OBJECTIVE: To study the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF, the Chinese Medicine) on hippocampal neuron apoptosis in diabetes mellitus complicated with depression (DD). METHODS: The primary cultured hippocampal neurons were treated with high glucose (150 mmol/L) and corticosterone (200 micromol/L) to establish the cell model of DD in vitro. The cultured hippocampal neurons were randomly divided into five groups: blank serum group, normal group, Zuogui Jiangtang Jieyu recipe drug-containing serum group, positive drug (metformin + fluoxetine) drug-containing serum group and model group (three compound holes in each group). The model group and the normal group were given the same amount of culture medium, and the other groups were given the corresponding serum with 10% volume fraction for 18 hours. Hoechst staining, high content cell imaging and RT-PCR were used to detect the apoptosis of hippocampal neurons and the expressions of apoptosis-related ETS-like 1 transcription factor(ELK-1), C-Jun N-terminal kinase(JNK) and c-Fos proteins and genes. RESULTS: Compared with the blank group, the apoptotic number of hippocampal neurons in the model group was increased significantly, and the expression levels of ELK-1, JNK and c-Fos were increased significantly (P＜0.05). Compared with the model group, the local bright spots of hippocampal neurons in the Zuogui Jiangtang Jieyu recipe-containing serum group and the positive drug-containing serum group were decreased significantly, and the number of apoptotic cells was decreased significantly. The expressions of JNK, c-fos protein and mRNA were down-regulated significantly (P＜ 0.05), and the neural network and dendritic junction were improved significantly. CONCLUSION Zuo Gui Jiang Tang Jie Yu Formula can reverse the expressions of ELK-1, JNK and c-Fos signals in hippocampal neurons under DD environment and play an anti-apoptotic effect.
Animals ; Apoptosis ; drug effects ; Depression ; drug therapy ; Diabetes Complications ; drug therapy ; Diabetes Mellitus ; Drugs, Chinese Herbal ; pharmacology ; Hippocampus ; drug effects ; MAP Kinase Kinase 4 ; drug effects ; Neurons ; Proto-Oncogene Proteins c-fos ; drug effects ; Random Allocation ; Rats ; ets-Domain Protein Elk-1 ; drug effects

OBJECTIVETo investigate the effect of simulated microgravity on erythroid differentiation of K562 cells and explore the possible mechanism.

METHODSThe fourth generation rotating cell culture system was used to generate the simulated microgravity environment. Benzidine staining was used to evaluate the cell inhibition rate, and real-time quantitative PCR (qRT-PCR) was used to detect GATA-1, GATA-2, Ets-1, F-actin, β-Tubulin and vimentin mRNA expressions. The changes of cytoskeleton were observed by fluorescence microscopy, and Western blotting was employed to assay F-actin, β-tubulin and vimentin protein expression levels.

RESULTSBenzidine staining showed that simulated microgravity inhibited erythroid differentiation of K562 cells. K562 cells treated with Hemin presented with increased mRNA expression of GATA-1 and reduced GATA-2 and Ets-1 mRNA expressions. Simulated microgravity treatment of the cells resulted in down-regulated GATA-1, F-actin, β-tubulin and vimentin mRNA expressions and up-regulated mRNA expressions of GATA-2 and Ets-1, and reduced F-actin, β-tubulin and vimentin protein expressions. Exposure to simulated microgravity caused decreased fluorescence intensities of cytoskeletal filament F-actin, β-tubulin and vimentin in the cells.

CONCLUSIONSimulated microgravity inhibits erythroid differentiation of K562 cells possibly by causing cytoskeleton damages to result in down-regulation of GATA-1 and up-regulation of GATA-2 and Ets-1 expressions.

Actins ; metabolism ; Cell Differentiation ; Down-Regulation ; GATA1 Transcription Factor ; metabolism ; GATA2 Transcription Factor ; metabolism ; Hemin ; pharmacology ; Humans ; K562 Cells ; Proto-Oncogene Protein c-ets-1 ; metabolism ; Tubulin ; metabolism ; Up-Regulation ; Vimentin ; metabolism ; Weightlessness Simulation

OBJECTIVETo assess the association between 2 single nucleotide polymorphisms (SNPs) of ETS1 gene and susceptibility to systemic lupus erythematosus (SLE) in a northern Chinese Han population.

METHODSTwo SNPs within the ETS1 gene mapped to 11q23 were selected based on HapMap data. Genotyping was conducted with Taqman method in 231 patients with SLE and 474 healthy controls from Qilu Hospital, Shandong and analyzed with PLINK1.07 software. Haplotypes were analyzed with SHEsis software.

RESULTSA statistically significant difference was detected in the distribution of rs1128334 and rs4937333 genotypes between the two groups (all P< 0.01). For rs1128334, the frequency of the minor allele was 0.291 and 0.428 in controls and cases, respectively. For rs4937333, the minor allele frequency was 0.381 and 0.476 in controls and cases respectively. An A-C haplotype was found to be strongly associated with increased risk for SLE, while another haplotype G-C may reduce this risk.

CONCLUSIONOur study has suggested that rs1128334 and rs4937333 are strongly associated with the risk for SLE in northern Chinese Han population.

3' Untranslated Regions ; Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Female ; Genetic Association Studies ; Humans ; Lupus Erythematosus, Systemic ; ethnology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Proto-Oncogene Protein c-ets-1 ; genetics ; Young Adult

OBJECTIVE: To investigate the expression of matrix metalloproteinase-1 (MMP-1), E26 transformation-specific-1 (Ets-1) in laryngeal carcinoma and to discuss their relevance and the roles in carcinogenesis and development of laryngeal carcinoma. METHOD: Immunohistochemical technique was used to detect the expression of MMP-1 and Ets-1 protein in 34 tissues of laryngeal carcinoma and 34 para-carcinoma tissues, 15 cases of vocal cord polyps, and the use of the pathological image analysis software, we analysis the results of immunohistochemical semi-quantitatively. RESULT: (1) The expression of MMP-1 and Ets-1 protein in laryngeal carcinoma tissues is obviously higher than that in para-carcinoma and in vocal cord polyps respectively (P < 0.05). There is no significant difference between the expression of para-carcinoma and vocal cord polyps(P > 0.05). (2) The expression of MMP-1, Ets-1 protein isn't related to patients' age and sex, tumor size,clinical classification (P > 0.05), but related to pathological grade, clinical stage and lymph nodes metastasis (P < 0.05). (3) There is a positive correlation between the expression of MMP-1 and Ets-1 in laryngeal carcinoma. CONCLUSION Overexpression of MMP-1 and Ets-1 was observed in laryngeal carcinoma. The high expression of MMP-1 and Ets-1 may contribute to the carcinogenesis and development of laryngeal carcinoma,which is a important value to judge the malignant degree and progress of laryngeal carcinoma.
Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Female ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Matrix Metalloproteinase 1 ; metabolism ; Middle Aged ; Proto-Oncogene Protein c-ets-1 ; metabolism

OBJECTIVETo evaluate the expression and prognostic significance of T-bet and its cofactors EOMES, ETS-1 and MEF [which are transcription factors and responsible for development of natural killer (NK) cells] in the extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT).

METHODSThe expression status of T-bet, EOMES, ETS-1 and MEF in 40 cases of EN-NK/T-NT occurring in Chinese population was studied by immunohistochemistry and in-situ hybridization (ISH). The clinical relevance was also evaluated. The control cases included 18 cases of peripheral T-cell lymphoma, 10 cases of B-cell lymphoma, 5 cases of normal spleen, 5 cases of normal thymus and 10 cases of nasal mucosal tissues affected by chronic inflammation.

RESULTSThe expression levels of T-bet mRNA and protein were high in EN-NK/T-NT (82.5% and 100%, respectively) and in peripheral T cell lymphoma (17/18 and 72.2%, respectively). There was no expression in B-cell lymphoma. The expression of EOMES (80.0% by ISH), ETS-1 (82.5% by ISH) and MEF (62.5% by ISH) was high in EN-NK/T-NT, but not in the control group. The frequency of co-expression of T-bet and EOMES (75%, 30/40) was significantly higher than that of the other genes. Follow-up study showed that the mean and median survival of the 19 cases of EN-NK/ T-NT was 33 months and 10 months, respectively. The five-year survival rate was 10.5%. Statistical analysis showed that only treatment modalities significantly affected the patients' overall survival; and none of the four transcription factors had significant impact on survival. The expression rates of T-bet, EOMES, ETS-1 or MEF had no significant difference between the 9 alive and the 10 dead cases.

CONCLUSIONSThe expression of T-bet correlates with the lymphoma types. It is mainly expressed in peripheral NK and T-cell lymphomas. The important functional gene engaged in NK cells development is highly expressed in EN-NK/T-NT. They may play a crucial role in pathogenesis and aggressive biologic behavior.

Adolescent ; Adult ; Aged ; China ; epidemiology ; DNA-Binding Proteins ; metabolism ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Extranodal NK-T-Cell ; Lymphoma, T-Cell, Peripheral ; metabolism ; Male ; Middle Aged ; Nose Neoplasms ; drug therapy ; metabolism ; pathology ; radiotherapy ; Proto-Oncogene Protein c-ets-1 ; metabolism ; RNA, Messenger ; metabolism ; Survival Rate ; T-Box Domain Proteins ; genetics ; metabolism ; Transcription Factors ; metabolism ; Young Adult

Adult ; Humans ; Leukocytes, Mononuclear ; metabolism ; Lupus Erythematosus, Systemic ; genetics ; Proto-Oncogene Protein c-ets-1 ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

AIMUnderstanding the response of mesenchymal stem cells (MSCs) to mechanical strain and their consequent gene expression patterns will broaden our knowledge of the mechanobiology of distraction osteogenesis.

METHODOLOGYIn this study, a single period of cyclic mechanical stretch (0.5 Hz, 2,000 microepsilon) was performed on rat bone marrow MSCs. Cellular proliferation and alkaline phosphatase (ALP) activity was examined. The mRNA expression of six bone-related genes (Ets-1, bFGF, IGF-II, TGF-beta, Cbfa1 and ALP) was detected using real-time quantitative RT-PCR.

RESULTSThe results showed that mechanical strain can promote MSCs proliferation, increase ALP activity, and up-regulate the expression of these genes. A significant increase in Ets-1 expression was detected immediately after mechanical stimulation, but Cbfa1 expression became elevated later. The temporal expression pattern of ALP coincided perfectly with Cbfa1.

CONCLUSIONThe results of this study suggest that mechanical strain may act as a stimulator to induce differentiation of MSCs into osteoblasts, and that these bone-related genes may play different roles in the response of MSCs to mechanical stimulation.

Alkaline Phosphatase ; analysis ; Animals ; Antigens, Surface ; analysis ; Biomechanical Phenomena ; Bone Marrow Cells ; physiology ; Cell Culture Techniques ; Cell Differentiation ; physiology ; Cell Proliferation ; Core Binding Factor Alpha 1 Subunit ; analysis ; Fibroblast Growth Factor 2 ; analysis ; Insulin-Like Growth Factor II ; analysis ; Mesenchymal Stromal Cells ; physiology ; Osteoblasts ; physiology ; Osteogenesis, Distraction ; Pluripotent Stem Cells ; physiology ; Proto-Oncogene Protein c-ets-1 ; analysis ; Rats ; Stress, Mechanical ; Transforming Growth Factor beta ; analysis ; Up-Regulation ; physiology

Animals ; Arginine Vasopressin ; physiology ; Connective Tissue Growth Factor ; physiology ; Glomerular Mesangium ; pathology ; Humans ; Integrin alpha1beta1 ; physiology ; Kidney Diseases ; etiology ; Proto-Oncogene Protein c-ets-1 ; physiology

OBJECTIVETo investigate the expression of Ets-1 in gastric carcinoma, para-cancerous tissue and metastatic lymph nodes, and to determine the relationship between Ets-1 expression and clinicopathological features, angiogenesis and survival of patients with gastric carcinoma.

METHODSGastric carcinoma tissue microarray was used to determine Ets-1 protein expression by SP immunohistochemical staining in 189 advanced gastric cancer, 54 papacancerous tissues, 41 metastatic lymph nodes and 32 control tissues.

RESULTSThe positive rates for Ets-1 expression of the carcinoma, paracancerous and control tissues were 71.4%, 29.6% and 18.8%, respectively, with a significant difference among the three groups (P < 0.01). In the cancer tissues, the positive rate of Ets-1 protein expression was significantly associated with depth of invasion and lymph node metastasis (P < 0.01), but not associated with degree of differentiation, Lauren's histological type, sex, age, and size of tumor (P > 0.05). The positive rates for Ets-1 expression of the 41 gastric cancer and 41 metastatic lymph nodes were significantly different (P < 0.05). In metastatic lymph nodes, the positive rate for Ets-1 expression was higher. The MVD in Ets-1 positive tumors was higher than that in the Ets-1 negative tumors, with a significant difference (P < 0.05). Kaplan-Meier survival analysis showed that the survival time of Ets-1-negative patients was longer than that of Ets-1-positive patients (P < 0.05). Cox regression analysis showed that Ets-1 expression was not an independent prognostic factor of gastric carcinoma.

CONCLUSIONA higher expression of Ets-1 is involved in carcinogenesis, development, invasion, and metastasis of gastric cancer. Ets-1 plays an important role in angiogenesis in gastric cancer. Ets-1 is a useful marker for predicting the outcome for patients with gastric carcinoma, though it is not an independent prognostic indicator.

Adult ; Aged ; Female ; Humans ; Lymphatic Metastasis ; Male ; Microvessels ; metabolism ; pathology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Neovascularization, Pathologic ; metabolism ; pathology ; Paraffin Embedding ; Proportional Hazards Models ; Proto-Oncogene Protein c-ets-1 ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Survival Rate

Adenocarcinoma ; metabolism ; pathology ; Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Lymphatic Vessels ; pathology ; Male ; Microvessels ; pathology ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Protein c-ets-1 ; metabolism ; Vascular Endothelial Growth Factor C ; metabolism