MMP-1 Expression Research Articles

Neutrophils Respond Selectively to Physical Cues: Roughness Modulates Its Granule Release, and NETosis

Our study examined how different titanium alloy Ti6Al4V (Ti64) and zirconia (ZrO2) surfaces, ranging from rough to very smooth, affect the expression of elastase (NE), matrix metalloproteinase (MMP)-8, MMP-9, and extracellular traps (NETs) by neutrophils. Discs of Ti64 and ZrO2, 10 mm in diameter and 1.5 mm thick, were created using diamond-impregnated polishing burs and paste to produce rough (Ra > 3 µm), smooth (Ra ≥ 1 to 1.5 µm), and very smooth (Ra < 0.1 µm) surfaces. Neutrophils from Wistar rats were cultured on these surfaces, and the culture supernatants were then examined for NE, MMP-8, and MMP-9 using ELISA. At the same time, NET formation was demonstrated immunohistochemically by staining neutrophils with CD16b and DNA with DAPI. Overall, the expressions of NE and MMP-8 were significantly higher from neutrophil culture on Ti64 and ZrO2 rough surfaces compared to the very smooth surface (R > S > VS) after 2 h and 4 h of culture. The expression of MMP-9 also increased with culture time; however, no significant surface effects on expression were observed. Similarly, rough Ti64 and ZrO2 surfaces (R & S) also showed significantly larger NET formation compared to the very smooth surface (VS) after 4 h and 8 h cultures. Our findings suggest that increasing surface roughness on Ti64 and ZrO2 triggers higher NE, MMP-8, and NET formation secretion.

Role of DDR1 in Regulating MMPs in External Root Resorption

Human periodontal ligament cells (hPDLCs) express matrix metalloproteinases (MMPs), a group of enzymes responsible for the destruction of most extracellular matrix proteins in dental tissues, especially MMP-1, MMP-2, and MMP-13. Exploring the regulatory mechanism of MMPs is crucial for understanding external root resorption (ERR), one of the most severe complications, along with substantial loss of dental tissue, induced by trauma, pulpal infection, tooth bleaching, and orthodontic treatment, etc. Discoidin domain receptor 1 (DDR1), a cell surface receptor binding to collagen, has the potential to regulate the expression of MMP-1, MMP-2, and MMP-13, but the mechanism remains unclear. Thus, the present study aimed to investigate the connection and underlying mechanism between MMP-1, MMP-2, MMP-13, and DDR1 in hPDLCs. Our post-replantation ERR model revealed that Mmp-1, Mmp-2, Mmp-13, and Ddr1 all increased in the sites of ERR. hPDLCs with DDR1 knockdown exhibited a substantial reduction in MMP-1, MMP-2, and MMP-13 expression. To further confirm the underlying mechanism, we conducted further in vitro experiments, including RNA sequencing, RNA interference, RT-qPCR, Western blotting, and ELISA. Based on our results, MMP-1 was positively regulated by the Smad2/3 and MEK-ERK1/2 pathways and negatively regulated by the PI3K-Akt pathway through CCN2. MMP-2 and MMP-13 were positively regulated by the Smad2/3 pathway. MMP-13 was positively regulated by the MEK-ERK1/2 and PI3K/Akt signaling pathways. Collectively, DDR1 is a potent regulator of MMP-1, MMP-2, and MMP-13 expression through the Smad2/3, MEK-ERK1/2, and PI3K/Akt signaling pathways. Clarifying the significance and underlying mechanism by which DDR1 is involved in ERR might bring the chances to hinder the pathogenic process of ERR, hence reducing its incidence rate.

Structure optimization and molecular dynamics studies of new tumor-selective s-triazines targeting DNA and MMP-10/13 for halting colorectal and secondary liver cancers

A series of triazole-tethered triazines bearing pharmacophoric features of DNA-targeting agents and non-hydroxamate MMPs inhibitors were synthesized and screened against HCT-116, Caco-2 cells, and normal colonocytes by MTT assay. 7a and 7g surpassed doxorubicin against HCT-116 cells regarding potency (IC50 = 0.87 and 1.41 nM) and safety (SI = 181.93 and 54.41). 7g was potent against liver cancer (HepG-2; IC50 = 65.08 nM), the main metastatic site of CRC with correlation to MMP-13 expression. Both derivatives induced DNA damage at 2.67 and 1.87 nM, disrupted HCT-116 cell cycle and triggered apoptosis by 33.17% compared to doxorubicin (DNA damage at 0.76 nM and 40.21% apoptosis induction). 7g surpassed NNGH against MMP-10 (IC50 = 0.205 μM) and MMP-13 (IC50 = 0.275 μM) and downregulated HCT-116 VEGF related to CRC progression by 38%. Docking and MDs simulated ligands-receptors binding modes and highlighted SAR. Their ADMET profiles, drug-likeness and possible off-targets were computationally predicted.

The Role of Epigallocatechin-3-gallate (EGCG) In Inhibiting MMP3 Expression and Human Pterygium Fibroblast Migration: A Review

Background: Pterygium is characterized by the overgrowth of fibroblasts and the remodeling of the extracellular matrix (ECM), driven by MMPs. The review outlines the pathophysiology of pterygium, emphasizing the role of MMP-3 in cell motility, proteolysis, and angiogenesis. The recurrence rate of pterygium following surgical excision remains a significant challenge, with current adjuvant therapies like mitomycin-C presenting serious side effects. Methods: The review synthesizes findings from various studies on the effects of EGCG on MMP-3 expression and fibroblast migration. It discusses the mechanisms by which EGCG inhibits MMP-3 activity and its potential impact on pterygium progression. Findings: EGCG has been shown to inhibit MMP-3 expression and activity in several models, including mouse Lewis lung carcinoma-derived cells and photoaged hairless mouse models. It also suppresses the migration of human pterygium fibroblast cells, potentially preventing pterygium formation. EGCG's ability to reduce oxidative stress and modulate inflammatory pathways further supports its therapeutic potential. Conclusion: EGCG emerges as a promising agent for inhibiting MMP-3 expression and human pterygium fibroblast migration, offering a safer alternative to current adjuvant therapies. Its anti-inflammatory, antioxidant, and anti-angiogenic properties make it a potential therapeutic option for managing pterygium, warranting further clinical investigation.

Hepatocyte growth factor upregulates MMP1 and MMP10 expression and resolves corneal fibrosis

Different therapeutic modalities, including steroids, have been used to treat corneal scarring. However, the ability of steroids to reduce corneal scarring is limited and associated with numerous side effects. Our previous studies have demonstrated that topical hepatocyte growth factor (HGF) after corneal injury suppresses the development of stromal scars. Here, we investigated whether HGF can re-establish corneal clarity and normalize tissue structure in corneas with pre-existing scars. Corneal scarring was induced by mechanically removing the corneal epithelium and the anterior third of the stroma using a hand-held Algerbrush II in C57BL/6 mice. Substantial scar tissue formed by day 10 post-injury, at which time the epithelium was debrided and treated with 0.1% recombinant mouse HGF, 0.1% dexamethasone (steroid) or 0.1% control protein thrice a day for 10 days. Corneal clarity was significantly restored in the HGF treatment group, compared to both the steroid and control protein treatment groups. Moreover, HGF treatment downregulated the expression of αSMA and upregulated the expression of extracellular matrix-remodeling matrix metalloproteinases 1 and 10 (MMP1 and MMP10), suggesting HGF upregulates tissue remodeling molecule MMP1 and 10 to promote tissue restoration. These findings offer novel insights into the mechanisms by which HGF re-establishes corneal clarity, and promotes epithelial regeneration in corneas with pre-existing stromal scarring.

Development of optimized standardized extracts of Echinodorus macrophyllus for arthritis management

Ethnopharmacological relevanceEchinodorus macrophyllus is a medicinal plant traditionally used in Brazil to treat rheumatic diseases. It is listed as a priority species for the development of herbal preparations for the Brazilian Unified Health System (SUS). Previous studies have demonstrated the anti-inflammatory and antiedematogenic properties of extracts and fractions from this species, but these preparations were neither standardized nor optimized for anti-arthritis effects. Aim of studyThis study aimed to investigate the anti-inflammatory and antiarthritic effects of various standardized extracts from the aerial parts of E. macrophyllus and to outline their mechanisms of action. The goal was to define an extract suitable for future scientific validation and clinical use. Material and methodsExtracts from the aerial parts of E. macrophyllus were prepared through percolation with 96°GL ethanol (EtOH) and hydroethanolic solutions at 90%, 70%, and 50% (v/v). They were standardized based on the contents of six chemical markers quantified by UPLC-DAD. Mice with acute or chronic antigen-induced arthritis (AIA) were treated with the extracts orally. The effects were evaluated by counting total and differential inflammatory cells, measuring cytokines by ELISA, and by histological analysis with toluidine blue staining. The mechanism of selected extracts was investigated in LPS-stimulated murine chondrocytes. ResultsAll extracts, except for the 90% EtOH extract, exhibited significant anti-inflammatory activity in acute AIA, reducing the migration of total inflammatory cells, neutrophils, and monocytes to the intra-articular cavity. In chronic AIA, both the 96°GL EtOH and 70% EtOH extracts markedly reduced the migration of total inflammatory cells, neutrophils, and monocytes to the intra-articular cavity, decreased IL-1β and CXCL1 levels in the periarticular tissue, and diminished proteoglycan loss in the articular cartilage. Both extracts reduced IL-6 release and MMP-3 expression in LPS-stimulated chondrocytes. The 70% EtOH and 50% EtOH extracts showed heightened activity and higher levels of chemical markers, notably cinnamoyl-tartaric acid derivatives. ConclusionsThe standardized 70% EtOH and 50% EtOH extracts from the aerial parts of E. macrophyllus, which contain higher levels of chemical markers, exhibit potent anti-inflammatory activity and reduce proteoglycan degradation. These extracts are potentially useful for developing herbal preparations to manage arthritic conditions and should be prioritized for further studies.

Matrikine stimulation of equine synovial fibroblasts and chondrocytes results in an in vitro osteoarthritis phenotype.

Osteoarthritis (OA) is a debilitating disease that impacts millions of individuals and has limited therapeutic options. A significant hindrance to therapeutic discovery is the lack of in vitro OA models that translate reliably to in vivo preclinical animal models. An alternative to traditional inflammatory cytokine models is the matrikine stimulation model, in which fragments of matrix proteins naturally found in OA tissues and synovial fluid, are used to stimulate cells of the joint. The objective of this study was to determine if matrikine stimulation of equine synovial fibroblasts and chondrocytes with fibronectin fragments (FN7-10) would result in an OA phenotype. We hypothesized that FN7-10 stimulation of equine articular cells would result in an OA phenotype with gene and protein expression changes similar to those previously described for human chondrocytes stimulated with FN7-10. Synovial fibroblasts and chondrocytes isolated from four horses were stimulated in monolayer culture for 6 or 18 h with 1 µM purified recombinant 42 kD FN7-10 in serum-free media. At the conclusion of stimulation, RNA was collected for targeted gene expression analysis and media for targeted protein production analysis. Consistent with our hypothesis, FN7-10 stimulation resulted in significant alterations to many important genes that are involved in OA pathogenesis including increased expression of IL-1β, IL-4, IL-6, CCL2/MCP-1, CCL5/RANTES, CXCL6/GCP-2, MMP-1, MMP-3, and MMP13. The results of this study suggest that the equine matrikine stimulation model of OA may prove useful for in vitro experiments leading up to preclinical trials.

Protective Effect of Protocatechuic Aldehyde on Cerebral Ischemia/Reperfusion Injury in Rats through Blood-Brain Barrier Protection.

Cerebral ischemia can lead to destruction of the blood-brain barrier (BBB), the main cause of cerebral edema and cerebral infarction. BBB damage is also one of the key factors affecting the result of drug therapy. We studied the protective effect of 5-day pretreatment with protocatechuic aldehyde (PAL) at doses of 10 and 20 mg/kg on BBB function and structure after middle cerebral artery occlusion/reperfusion (MCAO/R) in rats. The infarct volume, behavioral neurological deficit score, and Evans blue content in the brain were estimated. We also evaluated the content of nitric oxide (NO) and activities of inducible and neuronal NO synthases. Expression of aquaporin-4 (AQP-4), occludin, claudin-5, and MMP-3 in the brain tissues was estimated by Western blotting. The BBB ultrastructure was analyzed under an electron microscope. We revealed that PAL at both used doses significantly reduced the neurological deficit score, brain infarct volume, and Evans blue extravasation. Electron microscopy showed that PAL significantly improved the ultrastructure of BBB and alleviated its injury. Pretreatment with PAL increased expression of occludin and claudin-5 and reduced expression of AQP-4 and MMP-3. At the same time, the release of NO and activities of NO synthases were notably inhibited. Our results suggest that PAL can be a promising compound to attenuate cerebral ischemia resulting from occlusion/reperfusion injury via BBB protection.

MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, MUC1 and CD29 Expression in Endometrial Polyps at Implantation Window Compared to Neighbouring Normal Endometrium

MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, MUC1 and CD29 Expression in Endometrial Polyps at Implantation Window Compared to Neighbouring Normal Endometrium

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.

Jiangu Recipe Suppresses ER Stress-Induced Apoptosis and Inhibits Extracellular Matrix Degradation in Chondrocytes through Upregulating SIRT1 Expression.

This study aimed to explore the effects of Jiangu Recipe (JGR) on chondrocyte responses under tert-Butyl hydroperoxide (TBHP)-induced oxidative stress, specifically focusing on apoptosis and extracellular matrix (ECM) degradation. Chondrocytes were treated with varying JGR concentrations, and cell viability was assessed. The impact of JGR on TBHP-induced apoptosis and protein expression levels of apoptosis- related molecules (Bcl-2, Bax, and cleaved caspase-3) and ECM components (Collagen II, Aggrecan, MMP-13) was evaluated. JGR exhibited protective effects against oxidative stress in chondrocytes. Moreover, it maintained cell viability under tert-butyl hydroperoxide (TBHP) induction, suppressing apoptosis (Bax, cleaved caspase-3) and enhancing anti-apoptotic Bcl-2. JGR also attenuated extracellular matrix (ECM) degradation, promoting Collagen II and Aggrecan while reducing MMP-13 expression. Investigating endoplasmic reticulum (ER) stress, it was found that JGR downregulated TBHP-induced GRP78, CHOP, ATF4, p-PERK, and p-eIF2α, thus indicating ER stress modulation. SIRT1 played a key role, as JGR upregulated SIRT1, mitigating TBHP-induced downregulation. SIRT1 knockdown reversed JGR's protective effects, highlighting its crucial role in JGR-mediated responses. Our findings suggest that JGR mitigated TBHP-induced chondrocyte apoptosis and ECM degradation, highlighting its potential therapeutic application in osteoarthritis. Mechanistically, our study highlights that SIRT1 plays a crucial role in mediating the protective effects of JGR against ER stress-induced chondrocyte apoptosis and ECM degradation, providing a foundation for further clinical exploration in managing osteoarthritic conditions.

The major vault protein integrates adhesion-driven signals to regulate collagen remodeling

DDR1 interacts with fibrillar collagen and can affect β1 integrin-dependent signaling, but the mechanism that mediates functional interactions between these two different receptors is not defined. We searched for molecules that link DDR1 and β1 integrin-dependent signaling in response to collagen binding. The activation of DDR1 by binding to fibrillar collagen reduced by 5-fold, β1 integrin-dependent ERK phosphorylation that leads to MMP1 expression. In contrast, pharmacological inhibition of DDR1 or culturing cells on fibronectin restored ERK phosphorylation and MMP1 expression mediated by the β1 integrin. A phospho-site screen indicated that collagen-induced DDR1 activation inhibited β1 integrin-dependent ERK signaling by regulating autophosphorylation of focal adhesion kinase (FAK). Immunoprecipitation, mass spectrometry, and protein-protein interaction mapping showed that while DDR1 and FAK do not interact directly, the major vault protein (MVP) binds DDR1 and FAK depending on the substrate. MVP associated with DDR1 in cells expressing β1 integrin that were cultured on collagen. Knockdown of MVP restored ERK activation and MMP1 expression in DDR1-expressing cells cultured on collagen. Immunostaining of invasive cancers in human colon showed colocalization of DDR1 with MVP. These data indicate that MVP interactions with DDR1 and FAK contribute to the regulation of β1 integrin-dependent signaling pathways that drive collagen degradation.

Exploring the Therapeutic Potential of Green Tea (Camellia sinensis L.) in Anti-Aging: A Comprehensive Review of Mechanisms and Findings.

Green tea (GT) is rich in Phyto-active compounds such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), epicatechin (EC), catechin, and tannic acid, which exhibit synergistic effects when combined. Preclinical studies demonstrate that GT and its compounds can reduce reactive oxygen species (ROS), enhance antioxidant capacity, and alleviate aging-related issues such as memory impairments, cognitive decline, and shortened lifespan. Clinical trials corroborate the efficacy of topical GT formulations in improving skin tone, texture, and elasticity and reducing wrinkles. The present manuscript summarizes the recent update on the anti-aging potential of GT and its possible mechanisms. The literature survey suggested that GT consumption is linked to improved cognition, reduced depression levels, and activation of pathways in model organisms like C. elegans. Additionally, tea polyphenols enhance fibroblast mitophagy, boost hippocampal synaptic plasticity in rodents, and mitigate age-related cognitive decline. Moreover, EGCG exhibits anti-aging properties by reducing TNF-induced MMP-1 expression, suppressing ERK signaling, and inhibiting MEK and Src phosphorylation in human dermal fibroblasts. In the context of skin permeation and deposition, optimized transpersonal formulation (TF) incorporating EGCG and hyaluronic acid (HA) demonstrated significantly increased skin permeation and deposition of EGCG compared to plain EGCG. Furthermore, EGCG protects cardiomyocytes via the PPARγ pathway and combats age-related muscle loss through miRNA-486-5p regulation, AKT activation, and FoxO1a-mediated expression of MuRF1 and Atrogin-1. In conclusion, the regular consumption of GT holds promise for promoting physical and mental health, delaying brain and skin aging, and improving overall health by enhancing total antioxidant capacity.

Gelatinase MMP Expression Is Correlated with Muscle Fiber Growth in Maiwa Yak Gluteus Maximus.

Yak (Bos grunniens) is the only large mammal species in the Qinghai-Tibet Plateau. The most of the studies in yak remain confined for the main contributor of meat, which requires a good understanding of muscle growth. Matrix metalloproteinases-2 (MMP-2) and MMP-9 are widely expressed in mammal tissues they mainly degrade collagen in the extracellular matrix for muscle development. However, the influence of MMPs on yak muscle remains unclear. Hence, we assessed the expression of MMP-2, MMP-9, and related factors with ages in Maiwa yak for study the correlation between MMPs expression and yak muscle growth. The mRNA expression of MMP-2, MMP-9, MMP-14, and collagen III increased with age, except collagen I by quantitative real-time PCR. Moreover, muscle fiber diameter increased with age, whereas the density decreased, which showed that fiber grew thicker with age using hematoxylin-eosin staining. Interestingly, MMP and collagen expression significantly decreased with age using western blotting. Pearson correlation method showed that both mRNA and protein expression of MMP-14 and collagen were strongly correlated with muscle fiber growth, but MMP-2 protein and MMP-9 mRNA expression were moderately correlated with muscle fiber growth. Overall, the expression of MMPs and collagen significantly changed with age, which means that MMPs and their function related genes could correlate with Maiwa yak muscle fiber growth.

Radiofrequency Currents Modulate Inflammatory Processes in Keratinocytes.

Keratinocytes play an essential role in the inflammatory phase of wound regeneration. In addition to migrating and proliferating for tissue regeneration, they produce a large amount of cytokines that modulate the inflammatory process. Previous studies have shown that subthermal treatment with radiofrequency (RF) currents used in capacitive resistive electric transfer (CRET) therapy promotes the proliferation of HaCat keratinocytes and modulates their cytokine production. Although physical therapies have been shown to have anti-inflammatory effects in a variety of experimental models and in patients, knowledge of the biological basis of these effects is still limited. The aim of this study was to investigate the effect of CRET on keratinocyte proliferation, cytokine production (IL-8, MCP-1, RANTES, IL-6, IL-11), TNF-α secretion, and the expression of MMP9, MMP1, NF-κB, ERK1/2, and EGFR. Human keratinocytes (HaCat) were treated with an intermittent 448 kHz electric current (CRET signal) in subthermal conditions and for different periods of time. Cell proliferation was analyzed by XTT assay, cytokine and TNF-α production by ELISA, NF-κB expression and activation by immunofluorescence, and MMP9, MMP1, ERK1/2, and EGF receptor expression and activation by immunoblot. Compared to a control, CRET increases keratinocyte proliferation, increases the transient release of MCP-1, TNF-α, and IL-6 while decreasing IL-8. In addition, it modifies the expression of MMPs and activates EGFR, NF-κB, and ERK1/2 proteins. Our results indicate that CRET reasonably modifies cytokine production through the EGF receptor and the ERK1/2/NF-κB pathway, ultimately modulating the inflammatory response of human keratinocytes.

Exploring the Mechanism of Sempervirine Inhibiting Glioblastoma Invasion Based on Network Pharmacology and Bioinformatics

Background: Invasion is an important characteristic of the malignancy of glioblastoma (GBM) and a significant prognostic factor. Sempervirine (SPV), a yohimbine-type alkaloid, has been proven to inhibit GBM cells proliferation in previous research and found to have a potential effect in anti-invasion, but its mechanism of anti-invasion is still unknown. Methods: To explore its pharmacodynamics in inhibiting GBM cell invasion in this study, we combined network pharmacology and bioinformatics to comprehensive exploratory analysis of SPV and verified the mechanism in vitro. Results: Firstly, targets of SPV and invasion-related genes were collected from public databases. Moreover, GBM samples were obtained to analyze differentially expressed genes (DEGs) from The Cancer Genome Atlas (TCGA). Then, the relevant targets of SPV inhibiting GBM invasion (SIGI) were obtained through the intersection of the three gene sets. Further, GO and KEGG analysis showed that the targets of SIGI were heavily enriched in the AKT signaling pathway. Subsequently, based on the method of machine learning, a clinical prognostic model of the relevant targets of SIGI was constructed using GBM samples from TCGA and the Gene Expression Omnibus (GEO). A four-genes model (DUSP6, BMP2, MMP2, and BMP2) was successfully constructed, and Vina Scores of MMP2 and MMP13 in molecular docking were higher, which may be the main targets of SIGI. Then, the effect of SIGI was confirmed via functional experiments on invasion, migration, and adhesion assay, and the effect involved changes in the expressions of p-AKT, MMP2 and MMP13. Finally, combined with AKT activator (SC79) and inhibitor (MK2206), we further confirmed that SPV inhibits GBM invasion through AKT phosphorylation. Conclusions: This study provides valuable and an expected point of view into the regulation of AKT phosphorylation and inhibition of GBM invasion by SPV.

Molybdenum nanodots act as antioxidants for photothermal therapy osteoarthritis

Osteoarthritis (OA) manifests as the degradation of cartilage and remodeling of subchondral bone. Restoring homeostasis within the joint is imperative for alleviating OA symptoms. Current interventions primarily target singular aspects, such as anti-aging, inflammation inhibition, free radical scavenging, and regeneration of cartilage and subchondral bone. Herein, we developed molybdenum nanodots (MNDs) as bionic photothermal nanomaterials to mimic the antioxidant synthase to concurrently protected cartilage and facilitate subchondral bone regeneration. With near-infrared (NIR) irradiation, MNDs effectively eliminate reactive oxygen and nitrogen species (ROS/RNS) from OA chondrocytes, thereby reversed mitochondrial dysfunction, mitigating chondrocyte senescence, and simultaneously suppresses inflammation, hence preserving the inherent homeostasis between cartilage matrix synthesis and degradation while circumventing safety concerns. RNA sequencing of OA chondrocytes treated with MNDs-NIR revealed the reinstatement of chondrocyte functionality, activation of antioxidant enzymes, anti-aging properties, and regulation of inflammation. NIR irradiation induces thermogenesis and synergistically promotes subchondral bone regeneration via MNDs, as validated through histological assessments and microcomputed tomography (Micro-CT) scans. MNDs-NIR effectively attenuate cellular senescence and inhibit inflammation in vivo, while also remodeling mitochondrial dynamics by upregulating fusion proteins and inhibiting fission proteins, thereby regulating the oxidative stress microenvironment. Additionally, MNDs-NIR exhibited remarkable therapeutic effects in alleviating articular cartilage degeneration in an OA mouse model, evidenced by a 1.67-fold reduction in subchondral bone plate thickness, an 88.57% decrease in OARSI score, a 5.52-fold reduction in MMP13 expression, and a 6.80-fold increase in Col II expression. This novel disease-modifying approach for OA utilizing MNDs-NIR offers insight and a paradigm for improving mitochondrial dysfunction by regulating the accumulation of mitochondrial ROS and ultimately alleviating cellular senescence. Moreover, the dual-pronged therapeutic approach of MNDs-NIR, which addresses both cartilage erosion and subchondral bone lesions in OA, represents a highly promising strategy for managing OA.

Prediabetes Associates with Matrix Metalloproteinase-8 Activation and Contributes to the Rapid Destruction of Periodontal Tissues.

The aim of this cross-sectional study was to investigate the relationship between periodontitis, potential periodontitis oral fluid biomarkers, and prediabetes. This study included 150 Greek adults aged 25 to 78 years who were tested with an Hemoglobin A1C (HBA1c) diagnostic system, an active-matrix metalloproteinase-8 (aMMP-8) point-of-care (PoC) test, and several salivary biomarkers enzyme-linked immunosorbent assay tests and gelatin zymography. A full-mouth clinical examination was performed to assess their periodontal and oral health status. The Kruskal-Wallis test was used to determine the statistically significant difference in the levels of periodontal oral fluid biomarkers between the different periodontitis stages, periodontitis grades, and the stages and grades of periodontitis combined. Spearman's rank correlation was performed to assess the strength and direction of the association between aMMP-8 and HbA1c levels (<5.7 and ≥5.7%) and with the other oral fluid biomarkers among patients with severe periodontitis. A two-sided p-value below 0.05 was considered statistically significant in this study. aMMP-8, but not total MMP-8 or other biomarkers, associated significantly with the stage and grade of periodontitis combined (p < 0.001, Kruskal-Wallis test). Among stage III grade C periodontitis patients, aMMP-8 levels were significantly positively correlated with prediabetes (Spearman's rho = 0.646, p = 0.044), total MMP-8 (rho = 0.636, p = 0.048), PMN Elastase (rho = 0.729, p = 0.017), total MMP-9 (rho = 0.721, p = 0.019), and total MMP-8/TIMP-1 molar ratio (rho = 0.879, p < 0.001). Prediabetic disease development can upregulate MMP-8 expression (total MMP-8) in rapidly progressing, severe periodontitis, where MMP-8 latent species are further activated into their active forms (aMMP-8). Simultaneously, several proinflammatory biomarker levels are elevated in this tissue-destructive biomarker cascade. This development is easily detectable online/in real-time within 5 minutes by aMMP-8 PoC testing at the dentist's office.

Syn-COM: A Multi-Level Predictive Synergy Framework for Innovative Drug Combinations.

Drug prediction and treatment using bioinformatics and large-scale modeling have emerged as pivotal research areas. This study proposes a novel multi-level collaboration framework named Syn-COM for feature extraction and data integration of diseases and drugs. The framework aims to explore optimal drug combinations and interactions by integrating molecular virtuality, similarity clustering, overlap area, and network distance. It uniquely combines the characteristics of Chinese herbal medicine with clinical experience and innovatively assesses drug interaction and correlation through a synergy matrix. Gouty arthritis (GA) was used as a case study to validate the framework's reliability, leading to the identification of an effective drug combination for GA treatment, comprising Tamaricis Cacumen (Si = 0.73), Cuscutae Semen (Si = 0.68), Artemisiae Annuae Herba (Si = 0.62), Schizonepetae Herba (Si = 0.73), Gleditsiae Spina (Si = 0.89), Prunellae Spica (Si = 0.75), and Achyranthis Bidentatae Radix (Si = 0.62). The efficacy of the identified drug combination was confirmed through animal experiments and traditional Chinese medicine (TCM) component analysis. Results demonstrated significant reductions in the blood inflammatory factors IL1A, IL6, and uric acid, as well as downregulation of TGFB1, PTGS2, and MMP3 expression (p < 0.05), along with improvements in ankle joint swelling in GA mice. This drug combination notably enhances therapeutic outcomes in GA by targeting key genes, underscoring the potential of integrating traditional medicine with modern bioinformatics for effective disease treatment.

Doxycycline versus Curcumin for Inhibition of Matrix Metalloproteinase Expression and Activity Following Chemically Induced Inflammation in Corneal Cells.

Sulfur mustard (SM) is a potent blistering agent. This alkylating chemical agent has extremely toxic effects on the eye. MMP-2 and MMP-9 are the two most important matrix metalloproteinase enzymes involved in the pathology of chemical eye injuries. Curcumin is regarded as a natural anti-inflammatory agent. This study aims to compare the anti-inflammatory effects of curcumin versus doxycycline on chemically induced corneal injuries. The HCE-2 cell line was used as a model for corneal cells. The effective concentrations of 2-chloroethyl ethyl sulfide (CEES) - as an analog of SM - doxycycline, and curcumin were determined using the MTT assay. The gene expression of MMP-2, MMP-9, and tissue inhibitors of metalloproteinase (TIMP-1) was evaluated by the real-time PCR method. Also, the activity of MMP-2 and MMP-9 enzymes was determined by zymography. The expression of the MMP-2 and MMP-9 genes increased 5- and 3.3-fold after exposure to CEES, respectively. Following the treatment with curcumin and doxycycline, MMP-2 expression decreased significantly. Also, after treatment with curcumin and doxycycline, the MMP-9 expression decreased 2.5- and 1.6-fold, respectively. The reduction in activity was 32% for MMP-2 and 56% for MMP-9 after treatment with curcumin. The corresponding values were 12% and 40% following doxycycline treatment. There was no significant difference between the effects of curcumin and doxycycline on reducing MMP-2 expression, but the difference was statistically significant in the case of MMP-9. Doxycycline and curcumin can inhibit MMP expression and activity in chemically exposed corneal cells. Curcumin has a greater ability than doxycycline to inhibit MMP-2 and MMP-9 enzymes; however, the difference is statistically significant only in the case of MMP-9. After further validation, these substances can be introduced as anti- inflammatory agents to treat corneal chemical burns.