Extracellular Matrix Degradation Research Articles

BRD4/MAP2K7/PGF Signaling Axis Promotes Senescence and Extracellular Matrix Metabolism of Nucleus Pulposus Cells in Intervertebral Disk Degeneration.

Intervertebral disk degeneration (IDD) is a common age-related degenerative disease of the spine that imposes a substantial economic burden on both families and society. Despite substantial advances in understanding the mechanisms underlying IDD, effective therapeutic interventions for its treatment and prevention remain elusive. Our previous study identified a positive correlation between IDD severity and bromodomain-containing protein 4 (BRD4) expression. However, the multifaceted role of BRD4 in IDD is still not fully understood. This study explored the abnormal elevation of BRD4 expression in nucleus pulposus (NP) tissues from patients with IDD and in an age-related rat model of IDD. We found that BRD4 levels were positively correlated with NP senescence and extracellular matrix (ECM) degradation and inversely correlated with ECM anabolism. These relationships were further confirmed through assays measuring senescence-associated β-galactosidase activity, the expression of senescence markers P21 and P16, senescence-associated secretory phenotype indicators (IL-6, IL-8, MMP3, and MMP13), as well as ECM metabolism markers such as collagen II and aggrecan. Mechanistically, aberrant BRD4 expression was found to upregulate MAP2K7, which in turn enhances PGF expression, promoting NP cell senescence and ECM metabolism. These findings highlight the crucial role of the BRD4/MAP2K7/PGF signaling axis in cellular senescence and ECM regulation, suggesting that BRD4 represents a promising therapeutic target for IDD.

Targeting Txnip-mediated metabolic reprogramming has therapeutic potential for osteoarthritis

Osteoarthritis (OA) inflammatory microenvironment triggered glucose metabolism and mitochondrial dysfunction in chondrocytes, leading to a shift of metabolic tendency between oxidative phosphorylation and anaerobic glycolysis. Thioredoxin-interacting protein (Txnip) increased production of reactive oxygen species (ROS), which exacerbates oxidative stress, inflammation and further accelerates cartilage degeneration and extracellular matrix (ECM) degradation. Txnip expression is also positively correlated with several critical pathological glucose and lipid metabolism processes beyond inflammation and endoplasmic reticulum stress (ERS). While the role of Txnip-mediated chondrocyte metabolic reprogramming in OA has not been explored. This study focuses on the unexplored role of Txnip-mediated chondrocyte metabolic reprogramming in chondrogenesis and ECM deposition. The study reveals that upregulated glycolysis after Txnip knockdown significantly contributes to mouse chondrogenesis and ECM deposition. Moreover, verapamil, a clinically used drug that targets Txnip, shows potential for treating mouse OA. These findings suggest that targeting Txnip-mediated metabolic reprogramming could offer a novel therapeutic strategy for OA treatment.

Trimethylamine N-oxide Aggravates Thoracic Aortic Aneurysm by Inhibiting Axl to Promote Vascular Smooth Muscle Cell Dysfunction.

Thoracic aortic aneurysm (TAA) is a life-threatening condition that currently lacks an effective therapeutic strategy. Phenotypic switching in vascular smooth muscle cells (VSMCs) and extracellular matrix (ECM) degradation are considered to be among the causes of TAA development. Trimethylamine N-oxide (TMAO) is a gut microbial metabolite that has been associated with the increased risk of cardiovascular diseases. However, its general association with TAA remains unclear. Therefore, the present study aimed to assess the possible role of TMAO in TAA development. In the mouse TAA model, TMAO exacerbates aortic dilation and degeneration, promoting the development of thoracic aortic aneurysm. Furthermore, TMAO was observed to impair murine cardiac function. In vitro, it was demonstrated that TMAO inhibited proliferation whilst promoting migration and apoptosis in VSMCs. RNA-sequence analysis of TMAO targets subsequently identified Axl and a cohort of genes associated with extracellular matrix signaling. Mechanistically, it was found that TMAO inducing a shift from a contractile to a synthetic phenotype by inhibiting Axl. Overexpressing Axl suppresses this transition. In summary, TMAO worsens TAA progression by impairing vascular smooth muscle cell function, and restoring Axl expression can counteract the phenotypic shift caused by high TMAO levels. Thus, targeting the TMAO-Axl regulatory axis could be a therapeutic strategy for TAA patients with elevated TMAO expression.

Selenium deficiency exacerbates cartilage degradation caused by HT-2 toxin via notch signaling pathway activation.

This study aims to explore the interaction of Selenium (Se) deficiency and HT-2 toxin on cartilage homeostasis and the effect of Notch signaling pathway in this process. Male C57BL/6 mice were randomly assigned to different dietary groups and subjected to either a Se-deficiency diet or a control diet for 4weeks, followed by exposure to varying doses of HT-2 toxin for 4weeks. Primary mouse chondrocytes were extracted and treated with DAPT (N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester), a γ-secretase inhibitor for the Notch signaling pathway, before combined intervention. Histological evaluation and transmission electron microscopy (TEM) were applied to assess cartilage damage, while immunohistochemical (IHC) analysis and Quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect extracellular matrix (ECM) metabolism and Notch signaling. HT-2 toxin, alone or in combination with Se deficiency, led to significant cartilage injury characterized by chondrocyte necrosis and ultrastructural abnormalities. IHC revealed increased expression of Adamts5 and decreased expression of Col2a1 and Acan in cartilagefollowing exposure to HT-2 toxin, indicative of ECM degradation, which could be aggravated under Se deficiency. Additionally, activation of the Notch signaling pathway was observed in response to HT-2 toxin and Se deficiency, with upregulation of Notch pathway-related components. In vitro experiments further confirmed the role of the Notch pathway in ECM metabolism regulation, with partial protection against ECM depletion caused by HT-2 toxin and Se deficiency observed upon inhibition of the Notch pathway using DAPT. This study demonstrate that Se deficiency exacerbates HT-2 toxin-induced cartilage degradation via Notch signaling activation, highlighting the interplay of environmental mycotoxins and nutritional deficits in KBD etiology and identify Notch signaling as a therapeutic target to mitigate disease progression.

Enhancing therapeutic efficacy through degradation of endogenous extracellular matrix in primary breast tumor spheroids.

Solid tumors have a complex extracellular matrix (ECM) that significantly affects tumor behavior and response to therapy. Understanding the ECM's role is crucial for advancing cancer research and treatment. This study established an in vitro model using primary cells isolated from a rat breast tumor to generate three-dimensional spheroids. Monolayer cells and spheroid cultures exhibited different protein expression patterns, with primary tumor spheroids presenting an increased level of ECM-related proteins and a more complex extracellular environment. Furthermore, spheroids produce endogenous collagen type I matrix, which is the main component of the tumoral ECM. This matrix is arranged predominantly around the 3D structure, mimicking the conditions of solid tumors. Treatments with recombinant collagenases class II (acting on the linear collagen region) and class I (acting on the 3D-helix region) completely degrade collagen within the spheroid structure. Collagenase pretreatment enhances the accessibility of the anticancer drug doxorubicin to penetrate the core of spheroids and sensitize them to doxorubicin-induced cytotoxicity. Our findings highlight the importance of overcoming drug resistance in breast cancer by targeting the ECM and proposing a novel strategy for improving therapeutic outcomes in solid tumors. By employing a three-dimensional spheroid model, with an endogenous ECM, we can offer more relevant insights into tumor biology and treatment responses.

Targeting FABP4 to Inhibit AGEs-RAGE/NF-κB Signalling Effectively Ameliorates Nucleus Pulposus Dysfunction and Angiogenesis in Obesity-Related Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a primary contributor to low back pain, posing significant social and economic burdens. Increasing evidence shows that obesity contributes to IVDD, yet the underlying mechanisms remain elusive. Here, we firstly revealed a causal correlation between obesity and IVDD via a two-sample mendelian randomization analysis and identified fatty acid-binding protein 4 (FABP4) as the potential regulator to associate IVDD and obesity. Elevated FABP4 expression promoted extracellular matrix (ECM) disequilibrium and angiogenesis to exacerbate IVDD progression. Genetically knocking out or pharmacologically inhibiting FABP4 in high-fat diet-induced mice alleviated IVDD. Mechanistically, obesity activated the mammalian target of rapamycin complex 1 (mTORC1), which upregulated FABP4 expression, leading to the accumulation of advanced glycation end-products (AGEs) in intervertebral disc tissue. AGEs further activated the NF-κB signalling pathway, exacerbating ECM degradation and neovascularization. Conversely, rapamycin-mediated inhibition of mTORC1 suppressed FABP4 expression in nucleus pulposus cells (NPCs), alleviating IVDD invivo. Collectively, our findings reveal a critical role of the obesity-induced mTORC1-FABP4 axis in ECM degradation and angiogenesis during IVDD progression. Targeting FABP4 may represent a promising therapeutic strategy for IVDD in obese individuals.

Orientin alleviates chondrocyte senescence and osteoarthritis by inhibiting PI3K/AKT pathway.

Osteoarthritis (OA) is a common degenerative disease that leads to pain, disability, and reduced quality of life. Orientin exhibits considerable anti-inflammatory and antioxidative properties, but its role in chondrocyte senescence and OA progress has not yet been fully characterized. The aim of this study was to evaluate the protective effects of orientin on OA. The role of orientin in extracellular matrix (ECM) degradation, mitochondrial homeostasis, and chondrocyte senescence was investigated in vitro. Meanwhile, we used molecular docking, small molecular inhibitors, and RNA interference to screen and validate candidate proteins regulated by orientin. In an anterior cruciate ligament transection (ACLT) rat model, radiograph, micro-CT, and various histological examinations were applied to evaluate the therapeutic effects of orientin on OA. We found that orientin inhibited ECM degradation and senescence-associated secretory phenotype (SASP) factor expression in interleukin (IL)-1β-treated chondrocytes. Additionally, orientin reduced the level of reactive oxygen species (ROS) and improved mitochondrial homeostasis. Furthermore, orientin suppressed IL-1β-induced activation of the nuclear factor kappa B (NF-κB) signalling pathway. We also found that orientin bound to phosphoinositide 3-kinase (PI3K) and inhibited NF-κB cascades via the PI3K/AKT pathway. In vivo, we demonstrated that orientin improved cartilage wear and reduced synovial inflammation and osteophyte in an ACLT rat model. Orientin improves mitochondrial homeostasis, inhibits chondrocyte senescence, and alleviates OA progress via the PI3K/AKT/NF-κB axis, which suggests that orientin is a potential effective therapeutic agent for OA.

Differential neuropilin isoform expressions highlight plasticity in macrophages in the heterogenous TME through in-silico profiling

IntroductionThe nuanced roles of neuropilin (NRP) isoforms, NRP1 and NRP2, have attracted considerable scientific interest regarding cancer progression. Their differential expressions across various cancer types are specific to NRP isoforms which are shown in a cancer type-dependent manner. It accounts for the different mechanisms involved, driven by a co-expression of gene-sets associated with overexpressed NRP1 or NRP2. Their different expressions on tumour-associated macrophages (TAMs) with disparate markers are associated with the heterogenous tumour microenvironment (TME) through their plasticity and pro-tumorigenic activities.MethodsSingle-cell RNA sequencing (scRNA-seq) analyses were performed on tumours from clear cell Renal Cell Carcinoma (ccRCC) and skin cutaneous melanoma (SKCM) which exhibit the highest expressions of NRP1 and NRP2, respectively. Datasets were processed using established bioinformatics pipelines, including clustering algorithms, to determine cellular heterogeneity and quantify NRP isoform expression within distinct macrophage populations. Using differential gene expression analysis (DEGA) alongside co-enrichment studies, we explored gene-sets associated with NRP1 or NRP2 overexpression in TAMs.ResultsOur analysis revealed a marked upregulation of NRP1 in TAMs isolated from ccRCC and elevated NRP2 expression in SKCM-derived TAMs. Both NRP1+ and NRP2+ macrophages showed an M2-like polarisation characterised by immune suppression and extracellular matrix degradation. Coupled with the previously uncharacterised NRP isoform specific- subpopulations within these cancers identified by DEGA, co-enrichment analyses demonstrated that the upregulation of gene-sets associated with NRP1 is associated with angiogenesis and tumour progression through VEGF signalling, while gene-sets with NRP2 showed dual functionality in the TME-dependent manner. Their distinct roles in regulating macrophage plasticity, tumour invasion, and metastasis were highlighted.DiscussionThese findings underscore distinct isoform-specific mechanisms by which NRP1 and NRP2 contribute to TAM-mediated cancer progression. This study aims to establish a foundation for future research, leading to biological experiments with focused gene-sets derived from our findings. This approach can contribute to the development of immunomodulatory strategies targeting specific NRP isoforms in macrophages, tailored to individual cancer types and abnormal expressions of those gene markers, potentially offering a more effective therapeutic approach compared to broad-spectrum NRP inhibition strategies.

Abstract B027: Spatial transcriptomic profiling of the head and neck cancer tumor microenvironment to guide design of microphysiological systems for reporting treatment response

Abstract Background: Microphysiological systems (MPS), advanced 3D models that reproduce organ form and function, show promise for modeling patient-specific treatment outcomes in head and neck cancer (HNC) as they aim to recapitulate the architecture and function of the tumor microenvironment (TME). However, cell and extracellular matrix (ECM) composition within these environments is often decided arbitrarily and may struggle to mimic different microenvironments i.e. primary tumors or metastatic lymph nodes. To guide the cellular and physical composition of the TME in vitro we employed spatial transcriptomic profiling of a tissue microarray (TMA) from patients with HNC to aid in identification of ECM components and cell populations that can be translated into MPS to improve their fidelity to tumor tissue. Methods: Spatial transcriptomic profiling was performed using the GeoMx whole transcriptome atlas on a TMA containing matched primary and lymph node tissue from 44 patients with HNC. Each patient was analyzed in duplicate, with segmentation between tumor (pan-cytokeratin staining) and stroma (collagen staining) for a total of 366 areas of interest profiled. Data was analyzed using differential gene expression, gene set enrichment analysis and linear mixed effect models. MPS were constructed using cells isolated from HNC tumor tissue, comprising tumor epithelial cell spheroids surrounded by a hydrogel matrix containing fibroblasts and tumor infiltrating leukocytes. Molded lumens seeded with blood and lymphatic endothelial cells form vasculature. This MPS permits visualization of readouts such as tumor spheroid growth, migration and viability, angiogenesis, and treatment response modulated by different ECM and cell combinations. Results: 91% of the samples returned acceptable data with a gene detection rate of >5%. Differential gene expression analysis demonstrated that 68.9% of the expressed genes were shared between primary and lymph node tumors while 58.3% were shared between primary and lymph node stroma. Pathway analysis identified significant differences between primary and lymph node tumor in pathways associated with ECM organization and degradation and immune cell cytokine signaling. Identification of ECM proteins enriched in primary and lymph node stroma can guide modulation of biological hydrogels for MPS construction by including these additional proteins in the matrix. Deconvolution of cell type composition using CIBERSORTx also permits modulation of cell proportions in the MPS to more closely mimic tumor tissue. MPS representing primary or lymph node TME’s created with a standard collagen/fibronectin or enhanced guided matrix or standard vs guided cell ratio’s will be built and analyzed for metrics of cell growth, viability, angiogenesis and response to cisplatin. Conclusions: We performed spatial transcriptomic analysis of primary and lymph node tumor tissue from patients with HNC. These data are guiding the ECM and cellular composition of MPS to develop models that faithfully represent patient tumor tissue and response to treatment. Citation Format: Rene Welch Schwartz, Adeel Ahmed, Rong Hu, Randall J Kimple, Paul M Harari, Irene M Ong, Sheena C Kerr. Spatial transcriptomic profiling of the head and neck cancer tumor microenvironment to guide design of microphysiological systems for reporting treatment response [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr B027.

Role of periepithelial microenvironment changes in the malignant transformation of oral potential malignant disorders

Oral potential malignant disorders (OPMDs) are a group of oral mucosal lesions with a risk of cancer transformation. The microenvironment surrounding the epithelial tissue is closely related to the malignant transformation of OPMDs. However, the changes and role of the periepithelial microenvironment during the malignant progression of OPMDs are not yet fully understood. This review discuss the impact of changes in the periepithelial microenvironment on the malignant transformation of OPMDs from following aspects: the immune microenvironment, stromal microenvironment, metabolic microenvironment, and oral microorganism. In the immune microenvironment, the immune surveillance capacity of periepithelial immune cells weakens, and some of these cells interact with malignant cells, resulting in an immunosuppressive microenvironment. Cells in the matrix promote the malignant transformation of OPMDs through the secretion of cytokines and nutritional support, along with extracellular matrix degradation and local angiogenesis. Epithelial cells undergo metabolic reprogramming during malignant transformation, while the resulting hypoxic microenvironment can further promote the malignant transition of epithelial cells. Oral microorganism fosters the malignant transformation of OPMDs by inducing inflammatory responses and creating hypoxic conditions.

Unraveling the Molecular Mechanisms of Osteoarthritis: The Potential of Polyphenols as Therapeutic Agents.

The complex nature of osteoarthritis (OA), driven by the intricate interplay of genetic, environmental, and lifestyle factors, necessitates the development of a single treatment method, which is highly challenging. The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids often leads to adverse side effects like kidney damage and stomach ulcers. Major health threats like obesity and aging create a milieu of chronic low-grade inflammation and increased mechanical stress on the joints resulting in cartilage deterioration. Additionally, postmenopausal women with lower circulating 17β-estradiol levels experience accelerated joint deterioration due to increased immune activity resulting in the increased production of pro-inflammatory cytokines, with elevated MMP expression and decreased type II collagen synthesis. Polyphenols are nature's gifted magic molecules, which possess diverse biological properties like anti-oxidant, anti-bacterial, anti-inflammatory, estrogenic, and insulin-sensitizing effects, which can manage and treat all the multi-factorial contributing factors of OA effectively. Certain polyphenols can act as phytoestrogens and mimic the effects of natural estrogen by binding to ERα and ERβ and can act as SERMs and prevent degradation of the articular cartilage thereby alleviating osteoarthritic conditions. These molecules downregulate the expression of various pro-inflammatory cytokines, apoptotic genes, and matrix-degrading proteases (MMPs) while upregulating major ECM proteins like type II collagen, aggrecan, and proteoglycans in various osteoarthritic animal models. This review provides a comprehensive overview of the molecular mechanisms involved in OA development and also explores the therapeutic potential of different polyphenols in mitigating joint inflammation and their protective effect in inhibiting the degradation of cartilage extracellular matrix (ECM) and enhancing joint homeostasis.

Magnoflorine ameliorates cartilage degradation in osteoarthritis through inhibition of mitochondrial reactive oxygen species-mediated activation of the NLRP3 inflammasome.

This study investigated the role of magnoflorine (MAG) on cartilage protection in osteoarthritis. In vitro studies showed that MAG decreased the expression of inflammatory factors and inhibited extracellular matrix degradation in lipopolysaccharide- and ATP-stimulated C28/I2 cells. Importantly, MAG reduced the levels of pyroptosis-related proteins, including NLRP3, ASC, cleaved-caspase 1, GSDMD-N, IL-18, and IL-1β. Mechanistically, MAG reduced mtROS production and inhibited the activation of the NF-κB signaling pathway. In vivo study demonstrated that sodium iodoacetate-induced cartilage degradation and inflammatory factor release were reversed by MAG. Overall, MAG could inhibit mtROS-mediated NLRP3 inflammasome activation by suppressing mitochondrial dysfunction to ameliorate osteoarthritis.

Phytoextracts as Natural Anti-Aging Agents: Mechanisms and Strategies for Skin Rejuvenation.

Skin aging is a complex biological process driven by intrinsic factors, such as genetics and cellular metabolism, and extrinsic factors, including environmental stressors like UV radiation, pollution, and lifestyle choices. These factors result in visible signs of aging, such as wrinkles, reduced skin elasticity, and pigmentation. This review presents the recent findings on phytoextracts as natural anti-aging agents, highlighting their bioactive compounds, mechanisms of action, and applications in skin rejuvenation. A comprehensive literature search was conducted in databases including Scopus, PubMed, and Web of Science, focusing on articles published from 2000 to 2023. Search terms such as "phytoextracts and skin aging," "natural antioxidants and collagen synthesis," and "bioactive compounds and skin rejuvenation" were used. Inclusion criteria involved peer-reviewed studies on phytoextracts with experimental evidence of anti-aging effects, focusing on human and in-vitro models. Exclusion criteria included non-English articles, review papers without experimental data, and studies unrelated to skin aging. Recent research articles focusing on skin aging mechanisms and the efficacy of phytoextracts were identified. Particular attention was given to the antioxidant, anti-inflammatory, and collagen-boosting properties of phytoextracts. This study provides novel insights into the mechanisms through which phytoextracts counteract oxidative stress, inflammation, and extracellular matrix degradation. Notable examples include the role of resveratrol in activating longevity genes, curcumin in reducing UVinduced damage, and ginseng in improving skin elasticity. These compounds were found to exhibit potent anti-aging mechanisms through their antioxidant activity and collagen-boosting effects. Advanced delivery technologies, such as nanocarriers, enhance the efficacy of these bioactives. Phytoextracts demonstrate significant potential in combating skin aging by reducing oxidative stress and inflammation, and enhancing collagen production. While the results are promising, further clinical studies are required to validate their long-term efficacy and safety in skin aging management.

From Bench to Bedside: Transforming Cancer Therapy with Protease Inhibitors

Proteases play a pivotal role in cancer progression, facilitating processes such as extracellular matrix degradation, angiogenesis, and metastasis. Consequently, protease inhibitors have emerged as promising therapeutic agents in oncology. This review provides a comprehensive overview of the mechanisms by which protease inhibitors modulate cancer biology, categorizing inhibitors by their target protease classes, including matrix metalloproteinases, cysteine proteases, and serine proteases. We discuss the therapeutic potential of both synthetic and natural protease inhibitors, highlighting their applications in preclinical and clinical settings. Furthermore, challenges such as specificity, toxicity, and resistance mechanisms are addressed, alongside strategies to overcome these limitations through innovative drug designs and combination therapies. The future of protease inhibitors in cancer treatment lies in precision medicine, leveraging proteomic profiling to tailor therapies to individual tumors. This review underscores the importance of ongoing research and the development of novel approaches to harness protease inhibitors effectively for cancer management.

Nutraceutical Interventions for Mitigating Skin Ageing: Analysis of Mechanisms and Efficacy.

Skin ageing is influenced by intrinsic factors such as genetics and hormones, as well as extrinsic factors like environmental exposure, ultraviolet (UV) radiation, and diet. These factors lead to biochemical, biological, and structural changes in the skin. Plant-derived compounds with antioxidant and anti-inflammatory properties have emerged as potential anti-ageing agents. This comprehensive review, spanning data from 1997 to 2024, explores the role of nutraceuticals in skin anti-ageing. The research data were drawn from Google, PubMed, PubMed Central, Scopus, and various journal databases, including ScienceDirect, Springer, and Taylor & Francis. This review specifically examines plant-derived polyphenols, carotenoids, and other bioactive compounds, analysing their mechanisms through signalling pathways and cellular processes, using data from in vitro, in vivo, and clinical studies. Polyphenols like quercetin, curcumin, and epigallocatechin gallate (EGCG) have antioxidant and anti-inflammatory properties, helping to reduce oxidative stress, inflammation, UV-induced collagen degradation, and inflammatory cytokines. Notably, curcumin enhances collagen production and decreases the number of senescent cells. Carotenoids such as β-carotene, lutein, zeaxanthin, and lycopene protect against UV damage, and lycopene-rich tomato paste was specifically noted for its ability to reduce erythema and DNA damage. Additionally, compounds like resveratrol, fisetin, and wogonin exert protective effects against oxidative stress and inflammation, with resveratrol improving collagen synthesis and reducing the appearance of wrinkles. These plant-derived compounds can effectively combat skin ageing through various mechanisms, including the inhibition of oxidative stress, inflammation, and extracellular matrix degradation. They present a natural and sustainable approach to skincare in accord with the growing trend of conscious consumption. Future research should focus on understanding the long-term effects and determining the optimal dosage for clinical applications, highlighting the potential of integrating plant-based nutraceuticals into skincare regimens.

Targeting the S100A9/P38 MAPK/HSPB1 axis as a novel approach for aortic dissection therapy.

Targeting the S100A9/P38 MAPK/HSPB1 axis as a novel approach for aortic dissection therapy.

Meteorin-like protein alleviates intervertebral disc degeneration by suppressing lipid accumulation in nucleus pulposus cells via PPARα-CPT1A activation.

Meteorin-like protein alleviates intervertebral disc degeneration by suppressing lipid accumulation in nucleus pulposus cells via PPARα-CPT1A activation.

Durotaxis and extracellular matrix degradation promote the clustering of cancer cells.

Early stages of metastasis depend on the collective behavior of cancer cells and their interaction with the extracellular matrix (ECM). Cancer cell clusters are known to exhibit higher metastatic potential than single cells. To explore clustering dynamics, we developed a calibrated computational model describing how motile cancer cells biochemically and biomechanically interact with the ECM during the initial invasion phase, including ECM degradation and mechanical remodeling. The model reveals that cluster formation time, size, and shape are influenced by ECM degradation rates and cellular compliance to external stresses (durotaxis). The results align with experimental observations, demonstrating distinct cell trajectories and cluster morphologies shaped by biomechanical parameters. The simulations provide valuable insights into cancer invasion dynamics and may suggest potential therapeutic strategies targeting early-stage invasive cells.

Peroxidasin is associated with a mesenchymal-like transcriptional phenotype and promotes invasion in metastatic melanoma.

Peroxidasin is associated with a mesenchymal-like transcriptional phenotype and promotes invasion in metastatic melanoma.

The role of HIF-1α in hypoxic metabolic reprogramming in osteoarthritis.

The role of HIF-1α in hypoxic metabolic reprogramming in osteoarthritis.