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Ma X.,Shandong University | Bao W.,Shanghai JiaoTong University | Wang X.,The Third Hospital of Jinan | Wang Z.,Shandong University | And 5 more authors.
Experimental Brain Research | Year: 2014

The mechanisms underlying stress-induced hyperalgesia (SIH) remain poorly understood. Recent findings have provided strong evidence indicating that SIH could be related, at least in part, to alterations in spinal cord GABA activity. In the present study, we first investigated how acute restraint stress impacted pain responses as assessed using the tail flick immersion test. These results showed that rats developed hyperalgesia at 6 h after being subjected to 1-h acute restraint stress. Second, we measured the activation of spinal neurons and alterations in expression of GABAA receptor β2 and β3 subunits as related to stress-induced hyperalgesia. Results from Western blot and immunofluorescence assays showed that c-fos protein increased in the dorsal horn of the lumbar spinal cord and GABAA receptor β2 and β3 subunit proteins decreased significantly at 6 h after exposure to 1 h of acute restraint stress. Finally, the effects of spinal GABAA receptor alteration on SIH were evaluated. These results showed that intrathecal administration of muscimol inhibited hyperalgesia induced by stress while bicuculline enhanced hyperalgesia in the control groups. Taken together, the present data reveal that GABAA receptor β2 and β3 decrease following 1 h of acute restraint stress and may play a critical role in SIH. © 2014, Springer-Verlag Berlin Heidelberg.

Wang L.,Shandong University | Cai W.,The Third Hospital of Jinan | Zhang W.,Shandong University | Chen X.,Shandong University | And 5 more authors.
Oncotarget | Year: 2015

An abnormal expression of poly(ADP-ribose) polymerase 1 (PARP-1) has been described in many tumors. PARP-1 promotes tumorigenesis and cancer progression by acting on different molecular pathways. PARP-1 inhibitors can be used with radiotherapy or chemotherapy to enhance the susceptibility of tumor cells to the treatment. However, the specific mechanism of PARP-1 in acute myeloid leukemia (AML) remains unknown. Our study showed that expression of PARP-1 was upregulated in AML patients. PARP-1 inhibition slowed AML cell proliferation, arrested the cell cycle, induced apoptosis in vitro and improved AML prognosis in vivo. Mechanistically, microarray assay of AML cells with loss of PARP-1 function revealed that the myeloproliferative leukemia virus oncogene (MPL) was significantly downregulated. In human AML samples, MPL expression was increased, and gainof- function and loss-of-function analysis demonstrated that MPL promoted cell growth. Moreover, PARP-1 and MPL expression were positively correlated in AML samples, and their overexpression was associated with an unfavorable prognosis. Furthermore, PARP-1 and MPL consistently acted on Akt and ERK1/2 pathways, and the anti-proliferative and pro-apoptotic function observed with PARP-1 inhibition were reversed in part via MPL activation upon thrombopoietin stimulation or gene overexpression. These data highlight the important function of PARP-1 in the progression of AML, which suggest PARP-1 as a potential target for AML treatment.

Sun G.P.,The Third Hospital of Jinan | Jiang T.,Jinan Stomatological Hospital | Xie P.F.,Jinan Stomatological Hospital | Lan J.,Shandong University
Molecular Biology | Year: 2016

The aim of this study was to investigate the disease-associated genes in periodontitis. In the present experiments, the topological analysis of the differential co-expression network was proposed. Using the GSE16134 dataset downloaded from the European Molecular Biology Laboratory-European Bioinformatics Institute, a co-expression network was constructed after the differentially expressed genes (DEGs) were identified between the diseased (242 samples) and healthy (69 samples) gingival tissues from periodontitis patients. The topological properties of the modules obtained from the network as well as an analysis of transcription factors (TFs) were used to determine the disease-associated genes. The gene ontology and pathway enrichment analysis was performed to investigate the underlying mechanisms of these disease related genes. A total of 524 DEGs, including 19 TFs were identified and a co-expression network with 2569 edges was obtained. Among the 7 modules gained in the network, the TFs (ZNF215, ZEN273, NFAT5, TRPS1, MEF2C and FLI1) were considered to be important in periodontitis. The functional and pathway enrichment analysis revealed that the DEGs were highly involved in the immune system. The co-expression network analysis and TFs identified in periodontitis may provide opportunities for biomarker development and novel insights into the therapeutics of periodontitis. © 2016, Pleiades Publishing, Inc.

Zhang F.-Y.,Peoples Hospital of Yucheng City | Zhang Z.-Z.,First Peoples Hospital of Jinan City | Huang J.-C.,First Peoples Hospital of Jinan City | Zhang S.-X.,Shandong University | Zhao X.-C.,The Third Hospital of Jinan
Tumor Biology | Year: 2014

The objective of this study is to evaluate whether high-dose chemotherapy is more efficacious than standarddose chemotherapy in the treatment of primary welldifferentiated osteosarcoma. The Cochrane systematic evaluation method was adopted. A database search was conducted in MEDLINE, Embase, OVID, the Cochrane Central Register of Controlled Trials database and the Chinese Biomedical Literature CD-ROM Database. The quality of the included studies was jointly evaluated by two reviewers, and homogeneous studies were included for meta-analysis. A total of five studies were included in this meta-analysis, with 1,415 subjects with primary, nonmetastatic, well-differentiated osteosarcoma in the limbs. No statistically significant differences were found between the high-dose chemotherapy group and the low-dose group in 5-year event-free survival [RR 1.04, 95 %CI (0.95, 1.13)], 5-year overall survival [RR 1.02, 95 %CI (0.95, 1.10)], local recurrence rate [RR 0.90, 95 %CI (0.59, 1.39)], proportion of subjects with good histological response [RR 0.93, 95 %CI (0.81, 1.07)], or limb salvage rate [RR 0.97, 95 %CI (0.92, 1.02)]. A statistically significant difference was observed in the 5-year event-free survival between the subjects with good histological response to preoperative chemotherapy and the subjects with poor histological response [RR 1.55, 95 %CI (1.19, 2.00), P<0.001]. High-dose chemotherapy did not show superior efficacy to low-dose chemotherapy in the treatment of primary well-differentiated osteosarcoma. Further high-quality randomized controlled trials are needed to provide additional reliable evidence for our observation. © International Society of Oncology and BioMarkers (ISOBM) 2014.

Wang Y.B.,The Third Hospital of Jinan | Jia N.,The Third Hospital of Jinan | Xu C.M.,The Third Hospital of Jinan | Zhao L.,The Third Hospital of Jinan | And 3 more authors.
Genetics and Molecular Research | Year: 2015

Despite recent advances in osteosarcoma diagnosis and therapy, much remains unclear about the molecular mechanisms involved in the disorder, and the discovery of novel drug-targeted genes is essential. We explored the potential molecular mechanisms and target genes involved in the development and progression of osteosarcoma. First, we identified the differentially expressed genes in osteosarcoma patients and matching normal controls. We then constructed a differential expression network based on differential and non-differential interactions. Pathway-enrichment analysis was performed based on the nodes contained in the main differential expression network. Centrality analysis was used to select hub genes that may play vital roles in the progression of human osteosarcoma. Our research revealed a total of 176 differentially expressed genes including 82 upregulated and 94 downregulated genes. A differential expression network was constructed that included 992 gene pairs (1043 nodes). Pathway-enrichment analysis indicated that the nodes in the differential expression network were mainly enriched in several pathways such as those involved in cancer, cell cycle, ubiquitin-mediated proteolysis, DNA replication, ribosomes, T-cell receptor signaling, spliceosomes, neurotrophin signaling, oxidative phosphorylation, and tight junctions. Six hub genes (APP, UBC, CAND1, RPA, YWHAG, and NEDD8) were discovered; of these, two genes (UBC and RPA) were also found to be disease genes. Our study predicted that UBC and RPA had potential as target genes for the diagnosis and treatment of osteosarcoma. © FUNPEC-RP.

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