Search Results (1,991)

Hepassocin, also known as fibrinogen-like protein 1 (FGL-1), is a liver-derived secretory protein initially identified as a mitogenic factor involved in hepatocyte proliferation and liver regeneration. Increasing evidence has subsequently suggested that FGL-1 functions as a hepatokine linking hepatic metabolic stress to systemic metabolic regulation. Experimental and clinical studies have demonstrated that circulating FGL-1 levels are associated with obesity, insulin resistance, metabolic dysfunction-associated steatotic liver disease (MASLD), and type 2 diabetes mellitus (T2DM). Mechanistically, FGL-1 appears to contribute to metabolic dysfunction by impairing insulin signaling and promoting hepatic lipid accumulation, although its precise molecular targets remain incompletely defined. In addition to its metabolic roles, FGL-1 has been identified as a major ligand of lymphocyte activation gene-3 (LAG-3), implicating it in immune modulation and tumor progression, particularly in hepatocellular carcinoma (HCC). However, most available human data are observational, and conflicting findings from experimental models suggest that FGL-1 may function as a context-dependent mediator rather than a purely pathogenic factor. Given the expanding but sometimes conflicting evidence, a comprehensive understanding of FGL-1 biology may provide important insights into the complex interactions among hepatic stress responses, metabolic dysfunction, and immune regulation. This review therefore examines the current evidence regarding the physiological and pathological roles of FGL-1 and highlights key unresolved questions that may influence future translational research and therapeutic development. Full article

Nanobubbles have attracted increasing interest in food systems because they can modify gas dispersion, interfacial transport, washing performance, preservation processes, and the structures of dispersed matrices. However, their behavior cannot be interpreted based on bubble size alone. Proteins, polysaccharides, lipids, salts, colloidal particles, gas composition, and processing conditions can alter interfacial adsorption, gas transfer, bubble persistence, and matrix organization in food systems. This review examines the physicochemical mechanisms proposed to explain nanobubble persistence and functionality, with an emphasis on surface charge, interfacial adsorption, gas supersaturation, confinement, and interactions with food biopolymers. A central distinction is made between passive nanobubble-containing systems and externally activated systems involving hydrodynamic cavitation, ultrasound, plasma, pressure fluctuations, and reactive gases. Under passive conditions, nanobubbles mainly act as gas–liquid interfaces that influence local transport and adsorption. In activated systems, microbial inactivation, reactive oxygen species formation, and apparent mass-transfer enhancement often arise from external energy input, gas chemistry, turbulence, and transient supersaturation rather than from nanobubbles alone. Interfacial stability is used here as an organizing concept to connect nanobubble persistence, food-matrix interactions, generation methods, characterization limitations, and interpretation of reported technological effects. Current methods, such as dynamic light scattering and nanoparticle tracking analysis, provide useful size and concentration estimates but cannot unambiguously distinguish nanobubbles from protein aggregates, fat droplets, micelles, polysaccharide assemblies, and other colloidal structures in complex matrices. Therefore, reliable interpretation requires complementary methods, appropriate controls, and standardized reporting of gas composition, generation method, energy input, matrix properties, and processing conditions. Thus, nanobubble-containing technologies show promise for food processing; however, their value depends on the separation of nanoscale interfacial effects from concurrent hydrodynamic, chemical, and matrix-dependent phenomena. Full article

Introduction: Aquatic chemical pollution is among the most worrying threats to ecosystem health. There is an ever-increasing variety of pollutant substances detected across the source-to-sea continuum, causing loss of biodiversity and ecological disequilibrium. Achieving cleaner and healthier systems relies on carrying out sustained, cost-effective, diagnosis and aquatic effects monitoring, within the adaptive management cycle. The available methods are, however, cumbersome, which creates a clear need for innovative expeditious approaches for low-cost surveillance monitoring. In the last decade, Raman Spectroscopy (RS) has gained wide recognition for application to biological questions, for its ability to uncover the complexity of molecules and their interactions. Various fields, from pharmacology to disease diagnosis and prognosis, have suffered an innovation revolution through the application of RS. In this technique inelastic light scattering of a small part of photons of an incident electromagnetic monochromatic light beam (ranging from near-infrared to visible or ultraviolet) is caused by the molecular vibration of chemical bonds. This results in shifts in energy, which indicate discrete vibrational modes of polarisable molecules, providing qualitative and quantitative assessments of the chemical composition and molecular structure of the sample. The technique shows high sensitivity, no need for sample preparation and the possibility of use in non-invasive and label-free analysis. Objective: The aim of this work is to present and discuss evidence about the application of Raman Spectroscopy (RS) to environmental diagnosis and aquatic effect monitoring of pollution. Methodology: The technique was applied to different biological models, i.e., diatoms, zebrafish embryos and larvae and freshwater snails. Quality assessments with diatoms were tested in environmental monitoring, while assessments with other models were done upon exposure to metals and organic contaminants. Results and conclusions: The Raman spectra obtained from the samples analysed comprised bands detected within the 800 to 2000 cm⁻¹ wavenumber range. These were related to bond vibrations of carbohydrates, DNA phosphate groups, proteins or CH, NH and OH stretching in lipids and proteins. Data analysis using chemometric methods clearly distinguished pollutant exposure from control sites or treatments, pointing out the potential for surveyance monitoring. The next steps include the comparison with other sensitive methods (e.g., locomotion and avoidance behaviours, omics methods) to assess efficiency and bring further mechanistic understanding. Full article

Proteins are the most common targets for antibody discovery and vaccine development, but their sequence variability can limit the breadth of resulting antigens. Lipids represent an alternative class of antigens due to their structural conservation and roles in host–pathogen interactions. Here, we describe the development and optimization of an in vitro antibody selection workflow using lipid-containing nanodiscs as antigen presentation platforms to enable phage and yeast display selections under conditions adapted for these non-protein targets. Lipopolysaccharide (LPS) nanodiscs were first used as a model system to evaluate selection strategies, including competitive and subtractive approaches to reduce non-specific binders, yielding peptide and single-chain variable fragment (scFv) binders that were affinity matured to improve binding signals. The same approach was subsequently used to select scFv antibodies that recognize lipid nanodiscs prepared from Yersinia pestis membrane lipid extracts. These antibodies show binding to lipid nanodiscs derived from Y. pestis, with evidence of selectivity relative to control nanodiscs. Overall, this work establishes a workflow for antibody selection against lipid-containing nanodisc antigens and highlights practical considerations associated with these targets. The approach may be useful for generating affinity reagents to membrane-associated lipids, although further characterization is required to define antigen specificity and functional activity. Full article

In addition to its role in energy storage, adipose tissue contributes substantially to energy metabolism, endocrine regulation, and inflammatory processes. Sujiang pigs, a hybrid breed approved by the National Livestock and Poultry Genetic Resources Committee of China as a new national breed in 2013, possess a genetic predisposition for substantial fat deposition, making them an ideal model for investigating the mechanisms underlying adipose tissue accumulation. In this study, back fat (BF; subcutaneous adipose tissue), greater omentum (GOM; visceral adipose tissue), and mesenteric adipose tissue (MAD; visceral adipose tissue) were collected from three 6-month-old male Sujiang pigs for RNA-seq analysis. Comparative analyses identified 3005 differentially expressed genes (DEGs) between BF and GOM, 975 DEGs between BF and MAD, and 892 DEGs between GOM and MAD. To validate the reliability of the sequencing data, five DEGs were randomly selected for RT-qPCR verification. The DEGs were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. By integrating protein–protein interaction (PPI) networks with bioinformatics analyses, we identified candidate genes potentially associated with lipid metabolism (e.g., WNT9A, WNT5A, and PDGFRA) and inflammatory responses in adipose tissue (e.g., CSF1R, C1QB, and CD4). These findings indicate potential molecular differences between porcine visceral and subcutaneous adipose tissues and may serve as a reference for further studies on the molecular regulation of adipose tissue metabolism. Full article

Even though the functional food market has rapidly increased in recent years, the links between bioactive-rich formulations and consumers’ health benefit are not fully established, mainly because of insufficient consideration of food matrix effects. This review provides a comprehensive and integrated evaluation of how food matrix properties (structural and physicochemical) affect the bioaccessibility of plant bioactive compounds. Unlike many reviews that focus on a single nutrient approach, we highlight quantitative evidence of how bioaccessibility can be affected by matrix properties, illustrating the interactions between main food components (lipids, proteins, dietary fiber and minerals). This review integrates fragmented information among different areas of food and nutrition sciences, i.e., food structure, gastrointestinal science, mineral chemistry, protein chemistry, providing a holistic framework for Quality by Design (QbD) functional food development. Synergisms and antagonistic behaviors, threshold effects, and concentration-dependent behaviors are analyzed comparatively for the most common plant-derived bioactives, such as polyphenols, carotenoids, curcuminoids and minerals (iron, zinc and calcium). We propose a matrix-informed optimization as a prerequisite for credible health claims and sustainable plant-based nutrition strategies. This can ultimately serve as a foundation for next-generation functional food development based on bioaccessibility, supporting the central argument that functional food development should move from composition-based fortification to bioaccessibility-based matrix engineering. Full article

Dysregulated lipid metabolism is a core pathogenic driver of type 2 diabetes. Honokiol (HKL), the major bioactive constituent of Magnolia officinalis, possesses anti-diabetic and lipid-regulatory properties. However, the underlying molecular mechanism remains elusive. This study investigates how HKL ameliorates high-glucose/high-fat (HGHF)-induced hepatic lipid accumulation, with a focus on the role of SIRT3-mediated deacetylation of peroxisome proliferator-activated receptor γ (PPARG). The core targets of HKL were identified through network pharmacology and molecular docking. Human hepatic MIHA cells were treated with glucose (Glu, 40 mM) and palmitic acid (0.2~0.3 mM PA) to establish a lipid accumulation model, followed by treatment with HKL (5–10 μM) with or without a confirmed selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP). Lipid accumulation was assessed by Oil Red O staining and by measuring triglyceride (TG) and total cholesterol (TC) levels. Protein expression and the SIRT3-PPARG interaction were analyzed by Western blot and co-immunoprecipitation (Co-IP). SIRT3 and PPARG were identified as core targets of HKL, exhibiting strong binding with calculated energies of −6.834 and −6.579 kcal/mol, respectively. In MIHA cells, HGHF (40 mM Glu + 0.2–0.3 mM PA) induced lipid accumulation, including increased lipid droplets, and elevated TG (2.5–3.2-fold) and TC (2.2–2.8-fold) contents in a dose-dependent manner, accompanied by downregulated SIRT3/PPARG expression and heightened global protein acetylation. The non-cytotoxic HGHF-M condition (40 mM Glu + 0.2 mM PA) was selected for further experiments. HKL (5–10 μM) dose-dependently reduced lipid accumulation by ~38–60%, decreased TG and TC levels by up to ~13% and ~30%, and restored SIRT3/PPARG expression. The protective effects of HKL were reversed by inhibition of SIRT3 with 3-TYP. Co-IP confirmed the interaction between SIRT3 and PPARG, and SIRT3 overexpression significantly decreased the acetylation level of PPARG. This study suggests that HKL ameliorates hepatic lipid accumulation via SIRT3-mediated deacetylation of PPARG, providing an experimental basis for considering HKL as a potential therapeutic agent against metabolic disorders. Full article

Background: Renal ischemia–reperfusion injury (RIRI) is a major cause of acute kidney injury (AKI) and contributes to delayed graft function and progression toward chronic kidney disease. In addition to oxidative stress and inflammation, RIRI induces profound metabolic derangements, particularly suppression of tubular fatty-acid β-oxidation (FAO), leading to energetic stress, lipid accumulation, and maladaptive repair. Peroxisome proliferator–activated receptor-α (PPARα) is a key regulator of tubular FAO, but whether Schisandrin B (Sch B) mitigates RIRI through restoration of a PPARα-associated metabolic program remains unclear. Objective: To determine whether Sch B alleviates RIRI in association with restoration of tubular FAO and attenuation of lipid accumulation and fibrotic remodeling. Methods: A unilateral murine renal I/R model and an HK-2 hypoxia/reoxygenation (H/R) model were used. Mice received Sch B (20 or 40 mg/kg/day) before I/R, and a subset was co-treated with the PPARα antagonist GW6471. Renal function, tubular injury, fibrosis, lipid accumulation, and FAO-related proteins were assessed by serum biochemistry, histopathology, Oil Red O staining, transmission electron microscopy, immunohistochemistry, immunofluorescence, and Western blotting. Bulk RNA-seq and public single-cell RNA-seq datasets were integrated to characterize metabolic pathway remodeling and cell-type-associated PPARα changes. Molecular docking and molecular dynamics simulations were performed to explore the potential interaction between Sch B and PPARα. Results: Sch B significantly improved renal function, reduced tubular injury, and attenuated interstitial collagen deposition after I/R. Sch B also reduced lipid droplet accumulation, preserved mitochondrial ultrastructure, and restored the expression of FAO-related proteins, including CPT1A, CPT2, and ACADM. In vivo and in vitro, Sch B decreased α-SMA, COL1A1, and vimentin expression, indicating attenuation of EMT-associated/profibrotic remodeling. Integrated transcriptomic analyses supported marked metabolic reprogramming after I/R, with enrichment of FAO- and PPAR-related pathways and reduced PPARα expression predominantly in tubular compartments. Sch B was associated with restoration of tubular PPARα expression, while docking and molecular dynamics analyses supported a plausible Sch B–PPARα interaction in silico. GW6471 blunted the beneficial effects of Sch B on fibrosis-related and FAO-related readouts. Conclusions: Sch B alleviates RIRI and limits subsequent fibrotic remodeling in association with restoration of a PPARα-related tubular FAO program, reduced lipid accumulation, and preservation of tubular metabolic homeostasis. These findings identify metabolic reprogramming as an important component of Sch B-mediated renoprotection, although the precise mode by which Sch B regulates PPARα requires further investigation. Full article

The rate of fatty acid (FA) uptake by cells depends on the presence of the CD36 receptor on the cell surface. However, unesterified FAs cannot circulate freely in plasma; they are bound to serum albumin. The molecular mechanisms of FA transfer from albumin to CD36 remain poorly understood. This study used macromolecular docking and molecular dynamics methods to investigate the interaction of the CD36 receptor with human serum albumin (HSA) loaded with oleic acid at the FA1-7 fatty acid-binding sites, with the aim of identifying potential mechanisms of FA transfer from HSA to CD36. The data obtained indicate that the interaction of HSA with CD36 does not result in direct FA transfer, but rather causes a local weakening of the affinity of individual FA sites on HSA. A comparative analysis was performed between the interaction interfaces predicted by macromolecular docking and those generated by AlphaFold 3. To further evaluate the influence of ligand nature, an additional molecular docking of HSA loaded with saturated (palmitic, PALM) and polyunsaturated (arachidonic, ARA) acids to the CD36 receptor was performed. This revealed a marked sensitivity of the protein–protein interface architecture to the type of lipid ligand, with the effect of ARA being more pronounced than PALM. Conversely, an alternative structure prediction using the AlphaFold3 algorithm demonstrated the opposite trend, indicating high geometric invariance and reproducibility of the complex. Ultimately, the proposed dynamic mechanism expands our understanding of the multi-stage processes governing FA transport across the endothelium. Full article

Objectives: This study aimed to identify core genes associated with mitochondria-related transcriptomic signatures and evaluate their potential as computational biomarkers, immune characteristics, regulatory mechanisms, and potential therapeutic relevance. Methods: Obesity-related transcriptome datasets were obtained from the GEO database. Differentially expressed genes (DEGs) were intersected with mitochondria-related genes (MRGs) to identify obesity-related MRGs. Functional enrichment, protein–protein interaction (PPI) analysis, CytoHubba, LASSO and random forest algorithms were used to screen core genes. External validation, ROC analysis, immune infiltration analysis, regulatory network construction, candidate drug prediction, and molecular docking were further performed. Results: A total of 527 DEGs and 15 differentially expressed MRGs were identified. Enrichment analysis suggested that these mitochondria-related genes were mainly associated with disrupted mitochondrial energy metabolism, lipid metabolic remodeling, and altered substrate utilization. ECHDC2, FASN, NAT8L, and AASS were identified as core MRGs; these genes are respectively associated with mitochondrial metabolic regulation, de novo fatty acid synthesis, N-acetylaspartate-related mitochondrial metabolism, and lysine degradation. These genes were significantly downregulated in obesity and showed good diagnostic performance. Immune infiltration analysis revealed alterations in the immune microenvironment, and the core genes were negatively correlated with multiple immune cell types. Molecular docking showed that Genistein had the lowest predicted binding free energy with NAT8L (−8.89 kcal/mol), suggesting relatively favorable binding among the tested ligand–target pairs. Conclusions: ECHDC2, FASN, NAT8L, and AASS may serve as candidate computational biomarkers, among which FASN represents a known lipid metabolism-related gene, supporting the biological plausibility of the workflow. Full article

Background/Objectives: The present study estimated the potential therapeutic effects of Borassus flabellifer immature endosperm extract (BFE) on the metabolic disorders of diabetes and hypothyroidism using a mixed research design. Methods: Characterization of phytochemicals via GC-MS demonstrated a highly abundant list of bioactive compounds, and it encompassed phenolic derivatives, methylxanthines, fatty acids, and inositol-related compounds. Molecular docking indicated that the major phytoconstituents showed positive binding affinities to the most vital metabolism and endocrine receptors, namely, TRβ1, PPARγ, and AMP-activated protein kinase (AMPK). Notably, both compounds C1 and C2 were highly affined towards TRβ1 (−7.8 and −7.6 kcal/mol), which is attributed to interactions in the active site through hydrogen bonding and hydrophobic responses, which means that the identified compounds were found to have good predicted interactions with some metabolic- and thyroid-associated targets and could be used to form preliminary hypotheses for further mechanistic studies. The in vivo data showed that the disease-induced groups were marked by hyperglycemia, imbalance in thyroid hormones, and dyslipidemia, as well as liver, kidney, and heart dysfunction. BFE caused significant decreases in these changes, which were also observed through improvements in fasting blood glucose, T3, T4, and TSH; partial restoration of lipid profiles; and dampening of liver and kidney injury signalers. The cardiac risk indices were also reduced significantly after BFE administration. Positive changes in body weight gain, feed ratio, and metabolic ratio further reflected better physiological stability. Results: These findings were corroborated by histopathological analysis, which showed that the tissue architecture of the pancreas, liver, kidney, and heart had significantly recovered in the study. BFE still showed constant therapeutic activity even though the magnitude of response was attenuated when combined disease conditions were used. Conclusions: Comprehensively, the results indicate that BFE potentially plays a role in the amelioration of metabolic and endocrine abnormalities of diabetic and hypothyroid conditions. These observations should be regarded as hypothesis-generating, as further mechanistic and translational studies are needed to substantiate their biological relevance. Full article

Despite extensive research, formation and properties of protein corona (PC) remain largely unknown. The composition and properties of PC are unique to each particle type. Our research focuses on multilevel nanoconstructs (MLNCs) containing a core (AuNP coated with oligonucleotide) encapsulated in lipid envelope (LE). We are developing particles of this type as nucleic acid delivery systems and platforms for studying PC on lipid surfaces. The goal of this work is to optimize the assembly of MLNCs with a negatively charged LE encapsulating a negatively charged core. Magnesium ions successfully acted as electrostatic bridges between like-charged components to facilitate self-assembly. The resulting particles were characterized using DLS (hydrodynamic diameter of ~36 nm) and TEM, which revealed stable LE. However, we encountered a critical issue: mechanical strength of the phosphatidylcholine/phosphatidic acid/cholesterol envelope proved to be highly sensitive to centrifugation forces and interactions with proteins. Incubation with albumin destabilized the LE, resulting in core release. In contrast, exposure to serum maintained the integrity of LE, allowing isolation of MLNC particles bearing PC. These results demonstrate that the assembly protocol can be adapted to negatively charged lipid compositions. However, stability of MLNCs during isolation is strictly dependent on medium protein composition. Thus, MLNCs represent a valuable platform for studying the interactions of LE with the PC. Full article

DMG, including DIPG, is a highly aggressive pediatric brain tumor with dismal clinical outcomes. Radiotherapy remains the cornerstone of treatment, yet responses are transient and resistance is nearly universal. Emerging evidence indicates that EVs are key mediators of radiation response, facilitating intercellular communication and the propagation of radioresistant phenotypes within the tumor microenvironment. EVs carry diverse molecular cargo, including RNAs, proteins, and lipids, that can dynamically influence tumor behavior and treatment response. In this review, we focus on the role of EVs in shaping radiation response in DMG, while also examining their broader functions in tumor biology, biomarker development, and therapeutic delivery. We summarize evidence for EV-mediated regulation of tumor growth, invasion, microenvironmental interactions, and immune modulation. We further discuss the potential of EVs as minimally invasive biomarkers for liquid biopsy, highlighting both their advantages and current limitations relative to circulating tumor DNA (ctDNA) approaches. In addition, we review emerging strategies utilizing EVs as therapeutic delivery platforms capable of crossing the blood–brain barrier (BBB) and delivering small molecules and nucleic acid-based therapies. Finally, we explore the role of EVs in modulating radiation response, including their contribution to radioresistance and their potential as biomarkers of treatment efficacy. Although EV-based approaches hold significant promise in DMG, challenges related to standardization, specificity, and clinical validation remain. Continued investigation into EV biology and translational applications may provide new opportunities for improving diagnosis, monitoring, and treatment of this devastating disease. Full article

As the direct biosynthetic precursor of creatine, guanidinoacetic acid (GAA) exerts a pivotal regulatory role in energy homeostasis and protein metabolism. Rabbit meat has garnered increasing global recognition as a healthy food source, characterized by its outstanding high-protein and low-fat nutritional profile. Accordingly, the optimization of rabbit meat quality has attracted growing attention from both consumers and animal production practitioners. In the present study, we evaluated the impacts of dietary GAA supplementation on meat quality traits, in vivo antioxidant capacity, muscle fiber characteristics, and fatty acid metabolism in New Zealand white rabbits. A total of 960 male New Zealand white rabbits were assigned to two age groups: 40-day-old group and 60-day-old group (40 ± 2 days, 1.19 ± 0.09 kg; 60 ± 2 days, 1.82 ± 0.15 kg). Within each age group, rabbits were randomly allocated to a control diet or a diet supplemented with 100 mg/kg GAA (CON-40, GAA-40, CON-60, GAA-60). After a 45-day feeding period, two-way ANOVA revealed that GAA supplementation significantly reduced shear force (p < 0.01, diet main effect) and muscle fiber density (p < 0.01, diet main effect), with an age-dependent effect on shear force (age × diet interaction, p < 0.05). Moreover, GAA enhanced systemic antioxidant capacity, as indicated by increased serum superoxide dismutase (SOD) activity (p < 0.01) and total antioxidant capacity (T-AOC) (p < 0.05), while no significant effect on malondialdehyde (MDA) was detected under the current experimental conditions. GAA also regulated the expression of lipid metabolism-related genes (FAS, HSL, ACC) in intramuscular and perirenal fat, indicating its regulatory effect on fatty acid metabolism. In conclusion, dietary GAA supplementation improves rabbit meat tenderness and antioxidant capacity, with no negative effects on growth performance. These findings confirm that GAA has the potential to serve as a nutritional strategy to improve rabbit meat quality, supporting the development of rabbit meat as a functional food for human consumption. Full article

Soil salinity severely restricts castor (Ricinus communis L.) seed germination, yet the molecular basis of this trait remains poorly understood. Here, we identified and functionally characterized RcnsLTPC, a nonspecific lipid transfer protein gene strongly induced by salt stress, which encodes a plasma membrane-localized nsLTP1 protein. Promoter analyses indicated that RcnsLTPC is responsive to stress-, hormone-, and light-related signals, supporting its potential role in environmental adaptation. Heterologous expression in Saccharomyces cerevisiae and overexpression in Nicotiana tabacum consistently demonstrated that RcnsLTPC acts as a positive regulator of salt tolerance, improving germination, root development, biomass accumulation, antioxidant capacity, and ion homeostasis under NaCl stress. Notably, ZnO-NPs priming further amplified the protective effects of RcnsLTPC, suggesting a synergistic interaction between nanopriming and gene-mediated stress adaptation. Collectively, these findings establish RcnsLTPC as a key regulator of salt tolerance in castor and provide a conceptual basis for combining nanotechnology with genetic enhancement to improve crop performance on saline soils. Full article