Effects of Muscone on Cartilage Morphology and Matrix Metalloproteinases-3 (MMP-3h) and Matrix Metalloproteinases-9 (MMP-9) Expression in Rheumatoid Arthritis Rat Models

Aim: To discuss Muscone treatment in Rheumatoid Arthritis Rat Models and relative mechanisms. Materials and methods: Dividing 36 rats as 4 groups as Normal, Model, DMSO and Muscone groups (n = 9). Rats of Model, DMSO and Muscone groups were made Rheumatoid Arthritis model. Muscone group were treated with 2 mg/kg Muscone after modeling. HE staining and Masson staining were used to observe the morphological changes of cartilage tissue, measuring MMP-3 and MMP-9 expression by RT-PCR, Western Blotting (WB) and Immunohistochemistry (IHC). Results: Compared with Model group, the pathological changes of Muscone group was significantly improved and average optical density of collagen fibers was significantly depressed (P < 0.001, respectively) via MMP-3 and MMP-9 proteins significantly depressing (P < 0.001, respectively). Conclusion: Muscone improved Rheumatoid Arthritis by depressing MMP-3 and MMP-9 proteins in vivo study.

miR-140-5p Affects TCC8113 Cell Biological Activity and Matrix Metalloproteinases 9 (MMP-9) in Oral Squamous Cell Carcinoma (OSCC) Cell Line

Whether the miR-140-5p affects the biological activity of Tca8113 cells and MMP-9 in OSCC cell line was explored. Tca8113 cells were divided into Tc group (normal Tca8113 cells), Tm group (Tca8113 cell transfection+miR-140-5p mimic), and Nc group (Tca8113 cell transfection+miR-140-5p-negative control) followed by analysis of MMP-9 expression by western blot, cell migration by Transwell assay, cell viability by MTT method, and apoptosis by flow cytometry. Compared with TC group and NC group, mir-140-5p in TM group was significantly higher (P <0.05), however, the MMP-9 level of TM group was significantly lower (P <0.05).Western blot analysis showed that there was no significant difference (P <0.05) in the comparison of MMP-9 protein expression between TC group and NC group, and MMP-9 expression in the TM group was decreased significantly (P <0.05). MTT assay showed that the cell viability of TM group was increased slowly and lower than that of group (P <0.05). In conclusion, mir-140-5p can induce apoptosis of OSCC cell line Tca8113, which may be achieved by reducing the expression of MMP-9.

Citrus sinensis (L) Peels Extract Inhibits Metastasis of Breast Cancer Cells by Targeting the Downregulation Matrix Metalloproteinases-9

Introduction: Long-term use of doxorubicin (DOX) chemotherapy causes several side effects, especially induction of metastasis on breast cancer (BC). There is an urgent need to identify novel agent with low side effect targeting BC metastasis. Citrus sinensis (L.) peels extract (CSP) has long been used for the treatment of several cancer. However, its anti-metastatic potential against BC metastatic remains unclear. Objective: This study aimed to explore the role of CSP in combination with DOX in inhibiting the migration of metastatic breast cancer MDAMB-231 cells. Material and Methods: Potential cytotoxic in single and combination was analysed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT assay). The anti-metastatic activities of several major compound on CSP including hesperetin, tangeretin, nobiletin, naringenin and hesperidin were screened by molecular docking under PLANTS software. Results: Based on molecular docking we revealed that the selected protein target MMP-9 (PBD ID:2OVX) has lower docking score for hesperetin, tangeretin, nobiletin, naringenin and hesperidin compare to DOX. CSP and DOX individually exhibited strong cytotoxic effect on MDA-MB-231 cells under MTT assay with IC50 value of 344 µg/mL and 85 nM, respectively. Furthermore, CSP in combination with DOX synergistically increased the cytotoxicity of DOX. Here, we showed that CSP can specifically suppress the side effect of DOX-induced metastasis by reduces doses of DOX. However, low doses of DOX in combination with CSP still potential inhibited cancer cells growth. Conclusion: In conclusion, CSP increased the cytotoxicity and inhibited the induction of metastasis by DOX in breast cancer cells. So that, CSP potential to be developed as co-chemotherapeutic agent.

Up-regulation of matrix metalloproteinases-9 in the kidneys of diabetic rats and the association with neutrophil gelatinase-associated lipocalin

Background Matrix metalloproteinases-9 (MMP-9) can regulate extracellular matrix deposition in diabetic glomerular injury. However, it remains unknown whether MMP-9 is involved in the renal tubular injury. Meanwhile, neutrophil gelatinase-associated lipocalin (NGAL), defined as a biomarker of proximal tubular injury, may influence MMP-9 by forming the MMP-9/NGAL complex. The aim of this study was to investigate MMP-9 expression in proximal renal tubules and the relationship of MMP-9 and NGAL in diabetic rat model treated with Valsartan. Methods Sprague Dawley rats were randomly divided into three groups: Diabetic group, Control group, and Treated group. The diabetic rat model was established by injection of streptozotocin. Related indexes were measured at the end of the 2nd, 4th, 8th and 12th week post-modeling. Results In diabetic groups, the concentrations of MMP-9 markedly increased in the serum and urine of rats in the early stage, even before the appearance of pathological albuminuria. Markedly elevated MMP-9/NGAL complex concentrations were also tested in diabetic groups. Western blot and qPCR tests confirmed that MMP-9 expression levels in the proximal renal tubular epithelial cells of diabetic rats were significantly higher than in control groups (P < 0.05). Correlation analysis showed that MMP-9 was positively correlated with NGAL at both protein and gene expression levels. In addition, Valsartan observably reduced tubular injury as well as MMP-9 expression in diabetic rats. Conclusions In diabetic kidney injury, the expression of MMP-9 in the proximal renal tubular epithelial cells was significantly increased. Besides, a positive correlation was found between MMP-9 and NGAL expression, along with high levels of MMP-9/NGAL complex, which indicated that NGAL might participate in the regulation of MMP-9 expression. The administration of Valsartan may reduce this effect.

Intranasal Curcumin Attenuates Silicosis by Inhibiting Matrix Metalloproteinase-9 (MMP-9) Activity in Mice

Inhalation of crystalline silica causes silicosis, a type of occupational pulmonary fibrosis, is most prevalent among people working in industries related to construction.Curcumin being an antioxidant and anti-inflammatory in nature has shown anti-asthmatic effectsbut it has not yet been investigated to have any impact on silicosis. Therefore,our aim was to study impact of intranasal curcumin on lung fibrosis after sequentialsilica exposure. The mice model of silicosis was developed by intranasal silica instillation(2.5 mg/mice) for every alternate dayfor different durations, mainly 7, 14 and 21 days. This model of silicosis mimic chronic occupational exposure of silica dustand severe features of silicosis were developed in 21 days of silica exposure.One hour prior to silica administration, curcumin (5 mg/kg,i.n) and /or dexamethasone, a known corticosteroid (10 mg/kg,i.p)was administered in mice.Results haveshown that apart from being anti-inflammatory, curcumin is being reported here for the first time to possess anti-fibrotic effects where silica exposed airway inflammation and fibrosis was reduced after intranasal curcumin treatment. Reduced inflammatory cell recruitment, collagen deposition around the bronchioles and the alveolar spaces, hydroxyproline level and matrix metalloproteinases 9 (MMP 9) activity was noted in silicosis affected mice after curcumin administration.Remarkable reduction in oxidative stress markers like reactive oxygen species (ROS), nitric oxide, myeloperoxidases (MPO) and eosinophil peroxidase (EPO) levels wereobserved in curcumin treatment groupswhich was better and/or comparable to corticosteroid, dexamethasone.

Valproate Sodium Protects Blood Brain Barrier Integrity in Intracerebral Hemorrhage Mice

Valproate sodium (VPA) is a traditional antiepileptic drug with a neuroprotective role in cerebrovascular disease. After intracerebral hemorrhage (ICH), mechanical compression by hematoma, neuroinflammation, oxidative stress, and cytotoxicity of hematoma lysates caused the destruction of the blood brain barrier (BBB). Targeting BBB is a major therapeutic method for patients with ICH. The purpose of the present study was to explore the role of VPA in preserving BBB integrity in the ICH model and investigate the underlying molecular mechanisms. One hundred and thirty-six adult male CD1 mice were randomly divided into five groups in the study. Mice subjected to ICH were administered intraperitoneally with VPA at 3, 24, and 48 h post-ICH, respectively. Neurobehavioral assessments, BBB permeability, Evans blue fluorescence, hematoma volume, and protein expression were evaluated. The administration of VPA reduced BBB permeability and improved the neurobehavior significantly post-ICH. VPA administration significantly decreased the expression of phosphorylated nuclear factor-kappa B (p-NFκB), matrix metalloproteinases 9 (MMP9), tumor necrosis factorα (TNFα), and interleukin-6 (IL-6), while it enhanced the expression of claudin 5 and occludin in the brain. In conclusion, VPA administration maintained the integrity of BBB after experimental ICH, thus reducing brain edema and improving the neurological outcomes. Therefore, VPA administration might be a new therapeutic method to protect BBB integrity for patients with ICH.

Matrix metalloproteinases 9 and 14 polymorphisms and long-term complications in surgically treated breast cancer patients.

e24074 Background: Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases that are involved in tissue remodeling. They can regulate interactions of cells with extracellular matrix and can play a role in wound healing. High levels of metalloproteinases have been correlated with significantly delayed wound healing in wounds of a variety of etiologies. The aim of our present study was to evaluate the association of MMP9 and MMP14 genetic polymorphisms with long-term complications of surgical treatment in breast cancer patients. Methods: The study included 99 breast cancer patients treated with either 75 or 37.5 mg of tramadol for pain relief after axillary breast cancer surgery as part of a randomized clinical trial KCT 04/2015-DORETAonko/si at Institute of Oncology Ljubljana. All patients were genotyped for MMP9 polymorphisms rs2250889, rs17577, rs17576, and rs20544 as well as MMP14 rs1042703, rs1042704, and rs743257. The association of genetic factors with long-term complications was evaluated using logistic regression. Results: One year after surgery, 24 (24.2%) patients had lymphedema, 25 (25.3%) experienced neuropathic pain and 21 (21.1%) experienced chronic pain. Carriers of polymorphic MMP9 rs2250889 allele experienced significantly more lymphedema compared to carriers of two wild-type alleles (OR = 3.45, 95% CI = 1.10-10.84, P = 0.034), even after adjustment for tramadol dose (OR = 3.76, 95% CI = 1.16-12.18, P = 0.027). Carriers of polymorphic MMP14 rs1042704 allele experienced more neuropathic pain compared to carriers of two wild-type alleles (OR = 3.21, 95% CI = 1.26-8.20, P = 0.015), even after adjustment for tramadol dose (OR = 3.80, 95% CI = 1.42-10.17, P = 0.008). Conclusions: MMP genetic variability was associated with long-term complications after axillary surgery in breast cancer patients, suggesting that MMPs may have an important role as modulators of wound healing.