Potent bromodomain and extraterminal domain inhibitor JAB-8263 suppresses MYC expression and exerts anti-tumor activity in colorectal cancer models.

BACKGROUND: The overexpression of the MYC gene plays an important role in the occurrence, development and evolution of colorectal cancer (CRC). Bromodomain and extraterminal domain (BET) inhibitors can decrease the function BET by recognizing acetylated lysine residues, thereby downregulating the expression of MYC. AIM: To investigate the inhibitory effect and mechanism of a BET inhibitor on CRC cells. METHODS: The effect of the BET inhibitor JAB-8263 on the proliferation of various CRC cell lines was studied by CellTiter-Glo method and colony formation assay. The effect of JAB-8263 on the cell cycle and apoptosis of CRC cells was studied by propidium iodide staining and Annexin V/propidium iodide flow assay, respectively. The effect of JAB-8263 on the expression of c-MYC, p21 and p16 in CRC cells was detected by western blotting assay. The anti-tumor effect of JAB-8263 on CRC cells in vivo and evaluation of the safety of the compound was predicted by constructing a CRC cell animal tumor model. RESULTS: JAB-8263 dose-dependently suppressed CRC cell proliferation and colony formation in vitro. The MYC signaling pathway was dose-dependently inhibited by JAB-8263 in human CRC cell lines. JAB-8263 dose-dependently induced cell cycle arrest and apoptosis in the MC38 cell line. SW837 xenograft model was treated with JAB-8263 (0.3 mg/kg for 29 d), and the average tumor volume was significantly decreased compared to the vehicle control group (P < 0.001). The MC38 syngeneic murine model was treated with JAB-8263 (0.2 mg/kg for 29 d), and the average tumor volume was significantly decreased compared to the vehicle control group (P = 0.003). CONCLUSION: BET could be a potential effective drug target for suppressing CRC growth, and the BET inhibitor JAB-8263 can effectively suppress c-MYC expression and exert anti-tumor activity in CRC models.

Predictive Value of the Systemic Immune Inflammation Index for Adverse Outcomes in Patients With Acute Ischemic Stroke.

Background and Purpose: The systemic immune-inflammation index, a new index based on platelets, neutrophils and lymphocytes, has been shown to be associated with outcomes of patients with venous sinus thrombosis and cancer. However, its application in acute ischemic stroke has rarely been reported. Therefore, we examined the relationship between systemic immune-inflammation index levels at hospital admission and the outcomes of patients 3 months after onset, and plotted a nomogram to predict the probability of adverse outcomes in patients with acute ischemic stroke. Methods: We retrospectively analyzed a total of 208 patients with acute ischemic stroke who were admitted between January 2020 and December 2020, and recorded the modified Rankin score 3 months later. A modified Rankin score ≥ 3 was defined as an adverse outcome. Age, sex, NIHSS score, SII, hypertension and coronary heart disease were included in the binary logistic regression, and the nomogram was plotted with a regression equation. Results: Receiver operating characteristic (ROC) curve analysis indicated that the best cutoff value of the systemic immune-inflammation index was 802.8, with a sensitivity of 70.9% and specificity of 58.2% (area under the curve: 0.657, 95% confidence interval: 0.572-0.742). The nomogram had a C index of 0.802. The average error of the calibration curves of the training set and the validation set was 0.021 and 0.034, respectively. Conclusion: The systemic immune-inflammation index is associated with short-term adverse outcomes in patients with acute ischemic stroke, and the nomograms can predict the risk of adverse outcomes in patients with acute ischemic stroke.

Path of social organizations participation in management of mental health in primary and middle schools / 中国学校卫生

Abstract@#As an important part of the social psychological service system, social organizations provide collaborative support for the management of mental health in primary and middle schools. Based on a case of Wuhan psychological service center, the significant contributions were made by social organizations, including system building,technique provides,field supervision and resource aggregation. Social organizations efforts include improving school psychology service system, exploring school based curriculum in respond to needs, seeking solutions of the crisis, and collaborating with social resources to guide multilateral support. The path of social organizations in participating in the mental health management, the limitations and needed support would be explored.

Analysis of genetic variant in a Chinese pedigree affected with neurofibromatosis type I / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with neurofibromatosis type I (NF1).@*METHODS@#Target capture high-throughput sequencing and Sanger sequencing were carried out to detect the pathological variant in a NF1 patient and his parents.@*RESULTS@#The proband and his similarly affected father have both harbored a novel nonsense variant of c.2511G>A (p.trp837x) in the NF1 gene. The same variant was not found in his mother and 200 healthy controls.@*CONCLUSION@#The heterozygous nonsense variant of c.2511G>A (p.trp837x) of the NF1 gene probably underlay the pathogenesis of NF1 in this pedigree.

Swallowing function and its related factors in elderly people in welfare homes of Wenzhou City / 上海预防医学

Objective:To understand the swallowing function of the elderly in welfare homes of Wenzhou City，Zhejiang Province and to analyze the related factors of swallowing dysfunction. Methods:A total of 507 elderly people aged 60 years and over were surveyed by questionnaires in three welfare homes of Wenzhou City from January 2018 to January 2020.Hinds time-limited water drinking test was used to screen dysphagia. Multivariate unconditional logistic regression analysis was used to analyze the related factors of swallowing dysfunction. Results:The incidence of swallowing dysfunction was 26.04% （132 out of 507）. Univariate analysis showed that there were significant differences in the incidence of swallowing dysfunction among the elderly in terms of age， spouse condition， self-care ability， health status， taking sleeping pills， cerebrovascular disease， nervous system disease and depression （P<0.05）. Multivariate logistic regression analysis showed that the following factors were related to swallowing dysfunction among the elderly： age ≥80 years old， taking sleeping pills， cerebrovascular diseases， nervous system diseases and depression. Conclusion:The incidence of swallowing dysfunction in elderly people in welfare homes of Wenzhou City is high， especially those aged ≥80 years who need more attention. In addition， taking sleeping pills， cerebrovascular diseases， nervous system diseases and depression all increase the risk of swallowing dysfunction. Corresponding preventive and intervention measures should be formulated.

The impact of COVID-19 on gastric cancer surgery: a single-center retrospective study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been declared a global pandemic by the World Health Organization. Patients with cancer are more likely to incur poor clinical outcomes. Due to the prevailing pandemic, we propose some surgical strategies for gastric cancer patients. METHODS: The 'COVID-19' period was defined as occurring between 2020 and 01-20 and 2020-03-20. The enrolled patients were divided into two groups, pre-COVID-19 group (PCG) and COVID-19 group (CG). A total of 109 patients with gastric cancer were enrolled in this study. RESULTS: The waiting time before admission increased by 4 days in the CG (PCG: 4.5 [IQR: 2, 7.8] vs. CG: 8.0 [IQR: 2,20]; p = 0.006). More patients had performed chest CT scans besides abdominal CT before admission during the COVID-19 period (PCG: 22 [32%] vs. CG: 30 [73%], p = 0.001). After admission during the COVID period, the waiting time before surgery was longer (PCG: 3[IQR: 2,5] vs. CG: 7[IQR: 5,9]; p < 0.001), more laparoscopic surgeries were performed (PCG: 51[75%] vs. CG: 38[92%], p = 0.021), and hospital stay period after surgery was longer (7[IQR: 6,8] vs.9[IQR:7,11]; p < 0.001). In addition, the total cost of hospitalization increased during this period, (PCG: 9.22[IQR:7.82,10.97] vs. CG: 10.42[IQR:8.99,12.57]; p = 0.006). CONCLUSION: This study provides an opportunity for our surgical colleagues to reflect on their own services and any contingency plans they may have to tackle the COVID-19 crisis.

Progress in Molecular Mechanisms and Cell Transplantation Therapy of Parkinson's Disease / 中国药学杂志

Neuron is the basic structure and functional unit of nervous system. Once the neurons are damaged or lost, the balance of neuroregulation will be destroyed and a series of nervous system diseases will be induced. Parkinson's disease (PD) is a kind of chronic neurodegenerative disease caused by selective loss of many dopaminergic neurons in the dense region of the substantia nigra in the ventral midbrain. At present, conventional drugs and adjuvant therapies can only relieve clinical symptoms to a certain extent, but cannot fundamentally delay the progress of the disease. With the rapid development of stem cells and reprogramming technologies around the world, cell transplantation to deal with neurodegenerative diseases including Parkinson's disease has become a new and potential therapy. This paper mainly summarizes the molecular mechanisms of Parkinson's disease, the preparation of autogenous dopaminergic neurons and the research progresses of dopaminergic neurons transplantation in the treatment of Parkinson's disease.

Curative effect and aesthetics analysis of 40 patients with breast fibroadenoma treated by ring -areola incision / 中国基层医药

Objective To analyze the immune function and shoulder function of sentinel lymph node biopsy combined with mastectomy in patients with early breast cancer.Methods A total of 80 patients with breast fibroadenoma were selected ,and they were randomly divided into surround -mammary areola incision group ( n=40 ) and conven-tional radial incision group(n=40) according to the digital table.The bleeding volume,operation time,hospital stay, satisfaction and curative effect were compared between the two groups .Results The markedly effective rate of surround-mammary areola incision group was 87.50％,which was significantly higher than that of the radial incision group(62.50％),and the difference was statistically significant (χ2 =10.400,P=0.001).The total effective rate was 100.00％in the surround -mammary areola incision group ,which was significantly higher than that in the radical incision group(χ2 =6.500,P=0.010).The time of operation,the amount of bleeding and the length of hospital stay in the surround-mammary areola incision group were (56.7 ±3.2) min,(62.1 ±1.8) mL and(8.3 ±0.8) d, respectively,which were lower than those in the radial incision group [(69.8 ±4.3)min,(71.1 ±2.4)min,(11.2 ± 1.3)d],there were statistically significant differences between the two groups (t=15.262,P=0.000;t=18.735, P=0.000;t=11.864,P=0.000).The incidence rates of breast milk symmetry,scar acceptance and adverse reaction in surround-mammary areola incision group were 87.50％,87.50％ and 2.50％,respectively,which were significantly better than those in the radial incision group(67.50％,65.00％ and 15.00％),there were statistically significant differences between the two groups (χ2 =5.032,P=0.024;χ2 =7.862,P=0.005;χ2 =3.923,P=0.047).The total satisfaction rate was 87.50％in the surround-mammary areola incision group ,which was higher than 62.50％in the radial incision group (χ2 =7.222,P=0.007).Conclusion The use of surround -mammary areola incision in the treatment of patients with breast fibroadenoma has obvious effect ,can reduce the degree of breast injury ,improve the physical appearance of the breast ,with high satisfaction .

[Effect of agricultural application of municipal sewage sludge on plant-soil system: A review]. / 城市污泥农用对植物-土壤系统的影响.

Currently, reasonable disposal of municipal sewage sludge is one of the important issues in the field of resources and environmental science. Sludge is rich in large amounts of organic matter and available nutrients, promoting soil fertility, soil physical structure and biological properties. However, sludge contains a variety of heavy metals, organic contaminants and other hazardous substance, especially heavy metals, which are the bottlenecks of agricultural application of sludge. To improve the sewage sludge utilization efficiency and decrease the effect on soil, this essay made a summary on domestic and foreign studies on plant-soil interaction ecosystem with sewage sludge to provide a theoretical basis and scientific guidance for advancing sewage sludge utilization efficiency.

Ethanol extract of propolis protects vascular endothelial cells from oxidized low-density lipoprotein-induced apoptosis by inhibiting C/EBP homologous protein expression / 中国病理生理杂志

AIM:To investigate the inhibitory effect of ethanol extract of propolis (EEP) on oxidized low-density lipoprotein (ox-LDL)-induced vascular endothelial cell apoptosis and the underlying molecular mechanisms.METHODS:Human umbilical vein endothelial cells (HUVECs) were pretreated with EEP (7.5,15 and 30 mg/L) or 4-phenylbutyric acid (PBA,4 mmol/L) for 1 h and then treated with ox-LDL (100 mg/L) or tunicamycin (TM,4 mg/L) for 24 h.The cell viability and apoptosis were determined by MTT assay and Annexin V-FITC/PI double staining,respectively.The activities of lactic dehydrogenase (LDH) in the medium and caspase-3 in the HUVECs were measured.The protein and mRNA levels of C/EBP homologous protein (CHOP),a proapoptotic molecule under endoplasmic reticulum stress (ERS),and its downstream Bcl-2 were examined by Western blot and real-time PCR,respectively.RESULTS:Like PBA (an ERS inhibitor),EEP protected HUVECs from ox-LDL-induced injury in a dose-dependent manner,as assessed by the increased cell viability and the decreased LDH release,apoptotic rate and caspase-3 activation.The decrease in cell viability and the increases in LDH release,apoptotic rate and caspase-3 activation induced by TM,an ERS inducer,were also attenuated by EEP.Moreover,EEP suppressed ox-LDL-induced CHOP upregulation and Bcl-2 downregulation,and this effect was similar to that of PBA.Similarly,EEP significantly suppressed TM-induced CHOP upregulation both at the protein and mRNA levels.CONCLUSION:EEP may protect HUVECs from ox-LDL-induced apoptosis,and the mechanism is at least partially involved in suppressing CHOP-mediated ERS-associated apoptotic pathway.

Ethanol extract of propolis protects vascular endothelial cells from oxidized low-density lipoprotein-induced apoptosis by inhibiting C/EBP homologous protein expression / 中国病理生理杂志

AIM:To investigate the inhibitory effect of ethanol extract of propolis (EEP) on oxidized low-density lipoprotein (ox-LDL)-induced vascular endothelial cell apoptosis and the underlying molecular mechanisms.METHODS:Human umbilical vein endothelial cells (HUVECs) were pretreated with EEP (7.5,15 and 30 mg/L) or 4-phenylbutyric acid (PBA,4 mmol/L) for 1 h and then treated with ox-LDL (100 mg/L) or tunicamycin (TM,4 mg/L) for 24 h.The cell viability and apoptosis were determined by MTT assay and Annexin V-FITC/PI double staining,respectively.The activities of lactic dehydrogenase (LDH) in the medium and caspase-3 in the HUVECs were measured.The protein and mRNA levels of C/EBP homologous protein (CHOP),a proapoptotic molecule under endoplasmic reticulum stress (ERS),and its downstream Bcl-2 were examined by Western blot and real-time PCR,respectively.RESULTS:Like PBA (an ERS inhibitor),EEP protected HUVECs from ox-LDL-induced injury in a dose-dependent manner,as assessed by the increased cell viability and the decreased LDH release,apoptotic rate and caspase-3 activation.The decrease in cell viability and the increases in LDH release,apoptotic rate and caspase-3 activation induced by TM,an ERS inducer,were also attenuated by EEP.Moreover,EEP suppressed ox-LDL-induced CHOP upregulation and Bcl-2 downregulation,and this effect was similar to that of PBA.Similarly,EEP significantly suppressed TM-induced CHOP upregulation both at the protein and mRNA levels.CONCLUSION:EEP may protect HUVECs from ox-LDL-induced apoptosis,and the mechanism is at least partially involved in suppressing CHOP-mediated ERS-associated apoptotic pathway.

Detection of KIT gene of a case with serious phenotypes of piebaldism / 中山大学学报(医学科学版)

[Objective]To investigate the mutations of KIT gene and SLUG(SNAI2)gene in one patients with piebaldism in Chi?na.[Methods]All coding exons and exon-intron boundaries of KIT gene and SLUG gene were amplified by PCR. The PCR products were sequenced. The DNA samples from 50 normal subjects were also sequenced for control.[Results]The novel mutation,c.860T>A (p.V287E),was detected in patient. This mutation was absent in his parents and the controls ,indicating a de novo mutation. The de?tection result of all coding exons and exon-intron boundaries of SLUG gene was normal.This p.V287E mutation was located in the ex?tracellular ligand-bindingdomain(ectodomain)of KIT,which may generate clash with E249 and disrupt the conformation ofβD andβD/βE of D3 that required for SCF(stem cell factor)binding.[Conclusion]We have identified a novel mutation of KIT gene,c.860T>A(p.V287E),which is probably associated with serious phenotypes of piebaldism.

The expression of cancer-related gene gankyrin in pancreatic cancer / 中华胰腺病杂志

Objective To investigate the clinical significance of tumor related gene gankyrin expression in pancreatic cancer.Methods The immunohistochemical staining was performed to study the gankyrin expression in 62 pairs of pancreatic cancer and matched non-tumor tissues.The correlations ofgankyrin expression with pathological parameters and the influences on the prognosis were analyzed.Results Ggankyrin positivity in pancreatic cancer and matched non tumor tissue was 2.5％ (45/62)and 19.4％ (12/62),respectively.The positivity of gankyrin was significantly higher in pancreatic cancer compared with matched non-tumor tissues,and the differences were statistical significant (P ＜ 0.01).Gankyrin expression in pancreatic cancer tissues were significantly correlated with TNM stage,differentiation and metastasis (P ＜ 0.05),but not with age,gender or tumor location (P ＞ 0.05).The 3-year survival rates of patients with positive and negative gankyrin expression were 17.8 ％ (8/45)and 41.2％ (7/17),respectively.Patients with positive gankyrin expression had a significantly shorter survival period compared with these with negative expression in pancreatic cancer tissues (P =0.034).Conclusions Gankyrin was overexpressed in pancreatic cancer,which was correlated with poor prognosis.

Analysis and strategy of family caregiving behavior in children with recurrent lower respiratory tract infection / 中国实用护理杂志

Objective To explore and analyze the influencing factors of family caregiving behavior and protective strategies in children with recurrent lower respiratory tract infection. Methods By reviewing the literature, a self-designed questionnaire for family caregiving behavior related to recurrent lower respiratory tract infection were adopted, including feeding behavior, hand hygiene, environmental factors, time of outdoor activities and family health-seeking behavior. Totally 206 cases with recurrent lower respiratory tract infection (the study group) and 206 cases with acute lower respiratory tract infection (the control group) were included and all cases were investigated by family caregiving behavior questionnaire. The influencing factors of family caregiving behavior of two groups were analyzed and compared. Results The feeding behavior in the study group was worse than that in the control group(χ2=5.14-14.76, P0.05). Conclusions We should guide parents to establish the right and reasonable family care behavior to effectively enhance children's physical fitness and disease resistance and to avoid exposure to infectious agents and harmful substances, reduce the occurrence of Recurrent Lower Respiratory Tract Infections.

Relationship between Mycoplasma pneumoniae infection and secondary allergic diseases in children / 第二军医大学学报

Objective We sought to determine the relationship between MP infection and secondary allergic disease and to clarify the associated mechanisms. Methods A prospective study was performed to investigate the patient’ immune status by determining serum cytokines spectrum and immunoglobulin E (IgE) levels, and to compare these indicators with sepsis patients and healthy children. Results Comparing with healthy children, children with mycoplasma pneumoniae infection Th2 cytokines, such as, IL - 4, IL - 6 and IL - 10 increased significantly. Comparing with healthy children, sepsis patients’ IL - 6 and IL - 10 levels raised significantly, but there was no significant change on IL - 4 level. Only when children infected with mycoplasma pneumoniae, the serum IgE level significantly increased. Conclusion When children with mycoplasma pneumoniae infection, the serum IgE level significantly increased, IL-4 level is the key factor for determining serum IgE levels. ThisSstudySalso shows that Th1/Th2 imbalance happened in the process of mycoplasma pneumoniae infection.

Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling.

Chondrocyte apoptosis is an important mechanism involved in osteoarthritis (OA). Berberine (BBR), a plant alkaloid derived from Chinese medicine, is characterized by multiple pharmacological effects, such as anti-inflammatory and anti-apoptotic activities. This study aimed to evaluate the chondroprotective effect and underlying mechanisms of BBR on sodium nitroprusside (SNP)-stimulated chondrocyte apoptosis and surgically-induced rat OA model. The in vitro results revealed that BBR suppressed SNP-stimulated chondrocyte apoptosis as well as cytoskeletal remodeling, down-regulated expressions of inducible nitric oxide synthase (iNOS) and caspase-3, and up-regulated Bcl-2/Bax ratio and Type II collagen (Col II) at protein levels, which were accompanied by increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased phosphorylation of p38 mitogen-activated protein kinase (MAPK). Furthermore, the anti-apoptotic effect of BBR was blocked by AMPK inhibitor Compound C (CC) and adenosine-9-ß-D-arabino-furanoside (Ara A), and enhanced by p38 MAPK inhibitor SB203580. In vivo experiment suggested that BBR ameliorated cartilage degeneration and exhibited an anti-apoptotic effect on articular cartilage in a rat OA model, as demonstrated by histological analyses, TUNEL assay and immunohistochemical analyses of caspase-3, Bcl-2 and Bax expressions. These findings suggest that BBR suppresses SNP-stimulated chondrocyte apoptosis and ameliorates cartilage degeneration via activating AMPK signaling and suppressing p38 MAPK activity.

RNF43 Inhibits Cancer Cell Proliferation and Could be a Potential Prognostic Factor for Human Gastric Carcinoma.

BACKGROUND/AIMS: RNF43 is a member of transmembrane E3 ubiquitin ligases and plays important roles in tumor formation progression. In current study, we aimed to explore RNF43 expression and analyze its role in gastric carcinoma. METHODS AND RESULTS: The level of RNF43 was detected in 77 cases of gastric carcinoma and matched normal tissues by real-time PCR, western blotting and immunohistochemistry. We found that the expression of RNF43 was significantly down-regulated in the gastric carcinoma tissues compared to the normal mucosae (all P<0.001). In addition, RNF43 was significantly correlated with histological differentiation (P = 0.001), T-stage cancer (P<0.001), depth of invasion (P<0.001), metastasis of regional lymph nodes (P<0.001), pTNM stage (P<0.001) and survival (P = 0.021). We further explored the biological functions of RNF43 in gastric carcinoma cell lines. Both gain- and loss-function assays show that RNF43 could suppress cell proliferation while promotes cell apoptosis. Further, we found that RNF43 was positively correlated with p53 and cleaved-caspase3 and negatively correlated with Ki67 and Lgr5. CONCOLUSION: In conclusion, RNF43 might act as a tumor suppressor in gastric carcinoma and might be a potential indicator for the clinical assessment of gastric cancer prognosis.

Clinical significance of immunotherapy with combined three kinds of cells for operable colorectal cancer.

Surgery, chemotherapy, and radiotherapy have presented with the ability of killing tumor cells, as well as damaging the immune function, which can be corrected by the immunotherapy. The purpose of this perspective cohort study was to evaluate the efficacy of postoperative immunotherapies of tumor lysate-loaded dendritic cells (DC), in vitro DC-activated T (DC-AT), and activated T cells (ATC) combined with chemotherapy on the survival of patients with operable colorectal cancer. A total of 253 patients with primary colorectal cancer resection including 181 patients receiving postoperative simple chemotherapy (control group) and 72 patients receiving immunotherapies of DC, DC-AT, and ATC combined with chemotherapy during the corresponding period (immunotherapy group) were enrolled in this perspective cohort study. The survival of these patients was analyzed. The immunotherapy group presented a higher 5-year overall survival rate than the control group (75.63 vs 67.81 %, P = 0.035), as well as 3-year overall survival rate (87.07 vs 74.80 %, P = 0.045). For patients with advanced cancer (TNM stages III and IV), immunotherapy significantly promotes mean survival than control subjects (59.74 ± 3.21 vs 49.99 ± 2.54 years, P = 0.034). Patients who received more than three cycles of immunotherapies had a higher 5-year overall survival rate than those with less than three cycles (82.10 vs 69.90 %, P = 0.035). No serious adverse effect was observed in the immunotherapy group. Postoperative immunotherapies with DC, DC-AT, and ATC combination can promote the survival of patients with operable colorectal cancer (Clinical Trials, ChiCTR-OCH-12002610).

Curative effect of nasal irrigation combined with backslapping for sputum suctioning on respiratory tract infections in infants / 现代临床护理

Objective To study the curative effect of nasal irrigation combined with backslapping for sputum suctioning on respiratory tract infections in infants . Methods Two hundred and forty-seven infants with respiratory tract infections were enrolled in the study and divided into the control group and the experiment group by the medical record number . On the basis of routine care , the experiment group was treated with nasal irrigation to clear secretions . Result The time for rales and cough disappearing in the experiment group was shorter than that in the control group , and the difference was statistically significant ( P<0 . 05 ) . Conclusions Nasal irrigation combined with backslapping for sputum suctioning can effectively ease the main symptoms and signs , enhance the ventilation function , enhance sleep quality and promote the rehabilitation of the disease .

Berberine suppresses in vitro migration of human aortic smooth muscle cells through the inhibitions of MMP-2/9, u-PA, AP-1, and NF-κB.

Berberine, a type of isoquinoline alkaloid isolated from Chinese medicinal herbs, has been reported to have various pharmacological activities. Studies have demonstrated that berberine has beneficial effects on vascular remodeling and alleviates restenosis after vascular injury. However, its mechanism of action on vascular smooth muscle cell migration is not fully understood. We therefore investigated the effect of berberine on human aortic smooth muscle cell (HASMC) migration. Boyden chamber assay was performed to show that berberine inhibited HASMC migration dosedependently. Real-time PCR and Western blotting analyses showed that levels of matrix metalloproteinase (MMP)-2, MMP-9, and urokinase-type plasminogen activator (u-PA) were reduced by berberine at both the mRNA and protein levels. Western blotting assay further confirmed that activities of c-Fos, c-Jun, and NF-κB were significantly attenuated. These results suggest that berberine effectively inhibited HASMC migration, possibly by down-regulating MMP-2, MMP-9, and u-PA; and interrupting AP-1 and NF-κB mediated signaling pathways.