Matrix Degradation Research Articles

Selenium nanoparticles ameliorate lumbar disc degeneration by restoring GPX1-mediated redox homeostasis and mitochondrial function of nucleus pulposus cells

Intervertebral disc degeneration (IVDD) is a prevalent musculoskeletal disorder that involves the excessive accumulation of reactive oxygen species (ROS), resulting in mitochondrial dysfunction and matrix metabolism imbalance in nucleus pulposus cells (NPCs). Selenium, an indispensable trace element, plays a crucial role in maintaining mitochondrial redox homeostasis by being incorporated into antioxidant selenoproteins as selenocysteine. In this study, we employed a straightforward synthesis method to produce selenium nanoparticles (SeNPs) with consistent size and distribution, and evaluated their potential protective effects in ameliorating IVDD. In a simulated inflammatory environment induced by interleukin-1beta (IL-1β) in vitro, SeNPs demonstrated a protective effect on the matrix synthesis capacity of NPCs through the up-regulation of aggrecan and type II collagen, while concurrently suppressing the expression of matrix degradation enzymes including MMP13 and ADAMTS5. Additionally, SeNPs preserved mitochondrial integrity and restored impaired mitochondrial energy metabolism by activating glutathione peroxidase1 (GPX1) to rebalance redox homeostasis. In a rat lumbar disc model induced by puncture, the local administration of SeNPs preserved the hydration of nucleus pulposus tissue, promoted matrix deposition, and effectively mitigated the progression of IVDD. Our results indicate that the enhancement of GPX1 by SeNPs may offer a promising therapeutic approach for IVDD by restoring mitochondrial function and redox homeostasis.

HO-1: An emerging target in fibrosis.

Fibrosis, an aberrant reparative response to tissue injury, involves a disruption in the equilibrium between the synthesis and degradation of the extracellular matrix, leading to its excessive accumulation within normal tissues, and culminating in organ dysfunction. Manifesting in the terminal stages of nearly all chronic ailments, fibrosis carries a high mortality rate and poses a significant threat to human health. Heme oxygenase-1 (HO-1) emerges as an endogenous protective agent, mitigating tissue damage through its antioxidant, anti-inflammatory, and antiapoptotic properties. Numerous studies have corroborated HO-1's potential as a therapeutic target in anti-fibrosis treatment. This review delves into the structural and functional attributes, and the upstream and downstream pathways of HO-1. Additionally, the regulatory networks and mechanisms of HO-1 in cells associated with fibrosis are elucidated. The role of HO-1 in various fibrosis-related diseases is also explored. Collectively, this comprehensive information serves as a foundation for future research and augments the viability of HO-1 as a therapeutic target for fibrosis.

A Universal Plug-and-Play Approach to In Situ Multinuclear Magnetic Resonance Analysis of Electrochemical Phenomena in Commercial Battery Cells.

Advancing electrochemical energy storage devices relies on versatile analytical tools capable of revealing the molecular mechanisms behind the function and degradation of battery materials in situ. The nuclear magnetic resonance phenomenon plays a pivotal role in fundamental studies of energy materials and devices because of its exceptional sensitivity to local environments and the dynamics of many electrochemically relevant elements. The jelly roll architecture is one of the most energy-dense and, therefore, most popular concepts implemented in pouch, prismatic, and cylindrical Li- and Na-ion cells. Such widely commercialized designs, however, represent a significant obstacle for a range of powerful in situ magnetic resonance-based methodologies due to negligible radio frequency electromagnetic field penetration through conductive metal casings and current collectors. In this work, we introduce an experimental setup that enables direct RF wave transmission through the cell terminals and current collectors, and provides efficient excitation and detection of NMR signals. An RF adapter designed as a plug-and-play device effectively turns the battery cell into an NMR probe that can be tuned to a broad range of Larmor frequencies. Due to its exceptional sensitivity, versatility, and multinuclear capability, the proposed methodology is suitable for fundamental research and industrial high-throughput screening applications. In situ NMR lineshapes provide a direct quantitative description of the chemical environments of electrochemically active elements and enable new metrics for the accurate assessment of state-of-charge (SoC) and state-of-health (SoH). Specifically, in commercial pouch cells based on lithium cobalt oxide, lithium nickel manganese cobalt oxide, and sodium nickel iron manganese oxide chemistries, 7Li and 23Na NMR data unambiguously show electrochemical transformations between intercalated and metallic forms of charge carrier ions, and reveal anisotropic magnetic properties of the electrode coating.

Jianpi qingre tongluo prescription alleviates the senescence-associated secretory phenotype with osteoarthritis by regulating STAG1/TP53/P21 signaling pathway

Ethnopharmacological relevanceJianpi Qingre Chubi prescription primarily consists of a compound formula, also known as Huangqin Qingre Chubi Capsules (HQC), which strengthens the spleen and resolves dampness, clear heat, and collaterals. Long-term clinical use has shown that HQC improves joint swelling and pain in patients with osteoarthritis. Mechanistically, we demonstrated that HQC inhibits inflammatory responses, extracellular matrix degradation, and delays chondrocyte senescence. AimTo determine the bioactivity and mechanism of action of Jianpi Qingre Tongluo prescription (HQC) on osteoarthritis (OA). Materials and methodsFirst, the chondroprotective effects of HQC were assessed using histopathology, immunohistochemical staining and protein blotting in an OA rat model. Additionally, we identified key targets for crucial targets of HQC in OA using the Network Pharmacology and Gene Expression Omnibus (GEO) dataset (GSE98918 and GSE152805). In vitro conditions, IL-1β-treated chondrocytes served to study the impact of HQC on OA development and the senescence-associated secretory phenotype (SASP). This was evaluated using a series of approaches, such as flow cytometry assays, and immunofluorescence staining, and then verified by rescue experiments. ResultsTherapy with HQC attenuated the severity of osteoarthritis (demonstrated by histopathology, OARSI grading scores, and Mankin scores) and SASP factors (as indicated by IL-1β, IL-6, IL-4, IL-37, MMP13, ADAMTS5, COL2A1, and ACAN levels, and apoptotic cell death). HQC might treat osteoarthritis via four important targets (STAG1, TP53, P21, and P16), with the p53 signalling pathway representing one of the main pathways. The HQC acts primarily on chondrocyte clusters. In vitro experiments indicated that STAG1 overexpression accelerates chondrocyte apoptosis, promotes SASP factor expression and extracellular matrix (ECM) degradation, and facilitates OA progression. HQC-containing serum suppressed the expression of the STAG1/TP53/P21 pathway, regulated SASP factors, and restored ECM balance. ConclusionJianpi Qingre Tongluo prescription modulated SASP factors by regulating the STAG1/TP53/P21 signal transduction axis and decelerating cartilage senescence and degradation in patients with OA. Jianpi Qingre Tongluo may be an effective drug candidate.

Assessment of the impact of smoke from thermal destruction of materials of different origins on soil health.

The results of the study of the influence of smoke from the thermal destruction of materials of vegetable and synthetic origin on the enzymatic activity of ordinary chernozem are presented. The decrease of activity of investigated indicators (catalase, peroxidase, polyphenol oxidase, invertase) from thermal destruction of pine sawdust, straw, coniferous and leaf fall, peat, and materials based on polystyrene, rubber, and polyvinyl chloride was revealed. A significant decrease in the activity of soil enzymes after exposure to gaseous products of combustion during 15-60min of soil fumigation was found. Oxidoreductases turned out to be the most sensitive to smoke. Smoke from peat burning has minimal inhibitory effect, activity of catalase after 30min of fumigation decreased only by 15%, and peroxidase and polyphenol oxidase - by 8 and 12%. While the activity of the same enzymes when exposed to smoke from thermal degradation of rubber-based materials decreased by 16-42%, and polyvinyl chloride - by 29-73%, to a lesser extent from polystyrene (decrease by 7-29%). All obtained data on changes in the enzymatic activity of soils are reliable with the level of statistical significance p < 0.05.

Unraveling Interdiffusion Phenomena and the Role of Nanoscale Diffusion Barriers in the Copper-Gold System.

Diffusion is one of the most fundamental concepts in materials science, playing a pivotal role in materials synthesis, forming, and degradation. Of particular importance is solid state interdiffusion of metals which defines the usable parameter space for material combinations in the form of alloys. This parameter space can be explored on the macroscopic scale by using diffusion couples. However, this method reaches its limit when going to low temperatures, small scales, and when testing ultrathin diffusion barriers. Therefore, this work transfers the principle of the diffusion couples to small scales by using core-shell nanowires and in situ heating. This allows us to delve into the interdiffusion dynamics of copper and gold, revealing the interplay between diffusion and the disorder-order phase transition. Our in situ TEM experiments in combination with chemical mapping reveal the interdiffusion coefficients of Cu and Au at low temperatures and highlight the impact of ordering processes on the diffusion behavior. The formation of ordered domains within the solid-solution is examined using high-resolution imaging and nanodiffraction including strain mapping. In addition, we examine the effectiveness of ultrathin Al2O3 barrier layers to control interdiffusion of the diffusion couple. Our findings indicate that a 5 nm thick layer serves as an efficient diffusion barrier. This research provides valuable insights into the interdiffusion behavior of Cu and Au on the nanoscale, offering potential applications in the development of miniaturized integrated circuits and nanodevices.

Operando lateral state-of-charge inhomogeneity mapping via wavelength-resolved neutron imaging

The continuous advancement in battery technology requires the development of robust and more precise diagnostic tools for the characterization of commercial-scale battery cells. In this work, operando Bragg edge imaging (BEI), based on a time-of-flight approach, provides spatially resolved state-of-charge (SoC) mapping of a commercial-size pouch cell. The changes in the position and intensity of Bragg edges are used to track the Li intercalation into the graphite, thereby identifying the spatial distribution of various lithiation stages and the corresponding SoC. The operando wavelength-resolved BEI assessment revealed an inhomogeneous Li+ intercalation, dependent on the distance to the electrical tabs, effectively identifying features that contribute to the overall loss of performance and the accelerated degradation of battery materials. The presented results demonstrate the potential of advanced wavelength-resolved neutron imaging to be used as a diagnostic tool for commercial battery cells in a configuration without special casings or isotopes for enhancement of imaging contrast. It thus highlights its applicability for operando characterization of future batteries for portable and automotive applications.

Amentoflavone maintaining extracellular matrix homeostasis and inhibiting subchondral bone loss in osteoarthritis by inhibiting ERK, JNK and NF-κB signaling pathways

Amentoflavone (AF), a plant biflavone isolated from Selaginella sinensis ethanol extract, is characterized by anti-inflammatory and anti-oxidant properties. According to previous studies, inflammation and oxidative stress are closely related to the pathophysiology of osteoarthritis (OA). However, the effects and mechanisms of AF on OA have not been elucidated.To investigate the inhibitory effects and its molecular mechanism of AF on extracellular matrix (ECM) degradation stimulated by IL-1β as well as subchondral bone loss induced by RANKL in mice chondrocytes. Quantitative PCR was used to detect the mRNA expression of genes related to inflammation, ECM, and osteoclast differentiation. Protein expression level of iNOS, COX-2, MMP13, ADAMTS5, COL2A1, SOX9, NFATc1, c-fos, JNK, ERK, P65, IκBα was measured by western blotting. The levels of TNF-α and IL-6 in the supernatants were measured by ELISA. The amount of ECM in chondrocytes was measured using toluidine blue staining. The levels of Aggrecan and Col2a1 in chondrocytes were measured using immunofluorescence. Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and immunofluorescence were used to detect the effect of AF on osteoclast differentiation and bone resorption. The effect of AF on destabilization of the medial meniscus (DMM)-induced OA mice can be detected in hematoxylin–eosin (H&E) staining, Safranin O green staining and immunohistochemistry.AF might drastically attenuated IL-1β-stimulated inflammation and reduction of ECM formation by blocking ERK and NF-κB signaling pathways in chondrocytes. Meanwhile, AF suppressed the formation of osteoclasts and the resorption of bone function induced by RANKL. In vivo, AF played a protective role by stabilizing cartilage ECM and inhibiting subchondral bone loss in destabilization of the medial meniscus (DMM)-induced OA mice, further proving its protective effect in the development of OA. Our study show that AF alleviated OA by suppressing ERK, JNK and NF-κB signaling pathways in OA models in vitro and DMM-induced OA mice, suggesting that AF might be a potential therapeutic agent in the treatment of OA.

Hypothesizing the interplay of thrombus formation, wall enhancement, and perifocal edema as predictive factors for rupture in brain AVMs

The presence of shear stress within intracranial AVMs (arteriovenous malformations) due to high flow, perinidal angiogenesis, intranidal aneurysms, and biological factors are presumed risk factors for rupture. However, emerging imaging and histological evidence suggests that risk factors for AVM rupture may extend beyond the classical understanding. The presence of perifocal edema at the time of rupture, luminal thrombosis, and vessel wall enhancement on vessel wall MRI elucidate the possibility of an underlying inflammatory process within AVMs, which may predispose them to instability and eventual rupture. We hypothesize that for some AVM ruptures, the occurrence of thrombosis within vascular outpouchings of the AVM initiates a cascade of events, including local hypoxia, inflammation, breakdown of the blood–brain barrier and wall matrix degradation, which is evident from the presence of perifocal edema and vessel wall enhancement observed on imaging. These changes might ultimately raise the risk of AVM rupture and subsequent hemorrhage. Understanding this inflammatory component offers promising insights into AVM pathogenesis and may facilitate the development of preventive strategies to mitigate rupture risk.

Applying Alkali Activator and Hydrophobic Agents in Clay-Based Mortars for Enhanced Properties

Clay-based mortars are susceptible to water intake and exhibit low mechanical strength, presenting challenges in their application within the construction sector. This research addresses these vulnerabilities by investigating the combination of alkali activators with waterproofing agents, specifically a nano-clay and an acrylic emulsion, to enhance the properties of clay mortars. Alkali-activated materials are known for their superior mechanical properties and sustainable potential, especially when derived from low-cost by-products. Recent studies have focused on alkali activation using clays and soils as precursors to improve their physical and mechanical properties while increasing durability. However, the high absorbency of these mortars remains a concern, as it can lead to matrix degradation. Therefore, to address these problems, this research studied the combination of a highly alkaline activator (potassium metasilicate) with hydrophobic agents, such as a nano-clay and an acrylic emulsion, using two different clayey soils. The results indicated that potassium metasilicate (PO) enhanced the mechanical properties and stability for both aluminosilicate systems, while nano-clay (PONC) significantly reduced the capillary absorption through time, especially in A2 systems. The addition of acrylic emulsion (POD) proved highly effective in both systems, significantly improving durability. By integrating these agents, the mortar systems were protected against water intake, while durable construction materials were formed.

Characterizing temporal stability of supercontinuum generation in higher-order modes supported by liquid-core fibers

The generation of tailored supercontinua is essential for studying ultrafast light-matter interactions and for a variety of practical applications requiring broadband light. Liquid-core fibers (LCFs) have emerged as an innovative nonlinear photonic platform, demonstrating high efficiency in nonlinear frequency conversion. In this study, we showcase that LCFs provide a stable platform for ultrafast supercontinuum generation in a selected higher-order vector mode at 1.55μm\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$1.55\\;\\upmu \\hbox {m}$$\\end{document}. Specifically, we demonstrate soliton fission and double-dispersive wave generation using a radially polarized mode in a CS2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\hbox {CS}_{2}$$\\end{document}-silica liquid-core fiber. The experiments were performed in a temperature-controlled laboratory, showing excellent stability with no evidence of fiber degradation, material degradation, or drift-induced changes in mode excitation over extended periods under standard environmental conditions. Our results confirm that liquid-core fibers are a reliable platform for nonlinear photonics, suitable for applications such as computationally tailored supercontinuum generation, single pulse spxectroscopy, and tailored light sources, all of which rely on consistent and stable nonlinear frequency conversion.

Identification of stiffness and damping characteristics of magnetorheological elastomers due to immersion in seawater

ABSTRACT Magnetorheological elastomer (MRE) materials are commonly used as vibration dampers in offshore structures. Therefore, it is urgent to investigate the degradation of this smart material because of seawater interaction. This work focuses on the immersion of MRE material in seawater, which alters its rheological and mechanical characteristics. Hence, it is important to investigate the impact of seawater immersion on the rheological characteristics of substances. This study contributes to the assessment of the stiffness and damping characteristics of MRE materials after exposure to seawater for one year. The MRE samples comprise MRE with a silicone matrix devoid of any Carbonyl Iron Particle (CIP) and MRE with 70% CIP, exhibiting both isotropic and anisotropic properties. Immersing the subject in seawater was carried out for one year. The study involved doing multiple tests, such as scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and rheological testing. The findings indicated that the samples underwent harm, erosion, and deterioration of their rheological characteristics during immersion. The stiffness values for isotropic MRE and anisotropic MRE decreased by 97% and 11%, respectively. Meanwhile, the deterioration of the damping characteristics values of isotropic MRE and anisotropic MRE was 96% and 14%, respectively.

Application of Galvanostatic Non-Linear Impedance Spectroscopy to the Analysis of Metallic Material Degradation.

This study presents a novel application of Non-Linear Electrochemical Impedance Spectroscopy (NLEIS) in galvanostatic mode for the rapid, non-destructive assessment of metal degradation. By using galvanostatic mode instead of traditional potentiostatic methods, polarization-related challenges are mitigated, enabling more accurate and reliable analysis. The technique allows for the determination of corrosion rates (corrosion current) and material susceptibility to oxidation (Tafel coefficient) through a single measurement with a modulated AC perturbation signal. Theoretical assumptions of the method were validated through tests on both a non-linear model system and an experimental system. The proposed research methodology is highly effective for monitoring the condition of metallic materials in various environments, covering both anodic and cathodic processes.

Hydrogen diffusion and trapping in a cryogenic processed high-Cr ferrous alloy

The effect of hydrogen diffusion and trapping was studied in a high-Cr ferrous alloy using an inverted scanning Kelvin probe and thermal desorption spectroscopy in correlation with microstructure and residual stress study. In addition, different processing of ferritic/martensitic 9Cr1WTaV alloy (EUROFER97) was tested in correlation with observed selected properties to observe induced changes in material degradation and surface. The activation energies for hydrogen traps were shown to have distinct peaks corresponding to different trapping mechanisms, including matrix dislocations and grain boundaries. For the cryogenically treated sample, an additional peak was also identified and correlated with increased carbide precipitation.

Multiple Recycling of Wood–Plastic Recycled Composite (WPRC): Developing a Method to Evaluate the Degree of Degradation of Used WPRC

Wood–plastic recycled composite (WPRC) are composites obtained by heating and mixing the main raw material, wood flour, with thermoplastic resin, containing at least 40% by mass of recycled material in the raw material. In order to promote the multiple-recycling of WPRC to reduce greenhouse gas emissions and ensure the sustainability of resources, three types of WPRC decking materials with different exposure conditions (outdoor-exposed product, unexposed product and product stored in the factory for a long time) and samples after accelerated weathering tests (WPRC and recycled plastics from raw materials) were evaluated and compared by a TG-DTA in order to develop a method for evaluating the degree of degradation of used WPRC. Exothermic behavior with weight loss was observed in the temperature range of 30–500 °C for the WPRC product in two temperature ranges. In order to focus on the change in the first exotherm by oxidative degradation, where the rapid weight loss begins, this paper will focus on the exothermic behavior that develops in the temperature range of 150–300 °C on the lower temperature side. The results obtained are as follows. (1) Initial oxidation temperature (IOT) measurement from DTA behavior suggested that it is possible to evaluate the degree of degradation of WPRC. (2) On the exposed surface of WPRC exposed outdoors for more than 9 years and 8 months, significant decreases in the IOT were observed up to 1 mm from the surface, and a slight decrease in the IOT was observed between 1 and 2 mm from the surface. On the other hand, for the indoor long-term storage of 11 years and 6 months, there were almost no changes in the IOT with respect to the depth from the surface. Regarding the outdoor long-term-exposed WPRC, significant decreases in the IOT were observed not only on the exposed surface but also on the hollow and ribbed surfaces up to a depth of 1 mm from the surfaces. (3) A similar decrease in the IOT with increasing accelerated degradation time was observed for the WPRC and raw recycled plastic samples after accelerated weathering tests as for outdoor exposure. Furthermore, FTIR-ATR spectra also revealed that accelerated degradation caused oxidative degradation of the plastic. Therefore, it is thought that the decrease in the IOT can be used as an indicator to evaluate the degree of degradation of the plastic raw material in WPRC.

Biogenesis of omegasomes and autophagosomes in mammalian autophagy.

Autophagy is a highly conserved catabolic pathway that maintains cellular homeostasis by promoting the degradation of damaged or superfluous cytoplasmic material. A hallmark of autophagy is the generation of membrane cisternae that sequester autophagic cargo. Expansion of these structures allows cargo to be engulfed in a highly selective and exclusive manner. Cytotoxic stress or starvation induces the formation of autophagosomes that sequester bulk cytoplasm instead of selected cargo. This rather nonselective pathway is essential for maintaining vital cellular functions during adverse conditions and is thus a major stress response pathway. Both selective and nonselective autophagy rely on the same molecular machinery. However, due to the different nature of cargo to be sequestered, the involved molecular mechanisms are fundamentally different. Although intense research over the past decades has advanced our understanding of autophagy, fundamental questions remain to be addressed. This review will focus on molecular principles and open questions regarding the formation of omegasomes and phagophores in nonselective mammalian autophagy.

Numerical Investigation of Erosion in Pipeline Bends Using CFD Simulation

Erosion in pipeline bends is a significant issue in various industrial applications, particularly in oil and gas transportation systems. This study presents a numerical investigation of erosion in pipeline bends using Computational Fluid Dynamics (CFD) simulation. The primary focus is to predict erosion rates and identify erosion-prone areas based on different flow conditions, particle properties, and bend geometries. A multiphase flow model incorporating Eulerian-Lagrangian approaches was used to simulate the interaction between fluid and solid particles. The erosion rates were evaluated using empirical models that relate particle impact characteristics, such as velocity and angle of impingement, to material degradation. Simulations were conducted for various particle sizes, velocities, and flow rates, allowing for a comprehensive analysis of erosion patterns. Results indicate that erosion is concentrated on the outer walls of the bend, with higher particle velocities exacerbating material wear. Additionally, increasing particle size and flow velocity significantly influence the erosion rates. The findings of this study provide valuable insights into optimizing pipeline design and flow conditions to mitigate erosion, thereby extending the lifespan of pipeline systems in industrial applications.

Epidemiology and pathogenesis of osteoarthritis

Background: Osteoarthritis (OA) is the most common form of arthritis and poses a considerable socioeconomic burden, contributing to disability and decreased quality of life, particularly in older adults. However, the current treatment for OA is limited to pain relief, and it is necessary to develop disease-modifying OA drugs that target specific molecular mechanisms of its pathogenesis.Current Concepts: The prevalence of OA increases with age, with the incidence being higher in individuals aged over 60 years. Furthermore, women are more likely to develop knee and hand OA, whereas hip OA is more common in men. The global burden of OA is increasing, driven by an aging population and increasing obesity. The main pathological feature of OA is the degradation of the cartilage extracellular matrix by catabolic proteases such as matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (Adamts5), which are regulated by various signaling pathways and transcription factors. The metabolic shift towards glycolysis, which is associated with mitochondrial dysfunction, increases oxidative stress, ultimately leading to chondrocyte senescence and apoptosis. Chondrocytes in the superficial zone have stem cell-like properties and secrete anabolic proteins such as lubricin and fibulin-3. Subchondral bone remodeling and chondrocyte senescence have emerged as critical mechanisms of OA progression.Discussion and Conclusion: The understanding of OA has markedly evolved in recent years, shifting from the traditional view of OA as a “wear and tear” disease to a multifaceted condition with a complex pathogenesis. This paradigm shift could contribute to the development of novel strategies to halt OA progression.

Wedelolactone alleviates inflammation and cartilage degeneration by suppressing the NF-κB signaling pathway in osteoarthritis

Inflammation and extracellular matrix (ECM) degradation are two major factors involved in the pathogenesis of osteoarthritis (OA). Wedelolactone, a natural compound classified as a coumestan, is isolated from the medicinal plants Eclipta alba and Wedelia calendulacea. In this study, we assessed the protective effects of Wedelolactone on chondrocytes in OA. Our findings show that pretreatment with Wedelolactone effectively inhibited the IL-1β-induced upregulation of COX‑2, iNOS, TNF-α, and IL6 in chondrocytes, contributing to inflammation suppression. Moreover, pretreatment with Wedelolactone followed by IL-1β treatment significantly increased the expression of Collagen II and SOX9, while decreasing the expression of Adamts5, MMP1, MMP3, and MMP13, thereby promoting ECM protection. Through Network pharmacology Analysis, we identified 14 key targets that link Wedelolactone and OA. GO and KEGG pathway analysis suggested that Wedelolactone primarily impacted OA by targeting inflammatory responses, particularly the NF-κB signaling pathway. Further studies demonstrated Wedelolactone prevented IL-1β-induced activation of NF-κB signaling pathway by inhibiting the translocation of p65 and the preventing the degradation of IκBα in human chondrocytes. Molecular docking studies also indicated that Wedelolactone can directly bind to the NF-κB complex, thereby inhibited the nuclear localization of p65. In vivo experiments demonstrated that Wedelolactone can alleviate cartilage damage in DMM mice model. In summary, Wedelolactone appears to mitigate inflammation and cartilage degeneration by suppressing the NF-κB signaling pathway, thereby alleviating OA progression. Our results suggested Wedelolactone may offer therapeutic advantages for OA treatment.

Unveiling the role of CXCL8/CXCR2 in intervertebral disc degeneration: A path to promising therapeutic strategies

BackgroundIntervertebral disc degeneration(IVDD) is the primary etiology of low back pain and radicular pain. Recent studies have found that chemokines play a role in IVDD, but the underlying mechanism is largely unclear. MethodsBioinformatics analysis was employed to screen CXCL8 as the target gene. The expression levels of CXCL8 and CXCR2 were quantified using RT-qPCR, western blot(WB), immunohistochemistry(IHC), and enzyme-linked immuno-sorbent assay(ELISA). In the IVDD mouse model, X-ray images, Safranin O-fast green staining(SO-FG), IHC, and WB were conducted to assess the therapeutic effects of CXCL8 on IVDD. Reactive oxygen species (ROS) production, apoptosis of nucleus pulposus cells (NPCs), and the involvement of the NF-κB pathway were evaluated through WB, flow cytometry, immunofluorescence(IF), and Tunnel assay. ResultsIn our study, we observed that CXCL8 emerged as one of the chemokines that were up-regulated in IVDD. The mitigation of extracellular matrix degradation (ECM) and the severity of IVDD were significantly achieved by neutralizing CXCL8 or its receptor CXCR2(SB225002, CXCR2 antagonist). The release of CXCL8 from infiltrated macrophages within intervertebral discs (IVDs) was predominantly observed upon stimulation. CXCL8 exerted its effects on NPCs by inducing apoptosis and ECM degradation through the activation of CXCR2. Specifically, the formation of the CXCL8/CXCR2 complex triggered the NF-κB signaling pathway, resulting in an abnormal increase in intracellular ROS levels and ultimately contributing to the development of IVDD. ConclusionOur findings suggest that macrophage-derived CXCL8 and subsequent CXCR2 signaling play crucial roles in mediating inflammation, oxidative stress, and apoptosis in IVDD. Targeting the CXCL8/CXCR2 axis may offer promising therapeutic strategies to ameliorate IVDD. The translational potential of this articleThis study indicates that CXCL8 can effectively exacerbate the excessive apoptosis and oxidative stress of NPCs through activating the NF-κB pathway. This study may provide new potential targets for preventing and reversing IVDD.