The absence of dystrophin protein causes cardiac dysfunction in boys with Duchenne Muscular Dystrophy (DMD). However, the common mouse model of DMD (B10-mdx) does not manifest cardiac deficits until late adulthood limiting our understanding of the mechanism and therapeutic approaches to target the pediatric-onset cardiac pathology in DMD. We show the mdx mouse model on the DBA/2J genetic background (D2-mdx) displays juvenile-onset cardiomyopathy. Molecular and histological analysis revealed heightened leukocyte chemotactic signaling and failure to resolve inflammation, leading to chronic inflammation and extracellular matrix (ECM) fibrosis, causing cardiac pathology in juvenile D2-mdx mice. We show that pharmacologically activating the N-formyl peptide receptor 2 (FPR2) - a receptor that physiologically resolves acute inflammation, mitigated chronic cardiac inflammation and fibrosis, and prevented juvenile onset cardiomyopathy in the D2-mdx mice. These studies offer insights into pediatric onset of cardiac damage in DMD, a new therapeutic target, and identify a drug-based potential therapy.

UNASSIGNED: Hepatocellular carcinoma accounts for 80% of primary liver cancers, is the most common primary liver malignancy. Hepatocellular carcinoma is the third leading cause of tumor-related deaths worldwide, with a 5-year survival rate of approximately 18%. Chemotherapy, although commonly used for hepatocellular carcinoma treatment, is limited by systemic toxicity and drug resistance. Improving targeted delivery of chemotherapy drugs to tumor cells without causing systemic side effects is a current research focus. Chitosan, a biopolymer derived from chitin, possesses good biocompatibility and biodegradability, making it suitable for drug delivery. Enhanced chitosan formulations retain the anti-tumor properties while improving stability. Chitosan-based biomaterials promote hepatocellular carcinoma apoptosis, exhibit antioxidant and anti-inflammatory effects, inhibit tumor angiogenesis, and improve extracellular matrix remodeling for enhanced anti-tumor therapy.
UNASSIGNED: We summarized published experimental papers by querying them.
UNASSIGNED: This review discusses the physicochemical properties of chitosan, its application in hepatocellular carcinoma treatment, and the challenges faced by chitosan-based biomaterials.

OBJECTIVE: To explore the phenotype of sclera macrophages in form-deprivation (FD) myopia mice and the effects of M2 macrophage in FD myopia development.
METHODS: C57BL/6 mice were under 2 weeks of unilateral FD treatment. and they were separated into two groups, including an intraperitoneally injected(IP) vehicle group and Panobinostat (LBH589) (10 mg/kg per body weight) treatment group. All biometric parameters were measured before and after treatments, and the type and density of sclera macrophages were identified by immunofluorescence and RT-qPCR. In vitro, we analyzed the M2 macrophage and primary human sclera fibroblast (HSF) co-culture system by using the transcriptome sequencing method. Gene ontology (GO) and KEGG enrichment analyses were used to pinpoint the biological functions and pathways associated with the identified Differentially Expressed Genes (DEGs). The hub genes were investigated using the STRING database and Cytoscape software and were confirmed using RT-qPCR.
RESULTS: We found that the M2-type sclera macrophage density and expression increased in FD-treated eyes. The results showed that LBH589 inhibited the M2 macrophage polarization, and reduced FDM development. GO and KEGG analyses revealed that the DEGs were predominantly involved in the synthesis and breakdown of the extracellular matrix (ECM), as well as in pathways related to ECM-receptor interaction and the PI3K-Akt signaling pathway. Five hub genes (FN-1, MMP-2, COL1A1, CD44, and IL6) were identified, and RT-qPCR validated the variation in expression levels among these genes.
CONCLUSIONS: M2 macrophage polarization occurred in the sclera in FDM mice. Panobinostat-mediated inhibition of M2 macrophage polarization may decrease FDM progression, as M2 macrophages are crucial in controlling ECM remodeling by HSFs.

Small-cell lung cancer (SCLC) is the most aggressive and lethal type of lung cancer, characterized by limited treatment options, early and frequent metastasis. However, the determinants of metastasis in SCLC are poorly defined. Here, we show that estrogen-related receptor gamma (ERRγ) is overexpressed in metastatic SCLC tumors, and is positively associated with SCLC progression. ERRγ functions as an essential activator of extracellular matrix (ECM) remodeling and cell adhesion, two critical steps in metastasis, by directly regulating the expression of major genes involved in these processes. Genetic and pharmacological inhibition of ERRγ markedly reduces collagen production, cell-matrix adhesion, microfilament production, and eventually blocks SCLC cell invasion and tumor metastasis. Notably, ERRγ antagonists significantly suppressed tumor growth and metastasis and restored SCLC vulnerability to chemotherapy in multiple cell-derived and patient-derived xenograft models. Taken together, these findings establish ERRγ as an attractive target for metastatic SCLC and provide a potential pharmacological strategy for treating this lethal disease.

BACKGROUND: Extracellular matrix (ECM) remodeling in skeletal muscle is a significant factor in the development of sarcopenia. This study aims to evaluate changes in ECM remodeling in the lumbar paravertebral muscles of sarcopenic rats using diffusion-tensor magnetic resonance imaging (DT-MRI) and compare them with histology.
METHODS: Twenty 6-month-old female Sprague Dawley rats were randomly divided into the dexamethasone (DEX) group and the control (CON) group. Both groups underwent 3.0T MRI scanning, including Mensa, T2WI, and DT-MRI sequences. The changes in muscle fibers and extracellular matrix (ECM) of the erector spinal muscle were observed using hematoxylineosin and sirius red staining. The expressions of collagen I, III, and fibronectin in the erector spinae were detected by western blot. Pearson correlation analysis was employed to assess the correlation between MRI quantitative parameters and corresponding histopathology markers.
RESULTS: The cross-sectional area and fractional anisotropy values of the erector spinae in the DEX group rats were significantly lower than those in the CON group (p < 0.05). Hematoxylin eosin staining revealed muscle fiber atrophy and disordered arrangement in the DEX group, while sirius red staining showed a significant increase in collagen volume fraction in the DEX group. The western blot results indicate a significant increase in the expression of collagen I, collagen III, and fibronectin in the DEX group (p < 0.001 for all). Correlation coefficients between fractional anisotropy values and collagen volume fraction, collagen I, collagen III, and fibronectin were - 0.71, -0.94, -0.85, and - 0.88, respectively (p < 0.05 for all).
CONCLUSIONS: The fractional anisotropy value is strongly correlated with the pathological collagen volume fraction, collagen I, collagen III, and fibronectin. This indicates that DT-MRI can non-invasively evaluate the changes in extracellular matrix remodeling in the erector spinal muscle of sarcopenia. It provides a potential imaging biomarker for the diagnosis of sarcopenia.

Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.

Chronic inflammatory lung diseases are characterized by disease-specific extracellular matrix accumulation resulting from an imbalance of matrix metalloproteinases (MMPs) and their inhibitors. Zinc is essential for the function of MMPs, and zinc deficiency has been associated with enhanced tissue remodeling. This study assessed if zinc iodide (ZnI) supplementation through dimethyl sulfoxide (DMSO) modifies the action of MMPs in isolated human lung fibroblasts. The expression and activity of two gelatinases, MMP-2 and MMP-9, were determined by gelatin zymography and enzyme-linked immuno-sorbent assay (ELISA). Collagen degradation was determined by cell-based ELISAs. Collagen type I and fibronectin deposition was stimulated by human recombinant tumor growth factor β1 (TGF-β1). Untreated fibroblasts secreted MMP-2 but only minute amounts of MMP-9. TGF-β1 (5 ng/mL) reduced MMP-2 secretion, but stimulated collagen type I and fibronectin deposition. All the effects of TGF-β1 were significantly reduced in cells treated with ZnI-DMSO over 24 h, while ZnI and DMSO alone had a lower reducing effect. ZnI-DMSO alone did not increase MMP secretion but enhanced the ratio of active to inactive of MMP-2. ZnI alone had a lower enhancing effect than ZnI-DMSO on MMP activity. Furthermore, MMP-2 activity was increased by ZnI-DMSO and ZnI in the absence of cells. Soluble collagen type I increased in the medium of ZnI-DMSO- and ZnI-treated cells. Blocking MMP activity counteracted all the effects of ZnI-DMSO. Conclusion: The data suggest that the combination of ZnI with DMSO reduces fibrotic processes by increasing the degradation of collagen type I by up-regulating the activity of gelatinases. Thus, the combination of ZnI with DMSO might be considered for treatment of fibrotic disorders of the lung. DMSO supported the beneficial effects of ZnI.

Matrix metalloproteinase-1 (MMP-1) plays a pivotal role in the pathogenesis of periodontal diseases, particularly periodontitis, by virtue of its collagenolytic activity targeting collagen type I, the primary component of periodontal tissues. This review abstract elucidates the intricate involvement of MMP-1 in periodontal tissue homeostasis and its dysregulation in disease states. Elevated MMP-1 levels, observed in gingival tissues and crevicular fluid of individuals with periodontitis, correlate with the degradation of collagen fibers within the periodontium. This degradation contributes to the detachment of teeth from surrounding tissues and exacerbates alveolar bone resorption, hallmark features of periodontal breakdown. Therapeutically, targeting MMP-1 activity emerges as a promising strategy, prompting ongoing research into MMP inhibitors and host modulation therapies. Understanding MMP-1\'s nuanced role in periodontal diseases paves the way for personalized treatment approaches and holds promise in reshaping periodontal disease management for improved patient outcomes and periodontal health.

Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer\'s disease (AD) risk; however, the underlying mechanisms are not fully understood. Here, it is found that the injection of chondroitinase ABC (ChABC), mimicking ECM remodeling, into the medial prefrontal cortex (mPFC) reversed short-term memory loss and reduced amyloid-beta (Aβ) deposition in 5xFAD mice. ECM remodeling also reactivated astrocytes, reduced the levels of aggrecan in Aβ plaques, and enhanced astrocyte recruitment to surrounding plaques. Importantly, ECM remodeling enhanced the autophagy-lysosome pathway in astrocytes, thereby mediating Aβ clearance and alleviating AD pathology. ECM remodeling also promoted Aβ plaque phagocytosis by astrocytes by activating the astrocytic phagocytosis receptor MERTK and promoting astrocytic vesicle circulation. The study identified a cellular mechanism in which ECM remodeling activates the astrocytic autophagy-lysosomal pathway and alleviates AD pathology. Targeting ECM remodeling may represent a potential therapeutic strategy for AD and serve as a reference for the treatment of this disease.

In crowded microenvironments, migrating cells must find or make a path. Amoeboid cells are thought to find a path by deforming their bodies to squeeze through tight spaces. Yet, some amoeboid cells seem to maintain a near-spherical morphology as they move. To examine how they do so, we visualized amoeboid human melanoma cells in dense environments and found that they carve tunnels via bleb-driven degradation of extracellular matrix components without the need for proteolytic degradation. Interactions between adhesions and collagen at the cell front induce a signaling cascade that promotes bleb enlargement via branched actin polymerization. Large blebs abrade collagen, creating feedback between extracellular matrix structure, cell morphology, and polarization that enables both path generation and persistent movement.