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Objective @#To investigate the histological damage recovery of temporomandibular joint condylar cartilage caused by chronic unpredictable moderate stress, aiming to provide an experimental basis for the prevention and treatment of temporomandibular disorder.@*Methods @#This animal experiment was approved by the Laboratory Animal Ethical Inspection, School of Stomatology, The Fourth Military Medical University (No. 2020081). 60 male SD rats were randomly divided into control group, stress group, and 2-, 4- and 8-week post-stress recovery groups. Rats were subjected to chronic unpredictable moderate stress (CUMS) for 8 weeks including damp sawdust for 24 hours, tilted cage for 12 hours, noise for 4 hours, light/dark cycle reversal, water immersion, tail clamp, and restraint stress. The serum assessment, behavioral tests, histological and ultrastructural observation were performed 2-, 4- and 8-weeks after stress factors were removed. Serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were determined with ELISA. The sucrose preference test (SPT) and the forced swim test (FST) were used to assess the depressive-like behavior. The expression level of interleukin-1α (IL-1α) and matrix metalloproteinases-3 (MMP-3) were determined by Immunohistochemistry and Western blot.@*Results @#At the end of 8 weeks of CUMS, the serum levels of CORT and ACTH were significantly higher in stress group compared with control group (P<0.01). The sucrose preference decreased significantly and the immobility time increased significantly in the stressed rats compared with those in the control group, indicating a successful establishment of CUMS. The condylar cartilage showed significant degenerative changes, with disorganized collagen fibers and reduced proteoglycan synthesis on the cartilage surface. IL-1α and MMP-3 were expressed in the intracellular and extracellular matrix of the condylar cartilage, and their expression levels were increased (P<0.01). After 2 weeks of stress removal, the serum levels of CORT and ACTH were decreased but higher than control group (P<0.01), and behavioral changes were still different from the control group (P<0.01); the loosened collagen fibers could still be seen on the surface of condylar cartilage, and some free cell areas were visible within the proliferative layer; additionally, IL-1α and MMP-3 expression in the condyle was reduced in all layers of cartilage when compared with the stress group, but was still higher than in the control group (P<0.01). After 4 weeks of stress removal, the serum levels of CORT and ACTH changes returned to normal levels and behavioral changes were still different from control group (P<0.05); a few collagen fibers could be seen on the surface of the condylar cartilage and the expressions of IL-1α and MMP-3 decreased significantly compared with the stress group (P<0.01), with the similar level of IL-1α (P>0.05) and higher expression of MMP-3 comparing with the control group (P<0.01). After 8 weeks of stress removal, behavioral changes returned to normal levels, with no statistically significant differences compared with the control group (P>0.05). The condylar collagen fibers increased and showed a corrugated pattern, and no serious subchondral bone damage as well as irreversible damage occurred. Both of the expression levels of IL-1α and MMP-3 approached those of the control group after 8 weeks of stress removal (P>0.05). @*Conclusion@# The behavioral changes and condylar cartilage damage caused by CUMS could be self-repaired. The decline in IL-1α and MMP-3 expression may be one of the intrinsic mechanisms of this self-repair process.
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Objective: To observe the efficacy of knee-balancing manipulation plus heat-sensitive moxibustion in treating knee osteoarthritis (KOA) and its impact on the expression of C-telopeptide of type Ⅰ collagen (CTX-Ⅰ), tartrate-resistant acid phosphatase 5b (TRACP-5b), A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), and matrix metalloproteinase 3 (MMP-3). Methods: A total of 134 unilateral KOA patients were randomized into a knee-balancing group, a heat-sensitive moxibustion group, and a joint intervention group. The knee-balancing group received knee-balancing Tuina (Chinese therapeutic massage) manipulation for treatment. The heat-sensitive moxibustion group received heat-sensitive moxibustion treatment. The joint intervention group received the heat-sensitive moxibustion in addition to the knee- balancing manipulation. The intervention period lasted for four weeks. After the treatment, and at the 2-week and 6-week follow-ups, the three groups were assessed using the visual analog scale (VAS) for knee joint pain and Western Ontario and McMaster Universities arthritis index (WOMAC), and clinical efficacy was also evaluated. The enzyme- linked immunosorbent assay was adopted to detect the expression levels of serum CTX-Ⅰ, TRACP-5b, ADAMTS-4, and MMP-3. Results: The knee-balancing group had 44 participants, but one dropped out; there was no dropout case among the 44 participants in the heat-sensitive moxibustion group; among the 46 participants in the joint intervention group, two cases dropped out. After the treatment, and at the 2-week and 6-week follow-ups, the total effective rate was found higher in the joint intervention group than in the knee-balancing and heat-sensitive moxibustion groups (P<0.05). Compared with the baseline, the VAS and WOMAC scores and the serum levels of CTX-Ⅰ, TRACP-5b, ADAMTS-4, and MMP-3 decreased significantly in all three groups after treatment and at the 2-week and 6-week follow-ups (P<0.05). At the same three time points, the VAS and WOMAC scores and serum levels of CTX-Ⅰ, TRACP-5b, ADAMTS-4, and MMP-3 were lower in the joint intervention group than in the knee-balancing and heat-sensitive moxibustion groups (P<0.001). Conclusion: Either used alone or combined, the knee-balancing manipulation and heat-sensitive moxibustion therapy can improve the symptoms and down-regulate the serum levels of CTX-Ⅰ, TRACP-5b, ADAMTS-4, and MMP-3 in KOA patients, producing durable efficacy; nevertheless, a more significant efficacy can be achieved by combining the two methods.
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Objective:To analyze the expression and correlation of programmed death receptor ligand 1 (PD-L1) and matrix metalloproteinase-3 (MMP-3) in elderly esophageal squamous cell carcinoma, in order to provide an effective basis for early disease diagnosis, treatment plan formulation and prognosis evaluation of elderly patients with esophageal cancer.Methods:The clinical data of 83 elderly patients with esophageal squamous carcinoma who admitted in Qinghai Provincial Traffic Hospital from October 2018 to October 2019 were retrospectively analyzed and included in the esophageal squamous carcinoma group. Another 46 patients with para-carcinoma tissue were included in the para-carcinoma group. The immunohistochemistry was used to compare the positive rate of PD-L1 and MMP-3 expression in the two groups of tissues, and the relationship between PD-L1 and MMP-3 expression in esophageal squamous carcinoma tissues and clinical pathology was explored. Bivariate Pearson correlation test was used to analyze the correlation between the two and the clinical pathological features of elderly patients with esophageal squamous carcinoma.Results:The positive expression rates of PD-L1 and MMP-3 in the esophageal squamous carcinoma group (55.42%, 67.47%) were higher than those in the para-carcinoma group (23.91%, 30.43%) ( P<0.05); Pearson correlation analysis found that PD-L1 expression was positively correlated with the differentiated degree of esophageal squamous carcinoma ( r=0.449, P<0.001), and MMP-3 expression was positively correlated with the infiltration degree of esophageal squamous carcinoma, tumor node metastasis (TNM) stage, and lymph node metastasis ( r=0.255, 0.367, 0.361, P=0.020, 0.001, 0.001). Conclusions:PD-L1 and MMP-3 are highly expressed in elderly esophageal squamous carcinoma. PD-L1 expression can indicate the degree of differentiation of esophageal squamous carcinoma, and MMP-3 expression can indicate different infiltration degrees of esophageal squamous carcinoma, TNM stage, and lymph node metastasis. PD-L1 and MMP-3 can be used as clinical markers for the development of esophageal squamous carcinoma treatment plans and prognostic evaluation.
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Objective:To explore the curative effect of methylprednisolone combined with methotrexate in the treatment of ankylosing spondylitis (AS) and its regulation of serum interleukin (IL)-17/IL-4.Methods:A total of 117 patients with AS in the First Hospital of Baoding from July 2016 to June 2019 were selected as prospective research subjects, and they were simply randomized into three groups, with 39 cases in each group. The control group A was treated with methotrexate, the control group B was treated with methylprednisolone, and the observation group was treated with methotrexate combined with methylprednisolone. The chi-square test was used to compare the clinical efficacy and the incidence of adverse reactions in the three groups. F-test was used to compare the thoracolumbar spine mobility, Bath AS disease activity index (BASDAI), Bath AS function index (BASFI) scores, the levels of serum high mobility protein 1 (HMGB1), matrix metalloproteinase-3 (MMP-3), interleukin (IL)-4, IL-17, and IL-17/IL-4 before and after the treatment of the three groups. Results:The total effective rate of treatment in the observation group was better than that in the control groups A and B :92.31%(36/39) vs. 74.36%(29/39) and 69.23%(27/39), P<0.05. After the course of treatment, the BASDAI and BASFI scores in the observation group were lower than those in the control group A and B, and the thoracolumbar spine mobility were higher than those in the control group A and B: (3.36 ± 1.03) scores vs. (4.62 ± 1.19), (4.98 ± 1.25) scores; (3.70 ± 0.89) scores vs. (4.36 ± 0.96), (4.64 ± 0.95) scores; (4.96 ± 1.17) cm vs. (4.18 ± 1.02), (3.98 ± 1.15) cm, (5.93 ± 1.32) cm vs.(5.02 ± 1.15), (4.92 ± 1.25)cm, P<0.05. After the course of treatment, serum HMGB1, MMP-3, IL-17, IL-17/IL-4 in the observation group were lower than those in the control group A and B: (20.25 ± 6.41) μg/L vs. (27.81 ± 7.63), (29.26 ± 7.31) μg/L; (4.83 ± 1.06) μg/L vs. (9.26 ± 1.25), (9.71 ± 1.28) μg/L; (13.41 ± 5.06)ng/L vs.(17.62 ± 5.61), (19.06 ± 6.14) ng/L; 0.51 ± 0.27 vs. 0.92 ± 0.41, 1.04 ± 0.45, P<0.05; and IL-4 was higher than that in the control groups A and B: (26.15 ± 4.94) ng/L vs. (19.16 ± 5.14), (18.32 ± 5.26) ng/L, P<0.05. There was no significant difference in the incidence of adverse reactions among the three groups ( P>0.05). Conclusions:The combination of methylprednisolone and methotrexate in the treatment of AS can significantly reduce serum HMGB1 and MMP-3 levels, regulate serum IL-17/IL-4 and further improve the therapeutic effect, and it has high safety.
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Matrix metallopeptidase 3 or MMP3, is a zinc-dependent proteolytic enzyme that is involved in various physiological processes via modification of the extracellular matrix. In particular, its over-expression has been associated with cancer metastasis and tumor growth in various cancers including breast cancer. MMP3 gene expression is regulated by several factors such as DNA polymorphisms which also serve as risk factors for breast cancer. As such, DNA polymorphisms of MMP3 have the potential to be utilized as genetic biomarkers for prediction and prognosis of metastatic breast cancer. Presently, genome-wide association studies of MMP3 gene polymorphisms which are associated with breast cancer risk and patient survival in a variety of populations are reviewed. In order to understand the potential role of MMP3 polymorphisms as genetic markers for breast cancer metastasis, the domain structure of MMP3, the regulation of its expression and its role in breast cancer metastasis are also briefly discussed in this review. The emergence of MMP3 gene polymorphisms as prognostic biomarker candidates for breast cancer metastasis may contribute towards improving targeted therapies and categorization of breast cancer cases in order to provide a better and more accurate prognosis.
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Humans , Biomarkers , Breast Neoplasms , Breast , DNA , Extracellular Matrix , Gene Expression , Genetic Markers , Genome-Wide Association Study , Matrix Metalloproteinase 3 , Neoplasm Metastasis , Physiological Phenomena , Prognosis , Risk FactorsABSTRACT
BACKGROUND: In the development of osteoarthritis, the mechanism underlying cartilage damage is still unclear. Matrix metalloproteinases have been shown to play important roles in cartilage matric degradation. OBJECTIVE: To observe the correlation between the expression of matrix metalloproteinase 3, tissue inhibitor of metalloproteinase-1 and the pathological degree in knee osteoarthritis. METHODS: The study was approved by the Ethics Committee of Shenyang Orthopedic Hospital. The tibial plateaus of 40 patients with knee osteoarthritis who underwent total knee arthroplasty were collected, and all patients signed the informed consents. The classification of osteoarthritis was evaluated according to Kellgren-Lawrence (KL) scale system: 11 cases of KL grade 2, 15 cases of KL grade 3, and 14 cases of KL grade 4. Control group contained six cases. Samples received hematoxylin-eosin staining. The pathological changes of knee osteoarthritis cartilage were evaluated by Mankin score. Immunohistochemical staining was used to detect the contents of matrix metalloproteinase 3 and tissue inhibitor of metalloproteinase-1 in cartilage. RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining results showed that in the control group, the layer of cartilage was thick, and there were abundant chondrocytes that arranged regularly. The subcutaneous layer of cartilage in the KL grade 2 group was rugged, and fissure was observed occasionally. Fibrosis of cartilage layer was visible in the KL grade 3 group, and the chondrocytes arranged in disorder. In the KL grade 4 group, the structure of cartilage layer was lost, and there were few chondrocytes that arranged irregularly. (2) Immunohistochemical staining results showed that the expression level of matrix metalloproteinase 3 in the osteoarthritis group was significantly higher than that in the control group. The expression level of matrix metalloproteinase 3 was on a rise in the KL grade 2, 3 and 4 groups (all P < 0.05). The expression level of tissue inhibitor of metalloproteinase-1 in the osteoarthritis group was significantly lower than that in the control group. The expression level of tissue inhibitor of metalloproteinase-1 was on a descent in the KL grade 2, 3 and 4 groups (all P < 0.05). (3) There was significantly positive correlation between matrix metalloproteinase 3 expression level and Mankin score (r=0.899, P < 0.001), and tissue inhibitor of metalloproteinase-1 expression level was negatively correlated with Mankin score (r=-0.903, P < 0.001). There was significantly negative correlation between tissue inhibitor of metalloproteinase-1 expression level and matrix metalloproteinase 3 expression level (f=-0.881, P < 0.001). (4) These results indicate that in the articular cartilage of patients with osteoarthritis, the expression levels of matrix metalloproteinase 3 and tissue inhibitor of metalloproteinase-1 are correlated with the pathological changes, which can be used as an effective index to evaluate the progress of knee osteoarthritis.
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BACKGROUND: Clinical studies have shown that sodium hyaluronate at different molecular weights exhibits therapeutic effects on osteoarthritis. OBJECTIVE: To investigate the changes in interleukin-1 beta, tumor necrosis factor-alpha, and matrix metalloproteinase-3 in synovial fluid of osteoarthritis rabbits after treatment with different molecular weights of sodium hyaluronate injection. METHODS: Forty rabbits (purchased from Qinghai Experimental Animal Center, China) were randomly divided into normal, model, macromolecule, and small molecule groups, with 10 rabbits in each group. The control group did not undergo any treatment. Rabbits in the remaining three groups were injected with papain via the right knee joint cavity to establish rabbit models of osteoarthritis. At 7 days after successful modeling, the right knee joint cavity of rabbits in the macromolecule and small molecule groups were injected with 0.3 mL of (1.5-2.5)x106 Da and (0.8-1.5)x106 Da sodium hyaluronate injection. Rabbits in the model group were injected with equal amounts of physiological saline, once a week, for 5 successive weeks. At 7 days after the last injection, the right knee joint cavity was examined by MRI, cartilage tissue was stained with hematoxylin-eosin, the level of inflammatory factors in the washing fluid was determined, and proteoglycan and collagen gene expression was detected. This study was approved by the Medical Ethics Committee of Qinghai Red Cross Hospital, China (No. 201802065). RESULTS AND CONCLUSION: MR imaging: There were joint effusion and incomplete cartilage surface in the model group. In the macromolecule group, cartilage surface was rough and cartilage layer became thinner compared with the model group. Hematoxyin-eosin staining: Obvious cartilage injury was observed in the model, macromolecule, and small molecule groups, but the injury in the macromolecule, and small molecule groups was milder than that in the model group. The injury in the small molecular group was milder than that in the macromolecule group. Measurement of inflammatory factors: Compared with the control group, the levels of interleukin-1 beta, tumor necrosis factor-alpha and matrix metalloproteinase-3 increased in the model group (P < 0.05). Compared with the model group, the levels of interleukin-1 beta, tumor necrosis factor-alpha and matrix metalloproteinase-3 decreased in the macromolecule and small molecule groups (P < 0.05). The levels of interleukin-1 beta and matrix metalloproteinase-3 in the small molecule group were lower than those in the macromolecule group. There was no significant difference in the level of tumor necrosis factor-alpha between small molecule and macromolecule groups. Gene detection: Proteoglycan and collagen gene expression levels were significantly lower in the model group than in the control, macromolecule and small molecule groups (P < 0.05). Proteoglycan and collagen gene expression levels were significantly lower in the macromolecule group than in the small molecule group (P < 0.05). These results suggest that compared with large molecular weight of sodium hyaluronate, small molecular weight of sodium hyaluronate can promote the repair of cartilage tissue in osteoarthritis and alleviate synovitis inflammation.
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BACKGROUND: Studies have shown that Lycium barbarum polysaccharide (LBP) has the functions of anti-aging, nerve protection, anti-fatigue, blood sugar control, anti-oxidation, and anti-tumor. It may have some protective effects against osteoarthritis of the knee, but have been rarely reported. CD151 and matrix metalloproteinase 3 (MMP-3) are two common cytokines for assessing knee osteoarthritis. OBJECTIVE: To observe the effect of LBP on the expression of CD151 and MMP-3 in rabbit osteoarthritis. METHODS: Sixty-four healthy 6-month-old white rabbits were randomly divided into four groups: blank group, model group, LBP group and normal saline group. Animal models of knee osteoarthritis were made using Hulth method in the rabbits except those in the blank group. The rats in the LBP and normal saline groups were fed with normal dose of LBP and normal saline for 4 weeks, and then the articular cartilage tissues were taken from the affected side at 12 weeks after modeling. The morphological changes of the articular cartilage were observed by hematoxylin-eosin staining. The expression levels and spatial distribution of CD151 and MMP-3 in articular cartilage was observed by immunohistochemical staining and western blot. Ethic approval was given by the People’s Hospital of Ningxia Hui Autonomous Region (approval No. 2014-30817). RESULTS AND CONCLUSION: immunohistochemistry staining and western blot results showed that the absorbance values and protein expression of MMP-3 and CD-151 were significantly lower in the LBP group than the normal saline and model groups (P < 0.05). Therefore, the expression of CD151 and MMP-3 in the articular cartilage of osteoarthritis was increased, and LBP could inhibit the expression of CD151 and MMP-3 in osteoarthritis, so as to slow down the occurrence of osteoarthritis.
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The purpose of this study is to investigate the matrix metalloproteinase-3 (MMP-3) levels in patients with systemic lupus erythematosus (SLE) and its significance in identifying disease activity and pulmonary infections. A total of 122 SLE patients were enrolled, including 21 with pulmonary infections, 16 with arthritis, 26 with nephritis, 10 with vasculitis, and 23 healthy controls. Serum MMP-3, C-reactive protein (CRP), serum amyloid A (SAA), and haptoglobin (HPT) levels were measured in all subjects. The results showed that the levels of MMP-3 in SLE combined with pulmonary infections [(230.10±44.92) μg/L], arthritis [(140.20±20.76) μg/L], nephritis [(155.40±23.36) μg/L] were higher than those in SLE only [(91.74±10.47) μg/L]. The levels of MMP-3 [(210.30±45.71) μg/L], CRP [(12.11±5.21) mg/L], HPT [(1.57±0.23) g/L] in active SLE combined with pulmonary infections were higher than those inactive SLE without pulmonary infections including MMP-3 [(124.00±15.22) μg/L], CRP [(7.76±2.96) mg/L], HPT [(0.89±0.09) g/L]. The levels of CRP [(10.03±2.70) mg/L], SAA [(89.22±36.77) mg/L] in active SLE with pulmonary infections and CRP[(7.76±2.96) mg/L], SAA [(60.22±19.7) mg/L] in active SLE without pulmonary infections were higher than CRP [(1.90±0.39) mg/L], SAA [(17.60±3.89) mg/L] in stable SLE with pulmonary infections. It suggests that the levels of CRP and SAA are elevated in active SLE with pulmonary infections. Serum MMP-3 in combination with CRP may assist in differentiating from SLE pulmonary infections.
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Objective@#To detect the expression of matrix metalloproteinase-3 (MMP-3) in serum and gingival crevicular fluid in patients with rheumatoid arthritis (RA) and its correlation with chronic periodontitis (CP).@*Methods@#From March 2017 to July 2018, 26 patients with RA and CP [CP+RA group, (54.9±6.5) years old, 4 males and 22 females], 22 patients with RA only [RA group, (49.6±11.7) years old,5 males and 17 females] in the Department of Rheumatology and Immunology, Shengjing Hospital Affiliated to China Medical University, 22 patients with simple CP in the Department of Stomatology, Shengjing Hospital Affiliated to China Medical University [CP group, (51.4±12.5) years old, 8 males and 14 females] and 18 generally healthy controls in Physical Examination Center of Shengjing Hospital Affiliated to China Medical University [group H, (49.4±9.1) years old, 8 males and 10 females] were recruited. There were no significant differences in age and sex ratio amongst 4 groups. Patient′s general status, probing depth (PD) , clinical attachment loss (CAL), sulcus bleeding index (SBI), simplified calculus index (CI-S) and simplified debris index (DI-S) were recorded in 4 groups. Samples of serum and gingival crevicular fluid were collected from patients of each group, and the expression levels of MMP-3 in serum and gingival crevicular fluid samples were detected by using enzyme-linked immunosorbent assay. Erythrocyte sedimentation rate, rheumatoid factor, anti-cyclic citrulline peptide antibody and C-reactive protein were detected in the serum of subjects in RA group and CP+RA group. Correlation analysis was conducted between MMP-3 expression level and periodontal indices amongst 4 groups. The results were statistically analyzed using the SPSS 20.0 software package.@*Results@#The indices of CAL [(4.12±1.13) mm], SBI (2.58±0.64) and DI-S (2.65±0.69) in CP+RA group were significantly higher than indices of CAL [(3.00±0.00) mm], SBI (2.59±1.05) and DI-S, (2.36±0.49) in CP group (P<0.05); The expression levels of MMP-3 in serum samples of CP+RA group [(1 1645.6±6 903.4) μg/L] and CP group [(9 337.0±6 719.0) μg/L] were significantly higher than that of RA group [(2 389.9±1 320.3) μg/L] and H group [(1 493.5±292.1) μg/L] (P<0.05). The expression level of MMP-3 in gingival crevicular fluid samples of CP+RA group [(164.4±45.3) μg/L] was significantly higher than that of CP group [(84.6±92.5) μg/L], RA group [(49.0±18.1) μg/L] and H group [(20.4±6.3) μg/L] (P<0.05), respectively. The erythrocyte sedimentation rate, rheumatoid factor and anti-cyclic cirullinated peptide antibodies levels in the CP+RA group were significantly higher than those in the RA group (P<0.05). The expression level of MMP-3 in serum is positively correlated with PD (r=0.45, P=0.04) and the expression level of MMP-3 in gingival crevicular fluid is positively correlated with CAL (r=0.58, P<0.01).@*Conclusions@#The levels of MMP-3 in serum and gingival crevicular fluid of patients with RA and CP were significantly increased. MMP-3 may be associated with the development of CP and RA.
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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.
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@# 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.
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Objective@#To investigate the levels of matrix metalloproteinases-3 (MMP-3), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) in the hydrothorax and ascites, and to approach the diagnostic value of three combined indexes in benign and malignant hydrothorax and ascites.@*Methods@#Case-control study. A total of 278 patients with hydrothorax and ascites were enrolled in this study who were hospitalized in the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from August 2018 to July 2019 to detect the levels of MMP-3, ADA and LDH in the hydrothorax and ascites. The benign group (208 patients) and malignant group (70 patients) were compared with MMP-3, ADA, LDH, receiver operating characteristic (ROC) curve, sensitivity and specificity in the hydrothorax and ascites, and the results were compared comprehensively.@*Results@#(1)The MMP-3 level in the benign hydrothorax group was 89.21±61.93 ng/mL, the ADA level was (9.08±8.89) U/L, the LDH level was (143.34±68.63) U/L, and the MMP-3 level in the malignant hydrothorax group was (205.63±98.16) ng/mL, he ADA level was (10.96±5.04) U/L, the LDH level was (243.44±131.20) U/L. The MMP-3 level in the benign ascites group was (84.91±73.48) ng/mL, the ADA level was (3.48±2.80) U/L, the LDH level was (99.48±69.53) U/L, and the MMP-3 level in the malignant ascites group was (174.89±82.48) ng/mL, the ADA level was (6.31±4.42) U/L, the LDH level was (191.86±94.52) U/L. The levels of MMP-3, ADA and LDH in the hydrothorax and ascites of the malignant group were higher than those in the benign group, and the difference was statistically significant (Z1 values were 5.215, 2.549, 3.212, respectively, and Z2 values were 6.188, 4.524, 6.38, respectively, P1 and P2 were <0.05). (2)The area under the curve (AUC) of MMP-3 for diagnosis of hydrothorax, liver cancer ascites and gastric cancer ascites was 0.853, 0.826, and 0.763, respectively. The sensitivity was 76%, 96.9%, and 92.3%, respectively, and the specificity was 80%, 64.5%, 61.6%. The diagnostic efficacy of MMP-3 in lung cancer hydrothorax and liver cancer ascites was higher than ADA (AUC were 0.672, 0.691,respectively) and LDH (AUC were 0.717, 0.804, respectively), and the diagnostic efficacy of gastric cancer ascites was lower than ADA (AUC is 0.808) and LDH (AUC is 0.849), and LDH was the best. (3)The AUC of MMP-3, ADA and LDH combined diagnosis of lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites were 0.861, 0.842, and 0.879, respectively. The sensitivities were 64%, 96.9%, and 84.6%, respectively, and the specificities were 92.9%, 63.8%, and 80.4%, respectively. In the lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites, the combined efficacy of the three combined tests was better than the combined detection of MMP-3 and LDH (AUC were 0.86, 0.839, 0.872, respectively), combined detection of MMP-3 and ADA (AUC were 0.845, 0.831, 0.855, respectively), LDH and ADA combined detection (AUC were 0.713, 0.791, 0.846, respectively).@*Conclusions@#MMP-3 is important for the differential diagnosis of benign and malignant hydrothorax and ascites, and may be one of the important indicators for the differential diagnosis of benign and malignant hydrothorax and ascites. The diagnostic efficacy of MMP-3 combined with ADA and LDH and three combined detection is better than single index, which has certain clinical value for differential diagnosis of benign and malignant hydrothorax and ascites.
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Rheumatic immune disease is a kind of disease caused by the abnormal of autoimmune system, the pathogenesis is complex and affected by many factors. Matrix metalloproteinases are a kind of proteolytic enzyme that can degrade extracellular matrix components, while the matrix metalloproteinase3 is the main enzyme that promote their degradation. In recent years, studies have found that matrix metalloproteinase-3 participates in the development of rheumatic immune disease. It is a potential marker not only can reflect the activity of some diseases, but also to evaluate therapeutic effect.
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Objective To investigate the levels of matrix metalloproteinases-3 (MMP-3), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) in the hydrothorax and ascites, and to approach the diagnostic value of three combined indexes in benign and malignant hydrothorax and ascites. Methods Case-control study. A total of 278 patients with hydrothorax and ascites were enrolled in this study who were hospitalized in the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from August 2018 to July 2019 to detect the levels of MMP-3, ADA and LDH in the hydrothorax and ascites. The benign group (208 patients) and malignant group (70 patients) were compared with MMP-3, ADA, LDH, receiver operating characteristic (ROC) curve, sensitivity and specificity in the hydrothorax and ascites, and the results were compared comprehensively. Results (1)The MMP-3 level in the benign hydrothorax group was 89.21±61.93 ng/mL, the ADA level was (9.08±8.89) U/L, the LDH level was (143.34± 68.63) U/L, and the MMP-3 level in the malignant hydrothorax group was (205.63 ± 98.16) ng/mL, he ADA level was (10.96±5.04) U/L, the LDH level was (243.44±131.20) U/L. The MMP-3 level in the benign ascites group was (84.91±73.48) ng/mL, the ADA level was (3.48±2.80) U/L, the LDH level was (99.48±69.53) U/L, and the MMP-3 level in the malignant ascites group was (174.89 ± 82.48) ng/mL, the ADA level was (6.31 ± 4.42) U/L, the LDH level was (191.86±94.52) U/L. The levels of MMP-3, ADA and LDH in the hydrothorax and ascites of the malignant group were higher than those in the benign group, and the difference was statistically significant (Z1 values were 5.215, 2.549, 3.212, respectively, and Z2 values were 6.188, 4.524, 6.38, respectively, P1 and P2 were <0.05). (2)The area under the curve (AUC) of MMP-3 for diagnosis of hydrothorax, liver cancer ascites and gastric cancer ascites was 0.853, 0.826, and 0.763, respectively. The sensitivity was 76％, 96.9％, and 92.3％, respectively, and the specificity was 80％, 64.5％, 61.6％. The diagnostic efficacy of MMP-3 in lung cancer hydrothorax and liver cancer ascites was higher than ADA (AUC were 0.672, 0.691, respectively) and LDH (AUC were 0.717, 0.804, respectively), and the diagnostic efficacy of gastric cancer ascites was lower than ADA (AUC is 0.808) and LDH (AUC is 0.849), and LDH was the best. (3)The AUC of MMP-3, ADA and LDH combined diagnosis of lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites were 0.861, 0.842, and 0.879, respectively. The sensitivities were 64％, 96.9％, and 84.6％, respectively, and the specificities were 92.9％, 63.8％, and 80.4％, respectively. In the lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites, the combined efficacy of the three combined tests was better than the combined detection of MMP-3 and LDH (AUC were 0.86, 0.839, 0.872, respectively), combined detection of MMP-3 and ADA (AUC were 0.845, 0.831, 0.855, respectively), LDH and ADA combined detection (AUC were 0.713, 0.791, 0.846, respectively). Conclusions MMP-3 is important for the differential diagnosis of benign and malignant hydrothorax and ascites, and may be one of the important indicators for the differential diagnosis of benign and malignant hydrothorax and ascites. The diagnostic efficacy of MMP-3 combined with ADA and LDH and three combined detection is better than single index, which has certain clinical value for differential diagnosis of benign and malignant hydrothorax and ascites.
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Rheumatic immune disease is a kind of disease caused by the abnormal of autoimmune system, the pathogenesis is complex and affected by many factors. Matrix metalloproteinases are a kind of proteolytic enzyme that can degrade extracellular matrix components, while the matrix metalloproteinase3 is the main enzyme that promote their degradation. In recent years, studies have found that matrix metalloproteinase-3 participates in the development of rheumatic immune disease. It is a potential marker not only can reflect the activity of some diseases, but also to evaluate therapeutic effect.
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Objective To evaluate the protective effect of exogenous biliverdin on ultraviolet B (UVB)-radiated HaCaT cells,and to explore its mechanism.Methods Cultured HaCaT cells were divided into 5 groups:control group receiving no treatment,UVB group irradiated with 30 mJ/cm2 UVB,3 biliverdin + UVB groups treated with 100 nmol/L,1 μmol/L and 10 μmol/L biliverdin respectively for 1 hour followed by 30 mJ/cm2 UVB radiation.After 24-hour treatment,changes in the morphology of HaCaT cells were observed,and cell counting kit 8 (CCK8) assay was performed to determine cell survival rates in the above groups.Western blot analysis was conducted to measure the protein expression of antioxidant signaling molecule NF-E2-related factor-2 (Nrf-2) and the photodamage signaling molecules matrix metalloproteinase-1 (MMP-1) and MMP-3.Results CCK8 assay showed that the survival rate of HaCaT cells was significantly lower in the UVB group than in the control group (P ＜ 0.05),but significantly higher in the 100-nmol/L,1-μmol/L and 10-μmol/L biliverdin + UVB groups than in the UVB group (all P ＜ 0.05).Western blot analysis showed that the protein expression of MMP-1 and MMP-3 was significantly higher in the UVB group (1.150 ± 0.187,0.979 ± 0.054 respectively) than in the control group (0.116 ± 0.018,0.636 ± 0.035 respectively;both P ＜ 0.01),but was significantly lower in the 100-nmol/L,1-μmol/L and 10-μmol/L biliverdin + UVB groups (MMP-1:0.825 ± 0.139,0.313 ± 0.047 and 0.286 ± 0.036 respectively;MMP-3:0.888 ± 0.017,0.672 ± 0.042 and 0.569:±:0.037 respectively) than in the UVB group (all P ＜ 0.05).Moreover,the protein expression of Nrf-2 was significantly lower in the UVB group (0.906 ± 0.034) than in the control group (1.242 ± 0.141,P ＜ 0.05),but significantly higher in the 100-nmol/L,1-μmol/L and 10-μmol/L biliverdin + UVB groups (1.556 ± 0.112,1.897 ± 0.234 and 2.035 ±0.274) than in the UVB group (all P ＜ 0.01).Conclusion Exogenous biliverdin protects against UVB-induced photodamage in HaCaT cells,which may be associated with Nrf-2 antioxidant signaling pathway.
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Objective To study the function of interleukin (IL)-25 for rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) differentiation as well as on the expression of extracellular regulating protein kinase (ERK) and matrix metalloproteinases-3 (MMP-3).Methods The differences on ERK1/2 and MMP-3 protein levels were tested in RA-FLS of RA patients and healthy controls,then IL-17A (10 ng/ml) was tested when the RA-FLS were co-stimulated with different concentrations of IL-25 (0.01,0.1,1 and 10 ng/ml) and IL-17A(10 ng/ml) for 24 hours respectively.The expression of ERK1/2 and MMP-3 protein was detected by the Western blot.T test was used for the comparison between different groups.Results The expression of ERK1/2 (1.71±0.17) and MMP-3 (0.50±0.13) proteins in RA-FLS was higher than the healthy controls (0.50±0.15,0.17±0.05) (t=-9.13,P＜0.01 and t=-4.10,P＜0.05),after stimulated with IL-17A,the expression of ERK1/2 (0.77±0.22) and MMP-3 (0.59±0.13) proteins in RA-FLS were increased compared with the untreated groups (0.18±0.35,0.04±0.03) (t=-4.69,P＜0.01 and t=-7.47,P＜0.01).With increase of the concentration on IL-25,the level of ERK1/2 (0.54±0.26,0.48±0.18,0.48±0.23,0.23±0.06) and MMP-3 (0.58±0.09,0.59±0.14,0.21±0.04,0.04±0.02) in RA-FLS which were stimulated by IL-17A was decreased slowly (t=4.22,P＜0.05 and t=4.95,P＜0.01 and t=7.47,P＜0.01).Conclusion IL-25 can inhibit the stimulation of IL-17A on ERK1/2 and MMP-3 fractionally,which implies that it may take part in the development of RA through this pathway and may be a target for the RA treatment.
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Objective:To investigate the curative efficacy of combined use of dexamethasone palmitate,vitamin B12 and lidocaine in the treatment of knee osteoarthritis and its effects on the seum levels of interleukin-1 (IL-1),matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-1 (TIMP-1).Methods:84 patients with osteoarthritis of knee were selected from August 2014 to July 2015 in Sixth Affiliated Hospital of Xinjiang Medical University and divided into the observation group and the control group according to the order of admission,42 cases in each group.The observation group was given intra-articular injection of dexamethasone palmitate,vitamin B12 and lidocaine,and the control group was treated with traditional Chinese medicine.The clinical efficacy was evaluated after treatment.The changes of serum IL-1,MMP-3,TIMP-1 levels and visual analogue (VAS) score were compared before and at 1 months after treatment.Results:After treatment,the total effective rate of observation group was significantly higher than that of the control group (P＜0.05),the serum levels ofIL-1,MMP-3 levels and VAS score were significantly lower than those before treatment,serum TIMP-1 level was obviously higher than that before treatment(P ＜0.05),the serum levels of IL-1,MMP-3 levels were significantly lower in the observation group than those of the control group,while the serum TIMP-1 level was obviously higher than(P＜0.05) Conclusion:Intra-articular injection with dexamethasone palmitate,vitamin B12 and lidocaine could effectively decrease the levels of serum IL-1 and MMP-3,increase the level ofTIMP-1,and relieve the pain in the patients with knee osteoarthritis.
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Objective To study the effects of restructuring tissue inhibitor of matrix metatloproteinase-3 (rhTIMP-3) in combination with cisplatin (DDP) on the growth and apoptosis of A549 lung cancer cell line.Methods We made individual and combined use of different concentrations of rhTIMP-3 and DDP on A549 cells.Methyl thiazoyl terazolium (MTT) colorimetry was used to analyze cell growth inhibition,and flow cytometry technique was used to determine the cell cycle distribution and apoptosis rate.Results rhTIMP-3 and DDP both could inhibit the proliferation of A549 cells.rhTIMP-3 exerted its effect in the time-and concentration-dependent manners while DDP did so in the concentration-dependent manner;both induced the apoptosis of A549 cells.rhTIMP-3 could make the cells stay in S and G2/M phases,and DDP made the cells stay in S phase.The combination of them obviously strengthened the inhibition of A549 cell growth,and had obvious synergy in inducing apoptosis.Conclusion Both rhTIMP-3 and DDP can inhibit the proliferation of A549 cells and induce their apoptosis.The combined use of them not only can increase the inhibition of cell growth but also has synergy in inducing cell apoptosis.