Search Results (1,641)

Background and aims: Abdominal aortic aneurysm (AAA) is a vascular disease characterized by the progressive dilation of the aorta, culminating in rupture. At present, there are no pharmacological treatments to prevent AAA development or reduce rupture rate. A recent study showed that patients prescribed Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have significantly lower risks of mortality, AAA repair, and acute abdominal aortic syndrome. Semaglutide is a GLP-1RA with increased agonist capacity and longer half-life, compared to earlier generations of GLP-1RAs. In this study, we aimed to investigate the role and mechanisms of semaglutide in the prevention of AAA development and rupture in a murine model. Methods: AAA was induced in apolipoprotein-E-deficient mice, by continuous subcutaneous infusion of angiotensin II. Treatment with semaglutide (12 µg/kg) began seven days after disease induction (rescue trial) or simultaneously with disease induction (prophylactic trial). At experimental endpoint, aortic diameter was measured by high-frequency ultrasound and the aortic tissue was collected for histological analysis. Results: Prophylactic treatment with semaglutide drastically reduced mortality by dissection and rupture during the first seven days of disease development, but did not affect AAA formation at 28 days. Histological evaluation of the aorta at day seven showed a normal vessel wall thickness with a trend for a higher content of collagen in the aortic wall in mice treated with semaglutide, compared to controls. Conclusions: Semaglutide prevents aortic rupture and dissection in the early phases of AAA development in the angiotensin II mouse model, likely by promoting the maintenance of an adequate proportion of collagen in the vessel wall. Full article

Betaine-homocysteine methyltransferase (BHMT) is an enzyme involved in one-carbon metabolism and plays a crucial role in maintaining liver health. In this study, we investigated the impact of liver-specific deletion of BHMT on liver dysfunction using a mouse model. We generated BHMT floxed mice and bred them with albumin Cre to generate liver-specific BHMT knockout (BHMT LKO) mice. Liver tissues harvested from six-month-old chow-fed BHMT floxed and LKO mice were characterized through histological, biochemical, and molecular analyses. BHMT LKO mice displayed a complete loss of hepatic expression of BHMT mRNA, protein and enzyme activity. Histopathological analysis revealed the development of hepatic steatosis in BHMT LKO mice compared to the floxed mice. These morphological changes were supported by biochemical analysis showing elevated levels of hepatic triglycerides in conjunction with a profound decrease in the methylation potential (i.e., reduced S-adenosylmethionine (SAM): S-adenosylhomocysteine (SAH) ratio), which was mainly driven by a six- to sevenfold increase in SAH levels. BHMT LKO mice also exhibited increased lipid peroxidation and lysosomal dysfunction compared to floxed mice. Early signs of inflammation were seen in the livers of BHMT LKO mice of both sexes, as evident from significant increase in CD68-positive cells and interleukin 1β levels. Additionally, there was a moderate increase in fibrosis, as evidenced by the upregulated expression of α-smooth muscle actin and collagen II levels and the histological assessment of picrosirius red-stained liver sections of BHMT LKO mice of both sexes compared to their respective counterparts. These findings demonstrate that hepatic BHMT deficiency promotes lipid accumulation, lysosomal/proteasomal dysfunction, and early inflammatory and fibrotic changes in the liver by reducing the methylation potential. Collectively, our results underscore BHMT as a critical regulator of liver homeostasis and a potential therapeutic target in liver-related disorders. Full article

Mechano-sorptive phenomena (MSP) refer to the coupled mechanical response of polymers under simultaneous mechanical stress and fluid sorption. The most researched MSP are environmental stress cracking (ESC) and mechano-sorptive creep (MSC). ESC initiates at regions of localized stress and solvent sorption, presenting as brittle fracture, while MSC is characterized by large, time-dependent, and partially recoverable creep associated with transient bulk sorption. ESC experiments can however also result in significant plastic deformation, in which case the term environmental stress yielding (ESY) has been used. Similarly, MSC can evolve into tertiary creep followed by rupture, in which case the phenomenon is termed mechano-sorptive creep rupture (MSCR). Both behaviors originate from solvent diffusion into the amorphous phase, leading to disruption of non-covalent interactions between polymer chains. This review bridges seemingly disconnected research to illustrate that ESC and MSC represent extremes on a continuum of MSP, rather than disparate phenomena. We identify the principles of polymer thermodynamics and experimental methods necessary to separate polymer deformation under MSC into reversible stress-induced swelling and irreversible non-equilibrium deformation. Finally, we illustrate how MSP underline the functionality of several biomimetic materials including dentin adhesives, mutable collagenous tissue, spider silk, tendons, and articular cartilage, as well the synthesis of biomimetic materials by solvent vapor annealing assisted by soft shear. Full article

Effective hemostasis in deep and irregular wounds remains a critical clinical challenge. To address this, we developed a bioresorbable chitosan composite hydrogel reinforced with short eggshell membrane (ESM) nanofibers, which were obtained through cryogenic grinding. The resulting ESM/CCS hydrogel, crosslinked with citric acid, exhibited significantly enhanced properties compared to pure CCS hydrogel, including a 63% increase in mechanical strength, a two-fold improvement in shape memory, a 25.31% reduction in hemolysis, over 2% higher cytocompatibility, and more than 48% greater hemostatic efficiency. Structural characterization confirmed the successful integration of bioactive chitosan with collagen mimetic ESM nanofibers. This biomimetic approach synergistically combines mechanical reinforcement with biological functionality, highlighting its strong potential as an advanced hemostatic dressing for complex wound management. Full article

Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is a major complication and leading cause of mortality in SSc. Transforming growth factor-β (TGF-β) has been implicated as a central mediator of fibrosis; however, while TGF-β1 has been extensively studied, the roles of TGF-β2 and TGF-β3 remain incompletely defined. Here, we systematically compared the effects of TGF-β1, TGF-β2, and TGF-β3 in dermal and lung fibroblasts, evaluating extracellular matrix synthesis and contraction, cytokine secretion, proliferation, and myofibroblast differentiation. TGF-β2 and TGF-β3 induced greater profibrotic cytokine release of Interleukin (IL)-6 and IL-11 and increased collagen-I and fibronectin synthesis compared with TGF-β1 in dermal and lung fibroblasts (all p < 0.05). TGF-β2 and TGF-β3 stimulated greater collagen-I contraction in dermal fibroblasts (p < 0.05), but greater myofibroblast differentiation in lung fibroblasts (p < 0.05). The TGF-β isoforms did not affect proliferation. All TGF-β isoforms activated SMAD2/3 signalling; however, TGF-β2 and TGF-β3 reduced expression of TGF-β Receptor II and the inhibitory regulator, SMAD7. In summary, TGF-β2 and TGF-β3 have a more pronounced profibrotic effect than TGF-β1 on dermal and lung fibroblast functions, making them potential targets for treatment for skin and lung fibrosis in diseases such as SSc. Full article

In a previous study, we demonstrated that a novel surface treatment applied to laser-melted Ti6Al4V substrates supports osteoblast-like cell adhesion, proliferation, and the activation of early osteogenic pathways. Building on these preliminary findings, the present work aimed to further investigate the ability of the same surface to promote extracellular matrix (ECM) deposition, organization, and osteogenic maturation, which are critical events for the establishment of a stable bone–implant interface in subperiosteal dental implants. Human osteoblast-like MG-63 cells were cultured on Ti6Al4V discs subjected to different surface treatments, including a proprietary surface modification (ATcs) specifically designed for subperiosteal applications. ECM formation and maturation were evaluated through scanning electron microscopy coupled with energy-dispersive spectroscopy, immunofluorescence, and semiquantitative analyses of osteogenic markers type I collagen (COL1A1), secreted protein acidic and rich in cysteine (SPARC), and dentin matrix protein 1 (DMP1) through Western blotting. The results showed that, while all tested surfaces supported cell adhesion, the ATcs surface promoted a distinct osteogenic profile characterized by enhanced DMP1 expression, organized collagen deposition, and the formation of calcium–phosphate–rich mineralized structures. Compared to surfaces that primarily stimulated cell proliferation or early matrix production, ATcs appeared to favour progression toward late-stage osteogenic maturation and matrix mineralization. Taken together, these findings extend our previous observations and indicate that this novel surface treatment not only supports osteoblast viability and early differentiation but also promotes extracellular matrix maturation, a key prerequisite for effective osseointegration. Although further in vivo studies are required, the present data provide additional biological rationale for the use of ATcs-treated Ti6Al4V surfaces in next-generation custom-made subperiosteal implant designs. Full article

Background: In this study, type B gelatin was extracted from Oreochromis niloticus scales under hydrothermal conditions at 60 °C to evaluate the effect of ultrasound-assisted pretreatment on its structural, physicochemical, thermal, and functional properties. Methods: Gelatin obtained with and without ultrasound pretreatment was systematically characterized through molecular weight analysis, proteomic profiling, size determination, surface morphology, proximate composition, thermal behavior, and gelation-related functional properties in order to assess the influence of the extraction method on gelation performance. Results: Ultrasound pretreatment slightly increased gelatin yield from 1.46 to 1.70%, indicating enhanced collagen solubilization. Proteomic analysis confirmed the predominance of fibrillar collagen proteins in both samples, although differences in protein distribution were observed. Furthermore, weight-average molecular weight analysis revealed a reduction from 212.3 ± 11.8 to 170.9 ± 13.2 kDa in the ultrasound-treated sample, suggesting partial fragmentation of collagen chains induced by cavitation effects. Structural modifications were also reflected in increased porosity and surface changes, contributing to improved colloidal stability. However, these changes significantly affect the functional behavior of the gelatin. Ultrasound-treated sample exhibited limited gel-forming capacity and failed to form stable gels at the evaluated concentration, despite complete dissolution. In contrast, gelatin extracted without ultrasound treatment retained higher-molecular-weight fractions and formed stable gels at both 5 and 10% (w/w). Thermal and spectroscopic analyses suggested that the fundamental collagen structure was preserved in both samples, although differences were observed in thermal degradation behavior. Conclusions: These results highlight the importance of controlling ultrasound-assisted extraction conditions to balance collagen recovery with the preservation of molecular integrity required for gelation, providing insights for the development of sustainable fish-derived biomaterials for pharmaceuticals and biomedical applications. Full article

Chrome tanning of fish skins generates hazardous effluents and carcinogenic Cr(VI) residues; chromium-free routes to valorize collagen-rich by-products from aquaculture and coastal fisheries are therefore needed. We report a 12-stage ecological protocol employing acetic acid/NaCl pickling, Acacia mearnsii tannin, A. podalyriifolia retanning, mashed-papaya enzymatic bating, and cinnamon as antimicrobial/odor adjunct, scaled from bench to pilot using exclusively locally sourced inputs, for Nile tilapia (Oreochromis niloticus) and Patagonian flounder (Paralichthys patagonicus). Three trained operators evaluated macroscopic quality against five predefined criteria adapted from SATRA and ISO 3376 grading conventions, providing a structured feasibility baseline that does not substitute for the standardized instrumental testing designated as priority future work. Both species achieved satisfactory grain stability, complete tannin penetration, pliable handle, and cinnamon-dominant odor without residual amines; dark-brown coloration is a recognized practical limitation for fashion applications. In silico molecular docking (GNINA v1.0) was used to explore the mechanistic plausibility of each ecological substitution, generating testable hypotheses rather than definitive mechanistic conclusions: the multidentate polyphenol proxy (PGG) exhibited consistently superior collagen engagement over the flavanol monomer across both collagen constructs and all three scoring metrics (1CAG: Vina affinity −5.51 ± 0.13 vs. −3.54 ± 0.35 kcal/mol; CNNscore 0.874 ± 0.009 vs. 0.771 ± 0.010; 7CWK: Vina affinity −6.98 ± 1.43 vs. −4.37 ± 0.16 kcal/mol; CNNscore 0.858 ± 0.024 vs. 0.635 ± 0.094). Dipeptide probes were reproducibly accommodated in the papain catalytic cleft, with the closest configuration reaching 3.997 Å from the catalytic nucleophile (OCS25-SG). Trans-cinnamaldehyde occupied the quorum-sensing pocket with reproducible placement (CNNscore 0.718 ± 0.034) but without score-based selectivity over structural decoys, a result interpreted as hypothesis-generating for future microbiological validation. The protocol is reproducible from bench to pilot and generalizable across two species with distinct dermal architectures. Quantitative physical-mechanical testing (shrinkage temperature, tensile strength, elongation, tear load), CIELab colorimetric analysis, and effluent characterization (COD, BOD₅, total phenolics) are designated as priorities for future validation. Full article

Faba bean-fed crispy tilapia represents a commercially valuable aquaculture product, renowned for its exceptional muscle firmness. However, the dynamic changes in muscle metabolite profiles during the tilapia crisping process remain largely unelucidated. In this study, proton nuclear magnetic resonance spectroscopy (¹H-NMR) combined with multivariate statistical analysis was employed to characterize and compare the muscle metabolomes of tilapia subjected to different crispness grades (CD0, CD2, CD4). A total of 11 differential metabolites were successfully identified, among which glycine, threonine, and trans-4-hydroxy-L-proline were demonstrated to be potential crispness-related biomarkers. Specifically, as the crispness grade increased from 0 to 4, the muscle contents of these key metabolites exhibited a consistent downward trend: glycine decreased significantly from 19.86 mM to 7.15 mM, threonine from 1.21 mM to 0.58 mM, and trans-4-hydroxy-L-proline from 2.25 mM to 0.89 mM. Subsequent metabolic pathway enrichment analysis further revealed that the glycine-serine-threonine metabolic pathway represented the most significantly perturbed pathway associated with the crisping process. Collectively, our findings demonstrate that faba bean-based feeding regimens enhance tilapia muscle crispness by orchestrating metabolite signatures involved in collagen biosynthesis and lipid metabolism. These results not only provide novel insights into the intrinsic molecular mechanisms underlying tilapia crisping but also establish a solid theoretical framework for the precise quality control and standardized production of high-quality crispy tilapia. Full article

Background: Chronic kidney disease (CKD) is characterized by irreversible structural damage and functional deterioration of the kidneys. Esculetin (ES), with its anti-inflammatory, antioxidant, and immunomodulatory activities, shows potential in delaying renal function decline. This study aimed to investigate the protective effect of ES on adenine-induced CKD in mice and its underlying molecular mechanism, with a focus on its role in preventing the transition from acute kidney injury (AKI) to CKD. Methods: A AKI-to-CKD transition mice model was established by feeding mice a 0.2% adenine diet, and ES (30, 60 mg/kg) was co-administered for 4 weeks as a prophylactic intervention. Serum creatinine (SCr), blood urea nitrogen (BUN), and renal histopathology (HE, Masson, IHC) were evaluated to assess renal injury. Network pharmacology and transcriptomics were combined to screen the targets, and Western blot was used to verify the signaling pathways. Results: ES significantly reduced SCr and BUN levels in CKD mice and alleviated renal tubular dilation and inflammatory infiltration. ES decreased pro-inflammatory factors (IL-1β, IL-6, TNF-α) and MDA levels and enhanced SOD activity. Additionally, ES inhibited renal interstitial collagen deposition and reversed epithelial–mesenchymal transition (EMT) by upregulating E-cadherin and downregulating α-SMA levels. Mechanism studies confirmed that ES significantly inhibited the phosphorylation levels of p-EGFR, p-SRC, p-PI3K, p-AKT, and p-p65 in renal tissues. Conclusions: ES effectively inhibits inflammation, oxidative stress, and fibrosis by modulating the EGFR/SRC/PI3K/AKT/NF-κB signaling axis, thereby preventing the AKI-to-CKD transition in the adenine-induced renal injury model and alleviating the progression of chronic renal damage. Full article

Oleuropein, the principal secoiridoid phenolic compound of olive leaves (Olea europaea L.), is recognized for its broad-spectrum antimicrobial, antibiofilm, antioxidant, and tissue-regenerative properties. However, its effective local therapeutic application remains challenging due to rapid clearance from the site of administration and limited residence time. In this study, an oleuropein-rich aqueous olive leaf extract was incorporated into a thermoresponsive sol–gel delivery system designed for localized application. The formulation was engineered to remain in a low-viscosity sol state at room temperature and to undergo a temperature-triggered sol-to-gel transition near physiological temperature (~33 °C), enabling in situ gel formation. Oleuropein content was quantified using a validated HPLC method, and the formulation was characterized with respect to physicochemical parameters, thermoreversible gelation behavior, particle size distribution, mechanical properties, and spreadability. Biological performance was evaluated through in vitro cytocompatibility (MTT assay), fibroblast migration (scratch assay), and collagen deposition (Sirius Red staining) in L929 fibroblasts, as well as antibiofilm activity against representative Gram-positive and Gram-negative bacterial strains. The developed sol–gel system demonstrated stable physicochemical characteristics, rapid and reversible thermogelation, suitable mechanical and spreading properties, concentration-dependent inhibition of biofilm formation, and acceptable cytocompatibility within the tested concentration range. Notably, the formulation supported fibroblast viability and collagen-associated responses at optimized concentrations. Overall, the results indicate that the proposed thermoresponsive sol–gel formulation represents a promising strategy for the localized delivery of oleuropein-rich olive leaf extract, combining physicochemical stability with dual wound-healing and antibiofilm functionality. Full article

Background/Objectives: Radiotherapy following mastectomy induces persistent structural alterations in the chest wall, including fibrosis, extracellular matrix disorganization, and vascular changes that compromise reconstructive outcomes. Although autologous fat grafting is widely used to improve tissue quality in irradiated breasts, direct human histological evidence remains limited. The aim of this prospective pilot study was to evaluate intra-patient histological remodeling in irradiated postmastectomy breast tissue before and 4 months after autologous fat grafting using paired core needle biopsies. This study should be considered a hypothesis-generating histological pilot study. Methods: Five female patients with prior mastectomy and adjuvant radiotherapy underwent Tru-Cut core needle biopsy of irradiated chest wall tissue before lipofilling and at approximately four months (range between 3 and 12 months) post-procedure. Specimens were processed using formalin fixation, paraffin embedding, and hematoxylin and eosin staining. Histological assessment focused on collagen density, stromal organization, vascular structures, inflammatory infiltrate, and adipocyte integration. Comparative intra-patient analysis was performed descriptively. Results: Baseline biopsies demonstrated consistent post-radiation alterations, including collagen compaction, stromal disorganization, perivascular fibrosis, and variable inflammatory infiltrate. Post-lipofilling specimens showed heterogeneous remodeling characterized by focal collagen fiber insertion between adipocytes, areas of immature connective tissue formation, and variable preservation of adipose architecture. The extent and pattern of remodeling differed among patients. Inflammatory activity decreased or remained mild in most cases. Conclusions: Autologous fat grafting in irradiated postmastectomy tissue is associated with measurable histological remodeling. Structural adaptation appears heterogeneous and patient-specific, suggesting a dynamic multi-stage process rather than uniform regeneration. Further studies incorporating quantitative and molecular analyses are required to clarify the mechanisms underlying these changes. Full article

This study investigated the valorization of chicken feet, an underutilized poultry by-product, through enzymatic hydrolysis to obtain a protein hydrolysate with improved functional properties. Enzymatic treatment was carried out using Enzy-Mix U100 and collagenase from Streptomyces lavendulae, with cheese whey applied as a process medium. The resulting protein hydrolysate contained 59.1% protein and was characterized by high levels of glycine (31.64 g/100 g protein), hydroxyproline (10.91 g/100 g protein), and alanine (10.58 g/100 g protein). The hydrolysate exhibited strong techno-functional performance, with a water-binding capacity of 580%, an emulsifying activity index of 166 m²/g, and an emulsion stability index of 31 min. Microstructural analysis revealed irregular porous particles typical of freeze-dried protein hydrolysates, reflecting structural modification of collagen during enzymatic treatment. Mineral analysis showed notable levels of sodium (463.1 mg/100 g) and magnesium (351.8 mg/100 g). Microbiological evaluation demonstrated high sanitary quality, with a total viable count of 100 CFU/g and absence of coliforms, Escherichia coli, yeasts, and molds in 1 g of product. The technological process reduced the characteristic odor of chicken feet while maintaining a light color and good dispersibility. These findings confirm the potential of enzymatic hydrolysis as a sustainable strategy for converting poultry by-products into safe, value-added functional protein ingredients for food applications. Full article

Endoscopic sinus surgery (ESS) is commonly performed to treat chronic rhinosinusitis and selected sinonasal tumors, yet postoperative complications such as neo-osteogenesis and restenosis remain frequent, largely due to impaired mucosal regeneration after extensive epithelial and bony tissue loss. Successful nasal epithelial repair requires a microenvironment that preserves cell viability, phenotype, and barrier integrity. Conventional culture substrates often lack physiological relevance or rely on animal-derived components, limiting translational applicability. In this study, we evaluated nanofibrillar cellulose (NFC) hydrogel (GrowDex^®) as a xeno-free scaffold for primary human nasal epithelial cells (NECs). NECs isolated from healthy donor tissue were characterized by immunofluorescence and qPCR for basal, goblet, and ciliated cell markers. Cells embedded in NFC were assessed for viability, cytotoxicity, epithelial morphology, and barrier function. Transepithelial electrical resistance (TEER) and FITC-dextran permeability assays were used to quantify barrier integrity and compared with collagen- and polylysine-based controls. NECs cultured in NFC maintained high viability, stable epithelial morphology, and preserved subtype-specific marker expression without detectable cytotoxicity. NFC-supported cultures demonstrated enhanced barrier formation, indicated by higher TEER values and reduced paracellular permeability relative to controls, and sustained structural integrity during extended culture. These findings identify NFC hydrogel as a biocompatible, non-animal scaffold that supports functional human nasal epithelium regeneration and may contribute to advanced tissue engineering strategies for craniofacial bone repair. Full article

Collagen, the most abundant extracellular matrix (ECM) protein, has emerged as a cornerstone biomaterial in drug delivery and regenerative medicine due to its intrinsic biocompatibility, biodegradability, and low immunogenicity. Engineering collagen into microspheres transforms its functionality beyond bulk scaffolds by increasing surface area, enabling minimally invasive delivery, and providing precise control over degradation, mechanical properties, and therapeutic release. This review provides a comprehensive analysis of collagen-based microspheres, with a particular focus on their dual role as biomimetic microenvironments and delivery systems. Recent advances in fabrication strategies, including emulsification, microfluidics, spray-drying, and electrospraying, are discussed in the context of scalability, size control, and payload encapsulation. Composite approaches that incorporate bioactive minerals, polysaccharides, or synthetic polymers are highlighted for their ability to enhance mechanical performance and biological function. We further examine characterization frameworks that link microscale structure and physicochemical properties to biological outcomes, with emphasis on how collagen microspheres replicate key structural, mechanical, and signaling features of native tissue microenvironments. Collagen microspheres have demonstrated broad utility as controlled delivery platforms, cell-instructive microcarriers, and injectable systems for tissue regeneration, including applications in bone, cartilage, skin, and nerve repair, as well as advanced wound care and localized cancer therapy. Finally, we critically assess current challenges related to scalable manufacturing, sterilization compatibility, and batch reproducibility, and outline emerging solutions such as recombinant collagen, advanced biofabrication, and stimuli-responsive systems. Collectively, collagen microspheres represent a powerful and adaptable platform poised to advance next-generation regenerative and therapeutic technologies. Full article