Matrix Metalloproteinase-9 Expression Research Articles

The Anti-Inflammatory Effect of Nigella sativa Toothpaste on Porphyromonas gingivalis Bacteria Through Decreased TNF-α, MMP-9, PGE-2 Expression in Wistar Rats.

The main principle in preventing periodontal disease is to improve oral hygiene. The bacteria that cause the onset of periodontal disease, one of which is the Porphyromonas gingivalis bacterium, causes inflammation. Persistent inflammation causes tissue damage and alveolar bone resorption by secreting proinflammatory cytokines, matrix metalloproteinase-9 (MMP-9), prostaglandin E2 (PGE-2), and anti-inflammatory cytokines. In this case, preventive treatment is needed, such as using toothpaste that contains anti-inflammatories so that the progression of the disease does not get worse. The traditional ingredient currently being developed is Nigella sativa, which has anti-inflammatory properties. Therefore, this study analyzes the potential of toothpaste containing Nigella sativa on the expression of tumor necrosis factor-α (TNF-α), MMP-9, and PGE-2 in the Wistar rat model induced by Porphyromonas gingivalis bacteria. This study aims to prove the potential of Nigella sativa toothpaste to decrease the expression of PGE-2, TNF-α, and MMP-9 in the gingiva of rats induced by Porphyromonas gingivalis bacteria. Forty-five healthy male Wistar rats were used, consisting of the negative control group, which was only injected with Porphyromonas gingivalis bacteria ATCC3322. The positive control group was given enzyme toothpaste, and the treatment group was assigned 1 mg of Nigella sativa paste using a microbrush for 30 seconds on the gingiva incisors mandibular with a circular motion, given two times a day for a week. Immunohistochemical to see the expression of TNF-α, PGE-2, and MMP-9. Parametric comparative analysis using a one-way analysis of variance test was performed to analyze differences between groups. Nigella sativa toothpaste significantly reduced proinflammatory cytokines, as seen through the expression of TNF-α, PGE-2, and MMP-9 on days 3, 5, and 7 (p <0.05). In the limit of studied animal model, this trial indicates that giving toothpaste with black seed extract (Nigella sativa) could inhibit inflammatory mediators, as seen from the decreased expression of MMP-9, TNF-α, and PGE-2 seen from the 3rd, 5th, and 7th days.

Unraveling the Mechanisms Involved in the Beneficial Effects of Magnesium Treatment on Skin Wound Healing.

The skin wound healing process consists of hemostatic, inflammatory, proliferative, and maturation phases, with a complex cellular response by multiple cell types in the epidermis, dermis, and immune system. Magnesium is a mineral essential for life, and although magnesium treatment promotes cutaneous wound healing, the molecular mechanism and timing of action of the healing process are unknown. This study, using human epidermal-derived HaCaT cells and human normal epidermal keratinocyte cells, was performed to investigate the mechanism involved in the effect of magnesium on wound healing. The expression levels of epidermal differentiation-promoting factors were reduced by MgCl2, suggesting an inhibitory effect on epidermal differentiation in the remodeling stage of the late wound healing process. On the other hand, MgCl2 treatment increased the expression of matrix metalloproteinase-7 (MMP7), a cell migration-promoting factor, and enhanced cell migration via the MEK/ERK pathway activation. The enhancement of cell migration by MgCl2 was inhibited by MMP7 knockdown, suggesting that MgCl2 enhances cell migration which is mediated by increased MMP7 expression. Our results revealed that MgCl2 inhibits epidermal differentiation but promotes cell migration, suggesting that applying magnesium to the early wound healing process could be beneficial.

Expression of matrix metalloproteinase-9 (MMP-9) in human skin within 1 hour after injury through immunohistochemical staining: a pilot study.

Matrix metalloproteinase-9 (MMP-9) is involved in tissue remodeling and in skin wound healing. The present study focuses on the MMP-9 expression in epidermal wound healing within 1h after injury, to test whether MMP-9 can be used to estimate the time of injury in forensic practice.A sample consisting of 5 individuals undergoing surgery was analyzed. With the consent of the patients, sections of skin were removed from the surgical wound at predefined time intervals. For each subject, 8 sections were taken, one for each time interval defined at 0 '- 1' - 3 '- 5' - 10 '- 15' - 30 '- 60' minutes. The specimens were immunostained with MMP-9, and the number of positively stained cells was examined.The number of positively stained cells showed an increasing trend as a function of time. Less than 30 positively stained cells were found in all cases within 3min. At the post-infliction time of 5min, the number of positively stained cells exceeded 30 in 3 out of 5 cases. The number of MMP-positive cells exceeded 40 in all cases in over 10min.In the light of these results, the count of MMP-9 positive cells might be a useful marker in the wound-age estimation within 1h in forensic setting. More research is required to collect more samples and to compare samples from the hyperacute phase with those from several days after injury.

Characterization of Angiogenic, Matrix Remodeling, and Antimicrobial Factors in Preterm and Full-Term Human Umbilical Cords

Background: Little is known about morphogenetic changes in the umbilical cord during the maturation process. Extracellular matrix remodeling, angiogenesis, progenitor activity, and immunomodulation are represented by specific markers; therefore, the aim of this study was to determine the expression of matrix metalloproteinase-2 (MMP2), tissue inhibitor of metalloproteinases-2 (TIMP2), CD34, vascular endothelial growth factor (VEGF), and human β-defensin 2 (HBD2) in preterm and full-term human umbilical cord tissue. Methods: Samples of umbilical cord tissue were obtained from 17 patients and divided into two groups: very preterm and moderate preterm birth umbilical cords; late preterm birth and full-term birth umbilical cords. Routine histology examination was conducted. Marker-positive cells were detected using the immunohistochemistry method. The number of positive structures was counted semi-quantitatively using microscopy. Statistical analysis was carried out using the SPSS Statistics 29 program. Results: Extraembryonic mesenchyme cells are the most active cell producers, expressing MMP2, TIMP2, VEGF, and HBD2 at notable levels in preterm and full-term umbilical cord tissue. Statistically significant differences in the expression of CD34, MMP2, and TIMP2 between the two patient groups were found. The expression of VEGF was similar in both patient groups, with the highest number of VEGF-positive cells seen in the extraembryonic mesenchyme. The expression of HBD2 was the highest in the extraembryonic mesenchyme and the amniotic epithelium, where mostly moderate numbers of HBD2-positive cells were detected. Conclusions: Extracellular matrix remodeling in preterm and term umbilical cords is strongly regulated, and tissue factors MMP2 and TIMP2 take part in this process. The expression of VEGF is not affected by the umbilical cord’s age; however, individual patient factors can affect the production of VEGF. Numerous CD34-positive cells in the endothelium of the umbilical arteries suggest a significant role of progenitor cells in very preterm and moderate preterm birth umbilical cords. Antimicrobial activity provided by HBD2 is essential and constant in preterm and full-term umbilical cords.

Modulating Synovial Macrophage Pyroptosis and Mitophagy Interactions to Mitigate Osteoarthritis Progression using Functionalized Nanoparticles

Synovial macrophages play an important role in the progression of osteoarthritis (OA). In this study, we noted that synovial macrophages can activate pyroptosis in a gasdermin D-dependent manner and produce reactive oxygen species (ROS), aberrantly activating the mammalian target of rapamycin complex 1 (mTORC1) pathway and matrix metalloproteinase-9 (MMP9) expression in synovial tissue samples collected from both patients with OA and collagen-induced osteoarthritis (CIOA) mouse model. To overcome this, we constructed rapamycin- (RAPA, a mTORC1 inhibitor) loaded mesoporous Prussian blue nanoparticles (MPB NPs, for catalyzing ROS) and modified the NPs with MMP9-targeted peptides (favor macrophage targeting) to develop RAPA@MPB-MMP9 NPs. The inherent enzyme-like activity and RAPA released from RAPA@MPB-MMP9 NPs synergistically impeded the pyroptosis of macrophages and the activation of the mTORC1 pathway. In particular, the NPs decreased pyroptosis-mediated ROS generation, thereby inhibiting cGAS–STING signaling pathway activation caused by the release of mitochondrial DNA. Moreover, the NPs promoted macrophage mitophagy to restore mitochondrial stability, alleviate pyroptosis-related inflammatory responses, and decrease senescent synoviocytes. After the as-prepared NPs were intra-articularly injected into the CIOA mouse model, they efficiently attenuated synovial macrophage pyroptosis and cartilage degradation. In conclusion, our study findings provide a novel therapeutic strategy for OA that modulates the pyroptosis and mitophagy of synovial macrophage by utilizing functionalized NPs. Statement of SignificanceOsteoarthritis (OA) presents a significant global challenge owing to its complex pathogenesis and finite treatment options. Synovial macrophages have emerged as key players in the progression of OA, managing inflammation and tissue destruction. In this study, we discovered a novel therapeutic strategy in which the pyroptosis and mitophagy of synovial macrophages are targeted to mitigate OA pathology. For this, we designed and prepared rapamycin-loaded mesoporous Prussian blue nanoparticles (RAPA@MPB-MMP9 NPs) to specifically target synovial macrophages and modulate their inflammatory responses. These NPs could efficiently suppress macrophage pyroptosis, diminish reactive oxygen species production, and promote mitophagy, thereby alleviating inflammation and protecting cartilage integrity. Our study findings not only clarify the intricate mechanisms underlying OA pathogenesis but also present a promising therapeutic approach for effectively managing OA by targeting dysregulation in synovial macrophages.

Effect of Resveratrol on MMP-2 Expression in Scleral Fibroblasts: An In Vitro Study.

To investigate the effects of resveratrol (Res) on human fetal scleral fibroblasts (HFSFs) and its potential mechanism. HFSFs were randomly divided into the Res-treated group and the control group. Following, HFSFs were treated with or without a concentration of 10 μM Res for 48 h. To detect the expression of related genes, reverse transcription quantitative PCR (RT-qPCR) and western blotting were used. The apoptosis rate of different groups was determined using flow cytometry. The mRNA expression of matrix metalloproteinase 2 (MMP-2), Collagen, Type I, Alpha 1 (COL1A1), Janus Kinase 2 (JAK2), and Signal Transducer and Activator of Transcription 3 (STAT3)" was downregulated in the Res-treatment group compared to the control group, according to RT-qPCR. Western blotting revealed that Res therapy reduced the expression of MMP-2, JAK2, P-JAK2, STAT3, P-STAT3, and Bcl-2 associated protein X (Bax) while increasing the expression of COL1A1 and B-cell lymphoma-2 (Bcl-2). Flow cytometry showed that the cell apoptosis rate was significantly lower in HFSFs treated with Res. In conclusion, these findings suggest that Res increases COL1A1 expression while inhibiting MMP-2 and cell apoptosis in HFSFs, possibly through modulation of the JAK2/STAT3 signaling pathway.

Association of Matrix Metalloproteinase-9 Genotypes With Lung Cancer Risk in Taiwan.

Matrix metalloproteinase-9 (MMP-9) expression is upregulated in various diseases, including lung cancer. However, the role of MMP-9 genotype in lung cancer susceptibility remains uncertain. This study aimed to clarify the contribution of MMP-9 promoter rs3918242 genotypes to the risk of lung cancer in Taiwan. The MMP-9 rs3918242 genotypes of 358 lung cancer patients and 716 healthy controls were determined using polymerase chain reaction-restriction fragment length polymorphism methodology. Individuals carrying the variant CT or TT genotype of MMP-9 rs3918242 did not demonstrate an increased risk of lung cancer compared to wild-type CC carriers [odds ratio (OR)=1.11 and 1.85, 95% confidence interval (95%CI)=0.82-1.48 and 0.91-3.76; p=0.5541 and 0.1280, respectively]. Moreover, individuals carrying the T allele did not show a higher lung cancer risk compared to those with the C allele (OR=1.21, 95%CI=0.95-1.54, p=0.1444). However, a significant association was observed between the MMP-9 rs3918242 TT genotype and lung cancer risk among non-smokers (OR=5.48, 95%CI=1.31-22.89, p=0.0181). The presence of the TT genotype for MMP-9 rs3918242 may indicate an elevated risk of lung cancer among non-smokers.

PLD2 deficiency alleviates endothelial glycocalyx degradation in LPS-induced ARDS/ALI

- Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a life-threatening condition marked by severe lung inflammation and increased lung endothelial barrier permeability. Endothelial glycocalyx deterioration is the primary factor of vascular permeability changes in ARDS/ALI. Although previous studies have shown that phospholipase D2 (PLD2) is closely related to the onset and progression of ARDS/ALI, its role and mechanism in the damage of endothelial cell glycocalyx remains unclear. We used LPS-induced ARDS/ALI mice (in vivo) and LPS-stimulated injury models of EA.hy926 endothelial cells (in vitro). We employed C57BL/6 mice, including wild-type and PLD2 knockout (PLD2−/−) mice, to establish the ARDS/ALI model. We applied immunofluorescence and ELISA to examine changes in syndecan-1 (SDC-1), matrix metalloproteinase-9 (MMP9), inflammatory cytokines (TNF-α, IL-6, and IL-1β) levels and the effect of external factors, such as phosphatidic acid (PA), 1-butanol (a PLD inhibitor), on SDC-1 and MMP9 expression levels. We found that PLD2 deficiency inhibits SDC-1 degradation and MMP9 expression in LPS-induced ARDS/ALI. Externally added PA decreases SDC-1 levels and increases MMP9 in endothelial cells, hence underlining PA's role in SDC-1 degradation. Additionally, PLD2 deficiency decreases the production of inflammatory cytokines (TNF-α, IL-6, and IL-1β) in LPS-induced ARDS/ALI. In summary, these findings suggest that PLD2 deficiency plays a role in inhibiting the inflammatory process and protecting against endothelial glycocalyx injury in LPS-induced ARDS/ALI.

Acceleration of Wound Healing in Diabetic Rats through a Novel 3D Organo-Hydrogel Nanocomposite of Polydopamine/TiO2 Nanoparticles and Cu (PDA-TiO2@Cu).

Diabetic wound represents a serious issue with a substantial impact and an exceptionally complex pathology affecting patients' mental health and quality of life. So, we have developed a novel 3D organo-hydrogel nanocomposite of polydopamine/TiO2 nanoparticles and cu (PDA-TiO2@Cu) and examined its efficacy in diabetic wound healing. Forty-five adult male albino rats were divided into normal control rats (non-diabetic rats with non-treated skin wounds), diabetic control rats (diabetic rats with non-treated skin wounds), and organo-hydrogel-treated rats (diabetic wounds treated with topically applied organo- hydrogel once daily). Macroscopic changes of the wound were observed on days 0, 3, 5, 7, and 10 to measure wound diameters. Skin specimens from the wound tissue were taken on days 3, 7, and 10, respectively, and examined histologically and immunohistochemically. Also, the gene expressions of collagen I, Matrix Metalloproteinase-9 (MMP-9), and Epidermal Growth Factor (EGF), and levels of Interleukin 6 (IL-6) and Superoxide Dismutase (SOD) were assessed. Our observed results indicated that the developed patch significantly accelerated the healing time compared to the normal control and diabetic control groups. Moreover, the patchloaded group revealed complete re-epithelization and a highly significant increase in the mean area % of CD31 immunostaining on day 7. The organo-hydrogel-loaded group displayed a significant decrease in gene expression of MMP-9 and a significant increase in gene expression of EGF and collagen I. Additionally, the organo-hydrogel-loaded group exhibited a significant decrease in levels of IL-6 and a significant increase in levels of SOD, compared to the normal diabetic control groups. The organo-hydrogel can be used for treating and decreasing the healing period of diabetic wounds.

Relationship of FDG PET/CT imaging features with tumor immune microenvironment and prognosis in colorectal cancer: a retrospective study

BackgroundImaging features of colorectal cancers on 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) have been considered to be affected by tumor characteristics and tumor immune microenvironment. However, the relationship between PET/CT imaging features and immune reactions in tumor tissue has not yet been fully evaluated. This study investigated the association of FDG PET/CT imaging features in the tumor, bone marrow, and spleen with immunohistochemical results of cancer tissue and recurrence-free survival (RFS) in patients with colorectal cancer.MethodsA total of 119 patients with colorectal cancer who underwent FDG PET/CT for staging work-up and received curative surgical resection were retrospectively enrolled. From PET/CT images, 10 first-order imaging features of primary tumors, including intensity of FDG uptake, volumetric metabolic parameters, and metabolic heterogeneity parameters, as well as FDG uptake in the bone marrow and spleen were measured. The degrees of CD4+, CD8+, and CD163 + cell infiltration and interleukin-6 (IL-6) and matrix metalloproteinase-11 (MMP-11) expression were graded through immunohistochemical analysis of surgical specimens. The relationship between FDG PET/CT imaging features and immunohistochemical results was assessed, and prognostic significance of PET/CT imaging features in predicting RFS was evaluated.ResultsCorrelation analysis with immunohistochemistry findings showed that the degrees of CD4 + and CD163 + cell infiltration and IL-6 and MMP-11 expression were correlated with cancer imaging features on PET/CT. Patients with enhanced inflammatory response in cancer tissue demonstrated increased FDG uptake, volumetric metabolic parameters, and metabolic heterogeneity. FDG uptake in the bone marrow and spleen was positively correlated with the degree of CD163 + cell infiltration and IL-6 expression, respectively. In multivariate survival analysis, the coefficient of variation of FDG uptake in the tumor (p = 0.019; hazard ratio, 0.484 for 0.10 increase) and spleen-to-liver uptake ratio (p = 0.020; hazard ratio, 24.901 for 1.0 increase) were significant independent predictors of RFS.ConclusionsThe metabolic heterogeneity of tumors and FDG uptake in the spleen were correlated with tumor immune microenvironment and showed prognostic significance in predicting RFS in patients with colorectal cancer.

The Long Noncoding RNA Gall Bladder Cancer-Associated Suppressor of Pyruvate Carboxylase Inhibits the Proliferation, Migration, and Invasion of Colorectal Cancer Cells and Induces Their Apoptosis.

This study aimed to determine the role of the long noncoding RNA (lncRNA) gall bladder cancer-associated suppressor of pyruvate carboxylase (SOD2-1) in the progression of colorectal cancer (CRC). A total of 23 pairs of specimens, including CRC tissues and adjacent normal tissues, were collected, and the expression of lncRNA SOD2-1 (lnc-SOD2-1) was measured. lnc-SOD2-1 function was examined using HCT15 and HCT116 cells. A lnc-SOD2-1 overexpression vector was designed and transfected into both cell lines. MTS and colony formation assays were used to determine cell viability. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assays were performed to measure apoptosis. Cell migration and invasion were evaluated using the Transwell assay. Migration and invasion markers were validated using quantitative reverse transcription-polymerase chain reaction and western blot analysis. The results indicated that the expression of lnc-SOD2-1 was downregulated in CRC tissues. lnc-SOD2-1 overexpression evidently decreased cell viability and led to the formation of fewer cell colonies. lnc-SOD2-1 overexpression induced ~ twofold higher apoptosis than the control group. lnc-SOD2-1 overexpression reduced the proportion of migratory and invasive cells to 50% and 75% of the control group, respectively. lnc-SOD2-1 overexpression significantly decreased the expression of matrix metalloproteinase-2 and -9. In conclusion, lnc-SOD2-1 may act as a tumor suppressor that inhibits the proliferation, migration, and invasion of CRC cells and induces their apoptosis.

Correlation Between HIF1-A Expression and Airway Remodeling in COPD.

Airway remodeling is a significant pathological characteristic of chronic obstructive pulmonary disease (COPD). In recent years, hypoxia-inducible factor 1-α (HIF-1α), a member of the hypoxia-inducible factor protein family, has gained attention. However, the potential correlation between HIF-1α and COPD airway remodeling remains unclear. This study explored the expression patterns of HIF-1α in patients with COPD and its association with airway remodelling. This investigation aims to furnish novel insights for the clinical identification of prospective therapeutic targets for ameliorating COPD-related airway remodelling. A total of 88 subjects were included, consisting of 28 controls and 60 COPD patients. Various staining methods were employed to observe the pathological changes in airway tissues. Immunohistochemistry was utilized to detect the expression of HIF-1α and MMP9 (matrix metalloproteinase 9) in airway tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration in serum of HIF-1α and MMP9. Computed tomography (CT) airway parameters were measured in all participants to assess airway remodeling. The relationship between serum HIF-1α and MMP9 concentrations and airway parameters was analyzed. Staining of airway structures in COPD patients revealed significant pathological changes associated with airway remodelling, including mixed cilia and subepithelial fibrosis. The expression of HIF-1α and MMP9 was significantly higher in both human airway tissue and serum compared to controls. Chest CT scans exhibited typical imaging features of airway remodeling and increased airway parameters. The findings suggest a correlation between increased HIF-1α expression and COPD airway remodelling. This study provides novel evidence that HIF-1α may be a potential biomarker for airway remodelling in COPD patients.

Treatment of cholangiocarcinoma by pGCsiRNA-vascular endothelial growth factor in vivo.

The early diagnosis and treatment of cholangiocarcinoma may benefit from specific tumor markers to be used in clinical practice. To investigate whether the pGCsiRNA-vascular endothelial growth factor (VEGF) can affect the onset and progression of cholangiocarcinoma and its possible mechanism using the targeted therapy of nude mouse model of cholangiocarcinoma with attenuated Salmonella carrying the plasmid pGCsiRNA-VEGF. The nude mouse model of cholangiocarcinoma was established by tail vein injection of QBC939 cells and given attenuated Salmonella carrying the plasmid pGCsiRNA-VEGF. One month later, the tumor volume of nude mice was observed, and the tumor growth curve was plotted. The harvested tumors were weighed and detected for tissue structural changes and cell death status by hematoxylin-eosin staining. The protein and mRNA expressions of VEGF, matrix metalloproteinase 2 (MMP2), and MMP9 were detected by Western blotting and PCR, respectively. The tumor volume and weight of the pGCsiRNA-VEGF group were significantly smaller than those of the mock and the si-scramble groups (P < 0.05). The expressions of VEGF, MMP2, and MMP9 at the transcriptional and translational levels were inhibited by pGCsiRNA-VEGF. PGCsiRNA-VEGF promoted tissue apoptosis and destroyed the tissue structure. In vivo silencing of VEGF can affect cell survival and inhibit cell migration, invasion, and development, probably by enhancing apoptosis and inhibiting the expressions of MMP2 and MMP9.

Expression of matrix metalloproteinases-2, -9, -13 and -14 in canine mammary carcinoma

Expression of matrix metalloproteinases-2, -9, -13 and -14 in canine mammary carcinoma

Loranthus tanakae Franch. and Sav. Attenuates Respiratory Inflammation Caused by Asian Sand Dust.

Asian sand dust (ASD), generally produced in East Asia, including China, Japan, and Korea, directly leads to the development of pulmonary disease and exacerbates underlying pulmonary diseases. Loranthus tanakae Franch. and Sav. is a traditional herbal medicine applied to improve various inflammatory conditions. Here, we evaluated the curative properties of L. tanakae ethanol extract (LTE) against pulmonary inflammation caused by ASD. Additionally, to investigate the mechanism of action of LTE, we performed network pharmacological analysis. ASD was administrated on day 1, 3, and 5 by intranasal instillation, and LTE was orally administered for 6 days. Administration of LTE significantly decreased inflammatory cytokines and the number of inflammatory cells in bronchoalveolar lavage fluid, which was accompanied by a decrease in inflammatory cell accumulation in pulmonary tissue. Administration of LTE decreased the expression of cyclooxygenase2 and matrix metalloproteinase-9 in mice exposed to ASD with the decline in p65 phosphorylation. Additionally, administration of LTE significantly elevated hemeoxygenase (HO)-1 expression in the pulmonary tissue of mice exposed to ASD. These results were consistent with the data of network pharmacological analysis. This experiment showed that LTE attenuated pulmonary inflammation caused by ASD via inhibition of NF-κB and elevation of HO-1. Therefore, LTE may have potential as a therapeutic agent to treat pulmonary inflammation caused by ASD.

Increased matrix metalloproteinase-2 in ligamentum flavum hypertrophy and the regulation of MMP-2/TIMPs by elastin-derived peptides.

The study aimed to examine matrix metalloproteinase-2 (MMP-2) expression in a rat ligamentum flavum (LF) hypertrophy model in vivo, and the effect of elastin-derived peptides (EDPs) on MMP-2 and tissue inhibitors of metalloproteinases (TIMPs) in rat LF cells in vitro. Surgical destabilization was performed at the rat spinal L3/4 level to induce increased mechanical stress. Rats were killed at 6- and 12-weeks postsurgery for histological staining, immunohistochemical staining, RT-qPCR and western blot. 100 µg/mL EDPs were applied to isolated normal rat LF cells, with or without pretreatment of elastin receptor complex (ERC) inhibitors, to assess the expression of MMP-2, TIMP-1, and TIMP-2. Spinal destabilization led to LF hypertrophy, observed through increased LF thickness and area, along with histological changes of chondrometaplasia and elastic fiber degradation. LF was also stained positively for Col I and Col II, where elastic fiber has broken down. MMP-2 expression was notably elevated in the hypertrophied LF, accompanied by increased TIMP-2 and TIMP-3 levels. EDPs were found to suppress MMP-2 expression and reduce TIMP-1 and TIMP-2 levels in rat LF cells. Interestingly, exposure to EDPs led to a significant rise in MMP-2/TIMP-1 and MMP-2/TIMP-2 ratios, dependent on the ERC. Collectively, the study suggests that increased MMP-2 activity contributes to elastic fiber degradation in hypertrophied LF, generating EDPs that further enhance the MMP-2/TIMPs ratio in LF cells in an ERC-dependent manner. Further research is essential to delve into the mechanisms of EDPs in LF hypertrophy.

Activity of Matrix Metalloproteinase-7 (MMP-7) Related to Heparin-Binding Epidermal Growth Factor (HB-EGF) Activation in Squamous Cell as Diagnostic Biomarker for Early Detection And Treatment of Maxilarian Cancer: Review Article

Background: Squamous cell carcinoma (SCC) has a higher chance of occurance and progression in maxillary sinus cancer than other paranasal sinus cancers (80%). Matrix metalloproteinase-7 (MMP-7) is a protease specified in collagen type IV degradation and Heparin Binding Epidermal Growth Factor activation, which causes an increase in squamous cell carcinoma proliferation and metastasis Methods: This review aims to identify the potential role of MMP-7 as a target for prevention and therapeutic modality to manage SCC sinus maxillary cancer. We did literature searching in several databases to elucidate the importance of the MMP-7 pathway in SCC sinus maxillary cancer progression. Results: : Increasing expression and activity of MMP-7 are associated with maxillary sinus cancer progression. Squamous cells, the most impacted in maxillary sinus cancer, sustain dysplasia due to heparin-binding epidermal growth factor (HB-EGF) activation into EGF by MMP-7 and Cluster of Differentiation 44 (CD44) binding complexes that trigger high proliferation and mitogenic activity. The therapeutic function of MMP-7 occurs by affecting the protein 53 (p53) in cancer cell apoptosis initiation by specific interaction with CD44. Conclusion: MMP-7 could be an alternative therapeutic target and potential treatment option for maxillary sinus cancer. Furthermore, more trials should be done to test the relevancy of MMP-7 uses as an SCC sinus maxillary cancer modality

Electroacupuncture stimulation enhances the permeability of the blood-brain barrier: A systematic review and meta-analysis of preclinical evidence and possible mechanisms.

An important cellular barrier to maintain the stability of the brain's internal and external environment is the blood-brain barrier (BBB). It also prevents harmful substances from entering brain tissue through blood circulation while providing protection for the central nervous system. It should be noted, however, that the intact BBB can be a barrier to the transport of most drugs into the brain via the conventional route of administration, which can prevent them from reaching effective concentrations for the treatment of disorders affecting the central nervous system. Electroacupuncture stimulation has been shown to be effective at opening the BBB in a series of experimental studies. This study systematically analyzes the possibility and mechanism by which electroacupuncture opens the BBB. In PubMed, Web of Science, VIP Database, Wanfang Database, and the Chinese National Knowledge Infrastructure, papers have been published for nearly 22 years aimed at opening the BBB and its associated structures. A comparison of EB content between electroacupuncture and control was selected as the primary outcome. There were also results on vascular endothelial growth factor (VEGF), nerve growth factor (NGF), P-Glycoprotein (P-gp), Matrix Metalloproteinase 9 (MMP-9), and glial fibrillary acidic protein (GFAP). We utilized Review Manager software analysis to analyze correlations between studies with a view to exploring the mechanisms of similarity. Evans Blue infiltration forest plot: pooled effect size of 2.04, 95% CI: 1.21 to 2.87, P < 0.01. These results indicate that electroacupuncture significantly increases EB penetration across the BBB. Most studies have reported that GFAP, MMP-9, and VEGF were upregulated after treatment. P-gp expression decreased as well. Electroacupuncture can open the BBB, and the sparse-dense wave is currently the most effective electroacupuncture frequency for opening the BBB. VEGF plays an important role in opening the BBB. It is also important to regulate the expression of MMP-9 and GFAP and inhibit the expression of P-gp.

Abstract 6003: The TNF-α-induced protein 3-interacting protein1 (TNIP1) suppresses HGF mediated NF-kB pathway activation and growth in gastric cancer cells

Abstract Background: TNF-α-induced protein 3-interacting protein 1 (TNIP1), an integral component in the regulation of immune responses and cellular pathways, is gaining increased attention in the scientific community. Its ability to interact with A20, a crucial ubiquitin-editing enzyme, forms a significant part of the body's mechanism to control inflammation and prevent unregulated immune responses, which are pivotal in the pathogenesis of autoimmune diseases. TNIP1's role extends beyond autoimmunity; it is also implicated in the regulation of cancer cell proliferation and survival, making it a potential target in cancer therapy. However, TNIP1 has not yet been elucidated on the tumorigenesis, proliferation, and invasion of human gastric cancer, and needs to be researched and discovered. In this study, the HGF-mediated association of TNIP1, nuclear factor kappa-B (NF-κB), and matrix metalloproteinase 9 (MMP9) and cancer cell proliferation and invasion were investigated in two types of human gastric cancer cell lines. Methods: In this study, cell culture, cDNA microarray analysis, western blotting, Real-Time Polymerase chain reaction, Zymography, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, TNIP1 knock-down with short hairpin RNA (shRNA), apoptosis, reagents and antibodies, standard two chamber invasion assay. Results: In our study on gastric cancer cells, we found that hepatocyte growth factor (HGF) stimulation altered TNIP1 expression at both mRNA and protein levels, indicating a dynamic interaction between HGF and TNIP1. The use of LY294002, a PI3K/AKT pathway inhibitor, revealed TNIP1's involvement in the NF-kB pathway, showing changes in NFkB and TNIP1 expression post-HGF stimulation. TNIP1-shRNA expressing cells exhibited altered expression of p53, BCL-2, NFkB, and MMP9, markers crucial for tumor progression and metastasis. Notably, TNIP1 knockdown led to increased cell proliferation and enhanced invasion capabilities in gastric cancer cells. Furthermore, TNIP1 knockdown cells showed a significant decrease in apoptosis rates upon HGF treatment, as confirmed by propidium iodide staining and FACS analysis. Conclusions: In conclusion, our results demonstrate that TNIP1 is closely associated with the NF-kB pathway and plays a critical role in modulating tumor invasion and apoptosis in gastric cancer cells. These findings suggest that TNIP1 could be a potential therapeutic target for the treatment of gastric cancer, providing new insights into the mechanisms of tumor progression and the development of targeted therapies. Citation Format: Jiyoon Jung, Sungae Koh, Kyunghee Lee. The TNF-α-induced protein 3-interacting protein1 (TNIP1) suppresses HGF mediated NF-kB pathway activation and growth in gastric cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6003.

Abstract 207: Tumor suppressive role of NKX2-1 in advanced thyroid cancer progression

Abstract NKX2-1 is a homeodomain transcription factor, known as a master regulator of thyroid development. NKX2-1 is also crucial for lung epithelium differentiation, and the involvement of NKX2-1 in lung carcinogenesis and cancer progression has been intensely investigated. However, the role of NKX2-1 in thyroid cancer progression remains elusive. The Cancer Genome Atlas (TCGA) dataset analysis demonstrated that papillary thyroid cancer (PTC) patients with low NKX2-1 mRNA expression had significantly poorer prognosis than those with a combination of intermediate and high mRNA expression of NKX2-1. Lentivirus-transduced tetracycline (Tet)-inducible system was used to achieve NKX2-1 overexpression in advanced follicular thyroid cancer (FTC) cell lines, FTC-238 and WRO, and an anaplastic thyroid cancer (ATC) cell line 8305C, in which NKX2-1 expression is barely/not detected. All these thyroid cancer cell lines showed significant suppression of cell proliferation with NKX2-1 overexpression. In addition, NKX2-1 overexpression inhibited migration of FTC-238 cells. The levels of mRNA and protein expression of mesenchymal markers, matrix metalloproteinase-2 (MMP-2) and fibronectin, were decreased by NKX2-1 overexpression in FTC-238 cells, suggesting a possibility that NKX2-1 partially inhibits epithelial-mesenchymal transition (EMT). SNAIL and SLUG are essential EMT transcription factors involved in metastasis in cancer progression. NKX2-1 mRNA expression was significantly lower in high SNAI1 (encoding SNAIL) expressing PTC in TCGA database. Indeed, suppression of SNAIL protein expression was found upon overexpression of NKX2-1 in FTC-238 cells which naturally express high level of SNAIL. These findings suggest that NKX2-1 may inhibit the migration of advanced thyroid cancer cells through SNAIL-induced EMT. Similarly, suppression of SLUG protein expression by overexpression of NKX2-1 was observed in WRO and 8305C cells which express high level of SLUG protein. Whether NKX2-1 overexpression inhibits migration and invasion of WRO and 8305C cells through SLUG-induced EMT is currently under examination. The Tet-inducible NKX2-1 expressing thyroid cancer cells will be used for in vivo evaluation of their metastatic ability using an immunocompromised mouse model. The findings so far suggest that NKX2-1 exerts a tumor suppressive activity in advanced thyroid cancers through suppression of cell proliferation, and cell migration presumably via suppression of EMT transcription factors. Citation Format: Yo-Taro Shirai, Shioko Kimura. Tumor suppressive role of NKX2-1 in advanced thyroid cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 207.