ABSTRACT
Objective: To observe the effects of different combinations of Gentianae Macrophyllae Radix (Qinjiao) on the ankle joint matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) of rheumatoid arthritis (RA) model rats with wind-cold-dampness arthralgia.Method: Eighty healthy SD rats were randomly divided into 8 groups, namely blank control group, collage Ⅱ model group, wind-cold-dampness syndrome model group, positive control group, single-taste Gentianae Macrophyllae Radix group, Gentianae Macrophyllae Radix-Clematidis Radix et Rhizoma group (GC group), Gentianae Macrophyllae Radix-Taxilli Herba group (GT group), Gentianae Macrophyllae Radix-Stephanlae Tetrandrae Radix group (GS group), with 10 rats in each group. Rat model of wind-cold-dampness RA was induced through the injection with type Ⅱ collagen emulsion and wind-cold-dampness stimulation. After the establishment of the model, the blank control group, collage Ⅱ model group and wind-cold-dampness syndrome model group were given normal saline, and the corresponding liquid medicine was given to each administration group. In the experiment, the thickness of the left posterior metatarsal of rats was measured every 3 days, and the swelling degree of metatarsal was calculated. The arthritis index (AI) was evaluated on the 38th day of the experiment. The serum rheamatoid factor(RF) content of rats was detected by enzyme linked immunosorbent assay (ELISA). The expressions of MMP-3 and TIMP-1 in ankle joint were detected by Western blot. The expressions of MMP-3 and TIMP-1 mRNA in ankle joint were detected by real-time fluorescence quantitative PCR (Real-time PCR).Result: Compared with the blank group, the swelling degree, AI score, serum RF content, MMP-3 protein expression and MMP-3 mRNA expression in ankle joints of coll age Ⅱ model group and model wind-cold-dampness syndrome group were significantly increased (PPPPPPConclusion: For rheumatoid arthritis with wind-cold-dampness arthralgia, mild and warm traditional Chinese medicine (TCM) has a better effect than the combination of mild and cold TCM or mild TCM drugs. The experimental results are basically consistent with the principle of "treating cold diseases with hot medicine". The mechanism of the compatibility in treating rheumatoid arthritis due to wind-cold-dampness arthralgia may be related to the reduction of MMP-3, the increase of TIMP-1 expression and the reduction of articular cartilage damage.
ABSTRACT
@# Objective: To investigate the molecular mechanism of chemokine CCL20/CCR6 in promoting invasion and migration of colon cancer SW480 cells. Methods: Colorectal cancer SW480 cells with high expression of CCR6 receptor were screened by immunochemistry (IHC). After co-culture with recombinant human CCL20, the invasion and migration of SW480 cells were detected by Transwell assay and Wound-Healing assay, respectively. Expressions of EMT markers, AKT signal protein and target protein MMP3 were detected by immunofluorescence (IF) and WB. AKT signaling pathway as the key mechanism was confirmed by MK2206 blocking assay. The expressions of CCL20 and MMP3 in colorectal cancer tissues as well as their correlation were analyzed by TCGAdatabase resources (https://portal.gdc.cancer.gov/). Results: CCL20 promoted the invasion and migration ability of SW480 cells significantly (all P <0.01), and this was induced by activation of AKT signaling and up-regulation of downstream target protein MMP3, instead of EMT. Blocking AKT signaling could significantly inhibit the invasion and migration of SW480 cells, and down-regulate MMP3 expression (P<0.05). TCGA platform data showed that the expressions of CCL20 and MMP3 in colorectal cancer tissues were significantly higher than those in normal mucosa tissues (P<0.05 or P<0.01), and an evidently positive correlation was found between CCL20 and MMP3 (r =0.051, P<0.01). Conclusion: The chemokine CCL20 promotes the invasion and migration of SW480 cells throughAKT/MMP3 signal axis, but not the EMT.
ABSTRACT
Objective:To study the effects of green-tea polyphenol, (epigallocatechin gallate,EGCg) on the cellular inflammatory responses of gingival epithelial cells. In order to find out a safe and efficient inflammation-inhibitor for periodontitis prevention and treatment. Methods:A model of cellular inflammatory responses of gingival epithelial cells stimulated by Porphyromonas gingivalis vesicles in vitro was established. The effects of EGCg on PGE2 production of gingival epithelial cells was detected by ELISA. Further more, the effects of EGCg on COX (cyclooxygenase)-2 and MMP (matrix metalloproteinase)-3 mRNA expression were determined by Real-time RT-PCR. Results:EGCg dose-dependently inhibited PGE2 production and COX-2, MMP-3 mRNA expressions. Conclusion:EGCg has inhibitory effects on cellular inflammatory responses of gingival epithelial cells and possesses the potentiality to be a periodontal inflammation-inhibitor.
ABSTRACT
Matrix metalloproteinase 3 is one of matrix metalloproteinase family members, which degrades a wide range of components of the extracellular matrix and participates in tissue morphogenesis, wound healing and inflammation. In addition, matrix metalloproteinase 3 is involved in pathogenesis and progress of a spectrum of diseases and malignant tumors, such as rheumatic arthritis, arteriosclerosis, breast cancer, and so on. Recent studies have demonstrated that matrix metalloproteinase 3 may be a novel signaling proteinase from apoptotic neuronal cells to microglia, which results in degeneration of neurons in Alzheimer's disease and Parkinson's disease by activating microglia. There is also an association between genetic polymorphisms of matrix metalloproteinase 3 at promoter region 5A/6A and susceptibility of myocardial infarction. Decrease in serum concentration of matrix metalloproteinase 3 after myocardial infarction may be a useful parameter for diagnosing sudden death due to myocardial infarction in forensic practice. Expression of matrix metalloproteinase 3 varies with different types of brain injuries, suggesting that it may contribute to synaptic plasticity during functional recovery. To elucidate the time-dependent expression of matrix metalloproteinase 3 may provide a new way for wound age determination in the brain.