PubMed

Proc Natl Acad Sci U S A. 2025 Apr 15;122(15):e2411241122. doi: 10.1073/pnas.2411241122. Epub 2025 Apr 11.ABSTRACTMetastasis is an inefficient process requiring cancer cells to adapt metabolically for survival and colonization in new environments. The contributions of tumor metabolic reprogramming to lymph node (LN) metastasis and its underlying mechanisms remain elusive. Through single-cell RNA sequencing, we identified rare metastasis-initiating cells (MICs) with stem-like properties that drive early LN metastasis. Integrated transcriptome, lipidomic, metabolomic, and functional analyses demonstrated that MICs depend on oxidative phosphorylation (OXPHOS) fueled by fatty acid oxidation (FAO) in the lipid-rich LN microenvironment. Mechanistically, the NRF2-SLC7A11 axis promotes glutathione synthesis to mitigate oxidative stress, thereby enhancing stress resistance and metastatic potential of MICs. Inhibition of NRF2-SLC7A11 reduced LN metastasis and sensitized tumors to cisplatin. Clinically, elevated NRF2-SLC7A11 expression was observed in tumors, with high expression correlating with LN metastasis, chemoresistance, and poor prognosis in esophageal squamous cell carcinoma (ESCC). These findings highlight the pivotal roles of FAO-fueled OXPHOS and NRF2 in LN metastasis and suggest targeting these pathways as a promising therapeutic strategy for metastatic ESCC.PMID:40215279 | DOI:10.1073/pnas.2411241122

J Appl Physiol (1985). 2025 Apr 11. doi: 10.1152/japplphysiol.00987.2024. Online ahead of print.ABSTRACTA chronic increase in mTORC1 signaling is implicated in reduced longevity, altered metabolism, and mitochondrial dysfunction. Abnormal mTORC1 signaling may also be involved in the etiology of sarcopenia. To better understand the role of mTORC1 signaling in the regulation of muscle metabolism we developed an inducible muscle specific DEPDC5 knockout model which results in constitutively active mTORC1 signaling. We hypothesized that constitutively active mTORC1 signaling in skeletal muscle would alter the metabolomic and lipidomic response to an acute bout of exercise. Wild-type (WT) and DEPDC5 muscle specific knockout (KO) mice were studied at rest and following a 1 hr bout of treadmill exercise. Acute exercise induced an increased reliance on glycolytic and PPP metabolites in the muscle of mice with hyperactive mTORC1. Lipidomic analysis showed an increase in triacylglycerols (TGs) in KO mice. While exercise had a pronounced effect on muscle metabolism, the genotype effect was larger, indicating that constitutively active mTORC1 signaling exerts a dominant influence on metabolic and lipidomic regulation. We conclude that increased mTORC1 signaling shifts muscle metabolism toward greater reliance on non-oxidative energy sources in response to exercise. Understanding the mechanisms responsible for these effects may lead to the development of strategies for restoring proper mTORC1 signaling in conditions such as aging and sarcopenia.PMID:40215109 | DOI:10.1152/japplphysiol.00987.2024

Anal Chem. 2025 Apr 11. doi: 10.1021/acs.analchem.4c06669. Online ahead of print.ABSTRACTThe metabolome offers a direct snapshot of cell function and can respond to external changes within a very brief time scale of seconds or minutes. In situ in-cell mass spectrometry, with minimal pretreatment, enables direct analysis in a nonvolatile salt environment. However, it is challenging to obtain abundant metabolomes due to the inherent incompatibility of nonvolatile salts with mass spectrometry. Here, we developed a dual desalting electrospray ionization mass spectrometry (dd-ESI MS) technology for in-cell MS measurement to obtain a comprehensive and native cellular metabolome in nonvolatile salt buffers. The salt ions and metabolites were initially separated through the mild electrophoretic effect of induced nanoelectrospray ionization (InESI). In the following electrospray process, the complex interactions between aqueous droplets and methanol droplets further enhanced the desalting effect. Compared with nanoESI, dd-ESI MS exhibited stronger salt tolerance and higher sensitivity for cell metabolome analysis in PBS buffer. Interestingly, we observed a significant enrichment of the sphingolipid metabolism pathway during the epithelial-mesenchymal transition, a metabolic pathway not previously confirmed by metabolomics techniques. In addition, the transcriptome analysis also revealed consistent gene changes, further confirming the validity of our findings. dd-ESI MS enabled the acquisition of a more comprehensive and native metabolome, providing novel insights into complex physiological processes.PMID:40214983 | DOI:10.1021/acs.analchem.4c06669

Anal Bioanal Chem. 2025 Apr 11. doi: 10.1007/s00216-025-05867-3. Online ahead of print.NO ABSTRACTPMID:40214762 | DOI:10.1007/s00216-025-05867-3

Cells. 2025 Apr 4;14(7):547. doi: 10.3390/cells14070547.ABSTRACTTumor-derived extracellular vesicles (EVs) play an important role in cancer progression. Neutral sphingomyelinases (nSMases) are lipid-modifying enzymes that modulate the secretion of EVs from cells. How nSMase activity and therefore ceramide generation affect the composition and functionality of secreted EVs is not fully understood. Here, we aimed to investigate the expression of nSMases 1 and 2 in prostate cancer (PCa) tissue and their role in EV composition and secretion for prostate cancer cell migration. Reduced nSMase 1 and 2 expression was found in prostate cancer and correlated with the age of the patient. When nSMase 2 was inhibited by GW4869 in PCa cells (PC3 and DU145), the EV secretome was significantly altered, while the number of EVs and the total protein content of released EVs were not significantly changed. Using proteomic analysis, we found that extracellular matrix proteins, such as SDC4 (Syndecan-4) and SRPX-2, were differentially secreted on EVs from GW4869-treated PC3 cells. In scratch wound migration assays, GW4869 significantly increased migration compared to control PC3 cells but not DU145 cells, while SDC4 knockdown significantly reduced the migration of PC3 cells. These and other nSMase-2-dependent secreted proteins are interesting candidates for understanding the role of stress-induced EVs in the progression of prostate cancer.PMID:40214501 | DOI:10.3390/cells14070547

Cells. 2025 Apr 1;14(7):526. doi: 10.3390/cells14070526.ABSTRACTPlatelet-rich plasma (PRP) is an extract enriched with growth factors that facilitate skin regeneration and rejuvenation. Here, the functionalities of PRP derived from various animal sources have been investigated and compared, focusing on its potential therapeutic applications in skin regeneration. Total antioxidant capacity, wound closure, and melanin content in cultured keratinocytes were used to evaluate the efficacy of different animal PRP sources. The PRP derived from deer exhibited the highest performance and was selected for subsequent proteomic and metabolomic analyses. Our findings indicate that deer blood is an optimal source of animal-derived PRP, demonstrating significant properties in promoting wound healing, anti-inflammatory responses, and skin regeneration. This identified PRP from deer sources can be developed as a safe and effective product for skin rejuvenation and regeneration.PMID:40214480 | DOI:10.3390/cells14070526

Cells. 2025 Apr 1;14(7):525. doi: 10.3390/cells14070525.ABSTRACTAlzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by metabolic dysregulation, oxidative stress, amyloid-β (Aβ) aggregation, metal dyshomeostasis, and mitochondrial dysfunction. Current treatments provide only symptomatic relief, highlighting the need for novel therapeutic strategies. This study investigates the metabolic effects of the alkaloids galantamine (GAL) and lycorine (LYC) in differentiated SH-SY5Y neuroblastoma cells, an established in vitro model for AD, which acquire a neuronal phenotype upon differentiation. Using untargeted and targeted NMR-based metabolomics combined with multivariate statistical analysis, we analyzed extracellular metabolic profiles under basal conditions and following Aβ42 exposure, both in the presence and absence of GAL and LYC. Our findings reveal distinct metabolic responses to Aβ toxicity, with significant alterations in pyruvate and glutamine metabolism. Both GAL and LYC contributed to the restoration of glutamine and lysine homeostasis, but LYC had a more pronounced effect, better sustaining cellular energy balance and mitochondrial function. Unlike LYC, GAL treatment was associated with pyruvate accumulation, highlighting a distinct metabolic response between the two compounds. These variations may reflect distinct mechanisms of action, potentially influencing their therapeutic roles in counteracting Aβ-induced toxicity. This study highlights the value of metabolic profiling for assessing neuroprotective agents and reinforces the potential of natural alkaloids in this context.PMID:40214479 | DOI:10.3390/cells14070525

Cells. 2025 Mar 30;14(7):514. doi: 10.3390/cells14070514.ABSTRACTThe uterine smooth muscle (myometrium) is an immunomodulatory tissue capable of secreting multiple chemokines during pregnancy. We propose that before term labor, chemokines secreted as a result of mechanical stretch of the uterine walls by the growing fetus(es) induce infiltration of maternal monocytes into myometrium, drive their differentiation into macrophages, and induce pro-inflammatory (M1) polarization, leading to labor contractions. This study used high-throughput proteomic mass-spectrometry to investigate the underlying mechanisms and explored the therapeutic potential of a broad-spectrum chemokine inhibitor (BSCI, FX125L) in modulating these effects. Primary myocytes isolated from the myometrium of term pregnant women were subjected in vitro to static mechanical stretch. Proteomic analysis of stretched myocyte-conditioned media (CM) identified significant upregulation of chemokine-related pathways and ECM degradation proteins. CM induced in vitro differentiation of human monocytes to macrophages and polarization into an M1-like phenotype characterized by elevated ROS production. BSCI treatment altered the myocyte secretome, increasing tissue-remodeling and anti-inflammatory proteins, Annexin A1 and TGF-β. BSCI-treated myocyte secretions induced Annexin A1 expression in macrophages and enhanced their phagocytic activity. We conclude that factors secreted by mechanically stretched myocytes induce pro-inflammatory M1 macrophage polarization, while BSCI modulates myocyte secretome, which reprograms macrophages to a homeostatic M2-like phenotype, thus reducing inflammation. When treated with BSCI, M2-polarized macrophages reduced myocyte-driven collagen gel contraction, whereas M1 macrophages enhanced it. This study reveals novel insights into the myocyte-macrophage interaction and identifies BSCI as a promising drug to modulate myometrial activity. We suggest that uterine macrophages may represent a therapeutic target for preventing preterm labor in women.PMID:40214468 | DOI:10.3390/cells14070514

Plant Cell Environ. 2025 Apr 11. doi: 10.1111/pce.15536. Online ahead of print.ABSTRACTThe accumulation of the livestock-harming cyanogenic glucoside dhurrin in the vegetative tissues limits the use of sorghum as a major pasture crop. This study integrates transcriptomics and metabolomics data from the ICSV 93046, CSH 24-MF and ICSR 14001 genotypes, which differ in drought tolerance and cyanide potential (HCNp), to understand the molecular processes of cyanogenesis under drought stress conditions. While ICSV 93046 showed drought adaptation and reduced HCNp, ICSR 14001 and CSH 24-MF exhibited decreased drought stress tolerance with HCN accumulation. The differentially expressed gene (DEG) data showed drought-related genes were significantly upregulated in ICSV 93046 but downregulated in ICSR 14001. KEGG pathway analysis revealed enriched dhurrin biosynthesis and cyanoamino acid metabolism genes, with higher expression in ICSR 14001 than in ICSV 93046. WGCNA analysis revealed that hub genes are involved in drought-induced signalling components, such as phospholipases (PLPs) and lipoxygenases (LOXs), which are implicated in membrane protection. In drought-sensitive genotypes, stress-induced membrane damages lead to the release of dhurrin into the cytoplasm, thus elevating HCN content and activating defence responses. Conversely, the drought-adapted genotype could mitigate HCN production by averting membrane injury, thereby effectively modulating the oxidative stress and preventing the release of dhurrin into the cytoplasm.PMID:40214306 | DOI:10.1111/pce.15536

Microbiol Spectr. 2025 Apr 11:e0072124. doi: 10.1128/spectrum.00721-24. Online ahead of print.ABSTRACTDistiller's grains (DG) are a potential source of animal feeds, and many studies have indicated positive regulatory roles of feeding DG diets in animal breeding. However, there is currently a dearth of research on the actions and underlying mechanisms of probiotics-fermented distiller's grains (FDG)-based diets in cattle breeding. This study aimed to assess the impact of integrating FDG into the diet of finishing cattle on their fecal microbial community and metabolites. Thirty Simmental crossbred cattle (local yellow cattle × Simmental cattle, 8.5 months old, 420.38 ± 68.11 kg) were selected and randomly divided into three dietary treatments, including the basal diet group (CON group), the FDG replacing 10% concentrate (FDG-10%) group, and the FDG replacing 20% concentrate (FDG-20%) group. 16S and ITS sequencing of fecal samples collected from each group on the 30th day of the formal feeding suggested that feeding FDG diets had little effect on the composition and diversity of fecal bacterial and fungal communities in finishing cattle. However, the relative abundance of cellulose-degrading bacteria, including the Christensenellaceae R-7 group and Ruminococcaceae family was significantly higher in both the FDG-20% vs CON comparison and the FDG-20% vs FDG-10% comparison. Besides, the FDG-10% group had a significant drop in the relative abundance of Aspergillus and a noteworthy increase in the relative abundance of Candida when compared to the CON group. Non-targeted metabolomics analysis showed that the addition of FDG modified the levels of organoheterocyclic compounds, lipids and lipid-like molecules, and benzenoids in the feces of finishing cattle and significantly enhanced the metabolic pathway of bile secretion. Further correlation analyses suggested a close association between the significantly differential fecal microbiota and metabolites. In conclusion, these results suggest that FDG supplementation has little effect on the structure and diversity of the fecal microbiota in finishing cattle, but alters intestinal metabolite profiles and influences bile secretion pathways by modulating the relative abundance of genera of fecal bacteria and fungi Christensenellaceae R-7 group, Lachnospiraceae_NK3A20_group, Mucor, and Candida. These findings provide a scientific theoretical basis for the use of FDG in animal feeds.IMPORTANCE: Probiotics-fermented distiller's grains (FDG) are potential feed sources for livestock. Here, we investigated the effects of partially replacing concentrates with FDG on fecal bacterial and fungal community structure and metabolic profiles in finishing cattle. The results reveal that feeding FDG-based diets alters intestinal metabolite profiles and up-regulates bile secretion pathways through the regulation of relative abundance of certain fecal genera. These findings provide some new insights into clarifying the role and potential mechanisms of FDG diets and also offer a scientific basis for the development of FDG into functional feed resources.PMID:40214255 | DOI:10.1128/spectrum.00721-24

mBio. 2025 Apr 11:e0047025. doi: 10.1128/mbio.00470-25. Online ahead of print.ABSTRACTGrowing evidence suggests that inadequate dietary fiber intake, termed the "fiber gap," is linked to disease states through disruption of the gut microbiota. Despite this, our understanding of how various fiber structures influence the microbiota and health is limited by the lack of diverse commercially available fibers. Studies have primarily focused on a limited range of fibers, rather than the diverse array of fibers representative of those commonly found in our diets. In this study, we aimed to investigate how naturally derived fibers impact the human microbiota and their metabolic products. We performed a comprehensive structural characterization and functional evaluation of a unique and highly diverse set of new, highly soluble fibers with varied monosaccharide compositions, glycosidic linkages, and polymer lengths. Using an ex vivo high-throughput human microbiota platform coupled with metabolomic profiling, we demonstrate that these diverse fibers drive distinct and consistent microbial and metabolic profiles across cohorts of donors in a structure-dependent manner. These metabolic effects were accompanied by both general and donor-specific changes in microbial taxa. Finally, we demonstrate that integrating detailed glycomic characterization with microbial and metabolomic data allowed for prediction of functional outcomes driven by a novel material, pineapple pulp fiber. This work highlights the potential for targeted dietary fiber interventions to modulate the microbiota and improve health outcomes, paving the way for the development of new fiber-rich products with specific health benefits.IMPORTANCEFiber deficiency is associated with numerous disease states, many of which are linked to disruption of the gut microbiota. This study encompasses the first systematic and comprehensive characterization of a diverse collection of naturally derived solubilized fibers and their impacts on the microbiota. The results expand our understanding of the beneficial effects of specific carbohydrate structures naturally found in the human diet, highlighting the potential for designing fiber-based health interventions. The high solubility of these fibers increases both the range of products they can be incorporated in as well as their assayability in experiments, enabling a widespread increase in fiber consumption and positive health impacts.PMID:40214223 | DOI:10.1128/mbio.00470-25

Arch Immunol Ther Exp (Warsz). 2025 Apr 11;73(1). doi: 10.2478/aite-2025-0011. eCollection 2025 Jan 1.ABSTRACTParkinson's disease (PD) affects millions of people globally. Accurate early diagnosis remains a challenge due to the lack of specific biomarkers. This systematic review explores the potential of 1H-NMR metabolomics in identifying diagnostic markers and therapeutic targets for PD. A comprehensive analysis was conducted across databases such as Scopus, Web of Science, PubMed, and Embase, focusing on studies that utilized 1H-NMR spectroscopy to profile metabolites associated with PD progression. The review identifies key metabolites-glutamate, taurine, myo-inositol, glutamine, and creatine-that play critical roles in the pathophysiology of PD. Glutamate, linked to excitotoxicity and neuronal degeneration, emerges as a prominent target for therapeutic intervention, while taurine is associated with oxidative stress. Myo-inositol, a key regulator of autophagy, underscores the biochemical dysregulation associated with PD, similar to glutamine and glutamate. Creatine's role in neuronal energy metabolism suggests potential avenues for treatment focused on energy supplementation. The reproducibility of metabolite findings varied, indicating the complexity of PD's metabolomic landscape. Despite challenges in consistency, these metabolites hold promise as biomarkers for diagnosing PD and tracking disease progression. The review underscores the need for further validation of these markers and their integration with other omics technologies to enhance PD management. By identifying key metabolic pathways, this study opens new directions for personalized medicine, offering potential therapeutic targets to slow disease progression and improve patient outcomes.PMID:40214076 | DOI:10.2478/aite-2025-0011

Gut Microbes. 2025 Dec;17(1):2490207. doi: 10.1080/19490976.2025.2490207. Epub 2025 Apr 11.ABSTRACTInflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is considered significant global health concerns worldwide. Many studies have demonstrated that environmental and dietary factors influence the gut microbiota, which in turn orchestrates the host immune responses. These interactions are also involved in complex metabolic processes that contribute to the pathogenesis of IBD. Furthermore, recent studies in genomics and metabolomics have unveiled the intricate relationship between microbial influencers and host epigenetics. The dynamics of gut microbiota and its metabolites intricately align with DNA methylation, histone methylation, lactylation, glycosylation, and non-coding RNAs, which are key players in epigenetics. Here, we summarize and discuss the complex interplay among gut microbiota, epigenetics, and environmental and dietary factors, and their impact on the pathogenesis of IBD. Furthermore, we highlight the importance of multi-omics technologies in dissecting the host-microbe interactions in IBD, potentially offering a framework for developing effective treatment strategies.PMID:40213833 | DOI:10.1080/19490976.2025.2490207

Front Endocrinol (Lausanne). 2025 Mar 27;16:1433534. doi: 10.3389/fendo.2025.1433534. eCollection 2025.ABSTRACTINTRODUCTION: Pregnant women with subclinical hypothyroidism or clinical hypothyroidism often exhibit lipid metabolism disorders and are correlated with adverse pregnant outcomes. It was suggested that isolated positive thyroid peroxidase antibody (TPOAb) served as a risk factor for adverse outcomes. However, little was known about the lipid metabolism profile in pregnant women with isolated positive TPOAb. The purpose of this prospective observational study was to investigate the expression of lipid profiles among euthyroid pregnant women with positive TPOAb during there early pregnancy and to analyze their correlation with thyroid function.METHODS: Non-targeted liquid chromatography-mass spectrometry (LC-MS) technology was used to perform lipidomics analysis on serum samples collected during early pregnancy from pregnant women who with isolated positive TPOAb and those in the healthy control group. Partial least squares-discriminant analysis (PLS-DA), KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis, and correlation analysis were conducted to explore differential lipid molecules and their associations with clinical parameters.RESULTS: A total of 90 pregnant women in the first trimester were enrolled in the analysis: 46 were TPOAb-positive euthyroid pregnant women, and 44 were healthy pregnant women. A total of 1238 lipid molecules were identified, and 202 differential lipid molecules were screened between the two groups. KEGG pathway enrichment analysis revealed that the differentially expressed lipids participate in several pathways. Correlation analysis showed LPC(20:4), LPC(18:0), LPC(22:4), LPC(22:5), LPC(18:1), PC(20:1/20:4) were both positively correlated with TPOAb titers and sCD40L. LPC(20:0) was positively correlated with the level of remnant cholesterol (RC) and PC(20:1/20:4) was negatively correlated with RC.DISCUSSION: The lipid profile of isolated TPOAb-positive euthyroid pregnant women was significantly different from that of healthy pregnant women and involved in several pathways. The pathophysiological role of altered lipid molecules should be further investigated since they might be potential biomarkers for adverse pregnancy outcome in pregnant women with isolated positive TPOAb.PMID:40213108 | PMC:PMC11982940 | DOI:10.3389/fendo.2025.1433534

J Sci Food Agric. 2025 Apr 11. doi: 10.1002/jsfa.14274. Online ahead of print.ABSTRACTBACKGROUND: Sojae semen praeparatum (SSP) is an edible fermented product and traditional Chinese medicinal, with demonstrated bioactivity. Fermentation is an important factor that influences the bioactivity of SSP. However, the changes in the bioactivity and bioactive compounds of SSP during the fermentation process remain largely unknown.RESULTS: The study revealed that fermentation significantly enhanced the bioactivity of SSP, particularly in terms of antioxidant capacity and acetylcholinesterase (AChE) inhibition. Antioxidant assays demonstrated that the antioxidant capacity of SSP increased significantly with prolonged fermentation time, indicating that fermentation duration is a critical factor in enhancing its functionality. Metabolic profiling revealed a substantial accumulation of organic acids and isoflavone compounds during fermentation, with flavonoid compounds such as casticin, naringenin, kaempferide, genistein, quercetin and daidzein exhibiting superior in vitro AChE inhibitory activity. Furthermore, the release of flavonoid compounds was significantly elevated during simulated digestion, further contributing to the enhanced functional properties of SSP.CONCLUSION: These findings suggest that flavonoid compounds are key bioactive components in SSP, and further research on these compounds is beneficial for improving the quality of SSP, as well as providing scientific insights into the comprehensive effects of the fermentation process on SSP and its bioactivity. © 2025 Society of Chemical Industry.PMID:40213821 | DOI:10.1002/jsfa.14274

Theranostics. 2025 Mar 1;15(9):3713. doi: 10.7150/thno.104739. eCollection 2025.ABSTRACT[This corrects the article DOI: 10.7150/thno.18788.].PMID:40213655 | PMC:PMC11980663 | DOI:10.7150/thno.104739

Front Immunol. 2025 Mar 27;16:1537398. doi: 10.3389/fimmu.2025.1537398. eCollection 2025.ABSTRACTINTRODUCTION: Following the approval of Chimeric Antigen Receptor T-cell Immunotherapy(CAR-T) in multiple countries, the Food and Drug Administration (FDA) approved tumor-infiltrating lymphocytes (TILs) and T-cell receptor-engineered T cells (TCR-T) treatments this year. The utilization of adoptive immunotherapy in tumor treatment has become increasingly prominent. Optimizing the cytotoxic effects of immune cells under in vitro culture conditions represents a current hot research topic in this domain.METHODS: In the current experiment, we conducted in vitro heat treatment on Jurkat-derived T cells at 39°C. On this basis, we utilized nine distinct injectable solutions and over 70 monomer components of Traditional Chinese Medicine (TCM). Subsequently, we co-cultured these treated Jurkat cells with K562-eGFP cells, and the co-culture process was monitored in real-time using the IncuCyte live-cell analysis system. Equally important, we combined HiMAP high-throughput transcriptome sequencing, proteomics, and metabolomics for in-depth examination. We screened for compounds possessing anti-tumor properties and thoroughly investigated their mechanisms of action.RESULTS AND DISCUSSION: The findings indicated that heating treatment augmented the cytotoxic effect of Jurkat cells against malignant tumors, and the optimal effect was achieved when T cells were exposed to 39°C for a duration of 24 hours(48% increase in cell proliferation rate compared to 37°C treatment). By triggering the generation of heat shock proteins and facilitating mitochondrial energy supply, the 39°C treatment amplified the anti-tumor functions of T cells. By analyzing the data, we identified 3 injectable solutions and more than 20 effective monomers capable of further enhancing the tumor-killing ability of T cells. High-throughput transcriptomics studies disclosed that the combination of thermotherapy and TCM promoted Jurkat cell proliferation, activation, and cytotoxic functions of Jurkat cells, thereby activating the Regulation of mitotic cell cycle to exert anti-tumor effects. The integration of transcriptomic and proteomic data demonstrated that Shengmai Injection significantly enhances the tumor-killing effect of Jurkat cells by down-regulating the Regulation of Apoptosis and Regulation of mitotic cell cycle signaling pathways.PMID:40213558 | PMC:PMC11983556 | DOI:10.3389/fimmu.2025.1537398

Noncoding RNA Res. 2025 Feb 28;12:141-151. doi: 10.1016/j.ncrna.2025.01.003. eCollection 2025 Jun.ABSTRACTOBJECTIVE: Recent evidence underscores the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating bone remodeling and skeletal homeostasis by harmonizing osteoblast and osteoclast development. Notably, the oncogenic lncRNA, Hottip, implicated in osteogenesis regulation, remains insufficiently elucidated. This study aims to delineate Hottip's role in bone remodeling and skeletal homeostasis.METHODS: Hottip knockout mice were generated to discern its impact on bone metabolism. In vitro experiments probed cellular mechanisms influenced by Hottip, while molecular interactions were explored to understand its basis. The therapeutic potential of Hottip overexpression was investigated through in vivo experiments.RESULTS: Hottip knockout mice displayed disrupted bone metabolism, aberrant tissue, and compromised quality, leading to delayed fracture healing. In vitro, Hottip knockdown impeded osteoblast differentiation, while promoting osteoclast differentiation, with converse effects upon Hottip overexpression. Mechanistically, Hottip physically interacted with EZH2, inducing its degradation and enhancing osteogenic gene transcription by suppressing H3K9me3 and H3K27me3. In vivo experiments validated Hottip overexpression's potential to promote bone regeneration and hasten fracture healing.CONCLUSION: In summary, this study identifies Hottip as a critical regulator in osteoblast and osteoclast differentiation, crucial for maintaining skeletal homeostasis. Hottip emerges as a promising therapeutic target for enhancing bone regeneration. These findings contribute valuable insights into lncRNA-mediated mechanisms governing skeletal dynamics.PMID:40213386 | PMC:PMC11985131 | DOI:10.1016/j.ncrna.2025.01.003

Food Chem X. 2025 Mar 24;27:102410. doi: 10.1016/j.fochx.2025.102410. eCollection 2025 Apr.ABSTRACTTea quality in greenhouse was certain gap with open air. Metabolites and foliar microorganisms were investigated under seaweed fertiliser (CF) and gibberellin (CH) treatments using sensory evaluation, HPLC, untargeted metabolomics, 16S rDNA, and Internal Transcribed Spacer. CF tea was mellow, less astringent, and of better quality compared to CH. Catechin, -(-)Epicatechin, and Epigallocatechin were notably lower in CF. Differentially accumulated metabolites (DAMs) were notably enriched in Flavonoid and Phenylpropanoid biosynthesis, both involved in Catechin synthesis. DAMs in these pathways appeared down-regulated in CF. The CF improved quality by down-regulating metabolites in Phenylpropanoid biosynthesis in conjunction with microbial community metabolism enriched in amino acid and secondary metabolite biosynthesis. Metabolite- microbial correlation analysis indicated that the highest correlation with phenylpropane pathway metabolites was in bacteria Variovorax and Pseudomonas, and in fungi Filobasidium. The study provides theoretical basis for regulating flavour quality of greenhouse tea.PMID:40213339 | PMC:PMC11985128 | DOI:10.1016/j.fochx.2025.102410

Food Chem X. 2025 Mar 21;27:102407. doi: 10.1016/j.fochx.2025.102407. eCollection 2025 Apr.ABSTRACTKoumiss is a fermented mare's milk beverage with a long history. However, due to the current lack of specialized starters, the product quality is unstable. Therefore, we used dual-omics combined with pure culture technology to screen out strains with excellent fermentation performance for koumiss. The results showed that: (1) The dominant species in koumiss were mainly Lactobacillus and Lactococcus, and metabolites such as arachidonic acid and ascorbic acid were significantly enriched in koumiss. (2) There was a significant correlation between specific microbial species and metabolites. (3) Through preliminary screening using experiments such as milk-based curdling experiments and acid resistance tests, and then rescreening through fermentation tests, five strains with excellent fermentation characteristics were screened out. They are Lacticaseibacillus paracasei SXM-5, Lactobacillus kefianofaciens MGE42-8, Lactobacillus helveticus CFS12-11-1, Saccharomyces cerevisiae PFD-2, and Kluyveromyces marxianus PYM-1. The screened strains supply microbial resources for koumiss products and boost the development of milk beverages.PMID:40213331 | PMC:PMC11984606 | DOI:10.1016/j.fochx.2025.102407