Search Results (4,527)

Background:Alpiniae oxyphyllae-Saposhnikovia divaricata (AS), a traditional Chinese dietary supplement, exhibits potential therapeutic effects against diabetic kidney disease (DKD), though its active compounds and mechanisms require elucidation. Methods: Animal experiments integrated with UHPLC-QE-MS, bioinformatics, and experimental validation were employed to investigate AS’s pharmacodynamic basis against DKD. Results: Thirty-nine compounds were identified in AS, including four key flavonoids (daidzein, kaempferol, tectoridin, baicalin). Bioinformatics screening revealed 516 potential AS targets from PubChem/TCMSP/ETCM databases. Analysis of the GEO dataset (GSE30529) identified 482 DKD-related differentially expressed genes (DEGs). Venny 2.1 analysis yielded 42 co-DEGs and 6 co-core DEGs. Functional enrichment (GO/KEGG/GSEA) demonstrated AS’s modulation of apoptosis and extracellular matrix (ECM) pathways via these DEGs. ROC profiling and renal single-cell sequencing highlighted FOS as a specific regulator of podocyte apoptosis in DKD. Molecular docking confirmed stable binding between the four flavonoids and FOS. Experimentally, AS significantly suppressed expression of ECM-related proteins (Col-IV, LN, IL-6, IL-17) and pro-apoptotic proteins (Bax, Caspase-3), while restoring anti-apoptotic Bcl-2 levels and inhibiting phosphorylation of MEK4, JNK1, c-Jun, and FOS in DKD mice. Conclusion: This study elucidates that AS alleviates DKD by inhibiting the MAPK/FOS pathway, thereby attenuating podocyte apoptosis and ECM accumulation. These findings establish a foundation for targeted AS therapy in DKD. Full article

Keratoconus (KC) is a progressive, multifactorial corneal ectatic disorder characterized by localized stromal thinning and irregular astigmatism, with incidence and prevalence varying markedly among populations. These differences are influenced by environmental exposures, behavioral factors, and genetic predisposition. A positive family history is a well-established high-risk factor, and KC has also been documented in association with syndromic disorders such as Down syndrome, connective tissue disorders, and certain metabolic diseases. Over the past decades, numerous candidate genes have been investigated, encompassing those involved in extracellular matrix (ECM) assembly, collagen synthesis and cross-linking, oxidative stress defense, wound healing, and transcriptional regulation. Modern genomic approaches, including genome-wide association studies (GWAS), linkage analyses, and next-generation sequencing, have identified multiple loci and variants with potential pathogenic roles. Nonetheless, several genes have also been systematically tested and found to show no association in specific populations, highlighting the genetic variability of KC and the potential influence of population-specific factors. This dual landscape of positive and negative genetic findings underscores the complexity of KC pathogenesis and the necessity for ethnically diverse cohorts. In this review, we synthesize current evidence on genes implicated in KC, integrating confirmed pathogenic variants, associations, and negative findings across diverse populations, to provide a comprehensive overview of the genetic architecture of KC and to outline priorities for future research aimed at improving diagnosis, risk stratification, and therapeutic development. Full article

YKL-40 is a chitinase-like glycoprotein implicated in various pathological processes, yet its glycosaminoglycan (GAG) binding profile beyond heparin has not been examined. In this study, we performed a Microscale Thermophoresis (MST) analysis on the heparin-binding glycoprotein YKL-40 using low molecular weight GAG oligosaccharides. We identified two new GAG ligands, dermatan sulfate (DS) and hyaluronan (HA), while chondroitin sulfate (CS) showed no detectable binding affinity. The results show that heparin is bound with the strongest affinity, followed by DS and HA. To further investigate these differences, molecular docking was used to evaluate possible binding modes. Molecular docking results indicated that both heparin and DS interacted with the same site on YKL-40, the heparin-binding site at residues 143–149, suggesting a multifunctional binding region that may act as a competitive switch or integration hub for spatially regulated signaling. Together, these findings expand the known ligand profile of YKL-40 and offer new insights into its ECM-context-dependent roles, with implications for targeting YKL-40 in diseases involving chronic inflammation, fibrosis, and cancer progression. Full article

As sustainable tourism practices gain traction globally, immersive technologies such as augmented reality (AR) and virtual reality (VR) have emerged as effective tools to enrich visitor experiences while supporting heritage site preservation. Particularly within built cultural environments, these technologies facilitate non-invasive interpretation of architectural spaces, enabling sustainable interaction with fragile historical structures. Despite growing scholarly attention, existing research has primarily focused on the pre-adoption phase or the technical affordances of AR/VR, with limited understanding of user behavior in the post-adoption phase. To address this gap, this study integrates the Expectation Confirmation Model (ECM) with the experiential attributes of AR/VR-enabled heritage applications, proposing an integrated theoretical model to identify key determinants of tourists’ continuance intention. Based on 434 valid survey responses collected at the Terracotta Warriors Museum, a UNESCO World Heritage Site, and analyzed using structural equation modeling (SEM), the results reveal that perceived usefulness, perceived ease of use, satisfaction, and confirmation directly influence continuance intention, while visual appeal, entertainment, enjoyment, interactivity and confirmation exert indirect effects through mediating mechanisms. The findings contribute theoretically by extending ECM to the heritage tourism domain and empirically by providing robust evidence from a high-profile non-Western site. Practically, this study offers actionable implications for designing immersive experiences that enhance post-visit continuance intention and align with broader sustainability objectives. Full article

Collagens make up the main components of the extracellular matrix (ECM), and, in cancer, are often aberrantly secreted by both tumor cells and stromal cells in the tumor microenvironment (TME). Collagen prolyl 4-hydroxylase (C-P4H), an enzyme that hydroxylates proline into 4-hydroxyproline at the Y position of the collagen -X-Y-Gly- triplet motif, is essential for the stability of the mature collagen trimer and collagen secretion. In this review, we summarize the research on the structure and function of C-P4H, the regulation of C-P4H enzyme activity, and the role of overexpression of its α-subunit, P4HA1, in promoting cancer progression as well as its potential as a prognostic marker and therapeutic target. Overexpression of P4HA1 is displayed in almost all solid cancers, including breast, colorectal, and lung cancer, and is associated with cancer progression, worse response to therapy, and poorer patient survival. Characterization of P4HA1 overexpression has demonstrated links to key hallmarks of cancer, not only in the canonical collagen deposition role, but also in non-canonical functions, such as cell stemness, hypoxic response, glucose metabolism, angiogenesis, and modulation of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment. P4HA1 is thus an attractive target for developing novel targeted therapies to improve treatment response in many cancer types. Full article

Edamame beans, rich in protein, essential amino acids, and antioxidant compounds, are promising substrates for novel plant-based beverages. This study developed and comprehensively characterized edamame-based beverage formulations with enhanced nutritional and functional attributes. Six formulations were prepared at edamame–water ratios of 1:3 or 1:6, incorporating either coconut water or coconut milk. Physicochemical analyses included particle size distribution, viscosity, amino acid and mineral profiles, antioxidant activity, volatile compounds, and storage stability. Nutritional analysis revealed that the ECM (1:3) formulation exhibited the highest protein content (3.68 g/100 g), while all formulations delivered essential minerals, with calcium levels ranging from 19.25% to 27.64% of total mineral content. ECW formulations were particularly rich in potassium, calcium, and phosphorus, whereas the pure edamame-based beverage had higher concentrations of sulfur and magnesium. The E (1:3) formulation demonstrated the highest total amino acid concentration (24.85 mg/mL), with glutamic and aspartic acids predominating compounds known to contribute to umami taste and buffering capacity. Higher edamame concentrations also resulted in significantly greater total phenolic (16.25 mg GAE/100 mL) and flavonoid content (6.42 mg QE/100 mL), which correlated with improved DPPH radical scavenging activity. The addition of coconut milk significantly reduced particle size, improved emulsion stability, and increased viscosity, while also masking undesirable volatile compounds such as hexanal, commonly associated with the beany aroma of legumes. These findings highlight the synergistic potential of blending edamame with coconut-based ingredients to produce nutrient-dense, sensorially acceptable, and shelf-stable plant-based beverages. Full article

Hydrogels with protein–polysaccharide combinations are widely used in the field of tissue engineering, as they can mimic the in vivo environments of native tissues, specifically the extracellular matrix (ECM). However, achieving stability and mechanical properties comparable to those of tissues by employing natural polymers remains a challenge due to their weak structural characteristics. In this work, we optimized the fabrication strategy of a hydrogel composite, comprising gelatin and sodium alginate (Gel-SA), by varying reaction parameters. Magnetite (Fe₃O₄) nanoparticles were incorporated to enhance the mechanical stability and structural integrity of the scaffold. The changes in hydrogel stiffness and viscoelastic properties due to variations in polymer mixing ratio, crosslinking time, and heating cycle, both before and after nanoparticle incorporation, were compared. FTIR spectra of crosslinked hydrogels confirmed physical interactions of Gel-SA, metal coordination bonds of alginate with Ca²⁺, and magnetite nanoparticles. Tensile and rheology tests confirmed that even at low magnetite concentration, the Gel-SA-Fe₃O₄ hydrogel exhibits mechanical properties comparable to soft tissues. This work has demonstrated enhanced resilience of magnetite-incorporated Gel-SA hydrogels during the heating cycle, compared to Gel-SA gel, as thermal stability is a significant concern for hydrogels containing gelatin. The interactions of thermoreversible gelatin, anionic alginate, and nanoparticles result in dynamic hydrogels, facilitating their use as viscoelastic acellular matrices. Full article

Articular cartilage (AC) is a specialised connective tissue covering joint surfaces. It enables smooth movement, distributes mechanical loads, and protects the underlying bone. In response to loading, AC adapts by modifying both its thickness and composition. AC is organised in different zones, with low cellularity and a high abundance of extracellular matrix (ECM). Mechanical overloading or immobilisation can lead to structural changes, potentially resulting in osteoarthritis (OA), for which no causal treatment currently exists. However, smaller defects can be treated using chondrocyte/cartilage transplantation or tissue engineering. A better understanding of the molecular composition of AC at different locations is essential to improve such therapeutic approaches. For this purpose, we performed a comprehensive analysis of porcine femoral knee cartilage at eight defined anatomical sites. Cartilage thickness and proteoglycan (PG) content were analysed histologically, while specific ECM proteins were assessed by proteomics and validated by immunohistochemistry and Western blot. Significant differences were identified, particularly between medial and lateral compartments, in terms of cartilage thickness, PG abundance, and ECM composition. Some proteins also showed zone-specific localisation patterns. These structural differences likely reflect adaptation to mechanical loading and should be considered to optimise future cartilage repair and tissue engineering strategies. Full article

The adult heart has a limited ability to regenerate, which is partly due to the structural and metabolic specialization that cardiomyocytes (CMs) acquire during postnatal maturation. In this review, we explore how cytoskeletal remodeling, metabolic reprogramming, and interactions with the extracellular matrix (ECM) regulate CM maturation, proliferation, and the potential for regeneration. We describe how the assembly of microtubules, actin filaments, and sarcomeric structures is essential for developing contractile function, but also creates structural barriers that prevent cell division. Recent studies show that disassembling these cytoskeletal components, along with activating signaling pathways such as Hippo-YAP, Wnt, and NRG1/ErbB4, can promote CM dedifferentiation and re-entry into the cell cycle. Metabolic shifts also play a critical role. A return from oxidative phosphorylation to glycolysis also leads to CM dedifferentiation and proliferation. In addition, changes in ECM composition and mechanical signaling affect cytoskeletal dynamics and regenerative capacity. Understanding how these structural, metabolic, and signaling networks work together opens the door to new approaches for restoring heart function after injury. Full article

Wound healing is a complex, multifaceted biological process that plays a vital role in recovery and overall quality of life. However, conventional wound care methods often prove insufficient, resulting in delayed healing, higher infection risk, and other complications. In response, biomaterials—especially hydrogels—have gained attention for their advanced wound management capabilities, which support wound healing by maintaining moisture, mimicking the extracellular matrix (ECM), and enabling targeted drug delivery triggered by wound-specific signals. They frequently carry antimicrobial or anti-inflammatory agents, promote blood vessel and nerve regeneration, and are biocompatible with customizable properties suited to different healing stages. Natural hydrogels, derived from polysaccharides, proteins, and peptides, offer several advantages over synthetic options, including inherent bioactivity, enzymatic degradability, and cell-adhesive qualities that closely resemble the native ECM. These features facilitate cell interaction, modulate inflammation, and speed up tissue remodeling. Moreover, natural hydrogels can be engineered as delivery systems for therapeutic agents like antimicrobial compounds, nanoparticles, growth factors, and exosomes. This review discusses recent advances in the use of natural hydrogels as multifunctional wound dressings and delivery platforms, with a focus on their composition, mechanisms of action, and potential for treating chronic and infected wounds by incorporating antimicrobial and regenerative additives such as silver and zinc oxide nanoparticles. Full article

DNA methylation holds promise for the early detection of tissue damage, making it crucial for identifying polycyclic aromatic hydrocarbon (PAH)-associated epigenetic biomarkers in childhood asthma. Sulforaphane (SFN), as a potential epigenetic modulator, can alleviate the adverse effects of environmental pollutants. This study quantified serum PAHs in 370 children via gas chromatography–mass spectrometry, assessed the methylation of target genes using bisulfite sequencing PCR (BSP), and performed mediation analysis to estimate the mediating effects of methylation levels between PAHs and childhood asthma. Murine models exposed to PAHs prenatally or postnatally, with offspring challenged with ovalbumin (OVA), were analyzed for lung DNA methylation. In vitro, HBE cells and HBSMCs treated with benzo(a)pyrene (BaP) and/or SFN were tested for inflammatory cytokines, methylation-related enzymes, and matrix metallopeptidase 9 (MMP9) modifications. The results showed total PAHs were associated with childhood asthma, with mediating effects of long interspersed nuclear element-1 (LINE-1) methylation. Prenatal PAH exposure enriched differentially methylated genes in the extracellular matrix (ECM)-receptor interaction pathway, while postnatal exposure enriched those in purine metabolism, and postnatal exposure also elevated Mmp9 expression via hypomethylation. BaP increased the expression of interferon gamma (IFN-γ), interleukin-4 (IL-4), interleukin-17A (IL-17A), transforming growth factor beta 1 (TGF-β), and ten-eleven translocation methylcytosine dioxygenases (TETs), and it upregulated MMP9 via enhancer hypomethylation and H3K27ac enrichment, while SFN reversed these effects by downregulating histone methyltransferase (HMT), leading to reduced H3K4me1 and subsequent H3K27ac depletion, thus suppressing MMP9 transcription. This study demonstrates that DNA methylation mediates PAH–childhood asthma associations, with distinct patterns in different exposure windows; MMP9 could serve as a crucial target for epigenetic modification during lung inflammation induced by PAH exposure, and SFN reverses PAH-induced epigenetic changes, aiding prevention strategies. Full article

The understanding of medulloblastoma (MB) progression is limited by the lack of minimally invasive monitoring methods. Extracellular vesicles (EVs) carrying disease-specific signatures are promising for liquid biopsies, but clinical translation is hindered by inconsistent isolation techniques. This study compares small EVs (sEVs) and their proteomes from blood plasma (BP) and cerebrospinal fluid (CSF) in MB. Using ultrafiltration and size exclusion chromatography (UF-SEC), we isolated sEVs from pediatric patient samples. sEV proteins from matched CSF-BP samples from MB patients (MBCSF/MBBP), healthy BP controls (HCBP), and MB cell lines (MBCL) were analyzed by liquid chromatography-tandem mass spectrometry, subjected to Gene Ontology and Cytoscape analyses, and compared to published MB, CSF, and EV datasets. By optimizing UF-SEC for small volumes, we found that CSF-sEVs are smaller and elute in later SEC fractions. Proteins linked to the extracellular matrix (ECM) were enriched in MBCSF and MBCL, while integrin binding showed inconsistent patterns between MBCSF and MBBP. MBBP and HCBP showed no significant differences. Fourteen proteins from MB datasets were identified in our analysis and primarily enriched in CSF. These findings support CSF-sEVs as more informative than BP-sEVs for MB diagnosis and monitoring, emphasize the need for fluid-specific sEV isolation, and suggest that ECM components and integrins may mediate MB progression. Full article

The adaptability of the supervisory control strategy of plug-in hybrid electric buses (PHEBs) to different driving styles determines the energy-saving performance. This paper proposes a driver-oriented adaptive equivalent consumption minimization strategy (ECMS) for PHEBs. The strategy aims to improve the fuel economy of PHEBs as much as possible by adapting to different driving styles while satisfying the physical constraints of the hybrid power system. Firstly, an online driving style recognition algorithm based on the Fuzzy K-means (FKM) algorithm and the random forest (RF) method is devised, in which the FKM algorithm is used to preprocess the feature parameters related to driving styles and the RF method is utilized to identify the driver’s driving style. Secondly, the driving style recognition results are introduced into the ECMS framework to form a driver-oriented energy management strategy. Finally, the proposed control strategy is verified using both Matlab/Simulink and Hardware-in-the-Loop. The verification results demonstrate that the proposed control strategy improves the fuel economy of PHEBs. Full article

Background/Objectives: The most commonly diagnosed group of rheumatic diseases in children is juvenile idiopathic arthritis. It is characterized by a chronic inflammatory process that leads to the degradation of the bone and joint system and increased secretion of pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6. These cytokines contribute to the dysregulation of adipocytokine metabolism, including adiponectin and leptin, as well as extracellular matrix components, such as tenascin C. While it is known that children with JIA exhibit TNF-α-stimulated degradation of most ECM cartilage components, the effect of TNF-α antagonists, such as etanercept, on these processes has not yet been evaluated. Therefore, the aim of our study was to assess the dynamics of changes in tenascin C, adiponectin, and leptin levels in the blood of children with JIA, both before and during therapy. Methods: The study material consisted of blood samples collected from 66 children of both sexes, including 40 girls and 26 boys diagnosed with juvenile idiopathic arthritis and treated with etanercept, as well as from 40 healthy children (22 girls and 18 boys). The quantitative assessment of adiponectin, leptin, and tenascin C levels was performed using commercial ELISA tests. Results: The conducted study revealed that untreated children with JIA exhibit altered plasma levels of all examined parameters—adiponectin, leptin, and tenascin C. Specifically, there was an increase in adiponectin concentration and a decrease in leptin as well as TNC levels compared to healthy children. The results demonstrated the beneficial effects of the TNF-α antagonist, i.e., etanercept, which not only improved the clinical condition of children with JIA but also positively influenced the metabolism of both adipokines and tenascin C. Conclusions: The obtained results suggest the potential use of adiponectin, leptin, and tenascin C as biochemical markers of the effectiveness of etanercept therapy in inhibiting the progression of degenerative joint changes in children with JIA treated with TNF-α inhibitors. Full article

Background: Hypoxia is a hallmark of solid tumors, including hepatocellular carcinoma (HCC), where it drives oxidative stress and extracellular matrix (ECM) remodeling, promoting tumor invasion and metastasis. Investigating these mechanisms in patients remains challenging due to the complexity of the tumor microenvironment. Methods: We developed a scaffold-free three-dimensional (3D) spheroid model of HCC using human hepatocellular carcinoma HepG2 cells (ATCC HB-8065). To characterize hypoxia-driven processes, a multiparametric approach combining MTT assays for metabolic activity, confocal microscopy for viability and ECM organization, flow cytometry for apoptosis and ROS detection, qRT-PCR for gene expression, and FTIR spectroscopy for biochemical profiling were performed. Results: The 3D model exhibited progressive ROS accumulation, stabilization of HIF-1α, and metabolic reprogramming toward aerobic glycolysis. In parallel, ECM remodeling was evident, with increased expression of SPARC and FN1 and collagen fiber alignment, reflecting an invasive tumor phenotype. Conclusions: This scaffold-free 3D HCC model recapitulates key physiopathological features of tumor progression, providing a robust and physiologically relevant platform to investigate the hypoxia–ROS–ECM relationship and to support preclinical evaluation of targeted therapeutic strategies. Full article