1.Intravenous and intramyocardial administration of bone marrow mesenchymal stromal cells cannot improve heart function in a rat model of chronic myocardial infarction
Wei WANG ; Debin LIU ; Ying FENG ; Hao ZHANG ; Shixiong WANG ; Bingren GAO ; Jing ZHANG ; Weifan WANG
Chinese Journal of Tissue Engineering Research 2015;(10):1528-1532
BACKGROUND:It has been demonstrated to be effective for the improvement of heart function after acute myocardial infarction with intravenous or intramyocardial administration of bone marrow mesenchymal stromal cels. However, little is known regarding the effect of the combination of intravenous and intramyocardial administration of mesenchymal stromal cels on the heart function of a chronic myocardial infarction model. OBJECTIVE:To study the effect of intravenous and intramyocardial administration of bone marrow mesenchymal stromal cels on the heart function of a rat chronic myocardial infarction model and the relevant mechanism. METHODS:Bone marrow mesenchymal stromal cels isolated from Lewis rats were expandedex vivo. BrdU-labeled bone marrow mesenchymal stromal cels (3×106) were administeredvia the femoral vein and the myocardial surface respectively into rat models of chronic myocardial infarction in cel transplantation group. The equal volume of PBS was injected into the same place in control group. Four weeks after injection, echocardiography was performed to evaluate the heart function, and then the heart tissues were harvested for immunohistochemistry examination. The total blood vessel density in the scar area was evaluated. RESULTS AND CONCLUSION:At 4 weeks after cel implantation, the left ventricular function was not improved in the two groups. The immunohistochemistry staining showed that (1) the mesenchymal stromal cels in the myocardium did not differentiate to myocardial cels; (2) there was no significant difference in the total blood vessel density in the scar area between the cel transplantation and control groups. Taken together, the combined intravenous and intramyocardial administration of bone marrow mesenchymal stromal cels cannot improve heart function in a rat chronic myocardial infarction model.
2.Dosimetric impact of induction chemotherapy on intensity-modulated radiotherapy for locally advanced nasopharyngeal carcinoma and dosimetric characteristics of replanning
Jia WANG ; Feng XIAO ; Feng LIU ; Shixiong HUANG ; Longjun LUO ; Yu WANG ; Shilei XU ; Qiyuan ZHOU ; Xuping XI
Chinese Journal of Radiation Oncology 2017;26(11):1298-1302
Objective To investigate the benefits of replanning after induction chemotherapy(IC) by analyzing the dosimetric impact of IC on intensity-modulated radiotherapy(IMRT)for locally advanced nasopharyngeal carcinoma(NPC)and the dosimetric characteristics of replanning after IC, and to provide data for the rational design of clinical radiotherapy plans. Methods 16 NPC patients underwent contrast-enhanced CT scan once before and after IC.Target volumes were delineated and the chemotherapy plans were created,defined as Plan-1 and Plan-2,respectively. Then the target structure after IC was copied to Plan-1, generating the third plan, defined as Plan-1-2. The paired t-test was used to compare the dosimetric parameters between Plan-1 and Plan-1-2 and between Plan-2 and Plan-1-2. Results Plan-1 vs. Plan-1-2:Plan-1-2 showed significantly reduced D meanof target volume compared with Plan-1(P<0.05). Plan-1-2 significantly increased D meanand D maxof the spinal cord(P<0.05),although significantly reduced D mean of the brain stem and D maxof the temporal lobes compared with Plan-1. Plan-1-2 also had significantly reduced conformity index(CI)and significantly increased homogeneity index(HI)for the target volume compared with Plan-1(P<0.05). Plan-2 vs. Plan-1-2:Compared with Plan-1-2, Plan-2 significantly increased D meanand D minof gross tumor volume(GTV)and primary GTV(P<0.05)and significantly reduced D meanof the temporal lobes and D maxand D meanof the spinal cord(P<0.05), with D max decreased to 430.48 cGy;Plan-2 had significantly increased CI and significantly reduced HI for the target volume compared with Plan-1-2(all P<0.05). Conclusions IMRT plan-1 after IC has worse dosimetric distribution,while replanning after IC has more dosimetric benefits.
3.The research of VEPH1 regulates epithelial mesenchymal transition and proliferation of melanoma cells through the TGF-β signaling pathway
Hao FENG ; Junyi ZHANG ; Mengjiao CHEN ; Shixiong PENG ; Hua TANG
Journal of Chinese Physician 2021;23(6):842-847
Objective:To investigate the intervention effect of ventricular zone expressed PH domain-containing 1 (VEPH1) on epithelial mesenchymal transition (EMT) and proliferation of human cutaneous melanoma (CM) cells based onthe transforming growth factor-β (TGF-β) signaling pathway.Methods:The melanoma cells were cultured in vitro. After transfecting the melanoma cells with overexpression or interference plasmids of VEPH1 or TGF-β overexpression plasmids, or treating the cells with SB-431542 (TGF-β pathway inhibitor), we detected the expression of genes and proteins relevant to VEPH1, TGF-β, and EMT by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot to observe the effect of these proteins on CM cell proliferation. Results:qRT-PCR results showed that the expression of VEPH1 in melanoma cells (B16-BL6, B16 and A375 cells) was significantly lower than that in HaCaT cells, and the lowest expression was found in A375 cells, so A375 cells were selected for follow-up experiments. After transfection with VEPH1 overexpression plasmid or SB-431542, the mRNA and protein expression of E-cadherin in A375 cells were significantly increased, the mRNA and protein expressions of TGF-β, Smad4, N-cadherin and vimentin were significantly decreased, and the cell proliferation was significantly decreased ( P<0.05). Compared with the VEPH1 vector group, the expression of TGF-β, Smad4 and N-cadherin in the VEPH1 vector+ SB-431542 group was significantly reduced ( P<0.05); the expression of E-cadherin was increased, and the cell proliferation was also significantly decreased ( P<0.05). The expression of TGF-β, Smad4, N-cadherin and vimentin were increased after co-transfection with VEPH1 vector, while the expression of E-cadherin was decreased, and the cell proliferation was also enhanced ( P<0.05). The expression of VEPH1 in A375 cells was significantly decreased after transfection with si-VEPH1 plasmid, while that in SB-431542 and TGF-β vector group was not significantly decreased. Conclusions:VEPH1 can inhibit human CM cells by the intervention on TGF-β signaling pathway. This study reveals the potential of VEPH1 as a diagnostic, prognostic and therapeutic target for CM.
4.Epidemiological and virus molecular characterization of dengue fever outbreak in Hunan province, 2018
Liang CAI ; Hengjiao ZHANG ; Fangling HE ; Yale FENG ; Shixiong HU ; Juan WANG ; Fuqiang LIU ; Yonglin JIANG ; Xialin TAN ; Haiming PAN ; Binbin TANG ; Hao YANG ; Haoyu LONG ; Zhifei ZHAN ; Lidong GAO
Chinese Journal of Epidemiology 2020;41(12):2119-2124
Objective:To analyze the epidemiological and etiological characteristics of a dengue fever outbreak in Hunan province in 2018.Methods:Real-time PCR assay was performed for the laboratory diagnosis of 8 suspected dengue fever cases. Etiological surveillance was performed in 186 suspected dengue fever cases and fever cases who had close contacts with dengue fever patients. C6/36 cells was used for the virus isolation from acute phase serum. By sequencing the full length of E genes of 15 dengue virus strains, phylogenetic analysis was performed based on the sequences obtained, including reference sequences from the NCBI GenBank database, the serotypes and gene subtypes of the virus were analyzed to trace the possible source of transmission. An emergency monitoring of vector density and a retrospective survey of sero-epidemiology in healthy population were conducted in the epidemic area.Results:In the serum samples of 8 suspected patients, 6 were dengue virus RNA positive, and 4 were NS1 antigen positive. In 186 suspected patients, 96 were dengue virus nucleic acid, NS1 antigen or antibody positive in etiological test. A total of 64 dengue virus strains were isolated. The phylogenetic analysis showed that all the dengue virus strains belonged to type 2, which might be from Guangdong or Zhejiang provinces. The Bretub index was up to 65, indicating an extremely high risk of transmission. The positive rate of the dengue virus IgG antibody was 0.53%(2/377) in retrospective survey of 377 healthy people.Conclusion:The field epidemiologic and the molecular genetics analyses showed the outbreak of dengue fever in Hunan in 2018 was caused by imported cases and dengue virus 2.
5.Bioinformatics analysis of key genes and prognosis-related genes during the onset of hepatocellular carcinoma
Zewen ZHOU ; Xianguo ZHOU ; Yingchun LIU ; Moqin QIU ; Qiuping WEN ; Zihan ZHOU ; Yanji JIANG ; Shixiong FENG ; Hongping YU
Chinese Journal of Hepatology 2020;28(8):686-691
Objective:To screen and analyze the differentially-expressed genes (DEGs) in primary hepatocellular carcinoma tissues and adjacent tissues using bioinformatics methods to explore the molecular mechanism of the occurrence and prognosis of primary hepatocellular carcinoma.Methods:GSE76427 data set was collected through GEO database, and DEGs were identified using GEO2R online analysis. Go and KEGG databases were used for enrichment and functional annotation of DEGs. Protein interaction network was built based on the STRING database and Cytoscape software to analyze the key genes of hepatocellular carcinoma, and the survival curve of these key genes were analyzed using the GEPIA database.Results:A total of 74 hepatocellular carcinoma DEGs were screened, of which 3 and 71 were up-and-down-regulated genes. The results of GO enrichment analysis showed that the down-regulated DEGs were mainly involved in cell response to cadmium and zinc ions, negative growth regulation, heterologous metabolic processes and hormone-mediated signaling pathways. KEGG pathway enrichment analysis results showed that the down-regulated DEGs pathway were mainly involved in retinol metabolism, chemical carcinogenesis, drug metabolism-cytochrome P450, cytochrome P450 metabolizing xenobiotics, tryptophan metabolism and caffeine metabolism. Protein interaction network had screened out 10 down-regulated core genes: MT1G, MT1F, MT1X, MT1E, MT1H, insulin-like growth factor 1, FOS, CXCL12, EGR1, and BGN. Among them, the insulin-like growth factor 1 was related to the prognosis of primary hepatocellular carcinoma.Conclusion:Bioinformatics analysis results of HCC chip data showed that 10 key genes may play a key role in the occurrence and development of HCC and the insulin like growth factor 1 is associated with the prognosis of primary hepatocellular carcinoma.