Regulatory effect of Ac-SDKP on phosphorylated heat shock protein 27/SNAI1 pathway in silicotic rats / 中华劳动卫生职业病杂志

Objective: To study the effect of anti-fibrotic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on phosphorylated heat shock protein 27 (P-HSP27) and zinc finger family transcriptional repressor 1 (SNAI1) expression to explore the anti-silicosis fibrosis effect of Ac-SDKP. Methods: In December 2014, the rat silicosis animal model was prepared by one-time bronchial infusion of silicon dioxide (SiO(2)) dust. 80 SPF healthy adult Wistar rats were selected, and the rats were divided into 8 groups according to the random number table method, 10 in each group. Model control group for 4 weeks (feeding for 4 weeks) , model control group for 8 weeks (feeding for 8 weeks) : bronchial perfusion with normal saline 1.0 ml per animal. Silicosis model group for 4 weeks (feeding for 4 weeks) and silicosis model group for 8 weeks (feeding for 8 weeks) : bronchial perfusion of 50 mg/ml SiO(2) suspension 1.0 ml per animal. Ac-SDKP administration group for 4 weeks (feeding for 4 weeks) , Ac-SDKP administration group for 8 weeks (feeding for 8 weeks) : Ac-SDKP 800 μg·kg(-1)·d(-1) was administered by intraperitoneal pump. Ac-SDKP preventive treatment group: 48 h after Ac-SDKP 800 μg·kg(-1)·d(-1) administration, bronchial perfusion of SiO(2) suspension 1.0 ml per animal, raised for 8 weeks. Ac-SDKP anti-fibrosis treatment group: after bronchial perfusion of 1.0 ml of SiO(2) suspension for 4 weeks, Ac-SDKP 800 μg·kg(-1)·d(-1) was administered for 4 weeks. Western blotting was used to detect the expression of P-HSP27, SNAI1, α-smooth muscle actin (α-SMA) , and collage typeⅠ and Ⅲ in each group. The expression of P-HSP27 and SNAI1 was detected by immunohistochemistry, and the co-localized expression of P-HSP27 and α-SMA was detected by laser confocal microscopy. Results: Compared with the model control group, the expressions of P-HSP27, SNAI1, α-SMA, and collage typeⅠ and Ⅲ in the silicosis fibrosis area of the rats in the silicosis model group were enhanced, and the differences were statistically significant (P<0.05) . After Ac-SDKP intervention, compared with silicosis model group for 8 weeks, the expressions of P-HSP27, SNAI1 α-SMA, and collage typeⅠ and Ⅲ in the Ac-SDKP preventive and anti-fibrosis treatment groups were significantly decreased, and the differences were statistically significant (P<0.05) . However, the expressions of P-HSP27 SNAI1, and collage typeⅠ and Ⅲ between the Ac-SDKP administration group and the model control group did not change significantly, and the differences were not statistically significant (P>0.05) . Laser confocal results showed that the positive cells expressing P-HSP27 and α-SMA in the lung tissue of the silicosis model group were more than those in the model control group. Compared with the silicosis model group, the Ac-SDKP prevention and anti-fibrosis treatment groups expressing the positive cells of P-HSP27 and α-SMA decreased. Compared with the model control group for 8 weeks, there were some double-positive cells expressing P-HSP27 and α-SMA in the nodules of the silicosis model group for 8 weeks. Conclusion: Ac-SDKP may play an anti-silicic fibrosis effect by regulating the P-HSP27/SNAI1 pathway.

Curative efficacy of retetrexel combined with laparoscopic hepatectomy in treatment of patients with primary liver cancer and its effects on liver function and CIART, AFP-L3 and GP73 / 中国临床药理学与治疗学

AIM: To study the curative efficacy of retetrexel combined with laparoscopic hepatectomy in treatment of patients with primary liver cancer and its effects on liver function and the effects of diurnal transcription suppressor (CIART), fetoprotein heterosomes (AFP-l3), golgi membrane protein-73 (GP73). METHODS: A total of 100 patients with primary liver cancer who were treated in our hospital from July 2012 to July 2019 were selected as study subjects, the patients were divided into observation group (n=52) and control group (n=48) according to the order of admission. The control group was treated with laparoscopic hepatectomy, and the observation group was treated with retetroxel on the basis of the control group. Serum CIART, AFP-L3, GP73, ALT, AST, TBIL, 1-year, 3-year, 5-year tumor recurrence rates and adverse reactions were compared between the two groups before and after treatment. RESULTS:Before treatment, CIART, AFP-L3, GP73, ALT, AST and TBIL levels were not significantly different between the two groups. After treatment, the levels of CIART, AFP-L3 and GP73 in the observation group were significantly lower than those in the control group (P0.05). The 5-year recurrence rate in the observation group was significantly lower than that in the control group (P0.05). The total incidence of adverse reactions in the two groups was 53.84% and 52.08%, respectively, with no significant difference (P>0.05). CONCLUSION:Laparoscopic resection combined with letetrexed in the treatment of primary liver cancer can effectively reduce the level of ciart, AFP-L3 and GP73, and it is safe.

Effect of exposure to active allethrin on expression of HSF2 and Ovol1 genes in a rat spermatogenesis

Background: Heat shock factor protein 2 (HSF 2) and Ovo like transcriptional repressor 1 (Ovol1) genes are found in germ cells that control spermatogenesis. One reason is exposure to mosquito repellent drugs from allethrin. Allethrin is one of the causes of male reproductive dysfunction that affects male reproduction resulting in infertility.Methods: This study was an experimental post-test randomized control group design. Twenty-eight rats given exposure according to the experimental group were K (control), P1 (4 hours exposure), P2 (8hours exposure), and P3 (12hours exposure) for 30 days. Examination of HSF 2 and Ovol1 genes from testicular tissue using real-time PCR with a relatively quantitative calculation method. Implementation of research at animal houses and biomedical laboratories. Data analysis using one-way ANOVA with a significant level of p <0.05.Results: The results of this study found differences in the average number of expressions of the HSF2 and Ovol1 genes. The average expression of the HSF2 control group gene was 3.50, P1: 2.99, P2: 0.62, and P3: 0.49. Whereas in the Ovol1 gene control group were 1.17, P1: 0.80, P2: 0.57, and P3: 0.65. The results of statistical tests using one-way ANOVA are HSF2 (p = 0,000) and Ovol1 (p = 0.045).Conclusions: Based on the results of this study, it was concluded that there was an allethrin effect in decreasing the expression of the HSF 2 and Ovol1 genes in Wistar albino Rattus Novergicus strain.

Transcriptional repression by androgen receptor: roles in castration-resistant prostate cancer / 亚洲男科学杂志(英文版)

Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially successful in regressing prostate tumors, the disease ultimately comes back as castration-resistant prostate cancer (CRPC) or at the late stage as neuroendocrine prostate cancer (NEPC). CRPC remains largely dependent on hyperactive AR signaling in the milieu of low androgen, while NEPC is negative of AR expression but positive of many AR-repressed genes. Recent technological advances in genome-wide analysis of transcription factor binding sites have revealed an unprecedented set of AR target genes. In addition to its well-known function in activating gene expression, AR is increasingly known to also act as a transcriptional repressor. Here, we review the molecular mechanisms by which AR represses gene expression. We also summarize AR-repressed genes that are aberrantly upregulated in CRPC and NEPC and represent promising targets for therapeutic intervention.

Construction and transcriptional activity of human CREG promoter reporter gene plasmid / 解放军医学杂志

Objective To construct the promoter enhanced green fluorescent protein (pEGFP1) reporter gene vector of different truncated fragments of human cellular repressor of E1A-stimulated genes (hCREG), and compare the transcriptional activity of each promoter to determine the hCREG core promoter region. Methods The promoter fragment with length of 2003 (–1925/+78) bp was obtained by querying the hCREG sequence from US National Center of Biotechnology Information (NCBI) database and combining with the characteristics of the promoter. Five promoter fragments were truncated by PCR and double enzyme digestion and cloned into pEGFP1 to construct pEGFP1_hCREG_2003, pEGFP1_hCREG_945, pEGF P1_hCREG_586, pEGFP1_ hCREG_478 and pEG FP1_hCREG_358 reporter gene vector plasmid. The 293T cells were transiently co-transfected with the internal reference plasmid pGL4.73 [hRluc/SV40] for 48 hours. The green fluorescence expression of pEGFP1_hCREG promoter reporter gene was observed under fluorescence microscope, and the mRNA expression of each promoter was detected by real-time quantitative PCR, and the core promoter region was determined. Bioinformatics was used to predict the transcription factors that might bind to the core promoter region. Results Five hCREG promoter reporter gene vectors were successfully constructed by double enzyme digestion and gene sequencing. The results showed that the transcription activity of pEGFP1_ hCREG_586 was the highest (P0.05), implying that –867/ –509 bp is a negative regulatory region, and there existed enhancer sequences in –400/–281 bp and –508/–401 bp, so the core promoter region of hCREG gene is located in the upstream sequence of –508/–281 bp. Bioinformatics predicted that the possibly bound transcription factors in key promoter region –508/–281 bp were Pax5/P53, C/EBPβ, GR-β, GATA-1, GR-α, c-Jun, PRB/ PRA, YY1, RXR-α, AP-2, FOXP3, GR, TFIID, STAT4 and c-Ets-1. Conclusion The recombinant plasmid of hCREG gene promoter has been successfully constructed, the core promoter of which is located in –508/–281 bp, where several transcription factors might be bound.

Transcriptional repression by androgen receptor: Roles in castration-resistant prostate cancer / 亚洲男科学杂志(英文版)

Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially successful in regressing prostate tumors, the disease ultimately comes back as castration-resistant prostate cancer (CRPC) or at the late stage as neuroendocrine prostate cancer (NEPC). CRPC remains largely dependent on hyperactive AR signaling in the milieu of low androgen, while NEPC is negative of AR expression but positive of many AR-repressed genes. Recent technological advances in genome-wide analysis of transcription factor binding sites have revealed an unprecedented set of AR target genes. In addition to its well-known function in activating gene expression, AR is increasingly known to also act as a transcriptional repressor. Here, we review the molecular mechanisms by which AR represses gene expression. We also summarize AR-repressed genes that are aberrantly upregulated in CRPC and NEPC and represent promising targets for therapeutic intervention.

Changes in expression of repressor element silencing transcription factor in rapid amygdala kindling epilepsy rats / 中国比较医学杂志

Objective To detect changes in expression of repressor element silencing transcription factor(REST) in rapid amygdala kindling epilepsy rats. Methods Adult Sprague-Dawley rats were randomly divided into a sham group (group S),epilepsy 2 h group(group EP-2 h),epilepsy 14 d group(group EP-14 d),and epilepsy 35 d group(group EP-35 d). An experimental epilepsy kindling model of the amygdala was established by electrical stimulation. After 2 h, 14 d,and 35 d,rats were perfused and their brains were fixed and frozen for coronal sections. Immunohistochemistry was used to detect expression of REST and the neuron specific nuclear protein, NeuN. Results Expression of REST was significantly increased in the CA1, CA3, and dentate gyrus regions in groups EP compared with group S(P < 0.05), particularly in group EP-2 h. In contrast,NeuN staining was significantly decreased in groups EP compared with group S. Visible neuronal loss was observed in the hippocampus of the EP-35 d group. Conclusions Up-regulation of REST in rat hippocampus may be involved in epileptogenesis.

Roles of TRIM28 in tumorigenesis and embryogenesis / 上海交通大学学报（医学版）

TRIM28, known as a kind of macro-molecules, consists of multiple domains and belongs to one of human tripartite motif-containing proteins families. This superfamily contains more than 60 proteins in total and is characterized by four conservative domains, also referred to the RBCC domain, which is a RING (really interesting new gene) finger, two B-boxes (type 1 and type 2) and a leucine zipper coiled-coil region. TRIM28 plays its pivotal roles in transcriptional co-activation or co-repression by interacting directly with transcription factors, within which is a Kruppel-associated box domain (KRAB domain). Moreover, it is critical during the development of embryos, the differentiation of cells and the regulation of cancers.

Mechanism of Inhibition of Neuroblastoma Cell Proliferation by Elemene / 中国医科大学学报

Objective To investigate the effect of elemene and the mechanism of this effect on the proliferation of neuroblastoma.Methods We treated cultured SK-N-SH cells with elemene and used the MTT assay to determine the inhibition of cell proliferation.We used RT-qPCR and Western blotting to measure the effect of elemene on mRNA and protein expression,respectively,of repressor element-1 silencing transcription factor (REST) in SK-N-SH cells and evaluated the mRNA expression of CCND1 and CCNE1 in SK-N-SH cells by using RT-qPCR.Results Elemene significantly inhibited the proliferation of SK-N-SH cells in a dose-and time-dependent manner (P =0.001 16).Moreover,the mRNA (P =0.000 38) and protein (P =0.003 39) expression of REST were markedly suppressed by elemene.Furthermore,elemene significantly reduced the mRNA expression of CCND1 (P =0.001 91) and CCNE1 (P =0.000 15),which are related to the cell cycle.Conclusion Elemene significantly suppressed the proliferation of neuroblastoma cells through the reduction of REST,CCND1,and CCNE1.

Correlation between mutation of p53 gene 2-4 exons from peripheral blood and HPV16 positive cervical cancer susceptibility and clinical significance / 中华妇产科杂志

Objective To detect mutations of p53 gene 2-4 exons from peripheral blood and to explore their relevance in HPV16-positive cervical cancer susceptibility and clinical significance. Methods Collected firstly cases from the Third Affiliated Hospital of Kunming Medical University from October 2012 to April 2014, included 167 cases HPV16-postive cervical cancer and 160 cases HPV-negative healthy women. Genomic DNA from the host peripheral venous blood was taken, mutations of p53 gene 2-4 exons were analyzed with software DNAstar after PCR and bidirectional sequencing. Meanwhile,mutations of p53 gene 2-4 exons among different clinicopathological characteristics in HPV16-postive cervical cancer were distinguished. Results (1)Three mutations and an 16-bp insertion/deletion sequences were found in p53 gene exons 2-4, included C/G mutation of single nucleotide polymorphism(SNP)11827 in intron2, A/C mutation of SNP11992 in intron3, C/G mutation in codon 72 (rs1042522) of exon4 and 16-bp(acctggagggctgggg) repeat insertion or deletion in intron3 (rs17878362), while deletion recorded as A1, insertion recorded as A2. No significant differences were found in each point allele and genotype frequency(P＞0.05). (2) Stratified analysis for cervical cancer group resulted with some differences. Compared group of non-squamous carcinoma with squamous carcinoma group, there were obviously decreased in allete A2 [11.8%(4/34) vs 3.5%(10/284); χ2=4.90,P=0.027], genotype A1A2 [4/17 vs 7.0%(10/142); χ2=5.14,P=0.023], and haplotype C-A2 [11.8%(4/34)vs 3.5%(10/284);χ2=4.91,P=0.027]. Compared with poorly differentiated group,allele C of SNP11827 and rs1042522 were obviously decreased in medium high differentiation group [50.8%(61/120)vs 38.8%(62/160);χ2=4.07,P=0.044], while haplotype G-A1 were apparently higher [49.2%(59/120)vs 61.2%(98/160);χ2=4.07,P=0.044], genotype GG of SNP11827 and rs1042522 were obviously decreased in superficial myometrial invasion depth group than that in deep myometrial invasion depth group [46.3%(25/54) vs 21.1%(8/38); χ2=7.06,P=0.029]. No significant differences were found between stage Ⅰ and Ⅱ, pelvic lymph node metastasis or not (all P＞0.05). Conclusions No obvious correlation is found between polymorphisms in exons 2-4 of p53 gene and susceptibility of HPV16-postive cervical cancer. But the patient with allete C and A2, genotype GG and A1A2, haplotype C-A2 and G-A1 may be increase risk of poorly differentiation, deep muscular invasion and bad pathological type. Analysis of p53 gene polymorphism may be provide a basis for the prognosis evaluation and individualized treatment of cervical cancer.

Diagnostic value of combined detection of autoantibodies against p53 and Bmi-1 in lung cancer / 中国医师杂志

Objective To evaluate the diagnostic value of combined detection of serum autoantibodies against against p53 and Bmi-1 in lung cancer (LC).Methods Serum levels of autoantibodies against p53 and Bmi-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 92 patients with LC and 80 normal controls.The combined diagnostic value was evaluated with the receiver operating characteristic (ROC) curve.Results The serum levels of autoantibodies against p53 and Bmi-1 were significantly higher in LC than in normal controls (0.438 ±0.705 vs 0.045 ±0.035,Z =-7.667,P ＜0.01;0.117±0.061 vs 0.068 ±0.031,Z =-7.179,P ＜0.01).The levels of autoantibodies against p53 and Bmi-1 were not related to age,gender,pathological classification,lymph node status or tumor-node-metastasis (TNM) stage (P ＞ 0.05).The combined detection of two autoantibodies provided an enhanced sensitivity of 63.0％,a specificity of 91.2％ and an area under curve (AUC) of 0.881,which showed better diagnostic efficiency compared to individual autoantibodies.Conclusions Combined detection of autoantibodies against p53 and Bmi-1 shows good diagnostic value,which may aid diagnosis of LC.

Regulation of chromosome regulator EZH2 in cancer epigenetics and EZH2 targeted drugs in cancer therapy / 中国药理学与毒理学杂志

Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressor complex 2(PRC2),a complex that methylates lysine-27 of histone H3(H3K27). PRC2 facilitates chro?matin compaction and gene silencing by modulating the methylation of H3K27,which is thought to be the classical function of EZH2 in several types of cancer. In some other situations,EZH2 also acts as an acti?vator of transcription in a PRC2-independent manner. EZH2 has been demonstrated to be extensively involved in the development and progression of cancer by inducing aberrant histone modification and gene transcription via aberrant EZH2 expression,functional mutation or other mechanisms which are very context-dependent. EZH2 inhibitors targeting the catalytic activity of EZH2 or the stability of PRC2 have been designed for cancer therapies and some of them have produced positive effects. This review focuses on the regulation of EZH2 on cancer epigenetics and the development of therapeutic drugs targeting EZH2.

Effect of cellular repressor of E1A stimulated genes (CREG1) on cardiac function injury induced by angiotensin Ⅱ in mice / 解放军医学杂志

Objective To investigate the effect of cellular repressor of E1A stimulated genes (CREG1) on cardiac function in mouse with myocardial fibrosis. Methods CREG1 knockout mice (CREG1+/-) and CREG1 wild-type mice (CREG1+/+) were used to reproduce the model of myocardial fibrosis by subcutaneous pump burying of angiotensin Ⅱ (AngⅡ). After being stimulated with AngⅡ for 14 days, myocardial fibrosis was verified by HE staining and Masson trichrome staining. Western blotting and immunohistochemistry were used to detect the expression of CREG1 in myocardium before stimulation and 3, 7, 14 days after the AngⅡ stimulation. The cardiac function was evaluated by echocardiography after AngⅡ stimulation for 14 days. The CREG+/+ mice were given AngⅡ for 14 days, and at the same time recombinant CREG1 protein [respectively 15, 30, 60 and 300μg/(kg.d), intraperitoneal (IP) injections] (treatment group) and NaCl (control group) were administered for treatment, and then cardiac function and myocardiac apoptosis were examined. Results Western blotting and immunohistochemistry showed that the expression of CREG1 in heart tissue was significantly lower in CREG+/-mice than in CREG+/+ mice (P<0.05). After AngⅡ stimulation for 3, 7 and 14 days, the expression of CREG1 in heart tissue declined significantly in both CREG+/-and CREG+/+ mice (P<0.05), especially in CREG+/-mice (P<0.01). With HE and Masson staining, it was also found that CREG1 deficiency aggravated myocardial fibrosis and cardiac function deterioration in response to AngⅡ stimulation (P<0.05). Conversely, exogenous infusion of recombinant CREG1 protein significantly inhibited the occurrence of myocardial apoptosis (P<0.05), thus ameliorated cardiac function (P<0.05). Conclusions CREG1 deficiency may aggravate the deterioration of cardiac function in mouse with myocardial fibrosis induced by AngⅡ stimulation. The deterioration of cardiac function can be improved by administration of exogenous recombinant CREG1 protein.

Expression of Blimp1 mRNA in the PBMCs of patients with RA and the corresponding regulation of IL-21 / 中华检验医学杂志

Objective To Investigate the expression of IL-21 and Blimp1 mRNA in Rheumatoid arthritis ( RA) patients and the influence on the expression of Blimp 1 in peripheral blood mononuclear cells (PBMCs) of RA patients after IL-21 stimulated; To further explore the mechanism of IL-21 and blimp1 in the pathogenesis of RA.Methods Case control study.The samples of peripheral venous blood from 50 RA patients of department of rheumatology of The First Affiliated Hospital of Zhengzhou University and 50 healthy people were collected respectively , then the plasma and PBMCs was separated.IL-21 in plasma was measured by ELISA; the correlation between patients clinical index DAS 28, anti-CCP antibody and IL-21 was analyzed.Blimp1 mRNA of patients′PBMCs was detected by qPCR; PMBCs were isolated from RA patient and then cultured in vitro.Blimp1 mRNA level was measured by qPCR and the ratio of CD 20 positive B cell and the ratio of CD138 positive cells in all groups were detected by flow cytometry after 72 h stimulated by IL-21 and CD40L.Results IL-21 content in RA patient blood plasma (130.51 ±11.35)ng/L was significantly higher than that in healthy control (25.46 ±6.05)ng/L, t=5.39,P<0.05.Besides, IL-21 level also had a close relativity with patients DAS28(r=0.658) and anti-CCP antibody (r=0.674, P=0.039 and 0.035).In addition, the expression level of Blimp1 mRNA in RA patient PMBCs (1.321 ± 0.11)was higher than that in healthy control group (1.000 ±0.000), Z=-2.48, P<0.05.While after IL-21 and/or CD40L stimulation, Blimp1 mRNA of IL-21 group and CD40L+IL-21 group(1.084 ±0.029, 1.157 ±0.028)were higher than those of control (1.000 ±0.000)(P=0.002,P=0.001), moreover the expressive level of Blimp1mRNA of CD40L+IL-21 group was higher than that of control group (t=4.862, P=0.02).Compared to negative control group , the ratio of CD20 positive B cells [2.42 ±0.35, 2.63 ± 0.33, 6.35(4.85,6.57),F=278.363,P<0.001] and the ratio of CD138 positive cells(0.474 ±0.110, 0.668 ±0.120, 0.955 ±0.170,F=49.01, P<0.001) in CD40L group, IL-21 group and CD40L+IL-21 group were much higher and the differences among CD 40L+IL-21 group with CD40L group and IL-21 group were statistically significant.Conclusion IL-21 could promote the level of Blimp 1 mRNA in peripheral blood mononuclear cells in RA patient; IL-21 and CD40L could co-promote B cell maturation though regulating Blimp1 mRNA expression and eventually participate in RA pathogenesis.

The expression and significance of MTA1, MMP-9, and VEGF-C in the gastric adenocarcinoma / 中国医师杂志

Objective To investigate the expression and clinicopathological significance of metastasis-associated 1 (MTA1), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor-C (VEGF-C) in a gastric adenocarcinoma.Methods The expressions of MTA1, MMP-9, and VEGF-C were detected with immunohistochemical method in 120 cases of gastric adenocarcinoma tissues and 30 cases of normal gastric tissues.Results The positive percentage of MTA1, MMP-9, and VEGF-C proteins in gastric adenocarcinomas was 76.7％ , 71.7％ , and 64.2％ , respectively, which was significantly higher than that (33.3％, 36.7％, and 30.0％) in normal gastric mucosa tissues (P ＜0.05).The expressions of MTA1, MMP-9, and VEGF-C were significantly higher in gastric carcinoma invasion serous membrane, lymph node metastasis, clinical Ⅲ ～ than that in non-invasion serous membrane, non-lymph node metastasis, and clinical Ⅰ ～ Ⅱ (P ＜ 0.05).The expression of MTA1 had significantly positive correlation with that of MMP-9 (P ＜ 0.05) and VEGF-C (P ＜ 0.05) in gastric adenocarcinomas.Conclusions The expressions of MTA1, MMP-9, and VEGF-C were higher in gastric adenocarcinomas than normal gastric mucosa tissues.They may play an important role in the invasion and metastasis of gastric carcinomas.MTA1 may promote infiltration, invasion, and lymph node metastasis of gastric carcinoma through regulation of the expressions of MMP-9 and VEGF-C.The combined detection of MTA1, MMP-9, and VEGF-C expressions has important value to judge the grade malignance of gastric adenocarcinomas.

Correlation between TRIB3 gene rs2295490 polymorphism and coronary heart disease with dyslipidemia / 中华检验医学杂志

Objective To explore the correlation between the polymorphism of TRIB3 gene rs2295490 and coronary heart disease (CHD) with dyslipidemia.Methods In the case control study,we enrolled 220 CHD patients as observation group (60.15 years mean age,150 males and 70 females) and 151 age and gender matched healthy individuals as control group (59.22 years mean age,102 males and 49 fe males).Genotypes of TRIB3 gene rs2295490 polymorphisms in the two groups were detected by PCR and sequence-based testing.At the same time,blood glucose (GLU),total cholesterol (TC),triglyceride (TG),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C) were measured.The correlations between the polymorphism of TRIB3 gene rs2295490 and CHD,biochemical indicators of two groups were analyzed,respectively.The comparison of genotype and allele frequency between two groups used x2 test,while the comparison of biochemical indexes between two groups used t test.Results In the control group,genotypic frequencies of AA,AG and GG of TRIB3 gene rs2295490 were 57％,35％ and 8％,and the frequencies of A and G alleles were 75％ and 25％,respectively.In the CHD group,genotypic frequencies of AA,AG and GG of TRIB3 gene rs2295490 were 50％,41％ and 9％,and the frequencies of A and G alleles were 71％ and 39％,respectively.There was no significant difference of genotype and allele frequencies of polymorphism of TRIB3 gene rs2295490 between CHD and healthy controls(x2 =1.74,P =0.42;x2 =1.26,P =0.243).In the CHD group,the HDL-C levels of the AA genotype were higher than those of AG + GG genotype (t =-9.78,P =0.00);The TG,LDL-C levels of the AA genotype were lower than those of AG + GG genotype (t =2.59,P =0.01;t =6.15,P =0.00).All the differences were statistically significant.Conclusions TRIB3 gene rs2295490 polymorphism has no correlation with CHD,but the G allele may be correlated with dyslipidemia in CHD patients.

The change of cellular repressor of E1A-stimulated genes during adventitial fibroblast phenotypic switching / 中国介入心脏病学杂志

Objective To explore possible role of cellular repressor of E1A-stimulated genes(CREG) in the process of phenotypic switching of adventitial fibroblasts(AFs). Methods Immunofluorescent staining was performed with tissue sections from mouse carotid arteries to evaluate the relationship between the expression of CREG and smooth muscle actin-α(α-SMA) in injured arteries, especially in the adventitia. Tissue block pasted culture method was used to isolate and culture AFs. RT-PCR and Western-blot were used to detect the change of CREG andα-SMA mRNA and protein expression in AFs in the presence of different concentrations of AngⅡfor 12 h/24 h or in the presence of 100 nmol/L Ang Ⅱ for different times. Results Normal mouse carotid arteries had little α-SMA expression throughout the tunica adventitia. Arteries at day 1 and day 3 post-injury exhibited significantly higher immunofluorescence of α-SMA compared with non-injured arteries. Alpha-SMA expression began to decrease on day 7 and progressively declined on day 14. In contrast, immunofluorescent staining revealed that CREG was expressed in the adventitia of normal arteries. Expression of CREG in the adventitia of injured arteries was decreased on the 1st day, reached its lowest value on the 3rd day, and increased gradually from the 7th day, and was higher compared with that in non-injured arteries on the 14th day after injury. Similarly, the expression of CREG in AFs was very high, and AngⅡremarkably decreased mRNA and protein expression levels of CREG in a dose-dependent and time-dependent manner. Conclusions The changes in CREG expression correlate with AF phenotypic modulation, and CREG down-regulation may facilitate AF phenotypic switching into myofibroblasts (MFs).

Role of neuron-restrictive silencer factor in spinal cord in remifentanil-induced hyperalgesia in a mouse model of incisional pain / 中华麻醉学杂志

Objective To evaluate the role of neuron-restrictive silencer factor (NRSF) in the spinal cord in remifentanil-induced hyperalgesia in a mouse model of incisional pain (IP) .Methods Fifty-six male Kunming mice were randomly divided into 7 groups (n=8 each):control group (group C) ,IP group (group I) ,IP +remifentanil group (group IR ) , NRSF antisense oligonucleotide group (NAS group ) , IP + NRSF antisense oligonucleotide group (I+NAS group ) ,IP + remifentanil + NRSF mismatch oligonucleotide group (IR+NMS group) , and IP + remifentanil + NRSF antisense oligonucleotide group (IR + NAS group ) . Artificial cerebrospinal fluid 5 μl was injected intrathecally once a day for 3 consecutive days in C ,I and IR groups .NRSF antisense oligonucleotide NAS 10μg was injected intrathecally once a day for 3 consecutive days in NAS ,I+NAS and IR + NAS groups . NRSF mismatch oligonucleotide 10 μg was injected intrathecally once a day for 3 consecutive days in IR+NMS group .A 1-cm longitudinal incision was made through skin ,fascia and muscle of the plantar aspect of the right hindpaw to establish the model of incisional pain in sevoflurane-anesthetized rats .At 30 min after the last injection ,normal saline 0.4 ml was infused subcutaneously in C and NAS groups ,the model was established and normal saline 0.4 ml was subcutaneously infused simultaneously in I and I+NAS groups ,and the model was established and remifentanil 0.04 mg/kg was subcutaneously infused simultaneously in IR ,IR+NMS and IR+NAS groups .At 3 days before operation (T0 ) ,4 h before operation (T1 ) and 4 ,12 ,24 and 48 h after operation (T1-5 ) ,mechanical paw withdrawal threshold to von Frey stimuli (PMWT ) and paw withdrawal latency to thermal nociceptive stimulus (PTWL ) were measured .Results Compared with C group ,the PWMT and PWTL were significantly decreased at T2-5 in I ,IR ,I+NAS ,IR+NMS and IR+NAS groups ( P0.05 ) .Compared with I group ,the PWMT and PWTL were significantly decreased at T2-5 in IR and IR+NMS groups ( P0.05) . Compared with IR group ,no significant change was found in the PWMT and PWTL at each time point in IR+NMS group ( P>0.05) ,and the PWMT and PWTL were significantly increased at T2-5 in IR+NAS group ( P<0.05) . Conclusion NRSF in the spinal cord is involved in the development and maintenance of hyperalgesia induced by remifentanil in a mouse model of IP .

Spo0A positively regulates epr expression by negating the repressive effect of co-repressors, SinR and ScoC, in Bacillus subtilis.

Bacillus subtilis under nutritional deprivation exhibits several physiological responses such as synthesis of degradative enzymes, motility, competence, sporulation, etc. At the onset of post-exponential phase the global response regulator, Spo0A, directly or indirectly activates the expression of genes involved in the above processes. These genes are repressed during the exponential phase by a group of proteins called transition state regulators, e.g. AbrB, ScoC and SinR. One such post-exponentially expressed gene is epr, which encodes a minor extracellular serine protease and is involved in the swarming motility of B. subtilis. Deletion studies of the upstream region of epr promoter revealed that epr is co-repressed by transition state regulators, SinR and ScoC. Our study shows that Spo0A positively regulates epr expression by nullifying the repressive effect of co-repressors, SinR and ScoC. We demonstrate via in vitro mobility shift assays that Spo0A binds to the upstream region of epr promoter and in turn occludes the binding site of one of the co-repressor, SinR. This explains the mechanism behind the positive regulatory effect of Spo0A on epr expression.

Expression of KLF-8 and MMP-9 in placentas and their relationship with the pathogenesis of preeclampsia / 中华妇产科杂志

Objective To evaluate the expression of Krüppel-like factor 8 (KLF-8) and matrix metalloproteinase 9 (MMP-9) in placentas and their relationship with the pathogenesis of preeclampsia (PE).Methods Twenty-two women with PE (mild PE:4 cases; severe PE:18 cases) who received cesarean sections in the First Affiliated Hospital of Chongqing Medical University from September 2011 to March 2012 were recruited as the PE group (n =22).And twenty women who received elective term cesarean section without perinatal complications were chosen as the control group (n =20).Placentas were collected and immunohistochemical SP method were employed to detect the localization of KLF-8 protein.KLF-8 mRNA level was determined by quantitative real-time PCR technique and western blot analysis was used to quantify KLF-8 and MMP-9 protein levels.Results (1) There was no difference of KLF-8 protein distribution in placentas of the PE group and the control group.It was mainly located in the nuclear and cytoplasm of syncytiotrophoblasts.KLF-8 immunostaining was apparently decreased in the placentas of preeclamptic women when compared with the control group.(2)The KLF-8 mRNA levels were significantly decreased in placentas of the PE group (0.69 ±0.08) compared to those of the control group (1.14 ±0.09,P ＜0.01).(3) KLF-8 and MMP-9 protein levels significantly decreased in the PE placentas (0.68 ±0.05 and 0.21 ± 0.03) when compared to the control group (0.94 ± 0.06 and 0.34 ± 0.03,respectively,P ＜ 0.01).(4) There was a positive correlation between the expression of KLF-8 and MMP-9 protein in the placentas from PE and normal pregnancies (r =0.64,P ＜ 0.01).Conclusions KLF-8 mRNA and protein levels were decreased in placentas of PE patients compared to those of normotensive women.KLF-8 protein was primarily located in the invasion-related trophoblast cells and its expression had a positive correlation with MMP-9 levels.KLF-8 might have an important role in the pathogenesis of PE by regulation of trophoblast invasion.