Miao Q.,The Second Peoples Hospital Of Nantong |
Ge M.,The Second Peoples Hospital Of Nantong |
Huang L.,Nantong University
Neurochemical Research | Year: 2017
Guanylate binding protein 2 (GBP2) is one member of GBP family. Recently, GBP2 has been proposed to be a novel target of anti-cancer drugs. However, the role of GBP2 in the traumatic brain injury (TBI) is very limited. In this study, we sought to define GBP2’s role in brain injury. GBP2 protein levels were significantly increased in the brain 3 days after injury, suggesting a functional role for GBP2 in TBI. Neuronal cells overexpressing GBP2 exhibited up-regulation of co-location of GBP2 and NeuN following TBI, suggesting that GBP2 potentiates the neuron apoptosis. To confirm the role of GBP2 in neuron apoptosis process, we employed a highly potent inhibitor of GBP2 (GBP2 RNAi). In H2O2-stimulated PC12 cells, in vitro blockade of GBP2 activity using GBP2 RNAi markedly attenuated the neuron apoptosis number. GBP2 RNAi also inhibited the expression levels of active caspase3 and p-Stat1. Furthermore, we found the expression of p-Stat1 in line with GBP2 and GBP2 interacted with p-Stat1 following TBI. The Jak2 inhibitor, AG490 inhibited this interaction and decreased the active caspase3 expression as well as promoted the functional recovery. Taken together, these data suggest that GBP2 RNAi has a protective effect in a rat TBI. This study demonstrates that GBP2 is an important positive regulator of TBI and is a promising therapeutic target for brain injury. © 2017 Springer Science+Business Media New York
Gu J.-H.,Soochow University of China |
Gu J.-H.,Nantong University |
Ge J.-B.,Soochow University of China |
Ge J.-B.,The Second Peoples Hospital of Nantong |
And 5 more authors.
PLoS ONE | Year: 2013
Poloxamer 188 (P188), a multiblock copolymer surfactant, has been shown to protect against ischemic tissue injury of cardiac muscle, testes and skeletal muscle, but the mechanisms have not been fully understood. In this study, we explored whether P188 had a protective effect against cerebral ischemia/reperfusion injury and its underlying mechanisms. The in vivo results showed that P188 significantly reduced the infarct volume, ameliorated the brain edema and neurological symptoms 24 h after ischemia/reperfusion. In the long-term outcome study, P188 markedly alleviated brain atrophy and motor impairments and increased survival rate in 3 weeks of post stroke period. Additionally, P188 protected cultured hippucampal HT22 cells against oxygen-glucose deprivation and reoxygenation (OGD/R) injury. The ability in membrane sealing was assessed with two fluorescent membrane-impermeant dyes. The results showed that P188 treatment significantly reduced the PI-positive cells following ischemia/reperfusion injury and repaired the HT22 cell membrane rupture induced by Triton X-100. In addition, P188 inhibited ischemia/reperfusion-induced activation of matrix metalloproteinase (MMP)-9 and leakage of Evans blue. Therefore, the present study concludes that P188 can protect against cerebral ischemia/reperfusion injury, and the protection involves multi-mechanisms in addition to the membrane resealing. © 2013 Gu et al.
Li W.,The Second Peoples Hospital of Nantong |
Ji L.,The Second Peoples Hospital of Nantong |
Tao W.,The Second Peoples Hospital of Nantong
International Journal of Clinical and Experimental Medicine | Year: 2015
Objectives: To investigate the effect of vacuum sealing drainage in the patients with osteofascial compartment syndrome in comparison to conventional treatment. Methods: Fifty-two patients diagnosed with osteofascial compartment syndrome were enrolled in this study. They were randomly divided into two groups based on treatments: vacuum sealing drainage and conventional treatment. After operation, the length of hospital stay and antibiotics administration were recorded in the two groups, as well as swelling elimination and wound closure. Results: No significant difference was observed in terms of the baseline characteristics between the two groups. There are no obvious local or systemic complications in all cases. In contrast to conventional treatment group, the time of swelling elimination, wound closure, hospital stay and antibiotics application were reduced significantly in vacuum sealing drainage group. No allergic reactions or other side effects were observed after the application of vacuum sealing drainage material, indicating its safety. Conclusion: Vacuum sealing drainage is effective in treating osteofascial compartment syndrome with better clinical outcomes than conventional therapy. © 2015, E-Century Publishing Corporation. All rights reserved.
PubMed | Affiliated Maternal and Child Care Service Center, the Second Peoples Hospital of Nantong, Jiangyin Peoples Hospital, Nantong University and Yixing Peoples Hospital
Type: Journal Article | Journal: Cell proliferation | Year: 2016
Ovarian cancer is a leading cause of death among gynaecologic malignancies. Despite many years of research, it still remains sparing in reliable diagnostic markers and methods for early detection and screening. Transforming growth factor -activated protein kinase 1 (TAK1)-binding protein 3 (TAB3) was initially characterized as an adapter protein essential for TAK1 activation in response to IL-1 or TNF, however, the physiological role of TAB3 in ovarian cancer tumorigenesis is still not fully understood. In this study, we evaluated the effects of TAB3 on ovarian cancer cell lines. Expressions of TAB3 and PCNA (proliferating cell nuclear antigen) were found to be gradually increased in EOC tissues and cell lines, by western blot analysis and qRT-PCR. Distribution of TAB3 was further analysed by immunohistochemistry. In vitro, knockdown of TAB3 expression in HO8910 or SKOV3 ovarian cancer cells significantly inhibited bioactivity of ovarian cancer cells, including proliferation and cell-cycle distribution, and promoted chemical sensitivity to cisplatin and paclitaxel treatment via inhibiting NF-B pathways. In conclusion, our study strongly suggests a novel function of TAB3 as an oncogene that could be used as a biomarker for ovarian cancer. It provides a new insight into the potential mechanism for therapeutic targeting, in chemotherapy resistance, common in ovarian cancer.
PubMed | The Second Peoples Hospital of Nantong and Nantong University
Type: Journal Article | Journal: Pathology, research and practice | Year: 2016
The capability for DNA double-strand breaks (DSBs) repair is crucial for chromatin dramatic changes and DNA damage in normal and tumor cells. We have investigated the clinicopathological significance of DNA repair gene Ku70 expression in hepatocellular carcinoma. We demonstrated that Ku70 expression was significantly increased in HCC, and the high expression levels were significantly correlated with gender, maximal tumor size, HBsAg status, tumor nodule number, distant metastasis and Ki-67 expression by clinicopathological analysis. The Kaplan-Meier survival curves revealed that increasing Ku70 expression was associated with poor prognosis in HCC patients. Ku70 expression was an independent prognostic marker of overall HCC patient survival in a multivariate analysis. In addition, through serum starvation and refeeding, we found that Ku70 was lowly expressed in serum-starved Huh7 and HepG2 HCC cells, and was progressively increased after serum-additioning. Furthermore, knockdown of Ku70 inhibited cell proliferation accompanying an increase in p27(kip1) levels through interacting with FOXO4. These findings provide a rational framework for the progression of HCC and could be a potential molecular therapy by targeting the Ku70-FOXO4 interaction.
PubMed | The Second Peoples Hospital of Nantong, Nantong University and Dalian Medical University
Type: Journal Article | Journal: Molecular and cellular biochemistry | Year: 2016
Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and the sixth most prevalent human malignancies worldwide. However, the molecular mechanisms underlying hepatocarcinogenesis remain unclear. For HCC patients, there is not only a lack of effective therapeutic targets but also a lack of predictive or prognostic biomarkers. In this article, we reported that TRIM32 was obviously upregulated in HCC tumor tissues and HCC cell lines. Its expression patterns were positively correlated with histological grade, tumor sizes, and HBsAg of HCC patients. TRIM32 expression was a significant predictor for the overall survival time of HCC patients. Moreover, the overexpression of TRIM32 in cells accelerated the G1-S phase transition, promoted cell proliferation rates, and induced the resistance of HCC patients to oxaliplatin. All these findings suggest that TRIM32 might play important roles in the hepatocarcinogenesis. TRIM32 could be a novel direction to explore the mechanism underlying HCC pathogenesis.
PubMed | The second peoples hospital of Nantong, Nanjing Medical University and Nantong University
Type: Journal Article | Journal: Neurochemical research | Year: 2016
Promyelocytic leukemia zinc finger (PLZF) protein has been identified as a tumor suppressor in a variety of cancers, including leukemia, malignant mesothelioma, malignant melanoma, pancreatic cancer and prostate cancer. Studies have demonstrated that altered expression of PLZF affected its biological functions associated with tumorigenesis, such as proliferation, cell cycle, and apoptosis. However, information regarding its regulation and possible function in the central nervous system diseases is still limited. In this study, we performed a neuroinflammatory model by lipopolysaccharide (LPS) lateral ventricle injection in adult rats and detected increased expression of PLZF in the brain cortex. Immunofluorescence assay indicated that PLZF was significantly increased in neurons 3day after LPS injection, but not in astrocytes and microglia. Moreover, there was a concomitant upregulation of active caspase-3, cyclin D1, and CDK4 in vivo and vitro studies. In addition, the expression of these proteins in cortical primary neurons was inhibited after knocking down PLZF by siRNA. Collectively, all these results suggested that the upregulation of PLZF might be involved in neuronal apoptotic-like injury in neuroinflammation after LPS injection.
PubMed | The Second Peoples Hospital of Nantong and Nantong University
Type: Journal Article | Journal: Journal of molecular histology | Year: 2015
Src associated in mitosis (Sam68; 68 kDa) is a KH domain RNA-binding protein that belongs to the signal transduction and activation of RNA family, and has been implicated in the oncogenesis and progression of several human cancers. Our study aimed to investigated the clinicopathologic significance of Sam68 expression and its role in cell proliferation and the underlying molecular mechanism in hepatocellular carcinoma (HCC). We demonstrated that Sam68 expression was significantly increased in HCC and high expression of Sam68 was significantly associated with Edmondson grade, tumor size, tumor nodule number, HBsAg status and Ki-67 expression. The Kaplan-Meier survival curves showed that increased expression of Sam68 was correlated with poor prognosis in HCC patients and served as an independent prognostic marker of overall survival in a multivariable analysis. In addition, through serum starvation and refeeding assay, we demonstrated that Sam68 was lowly expressed in serum-starved HCC cells, and was progressively increased after serum-additioning. Furthermore, siRNA knockdown of endogenous Sam68 inhibited cell proliferation and tumourigenicity of HCC cells in vitro, through blocking the G1 to S phase transition. Moreover, we reported that the anti-proliferative effect of silencing Sam68 was accompanied with up-regulated expression of cyclin-dependent kinase inhibitors, p21(Cip1) and p27(Kip1), enhanced transactivation of FOXO factors (FOXO4), and dysreuglation of Akt/GSK-3 signaling. Taken together, these findings provide a rational framework for the progression of HCC and thereby indicated that Sam68 might be a novel and useful prognostic marker and a potential target for human HCC treatment.
PubMed | The Second Peoples Hospital of Nantong, Jiangyin Peoples Hospital, Nantong University and Yixing Peoples Hospital
Type: | Journal: Oncology reports | Year: 2017
ADP-ribosylation factor 1 (ARF1) is a small Gprotein that regulates many cellular processes such as reorganization of the actin cytoskeleton and is highly expressed in various tumor cells and tissues. However, the role of ARF1 in ovarian cancer progression remains unknown. In the present study, we explored the expression patterns of ARF1 in clinical ovarian cancer samples and adjacent noncancerous tissues. The results revealed that ARF1 overexpressed in EOC tissues and cell lines, compared with the adjacent non-tumorous tissues and normal ovarian cells. In addition, the immunoreactivity of ARF1 was positively correlated with EOC grade and Ki-67 expression. Knockdown of ARF1 expression notably inhibited cell proliferation and migration rate of EOC cells by the auxiliary of PI3K. Taken together, our findings provide new insights into the functional role of ARF1 on EOC cell growth and migration and it may serve as a diagnostic and therapeutic target.
PubMed | The Second Peoples Hospital of Nantong and Nantong University
Type: | Journal: Journal of clinical laboratory analysis | Year: 2016
This study was undertaken to determine the diagnostic and prognostic values of galectin-3 (Gal-3) in patients with chronic kidney disease (CKD).Patients with CKD (n=150) were enrolled as the CKD group, which was divided into six groups according to glomerular filtration rates (GFR) indexes. At the same time, 50 healthy adults were chosen for the control group (NC). Measured data included the levels of serum Gal-3, serum creatinine (SCr), There was no significant difference between CKD and NC group in age, gender and the level of Alb. CKD group had lower estimated glomerular filtration rate (eGFR) but higher Gal-3, CysC, SCr, Our study verified Gal-3, CysC and SCr were negatively related to eGFR. Besides, it is suggested that Gal-3 can be used as an indicating factor in the diagnosis of CKD; the joint analysis of Gal-3, CysC and SCr for CKD may distinctly improve diagnostic accuracy.