Matrix Metalloproteinase Research Articles

Caffeic acid stimulates migration and invasion of human trophoblast HTR-8/SVneo cells.

The placenta is a transient organ essential for development of the fetus. Adequate invasion of trophoblast cells, specialized cells of the placenta, is of utmost importance for the establishment and maintenance of healthy pregnancy. Caffeic acid (CA), one of the most abundantly present hydroxycynamic acids in everyday human diet, exhibits various physiological effects such as antioxidant, anti-inflammatory and anticancer activities including an inhibitory effect on migration and invasion of different cancer cell types. There are not many studies on CA safety in human pregnancy. Therefore, the aim of this research was to investigate the potential of CA to affect trophoblast cell function. We evaluated adhesion, migration and invasion of human trophoblast HTR-8/SVneo cells following CA treatment by functional assays. Furthermore, expression of molecular mediators of these processes such as integrin α1, α5 and β1 subunits and matrix metalloproteinase (MMP)-2 and MMP-9 was evaluated at the mRNA level by qPCR and the protein level by cell-based ELISA assay or zymography. Our results showed that 24 h treatment with 10 μM CA stimulated migration and invasion of HTR-8/SVneo cells as well as expression of the integrin α1 subunit. Furthermore, treatment with 100 μM CA stimulated expression of MMP2 and MMP9 mRNA in the treated HTR-8/SVneo cells as well as secretion of MMP-9. According to obtained results, we can conclude that CA could have the potential to affect processes important for placentation. However, further research is needed to elucidate all aspects of potential CA effects on placental function and pregnancy as a whole.

Prognostic utility of neutrophil gelatinase-associated lipocalin (NGAL) levels for cardiovascular events in patients with stable coronary artery disease treated with percutaneous coronary intervention: a prospective longitudinal cohort study

IntroductionNeutrophil gelatinase-associated lipocalin (NGAL) modulates the enzymatic activity of matrix metalloproteinase-9, which is an important mediator of plaque instability in atherosclerosis. High NGAL levels can independently predict all-cause mortality and major adverse cardiac events (MACE) in patients with acute myocardial infarction (AMI). However, studies that have measured NGAL levels in patients with stable coronary artery disease (CAD) are limited. Furthermore, no significant prognostic predictive value between NGAL levels and stable CAD has been established.HypothesisWe aimed to investigate the prognostic role of NGAL levels in a prospective cohort study of patients with stable CAD treated with percutaneous coronary intervention (PCI).MethodsA total of 2,238 stable patients with CAD and a previous PCI were enrolled in a multicenter prospective observational study (The National Taiwan Biosignature Research, NTBR) in Taiwan. The primary outcome was the occurrence of MACE (cardiovascular death, nonfatal myocardial infarction, and ischemic stroke). The secondary outcome was a composite of cardiovascular events (cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for heart failure).ResultsDuring the mean follow-up period of 4.6 ± 1.7 years, 441 patients reached the primary endpoints. Kaplan-Meier analysis showed that event-free survival was significantly different between the first and third tertile groups (log-rank test, p < 0.001) in subjects categorized by NGAL levels. In a multivariate Cox proportional hazard regression analysis, plasma NGAL levels were independently associated with an increased risk of MACE [adjusted hazard ratio (aHR) = 1.35; 95% confidence interval (CI) = 1.18–1.54, p < 0.001], AMI (aHR = 1.34; 95% CI = 1.12–1.59, p < 0.001), and target vessel revascularization (aHR = 1.35; 95% CI = 1.19–1.53, p < 0.001). Addition of serum NGAL levels to the traditional risk model improved its prediction value for future cardiovascular events.ConclusionsHigh plasma NGAL levels were independently associated with the occurrence of MACE and composite cardiovascular events in patients with stable PCI-treat CAD.

In vitro evaluation of anti-inflammatory, anti-plaque efficacy, and biocompatibility of Norway spruce (Picea abies) resin extract for oral care applications.

The periodontal disease is globally highly prevalent, and calls for novel, effective, and preferably bio-based raw materials. Accumulation of dental plaque causes gingivitis, which is reversible by treatments that control the bacterial biofilm. If left untreated, the gingivitis can lead to gingival inflammation and potentially progress to periodontitis. In this study, a natural antimicrobial and anti-inflammatory Norway spruce (Picea abies) resin extract was evaluated as a potential option in supportive periodontal care. Lipopolysaccharide-induced macrophage-like cells were used to study the anti-inflammatory properties in vitro. The spruce resin extract at 20 % concentration had the highest anti-inflammatory effect, comparable to a corticosteroid's effect on pro-inflammatory cytokines interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-3 (MMP-3). Consequently, the 20 % spruce resin extract was selected for toothpaste formulation. Its anti-plaque efficacy was evaluated by total aerobic colony counts and the proportions of streptococci grown on the surfaces of the treated glass rods using pooled human saliva. It was found that the toothpaste effectively reduced dental plaque biofilm, matching the anti-plaque efficacy of Corsodyl mouthwash, containing chlorhexidine digluconate. The toothpaste was also found to be non-damaging in biocompatibility studies on three-dimensional (3D) tissue models of human oral and gingival epithelium. These findings provide scientific validation of spruce resin's effectiveness in oral care, elucidating probable reasons why people have historically chewed resins for oral care purposes.

TGF-β induces cholesterol accumulation to regulate the secretion of tumor-derived extracellular vesicles

BackgroundCancer cells are avid extracellular vesicle (EV) producers. EVs transport transforming growth factor-β (TGF-β), which is commonly activated under late stages of cancer progression. Nevertheless, whether TGF-β signaling coordinates EV biogenesis is a relevant topic that remains minimally explored.MethodWe sought after specific TGF-β pathway mediators that could regulate EV release. To this end, we used a large number of cancer cell models, coupled to EV cell biological assays, unbiased proteomic and transcriptomic screens, followed by signaling and cancer biology analyses, including drug resistance assays.ResultsWe report that TGF-β, by activating its type I receptor and MEK-ERK1/2 signaling, increased the numbers of EVs released by human cancer cells. Upon examining cholesterol as a mediator of EV biogenesis, we delineated a pathway whereby ERK1/2 acted by phosphorylating sterol regulatory element-binding protein-2 that transcriptionally induced 7-dehydrocholesterol reductase expression, thus raising cholesterol abundance at both cellular and EV levels. Notably, inhibition of MEK or cholesterol synthesis, which impaired TGF-β-induced EV secretion, sensitized cancer cells to chemotherapeutic drugs. Furthermore, proteomic profiling of two distinct EV populations revealed that EVs secreted by TGF-β-stimulated cells were either depleted or enriched for different sets of cargo proteins. Among these, latent-TGF-β1 present in the EVs was not affected by TGF-β signaling, while TGF-β pathway-related molecules (e.g., matrix metalloproteinases, including MMP9) were either uniquely enriched on EVs or strongly enhanced after TGF-β stimulation. EV-associated latent-TGF-β1 activated SMAD signaling, even when EV uptake was blocked by heparin, indicating competent signaling capacity from target cell surface receptors. MMP inhibitor or proteinase treatment blocked EV-mediated SMAD signaling, suggesting that EVs require MMP activity to release the active TGF-β from its latent complex, a function also linked to the EV-mediated transfer of pro-migratory potential and ability of cancer cells to survive in the presence of cytotoxic drugs.ConclusionHence, we delineated a novel signaling cascade that leads to high rates of EV generation by cancer cells in response to TGF-β, with cholesterol being a key intermediate step in this mechanism.Graphical • TGF-β increases EV release by activating a MEK-ERK1/2-SREBP2-DHCR7 signaling and transcriptional pathway.• TGF-β-induced DHCR7 expression raises cholesterol abundance that promotes EV release.• EVs carry surface latent TGF-β and MMP9 that can activate TGF-β receptor signaling on the surface of recipient cells.

Rutin engages opioid/benzodiazepine receptors towards anti-neuropathic potential in a rat model of chronic constriction injury: relevance to its antioxidant and anti-inflammatory effects.

Neuropathic pain is a chronic type of pain caused by damage or dysfunction in the nervous system. It can be quite bothersome and often doesn't well respond to common painkillers. Among natural compounds, rutin (Rut) stands out for its remarkable antioxidant, and anti-inflammatory properties. In this research, our objective is to investigate the impact of Rut on an animal model of chronic constriction injury (CCI). A total of 54 adult Wistar rats were divided randomly into nine separate groups. Groups included sham, CCI, gabapentin (GBP, 100 mg/kg), Rut (10, 25 mg/kg), flumazenil (FLU, 0.5 mg/kg), naloxone (NAL, 0.1 mg/kg), Rut (10 mg/kg) + FLU (0.5 mg/kg), and Rut (10 mg/kg) + NAL (0.1 mg/kg). The aforementioned drug injection (intraperitoneal, i.p.) and sensorimotor behavioral tests were performed on days 1, 3, 5, 7, 9, 11, and 14. Biochemical (e.g., nitrite, catalase, glutathione), zymography (matrix-metalloproteinase 2 and 9), and histopathological tests were performed on day 14 after surgery. The findings demonstrated that Rut administration effectively alleviated symptoms of allodynia/hyperalgesia, and improved locomotor activity following CCI. Additionally, Rut administration resulted in increased catalase and glutathione activity, while reducing serum nitrite levels, as well as matrix metalloproteinase 2 and 9 activity. Additionally, histological results indicated that Rut improved sciatic nerve regeneration. Since the aforementioned effects of Rut were reversed by using opioid and benzodiazepine receptor antagonists (i.e., NAL and FLU, respectively), the receptors' involvement was revealed in the anti-neuropathic effects of Rut. In conclusion,Rut emerged as a potentially effective candidate for treating neuropathic pain and improving motor function by increasing antioxidant mediators, suppressing inflammation, and activating opioid/benzodiazepine receptors.

Monocytes and cervical ripening: a narrative review of prolonged labor pathophysiology

Prolonged labor, a major obstetric complication, is often linked to inadequate cervical ripening, which hinders labor progression. The process of cervical ripening is governed by complex hormonal and immune-mediated mechanisms, with monocytes playing a central role. These immune cells infiltrate the cervix and differentiate into macrophages, releasing cytokines and proteases that are essential for extracellular matrix remodeling, cervical softening, and dilation. However, in prolonged labor, an imbalance in monocyte activity may impede normal cervical ripening, contributing to stalled labor and increased risk of maternal and neonatal complications. Monocytes are critical to the inflammatory response that initiates cervical remodeling during labor. Upon recruitment to the cervix, monocytes release inflammatory cytokines like IL-1, IL-6, and TNF-α, which activate matrix metalloproteinases (MMPs) to degrade collagen and extracellular matrix proteins, facilitating cervical effacement and dilation. Dysregulated monocyte recruitment and prolonged inflammation, however, may lead to ineffective cervix remodeling, preventing labor from progressing efficiently. Furthermore, these immune responses can influence uterine contractility, either promoting or inhibiting uterine contractions, which further complicates the pathophysiology of prolonged labor.

Control the Gene Delivery and Anticancer Efficacy of Peptides through Chiral Modulation.

Incorporating d-amino acids into peptides can influence the intermolecular interactions of peptides, thus determining the morphology and functionality of self-assembled supramolecular structures. Based on this, we propose a modular chirality regulation strategy and designed four chiral peptides by adjusting the chirality of different functional modules. The chirality can control the coassembly of peptides and nucleic acids into virus-like vesicles with controlled diameters and enzyme-responsiveness. Compared with homochiral peptides, the heterochiral peptides with chirality inversion in their hydrophobic domain transformed into more hydrophobic assemblies in response to the highly expressed enzyme matrix metalloproteinase 7 (MMP-7) in cancer cells and showed higher endosomal membrane disruption activity. Moreover, the heterochiral peptides exhibit high efficiency and selectivity in delivering siRNA gene drugs and inhibiting cancer cell growth, achieving a mortality rate of 95% in cancer cells. These results provide a promising strategy for designing peptide-based nucleic acid delivery systems through chiral modulation.

Ginkgetin delays the progression of osteoarthritis by inhibiting the NF-κB and MAPK signaling pathways

BackgroundOsteoarthritis (OA) is considered an advancing chronic degenerative joint disease, leading to severe physical functional impairment of patients. Its development is closely related to increased inflammation and oxidative stress within the joint. Ginkgetin (GK), a natural non-toxic chemical, has proven anti-inflammatory, antioxidant, anti-tumor, and neuroprotective effects.MethodsFirst, this study utilizes network pharmacology to explore the intrinsic connection between GK and OA. In vitro, SW1353 human cartilage cells were stimulated with Tert-butyl hydrogen peroxide (TBHP), and different GK concentrations were pre-treated to evaluate its protective effects. GK's anti-inflammatory and antioxidative effects were comprehensively assessed via MTT assay, western blot, cell immunofluorescence, ELISA, and transcriptome sequencing. Potential underlying mechanisms were also explored. In vivo, OA was induced in rats via anterior cruciate ligament transection (ACLT), and GK's impact on cartilage protection was further assessed via histological analysis and western blot.ResultsNetwork pharmacology has revealed that GK regulates OA via several key pathways, especially NF-κB, HIF-1, PI3K-AKT, and substances like reactive oxygen species. In vitro experiments showed GK effectively reverses oxidative stress damage from TBHP, inhibits inflammatory factor release, and protects Extracellular matrix (ECM) from degradation. These functions may be achieved via the NF-κB and MAPK signaling pathways. In vivo experiments showed GK significantly reduced proteoglycan loss from ACLT and inhibited matrix metalloproteinase 13 (MMP13) and ADAMTS5 (A disintegrin and metalloproteinase with thrombospondin motifs 5) production, effectively preventing cartilage degeneration in rats.ConclusionThese findings suggest that GK has potential as a therapeutic agent for OA, offering new strategies and directions for OA treatment.

Exploring the anti-inflammatory effects of phytochemicals in attenuating interstitial cystitis-a literature review

Interstitial cystitis is a fierce syndrome affecting the quality of life of thousands of individuals around the globe. It causes immense pain in the bladder and associated viscera along with inflammation-like lesions. The current medicinal and pharmacological research focuses on the protective and curative effects of phytochemicals in several ailments. Phytochemicals derived from many medicinal plants have shown potent outcomes in protection against various pathological conditions including interstitial cystitis. This review has summarized the insights of in vitro and in vivo studies regarding the effects of phytochemicals in fading the inflammation in bladder tissue and exhibiting a protective effect on the urothelium. Hemorrhagic cystitis is a common manifestation in patients undergoing chemotherapy with cyclophosphamide and related alkylating agents. Sodium 2-mercaptoethane sulfonate (Mesna) has traditionally been employed in clinical practice to counter cyclophosphamide-induced cystitis in humans. However, cyclophosphamide has been employed in developing animal models of interstitial cystitis in in vivo studies. Phytochemicals including quercetin, beta-caryophyllene, curcumol, boswellic acid, caftaric acid, some flavonoids and other secondary metabolites being a consequential component of numerous medicinal plants, have displayed a significant reduction in the levels of proinflammatory cytokines including TNF-α, NFĸB, IL-1β, NLRP3 inflammasome, IL-6, IL-2, matrix metalloproteinases etc. Uroprotective outcomes of these phytochemicals have been found to result in diminished oxidative stress and restoration of glutathione, superoxide dismutase, and related proteins in the inflamed bladder tissue. Many in vivo studies involving cyclophosphamide-induced interstitial cystitis have confirmed these findings. The coupling of phytotherapy with novel drug delivery systems such as nanoparticles, liposomes, nanotubes, quantum dots, etc. can help translate these beneficial effects of phytochemicals into clinical practice. Further investigations of these phytochemicals can provide intuition regarding the development of newer drug molecules having exclusive activity for attenuating interstitial cystitis.

Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells

Abstract Objective To investigate how lathyrol affects aggressive behaviors and related proteins of the androgen receptor (AR) 786-O cells. Methods 786-O cells were cultured in vitro and divided into these groups at random: the dimethylsulfoxide (DMSO) control group (A group), negative control group (B group), and experimental group (C group). Cells in A group were grown in DMSO working medium (contained RPMI 1640 medium and 1% DMSO), B group cells were cultured in nilutamide working medium (contained DMSO working medium and 325 μg/mL nilutamide), while those in C group were cultured in lathyrol working medium (contained DMSO working medium and 300 μg/mL lathyrol). Cell proliferation was measured via CCK-8 assays, and cell apoptosis was examined through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. Scratch tests and Transwell invasion tests were used to evaluate cell movement and penetration. The expression information about p-AR, AR, p-Akt, ki67, caspase3, cleaved-caspase3, Bcl-2, Bax, caspase9, cleaved-caspase9, and GAPDH proteins was investigated through western blotting. Immunocytochemistry was used to identify the 786-O cells’ secretion level of matrix metalloproteinase 2 (MMP2), MMP9, and prostate-specific antigen (PSA) proteins. Results The negative control and experimental groups’ cells exhibited reduced proliferation, migration, and invasion and increased apoptosis after 24 h treatment. Furthermore, these two group cells exhibited a notable reduction in the status of Ki67, Bcl-2, MMP2, MMP9, and p-Akt (P &lt; 0.05) and significantly increased the expressions of AR, p-AR, Bax, cleaved-caspase3, and cleaved-caspase9 (P &lt; 0.05). There was no statistical distance in PSA, caspase3, and caspase9 expressions among the three groups (P &gt; 0.05). Conclusion In vitro, lathyrol and nilutamide exert notable anticancer effects by effectively suppressing the proliferation, migration, and invasion of 786-O cells while also inducing apoptosis.

The Anti-Inflammatory Effects of Liraglutide in Equine Inflammatory Joint Models.

This study investigates the anti-inflammatory properties of liraglutide, a glucagon-like peptide 1 receptor agonists, in equine in vitro models and in an in vivo acute synovitis model in Shetland ponies. The anti-inflammatory effect of liraglutide was assessed by measuring concentrations of inflammatory biomarker C-C Motif Chemokine Ligand 2 (CCL2) in culture media of equine whole blood, peripheral blood mononuclear cells (PBMCs), chondrocytes, and synoviocytes, with or without lipopolysaccharide (LPS) or interleukin-1β. In the in vivo experiment, acute synovitis was bilaterally induced with 0.25 ng LPS in the intercarpal joints of seven healthy Shetland ponies. The ponies were subsequently treated with either 6 mg liraglutide or a placebo as a paired control in each joint. The impact of liraglutide on biomarkers associated with inflammation (including white blood cell count, total protein, CCL2, and bradykinin) and cartilage metabolism (such as glycosaminoglycans, general matrix metalloproteinase activity, carboxypropeptide type II collagen, and collagen-cleavage neoepitope of type II collagen) was assessed across serial synovial fluid samples. Liraglutide was found to have an anti-inflammatory effect by reducing CCL2 concentrations in culture media of whole blood, PBMCs, chondrocytes, and synoviocytes. In contrast, no significant differences in synovial fluid inflammatory nor cartilage metabolism biomarker levels were found between joints treated with LPS and 6 mg liraglutide, versus LPS and placebo. In conclusion, liraglutide demonstrates the potential to attenuate inflammatory processes in joint cells. Additional research is necessary to validate its efficacy within the complex milieu of an inflamed joint.

Analysis of the Effect of Ct Angiography Combined with Three Tests, Mmp-9 and Paf, On the Assessment of Postoperative Vascular Stenosis in Acute Coronary Syndrome

Background: Acute Coronary Syndrome (ACS) is a very common cardiovascular disease in clinical practice with a very high risk of death. In this study, we observed the effectiveness of CT angiography (CTA), Matrix metalloproteinase-9 (MMP-9) amd Platelet activating factor (PAF) in the assessment of ACS. Materials and Methods: A total of 124 patients with ACS admitted to our hospital from June 2022 to March 2024 were enrolled as study subjects. All study subjects were examined by Coronary angiography (CAG) and CTA. To compare the detection rate of ACS by CAG and CTA, and the difference in effectiveness in assessing coronary plaque stenosis and plaque calcification. In addition, the levels of MMP-9 and PAF were detected in the patients to analyze their relationship with the degree of stenosis and plaque grade.Subsequently, the effect of the three combined tests, CTA, MMP-9 and PAF, was analyzed for the assessment of postoperative vessel restenosis. Finally, we analyzed the factors associated with poor CTA image quality. Results: There was no difference in the effectiveness of CTA in detecting ACS, assessing coronary plaque stenosis and plaque calcification compared with CAG (P&gt;0.05). There was a positive correlation between MMP-9, PAF and the degree of coronary stenosis and plaque severity (P&lt;0.05).The diagnostic accuracy of the combination of CTA, MMP-9, and PAF in the diagnosis of stenosis in postoperative ACS was 97.58% (Kappa=0.946). It was determined that 124 patients 21 patients had poor CTA images, and logistic regression analysis showed that shorter breath-hold time and arrhythmia were independent risk factors for poor CTA image quality. Conclusions: CTA, MMP-9 and PAF are excellent for the diagnosis of stenosis after ACS and shorter breath-hold time and arrhythmia are all independent risk factors for poor CTA image quality.

Uncovering the Impact of MMP-9 and TIMPs in Diabetic Nephropathy: A Review on Bioflavonoids in Disease Management

This article provides a thorough analysis of the complex roles played by tissue inhibitors of metalloproteinases (TIMPs) and matrix metalloproteinase-9 (MMP-9) in the development and progression of diabetic nephropathy (DN). Diabetic nephropathy, a notable complication of diabetes, is characterized by a progressive decline in kidney function, prompting a thorough examination of its fundamental molecular pathways. This article pre-sents a comprehensive overview of the function played by MMP-9, a key enzyme in the re-modeling of extracellular matrix, in developing tubulointerstitial and glomerular fibrosis, which are critical aspects of renal dysfunction in DN. Simultaneously, the review delves into the regulatory functions of TIMPs, emphasizing their crucial role in maintaining the delicate balance between matrix degradation and repair. The abnormal regulation of the MMP-9/TIMP axis is explored as a pivotal factor contributing to increased vascular permeability, inflammation, and structural alterations within the renal microenvironment. By synthesizing current research findings, the purpose of this review was to unravel the complex molecular interplay between MMP-9 and TIMPs in diabetic nephropathy. The insights derived from this comprehensive analysis hold promise for identifying potential therapeutic targets that could mitigate renal damage, arrest disease progression, and enhance clinical outcomes for individuals grappling with diabetic nephropathy. Finally, it concludes by emphasizing the necessity for additional research to validate these findings and facilitate the translation of this knowledge into targeted therapeutic interventions for improved management of diabetic nephropathy.

Idiopathic Pulmonary Fibrosis: In Silico Therapeutic Potential of Doxycycline, Pirfenidone, and Nintedanib, and the Role of Next-Generation Phenomics in Drug Discovery.

Innovation in drug discovery for human diseases stands to benefit from systems science and next-generation phenomics approaches. An example is idiopathic pulmonary fibrosis (IPF) that is a chronic pulmonary disorder leading to respiratory failure and for which preventive and therapeutic medicines are sorely needed. Matrix metalloproteinases (MMPs), particularly MMP1 and MMP7, have been associated with IPF pathogenesis and are thus relevant to IPF drug discovery. This study evaluates the comparative therapeutic potentials of doxycycline, pirfenidone, and nintedanib in relation to MMP1 and MMP7 using molecular docking, molecular dynamics simulations, and a next-generation phenomics approach. Adsorption, distribution, metabolism, excretion, and toxicity analysis revealed that doxycycline and nintedanib adhered to Lipinski's rule of five, while pirfenidone exhibited no violations. The toxicity analysis revealed favorable safety profiles, with lethal dose 50 values of doxycycline, pirfenidone, and nintedanib being 2240kg, 580, and 500 mg/kg, respectively. Homology modeling validated the accuracy of the structures of the target proteins, that is, MMP1 and MMP7. The Protein Contacts Atlas tool, a next-generation phenomics platform that broadens the scope of phenomics research, was employed to visualize protein contacts at atomic levels, revealing interaction surfaces in MMP1 and MMP7. Docking studies revealed that nintedanib exhibited superior binding affinities with the candidate proteins (-6.9 kcal/mol for MMP1 and -7.9 kcal/mol for MMP7) compared with doxycycline and pirfenidone. Molecular dynamics simulations further demonstrated the stability of protein-ligand complexes. These findings highlight the notable potential of nintedanib in relation to future IPF therapeutics innovation. By integrating in silico and a next-generation phenomics approach, this study opens up new avenues for drug discovery and development for IPF and possibly, for precision/personalized medicines that consider the molecular signatures of therapeutic candidates for each patient.

Pharmacodynamic characteristics of curcumin

Curcumin, an active ingredient derived from turmeric root (Curcuma longa), has significant pharmacological properties including anti-inflammatory, antioxidant, antimicrobial, anticancer and analgesic activities. Studies show that curcumin affects the expression of various microRNAs and long non-coding RNAs to regulate cell proliferation and apoptosis in various types of malignant tumours. In addition, curcumin modulates signalling pathways such as PI3K/Akt/mTOR, MAPK/ERK and AMPK, activating autophagy and inhibiting tumour angiogenesis. It also inhibits metastasis and invasion of tumour cells by affecting epithelial-mesenchymal transition and expression of matrix metalloproteinases. Curcumin exhibits antibacterial and antiviral activity by disrupting bacterial cell membranes and inhibiting viral replication. The antioxidant properties of curcumin are due to its ability to neutralise reactive oxygen species and stimulate antioxidant enzymes. Curcumin also promotes wound healing by modulating inflammatory processes and stimulating angiogenesis. The analgesic effect of curcumin is due to its ability to stimulate the release of endogenous opioid peptides and modulate the activity of GABA receptors and ASIC and TRPV ion channels. Curcumin has an effect on lipid and carbohydrate metabolism, which makes it a promising agent for the treatment of dyslipidaemia and insulin resistance. The effect of curcumin on haemostasis is manifested in its ability to inhibit platelet aggregation and blood clotting, which may be useful for the prevention of cardiovascular diseases.

The Antiglioma Potential of Plant Lectins: Molecular Targets, Mechanisms, and Future Directions

Gliomas, ranging from low-grade pilocytic astrocytomas to highly malignant glioblastomas, are primary brain tumors that originate from neural or glial stem cells. Classified by the WHO into grades 1 to 4, these tumors exhibit varying prognoses, with oligodendrogliomas and astrocytomas having better and intermediate outcomes, respectively, while glioblastomas are associated with a poor prognosis. Despite advancements in molecular and genetic research that have improved diagnosis and the development of targeted therapies, treating high-grade gliomas remains a significant challenge due to their diffuse nature. In this context, lectins, carbohydrate-binding proteins, have shown promise as diagnostic and therapeutic agents for cancer, including gliomas. Plant lectins, particularly those from legumes, exhibit significant antiproliferative effects on glioma cells. These effects include decreased cell viability and migration, alongside the induction of autophagy and apoptosis, suggesting their potential as therapeutic agents. Although the mechanisms underlying these effects are not yet fully understood, molecular targets and pathways involved in the antiglioma activity of lectins have been identified. Key targets include matrix metalloproteinases (MMPs), epidermal growth factor receptor (EGFR), CD98 (xc- system), AMPA receptor, and CD73. This review focuses on the antiglioma potential of legume lectins, their applications, and the main molecular targets based on their functions, structures, and associated molecular mechanisms.

Prognostic Value of Combined Detection of MMP-7 and ALP Levels in Children With Biliary Atresia Post-Kasai Surgery.

Biliary atresia (BA) remains a prevalent indication for pediatric liver transplantation (LT). We investigated the prognostic value of the serum matrix metalloproteinases 7 (MMP-7) and alkaline phosphatase (ALP) level combined detection for BA children post-Kasai surgery. This study retrospectively enrolled 85 BA children who underwent Kasai surgery. They were divided into the native liver (NL) and LT groups based on their three-year postoperative prognosis. Serum MMP-7 and ALP levels were measured by ELISA. The relationship of intraoperative serum MMP-7 and ALP levels with preoperative gamma-glutamyltransferase (GGT), and their impact on the risk of postoperative LT were analyzed by Pearson's correlation coefficient and Kaplan-Meier curves. The independent risk factors (IRFs) for postoperative LT and the predictive value of the serum MMP-7 and ALP level combined detection for postoperative LT in BA children were analyzed by Cox regression analysis and receiver operating characteristic (ROC) curves. MedCalc software compared the areas under the ROC curves (AUC). Significant differences were observed between the two groups in BA classification, postoperative jaundice clearance rate, and cholangitis occurrence. Intraoperative serum MMP-7 and ALP levels were higher in the LT group and positively correlated with preoperative GGT. High MMP-7 and ALP levels were IRFs for postoperative LT, while significant jaundice clearance was a protective factor. Combined MMP-7 and ALP detection (0.926 AUC, 91.30% sensitivity, 87.18% specificity) significantly improved the prediction for LT. High MMP-7 and ALP levels are IRFs for post-Kasai surgery LT in BA children, with their combination providing superior predictive value.

MMP13 as an effective target of an active trifluoromethyl quinazoline compound against osteosarcoma.

Osteosarcoma (OS) is a highly fatal malignant tumor with a high metastatic rate and poor prognosis. Matrix metalloproteinase-13 (MMP13) is involved in OS metastasis. Its increased expression is closely related to distant metastasis and poor prognosis. The trifluoromethyl quinazoline compound KZL-201 was designed and synthesized, and its inhibitory effect on the progression of OS cells was investigated. The aim of this study was to investigate the underlying mechanism of action of KZL-201 in OS using a combination of bioinformatics analysis, molecular biology, cytology, and zoology. The in vitro experiments showed that KZL-201 inhibited OS cell proliferation, invasion, and migration; KZL-201 induced apoptosis and arrested the cell cycle at the G2/M phase. The results of molecular docking, the cellular thermal shift assay, and gene silencing experiments showed that KZL-201 had a strong affinity for MMP13. KZL-201 inhibited the progression of 143B cells by regulating the TGF-β1/Smad2/3 pathway. Thus, MMP13 is an important target gene of KZL-201 in inhibiting 143B cell progression. The in vivo experiments showed that KZL-201 inhibited the growth of OS tissues and the expression of MMP13 in OS tissues. In summary, KZL-201 targeted MMP13 and inhibited its expression, consequently suppressing the progression of OS by regulating the TGF-β1/Smad2/3 pathway.

Myricetin Modulates Matrix Metalloproteinases Expression Induced by TEGDMA in Human Odontoblast-Like Cells.

The activity of matrix metalloproteinases (MMPs) plays a crucial role in the aging of the resin-dentin interface. The insitu action of MMP-2 and MMP-9 has been confirmed in the process of dentin-collagen degradation. However, the involvement of dental pulp cells in MMP secretion as a response to oxidative stress induced by contact with resin monomers has not been fully elucidated. Myricetin (MYR), like proanthocyanidin (PAC), has antioxidant properties and may help prevent extracellular matrix degradation. The objective was to evaluate the effect of MYR on the MMP expression and activity in response to reactive oxygen species (ROS) increase induced by triethylene glycol dimethacrylate (TEGDMA) in human odontoblast-like cells (hOLCs). hOLCs differentiated from dental pulp mesenchymal stem cells were exposed to TEGDMA released from dentin blocks using a barrier model with transwell inserts for 18, 24, and 36 h. Intracellular oxidation was evaluated using the 2',7'-dichlorofluorescein probe. The effect of 600 μM MYR on the MMP-2 and MMP-9 expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The extracellular MMP levels were quantified using enzyme-linked immunosorbent assay, and their activation by means of a proteolytic fluorometric assay. The results were analyzed by one-way analysis of variance and Tukey's post hoc test, p ≤ 0.05. TEGDMA exposure increased intracellular ROS and upregulated MMP-2 and MMP-9 mRNA in hOLCs (p < 0.001). The levels of MMPs increased significantly 24 h after TEGDMA exposure (p = 0.013). These secreted proteases exhibited high activation ability. MYR reduced ROS production and downregulated MMP expression and activity at both mRNA and protein levels, similar to the effect found for PAC, which was used as a control. A relationship was observed between MMP-2 and MMP-9 expression, secretion, and early activation with ROS increase due to TEGDMA exposure. MYR showed potential as a therapeutic strategy to control MMP expression and modulate redox imbalance, offering a protective effect on cellular response.

P75NTR antagonist THX-B increases mature nerve growth factor secretion by bladder cells through decreased activity of matrix metalloproteinase-9.

In urine samples from an aging female cohort with overactive bladder syndrome (OAB), the proteolytic activity of matrix metalloproteinase-9 (MMP-9), an enzyme which degrades mature NGF, was elevated and associated with low levels of nerve growth factor (NGF). Given that a substantial portion of urine constituents originate from bladder cellular processes, we examined the synthesis of NGF and MMP-9 in rat urothelial (UROs) and smooth muscle (SMCs) cells in culture. NGF and proNGF were found expressed and released by both cell types while UROs were the major source of secreted MMP-9. THX-B, a highly specific p75NTR antagonist, decreased the expression of MMP-9 resulting in increased mature NGF levels in culture medium of UROs while displaying minor effects on SMCs. Likewise, CRISPR-cas9 genomic deletion of MMP-9 potently increased mature NGF levels in both cell types. On the other hand, THX-B decreased the synthesis and release of α2 Macroglobulin (α2M), a protein that stabilizes proNGF in UROs but increased it in SMCs. THX-B also increased the activity of enzymes furin and matrix metalloproteinase-7 (MMP-7), that convert proNGF to mature NGF in UROs, yielding a net increase in mature NGF and a decrease of proNGF. We conclude that p75NTR is involved in the control of proNGF and mature NGF secretion from bladder cells through modulation of proteolytic activities. Since neurotrophins and binding to their receptors are relevant to pathologies, inhibition of p75NTR by THX-B may be exploited in a therapeutic strategy.