Search Results (8,038)

Background and Objectives: Pro-inflammatory diet and high-fat diet (HFD) often coexist in real-world, but their combined impact on the gut–liver axis and potential nutritional countermeasures remain insufficiently studied. This study aimed to evaluate a pro-inflammatory–high-fat composite dietary pattern on the intestine and liver in the population, and to further evaluate the protective potential of astaxanthin (ATX) in complementary experimental systems. Methods: Data from the NHANES 2005–2010 were used to construct four composite exposure groups based on the dietary inflammation index (DII) and energy from fat. Survey-weighted regression analyses were performed to examine associations with systemic inflammation and liver injury. Interaction and C-reactive protein (CRP)-mediated effect analyses were conducted. Fifty SD rats were randomly divided into control group, model group induced by HFD combined with inflammatory factors, and low-, medium-, and high-dose Haematococcus pluvialis (HP) intervention groups. Serum lipids, liver enzymes, liver and colon pathology, and inflammatory and oxidative markers were measured in rats. In an in vitro organ-on-chip barrier model, the effect of ATX was observed when colonic barrier damage was induced using palmitic acid and lipopolysaccharides. Results: The high DII combined with HFD showed the largest increases in CRP, liver enzymes, and fatty liver index. A synergistic interaction was observed between DII and HFD, with CRP mediating approximately 20% of the effect. In rat model, HP-derived ATX improved the lipid profile, attenuated hepatic steatosis and oxidative damage, and reduced colonic pro-inflammatory cytokines, while restoration of tight junction proteins was limited. In colon organoid model, ATX showed limited efficacy in improving inflammation and barrier function. Conclusions: The pro-inflammatory–high-fat dietary pattern synergistically exacerbates gut–liver dysfunction. HP-derived ATX alleviates metabolic and inflammation-induced enterohepatic comorbidity, but its effect on repairing barrier structure is limited. Full article

European armillarioid fungi (Armillaria and Desarmillaria) are white-rot fungi with soilborne pathogenic potential on woody hosts and clear relevance to forest pathology. This structured narrative review synthesizes the reported chemical composition of European armillarioid taxa across wild basidiocarps, infected host material, and laboratory-derived matrices, with emphasis on metabolites and biochemical traits that can be interpreted in a forestry context. The available evidence is taxonomically and methodologically uneven and is dominated by A. mellea and A. ostoyae, whereas infected host material remains less well characterized than culture-derived and basidiocarp-derived material. Protoilludene-derived aryl esters provide the clearest compound-resolved evidence for antifungal and phytotoxic activity across controlled assay systems, but these data derive from distinct experimental formats that are not directly comparable as a single potency scale, while lipid profiling offers the strongest support for chemistry-based diagnosis from infected material. Overall, current evidence supports forestry interpretation, diagnostic profiling, and selective screening of culture-derived metabolites, but practical application remains constrained by matrix dependence, taxonomic gaps, and the limited transferability of in vitro findings to forest conditions. Full article

Endothelial dysfunction, chronic inflammation, immune dysregulation, oxidative stress, mitochondrial dysfunction, and metabolic disturbances collectively contribute to cardiovascular diseases (CVDs) associated with blood stasis patterns. Xuefu Zhuyu Decoction (XFZYD) is widely used clinically for the management of CVDs. Based on serum-exposed prototype profiling in rats, two pharmacology-driven core component sets of XFZYD were defined as the core set for the promotion of blood circulation and the elimination of blood stasis (CPBEB; HSYA, GRo, FA, β-ECD, AMY, ALB, PF) and the core set for the regulation of qi and the relief of pain (CRQRP; LIQ, NR, NAR, ROF, HSD, NHP, LTG, NRG, ISL, FNT, NOB, PD, SSa). CPBEB primarily targets vascular pathology by regulating endothelial dysfunction with dyslipidemia-driven arterial lipid deposition. Mechanistically, CPBEB is associated with improved endothelial function, reduced plaque instability, attenuated chronic inflammation and oxidative stress, normalized lipid and bile acid metabolism, and decreased thrombosis. CRQRP primarily modulates vascular tone and systemic energy metabolism. These effects are linked to enhanced AMPK/SIRT1-driven antioxidant defenses and mitochondrial homeostasis, increased NO/cGMP signaling, coordinated crosstalk among the TLR4/NF-κB, JAK/STAT, NLRP3, and PPAR pathways, and remodeling of the gut microbiota–immune network. In summary, this review integrates modern analytical approaches with network pharmacology and the literature evidence to clarify the material basis underlying XFZYD’s therapeutic effects in CVDs, thereby supporting the modernization and internationalization of traditional Chinese medicine. Full article

Background/Objectives: Dihydroartemisinin (DHA), a bioactive metabolite of Artemisia annua, displays potent antitumor activity in multiple cancers. However, its dose-dependent transcriptional regulatory networks in colorectal cancer (CRC) remain insufficiently understood. This study aimed to clarify the molecular mechanisms of low- and high-dose DHA in human CRC cells and reveal the dose-dependent crosstalk among related biological processes. Methods: We integrated RNA-seq transcriptomic profiling and functional validation in HCT116 cells treated with 20 μM (low-dose) or 50 μM (high-dose) DHA. Differentially expressed genes (DEGs) were screened at FDR ≤ 0.05 and |log₂(fold change)| ≥ 1, followed by GO and KEGG enrichment analyses. Results: DHA inhibited cell viability dose-dependently, with an IC₅₀ of 50 μM. We identified 280 and 678 DEGs in low-and high-dose groups, respectively. Low-dose DHA induced apoptosis via GADD45α/β and ATF4/DDIT3-mediated endoplasmic reticulum stress and triggered senescence through G2/M phase arrest. High-dose DHA mainly modulated gene expression signatures associated with ferroptosis by regulating iron homeostasis and lipid peroxidation at the transcriptional level. Both doses suppressed glycolysis, lipid, and folate metabolism; high-dose DHA also inhibited MGAT5B-mediated glycosylation. DHA regulated five core signaling pathways dose-dependently, with high-dose DHA further repressing Wnt3a/16 and BMP4/6. Conclusions: This study first identifies ferroptosis-related gene networks as key transcriptional targets. It reveals dose-dependent crosstalk among cell death, senescence, metabolic reprogramming, and signaling, providing a transcriptomic framework and gene targets for optimizing DHA-based colorectal cancer therapy. Full article

Cardiovascular-kidney-metabolic (CKM) syndrome integrates excess adiposity, metabolic dysfunction, kidney impairment, subclinical cardiovascular diseases, and clinical events along a staged continuum that invites unified prevention and treatment. Ultra-processed foods (UPFs) are a complex, high-prevalence exposure that may influence risk across CKM stages through nutrient profiles, additives, processing-induced compounds, and packaging-related contaminants. This review synthesizes epidemiologic, mechanistic, and translational evidence with attention to exposure definition and analytic rigor. We summarize NOVA-based UPF operationalization across dietary assessment tools, highlighting misclassification of mixed dishes, brand heterogeneity, and energy under-reporting, and we propose further examination of energy-adjusted models, calibration, and harmonized metrics. Observational studies consistently associate higher UPF intake with adiposity, diabetes, chronic kidney disease, cardiovascular events, and mortality, with modest to moderate effect sizes that are heterogeneous across populations. Mechanistic data from metabolomics, lipidomics, proteomics, and the gut microbiome converge on pathways of inflammation, lipid metabolism, oxidative and metabolic stress, and intestinal barrier dysfunction; in selected cohorts, multi-omics modules account for a substantial minority of UPF-outcome associations. We outline quality-control pipelines, batch-effect prevention/correction, and multiple-testing control necessary for reproducible diet-omics. Translationally, targeted lipidomic and proteomic panels show promise for CKM risk stratification and monitoring but require validation, clinical thresholds, and guideline endorsement. Equity and global context, including differences in product mix, food systems, and care capacity, modify population impact. We conclude with a research agenda prioritizing harmonized exposure metrics, error-aware modeling, standardized multi-omics workflows, and adequately powered, stage-specific interventions capable of testing mediation and prognostic utility. Full article

Cancer cells resort to metabolic reprogramming to sustain proliferation. Lung cancer has one of the highest mortality rates of all types of cancer. An important factor in its high mortality rate is its tumors’ ability to undergo significant metabolic reprogramming. Phytochemicals can counteract this altered metabolism and exhibit anticancer properties. Coleus hadiensis, a plant used in traditional medicine, has shown such potential. This study evaluated the in vitro cytotoxic activity of its methanolic extract and its effects on the metabolism of HTB-177 lung cancer cells. Qualitative and quantitative phytochemical analysis of this extract was performed to characterize its main constituents. Lung cancer cells were treated with different extract concentrations to evaluate their response to the extract. Cytotoxicity was determined using an MTT assay, and metabolites were analyzed through ¹H-NMR spectroscopy combined with multivariate statistical analysis. Transcriptomic profiling was also conducted to assess gene expression changes in metabolic pathways. Three main phenolic compounds were identified in the extract. The HPLC profile revealed peaks corresponding to gallic acid (GA), ferulic acid (FA), and rosmarinic acid (RA). The extract exhibited cytotoxic activity with an IC₅₀ of 192.85 µg/mL. Metabolic alterations were observed mainly in glycolysis, the Krebs cycle, and lipid metabolism—key pathways for tumor growth. Transcriptomic data revealed altered metabolism-related genes. The upregulation of ME1 correlated with the observed increase in pyruvate levels, while the downregulation of ALDH7A1 and ASRGL1 was linked to altered amino acid catabolism. Furthermore, transcriptomic data revealed the upregulation of the pro-apoptotic gene HRK. These results indicate that the methanolic extract of C. hadiensis possesses cytotoxic activity against lung cancer cells by modulating central metabolic routes and gene expression linked to cancer cell survival and proliferation. Full article

Texture-modified foods (TMFs) are essential for individuals with dysphagia, yet conventional formulations often lack structural consistency, nutritional density, and sensory appeal. Three-dimensional (3D) food printing offers new opportunities to tailor texture and composition. This study developed 3D-printed TMFs based on a lentil-carrot matrix and formulated with pea protein isolate (PPI), a curcumin-enriched oleogel (O), or their combination (PPI–O), and compared them with a commercial dysphagia thickener reference. Printability was assessed through extrusion force measurements and dimensional deviation analysis. Texture profile analysis (TPA), International Dysphagia Diet Standardisation Initiative (IDDSI) tests, moisture and protein content determination, color measurements, and preliminary sensory evaluation were conducted. PPI-containing formulations required higher extrusion forces but showed improved dimensional stability, hardness, cohesiveness, and gumminess compared with the oleogel-only sample, likely due to the formation of a stronger protein network. In contrast, the oleogel-only formulation exhibited lower mechanical resistance and a more pronounced melting perception, reflecting the lubricating effect of the lipid-based matrix. Protein content significantly increased with PPI incorporation, and curcumin-enriched oleogel also markedly influenced color parameters. All samples were classified as compatible with IDDSI Level 5. The hybrid PPI–O formulation provided a balanced combination of printability, structural fidelity, enhanced protein content, and suitable textural properties. These findings suggest that extrusion-based 3D printing may represent a promising approach for designing plant-based TMFs for dysphagia-oriented foods. Full article

Background: Epithelial-to-mesenchymal transition (EMT) is a cellular reprogramming process characterized by coordinated changes in signaling, membrane organization and metabolism. In a previously established and deeply characterized Huh7 EMT model, it was demonstrated that TGF-β stimulation induces a reproducible shift toward a mesenchymal state accompanied by lipidomic and metabolic remodeling. Building on this framework, the present study evaluates whether extracellular vesicles (EVs)-enriched fractions derived from Capparis spinosa can modulate these EMT-associated alterations. Methods: After detailed physicochemical, molecular, lipidomic and metabolomic characterization, C. spinosa EVs were applied to EMT-induced Huh7 cells. The vesicles were efficiently internalized and, while not inducing a complete epithelial reversion, they attenuated mesenchymal features, indicating a modulatory rather than inhibitory action. Results: Lipidomic profiling showed a partial correction of TGF-β-induced changes including diacylglycerols, phosphoinositides and triglycerides, suggesting interference with lipid signaling and membrane turnover. Metabolomic data further points to reduced mitochondrial and fatty acid oxidation stress, reflected in the re-equilibration of carnitine and acylcarnitine species. Conclusions: Together, these findings indicate that C. spinosa EVs are able to attenuate EMT-associated metabolic and membrane remodeling, positioning them as promising modulators of tumor cell plasticity. Full article

This study evaluated the effects of the preharvest application of 0.2 g/L gibberellin A3 (GA₃) or 0.02 g/L forchlorfenuron (CPPU) at full bloom on postharvest storability and defense responses in ‘Brightwell’ blueberry. After ripening, berries were inoculated in vitro with a defined mixture of postharvest fungal pathogens. Fruit quality attributes and physio-logical indices were monitored during storage, and LC-MS metabolomics was performed to characterize treatment-associated metabolic alterations.GA₃-treated fruit exhibited higher antioxidant capacity and a lower decay incidence than CPPU-treated and control fruit. Metabolomic profiling showed that GA₃ was associated with the accumulation of specific polyphenols, coinciding with enhanced resistance to postharvest pathogens. In parallel, GA₃ treatment modulated glycerolipid metabolism and mitigated membrane lipid peroxidation, as indicated by reduced malondialdehyde levels, while enhancing enzymatic (superoxide dismutase and ascorbate peroxidase) and non-enzymatic (poly-phenol) antioxidant defenses. Overall, these results suggest that preharvest GA₃ application can improve blueberry storability by coordinating redox homeostasis and lipid-related metabolic remodeling. Full article

Lipid recovery efficiency from microalgal biomass is a critical factor in the commercial viability of biodiesel. Scenedesmus sp. presents a robust cell wall that necessitates the evaluation of specialised disruption techniques to enhance intracellular lipid release and subsequent fuel quality. This study investigated the efficacy of five cell disruption methods—microwaves, ultrasonication, lyophilisation, autoclaving, and electroporation—integrated with three distinct extraction procedures: cold extraction, Soxhlet extraction system, and microwave-assisted extraction. The qualitative and quantitative impacts of these treatments were assessed by analysing the fatty acid methyl ester (FAME) profiles via gas chromatography (GC) following transesterification. The highest total lipid yield (88.97%) was achieved through a combination of microwave disruption and Soxhlet extraction. However, the maximal proportion of methyl esters was obtained when ultrasonication was paired with microwave-assisted extraction (97.64%). Surface analysis using scanning electron microscopy (SEM) of samples subjected to different disruption procedures could support the conclusions. Similarly, when the microalgal biomass was lyophilised beforehand, microwave extraction increased the oleic acid content. These results indicate that the choice of disruption and extraction protocols significantly influences both lipid recovery rate and the proportion of fatty acids in the chemical composition of microalgae. Tailoring these processes is essential for optimising the fatty acid profile for high-quality biodiesel production. Full article

Chronic exposure to even low levels of pesticides is a serious public health issue, mainly due to the role of oxidative stress in damaging the liver and promoting cancer. This has driven interest in finding natural, plant-based antioxidants that can counteract this kind of chemical injury. In this study, we tested whether a methanol extract from the leaves of Pteropyrum scoparium (PSE) could protect the liver against oxidative harm caused by four common pesticides: acetochlor, deltamethrin, thiamethoxam, and rotenone. Chemical analysis showed that the extract contains high levels of phenolics (345.1 ± 7.6 mg GAE/g) and flavonoids (17.3 ± 1.3 mg CAE/g). GC–MS profiling revealed a diverse set of compounds, including fat-soluble antioxidants like squalene, α-tocopherol, and γ-sitosterol, and water-soluble phenolics like pyrogallol and catechol, suggesting PSE is equipped with a multi-layered antioxidant defence. In the animal experiment, rats were given each pesticide for 30 days, with or without PSE. All four pesticides caused clear oxidative stress in the liver: glutathione (GSH), total antioxidant capacity (TAC), antioxidant enzymes activities dropped, while markers of lipid damage (MDA) and free radical activity (DPPH) rose. Co-administration of PSE significantly restored GSH, TAC and antioxidant enzymes levels and reduced MDA and residual DPPH values compared to pesticide-only groups; these parameters were statistically comparable to the controls (p > 0.05), indicating a substantial recovery of hepatic redox balance. Histopathological examination of liver tissues confirmed these findings, as pesticide treatment caused visible liver injury; deltamethrin and thiamethoxam led to congestion in central veins, while rotenone and acetochlor triggered clusters of inflammatory Kupffer cells. In animals that also received PSE, liver structure remained largely normal, with much less congestion and inflammation. These results show that the combination of antioxidant constituents in PSE might contribute to hepatoprotection through redox modulation and preservation of endogenous antioxidant balance, as suggested by the observed biochemical and histological improvements. Full article

Background: Recurrent vulvovaginal candidiasis (RVVC) is a chronic inflammatory disease primarily caused by Candida albicans (C. albicans). Its pathogenesis remains incompletely understood, and clinical management is challenged by recurrence and drug resistance. Ferroptosis, an iron-dependent form of programmed cell death driven by lipid peroxidation, has been implicated in various infectious and inflammatory diseases. However, its role in RVVC remains unclear, with a particular lack of evidence from clinical samples and animal experiments. Objective: This study aimed to investigate the association between RVVC and ferroptosis. First, we analyzed high-throughput sequencing data from human RVVC samples in the Gene Expression Omnibus (GEO) database to identify the expression profile of ferroptosis-related genes. Second, using an established murine model of chronic vulvovaginal candidiasis (CVVC), we validated changes in ferroptosis-related markers in vaginal tissues in vivo. Furthermore, an in vitro model of C. albicans-infected bone marrow-derived macrophages (BMDMs) was employed to explore the underlying mechanisms. This study provides experimental evidence for elucidating the pathogenesis of RVVC and exploring novel therapeutic strategies. Methods: The RVVC-related gene expression dataset GSE278036 was obtained from the GEO database. Differentially expressed genes (DEGs) were screened using the DESeq2 algorithm and intersected with ferroptosis-related genes from the FerrDb database to identify key targets. A protein–protein interaction (PPI) network was constructed using the STRING database and Cytoscape software, and hub genes were identified via the Betweenness centrality algorithm. Functional and pathway analyses, including gene set enrichment analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and WikiPathways, were performed. Immune infiltration analysis characterized the immune microenvironment in RVVC patients. A CVVC mouse model was established in vivo, and a C. albicans-BMDMs infection model was established in vitro. The ferroptosis inhibitor ferrostatin-1 (Fer-1) was administered to investigate the pathological function and regulatory mechanisms of ferroptosis in RVVC at the molecular, cellular, and tissue levels. Results: Differential analysis identified 3132 DEGs in RVVC, which intersected with ferroptosis-related genes to yield 194 key targets. Among them, 20 hub genes were identified, including ferroptosis regulators and inflammatory factors. Functional enrichment analysis confirmed that these shared targets regulate RVVC pathology through a “ferroptosis-inflammation-immunity” multi-pathway network. Immune infiltration analysis revealed a specific immune disorder in RVVC patients characterized by “activation of the pro-inflammatory innate immune axis and suppression of the adaptive immune axis,” which was closely associated with ferroptosis-related genes. In vivo and in vitro experiments confirmed that C. albicans infection induced ferroptosis in vaginal tissues and macrophages, as manifested by lipid ROS accumulation, Fe²⁺ overload, GSH depletion, downregulation of GPX4 and SLC7A11, upregulation of ACSL4, 4-HNE, and MDA, and mitochondrial structural damage. Macrophages were identified as key target cells for ferroptosis, and their ferroptosis led to impaired antifungal function. Fer-1 treatment significantly inhibited ferroptosis, reduced vaginal histopathological damage and inflammatory cell infiltration, decreased fungal burden, downregulated abnormally elevated inflammatory factors, and restored Th1/Th2 immune balance. Furthermore, Fer-1 preserved macrophage viability and enhanced their antifungal killing capacity. Conclusions: This study provides the first evidence linking RVVC to ferroptosis through a combination of clinical data analysis and experiments, suggesting that ferroptosis is involved in its pathological process. These findings offer a new perspective for elucidating RVVC pathogenesis and developing targeted therapeutic strategies. Full article

This study was conducted to investigate the effect of different concentrate-to-roughage ratios on the lipid composition of camel milk. Thirty-six Qiangar Bactrian camels were randomly allocated to three groups: the control group (C, grazing plus roughage only), the low-concentrate group (L, grazing plus roughage with 2 kg/d concentrate supplementation), and the high-concentrate group (H, grazing plus roughage with 4 kg/d concentrate supplementation). The trial comprised an 18-day adaptation period followed by a 42-day feeding period (60 days total). A systematic lipidomics approach revealed significant differences in milk lipid profiles among the three dietary treatments. High-concentrate diets markedly remodeled the milk lipidome (especially in positive-ion mode mass spectrometry), with the most pronounced differences detected between the C and H groups. Multivariate analyses (PCA and PLS-DA) confirmed that varying concentrate levels significantly affected milk lipid composition, and the separation between H and C was greater than that between L and C. KEGG annotation and enrichment analysis indicated that lipid-related pathways, notably glycerophospholipid metabolism, were significantly affected by dietary concentrate levels. These findings provide theoretical support for optimizing camel feeding strategies to improve milk nutritional quality and offer scientific guidance for camel husbandry and dairy product development. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD, introduced in 2023), formerly termed non-alcoholic fatty liver disease (NAFLD), is a leading cause of chronic liver disease worldwide and is closely linked to obesity, insulin resistance, and cardiometabolic dysfunction. Exercise is widely recommended as a cornerstone of MASLD management; however, the magnitude of its hepatic and metabolic benefits and the underlying molecular mechanisms remain incompletely defined. We aim to synthesize evidence from randomized controlled trials assessing how structured exercise interventions influence hepatic steatosis and metabolic dysfunction in adults with MASLD. A targeted search of PubMed from database inception to February 2025 identified eligible trials, of which eleven were included in the qualitative synthesis. Across studies, aerobic and resistance exercise interventions were consistently associated with reductions in hepatic fat content, improvements in plasma lipid profiles and liver enzyme concentrations, and enhanced indices of insulin sensitivity, frequently occurring independently of substantial weight loss. Mechanistically, exercise-induced activation of pathways related to mitochondrial function, lipid oxidation, inflammation modulation, and insulin signaling likely contributes to these benefits. Despite heterogeneity in intervention design, duration, and outcome assessment, the collective evidence supports structured exercise as an effective non-pharmacological strategy for improving hepatic steatosis and metabolic dysfunction in MASLD. Future studies integrating molecular biomarkers with clinical endpoints are warranted to refine exercise prescriptions and elucidate mechanisms of therapeutic response. Full article

Industrial production of single-cell oils (SCOs) by oleaginous yeasts relies predominantly on nitrogen limitation, which constrains process flexibility when nitrogen-rich substrates are used. Although phosphate limitation has been reported as an alternative lipid induction strategy, its process-level performance relative to nitrogen limitation remains insufficiently resolved under controlled reactor-scale conditions. In this study, phosphate-limited, nitrogen-limited and nutrient-replete cultivations of Cutaneotrichosporon oleaginosum ATCC 20509, Saitozyma podzolica DSM 27192, Scheffersomyces segobiensis DSM 27193 and Apiotrichum porosum DSM 27194 were benchmarked in 2.5 L stirred-tank reactors operated under identical media compositions and process parameters. Biomass formation, lipid titres, specific lipid production rates, biomass composition and fatty acid profiles were systematically compared. Nitrogen limitation resulted in the highest lipid titres, reaching up to 9.2 g L⁻¹ (A. porosum), while maximum lipid titres under phosphate-limited conditions reached 5.0 g L⁻¹ (C. oleaginosum) and nutrient-replete conditions 3.9 g L⁻¹ (A. porosum), respectively. The highest specific lipid production rate under nitrogen limitation was 0.0028 g gCDW⁻¹ h⁻¹ (S. podzolica), while phosphate limitation yielded a maximum of 0.0037 g gCDW⁻¹ h⁻¹ (S. podzolica). These results demonstrate that phosphate limitation can decouple cellular lipid productivity from biomass formation and represents a process-relevant alternative for SCO production from nitrogen-rich feedstocks. Full article