine, 20 pg/mL for plasma, and 0.04 pg/mg for brain tissue. The method was applied to plasma and brain samples from control and p-cresol-treated mice, revealing significant increases in p-cresol levels in treated animals. For the first time, we successfully quantified p-cresol levels in the brain, demonstrating its ability to cross the blood-brain barrier. In summary, this validated method offers a powerful tool for exploring the role of p-cresol -and potentially other phenolic compounds-in the microbiota-gut-brain axis and neuropsychiatric disorders.PMID:40010114 | DOI:10.1016/j.talanta.2025.127770

Phytomedicine. 2025 Feb 19;139:156543. doi: 10.1016/j.phymed.2025.156543. Online ahead of print.ABSTRACTBACKGROUND: The underlying pathogenesis of psoriasis was attributed to insufficient kidney qi and blood stasis arising from impeded blood circulation. Jinkui Shenqi decoction (JKSQD), was renowned for its capacity to warm and tonify kidney yang, as well as to invigorate blood circulation. However, there remains a dearth of studies on its specific therapeutic effects and underlying mechanisms of psoriasis.PURPOSE: Aiming to investigate the effectiveness and mechanism of JKSQD in the treatment of psoriasis.METHODS: Initially, we identified the compounds of JKSQD by UPLC-Q-TOF-MS/MS and constructed psoriasis-like mice to explore the effect of JKSQD on psoriasis. Subsequently, proteomic sequencing was conducted to identify key proteins and pathways involved in the therapeutic effect of JKSQD. Neutrophil extracellular traps (NETs) and peptidylarginine deiminase 4 (PAD4)-related indicators were detected to validate JKSQD mechanisms. At last, we analyzed metabolomic data to elucidate what metabolic pathway or metabolites worked during this procedure.RESULTS: We found that JKSQD effectively reversed the progression of psoriasis and associated inflammation in mice. Proteomic analysis further illuminated that PAD4 involved in NETosis was notably downregulated in psoriasis-like mice after JKSQD treatment. And a series of experiments further revealed that JKSQD inhibited NETs formation and PAD4 expression. Moreover, metabolomics demonstrated JKSQD influenced D-Arginine and D-ornithine metabolism, offering deeper insights into the mechanisms of JKSQD on psoriasis.CONCLUSIONS: This study unveiled that JKSQD could improve psoriasis progression by targeting PAD4 to inhibit NETs formation.PMID:40010032 | DOI:10.1016/j.phymed.2025.156543

Phytomedicine. 2025 Feb 14;139:156518. doi: 10.1016/j.phymed.2025.156518. Online ahead of print.ABSTRACTBACKGROUND: Drug discovery from nature has a long, ethnopharmacologically-based background. Today, natural resources are undeniably vital reservoirs of active molecules or drug leads. Advances in (bio)informatics and computational biology emphasized the role of herbal medicines in the drug discovery pipeline.PURPOSE: This review summarizes bioinformatic approaches applied in recent drug discovery from nature.STUDY DESIGN: It examines advancements in molecular networking, pathway analysis, network pharmacology within a systems biology framework and AI for assessing the therapeutic potential of herbal preparations.METHODS: A comprehensive literature search was conducted using Pubmed, SciFinder, and Google Database. Obtained data was analyzed and organized in subsections: AI, systems biology integrative approach, network pharmacology, pathway analysis, molecular networking, structure-based virtual screening.RESULTS: Bioinformatic approaches is now essential for high-throughput data analysis in drug target identification, mechanism-based drug discovery, drug repurposing and side-effects prediction. Large datasets obtained from "omics" approaches require bioinformatic calculations to unveil interactions, and patterns in disease-relevant conditions. These tools enable databases annotations, pattern-matching, connections discovery, molecular relationship exploration, and data visualisation.CONCLUSION: Despite the complexity of plant metabolites, bioinformatic approaches assist in characterization of herbal preparations and selection of bioactive molecule. It is perceived as powerful tool for uncovering multi-target effects and potential molecular mechanisms of compounds. By integrating multiple networks that connect gene-disease, drug-target and gene-drug-target, drug discovery from natural sources is experiencing a remarkable comeback.PMID:40010031 | DOI:10.1016/j.phymed.2025.156518

J Chromatogr A. 2025 Feb 20;1746:465804. doi: 10.1016/j.chroma.2025.465804. Online ahead of print.ABSTRACTFissistigma polyanthum is a renowned medicinal plant traditionally used by over 10 ethnic groups in China to treat various ailments, including inflammation. However, research on its chemical composition and bioactivity remains limited. This study investigated the chemical profiles and biological activities across different parts of F. polyanthum, aiming to identify the bioactive molecules associated with anti-inflammatory and anti-Alzheimer's effects. To ensure accurate metabolite identification, an in-house Fissistigma compound library containing 654 chemicals was constructed and integrated with the Progenesis QI informatics platform. Using UPLC-ESI-QTOF-MS-based metabolomics, 97 compounds, including alkaloids, flavonoids and terpenoids, were identified, of which 86 were reported for the first time in this species. Heatmap analysis revealed significant content variations of these constituents across different plant parts: leaves were rich in flavonoids and terpenoids, while the root without bark was abundant in alkaloids. PCA and PLS-DA analyses confirmed significant metabolite differences among the plant parts, with 31 key differential compounds explaining the chemical variations. Comparative bioactivity assays showed that the root without bark exhibited strong anti-butyrylcholinesterase activity, with an IC50 value of 54.22 μg/mL, while the root bark and leaves demonstrated the strongest inhibition of NO production, with IC50 values of 62.64 and 71.85 μg/mL, respectively. The S-plot analysis further identified 25 potential bioactive compounds, primarily alkaloids and flavonoids, responsible for the observed bioactivities, including known anti-inflammatory and anti-Alzheimer's agents. These findings underscore the pharmaceutical potential of F. polyanthum and the effectiveness of integrating metabolomics and chemometrics to discover bioactive molecules in medicinal plants.PMID:40009970 | DOI:10.1016/j.chroma.2025.465804

Ecotoxicol Environ Saf. 2025 Feb 25;292:117948. doi: 10.1016/j.ecoenv.2025.117948. Online ahead of print.ABSTRACTDi(2-ethylhexyl) phthalate (DEHP) is recognised as a pollutant with multiple health risks. In this study, multi-omics approaches were used to examine the alterations in immunity, gut microbiota and metabolome, and liver transcriptome in the rats with DEHP-induced subacute liver injury. Following short-term subacute DEHP exposure, the rats exhibited decreased body weight, increased liver weight, impaired liver function and immunity, and signs of liver injury. DEHP exposure reduced the richness, diversity, and evenness of gut microbiota, resulting in elevated levels of Lactobacillus, Romboutsia, and Alistipes and decreased levels of unclassified Muribaculaceae, Oscillibacter, and Akkermansia in the intestine. Multiple gut metabolic pathways were altered by DEHP, among which sphingolipid metabolism was enriched with the most differentially expressed metabolites. In the liver tissues of rats exposed to DEHP, lipid metabolism-related pathways were altered, including downregulated steroid biosynthesis and upregulated fatty acid degradation. In conclusion, the relevant findings suggest that DEHP can cause immune alteration, gut microbiota dysbiosis, gut metabolome disruption, liver transcriptome dysregulation, and result in liver injury in rats. These results could benefit the clinical diagnosis of DEHP-induced subacute liver injury.PMID:40009945 | DOI:10.1016/j.ecoenv.2025.117948

Neoplasia. 2025 Feb 25;62:101146. doi: 10.1016/j.neo.2025.101146. Online ahead of print.ABSTRACTOral squamous cell carcinoma (OSCC) is characterized by aggressiveness and a poor prognosis, in part because most patients are diagnosed during the later stages of the disease. B cell-specific Moloney murine leukemia virus integration site 1 (BMI1), part of polycomb repressive complex 1 (PRC1), is a key transcription factor overexpressed in OSCC. Although increased BMI1 has been linked to tumor formation in mouse models of the disease, the molecular mechanisms have not been elucidated. Here we used a transgenic mouse line (KrTB) that selectively overexpresses BMI1 in the tongue basal epithelial stem cells (SCs) to delineate BMI1 actions during oral tumorigenesis. By tumor pathological classification after 4-nitroquinoline 1-oxide (4-NQO)-induced carcinogenesis we detected more severe tumors in mice with ectopic BMI1 expression. Genome-wide transcriptomics indicated that mRNAs associated with human OSCC, including SOX9, HIF1A, MMP9, INHBB, and MYOF, were further increased by ectopic BMI1 expression in murine tongue epithelia. mRNAs encoding multiple metabolic targets, such as SLC2A1 (GLUT1), PKM, LDHA, and HK2, were also increased upon BMI1 overexpression in 4-NQO-treated tongue epithelia. Furthermore, we detected BMI1, SOX9, and GLUT1 proteins in the infiltrating cells of invasion fronts identified by markers of invasive SCCs. Finally, metabolomic data show that BMI1 overexpression in tongue epithelia promotes glycolysis during 4-NQO-induced carcinogenesis. Thus, our data demonstrate that BMI1 causes OSCC cells to alter cell metabolism, as changes in many of these transcripts are linked to increased glycolysis and metabolic reprograming that occurs during carcinogenesis.PMID:40009939 | DOI:10.1016/j.neo.2025.101146

Proc Natl Acad Sci U S A. 2025 Mar 4;122(9):e2421489122. doi: 10.1073/pnas.2421489122. Epub 2025 Feb 26.ABSTRACTAldosterone-producing adenomas (APA), a major endocrine tumor and leading subtype of primary aldosteronism, cause secondary hypertension with high cardiometabolic risks. Despite potentially producing multiple steroid hormones, detailed cellular mechanisms in APA remain insufficiently studied. Our multiomics analysis focusing on APA with KCNJ5 mutations, which represent the most common genetic form, revealed marked cellular heterogeneity. Tumor cell reprogramming initiated from stress-responsive cells to aldosterone-producing or cortisol-producing cells, with the latter progressing to proliferative stromal-like cells. These cell subtypes showed spatial segregation, and APA exhibited genomic intratumor heterogeneity. Among the nonparenchymal cells, lipid-associated macrophages, which were abundant in APA, might promote the progression of cortisol-producing and stromal-like cells, suggesting their role in the tumor microenvironment. Intratumor cortisol synthesis was correlated with increased blood cortisol levels, which were associated with the development of vertebral fractures, a hallmark of osteoporosis. This study unveils the complex cellular ecosystem with clinical relevance in APA with KCNJ5 mutations, providing insights into tumor biology that could inform future clinical approaches.PMID:40009643 | DOI:10.1073/pnas.2421489122

Blood. 2025 Feb 26:blood.2024025924. doi: 10.1182/blood.2024025924. Online ahead of print.ABSTRACTMicrobial dysbiosis and metabolite changes in the gastro-intestinal (GI) tract have been linked to pathogenesis and severity of many diseases, including graft-versus-host disease (GVHD), the major complication of allogeneic hematopoietic stem cell transplantation (HCT). However, published studies have only considered the microbiome and metabolome of excreted stool and do not provide insight into the variability of microbial community and metabolite composition throughout the GI tract or the unique temporal dynamics associated with different gut locations. Because such geographical variations are known to influence disease processes, we utilized a multi-omics approach to characterize the microbiome and metabolite profiles of gut contents from different intestinal regions in well-characterized mouse models of GVHD. Our analysis validated analyses from excreted stool, but importantly, uncovered new biological insights from the microbial and metabolite changes between syngeneic and allogeneic hosts that varied by GI location and time after transplantation. Our integrated analysis confirmed the involvement of known metabolic pathways, including SCFA synthesis and bile acid metabolism, and identified additional functional genes, pathways, and metabolites, such as amino acids, fatty acids, and sphingolipids, linked to GI GVHD. Finally, we validated a biological relevance for one such newly identified microbial metabolite, phenyl lactate, that heretofore had not been linked to GI GVHD. Thus, our analysis of the geographic variability in the intestinal microbiome and metabolome offers new insights into GI GVHD pathogenesis and potential for novel therapeutics.PMID:40009444 | DOI:10.1182/blood.2024025924

Appl Biochem Biotechnol. 2025 Feb 26. doi: 10.1007/s12010-025-05200-9. Online ahead of print.ABSTRACTColorectal cancer (CRC) is one of the common deadliest cancers worldwide. In Malaysia, the numbers of new CRC cases were horrific and worrisome. Telomerase is both prognostic indicator and predictor of carcinogenesis in CRC patients. Berberine, a telomerase inhibitor, was used in clinical trials and metabolomic studies; however, the association of telomerase with metabolites and metabolic pathways was not fully understood. Colorectal cancer cell line HCT 116 was cultured and treated with 10.54 µg/mL berberine. The cells were harvested at different time points to conduct subsequent analyses. The methods used in this research were real time-polymerase chain reaction (RT-PCR) to assess RNA expressions; Western blot to determine protein levels; TELOTAGGG Telomerase PCR ELISA to determine relative telomerase activity (RTA); 4',6-diamidino-2-phenylindole (DAPI) staining to determine percentage of nuclei damage; fluorescence microscopy for cell area; spectrophotometric potassium iodide assay for intracellular hydrogen peroxide concentration [H2O2]; as well as liquid chromatography mass spectrometry (LCMS) and tandem mass spectrometry (MS/MS) to investigate the intracellular metabolites. Partial least square-discriminant analysis (PLS-DA) score plot exhibited an improved separation compared to principal component analysis (PCA) when metabolomic data analysis of HCT 116 at various berberine treatment durations was conducted. Time and berberine treatment had an impact on RTA in HCT 116. RTA was discovered to be positively and negatively correlated to 14 and 2 metabolites, respectively. Glutamic acid was consistently found correlated to RTA. Other four metabolites, i.e., MG(14:0), [3-[hydroxy(phosphonooxy)phosphoryl]oxyphenyl] phosphono hydrogen phosphate), (3S,6S)-6-[[(3S,6R)-6-[(2S,3S,5S)-2,5-diiodo-4-methoxy-6-methyloxan-3-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid, and 1-[5-O-(5'-adenylyloxyphosphonyl)-beta-D-ribofuranosyl]-5-amino-1H-imidazole-4-carboxamide, were newly discovered to be connected to RTA in HCT 116. Four metabolic pathways that majorly affected shared glutamic acid and glutamine. Nitrogen metabolism, D-glutamine and D-glutamate metabolism, glyoxylate and dicarboxylate metabolism, and aminoacyl-tRNA biosynthesis have been identified to be associated with RTA. Network analyses hinted that glutamic acid was also associated with oxidative stress mechanism. The multiple roles glutamic acid acted in diverse metabolic pathways and interaction networks emphasized the importance of glutamic acid in HCT 116 regarding RTA. This research establishes the association between RTA and several chosen RNAs, proteins, metabolites, and oxidative stress mechanisms, consequential in morphological alteration in HCT 116, to expand the knowledge of the intricate biological relationships and telomerase mechanism in CRC.PMID:40009339 | DOI:10.1007/s12010-025-05200-9

Theor Appl Genet. 2025 Feb 26;138(3):59. doi: 10.1007/s00122-025-04849-4.ABSTRACTA missense mutation that causes premature termination of the CmEGY1 protein leads to golden fruit in melon. Melon (Cucumis melo L.) is an economically important fruit crop that has been cultivated for thousands of years. Fruit color, a crucial trait influencing the appearance quality and economic value of melons, is primarily determined mainly by the type and concentration of pigments such as chlorophyll, carotenoids, and flavonoids. Identifying the genetic loci that govern melon fruit color contributes to breeding efforts aimed at enhancing melon rind coloration. This study reports an EMS-induced mutant, designated as gf1 (golden fruit 1), which produces fruit with both golden peel and flesh. Through MutMap and map-based cloning, we localized the gf1 locus to an 862 kb region containing 42 SNPs. Of these, a single SNP in the coding region caused a stop-gained mutation in the gene Cme13C08g017690, which exhibits the highest sequence similarity to Arabidopsis ETHYLENE-DEPENDENT GRAVITROPISM-DEFICIENT AND YELLOW-GREEN 1 (EGY1). Genome editing of CsEGY1, the cucumber homolog, confirmed its role in golden-fruit formation. Transcriptome and metabolome analyses revealed reduced flavonoid and carotenoid contents, accompanied by the downregulation of related biosynthetic genes. The identification and characterization of egy1 provide novel genetic insights and a valuable resource for improving melon appearance through breeding.PMID:40009196 | DOI:10.1007/s00122-025-04849-4

J Membr Biol. 2025 Feb 26. doi: 10.1007/s00232-024-00332-1. Online ahead of print.ABSTRACTTrans-membrane water transport and co-transport is ubiquitous in cell biology. Integrated over all the cell's H2O transporters and co-transporters, the rate of homeostatic, bidirectional trans-cytolemmal water "exchange" is synchronized with the metabolic rate of the crucial Na+,K+-ATPase (NKA) enzyme: the active trans-membrane water cycling (AWC) phenomenon. Is AWC futile, or is it consequential? Conservatively representative literature metabolomic and proteinomic results enable comprehensive free energy (ΔG) calculations for the many transport reactions with known water stoichiometries. Including established intracellular pressure (Pi) magnitudes, these reveal an outward trans-membrane H2O barochemical ΔG gradient comparable to that of the well-known inward Na+ electrochemical ΔG gradient. For most co-influxers, these two gradients are finely balanced to maintain intracellular metabolite concentration values near their consuming enzyme Michaelis constants. Our analyses include glucose, glutamate-, gamma-aminobutyric acid (GABA), and lactate- transporters. 2%-4% Pi alterations can lead to disastrous metabolite concentrations. For the neurotransmitters glutamate- and GABA, very small astrocytic Pi changes can allow/disallow synaptic transmission. Unlike the Na+ and K+ electrochemical steady-states, the H2O barochemical steady-state is in (or near) chemical equilibrium. The analyses show why the presence of aquaporins (AQPs) does not dissipate trans-membrane pressure gradients. A feedback loop inherent in the opposing Na+ electrochemical and H2O barochemical gradients regulates AQP-catalyzed water flux as integral to AWC. A re-consideration of the underlying nature of Pi is also necessary. AWC is not a futile cycle but is inherent to the cell's "NKA system"-a new, fundamental aspect of biology. Metabolic energy is stored in the trans-membrane water barochemical gradient.PMID:40009106 | DOI:10.1007/s00232-024-00332-1

Food Funct. 2025 Feb 26. doi: 10.1039/d4fo06449f. Online ahead of print.ABSTRACTObesity is a major global public health challenge, affecting billions and serving as a primary risk factor for many chronic diseases. Certain probiotics have shown promise in regulating energy balance and enhancing fat metabolism, offering potential strategies for managing obesity. In this study, we evaluated three strains of Bifidobacterium adolescentis and identified B. adolescentis FJSSZ23M10 as the most effective in alleviating high-fat diet (HFD)-induced obesity. This strain significantly reduced weight gain, improved abnormal serum biochemical indicators, decreased lipid accumulation in adipocytes, and enhanced energy expenditure. Furthermore, B. adolescentis FJSSZ23M10 treatment modulated the gut microbiota, notably increasing the abundance of Bifidobacterium and Faecalibaculum. Untargeted metabolomic analysis revealed that B. adolescentis FJSSZ23M10 uniquely upregulated beneficial metabolites, such as butyrate and pyruvic acid, suggesting its superior metabolic impact. Genomic analysis indicated that B. adolescentis FJSSZ23M10 harbored the highest abundance of unassigned genes and carbohydrate-active enzymes (CAZymes) compared to the other strains, highlighting its superior functional potential. Combining the shared and unique modifications in gut microbiota, metabolites, and genomic annotations, the study highlights that genomic differences among probiotics could shape their effects on gut microbiota and metabolites. Conclusively, the study underscores the critical role of probiotic genomic characteristics in determining their functional efficacy and suggests that the intake of the B. adolescentis FJSSZ23M10 strain with enriched genomic features, such as CAZymes, could represent a novel genomic-based strategy for alleviating obesity through gut microbiota modulation and metabolic regulation.PMID:40008925 | DOI:10.1039/d4fo06449f

Anal Chem. 2025 Feb 26. doi: 10.1021/acs.analchem.4c05560. Online ahead of print.ABSTRACTDefinitive structural elucidation of lipids is pivotal for unraveling the functions of lipids in biological systems. Despite advancements in mass spectrometry (MS) for lipid analysis, challenges in annotation scope and efficiency remain, especially in resolving isomers. Herein, we introduce an optimized method using liquid chromatography coupled with electron impact excitation of ions from organic tandem mass spectrometry (LC-EIEIO-MS/MS) for comprehensive analysis and structural annotation of lipids. This approach integrates a six-step analytical protocol for precise lipid annotation, including (1) extracting MS information, (2) classifying lipids, (3) aligning sum composition, (4) determining sn-positions, (5) locating C═C positions, and (6) ascertaining annotation levels. In analyzing 34 lipid standards spiked into serum, our method achieved 100% and 82.4% annotation accuracy at the sn- and C═C isomer levels, respectively, compared to 26.5% and 0% in the CID mode using MS-DIAL. A total of 1312 sn-positions and 1033 C═C locations of lipids were annotated in quality control plasma pooled from healthy individuals and patients with Alzheimer's disease. The isomers of lipids revealed more pronounced differences between the healthy and diseased groups compared to the sum compositions of the lipids. Overall, the LC-EIEIO-MS/MS approach provides a comprehensive profiling and efficient annotation method for lipidomics, promising to shed new light on lipid-related biological pathways and disease mechanisms.PMID:40008860 | DOI:10.1021/acs.analchem.4c05560