Identification of the Key Genes Involved in the Tumorigenesis and Prognosis of Prostate Cancer.

Background: Prostate cancer (PCa) is a malignant tumor in males, with a majority of the cases advancing to metastatic castration resistance. Metastasis is the leading cause of mortality in PCa. The traditional early detection and prediction approaches cannot differentiate between the different stages of PCa. Therefore, new biomarkers are necessary for early detection and clear differentiation of PCa stages to provide precise therapeutic intervention. Methods: The objective of the study was to find significant differences in genes and combine the three GEO datasets with TCGA-PRAD datasets (DEG). Weighted gene coexpression network analysis (WGCNA) determined the gene set and PCa clinical feature correlation module utilizing the TGGA-PRAD clinical feature data. The correlation module genes were rescreened using the biological information analysis tools, with the three hub genes (TOP2A, NCAPG, and BUB1B) for proper verification. Finally, internal (TCGA) and external (GSE32571, GSE70770) validation datasets were used to validate and predict the value of last hub genes. Results: The hub gene was abnormally upregulated in PCa samples during verification. The expression of each gene was favorably connected with the Gleason score and TN tumor grade in clinical samples but negatively correlated with the overall survival rate. The expression of these genes was linked to CD8 naive cells and macrophages, among other cells. Antitumor immune cells like NK and NKT were favorably and adversely correlated with infiltrating cells, respectively. Simultaneously, the GSCV and GSEA indicated that the hub gene is connected with cell proliferation, death, and androgen receptor, among other signaling pathways. Therefore, these genes could influence the incidence and progression of PCa by participating in or modulating various signaling pathways. Furthermore, using the online tool of CMap, we examined the individual medications for Hughes and determined that tipifarnib could be useful for the clinical therapy of PCa. Conclusion: TOP2A, NCAPG, and BUB1B are important genes intimately linked to the clinical prognosis of PCa and can be employed as reliable biomarkers for early diagnosis and prognosis. Moreover, these genes can provide a theoretical basis for precision differentiation and treatment of PCa.

Design, synthesis, and biological evaluation of indole-based hydroxamic acid derivatives as histone deacetylase inhibitors.

The equilibrium between histone acetylation and deacetylation plays an important role in cancer initiation and progression. The histone deacetylases (HDACs) are a class of key regulators of gene expression that enzymatically remove an acetyl moiety from acetylated lysine ε-amino groups on histone tails. Therefore, HDAC inhibitors have recently emerged as a promising strategy for cancer therapy and several pan-HDAC inhibitors have globally been approved for clinical use. In the present study, we designed and synthesized a series of substituted indole-based hydroxamic acid derivatives that exhibited potent anti-proliferative activities in various tumor cell lines. Among the compounds tested, compound 4o, was found to be among the most potent in the inhibition of HDAC1 (half maximal inhibitory concentration, IC50 = 1.16 nM) and HDAC6 (IC50 = 2.30 nM). It also exhibited excellent in vitro anti-tumor proliferation activity. Additionally, compound 4o effectively increased the acetylation of histone H3 in a dose-dependent manner and inhibited cell proliferation by inducing cell cycle arrest and apoptosis. Moreover, compound 4o remarkably blocked colony formation in HCT116 cancer cells. Based on its favorable in vitro profile, compound 4o was further evaluated in an HCT116 xenograft mouse model, in which it demonstrated better in vivo efficacy than the clinically used HDAC inhibitor, suberanilohydroxamic acid. Interestingly, compound 4k was found to have a preference for the inhibition of HDAC6, with IC50 values of 115.20 and 5.29 nM against HDAC1 and HDAC6, respectively.

Role of Ten eleven translocation-2 (Tet2) in modulating neuronal morphology and cognition in a mouse model of Alzheimer's disease.

Abnormal expression of Ten eleven translocation-2 (Tet2) contributes to the pathogenesis of Alzheimer's disease (AD). However, to date, the role of Tet2 in modulating neuronal morphology upon amyloid-ß (Aß)-induced neurotoxicity has not been shown in a mouse model of AD. Here, we have developed a model of injured mouse hippocampal neurons induced by Aß42 oligomers in vitro. We also investigated the role of Tet2 in injured neurons using recombinant plasmids-induced Tet2 inhibition or over-expression. We found that the reduced expression of Tet2 exacerbated neuronal damage, whereas the increased expression of Tet2 was sufficient to protect neurons against Aß42 toxicity. Our results indicate that the brains of aged APPswe/PSEN1 double-transgenic (2 × Tg-AD) mice exhibit an increase in Aß plaque accumulation and a decrease in Tet2 expression. As a result, we have also explored the underlying mechanisms of Tet2 in cognition and amyloid load in 2 × Tg-AD mice via adeno-associated virus-mediated Tet2 knockdown or over-expression. Recombinant adeno-associated virus was microinjected into bilateral dentate gyrus regions of the hippocampus of the mice. Knocking down Tet2 in young 2 × Tg-AD mice resulted in the same extent of cognitive dysfunction as aged 2 × Tg-AD mice. Importantly, in middle-aged 2 × Tg-AD mice, knocking down Tet2 accelerated the accumulation of Aß plaques, whereas over-expressing Tet2 alleviated amyloid burden and memory loss. Furthermore, our hippocampal RNA-seq data, from young 2 × Tg-AD mice, were enriched with aberrantly expressed lncRNAs and miRNAs that are modulated by Tet2. Tet2-modulated lncRNAs (Malat1, Meg3, Sox2ot, Gm15477, Snhg1) and miRNAs (miR-764, miR-211, and miR-34a) may play a role in neuron formation. Overall, these results indicate that Tet2 may be a potential therapeutic target for repairing neuronal damage and cognitive impairment in AD.

Enhanced expression of microtubule-associated protein 7 functioned as a contributor to cervical cancer cell migration and is predictive of adverse prognosis.

BACKGROUND: Cervical cancer (CC) is one of the most common female malignancies over the world. Microtubule-associated protein 7 (MAP7) belongs to the family of microtubule-associated proteins (MAPs) which involve in microtubule dynamics and are critical in several important cellular and intracellular activities. This study aimed to investigate the expression and potential role of MAP7 in CC. METHODS: The expression level of MAP7 in CC tissues and normal tissues were analyzed using the data obtained from The cancer genomes atlas (TCGA) and genotype-tissue expression (GTEx) databases. The prognostic value of MAP7 in patients with CC was analyzed by Kaplan-Meier analysis, Univariate and Multivariate analyses. Moreover, the influences of MAP7 expression alteration on the viability and motility of Caski, HeLa and C-33A cells was measured by CCK8 assay, colony formation assay, scratch assay, and transwell migration and invasion assays. Flow cytometry was conducted to determine cell apoptosis. Western blot was performed to evaluate the impact of MAP7 on the expression of apoptotic-related proteins as well as mitogen-activated protein kinase (MAPK) signaling pathway-related proteins. In vivo tumorigenicity assay was performed to explore the influence of MAP7 on tumor growth. RESULTS: Up-regulation of MAP7 was observed in CC tissues and high MAP7 expression was positively correlated with worse prognosis. Multivariate analyses suggested that MAP7 expression can be served as an independent predictor for overall survival of patients with CC. Knockdown of MAP7 markedly suppressed Caski and HeLa cell viability, migration and invasion while notably induced cell apoptosis. Furthermore, depletion of MAP7 in Caski and HeLa cells elevated the expression levels of Active-caspase 3 and Bax, but declined the level of Bcl-2. Whilst, overexpression of MAP7 in C-33A cells presented the opposite outcomes. Additionally, knockdown of MAP7 significantly decreased the phosphorylation of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) in Caski and HeLa cells, and overexpression of MAP7 increased their phosphorylation in C-33A cells, indicating that MAP7 may regulate the MAPK signaling pathway in CC cells. In vivo assays revealed that knockdown of MAP7 remarkably repressed the growth of CC tumors. CONCLUSION: The results of the present study suggest that MAP7 functions as a promoter during the occurrence and progression of CC, and that MAP7 may serve as a promising therapeutic target in CC.

Reduction of Tet2 exacerbates early stage Alzheimer's pathology and cognitive impairments in 2×Tg-AD mice.

Abnormal modification of 5-hydroxymethylcytosine (5hmC) is closely related to the occurrence of Alzheimer's disease (AD). However, the role of 5hmC and its writers, ten-eleven translocation (Tet) proteins, in regulating the pathogenesis of AD remains largely unknown. We detected a significant decrease in 5hmC and Tet2 levels in the hippocampus of aged APPswe/PSEN1 double-transgenic (2×Tg-AD) mice that coincides with abundant amyloid-ß (Aß) plaque accumulation. On this basis, we examined the reduction of Tet2 expression in the hippocampus at early disease stages, which caused a decline of 5hmC levels and led young 2×Tg-AD mice to present with advanced stages of AD-related pathological hallmarks, including Aß accumulation, GFAP-positive astrogliosis and Iba1-positive microglia overgrowth as well as the overproduction of pro-inflammatory factors. Additionally, the loss of Tet2 in the 2×Tg-AD mice at 5 months of age accelerated hippocampal-dependent learning and memory impairments compared to age-matched control 2×Tg-AD mice. In contrast, restoring Tet2 expression in adult neural stem cells isolated from aged 2×Tg-AD mice hippocampi increased 5hmC levels and increased their regenerative capacity, suggesting that Tet2 might be an exciting target for rejuvenating the brain during aging and AD. Further, hippocampal RNA sequencing data revealed that the expression of altered genes identified in both Tet2 knockdown and control 2×Tg-AD mice was significantly associated with inflammation response. Finally, we demonstrated that Tet2-mediated 5hmC epigenetic modifications regulate AD pathology by interacting with HDAC1. These results suggest a combined approach for the regulation and treatment of AD-related memory impairment and cognitive symptoms by increasing Tet2 via HDAC1 suppression.

TGR5 agonist INT-777 mitigates inflammatory response in human endometriotic stromal cells: A therapeutic implication for endometriosis.

Endometriosis is a condition characterized by the presence of endometrial tissues outside the uterus. Endometriotic stromal cells (ESCs) are known to undergo regeneration and are linked to the causation of endometriosis. Activation of stromal cells by local inflammatory cytokines is proposed to be one of the mechanisms of endometriosis development. Takeda-G-protein-receptor-5 (TGR5) is a G protein-coupled bile acid receptor that plays multiple roles in various cells and tissues. In this study, we show that activation of TGR5 by its specific agonist, INT-777, protects ESCs from inflammation and oxidative stress induced by tumor necrosis factor-α (TNF-α). TGR5 is fairly expressed in cultured ESCs, and TNF-α treatment suppresses TGR5 expression. Activation of TGR5 by its synthetic agonist, INT-777, dramatically reduces the production of pro-inflammatory cytokines and adhesion molecules by TNF-α, including interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Moreover, INT-777 suppresses TNF-α-induced NADPH oxidase 4 (NOX4) expression and ameliorates cellular oxidative stress. Mechanistically, our findings demonstrate that INT-777 suppresses TNF-α-induced c-Jun N-terminal kinase (JNK) activation via suppression of p-JNK. INT-777 inhibits TNF-α-induced activation of the activator protein-1 (AP-1) pathway owing to its suppression of c-Jun and c-fos as well as transfected AP-1 promoter. INT-777 also inhibits nuclear factor-κB (NF-κB) activation as revealed by its suppression of TNF-α-induced nuclear p65 accumulation and NF-κB promoter. Collectively, our data indicate that activation of TGR5 by its agonist has protective effects against inflammation and reactive oxygen species (ROS) in cytokine-induced activation of ESCs. Therefore, INT-777 may have an implication in the clinical treatment of endometriosis.

[Expression level of Dickkopf-1 protein in bone mesenchymal stem cells in Type 2 diabetic rats and its relationship with osteogenic activity].

OBJECTIVE: To examine the growth activity and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) in rats with Type 2 diabetes mellitus (T2DM) as well as the expression level of Dickkopf-1 (DKK-1) in bone marrow, and to explore the relationship between the osteogenic activity of BMSCs and the expression of DKK-1.
 Methods: The BMSCs were isolated from T2DM rats and were cultured in vitro. The BMSCs were divided into a T2DM group and a control group. The proliferation of BMSCs was detected by cell counting kit-8 (CCK8). Apoptosis rate was detected by annexin V- fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining. In the osteogenic induction phase, the expression level of alkaline phosphatase (ALP) in BMSCs was detected by ALP staining and ALP activity assay kit. The osteogenic differentiation of BMSCs was analyzed by alizarin red staining and mineralized nodule quantification. In addition, the expression of Runx2 and DKK-1 in BMSCs was detected by qRT-PCR.
 Results: Compared with the control group, the proliferation of BMSCs was decreased and the apoptosis was increased in the T2DM group (both P<0.01). In the osteogenic induction process of BMSCs, the expression of ALP significantly decreased, the formation of calcium nodules reduced, and the expression of osteoblast transcription factor Runx2 was down-regulated in the T2DM group compared with those in the control group (all P<0.01). The levels of DKK-1 protein and mRNA were up-regulated in the T2DM group, which were higher than those in the control group (both P<0.01). The levels of DKK-1 protein and mRNA were related to the increase of Runx2 (both P<0.01).
 Conclusion: The growth activity of BMSCs and the potential of osteogenic differentiation are attenuated in the T2DM rats, which may be related to the increase of DKK-1 expression in BMSCs.

Hormesis of mercuric chloride-human serum albumin adduct on N9 microglial cells via the ERK/MAPKs and JAK/STAT3 signaling pathways.

Mercury chloride (HgCl2), a neurotoxicant that cannot penetrate the blood-brain barrier (BBB). Although when the BBB are got damaged by neurodegenerative disorders, the absorbed HgCl2, mainly in form of Hg (II)-serum albumin adduct (Hg-HSA) in human plasma, can penetrate BBB and affect central nervous system (CNS) cells. Current study planned to evaluate the effect of Hg-HSA on the physiological function of N9 microglial cells. At low dosage (15 ng/mL) of Hg-HAS, the observed outcomes was: promoted cell propagation, Nitric Oxide (NO) and intracellular Ca2+ levels enhancement, suppressed the release of TNF-α and IL-1ß and inhibited cell proliferation. At high dosage (15 µg/mL) we observed decline in NO and intracellular Ca2+ levels, and increment in the release of TNF-α and IL-1ß. These biphasic effects are similar to hormesis, and the hormesis, in this case, was executed through ERK/MAPKs and JAK/STAT3 signaling pathways. Study of quantum chemistry revealed that Hg2+ could form stable coordination structures in both Asp249 and Cys34 sites of HSA. Although five-coordination structure in Asp249 site is more stable than four-coordination structure in Cys34 site but four-coordination structure is formed easily in-vivo in consideration of binding-site position in spatial structure of HSA.

Differential expression of neuroendocrine markers, TTF-1, p53, and Ki-67 in cervical and pulmonary small cell carcinoma.

Small cell carcinoma (SCC) is a highly malignant neuroendocrine tumor that may occur in many anatomic sites of the body.In this study, we compared the different expression of neuroendocrine markers, thyroid transcription factor 1 (TTF-1), p53, and Ki-67 in 23 cases of cervical SCC and 56 cases of pulmonary SCC using immunohistochemistry.Our study showed that cervical SCC had a younger onset age than pulmonary counterpart. Although both had the similar morphological features, different immunohistochemical expression panel was observed in this study. As neuroendocrine tumors, SCC of cervix and lung had similar immunoreactive staining for CD56 and chromogranin A, but the expression of the synaptophysin in cervical SCC was significantly higher than that in pulmonary SCC (P = .007). The TTF-1 expression of pulmonary SCC illustrating diffuse and strong positivity in tumor cell nuclei was significantly higher than that of the cervical SCC (P = .003). There was only 1 case showing p53 protein over-expression in the 23 cases of cervical SCC, and p53 over-expression was observed in 42.9% of pulmonary SCC (P = .001). Only 9 cases of cervical SCC showed ≥80% of the Ki-67 proliferation index, while it was found in 94.6% of pulmonary SCC (P < .001).The different immunohistochemical expressions of these 2 kinds of SCCs may be related with their pathogenetic mechanism, and these differences may be helpful in the identification of the origins of the metastatic SCC with unknown primary site.

Patterns of smoking initiation during adolescence and young adulthood in South-West China: findings of the National Nutrition and Health Survey (2010-2012).

OBJECTIVE: This study aims to understand the age patterns of smoking initiation during adolescence and young adulthood in South-West China, where the prevalence of tobacco use is reported as the highest in the country. DESIGN: A cross-sectional study. SETTING: The data were derived from the China National Nutrition and Health Survey in Yunnan Province, South-West China (2010-2012). PARTICIPANTS: A total of 4801 participants aged 15-65 years were included. PRIMARY OUTCOME MEASURES: A survival model was used to estimate the hazard of smoking initiation by age and log-rank test was used to compare the hazard curves across subgroups (men/women, urban/rural, Han Chinese/ethnic minority). RESULTS: The prevalence of current smoking among men and women were 60.4% (95% CI 58.2% to 62.6%) and 5.1% (95% CI 4.3% to 5.9%), respectively. Smoking was more prevalent among men and women of lower education and less income, as well as rural and ethnic minority women. Among the current smokers, cigarette (80.7%) was the most commonly used tobacco product, followed by waterpipe (10.8%) and pipe tobacco (8.5%). The hazards of smoking initiation were low for both men and women before the age of 15 years (1% for men and 0.05% for women); and the hazards increased quickly from age 15 years and peaked at 19years (21.5% for men and 1.0% for women). Rural and ethnic minority women were at higher risk of smoking initiation than their counterparts between 15 years and 19 years of age (χ2=44.8, p<0.01; χ2=165.2, p<0.01) and no such difference was found in men. CONCLUSIONS: Findings of this study underscore the importance to implement tobacco prevention interventions among older teens and young adults in South-West China, especially for rural and ethnic minority women.

miR-24 represses metastasis of human osteosarcoma cells by targeting Ack1 via AKT/MMPs pathway.

The expression levels of the protein tyrosine kinase Ack1 has been reported to be dysregulated in various cancers and involve in oncogenesis and progression. However, the expression and role of Ack1 in osteosarcoma remains unknown. In this study, we found that Ack1 were evidently upregulated in human osteosarcoma tissues and cell lines. In addition, the clinical data showed that high expression level of Ack1 is closely associated with clinical stage and positive distant metastasis, and negatively correlated with overall survival. Then, bioinformatics prediction and luciferase reporter assay indicated Ack1 as a direct target of miR-24, and Ack1 could be downregulated by miR-24 at both the mRNA and protein expression levels. Moreover, Ack1 expression levels were inversely correlated with that of miR-24 in osteosarcoma tissues. Furthermore, functional assay showed that miR-24 significantly suppressed osteosarcoma progression partially mediated by inhibiting Ack1 expression. Finally, western bolt assay revealed that miR-24 regulate AKT/MMPs pathway via Ack1 in osteosarcoma cells. In conclusion, our study demonstrated the suppression of miR-24 on osteosarcoma metastasis by targeting Ack1 via AKT/MMPs pathways, providing a novel strategy for the diagnosis and treatment of osteosarcoma patients.

Effect of N-Perfluorooctane on Hypoxia/Reoxygenation Injury in Human Umbilical Vein Endothelial Cells.

BACKGROUND: This study investigated the effect of n-perfluorooctane (PFC) on hypoxia/reoxygenation (H/R) injury in human umbilical vein endothelial cells (HUVECs). METHODS: In this study, the H/R models were prepared by chemical methods (using dithionite solution). The experimental groups included the control group, the PFC group with a culture volume ratio of 10%, the H/R model group, and treatment groups with various doses of PFC + H/R (i.e., 5%, 10%, or 20% PFC by volume). The cell counting kit-8 (CCK-8) method was used to assay cell viability. Colorimetric assays were used to estimate the leakage of lactate dehydrogenase (LDH) in the medium, the levels of intracellular malondialdehyde (MDA) and nitric oxide (NO), and the activity of superoxide dismutase (SOD). Western blot was used to analyze the expression of the apoptosis-related protein cystine aspartate proteolytic enzyme 3 (caspase-3). RESULTS: Compared with the control group, every detected index of 10% PFC group had no statistical significance (p > 0.05). Compared with the model group, 10% and 20% PFC treatment groups could increase cell viability A, decrease the content of NO and reduce caspase-3 expression (p < 0.05); Every PFC treatment group could significantly reduce the release of LDH and the contents of MDA, and also increase the activities of SOD (p < 0.01). CONCLUSIONS: PFC has a significant protective effect on HUVEC H/R injury, which may be related to the inhibition of oxidative stress and inflammation and further enhance cell antioxidant and anti-apoptotic characteristics.

Characterization of Soybean mosaic virus resistance derived from inverted repeat-SMV-HC-Pro genes in multiple soybean cultivars.

KEY MESSAGE: Soybean mosaic virus resistance was significantly improved in multiple soybean cultivars through genetic transformation induced by inverted repeat-SMV- HC - Pro genes based on RNAi and post-transcriptional gene silencing. Here, we demonstrate Soybean mosaic virus (SMV) resistance in transgenic soybean plants. Transformation of five soybean genotypes with a construct containing inverted repeat-SMV-HC-Pro genes-induced high-level SMV resistance. Through leaf-painting assays, polymerase chain reaction (PCR) verification and LibertyLink(®) strip detection, 105 T0 and 1059 T1 plants were confirmed as transgene-positive. Southern blotting confirmed insertion of the T-DNA into the genomic DNA and revealed a low-copy integration pattern. Most T0 plants were fertile and transmitted the exogenous genes to their progenies (ratios of 3:1 or 15:1). In the T1 generation, virus resistance was evaluated visually after inoculation with SMV (strain SC3) and 441 plants were highly resistant (HR). SMV disease rating was classified on a scale with 0 = symptomless and 4 = mosaic symptoms with severe leaf curl. In the positive T1 plants, the disease rating on average was 1.42 (range 0.45-2.14) versus 3.2 (range 2-4) for the nontransformed plants. With the T2 generation, 75 transgene-positive plants were inoculated with SC3, and 57 HR plants were identified. Virus-induced seed coat mottling was eliminated in the resistant lines. Analysis of SMV levels in the plants was performed using quantitative real-time PCR and double-antibody sandwich enzyme-linked immunosorbent assays; the results revealed no virus or a gradual reduction over time in the viral content, thereby supporting the visual examination results. This is the first report demonstrating pathogen-derived resistance to SMV induced by inverted repeat-SMV-HC-Pro genes in multiple soybean cultivars. Our findings contribute positively to the study of transgenic SMV-resistance using RNA interference.

Low-voltage direct-current stimulation is safe and promotes angiogenesis in rabbits with myocardial infarction.

This study evaluates safety and efficacy of low-voltage direct-current (DC) electrical stimulation of angiogenesis in rabbits with myocardial infarction (MI). Thirty Japanese rabbits were divided into treatment and control groups, and MI was induced by ligation of the left circumflex (LCX) artery. Two platinum electrodes were placed directly on the epicardium on either side of LCX artery. Low-voltage DC stimulation (4.0 V/cm, 30 min/day) was performed in the treatment group immediately after surgery until fourth week post-operatively. Cardio-electrophysiological, respiratory, hematological, blood biochemical, histopathological, immunohistochemical parameters, as well as capillary density at the marginal zone of myocardial infarct were compared between treatment and control groups. Capillary density in the treatment group (63.1 ± 2.2) was significantly higher (P < 0.01) than that in controls (45.4 ± 3.9). Overall mortality was 6.7%, and the prevalences of pneumothorax and intraoperative arrhythmia were 3.3 and 6.7%, respectively. Transient hypotension, anemia, leukocytosis, hypoxemia, and a slight increase in myocardial enzymes levels were observed in both groups. Regarding electrical stimulation, no adverse reactions except a minor infiltration of inflammatory cells and mild degeneration were observed in the myocardium. It was, therefore, concluded that low-voltage DC stimulation in the MI rabbits was not only safe but also effective in promoting angiogenesis in the myocardium.

Electrical stimulation inhibits neointimal hyperplasia after abdominal aorta balloon injury through the PTEN/p27Kip1 pathway.

Electric fields (EFs) exert biological effects on promoting wound healing by facilitating cell division, cell proliferation, and cell directional migration toward the wound. In this study, we examined the inhibitory effect of direct-current (DC) EFs on the formation of neointimal hyperplasia and the possible mechanism in an abdominal aorta balloon injury rabbit model. Sixty rabbits were divided into normal, control, and experimental groups. After establishment of the abdominal aorta balloon injury model, electrodes were implanted into the bilateral psoas major muscle in control and experimental groups. Only the experimental group received electric stimulation (EFs applied at 3 or 4 V/cm for 30 min/day) for 1, 2, and 4 weeks, respectively. Neointimal hyperplasia of the abdominal aorta and proliferation of vascular smooth muscle cells (VSMCs) were measured. Expressions of collagen, p27(Kip1), and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) were detected. Results showed that the ratio of the tunica intima area to the tunica media area, the expression of type-I collagen in the neointimal, and the proliferating cell nuclear antigen index in experimental groups were significantly less than those in control groups 2 weeks post-operation (P< 0.01). Expressions of p27(Kip1) and PTEN were increased in experimental groups compared with control groups (P< 0.01). In conclusion, our results suggested that the application of DC EFs could inhibit neointimal hyperplasia and reduce collagen expression after abdominal aorta balloon injury. This was probably induced by upregulation of PTEN/p27(Kip1) expression, thereby inhibiting VSMC proliferation.