Identification the key factor of pulmonary fibrosis following silica nanoparticles exposure based on bioinformatics analysis / 中华劳动卫生职业病杂志

Objective: To investigate the main mechanisms of pulmonary fibrosis following silica nanoparticles (SiNPs) exposure through constructing the macrophage-fibroblast model in vitro, which simulated the process of pulmonary fibrosis. Methods: In January 2021, human mononuclear leukemia cells (THP-1) were treated with 0, 25, 50, 100 μg/ml SiNPs for 24 h. The supernatant of THP-1 cells was collected and applied to human embryonic lung fibroblast cells (MRC-5) which divided into control and low, medium and high dose groups at the logarithmic growth stage for 24 h. MRC-5 cell viability was detected by CCK8. The hydroxyproline (Hyp), interleukin 6 (IL-6), interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) expression were detected in the supernatants of MRC-5. The changed proteins were detected by liquid-phase mass spectrometry in high dose group. GeneCard database were applied to identity the differential pulmonary fibrosis proteins in high dose group. Gene Ontology (GO) was performed to identity the key biological process in differential pulmonary fibrosis proteins of high dose group. The String database was used to construct the protein-protein interactions (PPI) network of differential pulmonary fibrosis proteins. The APP of CytoHubba was applied to calculate the key protein of differential pulmonary fibrosis proteins in PPI network. Correlation coefficients between key differential pulmonary fibrosis proteins were calculated using Pearson correlation analysis. Western blotting was applied to detect the expression of key proteins of differential pulmonary fibrosis proteins in different groups. Results: CCK8 results showed that MRC-5 cell viability was increasing in low, medium and high dose groups compared with control group (P<0.05). The expression levels of Hyp and IL-1β in different group were increased compared with control group, the expression levels of IL-6 and TNF-α were increased in high dose group compared with control group (P<0.05). GeneCard database identified 26 differential pulmonary fibrosis proteins, which were mainly involved in extracellular matrix hydrolysis, cell inflammatory response, tissue repair, cell proliferation, inflammation response by GO analysis. The APP of CytoHubba was calculated that matrix metalloproteinase 9 (MMP9) and tissue inhibitor metalloproteinase 1 (TIMP1) played an important role in PPI network. The results of correlation analysis showed that MMP9 was correlated with the expression of matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3), TIMP1 and epidermal growth factor receptor (EGFR) (r=0.97, 0.98, 0.94, 0.93, P<0.05). Western blotting results showed that TIMP1 protein expression was increased in low, medium and high dose groups, while MMP9 protein expression was increased only in high dose group (P<0.05) . Conclusion: Differential expression proteins related with pulmonary fibrosis in MRC-5 cells mainly regulate biological processes of extracellular matrix hydrolysis, tissue repair, and cellular inflammation response following SiNPs exposure. MMP9 and TIMP1 may be the key proteins, which affected the fibrosis process in vitro pulmonary fibrosis model.

Relationship of Matrix Metalloproteinases and the Tissue Inhibitor with Left Ventricular Hypertrophy in Patients with Primary Hypertension / 中国医科大学学报

Objective To investigate the relationship of matrix metalloproteinases(MMP?3 and MMP?9)and the tissue inhibitor TIMP?1 with left ventricular hypertrophy(LVH)in patients with primary hypertension. Methods Totally 140 patients with primary hypertension and 132 healthy controls were included. Matrix metalloproteinase?3(MMP?3),matrix metalloproteinase?9(MMP?9)and tissue inhibitor metalloproteinase?1 (TIMP?1)were measured. All subjects were taken echocardiography examination ,then left ventricular mass index(LVMI)was calculated. Re?sults MMP?3,MMP?9,TIMP?1(488.32±100.32 vs 314.59±99.78;340.56±43.21 vs 290.15±33.98;389.16±57.53 vs 243.45±62.31;P<0.001) and LVMI(113.7±9.9 vs 88.3±10.4,P<0.001)in patients with primary hypertension were significantly higher than those in controls. In a multiple stepwise regression analysis with LVMI as the variable,it was found that age,SBP,MMP?3,MMP?9 and TIMP?1 were main determinants for LVMI (r2=0.78,P<0.001). 3. Patients with primary hypertension were divided into two subgroups according to LVMI,i.e.,hypertension with LVH (group A)and hypertension without LVH(group B). SBP,MMP?3,MMP?9 and TIMP?1(178±31 vs 166±25;490.14±99.13 vs 405.56±53.12;340.56±43.21 vs 290.15±33.98;393.45±47.69 vs 301.58±39.57;P<0.05)of group A were significantly higher than those of group B. Conclusion MMP?3,MMP?9 and TIMP?1 are influencing factors for LVH in patients with primary hypertension.

Expressão de metaloproteinases de matriz e de seus inibidores teciduais em carcinomas basocelulares / Expression of matrix metalloproteinasis and their tissue inhibitors in basal cell carcinoma

INTRODUÇÃO: Aproximadamente 80 por cento das neoplasias malignas de pele não-melanomas são carcinomas basocelulares (CBC). Apesar das raras metástases, esses tumores são localmente agressivos. As metaloproteinases de matriz (MMPs), especialmente as MMP-2 e 9, são importantes no processo de invasão. Em contrapartida, os inibidores teciduais das MMPs (TIMPs) têm como principal função a inibição dessas enzimas. OBJETIVO: Investigar a associação de variáveis clinicopatológicas de pacientes portadores de CBC com a expressão de MMP-2, MMP-9, TIMP-1 e TIMP-2. MATERIAL E MÉTODOS: Foram selecionados 31 casos de CBC, sendo então obtidos, retrospectivamente, os dados referentes a idade, sexo e tamanho da lesão. Cortes histológicos das lesões foram submetidos a reação imuno-histoquímica pela técnica estreptavidina-biotina-peroxidase para detecção dos antígenos de interesse. Índices de imunomarcação foram construídos e comparados com os dados previamente obtidos. RESULTADOS: Observou-se correlação significativa entre idade e tamanho da lesão (R = 0,532; p = 0,008). Não foram observadas correlações significativas entre as outras variáveis e a expressão imuno-histoquímica dos antígenos de interesse. CONCLUSÃO: A expressão das metaloproteinases e de seus inibidores teciduais não parece ser influenciada pelos parâmetros investigados. Estudos adicionais são necessários para melhor compreensão de sua associação com o comportamento biológico do CBC.

INTRODUCTION: Approximately 80 percent of non-melanoma skin neoplasias are basal cell carcinomas (BCC). Although metastasis is rare, BBC carcinomas are locally aggressive tumors. Matrix metalloproteinases (MMPs), mainly MMP-2 and MMP-9, play an important role on the invasion process. On the other hand, tissue inhibitors of MMPs (TIMPs) have the main function of inhibiting these enzymes. OBJECTIVE: To investigate the association of clinical-pathological variables of BCC patients with the expression of MMP-2 and MMP-9, TIMP-1 and TIMP-2. Methods: Thirty-one BCC cases were selected. Gender, age of the patients and size of the lesions were obtained retrospectively. Histological cuts of the lesions were exposed to immunohistochemistry reaction by use of the streptavidine-biotin peroxidase technique in order to detect antigens. Immunomarking parameters were established and compared with previous data. RESULTS: A significant correlation between age and size of the lesion was observed (R = 0.532; p = 0.008). No significant correlations between other variables and immunohistochemical expression of antigens were observed. CONCLUSION: The expression of MMPs and TIMPs does not seem to be influenced by the parameters investigated in this work. Additional studies should be made to better understand its association with the biological behavior of basal cell carcinomas.

Effect of the matrix metalloproteinases-2, matrix metalloproteinases-9 and tissue inhibitor metalloproteinases-3 in the rats with cerebral infraction caused by injection of auto blood thrombus / 中华急诊医学杂志

Objective To investigate the effect of the cerebral infarction in rats and the role of matrix metalloproteinases-2 (MMP-2), matrix metalloproteinases-9 (MMP-9), and tissue inhibitor of metalloproteinases-3 (TIMP-3) in the pathogenesis. Method Sixty-six rats were randomly divided into 3 groups: blank group (n= 6), control group (n=30), model group (n=30). The rat model was established by carotid injection of auto blood thrombus, the control group was given the operation without injection. Each group was subdivided into 24 hours, 48 hours, 3 days, 5 days, 7 days after operative intervention. At serial intervals, the animals in each group were sacrificed and brain tissue samples were collected to determine MMP-2, MMP-9, TIMP-3 expression by immunohistoehemistry. The changes of behaviors were observed and the histopathological changes were investigated by hematoxylin and eosin stain. Results The experimental group had more obvious behavior change than other groups. Hematoxylin and eosin stain showed significant histopathological changes; MMP-2, MMP-9 and TIMP-3 expression was up-regulated in comparison with other groups (P

Therapeutic effects of Okam on asthmatic mice / 中国海洋药物

Objective To investigate the therapeutic effects and mechanism of Okam on asthmatic mice.Methods The mice model of asthma was established with the egg albumen sensitization, and were treated with low and large doses of Okam for four weeks.The pathological changes of lung tissues were observed.Immunohistochemistry was used to determine the contents of matrix metalloproteinases-9(MMP-9) and tissue inhibitor Metalloproteinase-1 (TIMP-1) in the lung tissues.Results Gasp and inflammation in the lung tissues were significantly relieved in the test groups than that in the model group.MMP-9,TIMP-1 and MMP- 9/TIMP-1 ratios were significantly lowered in the test group than that in the model group. Conclusion The marine drug of Okam shows therapeutic effects on mice with asthma,which may be the result of reduced contents of MMP-9 and TIMP-1 in the lung tissues and the correction of the imbalanced MMP-9/TIMP-1 ratio.Okam is likely to be a new choice for the treatment of asthma.