The CEBPE rs2239633 genetic polymorphism on susceptibility to childhood acute lymphoblastic leukemia: an updated meta-analysis

OBJECTIVES@#We performed an updated meta-analysis to clarify the relationship between the CEBPE rs2239633 polymorphism and the childhood acute lymphoblastic leukemia (CALL) susceptibility.@*METHODS@#All the case-control studies were updated on October 5, 2020, through Web of Science, PubMed, Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) electronic database. The heterogeneity in the study was tested by the Q test and I@*RESULTS@#A total of 20 case-control studies were selected, including 7014 patients and 16,428 controls. There was no association of CEBPE rs2239633 polymorphism with CALL (CC vs CT + TT: OR = 1.08, 95% CI = 0.94-1.26; CC + CT vs TT: OR = 1.10, 95% CI = 0.94-1.30; C vs T: OR = 1.02, 95% CI = 0.92-1.13). In the subgroup analysis by ethnicity, there is no significant association of this polymorphism and CALL risks among Asian and Caucasian populations in the three genetic models (CC vs CT + TT, CC + CT vs TT, and C vs T).@*CONCLUSION@#This meta-analysis found no significant association between the CEBPE rs2239633 polymorphism and susceptibility to CALL.

Efficacy of Haploidentical Hematopoietic Stem Cell Transplantation in Treatment of Intermediate Risk Acute Myeloid Leukemia with Negative for FLT3-ITD, NPM1 or Biallelic CEBPA Mutation / 中国实验血液学杂志

OBJECTIVE@#To compare the efficacy of haploidentical hematopoietic stem cell transplantation (hi-HSCT) HLA-matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and post-remission chemotherapy (PR-CT) in treatment of intermediate risk acute myeloid leukemia with negative for FLT3-ITD, NPM1 or biallelic CEBPA mutation.@*METHODS@#The clinical data of patients with intermediate risk NPM1/non-CEBPA/FLT3-ITD AML from October 2009 to May 2016 were retrospectively analyzed.@*RESULTS@#The overall survival rate of the patients treated with PR-CT, MSD-HSCT or hi-HSCT was 63.7%, 71.7%, 75.5%, respectively (P＜0.05); the disease-free survival (DFS) rate was 52.8%, 67.1%, 71.3% respectively (P＜0.001); the cumulative incidence of relapse was 24.7%, 16.9%, 14.4% respectively (P＜0.05); the non-relapse mortality was 26.2%, 17.3%, 14.4% reapectively (P＞0.05). The analysis of transplantation, related adverse events showed that II-IV grade of aGVHD in the MSD-HSCT group and hi-HSCT group was 48.9% and 45.6% respectively (P＞0.05); the extensive cGVHD event was 21.6% and 8.8% (P＜0.05) respectively.@*CONCLUSION@#The efficiency of hi-HSCT and MSD-HSCT is superior to that of PR-CT for treatment of patients with intermediate risk NPM1/non-CEBPA/FLT3-ITD AML after CR1, there is no statistically significant difference in the efficiency of consolidatorg treatment and the transplantation-related mortality between hi-HSCT and MSD-HSCT.

CD7 expression and its prognostic significance in acute myeloid leukemia patients with wild-type or mutant CEBPA / 中华血液学杂志

Objective: To analyze the prognostic value of CD7 expression in newly diagnosed acute myeloid leukemia (AML) patients, and to further explore the correlation between CD7 expression and CEBPA mutation, and to clarify the prognostic value of CD7(+) in AML patients with wild-type (WT) or mutant-type (MT) CEBPA. Methods: The clinical data of 298 newly diagnosed non-M(3) AML patients between January 2010 and December 2016 were analyzed retrospectively. The clinical characteristics and prognosis of CD7(+) and CD7(-) patients were respectively compared in all patients, and in patients with WT and MT CEBPA. The relationship between CD7 expression and CEBPA mutation was determined by chi-square, and the effects of CEBPA mutation on survival and prognosis in CD7(+) group by Kaplan-Meier method. Results: In CD7(+) group, the frequencies of CEBPA mutation were 10.1% (single site) and 33.9% (double site) , significantly higher than those of the CD7(-) group (5.3% and 4.2%) (P=0.000) . Subgroup prognostic analysis showed a lower CR rate (P=0.001) and a higher RR (P=0.023) in CD7(+) group comparing to those of CD7(-) group in AML patients with wild type CEBPA. There were no statistical difference between CD7(+) group and CD7(-) group in overall survival (OS) and disease free survival (P>0.05) , while in the CEBPA mutant group the CD7(+) group has higher OS (P=0.019) and DFS (P=0.010) . Based on the CD7 expression and CEBPA mutation, 298 cases were divided into 3 subgroups, named as CD7(+)-CEBPA MT group, CD7(-) and CD7(+)-CEBPA WT group. The 3-year OS of the 3 groups were 80.2%, 48.0% and 30.6%, respectively (P<0.001) , and the 3-year DFS were 74.1%, 37.4% and 22.2%, respectively (P<0.001) . Conclusion: The CEBPA mutation rate was higher in CD7(+) AML patients then that of CD7(-) patients. CD7 expression has opposite prognostic significance in AML patients carrying the wild-type or mutant-type CEBPA. Based on CD7 expression and CEBPA mutation, a new risk stratification model can be established, which is helpful to guide the clinical individualized treatment for AML patients.

Endoplasmic Reticulum Stress Induces MUC5AC and MUC5B Expression in Human Nasal Airway Epithelial Cells

OBJECTIVES: Endoplasmic reticulum (ER) stress is known to be associated with inflammatory airway diseases, and three major transmembrane receptors: double-stranded RNA-activated protein kinase-like ER kinase, inositol requiring enzyme 1, and activating transcription factor 6 (ATF6) play important roles in ER stress-related proinflammatory signaling. However, the effects of ER stress and these three major signaling pathways on the regulation of the production of airway mucins in human nasal airway epithelial cells have not been elucidated. METHODS: In primary human nasal epithelial cells, the effect of tunicamycin (an ER stress inducer) and 4-phenylbutyric acid (4-PBA, ER stress inhibitor) on the expression of MUC5AC and MUC5B was investigated by reverse transcriptasepolymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and immunoblot analysis. Small interfering RNA (siRNA) transfection was used to identify the mechanisms involved. RESULTS: Tunicamycin increased the expressions of MUC5AC and MUC5B and the mRNA expressions of ER stress-related signaling molecules, including spliced X-box binding protein 1 (XBP-1), transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP), and ATF6. In addition, 4-PBA attenuated the tunicamycin-induced expressions of MUC5AC and MUC5B and the mRNA expressions of ER stress-related signaling molecules. Furthermore, siRNA knockdowns of XBP-1, CHOP, and ATF6 blocked the tunicamycin-induced mRNA expressions and glycoprotein productions of MUC5AC and MUC5B. CONCLUSION.: These results demonstrate that ER stress plays an important role in the regulation of MUC5AC and MUC5B via the activations of XBP-1, CHOP, and ATF6 in human nasal airway epithelial cells.

Mutation profiling of 16 candidate genes in de novo acute myeloid leukemia patients / 医学前沿

This retrospective analysis aimed to investigate the mutation profile of 16 common mutated genes in de novo acute myeloid leukemia (AML) patients. A total of 259 patients who were diagnosed of de novo AML were enrolled in this study. Mutation profiling of 16 candidate genes were performed in bone marrow samples by using Sanger sequencing.We identified at least 1 mutation in 199 of the 259 samples (76.8%), and 2 or more mutations in 31.7% of samples. FLT3-ITD was the most common mutated gene (16.2%, 42/259), followed by CEBPA (15.1%, 39/259), NRAS (14.7%, 38/259), and NPM1 (13.5%, 35/259). Concurrence was observed in 97.1% of the NPM1 mutated cases and in 29.6% of the double mutated CEBPA cases. Distinct patterns of co-occurrence were observed for different hotspot mutations within the IDH2 gene: R140 mutations were associated with NPM1 and/or FLT3-ITD mutations, whereas R172 mutations co-occurred with DNMT3A mutations only. Concurrence was also observed in 86.6% of epigenetic regulation genes, most of which co-occurred with NPM1 mutations. The results showed certain rules in the mutation profiling and concurrence of AML patients, which was related to the function classification of genes. Defining the mutation spectrum and mutation pattern of AML will contribute to the comprehensive assessment of patients and identification of new therapeutic targets.

The protective effect of dexmedetomidine in a rat ex vivo lung model of ischemia-reperfusion injury

Abstract Purpose: To investigate the effect of dexmedetomidine (Dex) in a rat ex vivo lung model of ischemia-reperfusion injury. Methods: An IL-2 ex vivo lung perfusion system was used to establish a rat ex vivo lung model of ischemia-reperfusion injury. Drugs were added to the perfusion solution for reperfusion. Lung injury was assessed by histopathological changes, airway pressure (Res), lung compliance (Compl), perfusion flow (Flow), pulmonary venous oxygen partial pressure (PaO2), and lung wet/dry (W/D) weight ratio. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), 78 kDa glucose-regulated protein (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) were measured, respectively. Results: The introduction of Dex attenuated the post-ischemia-reperfusion lung damage and MDA level, improved lung histology, W/D ratio, lung injury scores and SOD activity. Decreased mRNA and protein levels of GRP78 and CHOP compared with the IR group were observed after Dex treatment. The effect of Dex was dosage-dependence and a high dose of Dex (10 nM) was shown to confer the strongest protective effect against lung damage (P<0.05). Yohimbine, an α2 receptor antagonist, significantly reversed the protective effect of Dex in lung tissues (P<0.05). Conclusion: Dex reduced ischemia-reperfusion injury in rat ex vivo lungs.

Inhibition of endoplasmic reticulum stress in high-fat-diet-induced obese C57BL/6 mice: Efficacy of a novel extract from mulberry (Morus alba) leaves fermented with Cordyceps militaris / 한국실험동물학회지

A few clues about correlation between endoplasmic reticulum (ER) stress and mulberry (Morus alba) leaves were investigated in only the experimental autoimmune myocarditis and streptozotocin-induced diabetes. To investigate whether a novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) could suppress ER in fatty liver, alterations in the key parameters for ER stress response were measured in high fat diet (HFD)-induced obese C57L/6 mice treated with EMfC for 12 weeks. The area of adipocytes in the liver section were significantly decreased in the HFD+EMfC treated group as compared to the HFD+Vehicle treated group, while their level was higher in HFD+Vehicle treated group than No treated group. The level of the eukaryotic initiation factor 2 alpha (eIF2α) and inositol-requiring enzyme 1 beta (IRE1α) phosphorylation and CCAAT-enhancer-binding protein homologous protein (CHOP) expression were remarkably enhanced in the HFD+Vehicle treated group. However, their levels were restored in the HFD+EMfC treated group, although some differences were detected in the decrease rate. Similar recovery was observed on the ER stress-induced apoptosis. The level of Caspase-3, Bcl-2 and Bax were decreased in the HFD+EMfC and HFD+orlistat (OT) treated group compared to the HFD+Vehicle treated group. The results of the present study therefore provide first evidence that EMfC with the anti-obesity effects can be suppressed ER stress and ER stress-induced apoptosis in the hepatic steatosis of HFD-induced obesity model.

Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer

ABSTRACT Introduction Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). Objective The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients’ clinical outcome. Materials and Methods In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction. Results UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease. Conclusions The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.

Cadmium-induced ER stress and inflammation are mediated through C/EBP–DDIT3 signaling in human bronchial epithelial cells

Cadmium (Cd), a major component of cigarette smoke, disrupts the normal functions of airway cells and can lead to the development of various pulmonary diseases such as chronic obstructive pulmonary disease (COPD). However, the molecular mechanisms involved in Cd-induced pulmonary diseases are poorly understood. Here, we identified a cluster of genes that are altered in response to Cd exposure in human bronchial epithelial cells (BEAS-2B) and demonstrated that Cd-induced ER stress and inflammation are mediated via CCAAT-enhancer-binding proteins (C/EBP)-DNA-damaged-inducible transcript 3 (DDIT3) signaling in BEAS-2B cells. Cd treatment led to marked upregulation and downregulation of genes associated with the cell cycle, apoptosis, oxidative stress and inflammation as well as various signal transduction pathways. Gene set enrichment analysis revealed that Cd treatment stimulated the C/EBP signaling pathway and induced transcriptional activation of its downstream target genes, including DDIT3. Suppression of DDIT3 expression using specific small interfering RNA effectively alleviated Cd-induced ER stress and inflammatory responses in both BEAS-2B and normal primary normal human bronchial epithelial cells. Taken together, these data suggest that C/EBP signaling may have a pivotal role in the early induction of ER stress and inflammatory responses by Cd exposure and could be a molecular target for Cd-induced pulmonary disease.

Transcription Factors Regulating Inflammatory Cytokine Production Are Differentially Expressed in Peripheral Blood Mononuclear Cells of Behçet Disease Depending on Disease Activity

BACKGROUND: Behçet disease (BD) is a relapsing inflammatory disease with increased production of inflammatory cytokines in peripheral blood mononuclear cells (PBMCs); however, the underlying molecular mechanisms are not well known. OBJECTIVE: To analyze whether the differential expression of transcription factors is involved in the increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production by PBMCs of BD patients compared to healthy controls (HCs). METHODS: Expression of transcription factors was examined by real-time reverse transcriptase-polymerase chain reaction and western blotting. Cytokine production by CD11b+ cells transfected with siRNAs against transcription factors was measured by enzyme-linked immunosorbent assay. RESULTS: In the absence of lipopolysaccharide stimulation, the transcript level of CCAAT-enhancer-binding proteins (C/EBP) β was increased in PBMCs from patients with active BD compared to that in PBMCs from patients with stable BD. The C/EBPδ transcript level was higher in PBMCs from patients with active BD than in those from HCs. The activating transcription factor 3 (ATF3) transcript level was increased in PBMCs from patients with stable BD compared to that in PBMCs from HCs. siRNAs targeting C/EBPβ and C/EBPδ significantly reduced the production of IL-6 and TNF-α in lipopolysaccharide-stimulated CD11b+ cells from patients with BD as well as from HCs. CONCLUSION: We found differential expression of C/EBPβ, C/EBPδ, and ATF3 in PBMCs from patients with BD depending on disease activity, indicating the involvement of these molecules in BD pathogenesis.

Family care of people with severe mental disorders: an integrative review / Cuidado familiar de pessoas com doenças mentais graves: uma revisão integrativa / Cuidado familiar de la persona con trastorno mental grave: una revisión integradora

OBJECTIVE: to analyze the scientific literature on home-based family care of people with severe mental illness. METHOD: integrative review of 14 databases (CINALH, Cochrane Plus, Cuidatge, CUIDEN, Eric, IBECS, EMI, ISOC, JBI COnNECT, LILACS, PsycINFO, PubMed, SciELO, and Scopus) searched with the key words "family caregivers", "severe mental illness", and "home" between 2003 and 2013. RESULTS: of 787 articles retrieved, only 85 met the inclusion criteria. The articles appeared in 61 journals from different areas and disciplines, mainly from nursing (36%). The countries producing the most scientific literature on nursing were Brazil, the UK, and the US, and authorship predominantly belonged to university centers. A total of 54.12% of the studies presented quantitative designs, with descriptive ones standing out. Work overload, subjective perspectives, and resources were the main topics of these papers. CONCLUSIONS: the international scientific literature on home-based, informal family care of people with severe mental disorder is limited. Nursing research stands out in this field. The prevalent topics coincide with the evolution of the mental health system. The expansion of the scientific approach to family care is promoted to create evidence-based guidelines for family caregivers and for the clinical practice of professional caregivers. .

OBJETIVO: analisar a produção científica sobre o cuidado familiar de pessoas com transtorno mental grave em casa. MÉTODO: revisão integrativa de 14 bases de dados (CINALH, Cochrane Plus, Cuidatge, CUIDEN, Eric, IBECS, EMI, ISOC, JBI Connect, LILACS, PsycInfo e PubMed, SciELO, e Scopus), com as palavras-chave "cuidadores familiares", "TMG" (transtornos mentais graves ) e "casa", realizada entre 2003 e 2013. RESULTADOS: dos 787 artigos retornados, somente 85 atenderam os critérios de inclusão. Os artigos vieram de 61 periódicos de diferentes áreas e disciplinas, principalmente de enfermagem (36%). Os países com maior produção científica sobre enfermagem foram o Brasil, o Reino Unido e os Estados Unidos, e a autoria era predominantemente de centros universitários. Um total de 54,12% dos estudos apresentou delineamento quantitativo, e os descritivos se destacaram. Os principais temas desses trabalhos foram sobrecarga de trabalho, perspectivas subjetivas e recursos. CONCLUSÕES: a produção cientifica internacional sobre o cuidado familiar informal de pessoas com doenças mentais graves em casa é limitada. A pesquisa em enfermagem se destaca nesse campo. Os temas prevalentes coincidem com a evolução do sistema de saúde mental. Estimula-se a expansão da abordagem científica do cuidado familiar de modo a encontrar evidências para criar guias para cuidadores familiares e para a prática clínica de cuidadores profissionais. .

OBJETIVO: analizar la producción científica sobre el cuidado familiar de la persona con trastorno mental grave en el hogar familiar. MÉTODO: revisión integradora en 14 bases de datos (CINALH, Cochrane Plus, Cuidatge, CUIDEN, Eric, IBECS, IME, ISOC, JBI ConNECT, LILACS, PsycInfo, PubMed, SciELO y Scopus), con las palabras clave "cuidadores familiares", "TMG" y "hogar"; realizada entre 2003 y 2013. RESULTADOS: de 787 artículos recuperados, sólo 85 cumplieron con los criterios de inclusión. Los artículos procedieron de 61 revistas de diferentes áreas y disciplinas destacando la disciplina de enfermería (36%). Los países con mayor producción científica sobre enfermería fueron Brasil, Reino Unido y EEUU. En la autoría predominaron los centros universitarios. El 54,12% de los estudios presentó diseño cuantitativo, sobresaliendo los descriptivos. Las temáticas destacadas fueron sobrecarga, perspectivas subjetivas y recursos. CONCLUSIONES: la producción científica internacional sobre el cuidado informal familiar de la persona con trastorno mental grave, en el contexto del hogar familiar, es limitada. En este campo, destaca la investigación de enfermería. Las temáticas prevalentes coinciden con la evolución del sistema de salud mental. Se estimula la ampliación del abordaje científico del cuidado familiar con el fin de encontrar evidencias para la elaboración de guías de cuidadores familiares y para la práctica clínica de cuidadores profesionales. .

Effects of chrysophanol on expression of SREBPs and lipid metabolism in Huh-7 cells / 药学学报

Rhubarb is a traditional Chinese medicines which possess laxative, lipid-lowering, and weight-loss activities, but the active compounds of lipid-lowering and underlying molecular mechanisms are not yet clear. This study aims to explore the effects of chrysophanol on the mRNA expressions of sterol regulatory element-binding proteins (SREBPs) and lipid metabolism in human liver carcinoma Huh-7 cells, which is one of the active compounds obtained from Rhubarb. A reporter gene assay was used to test the transcription of SREBP. The intracellular triglyceride and total cholesterol contents were measured by using commercially available test kits. The SREBPs target genes expressions were measured by Quantitative Real-Time PCR. Cell viability was evaluated by Cell Counting Kit-8. As the results shown, chrysophanol (40 μmol · L(-1), 16 h) could notably inhibited human SRE promoter activity in a dose-dependent manner and decrease intracellular cholesterol and triglyceride levels. Furthermore, the mRNA expressions of SREBPs target genes were significantly downregulated by chrysophanol treatment. However there are no significant differences on cell viability when compared with the control group. These results suggested that chrysophanol might improve lipid metabolism through suppressing the mRNA expressions of SREBPs target genes to attenuate intracellular lipid accumulation.

Recent Advances of Research on CEBPA Mutation in Acute Myeloid Leukemia / 中国实验血液学杂志

CCAAT/enhancer binding protein alpha gene (CEBPA) is an important transcription factor in maintenance of differentiation of granulocyte series of hematopoietic system. It plays a key role in regulating cell proliferation and differentiation. CEBPA mutation easily occurs in M1 and M2 type of acute myeloid leukemia, about 5%-14% in adult acute myeloid leukemia and 7.9% in children with acute myeloid leukemia. At present, domestic CEBPA mutation research is far less than abroad. This review focuses on the structual characteristics and detection method of CEBPA, CEBPA clinical features, the effect of CEBPA mutation on the prognosis of patients and the choice of treatment.

Expression and significance of C/EBPα and CK10 in nasal inverted papilloma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#The expression of C/EBPα, CK10 in nasal inverted papilloma (NIP) were detected in the study. Further discussed their significance in genesia, development and recurrence of NIP.@*METHOD@#Three groups including nasal cavity mucosae (NM 10 cases), nasal polyp (NP 20 cases) and NIP (30 cases) were selected in the study. Expretion of C/EBPα, CK10 were detected by immunohistochemisty PV-6000 method.@*RESULT@#(1) The different expression of C/EBPα and CK10 in the group of NM, NP and NIP was statistically significant (P < 0.05). (2) The different expression of C/EBPα, CK10 in the group of benign NIP and NIP with atypical hyperplasia was statistically significant (P < 0.05). (3) The different expression of C/EBPα and CK10 in the group of NIP with recurrence and NIP with no recurrence was statistically significant, P < 0.05, respectively. (4) Our result indicate that the relationship of C/EBPα and CK10 (r = 0.578, P < 0.01) was direct correlation. The difference was statistically significant.@*CONCLUSION@#In conclusion, the present results describe C/EBPα, CK10 expression in NIP and their possible implication in the regulation of tumor growth and differentiation. C/EBPα and CK10 production may prove useful in terms of a prognostic marker for the recurrence in nasal inverted papilloma.

A study of the lipoprotein lipase inhibitory mechanism of Poncirus trifoliata water extracts / 한국영양학회지

PURPOSE: Poncirus trifoliata has been reported to have anti-inflammatory, antioxidant, and immune activities. However, its anti-obesity activity and the mechanism by which the water extract of dried, immature fruit of Poncirus trifoliata (PF-W) acts are not clear. This study suggests a potential mechanism associated with the anti-obesity activity of PF-W. METHODS: We measured the effect of PF-W on lipoprotein lipase (LPL) regulation using enzyme-linked immunosorbent assay (ELISA) and an activity assay. The LPL regulation mechanism was examined by reverse transcription polymerase chain reaction (RT-PCR) to measure the mRNA expression of biomarkers related to protein transport and by western blot for analysis of the protein expression of the transcription factor CCAAT-enhancer-binding protein (C/EBPbeta) RESULTS: The total polyphenol and flavonoid content of PF-W was 52.15 +/- 4.02 and 6.56 +/- 0.47 mg/g, respectively. PF-W treatment decreased LPL content in media to 58 +/- 5% of that in control adipocyte media, and increased LPL content to 117 +/- 3.5% of that in control adipocytes, but did not affect the mRNA expression of LPL. PF-W also increased the mRNA expression of sortilin-related receptor (SorLA), a receptor that induces endocytosis and intracellular trafficking of LPL, in a concentration- and time-dependent manner. Finally, cell fractionation revealed that PF-W treatment induced the expression of C/EBPbeta, a SorLA transcription factor, in the nuclei of 3T3-L1 adipocytes. CONCLUSION: The LPL secretion and activity assay showed PF-W to be an LPL secretion inhibitor, and these results suggest the potential mechanism of PF-W involving inhibition of LPL secretion through C/EBPbeta-mediated induction of SorLA expression.

Incidences and Prognostic Impact of c-KIT, WT1, CEBPA, and CBL Mutations, and Mutations Associated With Epigenetic Modification in Core Binding Factor Acute Myeloid Leukemia: A Multicenter Study in a Korean Population

BACKGROUND: To identify potential molecular prognostic markers in core binding factor (CBF) AML, we analyzed incidences and prognostic impacts of mutations in c-KIT, WT1, CEBPA, CBL, and a number of epigenetic genes in CBF AML. METHODS: Seventy one and 21 AML patients with t(8;21) and inv(16) were enrolled in this study, respectively. NPM1, CEBPA, c-KIT, IDH1/2, DNMT3A, EZH2, WT1, and CBL mutations were analyzed by direct sequencing. Patients were categorized with respect to c-KIT and WT1 mutation status, and both clinical features and prognoses were compared. RESULTS: The incidences of FLT3 internal tandem duplication (ITD), NPM1, CEBPA, IDH1/2, DNMT3A, EZH2, and CBL mutations were low (< or =5%) in CBF AML patients. However, c-KIT and WT1 mutations occurred frequently (10.9% and 13.8%, respectively). t(8;21) patients with c-KIT mutations showed significantly shorter overall survival (OS) and disease free survival (DFS) periods than those without mutations (P<0.001, for both); however, although the limited number of t(8;21) patients were analyzed, WT1 mutation status did not affect prognosis significantly. Relapse or death during follow-up occurred more frequently in t(8;21) patients carrying c-KIT mutations than in those without the mutation, although the difference was significant only in a specific patient subgroup with no WT1 mutations (P=0.014). CONCLUSIONS: The incidences of mutations in epigenetic genes are very low in CBF AML; however, c-KIT and WT1 mutations occur more frequently than others. The poor prognostic impact of c-KIT mutation in t(8;21) AML patients only applies in a specific patient subgroup without WT1 mutations. The prognostic impact of WT1 mutation in CBF AML is not evident and further investigation is required.

NPM1 and CEBPA mutations in pediatric cytogenetically normal acute myeloid leukemia / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the frequency of the nucleophosmin (NPM1) gene and the CCAAT/enhancer binding protein α gene (CEBPA) through polymerase chain reaction (PCR) array in pediatric patients with cytogenetically normal acute myeloid leukemia (CN-AML) and explore the clinical significances of these mutations.</p><p><b>METHOD</b>Between August 2009 and December 2012, 30 children (<16 years old) with newly diagnosed CN-AML were included. The clinical characteristics were analyzed in these patients. PCR combined with direct sequencing was used to detect NPM1, CEBPA gene mutations. All the data were statistically analyzed using SPSS17.0 software.</p><p><b>RESULT</b>The gene mutations were detected in each of the 30 patients. NPM1 mutation was positive in three patients (10%) with type A mutation, while CEBPA mutation was positive in two patients (6.7%) with double mutations (TAD, bZIP) . Besides, FLT3/ITD mutation was positive in three patients. Patients with NPM1 or FLT3/ITD had a significantly elevated diagnostic WBC count with a median diagnostic WBC count of 102.80×10(9)/L compared with 18.56×10(9)/L for the patients without mutations(t = 2.353, P = 0.043), as well as the marrow blast percentage (94.0% vs. 80.0%, t = 3.804, P = 0.002). The complete remission was achieved in all the 3 patients with NPM1 mutations and 2 patients with CEBPA mutations. All the patients with these mutations also achieved 2-year event-free survival (EFS) and 2-year overall survival (OS), while 2-year EFS and 2-year OS of the other patients were (40.1 ± 11.2)% and (51.8 ± 10.9)% (P = 0.044, 0.091, respectively).</p><p><b>CONCLUSION</b>NPM1 and CEBPA mutations may indicate a favorable prognosis in pediatric CN-AML.</p>

Clinical characteristics and therapeutic efficacy of normal karyotype AML patients with CEBPA mutation / 中国实验血液学杂志

This study was aimed to explore the clinical characteristics and therapeutic efficacy of normal karyotype AML patients with CEBPA mutations. Fifty-five de novo AML patients with normal karyotype were retrospectively analyzed with regard to frequency of CEBPA mutation, clinical characteristics and therapeutic response. The results showed that CEBPA mutation was detected in 20 patients (36.4%), among them 17 cases displayed double mutations, three cases were with single mutation. The clinical characteristics of patients with CEBPA mutation displayed as follows: 75% of AML patients with CEBPA mutation were AML-M1 and AML-M2, the hemoglobin level at newly diagnosis was higher and the platelet count at newly diagnosis time was lower than those of AML patients without CEBPA mutation [(98.30 ± 20.33) g/L vs (81.69 ± 23.74) g/L (P < 0.05); and (33.30 ± 38.27) ×10(9)/L vs (64.79 ± 61.60) ×10(9)/L (P < 0.05)]. The leukemic cells highly expressed CD7 and CD34. The therapeutic efficacy of 1 cycle for AML patients with CEBPA mutation was satisfactory (72.2%), was higher than that of patients without CEBPA mutation(68.6%), but there was no statistical significance (P > 0.05). It is concluded that AML with CEBPA mutation is more observed in AML-M1 and AML-M2, and accompanies by high level of hemoglobin and lower platelet count, expression of CD7 and CD34. Early-term therapeutic efficacy is satisfactory. The frequency of CEBPA mutation may be higher in Chinese patients with AML compared with that reported in Western world.

Anti-adipogenic effect of mulberry leaf ethanol extract in 3T3-L1 adipocytes

BACKGROUND/OBJECTIVES: Adipogenesis is part of the cell differentiation process in which undifferentiated fibroblasts (pre-adipocytes) become mature adipocytes with the accumulation of lipid droplets and subsequent cell morphological changes. Several transcription factors and food components have been suggested to be involved in adipogenesis. The aim of this study was to determine whether mulberry leaf ethanol extract (MLEE) affects adipogenesis in 3T3-L1 adipocytes. MATERIALS/METHODS: The 3T3-L1 adipocytes were treated with different doses of MLEE for 8 days starting 2 days post-confluence. Cell viability, fat accumulation, and adipogenesis-related factors including CCAAT-enhancer-binding protein alpha (C/EBPalpha), peroxisome proliferator-activated receptor gamma (PPARgamma), PPARgamma coactivator 1 alpha (PGC-1alpha), fatty acid synthase (FAS), and adiponectin were analyzed. RESULTS: Results showed that MLEE treatments at 10, 25, 50, and 100 microg/ml had no effect on cell morphology and viability. Without evident toxicity, all MLEE treated cells had lower fat accumulation compared with control as shown by lower absorbances of Oil Red O stain. MLEE at 50 and 100 microg/ml significantly reduced protein levels of PPARgamma, PGC-1alpha, FAS, and adiponectin in differentiated adipocytes. Furthermore, protein level of C/EBPalpha was significantly decreased by the treatment of 100 microg/ml MLEE. CONCLUSION: These results demonstrate that MLEE treatment has an anti-adipogenic effect in differentiated adipocytes without toxicity, suggesting its potential as an anti-obesity therapeutic.

CEBPA gene mutation analysis in acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the incidence, molecular features and clinical significance of CCAAT/enhancer binding protein alpha (CEBPA) gene mutation in patients with acute myeloid leukemia (AML).</p><p><b>METHODS</b>Mutation analysis of the entire coding region of CEBPA gene in 206 de novo AML patients was performed by using polymerase chain reaction (PCR) followed by sequence analysis and fragment length analysis.</p><p><b>RESULTS</b>Of 206 AML patients, 31 (15%) had CEBPA gene mutations, including 23 with double mutations (duCEBPA) and 8 with single mutation (siCEBPA). CEBPA gene mutations presented mainly in M2 subtype or intermediate risk patients. As compared with those with wild type CEBPA gene, patients with mutated CEBPA gene were of higher white blood cell counts [20.92(0.86-351.43)× 10(9)//L vs 8.17(0.47-295.2) × 10(9)/L, P=0.003], higher hemoglobin levels [97.5(51-128) g/L vs 80.5(13-153) g/L, P=0.015] and lower platelet counts [27.5(5-81)× 10(9)//L vs 44(3-548)× 10(9)/L, P=0.004]. Patients with CEBPA gene mutation had higher complete remission (CR) rate than those with wild type (P=0.009). While co-existing of NPM1 and siCEBPA mutations was observed in M5 subtype (2/8, 25%), NPM1 gene mutation was not present in any patients with duCEBPA mutation (0/23, 0%). Dynamic tracking analysis showed that CEBPA mutations disappeared at CR, and the same mutations re-appeared at relapse. When compared to sequence analysis, the coincidence rate of CEBPA mutations detected by fragment length analysis was 100% (54/54).</p><p><b>CONCLUSION</b>CEBPA gene mutation is a recurring genetic change in AML patients and has a certain correlation with clinical and laboratory features. It could be reliably used as a potential marker for minimal residual disease follow up. The prognostic significance of co-existing of siCEBPA with NPM1 mutations in patients with AML-M5 subtype needs further investigation.</p>