Correlations of expressions of tissue inhibitor of matrix metalloproteinase-1 and fibronectin 1 in pregnancy associated breast cancer with expression of E-cadherin and prognosis / 肿瘤研究与临床

Objective:To investigate the expressions of tissue inhibitor of matrix metalloproteinase-1 (TIMP1) and fibronectin 1 (FN1) in pregnancy associated breast cancer (PABC) and their correlations with expression of E-cadherin (E-cad).Methods:The clinicopathological data of 55 PABC patients in Binzhou People's Hospital Affiliated to Shandong First Medical University from January 2011 to December 2020 were retrospectively analyzed. Immunohistochemistry was used to detect expressions of TIMP1, FN1 and E-cad in cancer tissues and corresponding paracancerous tissues (>3 cm from the edge of the tumor foci). The expressions of TIMP1 and FN1 proteins in fresh intraoperative frozen cancer tissues and paracancerous tissues of 10 PABC patients were detected by Western blotting. The correlations of TIMP1 and FN1 expressions with clinicopathological characteristics of patients were analyzed by χ2 test, the correlation of TIMP1 and FN1 expressions with E-cad expression was analyzed by Spearman method, and the correlation of TIMP1 and FN1 expressions with survival was analyzed by Kaplan-Meier method. Results:The positive rates of TIMP1 and FN1 in PABC tissues were 72.7% (40/55) and 58.2% (32/55), and 25.5% (14/55) and 18.2% (10/55) in paracancerous tissues, and the differences were statistically significant ( χ2 values were 24.59 and 18.64, both P < 0.001). The results of Western blotting showed that the relative expressions of TIMP1 and FN1 proteins in the fresh cancer tissues of 10 PABC patients was higher than those in the corresponding paracancerous tissues (1.60±0.76 vs. 0.62±0.29, 1.31±0.62 vs. 0.44±0.15), and the differences were statistically significant ( t values were 5.92 and 4.86, both P < 0.001). The expressions of TIMP1 and FN1 in PABC tissues were correlated with estrogen receptor expression, Ki-67 positivity index, TNM stage and lymph node metastasis (all P < 0.05). The expressions of TIMP1 and FN1 were negatively correlated with expression of E-cad in PABC ( r values were -0.471 and -0.432, both P < 0.001). Five cases were lost to follow-up, and the remaining 50 cases had a median follow-up time of 43 months (12-90 months). Among the 50 cases, 36 cases were TMP1-positive and 29 cases were FN1-positive. The overall survival of TIMP1-negative group and FN1-negative group were better than those of the corresponding positive group ( χ2 values were 4.49 and 6.06, both P < 0.05); the median overall survival time of TIMP1-positive group and FN1-positive group were 51 months (95% CI 37-65 months) and 43 months (95% CI 32-53 months), while that of TIMP1-negative group and FN1-negative group were 89 months (95% CI 84-93 months) and 87 months (95% CI 85-92 months). Conclusions:TIMP1 and FN1 expressions are elevated in PABC tissues and negatively correlated with E-cad expression, TIMP1 and FN1 may be involved in PABC invasion through epithelial-mesenchymal transition and affect the prognosis of patients.

Association of matrix metalloproteinase-1-1607 1G/2G single nucleotide polymorphism genotypes with periodontitis in Iraqi population / Associação entre genótipos de polimorfismo de nucleotídeo único de metaloproteinase-1-1607 1G/2G da matriz e periodontite em população iraquiana

Objective and background: Periodontitis is an inflammatory disease which is characterized by a progressive loss in the matrix of soft and hard tissue of periodontium particularly the collagen fibers which are cleaved by matrix Metalloproteinase (MMP). Indeed, increased activity of MMP mediates progression of periodontal diseases but population-based genetic variations could determine the susceptibility to the disease. The aim was to investigate association between MMP-1-1607 polymorphism with periodontitis among Iraqi individuals. Subjects and methods: The design of this study was a case-control for Iraqi individuals who were divided into two groups; periodontitis group (cases) and those with healthy periodontium (Control). For each subject, clinical periodontal parameters and demographic characteristics were recorded and venous blood was withdrawn for genetic analysis of MMP-1 by using PCR technique and DNA sequencing. Results: Analysis of MMP-1-1607 genotypes, by Hardy-Weinberg equilibrium, showed significant differences in the total sample. The most predominant MMP-1-1607 genotype among Controls was 1G/2G which was significantly different from periodontitis cohorts. Overall, 13 SNP were detected in periodontitis group versus 17 SNP in Control group. In addition, the periodontitis group showed a significant negative association between the probing pocket depth and MMP-1-1607. Conclusion: Results suggested that polymorphisms in MMP-1-1607 1G/2G may play a protective role and decreasing the susceptibility to periodontitis. (AU)

Introdução e objetivo: A periodontite é uma doença inflamatória caracterizada pela perda progressiva da matriz dos tecidos moles e duros do periodonto, particularmente as fibras de colágeno clivadas pelas metaloproteinases da matriz (MMPs). De fato, o aumento da atividade de MMPs medeia a progressão das doenças periodontais, mas as variações genéticas baseadas na população podem determinar a suscetibilidade à doença. O objetivo foi investigar a associação entre o polimorfismo MMP-1-1607 e periodontite em indivíduos iraquianos. População e método: O desenho deste estudo foi um caso-controle com indivíduos iraquianos, os quais foram divididos em dois grupos: grupo periodontite (casos) e indivíduos com periodonto saudável (controle). Para cada sujeito, os parâmetros clínicos periodontais e as características demográficas foram registrados, e o sangue venoso foi coletado para análise genética de MMP-1 por meio da técnica de PCR e sequenciamento de DNA. Resultados: A análise dos genótipos MMP-1-1607, pelo equilíbrio de Hardy-Weinberg, mostrou diferenças significativas na amostra total. O genótipo MMP-1-1607 mais predominante entre os controles foi 1G/2G, o qual foi significativamente diferente das coortes de periodontite. No geral, 13 SNP foram detectados no grupo periodontite versus 17 SNP no grupo controle. Além disso, o grupo periodontite mostrou uma associação negativa significativa entre a profundidade da bolsa de sondagem e MMP-1-1607. Conclusão: Os resultados sugerem que polimorfismos em MMP-1-1607 1G/2G podem desempenhar um papel protetor e diminuir a suscetibilidade à periodontite. (AU)

Changes of collagen and MMP-1 in liver, lung and kidney during growth of mice / 生物工程学报

The high performance liquid chromatography (HPLC) and enzyme-linked immunoassay (ELISA) were used to investigate the changes of collagen and matrix metalloproteinase-1 (MMP-1) in liver, lung and kidney during growth process of mice. The mice from 0 to 18 weeks were used as the research objects. The contents and proportions of hydroxyproline (Hyp), which were used to calculate the collagen contents, in liver, lung and kidney of different weeks were analyzed with HPLC. The contents and activity of MMP-1 in liver, lung and kidney of different weeks were analyzed with ELISA. The results showed that the collagen contents in liver, lung, and kidney were different (Lung(COL)>Kidney(COL)>Liver(COL)), and they all increased first and then decreased with weeks. The collagen contents in liver, lung, and kidney reached the highest level in the ninth (5.52 ng/mg), sixth (54.10 ng/mg) and ninth (19.20 ng/mg) week, respectively. Then it declined slowly from 9 to 18 weeks. The result of ELISA showed that the MMP-1 contents in liver, lung and kidney decreased first and then increased with weeks, and the trend of MMP-1 activity was opposite. It indicated that the increase of collagen contents in the tissues will inhibit the secretion of MMP-1.

Effects of different negative pressure suction devices on collagen, MMP-1 and TGF-β secretion of skin / 中华医学美学美容杂志

Objective:To compare the effects of circular arch device and dressing device on the secretion of collagen, matrix metalloproteinase (MMP-1), transforming growth factor (TGF-β) of fibroblasts in the treated skin, and to explore the changes and mechanisms.Methods:The animals were purchased from the Southern Medical University Laboratory Animal Center. Using the established animal model, 54 mice were randomly divided into three groups: 18 mice each group, including control group, dressing device group and and circular arch device group. At the first, third and fifth day after negative pressure suction treatment, dermal thickness and density of collagen levels were and eosin staining, collagen level in local skin was determined using spectrophotometry, and MMP-1 and TGF-β levels were determined using enzyme linked immunosorbent assay.Results:Dermal thickness level was increased significantly in negative suction treated groups [after 5 days of treatment, control group: (71±8) μm; circular arch device group: (351±9) μm; dressing device group: (267±12) μm, P< 0.05]. Compared with the control group, collagen level in the dermis was significantly higher in circular arch device groups [after 5 days of treatment, control group: (30.9±4.3) mg/g; circular arch device group: (72.7±3.6) mg/g, P< 0.05]. TGF-β level in circular arch device treated group was increasing gradually, and markedly higher than that in the dressing device group and the control group [after 5 days of treatment, control group: (0.24±0.1) ng/ml; circular arch device group: (0.78±0.08) ng/ml; dressing device group: (0.39±0.18) ng/ml, P< 0.05], while MMP-1 level was decreasing. In addition, TGF-β and MMP-1 levels in the dressing device treated group remained stable during the entire experiment. Conclusions:The interface of the circular arch negative pressure suction device can effectively activate the fibroblasts, promote the secretion of TGF-β and collagen, and thicken the skin tissue.

Association between matrix metalloproteinase-1 (MMP-1) protein level and the risk of rheumatoid arthritis and osteoarthritis: a meta-analysis

Recent publications have investigated the potential role of the protein level of matrix metalloproteinase-1 (MMP-1) in the susceptibility to rheumatoid arthritis (RA) and osteoarthritis (OA). However, no unanimous conclusion was obtained. Therefore, we carried out a meta-analysis to explore the association between MMP-1 expression and these two clinical disorders. After database searching and screening, we enrolled a total of eighteen articles for the pooled analysis. We observed a significant association between RA cases and controls in the whole population [SMD (standard mean difference)=1.01, P=0.017]. There were similar positive results in the subgroup analysis of "population-based control" (SMD=1.50, P=0.032) and "synovial fluid" (SMD=1.32, P=0.049). In addition, we observed an increased risk in OA cases, compared with controls, in the overall analysis (SMD=0.47, P=0.004) and subsequent subgroup analysis of "knee OA" (SMD=0.86, P<0.001), "Asian/China" (SMD=0.76, P=0.003), "cartilage-Asian/China" (SMD=1.21, P<0.001), and "synovial fluid-Asian/China" (SMD=0.73, P=0.004). In summary, a high protein level of MMP-1 in synovial fluid may be associated with the susceptibility to RA, and the high MMP-1 level in the cartilage tissue or synovial fluid may be related to the pathogenesis of knee OA in the Chinese population. This should be confirmed by larger sample sizes.

Effect of Different Combinations of Gentianae Macrophyllae Radix on MMP-3 and TIMP-1 in Rheumatoid Arthritis Rats with Wind-cold-dampness Arthralgia / 中国实验方剂学杂志

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.

Effects of Wenxin granules and bisoprolol fumarate combined with aerobic exercise on serum matrix metallo-proteinase-1 and N-terminal pro-brain natriuretic peptide levels in patients with unstable angina pectoris / 中国基层医药

Objective To investigate the influence of Wenxin granules and bisoprolol fumarate combined with aerobic exercise on serum matrix metalloproteinase－1(MMP－1) and N－terminal pro－brain natriuretic peptide (NT－proBNP) levels in patients with unstable angina pectoris.Methods From January 2016 to February 2018, 92 patients with unstable angina pectoris in Lishui Hospital of Traditional Chinese Medicine were selected and randomly divided into control group(n=46) and study group(n=46) according to the digital table.On the basis of routine intervention,the control group was given bisoprolol fumarate for 2 weeks and aerobic exercise for 1 month, while the study group was given bisoprolol fumarate,aerobic exercise and Wenxin granules for 2 weeks.The frequency and duration of angina pectoris before and after 1 month of treatment,clinical efficacy,serum MMP－1 and NT－proBNP levels,blood rheology index(plasma viscosity,whole blood high shear viscosity,total blood low－cut viscosity,fibrinogen) and incidence of adverse reactions were observed.Results After 1 month of treatment,the frequency of angina pectoris was lower than that before treatment,and the duration was shorter than that before treatment,which in the study group [(2.09 ± 0.65)times/week,(2.24 ± 0.83)min/time] were better than those in the control group(t1=10.898,t2= 9.302,all P<0.05).The total effective rate of the study group(91.30% ) was higher than that of the control group (73.91% )(χ2 =4.842,P<0.05).After 1 month of treatment,the serum levels of MMP－1 and NT－proBNP in the two groups were lower than those before treatment,which in the study group [(196.10 ± 55.01) g/L,(403.82 ± 114.15)ng/L] were lower than those in the control group ( t1 =3. 619, t2 =4. 185, P <0. 05 ). At the end of treatment,the plasma viscosity,whole blood high－viscosity,whole blood low－cut viscosity,fibrinogen level in the two groups were lower than those before treatment,which in the study group were lower than those in the control group(all P<0.05).The incidence rate of adverse reactions in the study group was 15.22% ,which in the control group was 10.87% ,there was no statistically significant difference between the two groups (χ2 =0.383,P>0.05).Conclusion The combination of Wenxin granules, bisoprolol fumarate and aerobic exercise for patients with unstable angina pectoris not only can reduce the frequency of angina pectoris,MMP－1 and NT－proBNP levels,but also can improve the treatment of disease.Besides,it does not increase the risk of adverse reactions.

Effects of the Syzygium aromaticum L. Extract on antioxidation and inhibition of matrix metalloproteinase in human dermal fibroblast

Objective: To investigate cosmetic potential of Syzygium aromaticum L. (S. aromaticum L.) and to determine its antioxidant and anti-wrinkling effects. Methods: Using high-performance liquid chromatography, eugenol component was quantitated. The antioxidant activity of S. aromaticum L. was analyzed by 2,2-diphenyl-1-picrylhydrazyl radical scavenging and superoxide dismutase like activities. To determine cell viability, elastase and matrix metalloproteinase-1 (MMP-1) activity, human dermal fibroblasts (HS68) were treated with S. aromaticum L. The inhibitory effect of S. aromaticum L. on tumor necrosis factor alpha induced MMPs expression in HS68 was analyzed by realtime-PCR. Results: The eugenol content was confirmed in S. aromaticum L. S. aromaticum L. was observed to have high 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and superoxide dismutase like activity. S. aromaticum L. had no cytotoxicity against the HS68 and dose-dependently increased elastase inhibition. Moreover, S. aromaticum L. significantly decreased MMP-1 content and inhibited gene levels of MMP-1, MMP-2, MMP-3 and MMP-9. Conclusions: The findings suggest that S. aromaticum L. has great potential as a cosmeceutical ingredient with antioxidant and anti-wrinkling effects.

Effects of the Syzygium aromaticum L. extract on antioxidation and inhibition of matrix metalloproteinase in human dermal fibroblast

Objective: To investigate cosmetic potential of Syzygium aromaticum L. (S. aromaticum L.) and to determine its antioxidant and anti-wrinkling effects. Methods: Using high-performance liquid chromatography, eugenol component was quantitated. The antioxidant activity of S. aromaticum L. was analyzed by 2,2-diphenyl-1-picrylhydrazyl radical scavenging and superoxide dismutase like activities. To determine cell viability, elastase and matrix metalloproteinase-1 (MMP-1) activity, human dermal fibroblasts (HS68) were treated with S. aromaticum L. The inhibitory effect of S. aromaticum L. on tumor necrosis factor alpha induced MMPs expression in HS68 was analyzed by realtime-PCR. Results: The eugenol content was confirmed in S. aromaticum L. S. aromaticum L. was observed to have high 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and superoxide dismutase like activity. S. aromaticum L. had no cytotoxicity against the HS68 and dose-dependently increased elastase inhibition. Moreover, S. aromaticum L. significantly decreased MMP-1 content and inhibited gene levels of MMP-1, MMP-2, MMP-3 and MMP-9. Conclusions: The findings suggest that S. aromaticum L. has great potential as a cosmeceutical ingredient with antioxidant and anti-wrinkling effects.

Effects of Wenxin granules and bisoprolol fumarate combined with aerobic exercise on serum matrix metallo-proteinase -1 and N - terminal pro - brain natriuretic peptide levels in patients with unstable angina pectoris / 中国基层医药

Objective To investigate the influence of Wenxin granules and bisoprolol fumarate combined with aerobic exercise on serum matrix metalloproteinase -1(MMP -1) and N - terminal pro - brain natriuretic peptide (NT - proBNP) levels in patients with unstable angina pectoris. Methods From January 2016 to February 2018, 92 patients with unstable angina pectoris in Lishui Hospital of Traditional Chinese Medicine were selected and randomly divided into control group(n = 46) and study group(n = 46) according to the digital table. On the basis of routine intervention,the control group was given bisoprolol fumarate for 2 weeks and aerobic exercise for 1 month, while the study group was given bisoprolol fumarate,aerobic exercise and Wenxin granules for 2 weeks. The frequency and duration of angina pectoris before and after 1 month of treatment,clinical efficacy,serum MMP -1 and NT - proBNP levels,blood rheology index(plasma viscosity,whole blood high shear viscosity,total blood low - cut viscosity,fibrinogen) and incidence of adverse reactions were observed. Results After 1 month of treatment,the frequency of angina pectoris was lower than that before treatment,and the duration was shorter than that before treatment,which in the study group [(2. 09 ± 0. 65)times/ week,(2. 24 ± 0. 83)min/ time] were better than those in the control group(t1 = 10. 898,t2 =9. 302,all P < 0. 05). The total effective rate of the study group(91. 30％ ) was higher than that of the control group (73. 91％ )(χ2 = 4. 842,P < 0. 05). After 1 month of treatment,the serum levels of MMP - 1 and NT - proBNP in the two groups were lower than those before treatment,which in the study group[(196. 10 ± 55. 01) g/ L,(403. 82 ± 114. 15)ng/ L] were lower than those in the control group ( t1 = 3. 619, t2 = 4. 185, P < 0. 05). At the end of treatment,the plasma viscosity,whole blood high - viscosity,whole blood low - cut viscosity,fibrinogen level in the two groups were lower than those before treatment,which in the study group were lower than those in the control group(all P < 0. 05). The incidence rate of adverse reactions in the study group was 15. 22％ ,which in the control group was 10. 87％ ,there was no statistically significant difference between the two groups (χ2 = 0. 383,P > 0. 05). Conclusion The combination of Wenxin granules, bisoprolol fumarate and aerobic exercise for patients with unstable angina pectoris not only can reduce the frequency of angina pectoris,MMP - 1 and NT - proBNP levels,but also can improve the treatment of disease. Besides,it does not increase the risk of adverse reactions.

Esculetin Prevents the Induction of Matrix Metalloproteinase-1 by Hydrogen Peroxide in Skin Keratinocytes

BACKGROUND: Reactive oxygen species (ROS) are involved in various cellular diseases. Excessive ROS can cause intracellular oxidative stress, resulting in a calcium imbalance and even aging. In this study, we evaluated the protective effect of esculetin on oxidative stress-induced aging in human HaCaT keratinocytes. METHODS: Human keratinocytes were pretreated with esculetin for 30 minutes and treated with H₂O₂. Then, the protective effects on oxidative stress-induced matrix metalloproteinase (MMP)-1 were detected by Flou-4-AM staining, reverse transcription-PCR, Western blotting, and quantitative fluorescence assay. RESULTS: Esculetin prevented H₂O₂-induced aging by inhibiting MMP-1 mRNA, protein, and activity levels. In addition, esculetin decreased abnormal levels of phospho-MEK1, phospho-ERK1/2, phospho-SEK1, phospho-JNK1/2, c-Fos, and phospho-c-Jun and inhibited activator protein 1 binding activity. CONCLUSIONS: Esculetin prevented excessive levels of intracellular calcium and reduced the expression levels of aging-related proteins.

Inhibitory effect of Qilan Capsules on the expressions of vasculogenic mimicry-related proteins in prostate cancer / 中华男科学杂志

<p><b>Objective</b>To investigate the effect of Qilan Capsules (QLC) on the expressions of the related proteins HIF-1α, VEGF-α, EphA2 and MMP-1 in the formation of vasculogenic mimicry (VM) in prostate cancer.</p><p><b>METHODS</b>Prostate cancer PC-3 cells were cultured, transfected with siRNA, and divided into eight groups, blank control, HIF-1α siRNA, VEGF-α siRNA, EphA2 siRNA, QLC intervention, QLC + HIF-1α siRNA, QLC + VEGF-α siRNA, and QLC + EphA2 siRNA. The expressions of the HIF-1α, VEGF-α and EphA2 proteins in the pathway of VEGF were determined by Western blot.</p><p><b>RESULTS</b>Compared with the blank control group, the expression of HIF-1α was evidently decreased in the HIF-lα siRNA and QLC + HIF-lα siRNA groups (0.624 7 ± 0.042 8 vs 0.032 8 ± 0.002 5 and 0.036 8 ± 0.018 1, P < 0.05), so were that of VEGF-α in the VEGF-α siRNA and QLC + VEGF-α siRNA groups (0.068 9 ± 0.005 1 vs 0.016 9 ± 0.000 7 and 0.010 9 ± 0.000 8, P < 0.05), that of EphA2 in the EphA2 siRNA and QLC + EphA2 siRNA groups though with no statistically significant difference (0.1684 ± 0.0126 vs 0.134 5 ± 0.028 6 and 0.165 4 ± 0.039 8, P > 0.05), and that of MMP-1 in the HIF-lα siRNA, VEGF-α siRNA and EphA2 siRNA groups (1.696 1 ± 0.152 7 vs 0.435 9 ± 0.036 9, 0.198 7 ± 0.009 0 and 0.0218 ± 0.000 7, P < 0.05).</p><p><b>CONCLUSIONS</b>Qilan Capsules can suppress VM formation in prostate cancer by inhibiting the expressions of HIF-1α, VEGF-α and MMP-1, which plays a role in the clinical treatment of prostate cancer by checking the growth and development of the blood supply system in the tumor tissue.</p>

Infradiaphragmatic Stasis-Expelling Decoction reduce the expression of TIMP-1 contributing to inhibition of rat liver fibrosis / 实用医学杂志

Objective To investigate the protective effect and its mechanism of infradiaphragmatic stasis-expelling decoction on hepatic fibrosis in rats. Method One hundred and ten SD rats were divided into four groups:the normal control group ,model group ,low dose group and high dose group of infradiaphragmatic stasis-expelling decoction. In addition to the normal control group,rats in other groups were subcutaneously given pure CCl4 to set up the liver fibrosis model. Twelve weeks later,the serum liver biochemical indexes,including ALT,AST, ALB,TP and T-bil,the Ishak score about liver fibrosis ,the positive expression of TIMP-1 were compared among groups. Results Compared with the fibrotic group,the levels of serum ALT,AST and T-bil were lower in low dose group,the level of serum TP and ALB were increased in high dose group Levels of serum ALT,AST and T-bil were significantly lowered in high dose group,the levels of serum of TP and ALB were significantly increased in high dose group. Compared with model group,the Ishak score about liver fibrosis was significantly lowered(P<0.05). Numbers of cells with positive expression of TIMP-1 in liver tissue was reduced. Conclusion Infradiaphragmatic stasis-expelling decoction could inhibit the expression and activity of TIMP-1 contributing to the effect of antiliver fibrosis.

Effects of ShenGuiBaoXin Decoction on Matrix Metalloproteinase-2, the Tissue Inhibitor of Matrix Metalloproteinase-1, Brain Natriuretic Peptide, and Ventricular Remodeling in Rats with Chronic Heart Failure / 中国医科大学学报

Objective To observe the effects of ShenGuiBaoXin decoction on matrix metalloproteinases-2 (MMP-2), the tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), brain natriuretic peptide (BNP) levels, and cardiac histopathology in rats with heart failure, and to investigate the mechanism of the inhibition effect on ventricular remodeling in rats with heart failure. Methods Ninety male SD rats were randomly divided into two groups, with 15 rats in the control group and 75 rats in the model group. Normal saline was injected in the normal control group. The model group was given an intraperitoneal injection of isoprenaline 3 mg/ (kg·d). After 4 weeks, an ejection fraction of ≤50％ on echocardiography was considered a successful model. Seventy-five rats were randomly divided into the model, Qiliqiangxin, and ShenGuiBaoXin groups (high, medium, and low doses), with 15 rats in each group. Eight weeks later, the cardiothoracic ratio and BNP level were measured, hematoxylin-eosin staining was performed, and the MMP-2 and TIMP-1 protein expressions in the myocardium was detected. Results In terms of cardiothoracic ratio and BNP level, all the groups showed decreases after treatment, especially the Qiliqiangxin and high-dose groups. The MMP-2 protein expression level was decreased in all the groups after the treatment, and the high-dose group was superior to the Qiliqiangxin group. Conclusion ShenGuiBaoXin decoction functions by reducing the MMP-2 expression level, regulating MMP-2/TIMP-1 dynamic balance, maintaining the balance of synthesis and degradation of the extracellular matrix, inhibiting ventricular remodeling, and improving cardiac function.

Protective effect of exogenous biliverdin against ultraviolet B-induced photodamage in HaCaT cells / 中华皮肤科杂志

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.

The relationship between MMP-1 genetic polymorphisms and dental implant early failure in Chinese Han nationality / 重庆医学

Objective To make clear the relationship between the genetic polymorphism of MMP-1 and implant early failure.Methods We conducted a case control study,53 cases patients (no smoking history and without periodontitis) who have underwent dental implant were divided into experimental group(with dental implant failure) and control group(with dental implant success) according to early failure of dental implant (within one month).DNA of 53 patients in Han nationality were extracted by using Chelex-100 method and polymorphisms of the mmp-1-1607 gene were detected by restriction fragment length polymorphism after polymerase chain reactions.Results Patients with MMP-1-1607(1G/2G) genotype exhibited a significantly higher occurrence of implant early failure than those with MMP-1-1607(1G/1G) gene type(P＜0.05).The OR of the 1G/2G versus the 1G/1G of the MMP-1-1607 genotype was 13.894(P＜0.05).Conclusion MMP-1-1607(1G/2G) genotype is associated with implant early failure.

The expression and significance of matrix metalloproteinases-9 and tissue inhibitors of matrix metalloproteinase-1 in serum of infant with severe pneumonia / 中国小儿急救医学

Objective To explore the expression and significance of matrix metalloproteinases-9(MMP-9) and tissue inhibitors of matrix metalloproteinase-1(TIMP-1) in serum at acute phase of severe pneumonia in infants.Methods A total of 45 infants of pneumonia were selected and divided into 20 cases of severe pneumonia group and 25 cases of mild pneumonia group according to the severity of the disease,and all 45 infants were also divided into virus group of 24 cases and non-virus group of 21 cases on the basis of etiology.Additionally,20 cases of healthy children who accepted the physical examination at the same time were selected as the control group.Serum levels of MMP-9 and TIMP-1 were detected by using ELISA.Tidal breathing lung function was measured in all selected infants.Results Compared with the control group,the serum levels of MMP-9,TIMP-1 and MMP-9/TIMP-1 ratio of the infants with acute pneumonia were significantly higher,the severe pneumonia group were higher than the mild pneumonia group,and the virus group were higher than the non-virus group(P＜0.05).The ratio of the time to reach peak tidal expiratory flow to total expiratory time (TPTEF/TE) and the volume to reach peak tidal expiratory flow to total expiratory volume(VPTEF/VE) of pneumonia group in recovery period were significantly lower than those in the control group,severe pneumonia group were lower than those in the mild pneumonia group,and the virus group were lower than those in the non-virus group (all P＜0.05).There were no statistically significant about VT/kg among three groups.The serum MMP-9 levels and the MMP-9/TIMP-1 ratio were negatively correlated with TPTEF/TE and VPTEF/VE (r1=-0.459,-0.376; r2=-0.413,-0.327; all P＜0.05).Conclusion The serum levels of MMP-9 and the MMP-9/TIMP-1 ratio in the acute phase of infantile pneumonia are correlated with pneumonia severity and pulmonary function injury in recovery period,and the performance is particularly prominent in the viral pneumonia,and can be used as a prognosis monitoring indicator.

Deposition of collagen Ⅰ in adipose tissue of obese mice was inhibited by toll like receptor 2 knockout / 中华内分泌代谢杂志

Objective To explore the effect of TLR2 on collagen Ⅰ(colⅠ) in adipose tissue of high-fat-diet induced obese mice.Methods Male C57bl/6J mice and TLR2 knockout mice were divided into groups according to high fat diet or normal chow.Total collagen, TLR2, colⅠ, MMP1, MMP2, TIMP1, colⅠα1 mRNA and colⅠα2 mRNA in adipose tissue were measured at the end of the experiments.Results Total collagen, TLR2, colⅠ, MMP2, TIMP1, colⅠα1 mRNA, and colⅠα2 mRNA in adipose tissue increased while MMP1 in adipose tissue decreased in mice with high fat diet.Decreased levels of total collagen, colⅠ, MMP2, TIMP1, colⅠα1 mRNA and colⅠα2 mRNA in adipose tissue were detected in TLR2 gene knockout mice with high fat diet.However, there was an increased level of MMP1 in TLR2 gene knockout mice with high fat diet.Conclusion In high-fat-diet induced obese mice, deposition of colⅠ in adipose tissue seems to be alleviated by TLR2 gene knockout via MMP1 and TIMP1.

Effect of prazosin on MMP-1 and TIMP-1 expression in atherosclerosis plaque of ApoE -/- mice model / 重庆医学

Objective To observe the effects of prazosin on matrix metalloproteinase‐1(MMP‐1) and tissue inhibitor of met‐alloproteinase 1 (TIMP‐1) expression in atherosclerosis plaque of ApoE knock‐out(ApoE-/- ) mice model and to explore its anti‐atherosclerotic effect and mechanism .Methods Twenty‐four 8‐week‐old ApoE-/- mice were randomly divided into the normal diet group ,high‐fat diet group and prazosin group ,8 cases in each group .The normal diet group was fed by common fodder ,while the high fat group and prazosin group were fed by high fat diet ;on the basis of the high fat diet ,the prazosin group was started to con‐duct gavage of prazosin hydrochloride 1 mg/kg every day ,while the normal diet group and the high fat diet group were daily ga‐vaged by the same volume of normal saline .The abdominal aortic venous blood after 12 weeks in each group was collected for detec‐ting the blood lipid levels .The aorta arterial blood sample was collected for detecting MMP‐1 and TIMP‐1 expression levels by im‐munohistochemistry .Results Compared with the high fat diet group ,the levels of serum TG ,TC and LDL‐C in the prazosin group were significantly decreased ,and the HDL‐C level was increased ,the differences were statistically significant (P< 0 .01 or P<0 .05);the area of aorta arterial atherosclerotic plaque and intima thickness were significantly increased ,while prazosin could signif‐icantly inhibit the plaque formation and intima hyperplasia ;compared with the normal diet group ,the expression level of MMP‐1 protein in the high fat diet group and prazosin group was significantly increased ,while the TIMP‐1 protein expression level was de‐creased ,moreover the MMP‐1 protein expression level in the prazosin group was lower than that in the high fat diet group ,while the TIMP‐1 protein expression level was higher than that in the high fat diet group ,the differences were statistically significant (P<0 .05) .Conclusion Prazosin can decrease the level of TC and LDL‐C ,increase the HDL‐C level and has certain anti‐atherosclerotic effect ,its mechanism may be related with the decrease of the MMP‐1 level and the increase of the TIMP‐1 level in plaque .

Metodologia alternativa para o estudo dos efeitos da radiação infravermelha-A sobre a pele humana / Alternative methodology for the study of infrared-A radiation effects on human skin

Introdução: A radiação infravermelha A (IV-A) causa alterações estruturais na pele, similares àquelas provocadas pela exposição prolongada à radiação ultravioleta. A avaliação de eficácia e segurança para produtos cosméticos concentra-se em ensaios in vitro e clínicos. Uma alternativa promissora é a utilização de fragmentos de pele humana provenientes de cirurgias plasticas eletivas, para avaliar os reais beneficios os reais benefícios clínicos de um produto aplicado topicamente. Objetivo: O objetivo desta investigação foi correlacionar os efeitos da radiação IV-A, em biópsias e em fragmentos de pele ex vivo e cultura de fibroblastos humanos, pela quantificação dos mediadores MMP-1, TIMP-1 e GADD45a. Métodos: Coleta de biópsias de 15 voluntárias após aplicações de IV-A durante cinco dias consecutivos. Exposição à radiação IV-A de fragmentos de pele humana provenientes de cirurgia plástica eletiva e cultura de fibroblastos humanos. Mensuração dos mediadores MMP-1, TIMP-1 e GADD45a para posterior comparação dos resultados. Resultados: Nos três modelos utilizados a radiação IV-A induziu aumento de MMP-1, inibiu a síntese de GADD45a e não alterou os valores de TIMP-1. Conclusão: Devido à correlação positiva dos modelos estudados, pode-se sugerir o uso de pele ex vivo como ferramenta plausível e sustentável para suprir diferenças entre conhecimentos gerados a partir de experimentos in vitro e clínico.

Introduction: Infrared radiation (IR-A) causes structural changes in the skin, similar to those caused by prolonged exposure to ultraviolet radiation. Evaluation of efficacy and safety of cosmetic products concentrates in in vitro tests and clinical trials. A promising alternative is the use of fragments of human skin from elective cosmetic surgery, to evaluate the actual clinical benefits of a product applied topically. Objective: The objective of this study was to correlate IR-A radiation effects in biopsies and in ex vivo skin fragments and in human fibroblasts culture by quantifying MMP-1, TIMP-1 and GADD45a mediators. Methods: Collection of biopsies from 15 volunteers after IR-A applications for 5 consecutive days. Exposure to IR-A radiation of human skin fragments from elective cosmetic surgery, and human fibroblasts culture. Measurement of MMP-1, TIMP-1 and GADD45a mediators for further comparison of results. Results: In the three models used, the IR-A radiation induced an increase in MMP-1, inhibited the synthesis of GADD45a, and did not changed TIMP-1 values. Conclusion: Due to the positive correlation of the models studied, it may be suggested the use of ex vivo skin as plausible and sustainable tool to overcome differences between knowledge generated from in vitro and clinical experiments.