Search Results (512)

The effects of long-term adjustments in body weight on the lipid balance in patients with severe obesity are not well understood. This study aimed to evaluate a non-invasive lipidomic approach to identifying biomarkers that could help predict which patients may require additional therapies before and after weight loss. Using mass spectrometry, 275 lipid species were analysed in non-obese controls, patients with severe obesity, and patients one year after bariatric surgery. The results showed that severe obesity disrupts lipid pathways, contributing to lipotoxicity, inflammation, mitochondrial stress, and abnormal lipid metabolism. Although weight loss improved these disturbances, surgery did not fully normalise the lipid profiles of all patients. Outcomes varied depending on their baseline liver health and genetic differences. Persistent alterations in cholesterol handling, membrane composition, and mitochondrial function were observed in partial responders. Elevated levels of sterol lipids, glycerophospholipids, and sphingolipids emerged as markers of complete metabolic recovery, identifying candidates for targeted post-surgical interventions. These findings support the use of lipidomics to personalise obesity treatment and follow-up. Full article

Quercetin is a biologically active flavonoid compound that exerts numerous beneficial effects in humans and animals, including anti-diabetic activity. Its action has been explored in rodent models of type 1 and type 2 diabetes. It was revealed that quercetin mitigated diabetes-related hormonal and metabolic disorders and reduced oxidative and inflammatory stress. Its anti-diabetic effects were associated with advantageous changes in the relevant enzymes and signaling molecules. Quercetin positively affected, among others, superoxide dismutase, catalase, glutathione peroxidase, glucose transporter-2, glucokinase, glucose-6-phosphatase, glycogen phosphorylase, glycogen synthase, glycogen synthase kinase-3β, phosphoenolpyruvate carboxykinase, silent information regulator-1, sterol regulatory element-binding protein-1, insulin receptor substrate 1, phosphoinositide 3-kinase, and protein kinase B. The available data support the conclusion that the action of quercetin was pleiotropic since it alleviates a wide range of diabetes-related disorders. Moreover, no side effects were observed during treatment with quercetin in rodents. Given that human diabetes affects a large part of the population worldwide, the results of animal studies encourage clinical trials to evaluate the potential of quercetin as an adjunct to pharmacological therapies. Full article

Trichomes are specialized epidermal structures that protect plants from environmental stresses, regulated by transcription factors integrating hormonal and environmental cues. This study investigates the roles of two C2H2 zinc finger proteins, GIS2 and ZFP8, in regulating trichome patterning in Arabidopsis thaliana. Using dexamethasone-inducible overexpression lines, transcriptomic profiling, and chromatin immunoprecipitation, we identified 142 GIS2- and 138 ZFP8-associated candidate genes involved in sterol metabolism, senescence, and stress responses. GIS2 positively and directly regulated the expression of SQE5, linked to sterol biosynthesis and drought tolerance, and repressed SEN1, a senescence marker associated with abscisic acid and phosphate signaling. ZFP8 modulated stress-related target genes, including PR-4 and SPL15, with partial functional overlap between GIS family members. Spatially, GIS2 functions in inflorescence trichomes via integrating gibberellin-cytokinin pathways, while ZFP8 influences leaf trichomes through cytokinin and abscisic acid signal. Gibberellin treatment stabilized GIS2 protein and induced SQE5 expression, whereas SEN1 repression was gibberellin-independent. Chromatin immunoprecipitation and DEX-CHX experiment confirmed GIS2 binding to SQE5 and SEN1 promoters at conserved C2H2 motifs. These findings highlight hormone-mediated transcriptional regulation of trichome development by GIS2 and ZFP8, offering mechanistic insight into signal integration. The results provide a foundation for future crop improvement strategies targeting trichome-associated stress resilience. Full article

Cholesterol stress profoundly modulates cellular processes, but its underlying mechanisms remain incompletely understood. To investigate cholesterol-responsive networks, we performed integrated transcriptome (RNA-seq) and metabolome (LC-MS) analyses on HeLa cells treated with cholesterol for 6 and 24 h. Through transcriptomic analysis of cholesterol-stressed HeLa cells, we identified stage-specific responses characterized by early-phase stress responses and late-phase immune-metabolic coordination. This revealed 1340 upregulated and 976 downregulated genes after a 6 h cholesterol treatment, including induction and suppression of genes involved in cholesterol efflux and sterol biosynthesis, respectively, transitioning to Nuclear Factor kappa-B (NF-κB) activation and Peroxisome Proliferator-Activated Receptor (PPAR) pathway modulation by 24 h. Co-expression network analysis prioritized functional modules intersecting with differentially expressed genes. We also performed untargeted metabolomics using cells treated with cholesterol for 6 h, which demonstrated extensive remodeling of lipid species. Interestingly, integrated transcriptomic and metabolic analysis uncovered GFPT1-driven Uridine Diphosphate-N-Acetylglucosamine (UDP-GlcNAc) accumulation and increased taurine levels. Validation experiments confirmed GFPT1 upregulation and ANGPTL4 downregulation through RT-qPCR and increased O-GlcNAcylation via Western blot. Importantly, clinical datasets further supported the correlations between GFPT1/ANGPTL4 expression and cholesterol levels in Non-Alcoholic Steatohepatitis (NASH) liver cancer patients. This work establishes a chronological paradigm of cholesterol sensing and identifies GFPT1 and ANGPTL4 as key regulators bridging glycosylation and lipid pathways, providing mechanistic insights into cholesterol-associated metabolic disorders. Full article

Amyotrophic lateral sclerosis (ALS) is characterized by upper and lower motor neuron failure and poor prognosis. This study performed a meta-analysis of gene expression datasets that compared bulk-processed post-mortem spinal cord from ALS and control (CTL) patients. The analysis included 569 samples (454 ALS, 115 CTL) from 348 individuals (262 ALS, 86 CTL). Patterns of differential expression bias, related to mRNA abundance, gene length and GC content, were discernable from individual studies but attenuated by meta-analysis. A total of 213 differentially expressed genes (DEGs) were identified (144 ALS-increased, 69 ALS-decreased). ALS-increased DEGs were most highly expressed by microglia and associated with MHC class II, immune response and leukocyte activation. ALS-decreased DEGs were abundantly expressed by mature oligodendrocytes (e.g., the MOL5 phenotype) and associated with myelin production, plasma membrane and sterol metabolism. Comparison to spatial transcriptomics data showed that DEGs were prominently expressed in white matter, with increased DEG expression strongest in the ventral/lateral white matter. These results highlight white matter as the spinal cord region most strongly associated with the shifts in mRNA abundance observed in bulk-processed tissues. These shifts can be explained by attrition of mature oligodendrocytes and an ALS-emergent microglia phenotype that is partly shared among neurodegenerative conditions. Full article

Background: The limited bioavailability of free phytosterols restricts their clinical application in managing hypercholesterolemia. This study aimed to develop phytosterol nanoparticles (PNs) to enhance bioactivity and investigate their cholesterol-lowering efficacy and underlying mechanisms in vivo. Methods: Phytosterol nanoparticles (PNs) (93.35 nm) were engineered using soy protein isolate and administered orally at concentrations of 4.00–12.50 mg/mL to high-fat-diet-induced hypercholesterolemic mice (n = 60) over a 4-week period. Serum and hepatic lipid profiles, histopathology, gene/protein expression related to cholesterol metabolism, and fecal sterol content were evaluated. Results: PNs dose-dependently reduced serum total cholesterol (TC: 28.6–36.8%), triglycerides (TG: 22.4–30.1%), and LDL-C (31.2–39.5%), while increasing HDL-C by 18.7–23.4% compared to hyperlipidemic controls (p < 0.01). Hepatic TC and TG accumulation decreased by 34.2% and 41.7%, respectively, at the highest dose, with histopathology confirming attenuated fatty degeneration. Mechanistically, PNs simultaneously suppressed cholesterol synthesis through downregulating HMGCR (3.2-fold) and SREBP2 (2.8-fold), while enhancing cholesterol catabolism via CYP7A1 upregulation (2.1-fold) at protein level. Although less potent than simvastatin (p < 0.05), the nanoparticles exhibited unique dual-pathway modulation absent in conventional phytosterol formulations. Fecal analysis revealed dose-responsive cholesterol excretion (36.01 vs. 11.79 mg/g in controls), indicating enhanced enteric elimination. While slightly less potent than simvastatin (p < 0.05), PNs offered unique dual-pathway modulation absent in conventional phytosterol formulations. Conclusions: Nano-encapsulation significantly improves the bioavailability and hypocholesterolemic efficacy of phytosterols. PNs represent a promising nutraceutical strategy for cholesterol management by concurrently regulating cholesterol synthesis and catabolism, with potential application in both preventive and therapeutic contexts. Full article

Caffeic acid phenethyl ester (CAPE) is identified to be an efficacious bioactive polyphenol in propolis for ameliorating glucose and lipid metabolism disorders and inflammation. In this study, an alcohol-induced zebrafish inflammation model was established. CAPE treatments at different concentrations (0.04, 0.2, and 1.0 μg/mL) were administered to alcohol-exposed zebrafish to investigate the underlying mechanisms of alleviating alcohol-induced liver inflammation using transcriptomic analysis and 16S rRNA gene sequencing methods. The results indicated that CAPE decreased the expressions of TNF-α and IL-1β and significantly increased the expression of IL-10 (p < 0.0001). Based on the KEGG enrichment analysis of transcriptomic sequencing, CAPE effectively alleviated the inflammation in zebrafish mainly through pancreatic secretion, complement and coagulation cascades, and protein digestion and absorption. Molecular docking supported the potential of CAPE in targeting cholecystokinin (CCK) A Receptor (CCKAR) and mediating the regulation of pancreatic secretion and related inflammation pathways. Moreover, intestinal microbiota analysis demonstrated that CAPE could improve the alcohol-induced microbiota disorder. Additionally, there was a significant correlation between the key genes related to lipid and sterol metabolism among the KEGG-enriched pathways and the specific intestinal microbial communities in zebrafish. Flavobacterium from Bacteroidota was significantly positively correlated with CEL1, CEL2, and LPIN (p < 0.01), which suggested that the anti-inflammatory function of CAPE was closely associated with the intestinal microbiota improvement. In conclusion, our findings demonstrated that CAPE could ameliorate liver inflammation in alcohol-induced zebrafish, which was mainly associated with the regulation of pancreatic secretion and intestinal microbiota disorder. This study emphasized the anti-inflammatory mechanisms of CAPE based on targeting the pancreatic secretion pathway, which will broaden the application of natural antioxidants in improving metabolic and inflammatory problems. Full article

Granulosa cell (GC) dysfunction contributes to diminished ovarian reserve (DOR). We collected GC and follicular fluid samples from the patients of normal ovarian reserve (NOR) and DOR. RNA-seq of GCs showed that cholesterol/sterol metabolism and biosynthesis and extracellular matrix organization were enriched in the DOR group. Metabolomics of follicular fluid revealed enrichment in steroid hormone biosynthesis, tryptophan metabolism, and fatty acid β-oxidation in DOR. The apoptosis rate was increased, whereas the proliferative rate was decreased in GCs of DOR. The Prussian blue staining rate was increased whilst GPX4 and SLC7A11 expression were downregulated in GCs of DOR. Mitochondrial morphology displayed the features of ferroptosis in GCs of DOR. FSHR, CYP19A1, NR5A1, and phosphorylated CREB levels were substantially downregulated in GCs, accompanied by increased androgen levels in follicular fluids in DOR. The key factors linked to the mevalonate pathway, HMGCR, SQLE, and SREBF2, were robustly increased in DOR. FSHR and NR5A1 levels were correlated with CYP19A1 levels, whilst CYP19A1 levels were positively correlated with GPX4 and SLC7A11 levels. Our findings indicate ferroptosis and dysregulation of cholesterol/sterol metabolism and biosynthesis occurrence in GCs of DOR, which might be associated with reduced FSHR signaling and decreased conversion of androgen to estrogen. Full article

Microalgae are increasingly recognised as sustainable, nutrient-dense sources of bioactive compounds with broad health-promoting potential. Rich in carotenoids, phenolics, polyunsaturated fatty acids, phycobiliproteins, sterols, and essential vitamins, microalgae offer a promising foundation for functional foods targeting chronic disease prevention. This narrative review explores the nutritional profiles and biological effects of key species, including Spirulina (Limnospira platensis), Chlorella, Haematococcus, and Nannochloropsis. Scientific evidence supports their antioxidant, anti-inflammatory, immunomodulatory, antimicrobial, and metabolic regulatory activities, contributing to reduced risks of cardiovascular, metabolic, inflammatory, and neurodegenerative disorders. Special emphasis is placed on the synergistic benefits of consuming whole biomass compared to isolated compounds and the technological strategies, such as encapsulation, cell wall disruption, and nutrient optimisation, that enhance the bioavailability of microalgal bioactives. Furthermore, the environmental advantages of microalgae cultivation, such as minimal land and freshwater requirements, carbon sequestration, and wastewater bioremediation, highlight their role in the transition toward sustainable food systems. Despite challenges related to high production costs, sensory attributes, scalability, and regulatory approval, advances in biotechnology, processing, and formulation are paving the way for their broader application. Overall, microalgae represent next-generation bioactive sources that promote human health and environmental sustainability, positioning them as key players in future functional foods and nutraceuticals. Full article

Cytochromes P450 (CYPs) form one of the largest enzyme superfamilies, with similar structural folds yet biological functions varying from synthesis of physiologically essential compounds to metabolism of myriad xenobiotics. Sterol 14α-demethylases (CYP51s) represent a very special P450 family, regarded as a possible evolutionary progenitor for all currently existing P450s. In metazoans CYP51 is critical for the biosynthesis of sterols including cholesterol. Here we determined the crystal structures of ligand-free CYP51s from the abyssal fish Coryphaenoides armatus and human-. Comparative sequence–structure–function analysis revealed specific structural elements that imply elevated conformational flexibility, uncovering a molecular basis for faster catalytic rates, lower substrate selectivity, and intrinsic resistance to inhibition. In addition, the C. armatus structure displayed a large-scale repositioning of structural segments that, in vivo, are immersed in the endoplasmic reticulum membrane and border the substrate entrance (the FG arm, >20 Å, and the β4 hairpin, >15 Å). The structural distinction of C. armatus CYP51, which is the first structurally characterized deep sea P450, suggests stronger involvement of the membrane environment in regulation of the enzyme function. We interpret this as a co-adaptation of the membrane protein structure with membrane lipid composition during evolutionary incursion to life in the deep sea. Full article

Marine microalgae have emerged as promising biofactories for the sustainable production of high-value bioactive compounds with significant applications in human health, cosmetics, and functional foods. This review offers a comprehensive overview of the primary classes of bioactives synthesised by marine microalgae, including polyunsaturated fatty acids, carotenoids, phycobiliproteins, peptides, sterols, polysaccharides, phenolic compounds, vitamins, mycosporine-like amino acids, and alkaloids. These compounds demonstrate diverse biological activities, such as antioxidant, anti-inflammatory, antimicrobial, anticancer, immunomodulatory, and photoprotective effects, increasingly validated through in vitro, and clinical studies. Their mechanisms of action and roles in disease prevention and wellness promotion are examined in detail, with an emphasis on pharmaceutical (e.g., cardiovascular, neuroprotective), cosmetic (e.g., anti-ageing, UV protection), and nutraceutical (e.g., metabolic and immune-enhancing) applications. The review also addresses critical challenges in strain selection, cultivation technologies, downstream processing, product standardisation, and regulatory approval. Simultaneously, emerging opportunities driven by synthetic biology, omics integration, and circular biorefinery approaches are transforming marine microalgae into precise platforms for next-generation bioproducts. By summarising current knowledge and future directions, this work underscores the essential role of marine microalgae in advancing the blue bioeconomy and tackling global sustainability challenges. Full article

This study investigates the potential of a biostimulant derived from the invasive brown alga Rugulopteryx okamurae (RoB) to enhance lettuce growth and improve its phytochemical profile. The extraction of the biostimulant was optimized through the implementation of a Box–Behnken design, and the resulting extract was then compared with a commercial Ascophyllum nodosum-based product (AnB). This comparison was made under both optimal and suboptimal fertigation conditions in a controlled, soilless culture. Lettuce plants were monitored for water and nutrient uptake, growth parameters, and accumulation of key phytochemicals such as carotenoids, tocols, sterols, and squalene. RoB significantly increased fresh and dry biomass, with enhanced nitrate and potassium uptake, in comparison to standard nutrient solution controls (p < 0.05). Treatments incorporating RoB consistently resulted in higher concentrations of lutein, β-sitosterol, and squalene, particularly under suboptimal conditions (p < 0.05), thus suggesting a strong biostimulant effect that mitigates nutrient stress. Furthermore, principal component analysis demonstrated that biostimulant application induces distinct metabolic profiles, highlighting the coordinated regulation of antioxidant pigments and sterol compounds. The findings support the dual benefits of algae-derived biostimulants in promoting sustainable crop production by improving yield quality and increasing health-promoting phytochemicals, paving the way for innovative, eco-friendly fertilization practices in modern agriculture. Full article

(1) Background: This study evaluated the potential of an aqueous extract from Quercus robur L. leaves for chronic wound healing. Its composition, rich in bioactive compounds (tannins and flavonoids), confers antioxidant and antimicrobial properties. (2) Methods: The toxicity and ability of the extract to enhance cell migration were tested in human keratinocytes (HaCaT cell line). Additionally, a proteomic analysis was performed on treated cells. (3) Results: The extract exhibited low cytotoxicity (IC50 = 943 µg·mL⁻¹) compared to other plant extracts. At 5 mg·mL⁻¹, it significantly accelerated wound closure at 8 h, surpassing negative control and Reoxcare; however, results were comparable at 12 h. Proteomic analysis identified 117 differentially expressed proteins (21 upregulated, 96 downregulated) involved in essential processes such as cell migration, blood clotting, and cholesterol biosynthesis. Specifically, the extract increased the expression of CYP51A1, LSS, and SQLE, while inhibiting Delta (14)-sterol reductase, key enzymes in cholesterol metabolism, suggesting a potential mechanism for tissue regeneration. (4) Conclusions: The aqueous extract of Q. robur leaves shows promise as a natural therapeutic agent for chronic wound healing, potentially aiding tissue regeneration and modulation of cholesterol metabolism. Full article

Background/Objectives: Obesity is a major health concern that can lead to various chronic diseases. Little is known about the anti-obesity effect of a standardized hot water extract from the stems of Ipomoea batatas (WIB). This study aimed to evaluate the therapeutic potential of WIB as a natural alternative to conventional anti-obesity treatments by assessing its effects on body weight, fat accumulation, and key metabolic biomarkers in a high-fat diet-induced obesity model. Methods: A high-fat diet (HFD) induced obesity in C57BL/6 mice. The mice were then treated orally with either orlistat (positive control) or WIB. Changes in body weight, food intake, and fat weight were measured, along with blood lipid profiles and adipokines. Western blot analyses were conducted to determine protein levels in each tissue. H&E staining in white adipose tissue and liver, and the gut microbiota composition were analyzed. Results: WIB treatment significantly reduced body weight and fat mass compared to the HFD group and demonstrated comparable effects to orlistat. WIB improved blood lipid profiles and adipokine levels. H&E staining revealed reduced fat accumulation in the white adipose tissue and liver. Also in those tissues, WIB restored expression levels of sterol regulatory element-binding protein-1 (SREBP-1) and CCAAT/enhancer-binding protein α (C/EBPα) and increased AMP-activated protein kinase (AMPK) phosphorylation. In brown adipose tissue, WIB enhanced AMPK phosphorylation and upregulated thermogenic-related proteins, including peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα), sirtuin 1 (SIRT1), uncoupling protein-1 (UCP-1), and cytochrome C oxidase subunit 4 (COX-IV). Analysis of gut microbiota revealed that WIB normalized β-diversity and reversed HFD-induced phyla imbalances (notably in Bacteroidetes, Firmicutes, and Proteobacteria). Conclusions: By reducing adiposity under the conditions tested in a murine model, improving metabolic markers, and favorably modulating gut microbiota, WIB demonstrates potential in mitigating obesity-related risks. These findings suggest that WIB may serve as a promising natural substance for the management of obesity. Further studies are warranted to confirm its efficacy and explore the potential underlying mechanisms in overweight or obese humans as a health supplement to help manage or prevent obesity. Full article

Group A rotavirus continues to be a leading global etiological agent of severe gastroenteritis in young children under 5 years of age. The replication of this virus in the host is associated with the occurrence of Lewis antigens and the secretor condition. Moreover, histo-blood group antigens (HBGAs) act as attachment factors to the outer viral protein of VP4 for rotavirus. Therefore, in this study, we employed a metabolomic approach to reveal potential signature metabolic molecules and metabolic pathways specific to rotavirus P[8] strain infection (VP4 genotype), which is associated with the expression of HBGA combined secretor and Lewis (Le) phenotypes, specifically secretor/Le^(a+b+). Further integration of the achieved metabolomics results with lipidomic and proteomics metadata analyses was performed. Saliva samples were collected from children diagnosed as negative or positive for rotavirus P[8] strain infection (VP4 genotype), which is associated with the HBGA combined secretor/Le^(a+b+). A total of 22 signature metabolic molecules that were downregulated include butyrate, putrescine, lactic acid, and 7 analytes. The upregulated metabolic molecule was 2,3-Butanediol. Significant pathway alterations were also specifically observed in various metabolism processes, including galactose and butanoate metabolisms. Butyrate played a significant role in viral infection and was revealed to exhibit different reactions with glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, and fatty acyls. Moreover, butyrate might interact with protein receptors of free fatty acid receptor 2 (FFAR2) and free fatty acid receptor 3 (FFAR3). The revealed metabolic pathways and molecule might provide fundamental insight into the status of rotavirus P[8] strain infection for monitoring its effects on humans. Full article