PubMed

Front Microbiol. 2025 Jan 6;15:1501951. doi: 10.3389/fmicb.2024.1501951. eCollection 2024.ABSTRACTMarine-derived actinobacteria isolated from sponge Cliona varians and soft coral Eunicea fusca were screened for antibacterial activity against acne-related bacteria, specifically Staphylococcus epidermidis ATCC 14990, methicillin-resistant Staphylococcus aureus ATCC BAA44, and Cutibacterium acnes ATCC 6919. Cytotoxicity assays were performed on human dermal fibroblast (HDFa) and keratinocyte (HaCaT) cell lines to assess the safety profile of the extracts. Chemical characterization was conducted using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Among the extracts, six derived from Kocuria sp., Rhodococcus sp., Nocardia sp., Micrococcus sp., and Streptomyces sp. demonstrated significant antibacterial activity. Notably, extract Z9.216 from Kocuria sp. exhibited the highest efficacy, inhibiting S. epidermidis by 68%, S. aureus by 93%, and C. acnes by 98.7% at a concentration of 0.003 mg/mL, which was comparable to the standard antibiotics erythromycin and vancomycin, while maintaining over 90% cell viability in both HDFa and HaCaT cell lines. Untargeted metabolomic analysis suggested that antibacterial activity might be associated with compounds from the chemical families of alkaloids, terpenoids, and fatty acids, among others. These findings highlight the therapeutic potential of marine actinobacteria in underexplored environments as a promising strategy for treating acne vulgaris, a chronic inflammatory skin condition.PMID:39834363 | PMC:PMC11743623 | DOI:10.3389/fmicb.2024.1501951

J Agric Food Chem. 2025 Jan 21. doi: 10.1021/acs.jafc.4c09001. Online ahead of print.ABSTRACTFluoroquinolone antibiotic enrofloxacin (ENR) is frequently detected in agricultural environments. The hormesis and detrimental effects of ENR on crops have been extensively observed. However, the molecular mechanisms underlying these crops' responses to ENR remain limited. Here, integrated physiological, transcriptomic, and metabolomic analysis revealed the key metabolic pathway responses underlying the ENR-induced effects on rice. The results showed that ENR mainly affected three metabolic pathways: 'biosynthesis of amino acids', "tryptophan metabolism", and 'phenylpropanoid/flavonoid biosynthesis'. A low level of ENR treatment promoted root elongation and enhanced the antioxidant capacity by increasing the phytohormone gibberellin A3 and the flavonol quercetin-3-O-neohesperidoside, respectively. However, the high dose of ENR significantly stimulated ROS production, inhibited photosynthesis, and ultimately impaired plant growth. In response to high ENR toxicity, plants accumulated more quercetin derivatives as antioxidants and produced defense-related substances, such as N-hydroxytryptamine, indole-3-acetonitrile, and jasmonic acid, to combat biotic stress. In conclusion, this study provides new insights into the molecular mechanism accounting for the ecological effects of antibiotic pollution in farmland.PMID:39834325 | DOI:10.1021/acs.jafc.4c09001

Int J Biol Markers. 2025 Jan 20:3936155241309927. doi: 10.1177/03936155241309927. Online ahead of print.ABSTRACTINTRODUCTION: Breast cancer is the most common cancer among women, and metabolic syndrome (MetS) is a risk factor for breast cancer, especially postmenopausal breast cancer. We evaluated the role of the advanced glycated end products (AGEs) levels contributing to the association between MetS and breast cancer risk.METHODS: Plasma AGEs were measured in a case-control study nested within the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort, including 40 incident postmenopausal breast cancer cases (20 with MetS and 20 without) and 40 postmenopausal controls (20 with MetS and 20 without). The association between AGEs and breast cancer was analyzed using Bayesian logistic regression models. An informative prior for the exposure coefficient, modeled as a normal distribution, centered on the natural logarithm of an odds ratio ((OR)=1.635) derived from prior evidence, was employed alongside weakly informative priors (WIPs). Bayesian linear regression with WIPs was used to examine the association between MetS and AGEs. Estimates were reported with SDs and 90% and 95% credible intervals (CI).RESULTS: AGEs were associated with higher breast cancer risk both with the informative prior (OR = 1.745, SD):0.362; 90% CI:1.218-2.390; 95% CI:1.137-2.548) and the WIP (OR = 1.861, SD = 0.661; 90% CI:1.026-3.082; 95% CI:0.924-3.528) specification. Although the difference in plasma AGEs in women with and without MetS was not significant, we found a suggestion of higher levels in women with MetS (mean difference in standardized AGEs between individuals with and without MetS = 0.155, SD = 0.245; 90% CI:-0.246 to 0.553; 95% CI:-0.322 to 0.625).CONCLUSIONS: These data, although from a small sample of women, support a role of endogenous AGEs in the pathological pathways underlying the association between MetS and breast cancer development.PMID:39834054 | DOI:10.1177/03936155241309927

Plant Cell Environ. 2025 Jan 20. doi: 10.1111/pce.15398. Online ahead of print.ABSTRACTFlower color is a crucial trait that attracts pollinators and determines the ornamental value of floral crops. Cymbidium lowianum, one of the most important breeding parent of Cymbidium hybrids, has two flower morphs (normal and albino) that differ in flower lip color. However, the molecular mechanisms underlying flower color formation in C. lowianum are not well understood. In this study, comparative metabolomic analysis between normal and albino flower lip tissues indicated that cyanidin-3-O-glucoside content was significantly higher in red epichiles than in other lip tissues. This finding suggests that cyanidin-3-O-glucoside is responsible for color variation and differentiation in the lip in C. lowianum. We also found that red coloration in C. lowianum flower is correlated with high levels of F3'H expression; further, anthocyanins, carotenoids and chlorophyll coordinate to influence sepal and petal coloration during flower development. In transgenic Arabidopsis lines, overexpression of F3'H increased anthocyanin concentration, overexpression of BCH increased carotenoid concentration, whereas overexpression of HEMG and CHLI both increased chlorophyll concentration. Identification and assessment of several transcription factors revealed that MYB308-1 activates BCH, MYB111 and PIF4-2 activate HEMG and CHLI expression during flower development. Importantly, MYB14-1 shows interaction with PIF4-2, and appears to act as a connector between anthocyanin and chlorophyll biosynthesis by either activating F3'H expression or inhibiting CHLI expression. These results indicate that, in C. lowianum, variation in flower color and differentiation of lip color patterns are primarily regulated by the types and concentrations of flavonoids; further, carotenoids and chlorophyll also influence flower coloration during development.PMID:39834034 | DOI:10.1111/pce.15398

Microbiome. 2025 Jan 20;13(1):15. doi: 10.1186/s40168-024-02002-9.ABSTRACTBACKGROUND: The human gut microbiome strongly influences host metabolism by fermenting dietary components into metabolites that signal to the host. Our previous work has shown that Intestinimonas butyriciproducens is a prevalent commensal bacterium with the unique ability to convert dietary fructoselysine to butyrate, a well-known signaling molecule with proven health benefits. Dietary fructoselysine is an abundant Amadori product formed in foods during thermal treatment and is part of foods rich in dietary advanced glycation end products which have been associated with cardiometabolic disease. It is therefore of interest to investigate the causal role of this bacterium and fructoselysine metabolism in metabolic disorders.RESULTS: We assessed associations of I. butyriciproducens with metabolic risk biomarkers at both strain and functional levels using a human cohort characterized by fecal metagenomic analysis. We observed that the level of the bacterial strain as well as fructoselysine fermentation genes were negatively associated with BMI, triglycerides, HbA1c, and fasting insulin levels. We also investigated the fructoselysine degradation capacity within the Intestinimonas genus using a culture-dependent approach and found that I. butyriciproducens is a key player in the butyrogenic fructoselysine metabolism in the gut. To investigate the function of I. butyriciproducens in host metabolism, we used the diet-induced obesity mouse model to mimic the human metabolic syndrome. Oral supplementation with I. butyriciproducens counteracted body weight gain, hyperglycemia, and adiposity. In addition, within the inguinal white adipose tissue, bacterial administration reduced inflammation and promoted pathways involved in browning and insulin signaling. The observed effects may be partly attributable to the formation of the short-chain fatty acids butyrate from dietary fructoselysine, as butyrate plasma and cecal levels were significantly increased by the bacterial strain, thereby contributing to the systemic effects of the bacterial treatment.CONCLUSIONS: I. butyriciproducens ameliorates host metabolism in the context of obesity and may therefore be a good candidate for new microbiota-therapeutic approaches to prevent or treat metabolic diseases. Video Abstract.PMID:39833973 | DOI:10.1186/s40168-024-02002-9

J Nanobiotechnology. 2025 Jan 20;23(1):30. doi: 10.1186/s12951-025-03121-7.ABSTRACTFullerenols, a water-soluble polyhydroxy derivative of fullerene, hold promise in medical and materials science due to their unique properties. However, concerns about their potential embryotoxicity remain. Using a pregnancy mouse model and metabolomics analysis, our findings reveal that fullerenols exposure during pregnancy not only significantly reduced mice placental weight and villi thickness, but also altered the classes and concentrations of metabolites in the mouse placenta. Furthermore, we found that fullerenols exposure reduced the levels of CYP3A4, ERα and estriol (E3), while increasing the levels of estradiol (E2) and oxidative stress both in mouse placenta and placental trophoblast cells, and exogenous supplementation with E3 and ER agonists was effective in restoring these changes in vitro. Moreover, CYP3A4 inhibition was effective in decreasing intracellular E3 levels, whereas overexpression of CYP3A4 resisted the fullerenols-induced decrease in E3 expression Additionally, we synthesized glutathione-modified fullerenols (C60-(OH)n-GSH), which demonstrated improved biocompatibility and reduced embryotoxicity by enhancing intracellular glutathione levels and mitigating oxidative stress. In summary, our results demonstrated that fullerenols exposure decreased E3 synthesis by inhibiting CYP3A4 and exacerbated oxidative stress through downregulation of estrogen receptor activation and decreased glutathione levels. These findings highlight the risks of fullerenols exposure during pregnancy and offer strategies for safer nanomaterial development.PMID:39833883 | DOI:10.1186/s12951-025-03121-7

Respir Res. 2025 Jan 20;26(1):29. doi: 10.1186/s12931-025-03099-8.ABSTRACTBACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disorder that can lead to right ventricular failure and severe consequences. Despite extensive efforts, limited progress has been made in preventing the progression of PAH. Mitochondrial dysfunction is implicated in the development of PAH, but the key mitochondrial functional alterations in the pathogenesis have yet to be elucidated.METHODS: We integrated three microarray datasets from the Gene Expression Omnibus (GEO), including 222 lung samples (164 PAH, 58 controls), for differential expression and functional enrichment analyses. Machine learning identified key mitochondria-related signaling pathways. PAH and control lung tissue samples were collected, and transcriptomic and metabolomic profiling were performed. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis investigated shared pathways, and canonical correlation analysis assessed gene-metabolite relationships.RESULTS: In the GEO datasets, mitochondria-related signaling pathways were significantly enriched in PAH samples, in particular the electron transport chain (ETC) in mitochondrial oxidative phosphorylation system. Notably, the electron transport from cytochrome c to oxygen in ETC was identified as the most crucial mitochondria-related pathway, which was down-regulated in PAH samples. Transcriptomic profiling of the clinical lung tissue analysis identified 14 differentially expressed genes (DEGs) related to mitochondrial function. Metabolomic analysis revealed three differential metabolites in PAH samples: increased 3-phenyllactic acid and ADP, and decreased citric acid. Mitochondria-related genes highly correlated with these metabolites included KIT, OTC, CAMK2A, and CHRNA1.CONCLUSIONS: Down-regulation of electron transport from cytochrome c to oxygen in mitochondrial ETC and disruption of the citric acid cycle homeostasis may contribute to PAH pathogenesis. 3-phenyllactic acid emerges as a potential novel diagnostic biomarker for PAH. These findings offer insights for developing novel PAH therapies and diagnostics.PMID:39833797 | DOI:10.1186/s12931-025-03099-8

Nat Metab. 2025 Jan 20. doi: 10.1038/s42255-024-01201-w. Online ahead of print.ABSTRACTIncreased glycolytic flux is a hallmark of cancer; however, an increasing body of evidence indicates that glycolytic ATP production may be dispensable in cancer, as metabolic plasticity allows cancer cells to readily adapt to disruption of glycolysis by increasing ATP production via oxidative phosphorylation. Using functional genomic screening, we show here that liver cancer cells show a unique sensitivity toward aldolase A (ALDOA) depletion. Targeting glycolysis by disrupting the catalytic activity of ALDOA led to severe energy stress and cell cycle arrest in murine and human hepatocellular carcinoma cell lines. With a combination of metabolic flux analysis, metabolomics, stable-isotope tracing and mathematical modelling, we demonstrate that inhibiting ALDOA induced a state of imbalanced glycolysis in which the investment phase outpaced the payoff phase. Targeting ALDOA effectively converted glycolysis from an energy producing into an energy-consuming process. Moreover, we found that depletion of ALDOA extended survival and reduced cancer cell proliferation in an animal model of hepatocellular carcinoma. Thus, our findings indicate that induction of imbalanced glycolysis by targeting ALDOA presents a unique opportunity to overcome the inherent metabolic plasticity of cancer cells.PMID:39833612 | DOI:10.1038/s42255-024-01201-w

Aging Clin Exp Res. 2025 Jan 21;37(1):28. doi: 10.1007/s40520-024-02923-3.ABSTRACTBACKGROUND: Osteopenia (ON) and osteoporosis (OP) are highly prevalent among postmenopausal women and poses a challenge for early diagnosis. Therefore, identifying reliable biomarkers for early prediction using metabolomics is critically important.METHODS: Initially, non-targeted metabolomics was employed to identify differential metabolites in plasma samples from cohort 1, which included healthy controls (HC, n = 23), osteonecrosis (ON, n = 36), and osteoporosis (OP, n = 37). Subsequently, we performed targeted metabolomic validation of 37 amino acids and their derivatives in plasma samples from cohort 2, consisting of healthy controls (HC, n = 10), osteonecrosis (ON, n = 10), and osteoporosis (OP, n = 10).RESULTS: The non-targeted metabolomic analysis revealed an increase in differential metabolites with the progression of the disease, showing abnormalities in lipid and organic acid metabolism in ON and OP patients. Several substances were found to correlate positively or negatively with bone mineral density (BMD), for example, N-undecanoylglycine, sphingomyelins, and phosphatidylinositols exhibited positive correlations with BMD, while acetic acid, phenylalanine, taurine, inosine, and pyruvic acid showed negative correlations with BMD. Subsequently, targeted validation of 37 amino acids and their metabolites revealed six amino acids related to ON and OP.CONCLUSION: Significant metabolomic features were identified between HC and patients with ON/OP, with multiple metabolites correlating positively or negatively with BMD. Integrating both targeted and non-targeted metabolomic results suggests that lipid, organic acid, and amino acid metabolism may represent important metabolomic characteristics of patients with OP, offering new insights into the development of metabolomic applications in OP.PMID:39833609 | DOI:10.1007/s40520-024-02923-3

J Gastrointest Cancer. 2025 Jan 20;56(1):48. doi: 10.1007/s12029-025-01173-4.ABSTRACTBACKGROUND: Metabolic reprogramming is increasingly recognized as a crucial factor influencing the development, progression, and prognosis of pancreatic ductal adenocarcinoma (PDAC). Despite this, the potential association of specific metabolic characteristics and PDAC remains ambiguous due to the variability introduced by individual patient differences. In this study, we aimed to find out metabolic pathways that may be associated with the overall survival (OS) of PDAC patients.METHODS: We utilized Mendelian randomization (MR) to assess the associations between 1400 metabolites and metabolite ratios and PDAC. We performed functional annotation and pathway enrichment analysis on both significant metabolites and the shared proteins corresponding to the significant metabolite ratios. Additionally, we analyzed peripheral blood metabolites from 32 PDAC patients to correlate metabolites with clinicopathological features and OS. Functional enrichment analysis was also conducted on the significant metabolites.RESULTS: Our MR analysis revealed 55 metabolites/metabolite ratios associated with PDAC. Among the top 20 enriched metabolic pathways involving proteins related to significant metabolite ratios, seven were associated with amino acid metabolism, three with carbohydrate metabolism, and two with lipid metabolism. Serum metabolomics of PDAC patients highlighted significant upregulation in pathways related to primary bile acid biosynthesis, as well as taurine and hypotaurine metabolism, which correlated negatively with OS. Conversely, pathways involved in arginine biosynthesis, arginine and proline metabolism, and aminoacyl-tRNA biosynthesis were notably downregulated and positively associated with OS. Both upregulated and downregulated differential metabolites were notably enriched in the pyrimidine metabolism pathway, which was linked to poorer OS. These associations were corroborated by MR analysis.CONCLUSION: The study provides valuable insights into the metabolic characteristics associated with PDAC, offering a reference point for improving diagnosis and treatment for PDAC.PMID:39833419 | DOI:10.1007/s12029-025-01173-4

Cell Death Differ. 2025 Jan 20. doi: 10.1038/s41418-024-01430-2. Online ahead of print.ABSTRACTAccumulating evidence suggests that genetic and epigenetic biomarkers hold potential for enhancing the early detection and monitoring of breast cancer (BC). Epigenetic alterations of the Homeobox A2 (HOXA2) gene have recently garnered significant attention in the clinical management of various malignancies. However, the precise role of HOXA2 in breast tumorigenesis has remained elusive. To address this point, we conducted high-throughput RNA sequencing and DNA methylation array studies on laser-microdissected human BC samples, paired with normal tissue samples. Additionally, we performed comprehensive in silico analyses using large public datasets: TCGA and METABRIC. The diagnostic performance of HOXA2 was calculated by means of receiver operator characteristic curves. Its prognostic significance was assessed through immunohistochemical studies and Kaplan-Meier Plotter database interrogation. Moreover, we explored the function of HOXA2 and its role in breast carcinogenesis through in silico, in vitro, and in vivo investigations. Our work revealed significant hypermethylation and downregulation of HOXA2 in human BC tissues. Low HOXA2 expression correlated with increased BC aggressiveness and unfavorable patient survival outcomes. Suppression of HOXA2 expression significantly heightened cell proliferation, migration, and invasion in BC cells, and promoted tumor growth in mice. Conversely, transgenic HOXA2 overexpression suppressed these cellular processes and promoted apoptosis of cancer cells. Interestingly, a strategy of pharmacological demethylation successfully restored HOXA2 expression in malignant cells, reducing their neoplastic characteristics. Bioinformatics analyses, corroborated by in vitro experimentations, unveiled a novel implication of HOXA2 in the lipid metabolism of BC. Specifically, depletion of HOXA2 leaded to a concomitantly decreased expression of PPARγ and its target CIDEC, a master regulator of lipid droplet (LD) accumulation, thereby resulting in reduced LD abundance in BC cells. In summary, our study identifies HOXA2 as a novel prognosis-relevant tumor suppressor in the mammary gland.PMID:39833374 | DOI:10.1038/s41418-024-01430-2

Nat Commun. 2025 Jan 20;16(1):859. doi: 10.1038/s41467-025-55870-6.ABSTRACTSomatic embryogenesis (SE) is a developmental process related to the regeneration of tissue-cultured plants, which serves as a useful technique for crop breeding and improvement. However, SE in cotton is difficult and elusive due to the lack of precise cellular level information on the reprogramming of gene expression patterns involved in somatic embryogenesis. Here, we investigate the spatial and single-cell expression profiles of key genes and the metabolic patterns of key metabolites by integrated single-cell RNA-sequencing (scRNA-seq), spatial transcriptomics (ST), and spatial metabolomics (SM). To evaluate the results of these analyses, we functionally characterized the potential roles of two representative marker genes, AATP1 and DOX2, in the regulation of cotton somatic embryo development. A publicly available web-based resource database ( https://cotton.cricaas.com.cn/somaticembryo/ ) in this study provides convenience for future studies of the expression patterns of marker genes at specific developmental stages during the process of SE in cotton.PMID:39833155 | DOI:10.1038/s41467-025-55870-6

Nat Commun. 2025 Jan 20;16(1):858. doi: 10.1038/s41467-025-55869-z.ABSTRACTCotton fibers are single cells that develop from the epidermal cells in the outer integument of developing seeds. The processes regulating fiber cell development have been extensively studied; however, the spatiotemporal transcriptome and metabolome profiles during the early stages of fiber development remain largely unknown. In this study, we profile the dynamics of transcriptome and metabolome during the early stages of cotton fiber cell development using a combination of spatial transcriptomic, single-cell transcriptomic, and spatial metabolomic analyses. We identify the key genes (e.g., DOX2, KCS19.4, BEE3, and HOS3.7) and metabolites (e.g., linoleic acid, spermine, spermidine, and α-linolenic acid) that may regulate the early development of fiber cells. Finally, knockdown and gain-of-function analyses identify the crucial role of GhBEE3/Gh_A09G062900 in cotton fiber initiation. We also construct a publicly accessible website ( https://cotton.cricaas.com.cn/ovule/ ) for visualization of the spatiotemporal gene expression in cotton, providing a reference dataset for further studies on cotton fiber development.PMID:39833150 | DOI:10.1038/s41467-025-55869-z

Redox Biol. 2025 Jan 19:103496. doi: 10.1016/j.redox.2025.103496. Online ahead of print.NO ABSTRACTPMID:39833011 | DOI:10.1016/j.redox.2025.103496

Comput Biol Chem. 2025 Jan 9;115:108325. doi: 10.1016/j.compbiolchem.2024.108325. Online ahead of print.ABSTRACTBACKGROUND: Non-alcoholic fatty liver disease (NAFLD) involves abnormal fat accumulation in the liver, mainly as triglycerides. It ranges from steatosis to non-alcoholic steatohepatitis (NASH), which can lead to inflammation, cellular damage, liver fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are crucial for regulating gene expression across various conditions. LncRNAs are emerging as potential putative diagnostic markers for NAFLD-associated HCC.METHODS: We used two human and two mouse datasets from the Gene Expression Omnibus to analyze the expression profiles of mRNAs and lncRNAs. We created a network linking lncRNAs, miRNAs, and mRNAs to investigate the relationships among these RNA types. Additionally, we identified NAFLD-related lncRNAs from existing literature. We then quantified the expression levels of four specific lncRNAs, including PVT1, DUBR, SNHG17, and SNHG14, in the serum of 92 Egyptian participants using qPCR. Finally, we performed a Receiver Operating Characteristic analysis to evaluate the diagnostic potential of the candidate lncRNAs.RESULTS: Our data suggests that maternally expressed gene 3 (MEG3), H19, and DPPA2 Upstream Binding RNA (DUBR) were significantly upregulated, and plasmacytoma variant translocation 1 (PVT1) was markedly downregulated. PVT1 showed the highest diagnostic accuracy for both NAFLD and NASH. The combined panels of PVT1 +H19 for NAFLD and PVT1 +H19 +DUBR for NASH demonstrated high diagnostic potential. Uniquely, PVT1 can distinguish between NAFLD and NASH. PVT1 exhibited strong diagnostic potential for NAFLD and NASH, individually and in combination with other lncRNAs.CONCLUSION: Our study identifies four lncRNAs as putative biomarkers with high specificity and accuracy, individually or combined, for differentiating between NAFLD and NASH. Healthy volunteers with PVT1 possess the highest diagnostic accuracy and significantly discriminate between NAFLD and NASH.PMID:39832417 | DOI:10.1016/j.compbiolchem.2024.108325

Bone. 2025 Jan 18:117401. doi: 10.1016/j.bone.2025.117401. Online ahead of print.ABSTRACTPorphyromonas gingivalis (P. gingivalis), a major pathogenic bacterium of chronic periodontitis and central player in the onset and subsequent progression of periodontitis, can cause alveolar bone resorption. The osteoblast dysfunction induced by P. gingivalis infection is a crucial pathological process causing bone loss. However, the comprehensive responses of osteoblasts, especially metabolism processes involved in osteoblast dysfunction under P. gingivalis invasion are largely unknown. In the present study, to profile the molecules switched in osteoblast dysfunction caused by P. gingivalis infection, the effect of P. gingivalis invasion on osteoblast differentiation was assessed and investigated through transcriptomics and metabolomics approaches. We found that P. gingivalis infection dramatically impaired osteoblast function. P. gingivalis invasion disrupted homeostasis of phosphorus (Pi)/calcium (Ca2+) and induced robust oxidative stress, cell apoptosis and massive activation of inflammatory response in osteoblasts. Notably, the exposure to P. gingivalis induced the inactivation of endocrines pathways, involved in bone formation, which is characterized by downregulated genes and less accumulated metabolites in "Parathyroid hormone synthesis, secretion and action", its downstream "Wnt signaling pathway" and related Pi/Ca2+ transport. Furthermore, we found that disrupted purine metabolism produced less ATP in P. gingivalis-infected osteoblasts and the reduced ATP may directly inhibit phosphorus transport. Collectively, these results provide a new insight into the molecular changes in P. gingivalis-infected osteoblasts in a comprehensive way.PMID:39832660 | DOI:10.1016/j.bone.2025.117401

J Plant Physiol. 2025 Jan 9;305:154430. doi: 10.1016/j.jplph.2025.154430. Online ahead of print.ABSTRACTAs our planet faces increasing environmental challenges, such as biotic pressures, abiotic stressors, and climate change, it is crucial to understand the complex mechanisms that underlie stress responses in crop plants. Over past few years, the integration of techniques of proteomics, transcriptomics, and genomics like LC-MS, IT-MS, MALDI-MS, DIGE, ESTs, SAGE, WGS, GWAS, GBS, 2D-PAGE, CRISPR-Cas, cDNA-AFLP, HLS, HRPF, MPSS, CAGE, MAS, IEF, MudPIT, SRM/MRM, SWATH-MS, ESI have significantly enhanced our ability to comprehend the molecular pathways and regulatory networks, involved in balancing the ecosystem/ecology stress adaptation. This review offers thorough synopsis of the current research on utilizing these multi-omics methods (including metabolomics, ionomics) for battling abiotic (salinity, temperature (chilling/freezing/cold/heat), flood (hypoxia), drought, heavy metals/loids), biotic (pathogens like fungi, bacteria, virus, pests, and insects (aphids, caterpillars, moths, mites, nematodes) and climate change stress (ozone, ultraviolet radiation, green house gases, carbon dioxide). These strategies can expedite crop improvement, and act as powerful tools with high throughput and instant database generation rates. They also provide a platform for interpreting intricate, systematic signalling pathways and knowing how different environmental stimuli cause phenotypic responses at cellular and molecular level by changing the expression of stress-responsive genes like RAB18, KIN1, RD29B, OsCIPK03, OsSTL, SIAGL, bZIP, SnRK, ABF. This review discusses various case studies that exemplify the successful implementation of these omics tools to enhance stress tolerance in plants. Finally, it highlights challenges and future prospects of utilizing these approaches in combating stress, emphasizing the need for interdisciplinary collaborations and bio-technological advancements for sustainable agriculture and food security.PMID:39832424 | DOI:10.1016/j.jplph.2025.154430

Nat Prod Bioprospect. 2025 Jan 20;15(1):12. doi: 10.1007/s13659-024-00492-6.ABSTRACTMosquitoes (Diptera: Culicidae) are vectors of various pathogens of public health concern and replacing conventional insecticides remains a challenge. In this regard, natural products represent valuable sources of potential insecticidal compounds, thus increasingly attracting research interest. Commiphora myrrha (T.Nees) Engl. (Burseraceae) is a medicinal plant whose oleo-gum resin is used in food, cosmetics, fragrances, and pharmaceuticals. Herein, the larvicidal potential of its essential oil (EO) was assessed on four mosquito species (Aedes albopictus Skuse, Aedes aegypti L., Anopheles gambiae Giles and Anopheles stephensi Liston), with LC50 values ranging from 4.42 to 16.80 μg/mL. The bio-guided EO fractionation identified furanosesquiterpenes as the main larvicidal compounds. A GC-MS-driven untargeted metabolomic analysis revealed 32 affected metabolic pathways in treated larvae. The EO non-target toxicity on Daphnia magna Straus (LC50 = 4.51 μL/L) and its cytotoxicity on a human kidney cell line (HEK293) (IC50 of 14.38 μg/mL) were also assessed. This study shows the potential of plant products as innovative insecticidal agents and lays the groundwork for the possible exploitation of C. myrrha EO in sustainable approaches for mosquito management.PMID:39832119 | DOI:10.1007/s13659-024-00492-6

Metabolomics. 2025 Jan 20;21(1):16. doi: 10.1007/s11306-024-02214-y.ABSTRACTINTRODUCTION: Hemodynamic forces play a crucial role in modulating endothelial cell (EC) behavior, significantly influencing blood vessel responses. While traditional in vitro studies often explore ECs under static conditions, ECs are exposed to various hemodynamic forces in vivo. This study investigates how wall shear stress (WSS) influences EC metabolism, focusing on the interplay between WSS and key metabolic pathways.OBJECTIVES: The aim of this study is to examine the effects of WSS on EC metabolism, specifically evaluating its impact on central carbon metabolism and glycolysis using transcriptomics and tracer metabolomics approaches.METHODS: ECs were exposed to WSS, and transcriptomic analysis was performed to assess gene expression changes related to metabolic pathways. Tracer metabolomics was used to track metabolic fluxes, focusing on glutamine and glycolytic metabolism. Additionally, chemical inhibition of glutamate dehydrogenase was conducted to evaluate its role in EC fitness under WSS.RESULTS: Transcriptomic data revealed upregulation of glutamine and glutamate pathways, alongside downregulation of glycolytic activity in ECs exposed to WSS. Tracer metabolomics confirmed that WSS promotes glutamine anaplerosis into the Krebs cycle, while decreasing glycolytic metabolism. Suppression of glutamate dehydrogenase impaired EC fitness under WSS conditions.CONCLUSION: Our findings illuminate that ECs subjected to WSS exhibit a preference for glutamine as a key nutrient source for central carbon metabolism pathways, indicating diminished reliance on glycolysis. This study elucidates the nutritional predilections and regulatory mechanisms governing EC metabolism under WSS in vitro, underscoring the pivotal role of physical stimuli in shaping EC metabolic responses.PMID:39832080 | DOI:10.1007/s11306-024-02214-y

Metabolomics. 2025 Jan 20;21(1):17. doi: 10.1007/s11306-024-02218-8.ABSTRACTINTRODUCTION: Breath Volatile organic compounds (VOCs) are promising biomarkers for clinical purposes due to their unique properties. Translation of VOC biomarkers into the clinic depends on identification and validation: a challenge requiring collaboration, well-established protocols, and cross-comparison of data. Previously, we developed a breath collection and analysis method, resulting in 148 breath-borne VOCs identified.OBJECTIVES: To develop a complementary analytical method for the detection and identification of additional VOCs from breath. To develop and implement upgrades to the methodology for identifying features determined to be "on-breath" by comparing breath samples against paired background samples applying three metrics: standard deviation, paired t-test, and receiver-operating-characteristic (ROC) curve.METHODS: A thermal desorption (TD)-gas chromatography (GC)-mass spectrometry (MS)-based analytical method utilizing a PEG phase GC column was developed for the detection of biologically relevant VOCs. The multi-step VOC identification methodology was upgraded through several developments: candidate VOC grouping schema, ion abundance correlation based spectral library creation approach, hybrid alkane-FAMES retention indexing, relative retention time matching, along with additional quality checks. In combination, these updates enable highly accurate identification of breath-borne VOCs, both on spectral and retention axes.RESULTS: A total of 621 features were statistically determined as on-breath by at least one metric (standard deviation, paired t-test, or ROC). A total of 38 on-breath VOCs were able to be confidently identified from comparison to chemical standards.CONCLUSION: The total confirmed on-breath VOCs is now 186. We present an updated methodology for high-confidence VOC identification, and a new set of VOCs commonly found on-breath.PMID:39832034 | DOI:10.1007/s11306-024-02218-8