Search Results (34,741)

Chronic heart failure [CHF] is a progressive clinical syndrome characterized by structural and functional impairment of the myocardium, in which energy metabolic remodeling plays a central role. Increasing evidence suggests that metabolic disturbances in CHF are not only a consequence of reduced cardiac output but also active regulators of epigenetic remodeling, thereby contributing to disease progression. Key metabolites, including α-ketoglutarate, acetyl-CoA, NAD⁺, S-adenosylmethionine, succinate, and 2-hydroxyglutarate, influence the activity of DNA methyltransferases, histone-modifying enzymes, and other chromatin regulators, thereby linking metabolic status to transcriptional control. Through these mechanisms, metabolic abnormalities promote persistent activation of pathological gene programs associated with cardiomyocyte hypertrophy, fibrosis, inflammation, apoptosis, and mitochondrial dysfunction, forming a self-reinforcing metabolic–epigenetic feedback loop in CHF. Although current guideline-directed medical therapies improve symptoms and clinical outcomes, they do not directly target this metabolic–epigenetic axis. Traditional Chinese medicine (TCM), including bioactive compounds, herbal formulas, patent medicines, and injections, has demonstrated potential in preclinical studies to modulate myocardial energy metabolism, improve mitochondrial function, and influence epigenetic regulators such as SIRT1, AMPK, and TET/JmjC-dependent pathways. However, most available evidence is derived from experimental models, and causal relationships between metabolite regulation, epigenetic remodeling, and cardiac functional improvement remain insufficiently validated. This review summarizes current knowledge on metabolite-driven epigenetic regulation in CHF and evaluates emerging evidence on the role of TCM in modulating this network. We also critically discuss key limitations, including reliance on non-clinical models, incomplete pharmacokinetic understanding, and insufficient causal validation. Finally, we propose future directions based on multi-omics integration, single-cell and spatial technologies, and systems biology approaches to facilitate mechanistic clarification and translational development of metabolism-targeted strategies for CHF. Full article

Optical fiber multi-analyte biosensors have become an important cutting-edge technology for the simultaneous detection of multiple biochemical substances in complex samples due to their unique advantages such as small size, anti-interference capability, and remote and label-free detection. This paper systematically reviews the recent research progress of optical fiber multi-analyte biosensors in the field of simultaneous detection of various types of targets. The review is organized by detection target type and elaborates on the simultaneous detection of biomarkers and proteins, viruses and bacteria, biological metabolites and nutrients, heavy metal ions, gases, organic pollutants, cells, and mixed detection of different types of biochemical substances. The advantages and disadvantages of existing optical fiber multi-analyte biosensors are summarized. Key technical challenges are also discussed, including issues of selectivity, long-term stability, real-sample validation, and system integration that currently hinder practical deployment. Finally, the future challenges and development directions of optical fiber multi-analyte biosensors are briefly discussed, providing references for relevant research teams. Full article

Background: Soil streptomycetes, particularly those isolated from extreme environments, are valuable sources of bioactive compounds. Their genomes encode a large number of biosynthetic gene clusters (BGCs), many of which can be simultaneously expressed. Methods: Molecular genetic methods were employed to identify Streptomyces anulatus 89 (Illumina NovaSeq 2 × 150 bp). Whole-genome phylogeny based on orthologous genes was employed using the Bacterial and Viral Bioinformatics Resource Centre services. Liquid chromatography–mass spectrometry analysis of biomass extract was carried out to identify antibiotics. Bioassays on cell lines were employed to evaluate the cytotoxicity and antitumor activity of the crude extract of the S. anulatus 89 strain. Results: Genome analysis identified 36 BGCs associated with secondary metabolites. The strain synthesized nactins, pladienolide, phenazinomycin, and 21-hydroxyoligomycin. The biomass extract demonstrated cytotoxicity against cancer cells and induced apoptosis. The A549 and A431 cell lines were the most sensitive. Changes in tumor cell morphology included rounding, shrinkage, increased granularity, and vacuolization. Conclusions: The ability of S. anulatus 89 to simultaneously synthesize different classes of anticancer antibiotics was reported. The investigated crude extract exhibited pronounced antitumor activity, making it a promising candidate for further studies. The underlying hypothesis suggested that strains with broad adaptive potential may serve as promising producers of natural products with antitumor properties. Full article

A major Chinese woody oil plant with unsaturated-fatty-acid-rich seeds for biodiesel and edible oil, Xanthoceras sorbifolium tolerates drought but not waterlogging; salicylic acid (SA), a key stress response signal, is inexpensive, safe, and effective for enhancing stress tolerance. Two-year-old saplings of Xanthoceras sorbifolium were used as materials. They were sprayed with 0.5 mmol·L⁻¹ SA for 3 days (based on prior studies), and then waterlogged for 10 days; physiological and transcriptomic data were collected. SA significantly increased height, diameter, and root dry weight by 392.6%, 450.0%, and 242.4% compared to water control; enhanced osmotic regulatory substances, antioxidant enzyme activities, secondary metabolites, and root activity; and reduced malondialdehyde content and relative electrical conductivity by 23.40% and 148.7%. SA-enhanced antioxidant defense correlated with synergistic transcriptional regulation. Transcriptome analysis showed that SA up-regulated key enzyme genes involved in flavonoid synthesis, such as PAL and 4CL, and regulated hormone signal transduction-related genes such as SAUR and DELLA. Key transcription factor genes were also screened, mainly including members of the MYB, bHLH, and ERF families. SA alleviated waterlogging damage. Meanwhile, this study provides valuable insights into the molecular basis of the response to waterlogging stress regulated by salicylic acid, and offers important theoretical and practical significance for the promotion and cultivation of Xanthoceras sorbifolium in rainy southern regions of China. Full article

Background/Objectives: Ceratonia siliqua L. (carob) is a rich source of bioactive compounds with potential health-promoting properties. This study investigated the kinetics of serum metabolites following the consumption of a carob beverage and evaluated associated changes in circulating antioxidant status. Methods: Fifteen apparently healthy adult men completed an acute postprandial intervention; only male participants were included to minimize the biological variability related to sex-dependent differences in phytochemical kinetics and antioxidant responses. Participants consumed a beverage from carob pod powder (30 g) dispersed in water (200 mL). Blood samples were collected at baseline and every 30 min for 6 h following intake. Serum metabolic profiling was performed using a non-targeted liquid chromatography–time-of-flight mass spectrometry (LC-TOF-MS) approach. Antioxidant responses were assessed by measuring ferric-reducing antioxidant power (FRAP) and serum resistance to copper sulphate-induced oxidation. Results: Twenty-four putative metabolites were detected, including phenolic compounds, fatty acids, amino acids, dipeptides, monosaccharides, pyridoxine, and gut microbiota-derived metabolites. Urolithin B appeared at 30 min (28.0 ± 4.0 × 10² a.u.), while p-cresol sulfate increased from 53.3 ± 6.5 × 10² a.u. at baseline to 130.0 ± 7.0 × 10² a.u. at 30 min. FRAP values did not change significantly over time (p = 0.332), whereas oxidation lag time showed a significant time effect (p = 0.001), reaching its highest mean at 180 min (9093.5 ± 1885.1 s). Conclusions: Carob beverage consumption resulted in a diverse postprandial serum metabolite profile. Antioxidant responses appeared to be only partly explained by circulating phenolics, suggesting that additional pathways and bioactive constituents may contribute. Full article

Rumen methane emissions contribute to global warming and energy loss in cattle. The use of plants rich in secondary metabolites to mitigate methane emissions has been extensively studied, with varying outcomes. The primary aim of this meta-analysis was to assess the impact of secondary metabolites on methane production, productive performance, and ruminal fermentation in beef cattle supplemented with plant-based additives. In accordance with the PRISMA guidelines, 43 of the 578 studies were selected for analysis, employing random-effects models to estimate the raw and standardized mean differences (RStudio: metafor and ggplot, with significance thresholds of p ≤ 0.05 and p ≤ 0.1). Heterogeneity was evaluated using the I² statistic, alongside a subgroup meta-regression examining variables such as dose, additive type, additive form, and forage-to-concentrate ratio. After performing Egger’s test and trim and fill analysis, it was determined that tannins reduced methane yield (g/kg DM, adjusted SDM = −0.463), increased propionate production (%, RMD = 0.066, p = 0.001), rumen pH (adjusted SMD = 0.307), and organic matter intake (RMD = 0.066, p = 0.01). Despite phenolic compounds, flavonoids, terpenes, and terpenoids successfully modulating methane production, fermentative parameters, and nutrient intake, the limited number of comparisons and publication bias suggest caution in generalizing these results. In conclusion, supplementation with plant-based additives containing tannins offers a promising nutritional strategy for reducing enteric methane emissions while maintaining beef cattle performance. Full article

Low temperatures limit the yield and stability of autumn-sown oats; thus, investigating cold resistance physiological responses is essential. In this study, we compared a cold-resistant variety (‘Aiwo’) and a cold-sensitive variety (‘Hewang’). ‘Aiwo’ exhibited a significantly higher overwintering survival rate (96.9%) and superior physiological traits, including elevated levels of soluble proteins, proline, putrescine, unsaturated fatty acids, and glutathione, alongside greater ATPase activity and reduced ROS levels. Exogenous putrescine application suggested a potential role of Put in alleviating lipid peroxidation. Metabolomic analysis showed that the arginine–proline and cysteine–methionine pathways were enriched among DAMs associated with ‘Aiwo’, accompanied by the accumulation of stress-protective metabolites. These metabolic changes may contribute to improved energy balance and membrane stability under low-temperature conditions. Our findings suggest that proline, putrescine, and glutathione are candidate physiological indicators associated with the cold-resistant phenotype, which may facilitate future screening of cold-resistant oat germplasm. Full article

Endophytic fungi from Malaysian medicinal plants constitute a metabolically prolific yet underexplored reservoir for natural product discovery. This scoping review of 56 studies published between 2015 and 2025 identified a fundamental methodological divergence within the field: while phenotypic bioactivity screening dominates the literature (>87% of studies), it is weakly supported by chemical characterization (<25%) and entirely disconnected from genomic investigation (0% biosynthetic gene cluster studies). This phenotype-first paradigm has largely confined the field to descriptive reporting, limiting mechanistic understanding and translational potential. Collectively, the evidence reveals a substantial disconnect between reported bioactivities and their underlying biosynthetic foundations. To address this limitation, a practical genotype-to-phenotype workflow is proposed that integrates strain prioritisation, multi-omics-guided activation, chemical mapping, and mechanism-oriented validation. By linking genomic potential with metabolite production and biological function, this framework provides a roadmap for advancing fungal natural product discovery beyond conventional phenotype-driven screening. Adoption of such approaches may improve the identification of chemically novel and biologically relevant metabolites while supporting the sustainable development of Malaysia’s endophytic fungal resources for biotechnological and pharmaceutical applications. Full article

Nicotine is the main psychoactive component of tobacco and is considered to be the main substance responsible for the development of tobacco addiction. The main enzyme responsible for nicotine metabolism, CYP2A6, catalyzes the conversion of nicotine to cotinine and the subsequent metabolism of cotinine to trans-3′-hydroxycotinine. CYP2A6 activity is known to be modulated by various compounds, such as quercetin. This repeated-measures study examined the effects of short-term quercetin supplementation on urinary nicotine metabolism biomarkers in adult users of conventional and alternative nicotine products. Seventy-two participants completed a two-week study protocol involving first-morning urine collection at four time points: baseline, immediately after three days of quercetin supplementation (500 mg/day), seven days after supplementation, and ten days after supplementation. Urinary nicotine, cotinine, and trans-3′-hydroxycotinine concentrations were measured, and the nicotine metabolite ratio was calculated as trans-3′-hydroxycotinine/cotinine. Repeated-measures analysis of variance was used to evaluate biomarker changes over time according to sex, nicotine product type, and self-reported nicotine consumption intensity. Quercetin supplementation did not consistently alter nicotine metabolism biomarkers, while a descriptive increase in median urinary nicotine concentration after supplementation was observed in participants reporting lower daily nicotine consumption compared with other groups. These findings suggest that further studies are warranted to better clarify the effects of quercetin on nicotine metabolism across different levels of nicotine exposure. Full article

Silver nanoparticles (AgNPs) synthesized via fungal-mediated biosynthesis have gained attention as eco-friendly alternatives to chemically produced nanomaterials, with broad biomedical potential. Fungi represent particularly attractive systems because their secretomes contain diverse biomolecules, including enzymes, proteins, polysaccharides, and secondary metabolites, capable of reducing silver ions and stabilizing the resulting nanoparticles. Despite extensive investigation, the molecular mechanisms underlying fungal-mediated AgNP formation remain poorly defined. This review critically examines the key biomolecular drivers involved in this process, with emphasis on nitrate reductases, oxidoreductases, extracellular proteins, polysaccharides, and secondary metabolites as potential reducing and capping agents. Proposed mechanisms, including nitrate reductase-dependent, superoxide-mediated, and metabolite-driven pathways, are evaluated. The influence of process parameters such as silver nitrate concentration, incubation time, culture medium composition, pH, temperature, and fungal species on nanoparticle yield, size, and stability is also assessed. Analysis of the current literature highlights significant knowledge gaps, including limited application of proteomic and metabolomic approaches, a lack of causal mechanistic studies, and insufficient standardization of experimental protocols. Overall, evidence indicates that fungal AgNP biosynthesis is governed by complex interactions among multiple biomolecular classes rather than a single universal mechanism, underscoring priorities for improving reproducibility, scalability, and mechanistic understanding. Full article

Usnic acid (UA) is a secondary metabolite produced by lichens that has attracted interest because of its antimicrobial, photoprotective, and antioxidant properties, suggesting its potential use as a biostimulant in agriculture. However, its evaluation in agricultural crops is limited. In the present study, we evaluated the effect of applying (+) UA on enzymatic and non-enzymatic antioxidant systems, photosynthetic pigments, photosynthetic enzyme activity, and markers of oxidative stress in “Albion” strawberry plants. The plants were grown in a peat moss:perlite substrate (1:1, v/v) and cultivated under tunnel greenhouse conditions using a nutrient solution applied via fertigation. (+) UA was applied at 400 µg/mL via three routes (foliar, drench, and a combination of foliar and drench) on three occasions. Leaf tissue was collected 117 days after transplantation, and the biochemical parameters were quantified. (+) UA increased the activity of glutathione peroxidase (GPX) (53% via foliar-drench) and catalase (CAT) by 73.5% (via drench), and reduced glutathione (GSH) content by 58% (via foliar). β-carbonic anhydrase (βCA) activity increased by 415% and 384% (foliar and foliar-drench, respectively). Likewise, Ribulose 1,5-bisphosphate carboxylase-oxygenase (RuBisCO) activity increased by 58.23% (drench) and phosphoenolpyruvate carboxylase (PEPC) by 25% and 46% (foliar and drench), suggesting positive effects on the processes associated with CO₂ assimilation and transport. In contrast, no significant changes were observed in the levels of hydrogen peroxide (H₂O₂), malondialdehyde (MDA), or proline, indicating the absence of oxidative stress. These findings suggest that (+) UA modulates the enzymatic antioxidant system, promoting favorable physilogical responses without inducing oxidative stress. The use of (+) UA has been proposed as a potential promoter of metabolism in agricultural crops. In addition, new avenues of research are being explored to investigate the role in modulating antioxidant responses under biotic and abiotic stress conditions. Full article

Although early-maturing table grapes possess significant commercial value, the metabolic impact of shortened ripening cycles on aroma-quality interactions remains underexplored. This study comprehensively characterized seven cultivars via integrated physicochemical phenotyping (firmness, total soluble solids, and phenolic content) coupled with a multi-platform volatile analysis using E-nose, GC–MS, and GC–IMS. Based on instrumental volatile profiling, the cultivars were classified into three aroma-related groups: a Muscat-type (HY, HMG, JM), enriched in floral monoterpenes; a Strawberry-type (XL, ZML), dominated by fruity, honey-like esters and aldehydes; and a Neutral-type (CG, SB), defined by herbaceous C₆ compounds. Notably, the combined use of E-nose, GC–MS, and GC–IMS provided complementary information for differentiating cultivar-specific volatile profiles. In particular, GC–IMS improved the detection of trace low-molecular-weight volatiles, thereby refining the characterization of cultivar-dependent aroma-related compounds. These findings provide an instrumental basis for understanding volatile differences among early-maturing table grapes and offer useful information for cultivar evaluation, flavor-oriented breeding, and postharvest quality management. Full article

Background/Objectives: Diagnostic metabolites measured in newborn screening, inherited metabolic disease, lysosomal storage disease, oncometabolite testing and routine clinical biochemistry are direct read-outs of human metabolic state. Their mechanistic interpretation requires linking measured metabolites to enzymes, pathways, regulatory context, disease knowledge and, increasingly, AI-assisted quantitative systems pharmacology (AI-QSP) workflows. We developed EHMN2026^®T as a license-aware AI-QSP integration framework that connects the EHMN2026^® metabolic backbone with licensed geneXplain knowledge resources while keeping ownership, licensing and redistribution constraints explicit. Methods: EHMN2026^®T integrates the SBML-encoded EHMN2026^® metabolic backbone with licensed TRANSFAC^® 2025.2, TRANSPATH^® 2025.2 and HumanPSD™ 2025.2 resources. TRANSFAC^® position weight matrices were used for promoter-level analysis of EHMN metabolic genes. The resulting transcription factor (TF)–gene connections were mapped to EHMN genes, TRANSPATH^® signalling/molecular-state entries and HumanPSD™ disease/drug context. The framework is positioned as a controlled component of the IQANOVA AI-QSP environment, but only aggregate statistics, non-proprietary EHMN-derived summaries and manuscript-level examples are reported publicly unless separate permission is obtained from the relevant rightsholders. Results: Promoter analysis of 1681 EHMN2026^® metabolic genes using 1147 mapped TRANSFAC^® matrices identified 291,387 ENSG-level TF–gene regulatory-potential connections involving 398 TFs and 1,107,264 predicted binding sites. The diagnostic panel contained 80 covered genes (63.5%), including complete coverage of oncometabolite enzymes and high coverage of organic acidaemia, steroidogenesis and fatty-acid oxidation categories. Mapping to TRANSPATH^® expanded the EHMN genes into 144,529 molecular-state representations and 14,879 gene–pathway or gene–chain pairs. HumanPSD™ was used as a licensed translational context layer; EHMN-specific HumanPSD™ outputs are treated as license-controlled derived outputs and are therefore not redistributed as open detailed tables in this manuscript. Conclusions: EHMN2026^®T provides a license-aware AI-QSP integration framework for tracing a diagnostic metabolite from a measured clinical value to candidate enzyme nodes, regulatory potential, signalling/molecular-state context and disease or therapeutic interpretation. PWM-derived TF–gene links are presented as regulatory hypotheses, not proof of active regulation. Public release should be limited to aggregate statistics and non-proprietary EHMN-derived components; detailed TRANSFAC^®, TRANSPATH^® and HumanPSD™-derived edges, mappings, annotations and SBML outputs remain subject to geneXplain ownership and licensing terms. Full article

The sustainable valorization of spontaneous flora biomass for the recovery of high value-added phytochemicals represents a key opportunity within the circular bioeconomy, yet it remains constrained by the environmental limitations of conventional extraction solvents and the lack of data-driven optimization frameworks. In this study, Natural Deep Eutectic Solvents (NADES) composed of betaine and 1,3-propanediol were designed and applied as bio-based extraction media for the recovery of bioactive metabolites from Artemisia annua L. spontaneous biomass in the context of green extraction and sustainable resource utilization. Two liquid–solid extraction techniques, namely vortex-assisted extraction and ultrasound-assisted extraction, were evaluated. The influence of key process parameters, including the eutectic component molar ratio, water content, solid-to-liquid (S/L) ratio, extraction temperature, and extraction time, was systematically investigated. Results demonstrated that extraction efficiency was strongly dependent on both solvent composition and process conditions, with distinct optimum parameters for different phytochemical classes. Maximum total polyphenol content (52.08 mg GAE/mL) was achieved via ultrasound-assisted extraction at 20 °C for 15 min, using a 1:3 NADES ratio with 40% water dilution and S/L = 1:5, while the highest flavonoid yield (17.34 mg QE/mL) was obtained by vortex-assisted extraction for 45 min using a 1:6 NADES ratio under the same dilution and S/L conditions. To identify extraction conditions associated with improved process efficiency, a hybrid modeling approach combining deep neural networks with the Success-History-based Adaptive Differential Evolution (SHADE) algorithm was employed, enabling high-accuracy prediction of extraction performance across a broad parameter space. The proposed framework demonstrates the feasibility of integrating green solvent design with machine learning-driven process modeling for the efficient valorization of underutilized plant biomass, contributing to the development of resource-efficient, sustainable extraction protocols, consistent with principles of process intensification and resource-efficient extraction strategies. Full article

Mangosteen peel (Garcinia mangostana L.) is widely recognized as a rich source of xanthone derivatives, particularly α-mangostin, which exhibits diverse pharmacological activities and is increasingly utilized in herbal medicines and nutraceutical formulations. This study aimed to develop an integrated chemical fingerprinting approach combining chromatographic quantification and spectroscopic profiling to discriminate and evaluate the quality of GMP (Garcinia mangostana peel) extract collected from different Indonesian provinces. Ethanolic extracts of GMP, originating from ten distinct geographical regions, were subjected to high-performance liquid chromatography (HPLC) for the quantitative determination of α-mangostin. Fourier transform infrared (FTIR) spectroscopy was employed to generate characteristic fingerprint profiles and assess the functional group patterns present in the extracts. The correlation between chromatographic data and spectroscopic signatures was evaluated to elucidate regional variability. The geographical origin of the GMP extract significantly influences its phytochemical composition and α-mangostin content. The combined FTIR–HPLC approach offers a robust and practical framework for extract differentiation, preliminary estimation of α-mangostin content, and quality assurance of mangosteen-derived raw materials intended for 6a-standardized herbal and nutraceutical products. Full article