Effect of ANKRD49 on migration of human lung adenocarcinoma cells and its mechanism / 中国生物制品学杂志

@#Objective To study the effect of ankyrin repeat domain 49(ANKRD49)on the migration of human lung adenocarcinoma cell line NCI-H1299 and its mechanism.Methods NCI-H1299 cells were infected with lentivirus vector carrying ANKRD49 gene and shRNA targeting ANKRD49 to construct the cell models stably overexpressing and knocking down ANKRD49. Meanwhile,the control cell models infected with empty lentivirus vector and lentivirus vector with scramble sequences were constructed respectively. The expression levels of ANKRD49 mRNA and protein were detected by real-time fluorescence quantitative PCR and Western blot. The effect of ANKRD49 on cell migration was measured by scratch test. The mRNA and protein levels of matrix metalloproteinase(MMP)-2/9 and tissue inhibitor of metalloproteinase(TIMP)-1/2 were detected by real-time fluorescence quantitative PCR and Western blot. The protein expression levels of p65,p-p65,IκBα and p-IκBα were detected by Western blot.Results The levels of ANKRD49 mRNA and protein in the ANKRD49 overexpression group were significantly higher than those in the control group(t = 70. 02 and 45. 68,respectively,each P < 0. 001). Compared with the control group,the migration ability of cells in the ANKRD49 overexpression group significantly increased at 24 h and 48 h(t = 5. 343 and 3. 282,P = 0. 005 9 and 0. 030 4,respectively);The mRNA transcription levels and protein expression levels of MMP-2 and MMP-9 significantly increased(t = 9. 304 and 6. 193,P =0. 000 7 and 0. 003 5,respectively),while the mRNA and protein expression of TIMP-1 and TIMP-2 decreased significantly(t = 3. 858 and 3. 517,P = 0. 018 2 and 0. 024 5,respectively),and the values of MMP-2/TIMP-1 and MMP-9/TIMP-2 significantly increased(t = 17. 7 and 9. 682,P < 0. 001 and < 0. 01,respectively);The expression of p-p65 and pIκBα significantly increased,the total protein levels of p65 and IκBα showed no obvious change,and the values of p-p65/p65 and p-IκBα/IκBα significantly increased(t = 3. 962 and 5. 370,P = 0. 016 7 and 0. 005 8,respectively). However,knocking down of ANKRD49 presented the opposite results.Conclusion ANKRD49 promotes the migration of NCI-H1299cells by enhan-cing the expression of MMP-2/9,the values of MMP-9/TIMP-1 and MMP-2/TIMP-2 via activating NF-κB/p65 signa-ling pathway.

Análisis inmunohistoquímico de MMP-1, MMP-2 y MMP-9 en ameloblastoma convencional / Immunohistochemical analysis of MMP-1, MMP-2, MMP-9 in conventional ameloblastoma

Introducción: las metaloproteinasas son enzimas que participan en la remodelación tisular y su función se relaciona con procesos fisiológicos y patológicos, como la invasión y la metástasis. El ameloblastoma convencional (AMC) es una neoplasia epitelial benigna odontogénica intraósea caracterizada por una progresión lenta y localmente invasiva, cuyo crecimiento se ha vinculado con el recambio ósea y la remodelación de la matriz extracelular. El objetivo del presente trabajo fue determinar la presencia inmunohistoquímica de MMP-1, MMP-2 y MMP-9 en el AMC. Material y métodos: se realizó un estudio piloto observacional analítico utilizando cinco muestras de AMC. Los especímenes fueron recolectados aleatoriamente del archivo del Departamento de Patología Oral y Maxilofacial, de la Escuela Nacional de Estudios Superiores (ENES) Unidad León, UNAM. Como grupo control se emplearon dos especímenes de folículo dental, obtenido de pacientes con indicación de su extracción por motivos ortodóncicos. Se realizó la técnica de inmunohistoquímica por peroxidasa, recolectando el nivel y proporción de inmunoexpresión de manera semicuantitativa. Resultados: cuatro pacientes fueron de género masculino y uno femenino, la edad promedio fue de 40.6 ± 14.9 años. Todas las muestras fueron obtenidas de la región mandibular posterior. Se observaron dos especímenes con patrón folicular y tres con plexiforme. Las MMP-2 y MMP-9 se detectaron sólo en uno de los cinco especímenes y únicamente en el parénquima de la lesión, con una proporción de 100%. Conclusión: según nuestro análisis inmunohistoquímico, las MMP-2 y MMP-9 son las metaloproteinasas que presentaron expresión positiva dentro de la patogénesis del AMC comparado a la MMP-1; no obstante, es necesario realizar este tipo de estudios en una población mayor (AU)

Introduction: metalloproteinases are enzymes involved in tissue remodeling and their function is related to physiological and pathological processes, such as invasion and metastasis. These enzymes are capable of degrading components of the extracellular matrix, which may promote tumor progression. Conventional ameloblastoma (CA) is described as a benign intraosseous epithelial odontogenic neoplasm characterized by a slow and locally invasive progression, whose growth has been linked to bone turnover and extracellular matrix remodeling. The aim of the present work was to determine the immunohistochemical presence of MMP-1, MMP-2 and MMP-9 in CA. Material and methods: an analytical observational pilot study was performed using 5 CA, randomly collected from the archive of the Department of Oral and Maxillofacial Pathology, Escuela Nacional de Estudios Superiores (ENES) Unidad León, UNAM. The control group used were two dental follicle samples, obtained from patients with extraction indication for orthodontic treatment. The peroxidase immunohistochemistry assay was performed, collecting semiquantitatively level and proportion of immunoexpression. Results: four patients were male and one female, the average age was 40.6 ± 14.9 years. All specimens were obtained from the posterior mandibular region. Two specimens were observed with follicular pattern and three with plexiform pattern. MMP-2 and MMP-9 were detected only in one of the five specimens, with presence in the parenchyma of the lesion, with a proportion of 100% of the cell analyzed. Conclusion: according to our immunohistochemical analysis, MMP-2 and MMP-9 are the metalloproteinases that presented positive expression within the pathogenesis of CA compared to MMP-1; however, it is necessary to perform this type of studies in a larger population (AU)

Assessment of YME1L and mitofusin2 as a possible diagnostic and/or therapeutic target in hepatocellular carcinoma

Mitochondrial dynamics are a contraversal issue in hepatocellular carcinoma. The present study tries to illustrate the role of mitochondrial dynamics proteins (mitofusin-2 (Mfn2) and YME1L) in hepatocarcinogenesis. Five groups were used: the control group and three HCC groups (after 8, 16, and 24 weeks from DENA induction). The last group was treated with Sorafenib (SP) (10 mg/kg), via oral gavage for 4 weeks after cancer induction. This study revealed that Mfn-2 was downregulated and YME1l was overexpressed in different HCC groups. This dysregulation of mitochondrial dynamics proteins was associated with high hepatic levels of cyclin D1, MMP-9, and MDA and overexpression of ki67 as well as decreasing the hepatic expression of tissue inhibitor of matrix metalloproteinase-3 (Timp-3) and Bax. To confirm the possible role of Mfn2 and YME1L in HCC, we assessed the effect of sorafenib on these parameters and its related HCC characteristics. Sorafenib corrected the level of Mfn2 and YME1L and decreased tumor cell proliferation as well. We also elucidated that mitochondrial dynamics proteins (Mfn2 and YME1L) could be a good therapeutic target for HCC.

Roles of pancreatic stellate cells and pancreatic cancer cells in angiogenesis of pancreatic cancer: an in vitro study / 中华消化外科杂志

Objective:To investigate the role and mechanism of pancreatic stellate cells (PSCs) and pancreatic cancer cells (PCCs) in the angiogenesis of pancreatic cancer.Methods:The experimental study was conducted. The human PSCs and PCCs and human umbilical vein endothelial cells (HUVECs) were cultured in vitro. HUVECs was treated with PSCs/PCCs supernatants and matrix metalloproteinase (MMP) inhibitor of different types and concentrations. As controls, HUVECs treated with complete endoprime medium (C/E) and DMEM/Ham's F12 medium (D/F) were set as the C/E group and the D/F group, respectively. Observation indicators: (1) proliferation of HUVECs under different conditions; (2) tube formation of HUVECs under different conditions; (3) migration of HUVECs under different conditions; (4) expression of MMP-2 in the supernatants of PSCs and PCCs; (5) effect of MMP inhibitor GM6001 on migration of HUVECs. Measurement data with normal distribution were represented as Mean± SD, comparison among groups was conducted using the one way ANOVA and comparison between groups was conducted using the LSD- t test. Results:(1) Proliferation of HUVECs under different conditions. Results of HUVECs proliferation assay using 5-ethynyl-2′-deoxyuridine (EdU) labeling showed that the binding rate of EdU in the HUVECs of D/F group and HUVECs treated with supernatants of different concentration (25%, 50%, 75%, 95%) of PSCs was 12.4%±1.0%, 24.5%±2.9%, 25.3%±3.0%, 22.8%±2.0%, 22.9%±2.8%, respectively, showing a significant difference among them ( F=8.60, P<0.05). There were significant differences in the binding rate of EdU between HUVECs in the D/F group and HUVECs treated with supernatants of different concentration (25%, 50%, 75%, 95%) of PSCs, respectively ( P<0.05). The binding rate of EdU between HUVECs in the D/F group and HUVECs treated with supernatants of different concentration (25%, 50%, 75%, 95%) of PCCs was 12.4%±1.0%, 30.0%±3.2%, 32.1%±1.0%, 32.3%±3.5%, 26.2%±5.6%, respectively, showing a significant difference among them ( F=11.93, P<0.05). There were significant differences in the binding rate of EdU between HUVECs in the D/F group and HUVECs treated with supernatants of different concentration (25%, 50%, 75%, 95%) of PSCs, respectively ( P<0.05). (2) Tube formation of HUVECs under different conditions. Number of tube formation, length of tube in the HUVECs of D/F group and HUVECs treated with PSCs supernatants was 15.2±2.3, (12.1±1.5)mm and 49.7±3.2, (39.8±2.3)mm, respectively, showing significant differences between the two groups of HUVECs ( P<0.05). (3) Migration of HUVECs under different conditions. Results of single cell tracing experiment showed that the migration rate of HUVECs treated with supernatants of different ratio of PSCs and PCCs was faster than that of HUVECs in the D/F group, and the enhancement effect of supernatants of PSCs and PCCs was dose-dependent. The migration rate of HUVECs treated with mix supernatants of different concentration of PSCs and PCCs and supernatants of co-cultured PSCs and PCCs was faster than that of HUVECs in the D/F group. The migration rate of HUVECs treated supernatants of co-cultured PSCs and PCCs was faster than that of HUVECs treated with mix supernatants of different concentration of PSCs and PCCs, showing a synergistic effect in the HUVECs treated supernatants of co-cultured PSCs and PCCs. (4) Expression of MMP-2 in the supernatants of PSCs and PCCs. Results of gelatine zymography showed that the MMP-2 expression levels decreased sequentially in super-natants of co-cultured PSCs and PCCs, supernatants of PSCs, mix supernatants of PSCs and PCCs and supernatants PCCs. (5) Effect of MMP inhibitor GM6001 on migration of HUVECs. Results of single cell tracing experiment showed that the migration rate of HUVECs treated with PSCs supernatants combined with different concentration of GM6001 (0, 1, 10, 25 μmol/L) was (25.70±2.06)μm/h, (18.37±1.61)μm/h, (16.20±0.26)μm/h, (15.99±0.58)μm/h, respectively, showing a significant difference among them ( F=11.39, P<0.05). There were significant differences in the migration rate between HUVECs treated with PSCs supernatants combined with 1, 10, 25 μmol/L GM6001 and HUVECs treated with PSCs supernatants ( P<0.05). The migration rate of HUVECs treated with mix super-natants of PSCs and PCCs combined with different concentration of GM6001 (0, 1, 10, 25 μmol/L) was (30.06±3.70)μm/h, (22.76±1.56)μm/h, (23.87±2.84)μm/h, (22.10±2.35)μm/h, respectively, showing a significant difference among them ( F=4.06, P<0.05). There were significant differences in the migration rate between HUVECs treated with mix supernatants of PSCs and PCCs combined with 1, 10, 25 μmol/L GM6001 and HUVECs treated with mix supernatants of PSCs and PCCs ( P<0.05). Conclusions:Both PSCs and PCCs can promote the proliferation, migration and angiogenesis of HUVECs in vitro experiment. Releasing of MMP-2 by interaction between PSCs and PCCs is an important factor to stimulate endothelial cell migration, which increases the stimulating activity of angiogenesis, especially the migration ability of HUVECs.

Research progress in the biological characteristics of matrix metalloproteinase-19 in tumor / 国际生物医学工程杂志

The matrix metalloproteinases family (MMPs) are proteins related to tumor formation and metastasis that have attracted the attention of scholars in recent years. Tumor cells can secrete MMPs during malignant transformation, and the expression of MMPs in different malignant tumors is diverse, and different members of MMPs do not have exactly the same biological properties. Matrix metalloproteinase-19 (MMP-19) is a new member of MMPs whose secretion increases rapidly during the malignant transformation of cells and is released into the extracellular space to participate in biological processes such as proliferation, adhesion, invasion, migration, and angiogenesis of tumor cells. In this paper, the progress of research on the biological properties of MMP-19 in tumors was reviewed to provide a theoretical basis for exploring the development of tumors, especially for studying the invasion and metastasis of tumor cells.

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.

Effects of ICMT gene silencing on the invasion and migration of human salivary adenoid cystic carcinoma cells in vitro / 口腔疾病防治

Objective @#To investigate the effect of isoprene cysteine carboxymethyltransferase (ICMT) gene on the migration and invasion of salivary adenoid cystic cancer cells (SACC) and the related mechanism, to provide experimental evidence for molecular targeted therapy of SACC.@*Methods@# Adenoid cystic cancer cells SACC-LM and SACC-83 were cultured in vitro, and siRNA was transfected into human SACC-LM and SACC-83 cells (experimental group) by transient transfection of a liposome vector. A blank control group and negative control group were set up respectively (transfected NC-siRNA). qRT-PCR was peformed to measure the mRNA expression of ICMT and RhoA in each group after transfection and to determine the silencing efficiency. The expression of ICMT, membrane RhoA, total RhoA, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and Rho associated with coiled helical binding protein kinase 1 (ROCK1) in each group was detected by Western blot. The proliferation abilityies of SACC cells was detected by CCK-8 assay. The migration and invasion ability of SACC cells were detected by comparing the relative healing area of cell scratch assay and the number of Transwell assay cells. @*Results@#After transfection of ICMT-siRNA into SACC-LM and SACC-83 cells, the expression of ICMT gene and protein in the experimental group was significantly decreased compared with the negative control group and blank control group (P<0.05), but there were no significant differences in the expression of RhoA gene and total protein among all groups (P>0.05). The expression of RhoA membrane proteins, ROCK1, MMP-2, MMP-9 in the experimental group was significantly decreased compared with that in the negative control group and blank control group (P<0.05). Cell proliferation ability was significantly decreased (P<0.05). The migration and invasion abilities were significantly decreased (P<0.05). @*Conclusion @#In vitro silencing of ICMT gene can effectively inhibit the migration and invasion of human SACC-LM and SACC-83 cells, and the mechanism may be related to RhoA-ROCK signaling pathway.

Expression pattern of MMP-12 in long-term optic nerve regeneration induced by lens injury / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression changes of MMP-12 during the long-term axon regeneration induced by the lens injury after the optic nerve clamp trauma in sprague-dawley(SD)rats.METHODS: The optic nerve injury model and lens injury model of SD rats were established, and the 24 experimental animals were divided into control group; lens injury group; optic nerve injury group; lens injury combined with optic nerve injury group, with 6 rats in each group. Reference transcriptome sequencing was used to analyze the expression changes of differentially expressed genes in the injured optic nerve region, and relevant differentially expressed genes with high expression were screened. Quantitative real-time polymerase chain reaction(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA)were used to quantify the expression changes of matrix metalloproteinase-12(MMP-12)in the injured optic nerve region.RESULTS: The Principal Component Analysis of transcriptome sequencing indicated that lens injury combined with optic nerve injury was the principal component of gene expression change. Analysis of gene expression differences showed that the expression of MMP-12 gene was up-regulated in the lens injury combined with optic nerve injury group. The mRNA expression level of MMP-12 in the lens injury combined optic nerve injury group was up-regulated compared with the control group, the optic nerve injury group and the lens injury group at 14d and 21d after successful modeling(P<0.05). At 7, 28d, there was no difference in expression among all groups. The protein expression level of MMP-12 in the lens injury combined with optic nerve injury group was up-regulated compared with the control group and optic nerve injury group at 7, 14 and 21d after successful modeling(P<0.05), and it was up-regulated in the lens injury group combined with optic nerve injury group compared with optic nerve injury group at 21d(P<0.05). At 28d, there was no difference in expression among all groups.CONCLUSION: The up-regulated expression of MMP-12 may be involved in the long-term regeneration of the optic nerve after lens injury.

Mechanism of Pachymic Acid in Inhibiting Invasion and Metastasis of Renal Carcinoma Cells via Regulating MMP/TIMP Balance by Smads / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of pachymic acid （PA） in Poria on the invasion and metastasis of renal carcinoma cells. MethodThe effect of PA （0， 20， 40， 80， 160 μmol·L-1） on cell viability was detected by cell counting kit-8（CCK-8）， and the dose of PA was selected for subsequent experiments. The effect of PA （0， 20， 40， 80 μmol·L-1） on cell proliferation was evaluated by colony formation assay. The effect of PA （0， 20， 40， 80 μmol·L-1） on cell adhesion ability was observed by cell adhesion assay. The effect of PA （0， 20， 40， and 80 μmol·L-1） on cell invasion and metastasis was investigated by Wound healing assay and Transwell invasion assay. The inhibitory effect of PA （0， 20， 40， 80 μmol·L-1） on cell motility was further observed and verified by high-content imaging technology. The effects of PA （0， 20， 40， 80 μmol·L-1） on the expression of matrix metalloproteinase （MMP）/tissue inhibitor of metalloproteinasas （TIMP） related to invasion and metastasis and Smads were detected by Western blot. ResultCCK-8 results showed that compared with the blank group， the PA groups showed decreased cell viability（P<0.01）， with the half-maximal inhibitory concentration （IC50） of ACHN cells of 70.42 μmol·L-1 at 24 h. Colony formation assay showed that the number of cell clonal groups in the PA groups was reduced compared with that in the blank group（P<0.01）. Cell adhesion assay showed that compared with the blank group， the PA groups displayed reduced cell adhesion（P<0.01）. Wound healing assay showed that the wound healing rate of cells in the PA groups was lower than that in the blank group （P<0.05，P<0.01）. Transwell invasion assay showed that compared with the blank group， the number of transmembrane cells in PA groups was reduced（P<0.01）. High-content imaging showed that the cumulative migration distance of cells in the PA groups was shorter than that in the blank group（P<0.01）. The results of Western blot showed that the protein expression of MMP-2 and MMP-9 in the PA groups decreased （P<0.01）， and TIMP-1 protein expression increased （P<0.01） compared with those in the blank group. In addition， compared with the blank group， the PA groups showed decreased protein expression of Smad2 and Smad3 （P<0.01）. ConclusionPA can inhibit the invasion and metastasis of renal carcinoma cells presumably through regulating the homeostasis of MMP/TIMP by Smad2/3.

Mechanism of Honghua Oral Liquid in Alleviating Neuropathic Pain / 中国实验方剂学杂志

ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg-1·d-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg-1·d-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.

Natural reversal of mandibular condylar cartilage histological damage caused by chronic unpredictable moderate stress in rats / 口腔疾病防治

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.

Traditinal Chinese Medicine Intervention in Intervertebral Disc Degeneration by Regulating Matrix Metalloproteinase Expression： A Review / 中国实验方剂学杂志

Intervertebral disc degeneration is one of the common causes of chronic low back pain. As a common spinal disease， its clinical symptoms are mainly low back pain and limited function， which seriously affects physical and psychological health. Because of its complex and unclear pathogenesis， the treatment of intervertebral disc degeneration has been the focus of scientific researchers and clinical workers. At present， the treatment of intervertebral disc degeneration mainly includes non-surgical therapy and surgical therapy， which can alleviate the clinical symptoms of patients to a certain extent， but easily induce new complications， and it is difficult to restore the normal physiological function of the intervertebral disc. In recent years， along with the advanced research on matrix metalloproteinases （MMPs） in the tissues of intervertebral disc degeneration， it has been found that MMPs can be used as molecular therapeutic targets. The expression of MMPs in the intervertebral disc tissues can be regulated by reducing the content and composition of the extracellular matrix of the intervertebral disc， so as to slow down intervertebral disc degeneration and even reverse the occurrence of intervertebral disc degeneration. This treatment is expected to delay intervertebral disc degeneration caused by changes in extracellular matrix composition or content. In recent years， with the continuous development of network pharmacology and bioinformatics research， a large number of researchers have explored the treatment of intervertebral disc degeneration by traditional Chinese medicine （TCM） and found that TCM can reduce the degradation of extracellular matrix by inhibiting the expression of MMPs， thus alleviating the symptoms of intervertebral disc degeneration and slowing down the progression of intervertebral disc degeneration. This paper reviewed the research progress of TCM intervention in MMP expression in the treatment of intervertebral disc degeneration， aiming at providing references for the application of TCM in the prevention and treatment of intervertebral disc degeneration.

A study on the biological effects of electromagnetic pulse with different high⁃intensity on condylar cartilage in rats / 口腔疾病防治

Objective@#To explore the biological effects of electromagnetic pulse (EMP) with different high intensities on condylar cartilage in rats. @*Methods@#SD rats were randomly divided into a sham group (Sham) and an irradiation group (EMP1: 500 kV/m, 10 Hz; EMP2: 270 kV/m, 10 Hz). Then, they were sacrificed at 1 h, 3 h, 12 h, 24 h and 3 d after irradiation. The degree of cartilage degeneration was evaluated by HE, safranine O-fast green, type Ⅱ collagen immunohistochemistry and TUNEL staining. Immunohistochemistry and western blot were performed to detect the expression of the matrix degradation factors: matrix metalloproteinase-13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5) and the apoptosis key factor cleaved-cysteinyl aspartate specific proteinase (cleaved-Caspase3) in condylar cartilage. @*Results @#HE staining showed that, compared with the Sham group, a small amount of exfoliation was found on the fibrous surface layer of the cartilage after irradiation in the EMP1 and EMP2 groups. Compared with the Sham group, the percentage of safranine O-fast green-positive area decreased significantly at 12 h and 24 h (both P<0.01) in the EMP1 group and 12 h and 24 h in the EMP2 group (both P<0.05); the percentage of type Ⅱ collagen-positive area decreased significantly at 3 h and 12 h (P<0.05, P<0.001) in the EMP1 group. In addition, the number of TUNEL-positive apoptotic cells increased significantly at 1 h, 3 h, 12 h, and 24 h in the EMP1 group and 1 h, 3 h, and 12 h in the EMP2 group (P<0.05). Moreover, at different timepoints (except at 3 d) in the EMP1 group and EMP2 group, the percentage of MMP-13, ADAMTS-5- and cleaved Caspase3-positive chondrocytes and their protein levels in condylar cartilage increased significantly after irradiation (P<0.05). @* Conclusion@# EMP with a certain degree of high-intensity can induce early transient damage to condylar cartilage. This effect is dose-and time-dependent.

The role of Nrf2 in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated MMP9 / 中华劳动卫生职业病杂志

Objective: To investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated matrix metalloproteinase 9 (MMP9) . Methods: In October 2020, immortalized rat choroid plexus epithelial cell line (Z310) cells were used as the blood-cerebrospinal fluid barrier in vitro, and were divided into control group and 0.125, 0.25, 0.5 mmol/L lanthanum chloride (LaCl(3)) treatment group. After treating Z310 cells with different concentrations of LaCl(3) for 24 hours, the morphological changes of Z310 cells were observed under inverted microscope, the protein expression levels of MMP9, occludin and zonula occludens-1 (ZO-1) were observed by cellular immunofluorescence method, and the protein expression levels of MMP9, tissue inhibitors of metalloproteinase1 (TIMP1) , occludin, ZO-1 and Nrf2 were detected by Western blotting. The level of reactive oxygen species (ROS) in cells was detected by flow cytometry. Results: Compared with the control group, Z310 cells in the LaCl(3) treatment group were smaller in size, with fewer intercellular junctions, and more dead cells and cell fragments. The expression level of MMP9 protein in cells treated with 0.25 and 0.5 mmol/L LaCl(3) was significantly higher than that in the control group (P<0.05) , and the expression level of TIMP1 and tight junction proteins occudin and ZO-1 was significantly lower than that in the control group (P<0.05) . Compared with the control group, the ROS production level in the 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly increased (P<0.05) , and the Nrf2 protein expression level in the 0.125, 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly decreased (P<0.05) . Conclusion: Lanthanum may increase the level of ROS in cells by down regulating the expression of Nrf2, thus activating MMP9 to reduce the expression level of intercellular tight junction proteins occludin and ZO-1.

Influence of two natural cross-linkers on microtensile bond strength durability ­ An in vitro study / Influência de dois reticuladores naturais na durabilidade da resistência de união à microtração ­ Um estudo in vitro

Objective: to investigate the effect of two natural cross-linkers on microtensile bond strength (µTBS) and evaluate their influence on the durability of the resin dentin bonds. Material and Methods: the Moringa oleifera and Centella asiatica plant extracts were qualitatively tested with high-performance thin layer chromatography (HPTLC) for the presence of phenols. The phenolic content ranged from 27 to 30 gallic acid equivalents (GAE), µg/mg of dry weight. After etching, two concentrations (5% and 1%) of these two extracts were prepared and used as pretreatment liners on dentin. They were applied for a min. After restoration with resin composite, dentin resin beams were prepared. The study groups were 5% Moringa, 1% Moringa 5% Centella 1% Centella, and control (without cross-linker application). For each group, half of the samples underwent µTBS testing after 24 hours, while the remaining half were immersed in artificial saliva to assess the bond's longevity after 6 months of ageing. Statistical analysis was performed using one-way ANOVA followed by Tukey's post hoc test. Results: both 5% and 1% Moringa showed a significant difference (p<0.05) compared to the other groups at both intervals. However, after ageing, the specimens in the control and 1% Centella groups resulted in a significant decrease in µTBS. Conclusion: overall, both concentrations of Moringa (5% and 1%) were effective in stabilising the bond during both intervals.(AU)

Objetivo: investigar o efeito de dois reticuladores naturais na resistência de união (µTBS) à microtração e avaliar sua influência na durabilidade da adesão da resina à dentina. Material e Métodos: extratos das plantas Moringa oleifera e Centella asiatica foram qualitativamente testados através de cromatografia em camada fina de alta performance (HPTLC) para a presença de fenóis. O conteúdo fenólico alcançou entre 27 a 30 equivalentes de ácido gálico (GAE), µg/mg de peso seco. Após o condicionamento, duas concentrações (5% e 1%) dos extratos foram preparadas e utilizadas como forros de pré-tratamento em dentina. Eles foram aplicados por um minuto. Após a restauração com resina composta, palitos de dentina e resina foram preparados. Os grupos foram 5% Moringa, 1% Moringa, 5% Centella, 1% Centella e controle (sem aplicação de reticulador). Para cada grupo, metade das amostras foram submetidas ao teste µTBS após 24 horas, enquanto a outra metade foi imersa em saliva artificial para avaliar a longevidade adesiva após 6 meses de envelhecimento. Foi realizada análise estatística através de ANOVA 1-fator, seguido do teste post hoc de Tukey. Resultados: ambas as concentrações de 5% e 1% de Moringa demonstraram diferença significativa (p<0.05) comparadas aos outros grupos em ambos os intervalos. No entanto, após o envelhecimento, os espécimes dos geupos controle e 1% de Centella resultaram em uma redução significativa de µTBS. Conclusão: no geral, ambas as concentrações de Moringa (5% e 1%) foram efetivas em estabelecer a adesão em ambos os intervalos (AU)

Do matrix metalloproteinase and cathepsin K inhibitors work synergistically to reduce dentin erosion?

Abstract Objectives To evaluate the effects of matrix metalloproteinase (MMP) and cathepsin K (catK) inhibitors on resistance to dentin erosion. Methodology A total of 96 dentin specimens (3×3×2 mm) were prepared and randomly assigned into four groups (n=24): deionized water (DW); 1 µM odanacatib (ODN, catK inhibitor); 1 mM 1,10-phenanthroline (PHEN, MMP inhibitor); and 1 µM odanacatib + 1 mM 1,10-phenanthroline (COM). Each group was further divided into two subgroups for the application of treatment solutions before (PRE) and after erosive challenges (POST). All specimens were subjected to four daily erosive challenges for 5 d. For each erosive challenge, the specimens in subgroup PRE were immersed in the respective solutions before cola drinks, while the specimens in subgroup POST were immersed in the respective solutions after cola drinks (the immersion duration was 5 min in both cases). All specimens were stored in artificial saliva at 37°C between erosive challenges. The erosive dentin loss (EDL) was measured by profilometry. The residual demineralized organic matrix (DOM) of specimens was removed using type VII collagenase and evaluated by profilometry. Both the EDL and thickness of the residual DOM were statistically analyzed by two-way analysis of variance (ANOVA) and Bonferroni's test (α=0.05). The surface topography and transverse sections of the specimens were observed using SEM. MMPs and catK were immunolabeled in the eroded dentin and in situ zymography was performed to evaluate the enzyme activity. Results Significantly lower EDL was found in the groups ODN, PHEN, and COM than in the control group (all p<0.05), while no significant difference in EDL was found among the groups ODN, PHEN, and COM (all p>0.05). The application sequence showed no significant effect on the EDL of the tested groups (p=0.310). A significantly thicker DOM was observed in the group ODN than in the control group regardless of the application sequence (both p<0.05). The treatment with ODN, PHEN, and COM inhibited the gelatinolytic activity by approximately 46.32%, 58.6%, and 74.56%, respectively. Conclusions The inhibition of endogenous dentinal MMPs and catK increases the acid resistance of human dentin but without an apparent synergistic effect. The inhibition of MMPs and catK is equally effective either before or after the acid challenge.

Effect of vascular endothelial growth factor-A165 on scleral remodeling of guinea pigs with form-deprivation myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of the intravitreal injection of vascular endothelial growth factor-A165(VEGF-A165)on the scleral remodeling of guinea pigs with form-deprivation myopia(FDM).METHODS: A total of 120 tricolor guinea pigs, aged three weeks, were randomly divided into 6 groups, with 20 in each group. The blank group did not undergo any intervention. In the FDM group, only the FDM model was established. In the phosphate buffer saline(PBS)group, 2.5 μL of PBS was injected into the vitreous cavity before establishing the FDM model. In the 1ng group, 5ng group, and 10ng group, VEGF-A165 was injected into the vitreous cavity at concentrations of 1, 5 and 10ng, respectively, before the establishment of the FDM model. The FDM model was established by covering the right eyes of guinea pigs with translucent balloons for 14d. The diopter and axial length of the right eyes were measured before and after covering. After 14d, the content of dopamine(DA)in retina was measured by high performance liquid chromatography. Additionally, the mRNA and protein expression levels of matrix metalloproteinase-2(MMP-2), tissue inhibitor of matrix metalloproteinase-2(TIMP-2), transforming growth factor(TGF)-β1, TGF-β2 and α-smooth muscle actin(α-SMA)in sclera were detected by reverse transcription polymerase chain reaction(RT-PCR)and Western blot.RESULTS: Before covering, there were no significant differences in the diopter and axial length of the right eyes of guinea pigs in all groups(P&#x003E;0.05). After 14d of modeling, when compared with the blank group, FDM group showed an increase in the degree of myopia in the right eye, a prolongation of the axial length, a decrease in the content of DA in the retina, and an increase in the expression of MMP-2, TGF-β2 and α-SMA in the sclera. Conversely, the expression of TIMP-2 and TGF-β1 were decreased(P&#x003C;0.01). However, in comparison to the FDM group, the degree of myopia in the 1ng, 5ng, and 10ng groups of guinea pigs decreased, the growth trend of axial length slowed, the content of DA in the retina increased, and the expression of MMP-2, TGF-β2 and α-SMA in the sclera decreased. Furthermore, the expression of TIMP-2 and TGF-β1 in the sclera increased(P&#x003C;0.01). As the concentration of intravitreal injection of VEGF-A165 increased, the degree of myopia in the right eye of guinea pigs gradually increased, and the axial length gradually prolonged. The content of DA in the retina gradually decreased, the expression of MMP-2, TGF-β2, and α-SMA in the sclera gradually increased, while the expression of TIMP-2 and TGF-β1 decreased gradually.CONCLUSION: Intravitreal injection of VEGF-A165 can increase the content of DA in the retina of FDM guinea pigs, affect the expression of MMP-2, TIMP-2, TGF-β1, TGF-β2 and α-SMA in the sclera, and inhibit scleral remodeling of guinea pigs. Notably, the VEGF-A165 at the concentration of 1ng showed the most significant efficacy.

Progresses and analysis in fibrinolytic drugs induced hemorrhage / 药学学报

At present, most clinical thrombolytic drugs are plasminogen activators, which are highly dependent on the plasminogen level of the patient. Therefore, the efficacy of those drugs is restricted. Unlike the conventional thrombolytic plasminogen activator drugs, fibrinolytic drugs have direct fibrinolytic activity. Thus, fibrinolytic drugs can directly dissolve the thrombus, and its thromlysis efficacy is not restricted by the patients' plasminogen. This is a new type of thrombolytic drug with higher thrombolytic efficiency and safety, and has become one of the research hotspots at present. Although more and more agents that can be used as fibrinolytic drugs have been discovered, only a few of them can successfully be applied in clinical practice. The mainly underlying reason is the risk of bleeding. In this paper, based on the latest research progress of fibrinolytic drugs, the bleeding mechanisms and coping strategies of fibrinolytic drugs were systematically reviewed, five types of bleeding mechanisms of fibrinolytic drugs were summarized, and three types of coping strategies were proposed. We hope our work can provide theoretical basis for the development of safer and more efficient fibrinolytic drugs.

Effect of Modified Zhenwutang on Interstitial Fibrosis in Rats with Chronic Renal Failure Based on IL-6/MMP-9/COL-Ⅳ Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the modulatory effect of modified Zhenwutang on the interleukin-6 （IL-6）， matrix metallopeptidase-9（MMP-9）， type Ⅳ collagen（COL-Ⅳ） in rats with chronic renal failure （CRF） and to investigate the potential mechanism of its treatment of CRF. MethodFifty male SD rats were randomly divided into a modeling group of 40 rats and a normal group of 10 rats， and the modeling group was prepared by continuous adenine gavage for 12 weeks. After successful modelling， the modelling group was divided into the model group， the low dose （7.2 g·kg-1·d-1） group， the medium dose （14.4 g·kg-1·d-1） group， the high dose （28.8 g·kg-1·d-1） group and the Benadryl hydrochloride （10 mg·kg-1·d-1） group for gavage according to the random number table method， In the normal group and the model group， equal volume of distilled water was administered by gavage for 4 weeks. After the administration， the levels of blood creatinine （SCr）， blood urea nitrogen （BUN） and 24 h urine protein （24 h-UTP） were measured， the levels of serum IL-6 were measured by enzyme linked immunosorbent assay（ELISA）. Immunohistochemistry （IHC） was used to detect intercellular cell adhesion molecule-1 （ICAM-1）， IL-6， MMP-9， and other molecules in the rat kidney. The expression of ICAM-1 mRNA， IL-6 mRNA， MMP-9 mRNA and COL-Ⅳ mRNA in rat kidney tissues was measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression levels of ICAM-1， IL-6， MMP-9 and COL-Ⅳ in rat kidney tissues were measured by Western blot. ResultCompared with the normal group， the levels of SCr， BUN and 24 h-UTP were significantly increased in the model group （P<0.01）； the serum IL-6 level was significantly increased （P<0.01）， the tubular lumen was dilated with atrophy， the tubular epithelial cells were necrotic， swollen and vacuolated， the interstitium was infiltrated by a large number of inflammatory cells and collagen fibers were deposited， the levels of IL-6， ICAM-1 and COL-Ⅳ were strongly positive in the tubular interstitium of the model group （P<0.01）， The levels of ICAM-1 mRNA， IL-6 mRNA and COL-Ⅳ mRNA were significantly increased （P<0.01） and MMP-9 mRNA was significantly decreased （P<0.05） in the model rats. ICAM-1， IL-6 and COL-Ⅳ protein expression was significantly increased （P<0.01） and MMP-9 protein expression was significantly increased （P<0.01） in the renal tissue， and MMP-9 protein expression was significantly decreased （P<0.01）. Compared with the model group， the 24 h-UTP， SCr and BUN levels of rats were significantly reduced after treatment with modified Zhenwutang （P<0.01）， the serum IL-6 level was significantly decreased （P<0.01）， the renal lesions of rats were significantly improved and collagen fiber deposition was reduced； the expression of IL-6， ICAM-1 and COL-Ⅳ in renal tubules and interstitium was weakened， and MMP-9 in ICAM-1 mRNA， IL-6 mRNA and COL-Ⅳ mRNA levels were significantly reduced （P<0.01） and MMP-9 mRNA levels were significantly increased （P<0.05）， ICAM-1， IL-6 and COL-Ⅳ protein expression was significantly reduced （P<0.01） and MMP-9 protein expression was significantly The expression of ICAM-1， IL-6 and COL-Ⅳ proteins was significantly decreased （P<0.01） and MMP-9 protein expression was significantly increased （P<0.01）. ConclusionModified Zhenwutang may regulate the IL-6/MMP-9/COL-Ⅳ signaling pathway， thereby reducing proteinuria， improving renal function， reducing renal pathological damage and delaying the progression of CRF interstitial fibrosis.

Effects of LncRNA MEG3 on the invasion and migration of prostate cancer cells by regulating microRNA-181b-5p/TIMP3 / 现代泌尿外科杂志

【Objective】 To explore the effects of long non-coding RNA maternally expressed gene 3 (lncRNA MEG3) on the invasion and migration of prostate cancer cells (PC3 cells) by regulating microRNA-181b-5p (miR-181b-5p)/tissue inhibitor of metalloproteinase 3 (TIMP3). 【Methods】 The prostate cancer tissues and adjacent tissues were collected from 20 prostate cancer patients treated in our hospital during Dec.2020 and Dec.2021. The expressions of MEG3 and miR-181b-5p in tissues were detected with quantitative real-time PCR (qRT-PCR). P3 cells were randomly divided into control group (untreated), pcDNA3.1-NC (transfected with pcDNA3.1-NC), pcDNA3.1-MEG3 group (transfected with pcDNA3.1-MEG), pcDNA3.1-MEG3+miR-NC group (pcDNA3.1-MEG3 co-transfected with miR-NC), pcDNA3.1-MEG3+miR-181b-5p mimic group (pcDNA3.1-MEG3 co-transfected with miR-181b-5p mimic). The expressions of MEG3 and miR-181b-5p in PC3 cells were detected with qRT-PCR. The cell viability, invasion and migration ability were determined with MTT assay, Transwell assay and scratch assay. The protein expressions of TIMP3, matrix metalloproteinase (MMP)9 and MMP2 in PC3 cells were detected with Western blot. The targeting relationship of MEG3, miR-181b-5p and TIMP3 was analyzed with dual luciferase assay. 【Results】 The expressions of MEG3 in prostate cancer tissues ( 0.37±0.05 vs. 1.00±0.04) and cells (0.31±0.06 vs. 1.00±0.01) were significantly decreased (P<0.05). Compared with the control group, the pcDNA3.1-MEG3 group had significantly decreased expression of miR-181b-5p (0.26±0.04 vs.1.00±0.02 ), cell survival rate (53.60±5.22 vs.100.00±0.00), number of invasive cells (62.33±9.85 vs.162.34±21.30), cell migration rate (32.85±3.80 vs.75.22±5.96), expressions of MMP9 (0.61±0.08 vs.1.62±0.23) and MMP2 (0.73±0.10 vs.1.20±0.16), but significantly higher expressions of MEG3 (2.31±0.36 vs. 1.00±0.01) and TIMP3 (1.32±0.24 vs. 0.53±0.08) (P<0.05). Overexpression of miR-181b-5p reversed the above changes (P<0.05). MiR-181b-5p had a targeting relationship with MEG3 and TIMP3. 【Conclusion】 Overexpression of lncRNA MEG3 can inhibit miR-181b-5p to promote the expression of TIMP3, thereby inhibiting invasion and migration of PC3 cells.