Dynamics of sequestering the limiting p300/CBP, viral cis-regulatory elements, and disease

Many studies showed that the p300/CBP coactivator is limiting. Here we review three studies that showed howtranscription complexes formed on viral cis-regulator elements compete with cellular transcription complexesby sequestrating the p300/CBP coactivator. According to the microcompetition model, this sequestering cancause disease. We use the microcompetition model to explain how a specific type of sequestering, caused by alatent virus that has an active cis-regulatory element in its promoter/enhancer that binds the transcriptioncomplex p300/CBPGABP can cause diseases such as cancer, atherosclerosis, diabetes, and certain autoimmune diseases.

Regulation of epigenetic state by non-histone chromatin proteins and transcription factors: Implications in disease

Besides the fundamental components of the chromatin, DNA and octameric histone, the non-histone chromatinproteins and non-coding RNA play a critical role in the organization of functional chromatin domains. Thenon-histone chromatin proteins therefore regulate the transcriptional outcome in both physiological andpathophysiological state as well. They also help to maintain the epigenetic state of the genome indirectly.Several transcription factors and histone interacting factors also contribute in the maintenance of the epigeneticstates, especially acetylation by the induction of autoacetylation ability of p300/CBP. Alterations of KATactivity have been found to be causally related to disease manifestation, and thus could be potential therapeutictarget.

Promotion of OIP5-AS1 expression by H3K27ac-induced radioresistance in esophageal squamous carcinoma / 西安交通大学学报(医学版)

Objective: Our study aims to investigate the radiation associated H3 modification in regulating OIP5-AS1 to lay foundation for developing therapeutic targets on reversing radiation resistance of esophageal squamous carcinoma. Methods: We recruited 137 ESCC patients from The First Affiliated Hospital of Xi'an Medical College. qRT-PCR and Western blotting were used for detecting the expressions of target genes. Wound healing assay and CCK8 assay were used to detect the migration and proliferation abilities. ChIP assay was used to detect the interaction between OIP5-AS1 and H3K27ac. Results: OIP5-AS1 was highly expressed in ESCC radiation resistant patients and promoted the migration and proliferation abilities of ESCC radiation resistant cells. H3K27ac was activated in ESCC radiation resistant cells and was enriched in the promoter region of OIP5-AS1. CBP was upregulated in ESCC radiation resistant cells; its inhibitor, C646, could suppress the enrichment of H3K27ac in the promoter region of OIP5-AS1. Results: OIP5-AS1 regulated radioresistance in ESCC. CBP promoted the interaction between H3K27ac and OIP5-AS1, thereby activating the expression of OIP5-AS1 and resulting in radioresistance.

Effects of CITED1 gene silencing on biological functions of papillary thyroid carcinoma K1 cells / 肿瘤

Objective: To investigate the effects of Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 1 (CITED1) gene silencing on the proliferation, apoptosis and migration of papillary thyroid carcinoma K1 cells. Methods: The recombinant lentivirus carrying CITED1-shRNA or the negative control (NC)-shRNA was successfully infected into thyroid cancer K1 cells. The silencing efficiency of CITED1 gene was detected by real-time fluorescent quantitative PCR and Western blotting, respectively. The cell proliferation was detected by CCK-8 method, the cell cycle distribution and apoptosis were detected by FCM, and the cell migration ability was detected by scratch wound healing assay. Results: After the recombinant lentivirus carrying CITED1-shRNA was successfully infected into papillary thyroid carcinoma K1 cells, the expression levels of CITED1 mRNA and protein were significantly decreased (both P < 0.01), which suggested that the K1 cells with CITED1 gene silencing were successfully obtained. After silencing CITED1 gene expression, the cell proliferation was significantly inhibited (P < 0.01), the apoptosis rate was significantly increased (P = 0.001), the proportion of G0/G1-phase cells was significanlty increased (P = 0.007), the proportion of G2/M- and S-phase cells was significanlty decreased (both P < 0.05), and the cell migration abilities at 12 h and 24 h were significantly decreased (both P < 0.01). Conclusion: Silencing CITED1 gene expression can inhibit the proliferation and migration of papillary thyroid carcinoma K1 cells, and promote the apoptosis of tumor cells.

Effects of CBP on blood lactate and hemodynamics in patients with severe sepsis / 中国生化药物杂志

Objective To explore the treatment of sepsis in patients with severe sepsis, the use of CBP (continuous blood purification) effect on lactic acid and hemodynamics in patients with blood.MethodsIn 40 cases of patients with severe sepsis treated by conventional methods, and classified as the control group, the other 40 patients using CBP (continuous blood purification treatment;blood lactic acid) after evaluation and hemodynamics of two groups of patients before and after treatment, and compared between groups, the patients were treated in our hospital from January 2015 to October 2016.ResultsThere was no significant difference in blood lactate level of the two groups of patients before treatment, after grouping After treatment, the patients in the observation group decreased more significantly, while the monitoring of patients in different time period, showed its obvious difference;hemodynamics of two groups were observed and compared, found before treatment all indexes had no significant difference after the treatment group were improved more obviously in patients in the observation group, group are P<0.05 shows obvious differences.ConclusionAnalysis of the influence of the dynamics of CBP in severe sepsis patients blood lactic acid and blood flow, which can significantly improve the patient's level of lactic acid, which decreased gradually, while helping the hemodynamic situation of the patient to recover, it is worthy of reference.

Identification of the MYST3-CREBBP fusion gene in infants with acute myeloid leukemia and hemophagocytosis

ABSTRACT Background: Acute myeloid leukemia presenting the MYST3-CREBBP fusion gene is a rare subgroup associated with hemophagocytosis in early infancy and monocytic differentiation. The aim of this study was to define the relevant molecular cytogenetic characteristics of a unique series of early infancy acute myeloid leukemia cases (≤24 months old), based on the presence of hemophagocytosis by blast cells at diagnosis. Methods: A series of 266 infant cases of acute myeloid leukemia was the reference cohort for the present analysis. Acute myeloid leukemia cases with hemophagocytosis by blast cells were reviewed to investigate the presence of the MYST3-CREBBP fusion gene by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. Results: Eleven cases with hemophagocytosis were identified with hemophagocytic lymphohistiocytosis being ruled out. Six cases were classified as myelomonocytic leukemia, three as AML-M7 and two as AML-M2. In five cases, the presence of the MYST3-CREBBP fusion gene identified by molecular cytogenetics was confirmed by fluorescence in situ hybridization. All patients received treatment according to the Berlin-Frankfürt-Münster acute myeloid leukemia protocols and only one out of the five patients with the MYST3-CREBBP fusion gene is still alive. Conclusions: Our findings demonstrate that the presence of hemophagocytosis in acute myeloid leukemia was not exclusively associated to the MYST3-CREBBP fusion gene. Improvements in molecular cytogenetics may help to elucidate more complex chromosomal rearrangements in infants with acute myeloid leukemia and hemophagocytosis.

Homocysteine induces glyceraldehyde-3-phosphate dehydrogenase acetylation and apoptosis in the neuroblastoma cell line Neuro2a

High plasma levels of homocysteine (Hcy) promote the progression of neurodegenerative diseases. However, the mechanism by which Hcy mediates neurotoxicity has not been elucidated. We observed that upon incubation with Hcy, the viability of a neuroblastoma cell line Neuro2a declined in a dose-dependent manner, and apoptosis was induced within 48 h. The median effective concentration (EC50) of Hcy was approximately 5 mM. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) nuclear translocation and acylation has been implicated in the regulation of apoptosis. We found that nuclear translocation and acetylation of GAPDH increased in the presence of 5 mM Hcy and that higher levels of acetyltransferase p300/CBP were detected in Neuro2a cells. These findings implicate the involvement of GAPDH in the mechanism whereby Hcy induces apoptosis in neurons. This study highlights a potentially important pathway in neurodegenerative disorders, and a novel target pathway for neuroprotective therapy.

Effect of over expression of C-terminal Src kinase binding protein (Cbp) and Cbp palmitoylation to proliferation of T-leukemia Jurkat cell in nude mice / 中国免疫学杂志

Objective:To establish T lineage leukemia Jurkat cell mice model of over expression of C-terminal Src kinase binding protein( Cbp ) and Cbp palmitoylation and to research the effect of Cbp and Cbp palmitoylation to proliferation of Jurkat cell.Methods:Virus transfected cell of neg-EGFP,Cbp-EGFP and Cbp-m-EGFP were used in mice model.24 female BALB/c-nu mice were randomly divided into blank control group,empty virus control group,over expression of CBP group and Cbp palmitoylation group, 6 mice in each group.The nude mice were weighed in 0,1,2,3,4,5 weeks.The amount of white blood cell in peripheral blood were counted in 0, 1, 2, 3, 4, 5 weeks.The proliferation of Jurkat cell in peripheral blood of mice were observed by laser confocal microscope.The pathological changes of liver were observed using HE staining.The proliferation of Jurkat cell in the bone marrow and peripheral blood of mice were detected with flow cytometry.Results:The weight of mice in over expression of Cbp group was less than that in blank control group,but higher than that in empty virus control group and Cbp palmitoylation group.The weight of mice in Cbp palmitoylation group was less than that in blank control group,empty virus control group and over expression of Cbp group.The amount of white blood cell in peripheral blood and proliferation of Jurkat cell in liver, bone marrow and peripheral blood of mice in over expression of Cbp group was higher than that in blank control group, but less than that in empty virus control group and Cbp palmitoylation group.The amount of white blood cell in peripheral blood and proliferation of Jurkat cell in liver, bone marrow and peripheral blood of mice in Cbp palmitoylation group was higher than that in blank control group,empty virus control group and over ex-pression of Cbp group.Conclusion:Over expression of Cbp and Cbp palmitoylation in T lineage leukemia Jurkat cell mice model was established.Over expression of Cbp has inhibitory effect on the proliferation of Jurkat cell.Cbp palmitoylation has promotable effect on the proliferation of Jurkat cell.

Research progress on P300/CBP in malignant tumors / 实用肿瘤学杂志

P300/CBP is one of the most important high molecular weight protein histone acetyltransferase ( HAT) Although it is encoded by multiple different genes , P300/CBP is highly homologous , Because they have the similar amino acid sequence and functions ,and belong to the same class of proteins ,normolly they are all called P300/CBP.P300/CBP is involved in the activation of many kinds of transcription factors ,the protein itself alsohas acetyltransferase activity ,and is capable of acetylation of 4 core histones and transcription factor .More and more studies have confirmed the relationship of P 300/CBP variation withmultiple human diseases , including in-flammation,diabetes,heart disease and especially cancer .In tumor P300/CBP is associated with some pathways , and these pathways play a different roles in the tumor .Although P300/CBP is usually regarded as a tumor sup-pressor factor ,is plays different roles in different tumors ,This review mainly introduces the relationship of P 300/CBP with some solid tumor disease genes ,related transcription factors and their signaling pathways .

Convergence role of transcriptional coactivator p300 and apparent modification on hmcs metabolic memory induced by high glucose / 解放军医学杂志

Objective To investigate the protein expression of transcriptional coactivator p300, acetylated histone H3 (Ac-H3) and Ac-H4 in human renal mesangial cell (HMCs) as imitative "metabolic memory" in vitro, and explore the potential role of convergence point of p300. Methods The HMCs were divided into the following groups: {circled digit 1} High glucose metabolic memory model: normal glucose group (NG, S.Smmol/L D-glucose × 2d), high glucose group (HG, 2Smmol/L D-glucose × 2d), memory groups (Ml, M2, M3, 2Smmol/L D-glucose × 2days + S.Smmol/L D-glucose × 3d, 6d or 9d), persisting normal glucose group (NG, S.Smmol/L D-glucose × 9d). {circled digit 2} Advanced glycation end products memory model: normal glucose group (NG, S.Smmol/ L D-glucose × 2d), NG+AGEs group (AGEs, S.Smmol/L D-glucose+2S0μg/ml AGEs × 2d); AGEs memory group (AGEs-M, S.Smmol/L D-glucose + 2S0μg/ml AGEs × 2d + S.Smmol/L D-glucose × 3d); BSA control group (NG+BSA, S.Smmol/L D-glucose + 2S0μg/ml BSA × 2d). {circled digit 3} H202 was used to simulate oxidative stress memory model: normal glucose group (NG, S.Smmol/L D-glucose × 2d), NG+H202 group (H202, S.Smmol/L D-glucose +100μmol/L H202 × 30min); H202 memory group [(S.Smmol/ L D-glucose + 100μmol/L H202 × 30min) + S.Smmol/L D-glucose × 3d]; normal glucose control group (NG3, S.Smmol/L D-glucose X 3d). {circled digit 4} Transfection with PKCβ2 memory model: normal glucose group (NG, S.Smmol/L D-glucose × 2d); high glucose group (HG, 2Smmol/L D-glucose × 2d); memory group (M, 2Smmol/L D-glucose × 2d + S.Smmol/L D-glucose × 3d); AdS-null memory group (HN, 2Smmol/L D-glucose + AdS-null × 2d + S.Smmol/L D-glucose × 3d); PKCβ2 memory group (PO, 2Smmol/L D-glucose + AdS-PKCβ2 × 2d + S.Smmol/L D-glucose × 3d); inhibitor of PKCβ2 memory group (PI, 2Smmol/L D-glucose × 2d + 10μmol/L CGPS33S3 + S.Smmol/L D-glucose × 3d). The expression of intracellular reactive oxygen species (ROS) was detected by fluorescence microscope and fluorescence microplate reader. The expression levels of p300, Ac-H3, Ac-H4 and PKCβ2 proteins were determined by Western blotting. Results The expression levels of p300, Ac-H3 and Ac-H4 protein in HG group increased, being 2.15, 1.93 and 1.87 fold of those in group NG (P<0.05), accompanying with the up-regulation of PKCβ2 protein and ROS levels in HG group. The p300, Ac-H3, Ac-H4, PKCβ2 protein expression and ROS levels in Ml, M2, M3 group were higher than those in NG group, and was 1.75, 1.49, 1.47, 1.98 and 1.48 fold higher in M3 group than in NG group. The protein expressions of p300, Ac-H3 and Ac-H4 in AGEs group were increased by 1.73, 1.08 and 1.05 folds, and in AGE-M group increased by 1.47, 0.95 and 1.03 folds of that in control group (P<0.05). The protein expression levels of p300, Ac-H3 and Ac-H4 in H202 group increased by 1.03, 0.85 and 0.79 folds of those in control group (P<0.05). However, no significantly difference in these indices was found between H202-M and control groups. The protein expression levels of p300, Ac-H3 and Ac-H4 in PO group increased more obviously by 1.25, 1.06 and 1.10 folds of those in M group (P<0.05). However, the elective PKCβ2 inhibitor CGP533S3 could lower those indices significantly. Conclusion Persistent activation of transcriptional coactivator p300 and apparent modification may be normalized in HMCs. p300 may be the convergent point of glucose-induced metabolic "memory" stimulations.

Factores asociados al síndrome de burnout en docentes de colegios de la ciudad de Cali, Colombia / Factors associated to Burnout Syndrome in high school teachers in Cali, Colombia

El objetivo de la investigación fue establecer los factores asociados al síndrome de burnout en docentes de dos instituciones educativas formales privada y pública de la ciudad de Cali, Colombia. Se describieron las dimensiones del síndrome (Agotamiento Emocional, Despersonalización y Falta de Realización Personal) y su relación con los factores organizacionales, el Estrés del Rol y las características sociodemográficas de los docentes. Para esto se aplicó el Cuestionario de Burnout en Profesores - Modificado (CBP-M) a una muestra de 82 docentes de un colegio público y uno privado. Los resultados muestran bajos niveles de burnout en ambas instituciones. Respecto a los factores asociados, se halló relación con el Estrés de Rol y los factores organizacionales de Supervisión, Condiciones Organizacionales y Preocupaciones Profesionales. Las variables sociodemográficas no presentaron relaciones significativas con el síndrome, a excepción del nivel de enseñanza en el cual los docentes imparten clases.

The goal of the study was to locate factors related to burnout syndrome in teachers of two formal private and public educational institutions from Cali, Colombia. The syndrome's dimensions (Emotional Exhaustion, Depersonalization and Reduced Sense of Personal Accomplishment) and their relation to organizational factors, the Stress of the Role and socio-demographic characteristics of the teachers were described. The Modified Burnout in Teachers Questionnaire (CBP-M) was applied to a sample of 82 teachers from one public and one private school. Results show a low level of burnout syndrome in both institutions. An association with the levels of stress of role and organizational factors such as supervision, job conditions and professional worries was found. The socio-demographic characteristics did not show significant relations with the syndrome, with the exception of the level of education in which the teachers give classes.

The biological characteristics of p300/CBP-associated factor and relationship with disease / 国际儿科学杂志

p300/CBP-associated factor (PCAF)is an important histone acetyltransferase in eukaryotic cells. PCAF can acetylizes histone and non-histone. PCAF participates in various biological processes of cells and in the interaction between virus and cells. The imbalance of PCAF would lead to abnormal development of various organs, and related to the development of some tumors.

A clinical study of ulinastatin combining with continuous blood purification in the treatment of patients with multiple organ dysfunction syndrome / 中华急诊医学杂志

Objective To observe the clinical efficacy of ulinastatin(UT) conjoined to high flow continuous blood purification( CBP) in the critical patients with multiple organ dysfunction syndrome(MODS). To evaluate the therapeutic potential of UT and CBP in systemic inflammatory response syndrome (SIRS) , severe sepsis( SS) , acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Method A total of 122 cases of emergency and critical patients with a score of more than 15 counted up from APACHE H (acute physiology and chronic health evaluation 11 ) were randomly divided into Ulinastatin treatment group (UT group, n = 35) .continuous blood pu-rification(CBP group, n = 31),UT plus CBP (combine group, n = 30) and routine treatment group (control group, n =26). Routine treatment was given to patients of all groups, and patients of UT group had Ulinastatin 0.4 MIU given intravenously every 8 hours for 7 days in addition. Patients of CBP group were managed with continuous blood purification round the clock for 7 days and those of combine group were treated with UT plus CBP for 7 days.The efficacy of the treatment in four groups was assessed,and serum high sensivity reactive protein(hs-CRP) and IL-6 levels were measured on admission and comparison was made between values of biomarkers taken before and 1 d,3 d,and 7 d after treatment in four groups. The changes in WBCs,arterial gas analysis and the oxygena-tion index PaO2/FiO2 were checked, and at the same time, the APACHE II values and the incidence of MODS were compared within four groups. Results (1)One, three and seven days after treatment the plasma hs-CRP and IL-6 levels in UT and CBP groups were reduced significantly more than those in control group ( P < 0. 05), and in combine groups those were more dramatically lowered ( P < 0.05, P < 0.01). Before treatment there was no significance diffience in those values between groups, and there was on diffience in those values between 3 rd day and 7 th day after treatment ( P > 0.05). (2) The 1 st,3 rd and 7 th day after treatment the arterial gas PaO2/FiO2 index in UT and CBP groups was improved more than that in control group ( P < 0.05) , and it in combine group was most significant improved (P < 0.05,P < 0.01). The ALT and creatinine were lower than those in control group ( P < 0.05), and there were no significant differences in ALT and creatinine between groups before treatment (P > 0.05). (3) The 1 st,3 rd and 7th day afer treatment,the APACHE II values in UT and CBP groups were decreased more than those in control group ( P < 0. 05) , and therefore, the incidence of MODS was lower ( P < 0.05). Conclusions Ulinastatin could significantly inhibit the production of inflammatory cytokines and CBP could effectively eliminate inflammatory factors from blood, and the combination of these two approaches produce a more effective therapeutic potential for preventing MODS development.

Transcriptional induction of DLC-1 gene through Sp1 sites by histone deacetylase inhibitors in gastric cancer cells

We previously reported that trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, induced DLC-1 mRNA expression and accumulated acetylated histones H3 and H4 associated with the DLC-1 promoter in DLC-1 non-expressing gastric cancer cells. In this study, we demonstrated the molecular mechanisms by which TSA induced the DLC-1 gene expression. Treatment of the gastric cancer cells with TSA activates the DLC-1 promoter activity through Sp1 sites located at -219 and -174 relative to the transcription start site. Electrophoretic mobility-shift assay (EMSA) revealed that Sp1 and Sp3 specifically interact with these Sp1 sites and showed that TSA did not change their binding activities. The ectopic expression of Sp1, but not Sp3, enhances the DLC-1 promoter responsiveness by TSA. Furthermore, the TSA-induced DLC-1 promoter activity was increased by p300 expression and reduced by knockdown of p300. These results demonstrated the requirement of specific Sp1 sites and dependence of Sp1 and p300 for TSA-mediated activation of DLC-1 promoter.

Comparison of Immunohistochemical Expression of CBP(cAMP- responsive Element Binding Protein) Transcriptional Co-activator between Premalignant Lesions and Squamous Cell Carcinomas in the Lungs / 결핵및호흡기질환

BACKGROUND: The pathogenesis of lung cancer includes the accumulation of multiple genetic abnormalities. The CREB-binding protein(CBP) is one of several transcriptional co-activators among various sequence-specific DNA-binding transcription factors. CBP is involved in a wide range of cellular activities, such as DNA repair, cell growth, differentiation, and apoptosis that are suspected of contributing to tumorigenesis. The goal of this study was to evaluate CBP expression in a series of human lung tissues containing normal epithelium, premalignant lesions(hyperplasia and dysplasia) and squamous cell carcinomas. MATERIALS AND METHODS: Immunohistochemical staining was performed on formalin-fixed paraffin-embedded sections by use of a monoclonal anti-CBP antibody. CBP expression was compared in samples from 120 patients with premalignant and malignant histological types including 20 metaplastic specimens, 40 dysplastic specimens, and 60 squamous cell carcinomas in the lung. RESULTS: CBP expression was seen in 35% (7/20) of the metaplastic specimens. 65% (26/40) of the dysplastic specimens, and 70% (42/60) of the squamous cell carcinomas (p<0.05). According to celluar atypism, CBP expression was 50% (10/20) of the low-grade dysplastic specimens and 80% (16/20) of the high-grade dysplastic specimens(p <0.01). By cellular differentiation, CBP expression was seen in 95% (19/20) of the well differentiated squamous cell carcinomas, 85% (17/20) of the moderately differentiated carcinomas and 30% (6/20) of the poorly differentiated lesions (p <0.05). CONCLUSION: These results suggest that CBP may have an important role in malignant transformation of precancerous lung lesions and may be a marker for malignancy.

Comparison of Immunohistochemical Expression of CBP(cAMP- responsive Element Binding Protein) Transcriptional Co-activator between Premalignant Lesions and Squamous Cell Carcinomas in the Lungs / 결핵및호흡기질환

BACKGROUND: The pathogenesis of lung cancer includes the accumulation of multiple genetic abnormalities. The CREB-binding protein(CBP) is one of several transcriptional co-activators among various sequence-specific DNA-binding transcription factors. CBP is involved in a wide range of cellular activities, such as DNA repair, cell growth, differentiation, and apoptosis that are suspected of contributing to tumorigenesis. The goal of this study was to evaluate CBP expression in a series of human lung tissues containing normal epithelium, premalignant lesions(hyperplasia and dysplasia) and squamous cell carcinomas. MATERIALS AND METHODS: Immunohistochemical staining was performed on formalin-fixed paraffin-embedded sections by use of a monoclonal anti-CBP antibody. CBP expression was compared in samples from 120 patients with premalignant and malignant histological types including 20 metaplastic specimens, 40 dysplastic specimens, and 60 squamous cell carcinomas in the lung. RESULTS: CBP expression was seen in 35% (7/20) of the metaplastic specimens. 65% (26/40) of the dysplastic specimens, and 70% (42/60) of the squamous cell carcinomas (p<0.05). According to celluar atypism, CBP expression was 50% (10/20) of the low-grade dysplastic specimens and 80% (16/20) of the high-grade dysplastic specimens(p <0.01). By cellular differentiation, CBP expression was seen in 95% (19/20) of the well differentiated squamous cell carcinomas, 85% (17/20) of the moderately differentiated carcinomas and 30% (6/20) of the poorly differentiated lesions (p <0.05). CONCLUSION: These results suggest that CBP may have an important role in malignant transformation of precancerous lung lesions and may be a marker for malignancy.

Immunohistochemical Expression of p53 Protein and CREB-binding Protein in Gastric Adenocarcinomas

PURPOSE: The wild-type p53 protein participates in suppressing cell transformations while its mutant forms has tumorigenic potential. Alterations in the structure of the p53 protein are one of the most common changes associated with human cancers. CREB-binding protein (CBP) and its homologue, p300, are transcriptional co-activators of various sequence-specific DNA-binding transcription factors and are involved in a wide range of cellular activities, such as DNA repair, cell growth, differentiation, and apoptosis. Several studies suggested that an association between p53 and p300 might account for the p53-responsible negative regulation. This study examined the relationship between p53 and CBP expression in terms of the clinicopathological factors and significance. METHODS: The level of p53 protein and CBP expression was measured in 150 gastric adenocarcinoma patients, who had undergone a gastrectomy, and the relationship between p53 and CBP was examined. Immunohistochemical stain was performed on formalin-fixed paraffin-embedded sections using monoclonal anti-p53 and anti-CBP antibody. RESULTS: 1. p53 protein was expressed in 46.3% (31/67) of early gastric cancers (EGC), 69.9% (58/83) of advanced gastric cancers (AGC)(P0.05), 47.8% (32/67) of EGC, 69.8% (58/83) of AGC (P0.05). 3. p53 protein and CBP expression was coincidentally observed in 66.7% of gastric adenocarcinomas, and there was a significant correlation between the expression of both (P<0.05). CONCLUSION: That the expression of the p53 protein and CBP indirectly indicate the malignant potential of a cell, and may play an indirect role in the CBP and p53-mediated tumorigenic potential.

Prokaryotic Expression and Acetylation Assays of Histone Acetyltransferase PCAF / 中国生物工程杂志

P300/CBP-associated factor(PCAF),an important member of histone acetyltransferase family(HATs) within eukaryotic cells,is capable of inducing the acetylation of histone,promoting the transcription of specific genes and involving in many biological effects.In the present study,full-length cDNA of PCAF was inserted into plasmid pGEX-5x-1,then the soluble protein GST-PCAF was expressed in E.coli BL21(DE3) after the optimization of inducing conditions.The recombinant protein was further purified with affinity chromatography and tested the activity by in vitro acetylation assays.High efficient PCAF protein produced by this method could serve for the study on the role of PCAF in gene regulation and the interaction between PCAF and other proteins.

Effect of Continuous Blood Purification on Multiple Organ Dysfunction Syndrome:33 Cases Report / 中国康复理论与实践

@#ObjectiveTo study the effect of continuous blood purification (CBP) on the multiple organ dysfunction syndrome(MODS). MethodsContinuous blood purification were used in 33 patients with MODS. Results Among 33 patients,24 mended and 8 died. The scores of Acute Physiology And Chronic Health Evaluation (APACHE Ⅱ) and MODS obviously declined(P<0.05), as well as the BUN and blood Cr (P<0.05), but the bilirubin did not (P>0.05). The haemodynamic variables were stabilized during CBP and no obvious side-effect related to CBP was found. ConclusionThe therapy of continuous blood purification can improve the prognosis to the patients with multiple organ dysfunction syndrome. The patients were able to bear at the quality better.

Effect of Continuous Blood Purification on Endotoxin Receptor and Signal Transduction of Patients with Multiple Organ Dysfunction Syndrome / 医学研究杂志

Objective To investigate the effct of continuous blood purification(CBP)on endotoxin receptor and signal transduction of patients with multiple organ dysfunction syndrome(MODS).Methods Thirty patients with MODS were selected and treated with low volume and high volume haemofiltration.Plasma level of TNF-?、IL-6 were messured before and after CBP at 6h,1d,3d.Express of PMN CD14mRNA,CD14 protein and activity of NF-?B were also observed.Results CBP had no effect on TNF-?,and plasma IL-6 decreased significantly(P