Search Results (3,499)

Fibrosis represents a terminal pathological manifestation encountered in numerous chronic diseases. The process involves the persistent infiltration of inflammatory cells, the transdifferentiation of fibroblasts into myofibroblasts, and the excessive deposition of extracellular matrix (ECM) within damaged tissues, all of which are characteristic features of organ fibrosis. Extensive documentation exists on fibrosis occurrence in vital organs such as the liver, heart, lungs, kidneys, and skeletal muscles, elucidating its underlying pathological mechanisms. Regular exercise is known to confer health benefits through its anti-inflammatory, antioxidant, and anti-aging effects. Notably, exercise exerts anti-fibrotic effects by modulating multiple pathways, including transforming growth factor-β1/small mother decapentaplegic protein (TGF-β1/Samd), Wnt/β-catenin, nuclear factor kappa-B (NF-kB), reactive oxygen species (ROS), microRNAs (miR-126, miR-29a, miR-101a), and exerkine (FGF21, irisin, FSTL1, and CHI3L1). Therefore, this paper aims to review the specific role and molecular mechanisms of exercise as a potential intervention to ameliorate organ fibrosis. Full article

Blood-based extracellular matrix (ECM) fragments have been identified as potential pharmacologic biomarkers in spondyloarthritis and diagnostic biomarkers in psoriatic arthritis and psoriasis vulgaris. This study aimed to explore whether ECM fragments can differentiate patients with psoriasis from healthy controls (HC) and determine their potential as biomarkers for response to treatment in psoriasis. The study population included 59 patients with moderate to severe psoriasis, not receiving systemic anti-psoriatic treatment at inclusion, and 52 HC matched by age, sex, and BMI. An EDTA plasma sample was taken from all subjects at inclusion. Nine patients with psoriasis who initiated treatment with adalimumab after inclusion and responded successfully had an additional EDTA plasma sample taken after three to six months. Twelve ECM fragments were measured using validated ELISAs and Immunodiagnostic Systems automated chemiluminescent assays. C4M, indicating collagen IV degradation, PRO-C3, indicating tissue fibrosis, and PRO-C4, indicating epidermal basement membrane turnover showed significantly elevated levels in psoriasis patients compared with HC (p = 0.005, p = 0.016, and p = 0.018, respectively). Despite successful treatment, adalimumab did not alter C4M, PRO-C3, or PRO-C4 levels. In conclusion, compared with controls, C4M, PRO-C3, and PRO-C4 were elevated in psoriasispatients, but treatment did not modulate these fragments. Full article

Extracellular vesicles (EVs) from Candida albicans can elicit immune responses, positioning them as promising acellular vaccine candidates. We characterized EVs from an avirulent C. albicans cell wall mutant (ecm33Δ) and evaluated their protective potential against invasive candidiasis. EVs from the yeast (YEVs) and hyphal (HEVs) forms of the SC5314 wild-type strain were also tested, yielding high survival rates with SC5314 YEV (91%) and ecm33 YEV immunization (64%). Surprisingly, HEV immunization showed a dual effect, resulting in 36% protection but also causing premature death in some mice. Proteomic analyses revealed distinct profiles among the top 100 proteins in the different EVs, which may explain these effects: a shared core of 50 immunogenic proteins such as Pgk1, Cdc19, and Fba1; unique, relevant immunogenic proteins in SC5314 YEVs; and proteins linked to pathogenesis, like Ece1 in SC5314 HEVs. Sera from SC5314 YEV-immunized mice showed the highest IgG2a titers and moderate IL-17, IFN-γ, and TNF-α levels, indicating the importance of both humoral and cellular responses for protection. These findings highlight the distinct immunogenic properties of C. albicans EVs, suggesting their potential in acellular vaccine development while emphasizing the need to carefully evaluate pathogenic risks associated with certain EVs. Full article

Corneal biomechanical properties are closely related to the cornea’s physiological and pathological conditions, primarily determined by the stromal layer. However, little is known about the influence of corneal cell interaction on the viscoelasticity of the stromal extracellular matrix (ECM). In this study, collagen-based hydrogels incorporated with keratocytes were reconstructed as corneal stromal models. Air-pulse optical coherence elastography (OCE) was used to characterize the viscoelastic properties of the corneal models. Plate compression, ramp–hold relaxation testing was performed on the initial corneal models. The findings demonstrated that the elastic modulus increased 5.27, 2.65 and 1.42 kPa, and viscosity increased 0.22, 0.06 and 0.09 Pa·s in the stromal models with initial collagen concentrations of 3, 5, and 7 mg/mL over 7 days. The elastic modulus and viscosity exhibited high correlation coefficients between air-pulse OCE and ramp–hold relaxation testing, with 92.25% and 98.67%, respectively. This study enhances the understanding of the influence of cell–matrix interactions on the corneal viscoelastic properties and validates air-pulse OCE as an accurate method for the mechanical characterization of tissue-engineered materials. Full article

Advancements in single-cell analyzis technologies, particularly single-cell RNA sequencing (scRNA-seq) and Fluorescence-Activated Cell Sorting (FACS), have enabled the analyzis of cellular diversity by providing resolutions that were not available previously. These methods enable the simultaneous analyzis of thousands of individual transcriptomes, facilitating the classification of cells into distinct subpopulations, based on transcriptomic differences, adding a new level of complexity to biomolecular and medical research. Fibroblasts, despite being one of the most abundant cell types in the human body and forming the structural backbone of tissues and organs, remained poorly characterized for a long time. This is largely due to the high morphological similarity between different types of fibroblasts and the lack of specific markers to identify distinct subpopulations. Once thought to be cells responsible solely for the synthesis of extracellular matrix (ECM) components, fibroblasts are now recognized as active participants in diverse physiological processes, including inflammation and antimicrobial responses. However, defining the molecular profile of fibroblast subpopulations remains a significant challenge. In this comprehensive review, which is based on over two thousand research articles, we focus on the identification and characterization of fibroblast subpopulations and their specific surface markers, with an emphasis on their potential as molecular targets for selective cell isolation. By analyzing surface markers, alongside intra- and extracellular protein profiles, we identified multiple fibroblast subtypes within the female reproductive system. These subtypes exhibit distinct molecular signatures and functional attributes, shaped by their anatomical localization and the surrounding physiological or pathological conditions. Our findings underscore the heterogeneity of fibroblasts and their diverse roles in various biological contexts. This improved understanding of fibroblast subpopulations paves the way for innovative diagnostic and therapeutic strategies, offering the potential for precision targeting of specific fibroblast subsets in clinical applications. Full article

Induced pluripotent stem cell (iPSC)-derived neurons (iNs) have been widely used as models of neurodevelopment and neurodegenerative diseases. Coating cell culture vessels with extracellular matrixes (ECMs) gives structural support and facilitates cell communication and differentiation, ultimately enhances neuronal functions. However, the relevance of different ECMs to the natural environment and their impact on neuronal differentiation have not been fully characterized. In this study, we report the use of four commonly used extracellular matrixes, poly-D-lysine (PDL), poly-L-ornithine (PLO), Laminin and Matrigel, which we applied to compare the single-coating and double-coating conditions on iNs differentiation and maturation. Using the IncuCyte live-cell imaging system, we found that iNs cultured on single Matrigel- and Laminin-coated vessels have significantly higher density of neurite outgrowth and branch points than PLO or PDL but produce abnormal highly straight neurite outgrowth and larger cell body clumps. All the four double-coating conditions significantly reduced the clumping of neurons, in which the combination of PDL+Matrigel also enhanced neuronal purity. Double coating with PDL+Matrigel also tended to improve dendritic and axonal development and the distribution of pre and postsynaptic markers. These results demonstrate that the extracellular matrix contributes to the differentiation of cultured neurons and that double coating with PDL+Matrigel gives the best outcomes. Our study indicates that neuronal differentiation and maturation can be manipulated, to a certain extent, by adjusting the ECM recipe, and provides important technical guidance for the use of the ECM in neurological studies. Full article

Cardiovascular diseases such as myocardial infarction or limb ischemia are characterized by regression of blood vessels. Local delivery of growth factors (GFs) involved in angiogenesis such as fibroblast blast growth factor-2 (FGF-2) has been shown to trigger collateral neovasculature and might lead to a therapeutic strategy. In vivo, heparin, a sulfated polysaccharide present in abundance in the extracellular matrix (ECM), has been shown to function as a local reservoir for FGF-2 by binding FGF-2 and other morphogens and it plays a role in the evolution of GF gradients. To access injectable biomaterials that can mimic such natural electrostatic interactions between soluble signals and macromolecules and mechanically tunable environments, the backbone of agarose, a thermogelling marine–algae-derived polysaccharide, was modified with sulfate, phosphate, and carboxylic moieties and the interaction and release of FGF-2 from these functionalized hydrogels was assessed by ELISA in vitro and CAM assay in ovo. Our findings show that FGF-2 remains active after release, and FGF-2 release profiles can be influenced by sulfated and phosphorylated agarose, and in turn, promote varied blood vessel formation kinetics. These modified agaroses offer a simple approach to mimicking electrostatic interactions experienced by GFs in the extracellular environment and provide a platform to probe the role of these interactions in the modulation of growth factor activity and may find utility as an injectable gel for promoting angiogenesis and as bioinks in 3D bioprinting. Full article

With increasingly stringent maritime environmental regulations, hybrid fuel cell ships have garnered significant attention due to their advantages in low emissions and high efficiency. However, challenges related to the coordinated control of multi-energy systems and fuel cell degradation remain significant barriers to their practical implementation. This paper proposes an innovative multi-timescale energy management strategy that focuses on optimizing the lifespan decay synergy of fuel cells and lithium batteries. The study designs an attention-based CNN-LSTM hybrid model for power prediction and constructs a two-stage optimization framework: The first stage employs Model Predictive Control (MPC) for long-term power planning to optimize equivalent hydrogen consumption, while the second stage focuses on real-time power allocation considering both power source degradation and system operational efficiency. The simulation results demonstrate that compared to single-layer MPC and the Equivalent Consumption Minimization Strategy (ECMS), the proposed method exhibits significant advantages in reducing single-voyage costs, minimizing differences in power source degradation rates, and alleviating power source stress. The overall performance of this strategy approaches the global optimal solution obtained through Dynamic Programming, comprehensively validating its superiority in simultaneously optimizing system economics and durability. Full article

Glioblastoma (GB) is one of the most aggressive and treatment-resistant cancers due to its complex tumor microenvironment (TME). We previously showed that GB progression is dependent on the aberrant induction of chaperone-mediated autophagy (CMA) in pericytes (PCs), which promotes TME immunosuppression through the PC secretome. The secretion of extracellular matrix (ECM) proteins with anti-tumor (Lumican) and pro-tumoral (Osteopontin, OPN) properties was shown to be dependent on the regulation of GB-induced CMA in PCs. As biomarkers are rarely studied in TME, in this work, we aimed to validate Lumican and OPN as prognostic markers in the perivascular areas of the peritumoral niche of a cohort of GB patients. Previously, we had validated their expression in GB xenografted mice presenting GB infiltration (OPN) or GB elimination (Lumican) dependent on competent or deficient CMA PCs, respectively. Then, patient sample classification by GB infiltration into the peritumoral brain parenchyma was related to GB-induced CMA in microvasculature PCs, analyzing the expression of the lysosomal receptor, LAMP-2A. Our results revealed a correlation between GB-induced CMA activity in peritumoral PCs and GB patients’ outcomes, identifying three degrees of severity. The perivascular expression of both immune activation markers, Iba1 and CD68, was related to CMA-dependent PC immune function and determined as useful for efficient GB prognosis. Lumican expression was identified in perivascular areas of patients with less severe outcome and partially co-localizing with PCs presenting low CMA activity, while OPN was primarily found in perivascular areas of patients with poor outcome and partially co-localizing with PCs presenting high CMA activity. Importantly, we found sex differences in the incidence of middle-aged patients, being significantly higher in men but with worse prognosis in women. Our results confirmed that Lumican and OPN in perivascular areas of the GB peritumoral niche are effective predictive biomarkers for evaluating prognosis and monitoring possible therapeutic immune responses dependent on PCs in tumor progression. Full article

Objective: Liver fibrosis, a hallmark of chronic liver diseases, is characterized by excessive extracellular matrix (ECM) deposition and scar tissue formation. Current antifibrotic nanomedicines face significant limitations, including poor penetration into fibrotic tissue, rapid clearance, and suboptimal therapeutic efficacy. The dense fibrotic ECM acts as a major physiological barrier, necessitating the development of a targeted delivery strategy to achieve effective therapeutic outcomes. Methods: We designed a liposomal delivery system functionalized with the GBI-10 aptamer and encapsulating obeticholic acid (OCA lips@Apt) to enhance selective delivery to fibrotic liver tissue while minimizing systemic toxicity. Results: Both in vitro and in vivo studies demonstrated that the aptamer-modified OCA liposomes effectively treated hepatic fibrosis through dual mechanisms: modulation of abnormal bile acid metabolism and attenuation of inflammation. The targeted delivery system leveraged the overexpression of Tenascin-C (TnC), a key ECM component in fibrotic tissues, for precise localization and enhanced endocytosis via the exposed cationic liposome surface. Conclusions: The OCA lips@Apt nanodrug demonstrated superior therapeutic efficacy with minimal off-target effects, offering a promising strategy to overcome critical barriers in liver fibrosis treatment. By precisely targeting the fibrotic ECM and modulating key pathological pathways, this TnC-guided liposomal delivery system provides a significant advancement in antifibrotic nanomedicine. Full article

The development of energy-saving vehicles is an important measure to deal with environmental pollution and the energy crisis. On this basis, more accurate and efficient energy management strategies can further tap into the energy-saving potential and energy sustainability of vehicles. The equivalent consumption minimization strategy (ECMS) has shown the ability to provide a real-time sub-optimal fuel efficiency performance. However, when taking the different market prices of fuel and electricity cost as well as battery longevity cost into account, this method is not very accurate for total operational economic evaluation. So, as an improved scheme, the instantaneous cost minimization strategy is proposed, where a comprehensive cost function, including the market price of the electricity and fuel as well as the cost of battery aging, is applied as the optimization objective. Simulation results show that the proposed control strategy for series-parallel hybrid electric buses can reduce costs by 41.25% when compared with the conventional engine-driven bus. The approach also impressively improves cost performance over the rule-based strategy and the ECMS. As such, the proposed instantaneous cost minimization strategy is a better choice for hybrid electric vehicle economic evaluation than the other main sub-optimal strategies. Full article

Rotator cuff tears are a common injury that can be treated with or without surgical intervention. Gel-based scaffolds have gained significant attention in the field of tissue engineering, particularly for applications like rotator cuff repair. Scaffolds can be biological, synthetic, or a mixture of both materials. Collagen, a primary constituent of the extracellular matrix (ECM) in musculoskeletal tissues, is one of the most widely used materials for gel-based scaffolds in rotator cuff repair, but other ECM-based and synthetic-based composite scaffolds have also been utilized. These composite scaffolds can be engineered to mimic the biomechanical and biological properties of natural tissues, supporting the healing process and promoting regeneration. Various clinical studies examined the effectiveness of these composite scaffolds with collagen, ECM and synthetic polymers and provided outstanding results with remarkable improvements in range of motion (ROM), strength, and pain. This review explores the material composition, manufacturing process and material properties of gel-based composite scaffolds as well as their clinical outcomes for the treatment of rotator cuff injuries. Full article

Thoracoabdominal aortic aneurysms (TAAAs) are rare but serious conditions characterized by dilation of the aorta characterized by remodeling of the vessel wall, with changes in the elastin and collagen content. Individuals with Marfan syndrome have a genetic predisposition for elastic fiber fragmentation and elastin degradation and are prone to early aneurysm formation and progression. Our objective was to analyze the medial collagen characteristics through histological, polarized light microscopy, and electron microscopy methods across the thoracic and abdominal aorta in twenty-five patients undergoing open surgical repair, including nine with Marfan syndrome. While age at surgery differed significantly between the groups, maximum aortic diameter and aneurysm extent did not. Collagen content increased from thoracic to infrarenal segments in both cohorts, with non-Marfan patients exhibiting higher collagen percentages, notably in the infrarenal aorta (729.3 nm vs. 1068.3 nm, p = 0.02). Both groups predominantly displayed mature collagen fibers, with the suprarenal segment containing the highest proportion of less mature fibers. Electron microscopy revealed comparable collagen fibril diameters across segments irrespective of Marfan status. Our findings underscore non-uniform histological patterns in TAAAs and suggest that ECM remodeling involves mature collagen deposition, albeit with lower collagen content observed in the infrarenal aorta of Marfan patients. Full article

Scaffolds resembling the extracellular matrix (ECM) provide structural support for cells in the engineering of tissue constructs. Various material sources and fabrication techniques have been employed in scaffold production. Cellulose-based matrices are of interest due to their abundant supply, hydrophilicity, mechanical strength, and biological inertness. Terrestrial and marine plants offer diverse morphologies that can replicate the ECM of various tissues and be isolated through decellularization protocols. In this study, three marine macroalgae species—namely Durvillaea poha, Ulva lactuca, and Ecklonia radiata—were selected for their morphological variation. Low-intensity, chemical treatments were developed for each species to maintain native cellulose structures within the matrices while facilitating the clearance of DNA and pigment. Scaffolds generated from each seaweed species were non-toxic for human dermal fibroblasts but only the fibrous inner layer of those derived from E. radiata supported cell attachment and maturation over the seven days of culture. These findings demonstrate the potential of E. radiata-derived cellulose scaffolds for skin tissue engineering and highlight the influence of macroalgae ECM structures on decellularization efficiency, cellulose matrix properties, and scaffold utility. Full article

Biofilms are a well-known multifactorial virulence factor with a pivotal role in chronic bacterial infections. Their pathogenicity is determined by the combination of strain-specific mechanisms of virulence and the biofilm extracellular matrix (ECM) protecting the bacteria from the host immune defense and the action of antibacterials. The successful antibiofilm agents should combine antibacterial activity and good biocompatibility with the capacity to penetrate through the ECM. The objective of the study is the elaboration of biofilm-ECM-destructive drug delivery systems: mixed polymeric micelles (MPMs) based on a cationic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA₃₅-b-PCL₇₀-b-PDMAEMA₃₅) and a non-ionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO₁₀₀-b-PPO₆₅-b-PEO₁₀₀) triblock copolymers, loaded with ciprofloxacin or azithromycin. The MPMs were applied on 24 h pre-formed biofilms of Escherichia coli and Pseudomonas aeruginosa (laboratory strains and clinical isolates). The results showed that the MPMs were able to destruct the biofilms, and the viability experiments supported drug delivery. The biofilm response to the MPMs loaded with the two antibiotics revealed two distinct patterns of action. These were registered on the level of both bacterial cell-structural alterations (demonstrated by scanning electron microscopy) and the interaction with host tissues (ex vivo biofilm infection model on skin samples with tests on nitric oxide and interleukin (IL)-17A production). Full article