Search Results (13,789)

Metabolic reprogramming is a core hallmark of malignancy, enabling tumor cells to sustain rapid proliferation, evade immune elimination, and develop resistance to therapy. Although a wide range of plant-derived phytochemicals exhibit anticancer activity with comparatively low toxicity, their capacity to disrupt specific metabolic dependencies exploited by tumors has not been comprehensively synthesized. This review brings together current mechanistic evidence showing how major phytochemical classes, including polyphenols, terpenes and terpenoids, glucosinolates, and alkaloids, interfere with pathways central to tumor metabolic fitness, such as aerobic glycolysis, pentose phosphate pathway flux, mitochondrial substrate oxidation, glutamine dependence, and redox homeostasis. It further introduces a pathway-focused framework that links phytochemical mechanisms to quantifiable metabolic outcomes and highlights their potential to remodel the tumor microenvironment by altering nutrient competition, oxidative stress responses, and hypoxia-driven signaling. Key barriers such as poor systemic bioavailability, rapid metabolic degradation, and limited tissue penetration are assessed alongside emerging formulation and delivery strategies designed to enhance therapeutic exposure while preserving low-toxicity profiles. Mapping these mechanistic insights onto clinical development needs allows prioritization of specific phytochemical-metabolic pathway pairs with the strongest potential for translation. This positions plant-derived metabolic disruptors as promising candidates for next-generation, low-toxicity anticancer therapies that strategically exploit defined metabolic vulnerabilities. Full article

The deep physiological dormancy of Zanthoxylum armatum DC. seeds severely limits its seedling propagation efficiency. Variable temperature stratification is an effective treatment for promoting dormancy release; however, the metabolic basis underlying this process remains poorly understood. In this study, we utilized a UPLC-MS/MS-based untargeted metabolomics approach, coupled with multivariate statistical analyses (PCA and OPLS-DA), to profile metabolic changes in Z. armatum seeds subjected to variable temperature stratification in a moist sand substrate (15 °C in the dark for 10 days, followed by 4 °C for 20 days). A total of 3687 metabolic features were detected, among which 33 structurally annotated differential metabolites were retained for biological interpretation, including 8 upregulated and 25 downregulated metabolites. Pathway enrichment analysis indicated that α-linolenic acid metabolism and linoleic acid metabolism were markedly altered after stratification. In particular, 9-(S)-HPOTE, colneleate, jasmonic acid (JA), and JA-ACC were significantly reduced, suggesting that attenuation of JA-related oxylipin metabolism may be associated with dormancy release in Z. armatum seeds. In addition, coordinated changes in phenylpropanoid- and cutin/wax-related metabolites implied remodeling of seed-coat-associated metabolism, whereas the accumulation of branched-chain amino acids and the alteration of sulfur- and purine-related metabolites suggested reorganization of metabolic reserves during the transition from dormancy to germination. Overall, these results provide metabolomic evidence that variable temperature stratification is associated with extensive metabolic reprogramming in Z. armatum seeds and highlight JA-related lipid metabolism as a candidate pathway involved in dormancy release. Full article

Micro/nanoplastics (MNPs) are emerging contaminants of concern for maternal and fetal health, yet their effects on the maternal–fetal circulation and serum metabolic homeostasis remain unclear. Here, we investigated the maternal and offspring toxicity of polystyrene microplastics (PS-MPs) and serum metabolomic alterations in dams and offspring. PS-MPs accumulated in multiple tissues, including blood, indicating maternal-to-offspring transfer. Continuous exposure reduced litter size, induced hepatic oxidative stress, and increased IL-6 and TNF-α levels in a dose-dependent manner in both dams and offspring. In dams, PS-MPs also decreased red blood cell and platelet counts and altered leukocyte composition, with increased lymphocyte and decreased neutrophil percentages at the high dose. Untargeted serum metabolomics revealed distinct exposure-related metabolic profiles, including 18 putatively annotated signature metabolites and 26 differentially abundant metabolites. Bilirubin and presqualene diphosphate were exclusively detected in exposed animals, whereas metabolites associated with lipid oxidation and mitochondrial fatty acid β-oxidation were elevated after exposure. RT-qPCR further supported altered expression of genes involved in these pathways. Overall, PS-MPs disrupted hematological homeostasis and metabolic regulation, likely through hepatic lipid peroxidation and systemic inflammation, and serum bilirubin and presqualene diphosphate may serve as candidate biomarkers of exposure. Full article

Lignocellulosic biomass represents an abundant and renewable carbon source, and its valorization through microalgal cultivation offers a sustainable route to resource-efficient bioprocessing. This study examined the effects of various carbon and nitrogen sources on the growth and lipid metabolism of Desmodesmus subspicatus, with a focus on ryegrass enzymatic hydrolysates as an alternative carbon source. Cultures were supplied with glucose, xylose, or arabinose at different concentrations, along with sodium nitrate or yeast extract, under different carbon-to-nitrogen ratios. Additionally, the impacts of alkaline- and acid-pretreated enzymatic ryegrass hydrolysates were evaluated. Growth was assessed by optical density and gravimetric analysis, and fatty acid profiles by gas chromatography. Glucose supplementation enhanced lipid accumulation, yielding fatty acid profiles dominated by C16 and C18 fatty acids, which are favorable for the quality of the produced biodiesel. Nitrogen limitation further promoted lipid accumulation; cultures supplied with sodium nitrate achieved higher total lipid content, while yeast extract favored greater proportions of PUFAs. Alkaline-pretreated ryegrass hydrolysate supported dose-dependent biomass formation reaching approximately 12 g L⁻¹ at 50%, whereas the acid-pretreated hydrolysate exhibited inhibitory effects at the same concentration. Scale-up in a 1 L photobioreactor yielded lower biomass but higher lipid content with a fatty acid profile shifted to SFA. These results support ryegrass as a viable alternative carbon source and highlight cultivation parameters that influence growth and lipid quality relevant for biofuel applications. Full article

Pregnancy is characterized by progressive maternal hyperlipidemia, including increased triglycerides, total cholesterol, and low-density lipoprotein, with dynamic fluctuations in high-density lipoprotein. Excess maternal free fatty acids induce oxidative stress through reactive oxygen species, causing mitochondrial dysfunction, lipid peroxidation, activation of inflammatory pathways, and epigenetic remodeling in the placenta and fetal tissues. These molecular alterations impair placental lipid transport and nutrient sensing, leading to hypertrophy of fetal liver, myocardium, and adipose tissue, while disrupting neonatal glucose and lipid homeostasis and increasing susceptibility to perinatal complications and long-term metabolic disorders. This review aims to evaluate mechanistic pathways linking maternal lipid metabolism, oxidative stress, placental function, and fetal organ remodeling. Mechanistic and translational studies were identified through searches of PubMed, Scopus, the Cochrane Library, and Web of Science (2000–2025) using predefined keywords including lipid metabolism, free fatty acids, oxidative stress, placental lipid transport, epigenetics, DNA methylation, fetal programming, and perinatal outcomes. Evidence indicates that maternal lipid imbalance drives placental oxidative and epigenetic modifications, directly contributing to fetal organ hypertrophy and neonatal metabolic dysregulation. In conclusion, maternal dyslipidemia represents a modifiable determinant of fetal organ hypertrophy and long-term metabolic risk, supporting the clinical relevance of maternal lipid monitoring and targeted metabolic interventions during pregnancy. Full article

Chicken manure and its potential to contaminate water systems through the dispersal of pathogenic bacteria are major concerns in environmental and public health. In this study, a metagenomic analysis was employed to systematically identify and compare bacterial assemblages in chicken manure (CM) and in a contaminated sample of chicken manure wastewater (CMW). Whole DNA was extracted from CM and CMW, followed by whole-genome shotgun sequencing; data analysis was done using online Galaxy software (ver. 26.0.1.dev1). Metagenomic analysis reveals a complex One Health challenge. Data showed that CM and CMW are different in their microbiota, as indicated by a distinct separation of beta diversity values and limited overlapping of species between sample types. In the current study, we found a greatly significant common functional set of adapted bacterial masses, including major pathogenic bacterial groups as well as opportunistic and environmental bacterial species, indicative of a direct contamination from CM and CMW. Notably, in both CM and CMW, a plethora of opportunistic, enteric, and environmental pathogens like Escherichia coli, Salmonella enterica, and Acinetobacter baumannii were found, coupled with an indication of a direct functional flow between both ecosystems as tangled reservoirs. Chicken manure samples showed differences in taxonomic composition and inferred functional profiles at the time of sampling: CM1 was pathogen-enriched, CM2 exhibited strong nitrogen-supportive metabolism, CM3 was dominated by fiber-degrading decomposers, and CM4 showed high methane-producing potential with environmental risk. Such findings underscore the raising of chickens as a potential source of harmful bacteria for the environment. It is important to note that this study represents a preliminary investigation with certain limitations, including the absence of biological replicates, lack of temporal sampling, and limited capacity to infer dynamic ecological interactions. Yet this metagenomic report is more about describing the taxonomy and functional potential of the bacteria, rather than discussing the actual ecological processes of these microorganisms in the environment. Future studies will be required to explore these aspects. Full article

This study evaluated the effects of an Astragalus membranaceus stem and leaf–Angelica sinensis stem and leaf mixture (AASL) as a medicinal feed supplement on immune function, antioxidant status, inflammatory responses, gut microbiota and the serum metabolome in weaned Simmental bull calves. Calves were fed diets containing different levels of AASL, and serum immunoglobulins, inflammatory cytokines, and antioxidant indices were determined. In addition, fecal short-chain fatty acid (SCFA) concentrations, gut microbiota composition, and serum metabolic profiles were analyzed, followed by correlation analyses among the microbiota, SCFAs and metabolites. The results showed that AASL was rich in crude protein, crude fat and trace elements. 4% AASL supplementation increased serum immunoglobulin (IgG and IgM) levels, decreased tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1 beta (IL-1β) levels, and enhanced superoxide dismutase (SOD), glutathione (GSH) and total antioxidant capacity (T-AOC) activities (p < 0.01 or p < 0.001), indicating improved immune and antioxidant status and attenuated inflammatory responses. AASL also enriched beneficial bacterial genera, suppressed potentially harmful taxa, and increased SCFA concentrations. Differential metabolites were mainly enriched in tryptophan metabolism, lipid metabolism, neuroactive ligand-receptor interaction, sphingolipid signaling, and ATP-binding cassette (ABC) transporter pathways. Integrated microbiota metabolite analysis further suggested that AASL improved host metabolic status through the coordinated regulation of gut microbiota, SCFAs production and related metabolic pathways. Overall, AASL shows promise as a functional feed supplement for improving calf health. Full article

Hair loss, particularly androgenetic alopecia (AGA) and alopecia areata (AA), is a prevalent condition with widespread psychosocial impact. Recently, low-level laser therapy (LLLT) has emerged as a promising non-invasive therapeutic alternative due to its bioregulatory effects and favorable safety profile compared to conventional pharmacological treatments. In this study, we employed fluorescence lifetime imaging microscopy (FLIM) to investigate the effects of red-light irradiation on hair follicle dynamics and the cutaneous microenvironment in a C57BL/6 mouse model. A hair regeneration model was established to evaluate the efficacy of 650 nm red-light irradiation (bandwidth ± 20 nm). Then, the skin tissue was stained with hematoxylin and eosin (H&E) and followed by FLIM analysis to provide a multidimensional assessment of tissue morphology and metabolic status. Results showed that red-light irradiation significantly increased hair follicle numbers and enhanced adenosine triphosphate (ATP) levels in the skin tissue. FLIM analysis further revealed prolonged fluorescence lifetime values across different epidermal and dermal layers in the irradiated group, indicating significant alterations in the skin metabolic microenvironment. Furthermore, phasor plot analysis enabled precise differentiation between hair follicles and their surrounding skin structures, highlighting FLIM’s high sensitivity and accuracy in evaluating hair growth. In conclusion, this study has provided novel imaging-based insights into the mechanisms of LLLT-induced hair regeneration, highlighting the potential of FLIM as a powerful tool for characterizing the cutaneous microenvironment and quantitatively evaluating phototherapeutic efficacy in future translational applications. Full article

The present study evaluated the effects of dietary supplementation with Bacillus coagulans DSM 32016 on growth performance, hematological and biochemical parameters, and nitrogen metabolism in weaned Danube White pigs reared under standard production conditions. While supplementation did not result in statistically significant changes in average daily gain (ADG), feed conversion ratio (FCR), hematological indices, or serum lipid profile, numerical trends indicated slightly higher ADG, improved FCR, and subtle stabilization of hematological parameters in the probiotic supplemented group. Notably, serum urea concentration was significantly reduced (3.78 vs. 3.21 mmol/L; p = 0.017; Cohen’s d = 1.01), suggesting a potential positive effect on nitrogen metabolism and protein utilization efficiency. These findings are consistent with previous reports that probiotics may exert beneficial physiological effects even in the absence of statistically significant systemic changes. The observed trends highlight the potential of Bacillus coagulans to support growth performance and metabolic efficiency in Danube White pigs, emphasizing the importance of breed and age-specific responses in probiotic supplementation. Full article

Hydrochar application to soil inevitably releases hydrochar-derived dissolved organic matter (HDOM), yet its specific impact on soil microbial communities, independent of the hydrochar solid matrix, remains poorly understood. This study investigated, for the first time, the dose-dependent effects of HDOM on bacterial communities in three distinct soil types (red, yellow-brown, and black soils). A concentration gradient, including undiluted stock solution and 10-, 100-, and 1000-fold dilutions with ultrapure water, was established to test for hormesis-like responses. High-throughput 16S rRNA gene sequencing revealed that HDOM induced profound, soil-specific shifts in bacterial community structure. The application of HDOM induced the emergence of numerous specific bacterial taxa, with unique ASVs reaching up to 15,372. However, no significant changes were observed in microbial community richness or evenness (alpha diversity). Drastic shifts in beta diversity were evident only in red soil and yellow-brown soil, and exclusively under the undiluted HDOM treatment. At the phylum level, HDOM application did not alter the dominant bacterial types (top 10 phyla); however, their relative abundances were jointly regulated by both HDOM dose and soil type. Significant HDOM-induced changes in key bacterial biomarkers were primarily detected in red soil (e.g., phylum Elusimicrobia, class Fimbriimonadia, and family Alicyclobacillaceae) and yellow-brown soil (e.g., phylum Proteobacteria, class Alphaproteobacteria, and family Rhizobiaceae), while in black soil, such changes were observed only under the undiluted HDOM treatment (e.g., species Streptomyces rochei). Predictive functional profiling suggested limited impact on major metabolic pathways, with soil type remaining the primary determinant. These findings demonstrate that HDOM exerts a direct, dose-dependent, and soil-specific influence on bacterial communities, providing key insights into the environmental behavior of hydrochar and guiding its safe application. Full article

Lipidomics has emerged as a transformative discipline in biomedical research, providing high-resolution insights into metabolic signaling and disease pathophysiology. The R programming language provides a widely adopted framework for extensible analysis of complex lipidomic datasets due to its robust biostatistical infrastructure. Herein, we present a comprehensive roadmap for lipidomics in R, structured around a standardized analytical lifecycle: from raw data acquisition and preprocessing to structural annotation, statistical modeling and functional interpretation. We critically contextualize and integrate a curated suite of widely adopted R packages (version 4.3.0), including xcms and MSnbase for feature extraction, LipidMS 3.0 for fragmentation-based identification, and lipidr for quality control and normalization. Furthermore, we demonstrate how advanced tools such as mixOmics and clusterProfiler can be integrated to bridge the gap between differential lipid abundance and systems-level biological insights. Particular emphasis is placed on reproducibility, nomenclature standardization and the emerging role of machine learning in biomarker discovery. By synthesizing these resources into a coherent pipeline, this guide provides a structured reference for researchers. Further discussion addresses methodological pitfalls, statistical assumptions and reproducibility constraints that frequently compromise lipidomics studies. Ultimately, this structured approach facilitates systematic tool selection, accelerating the translation of complex lipidomic signatures into reproducible and clinically meaningful discoveries. Full article

Background/Objectives: Evidence remains limited on how post-diagnosis changes in moderate-to-vigorous physical activity (MVPA) are associated with triglyceride and fasting glucose levels in newly diagnosed diabetes. We examined this association in a Korean national cohort. Methods: Using the National Health Insurance Service National Sample Cohort, we identified adults with newly diagnosed diabetes in 2009–2010 who completed health screenings in both 2010–2011 (period I) and 2012–2013 (period II). Period II MVPA frequency was examined within strata defined by period I MVPA category. Adjusted least-squares means for five metabolic indicators were estimated using multivariable linear regression. Results: Among 3719 participants, the clearest associations were observed among those performing MVPA five or more times per week during period I, in whom lower period II MVPA frequency was associated with higher triglyceride (P for trend = 0.036) and fasting glucose (P for trend = 0.015) levels. Increases in MVPA among initially inactive participants were not consistently associated with favorable metabolic profiles. Conclusions: A post-diagnosis decline in MVPA was associated with higher triglyceride and fasting glucose levels, particularly among initially active individuals. Preventing declines in MVPA after diabetes diagnosis may be clinically relevant. Full article

Rice grain quality is strongly influenced by starch composition and structure, which differ between the two major cultivated Oryza sativa subspecies, indica and japonica. Although allelic variation in several key genes has been linked to these differences, it remains unclear whether subspecies divergence in starch metabolism is more strongly reflected in gene repertoire, structural organization, promoter composition, or transcriptional regulation. Here, we identified 52 starch metabolism-related genes representing 26 orthologous gene pairs in indica and japonica rice and compared their gene structures, predicted promoter cis-regulatory elements, and grain-filling expression patterns. The analyzed gene set was largely conserved between the two subspecies, with limited structural variation among orthologs. Although promoter analysis revealed differences in predicted cis-regulatory element composition, the strongest divergence was observed at the transcriptional level during grain filling. At 10 days after flowering (DAFs), RNA-seq profiling revealed relatively higher expression of several starch biosynthesis genes, including SSI, SSIIa, and BEI, in japonica than in indica. qRT-PCR further confirmed higher expression of SSI, SSIIa, BEIIb, and GBSSI in japonica, whereas AGPS2b was more highly expressed in indica during early grain filling. By 30 DAFs, expression of most tested genes had declined markedly in both subspecies. These findings indicate that divergence between indica and japonica is more clearly associated with transcriptional regulation during grain filling than with major differences in core starch metabolism gene content or structural organization. Full article

Landmark epidemiological studies and clinical trials, such as the Seven Countries Study, the Lyon Diet Heart Study, the PREDIMED Study and the CORDIOPREV Study, have shown significant reductions in cardiovascular events in those following the Mediterranean diet (MD). The aim of the present work is to summarize the most robust available evidence and the major biological pathways underlying the protective effects of the MD, with particular emphasis on the role of PAF inhibitors. Mechanistically, MD functions through a complex synergy of antioxidant, anti-inflammatory, and antithrombotic effects that collectively improve lipid profiles, enhance endothelial function, optimize postprandial metabolism and cell membrane signaling, making it a functional model for human longevity. The PAF-Implicated Atherosclerosis Theory has emerged as a key unifying framework, proposing that Platelet-Activating Factor (PAF)—a highly potent lipid inflammatory mediator—plays a central role in the initiation and progression of atherosclerosis. Oxidized LDL promotes the production of PAF and PAF-like lipids, leading to endothelial dysfunction, vascular inflammation, and atherosclerotic plaque formation. Traditional Mediterranean foods are rich in natural PAF inhibitors, particularly the polar lipid fractions of extra virgin olive oil, as well as wine, fish, vegetables, onions, and garlic. Animal studies demonstrate that these compounds can reduce or even regress atherosclerotic lesions, independently of serum cholesterol levels. Human dietary interventions have further shown that MD-based meals and functional foods enriched with PAF inhibitors reduce PAF activity and improve thrombosis-related biomarkers. This mechanistic framework helps explain phenomena such as the “French Paradox” and the cardio-protective effects associated with fish consumption. Moreover, the extraction of PAF inhibitors from Mediterranean food by-products, such as olive pomace, offers promising ecological and economic advantages. Collectively, targeting PAF and increasing dietary intake of PAF inhibitors represent promising strategies for the prevention and management of atherosclerosis and other inflammatory diseases, supporting the view that PAF may function as a major, modifiable risk factor in these conditions. Full article

Drought stress is one of the most critical abiotic stresses restricting global crop production, and sorghum plays an important role in arid and semi-arid areas due to its inherent drought tolerance compared to many other cereals. However, significant variation in drought tolerance exists among different sorghum genotypes, which provides an opportunity to dissect the underlying mechanisms. In this study, a drought-tolerant sorghum line (LNR-6) and a drought-sensitive line (LR-2381) were used for comparative analysis. Plants were grown under two water regimes: well-watered conditions (CK, soil water content maintained at 40%) and drought stress (soil water content reduced to 24%). Integrated transcriptomic and non-targeted metabolomic analyses were conducted to investigate the physiological and molecular mechanisms underlying sorghum drought tolerance. Phenotypic analysis showed that drought stress significantly reduced plant height and chlorophyll content in the drought-sensitive genotype, whereas the drought-tolerant genotype showed only minor changes. Transcriptome analysis identified several enriched functional categories of differentially expressed genes between the two genotypes under drought stress. Among them, genes associated with limonene and pinene degradation, photosynthesis, and photosynthesis-antenna proteins were significantly enriched and may be involved in drought-response regulation. Metabolomic analysis revealed significant accumulation of flavonoids and phenylpropanoids under drought conditions. KEGG pathway enrichment further indicated that flavone and flavonol biosynthesis, flavonoid biosynthesis, and phenylpropanoid biosynthesis were the most significantly enriched metabolic pathways. Overall, these findings enhance our understanding of the coordinated transcriptional and metabolic responses underlying drought tolerance in sorghum. Full article