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1.
Article in English | WPRIM | ID: wpr-880568

ABSTRACT

OBJECTIVE@#To investigate whether blood-brain barrier (BBB) served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points (HTWP) in traumatic brain injury (TBI) and the potential molecular signaling pathways.@*METHODS@#Adult male Sprague-Dawley rats were assigned to the sham-operated (sham), TBI, and bloodletting puncture (bloodletting) groups (n=24 per group) using a randomized number table. The TBI model rats were induced by cortical contusion and then bloodletting puncture were performed at HTWP twice a day for 2 days. The neurological function and cerebral edema were evaluated by modified neurological severity score (mNSS), cerebral water content, magnetic resonance imaging and hematoxylin and eosin staining. Cerebral blood flow was measured by laser speckles. The protein levels of aquaporin 4 (AQP4), matrix metalloproteinases 9 (MMP9) and mitogen-activated protein kinase pathway (MAPK) signaling were detected by immunofluorescence staining and Western blot.@*RESULTS@#Compared with TBI group, bloodletting puncture improved neurological function at 24 and 48 h, alleviated cerebral edema at 48 h, and reduced the permeability of BBB induced by TBI (all P<0.05). The AQP4 and MMP9 which would disrupt the integrity of BBB were downregulated by bloodletting puncture (P<0.05 or P<0.01). In addition, the extracellular signal-regulated kinase (ERK) and p38 signaling pathways were inhibited by bloodletting puncture (P<0.05).@*CONCLUSIONS@#Bloodletting puncture at HTWP might play a significant role in protecting BBB through regulating the expressions of MMP9 and AQP4 as well as corresponding regulatory upstream ERK and p38 signaling pathways. Therefore, bloodletting puncture at HTWP may be a promising therapeutic strategy for TBI-induced cerebral edema.

2.
Article in Chinese | WPRIM | ID: wpr-880155

ABSTRACT

OBJECTIVE@#To investigate the quantitative expression of immunophenotype of CD34@*METHODS@#Multi-parameter flow cytometry (FCM) was used to detect the proportion and mean fluorescence intensity (MFI) of each antigen of bone marrow CD34@*RESULTS@#Bone marrow blast cell proportion (P<0.01), RBC level (P<0.01), and Hb level (P<0.05) of high-risk MDS patients were higher, while EPO level (P<0.05) was lower than those of low-risk patients. The proportion of CD34@*CONCLUSION@#The immunophenotype of CD34


Subject(s)
Antigens, CD34 , Bone Marrow , Bone Marrow Cells , Flow Cytometry , Humans , Immunophenotyping , Myelodysplastic Syndromes
3.
Article in Chinese | WPRIM | ID: wpr-829043

ABSTRACT

OBJECTIVE@#To investigate the effect of other gene mutations outside the fusion gene on the first complete remission (CR) induced by one course of induction chemotherapy in patients with core binding factor-associated acute myeloid leukemia (CBF-AML).@*METHODS@#DNA was extracted from bone marrow or peripheral blood samples of newly diagnosed CBF-AML patients admitted to the Hematology Department of the Second Hospital of Shanxi Medical University from January 2015 to January 2019. Next-generation sequencing was used for detection of 34 kinds of hematologic malignancy-related gene mutations in patients with CBF-AML, the effect of related gene mutations on the first complete remission (CR) rate in one course of induction chemotherapy was analyzed by combineation with clinical characteristics.@*RESULTS@#34 kinds of genes in bone marrow or peripheral blood of 43 patients were detected by high throughput sequencing and the gene mutations were detected in 16 out of 34 genes. The mutation rate of KIT gene was the highest (48.8%), followed by NRAS (16.3%), ASXL1 (16.3%), TET2 (11.6%), CSF3R (9.3%), FLT3 (9.3%), KRAS (7.0%). The detection rates of mutations in different functional genes were as follows: genes related with signal transduction pathway (KIT, FLT3, CSF3R, KRAS, NRAS, JAK2, CALR, SH2B3, CBL) had the highest mutation frequency (72.1% (31/43); epigenetic modification gene mutation frequency was 30.2% (13/43), including ASXL1, TET2, BCOR); transcriptional regulation gene mutation frequency was 7.0% (3/43), including ETV6, RUNX1, GATA2). Splicing factor related gene mutation frequency was 2.3% (1/43), including ZRSR2). The CR rate was 74.4% after one course of induction chemotherapy. At first diagnosis, patients with low expression of WT1 (the median value of WT1 was 788.9) were more likely to get CR (P=0.032) and the RFS of patients who got CR after one course of induction chemotherapy was significantly longer than that of patients without CR [7.6 (2.2-44.1) versus 5.8 (1-19.4), (P=0.048)]. The rate of CR in the signal transduction pathway gene mutation group was significantly lower than that in non-mutation group (64.5% vs 100%) (P=0.045), while the level of serum hydroxybutyrate dehydrogenase (HBDH) was significantly higher than that in non-mutation group [(418 (154-2702) vs 246 (110-1068)] (P=0.032). There was no difference in CD56 expression between the two groups (P=0.053), which was limited to the difference between (≥20%) expression and non-expression. (P=0.048).@*CONCLUSION@#CBF-AML patients with signal transduction pathway gene mutation are often accompanied by high HBDH level and CD56 expression, moreover, the remission rate induced by one course of treatment is low.


Subject(s)
High-Throughput Nucleotide Sequencing , Humans , Leukemia, Myeloid, Acute , Mutation , Prognosis , Signal Transduction
4.
Chinese Journal of Hematology ; (12): 16-20, 2013.
Article in Chinese | WPRIM | ID: wpr-323458

ABSTRACT

<p><b>OBJECTIVE</b>To screen the potential protein biomarkers in minimal residual disease (MRD) of the acute promyelocytic leukemia (APL) by comparison of differentially expressed serum protein between APL patients at diagnosis and after complete remission (CR) and healthy controls, and to establish and verify a diagnostic model.</p><p><b>METHODS</b>Serum proteins from 36 cases of primary APL, 29 cases of APL during complete remission and 32 healthy controls were purified by magnetic beads and then analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The spectra were analyzed statistically using FlexAnalysis(TM) and ClinProt(TM) software.</p><p><b>RESULTS</b>Two prediction model of primary APL/healthy control, primary APL/APL CR were developed. Thirty four statistically significant peptide peaks were obtained with the m/z value ranging from 1000 to 10 000 (P < 0.001) in primary APL/healthy control model. Seven statistically significant peptide peaks were obtained in primary APL/APL CR model (P < 0.001). Comparison of the protein profiles between the two models, three peptides with m/z 4642, 7764 and 9289 were considered as the protein biomarker of APL MRD. A diagnostic pattern for APL CR using m/z 4642 and 9289 was established. Blind validation yielded correct classification of 6 out of 8 cases.</p><p><b>CONCLUSIONS</b>The MALDI-TOF MS analysis of APL patients serum protein can be used as a promising dynamic method for MRD detection and the two peptides with m/z 4642 and 9289 may be better biomarkers.</p>


Subject(s)
Adolescent , Adult , Aged , Case-Control Studies , Child , Humans , Leukemia, Promyelocytic, Acute , Classification , Diagnosis , Male , Middle Aged , Neoplasm, Residual , Classification , Diagnosis , Prognosis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Methods , Young Adult
5.
Chinese Journal of Hematology ; (12): 804-807, 2009.
Article in Chinese | WPRIM | ID: wpr-283903

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of AML1B and AML1/ETO fusion gene on the transcription activity of TSC1 and TSC2 promotor and to explore its role in leukemogenesis.</p><p><b>METHODS</b>The luciferase reporter plasmids of TSCs gene promoter containing a AML1 binding site were constructed, and cotransfected into CV-1 cells with AML1B or AML1/ETO expression plasmids separately. The transactivity of TSCs gene promoter was assayed by luminometer.</p><p><b>RESULTS</b>AML1B exhibited a transactivity to TSC2 gene promoter in a dosage-dependant manner, but showed no significant transactivity to TSC1's. The transactivity to TSC2 gene promoter showed 8.55 fold increase as companed with control group at 75 ng of pCMV5-AML/B. AML1/ETO showed a significant transactivity to TSC1, but no transactivity to TSC2's. However, AML1/ETO antagonized the effect of AMLlB to TSC2 gene promoter.</p><p><b>CONCLUSION</b>AML1B and AML1/ETO can regulate the transcription of TSC genes.</p>


Subject(s)
Binding Sites , Core Binding Factor Alpha 2 Subunit , Genetics , Humans , Oncogene Proteins, Fusion , Genetics , Plasmids , Promoter Regions, Genetic , Transcription Factors , Genetics , Transcriptional Activation
6.
Chinese Journal of Hematology ; (12): 289-292, 2008.
Article in Chinese | WPRIM | ID: wpr-240025

ABSTRACT

<p><b>OBJECTIVE</b>To explore the mechanism of PTEN gene expression silence in leukemia cells, and the effect of induced PTEN gene expression in leukemia cells.</p><p><b>METHODS</b>Methylation status of PTEN in leukemic cell lines, including HL-60, Nalm-6, NB4, U937, Raji, K562 and KG-1a was assessed by methylation specific PCR (MSP). The cell lines were then treated with different concentrations of methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR). After that the changes in PTEN methylation status were detected by MSP, and PTEN mRNA expression level by reverse transcription PCR (RT-PCR). Growth inhibition and apoptosis of HL-60 and Nalm-6 cells induced by 5-Aza-CdR were observed by MTT assay, and Wright and Annexin V staining, respectively.</p><p><b>RESULTS</b>Hypermethylation of PTEN promoter was detected in HL-60, U937, Nalm-6, Raji and KG-1a, while hypomethylation was found in NB4 and K562 by MSP. After 5-Aza-CdR treatment, the hypermethylation status of PTEN promoter in HL-60 and Nalm-6 cells was reversed and their PTEN mRNA expression levels were up regulated in dose dependent manner with the 5-Aza-CdR concentrations, and the cell apoptosis was induced.</p><p><b>CONCLUSION</b>Hypermethylation in the promoter region is one of major mechanisms responsible for transcriptional suppression of PTEN. Methyltransferase inhibitor could induce the expression of PTEN gene and lead to the leukemia cells apoptosis.</p>


Subject(s)
Cell Line, Tumor , DNA Methylation , Humans , Leukemia , Genetics , PTEN Phosphohydrolase , Genetics , Promoter Regions, Genetic , Genetics
7.
Chinese Journal of Hematology ; (12): 592-594, 2008.
Article in Chinese | WPRIM | ID: wpr-239978

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the expression of cell surface E-cadherin in leukemia cell and the correlation of cell membrane localization of beta-catenin with E-cadherin expression.</p><p><b>METHODS</b>Bone marrow samples from 46 patients with acute leukemia and 17 normal donors were analyzed. Cell surface expression of E-cadherin and membrane localization of beta-catenin were labeled by immunofluorescence and analyzed with a laser scanning confocal fluorescence microscope in 14 specimens.</p><p><b>RESULTS</b>Cell surface E-cadherin expression level was significantly lower in leukemia cells (with the median fluorescent intensity of 16.78) than in normal hematopoietic progenitors (26.03). Correlation analysis showed that cell membrane localization of beta-catenin was correlated with E-cadherin expression (r = 0.74, P = 0.002). After E-cadherin was induced to express in leukemic cell by 5-Aza-CdR, membranous expression of beta-catenin was elevated while the nuclear expression reduced, indicating that E-cadherin-mediated adhesions could recruit beta-catenin to cell membrane.</p><p><b>CONCLUSION</b>The loss of E-cadherin in leukemia cells may result in beta-catenin translocating to the nuclear and transcriptional activation of its target genes.</p>


Subject(s)
Cadherins , Metabolism , Case-Control Studies , Cell Membrane , Metabolism , Humans , Leukemia , Metabolism , Pathology , beta Catenin , Metabolism
8.
Chinese Journal of Hematology ; (12): 532-536, 2007.
Article in Chinese | WPRIM | ID: wpr-262989

ABSTRACT

<p><b>OBJECTIVE</b>To investigate pig7 expression level in acute leukemia (AL) and its clinical significance and explore the possible mechanisms for pig7 silence in terms of methylation control.</p><p><b>METHODS</b>Expression levels of pig7 mRNA in bone marrow samples from 138 patients with de novo AL and 21 normal controls and in 6 leukemic cell lines were detected by quantitative real-time reverse transcription PCR (RT-PCR). Differentiation induction effect by all-trans retinoic acid (ATRA) and concomitant change in pig7 expression were also monitored in NB4 cells. Endonuclease analysis was employed to determined the identity of pig7 transcript present in AL samples. Methylation specific PCR (MSP) was used to elucidate if hypermethylation was responsible for pig7 silence in AL.</p><p><b>RESULTS</b>Compared with that in normal control, pig7 expression was markedly decreased (0.62 vs 18.30, median, P < 0.01) in AL patients on progression (at diagnosis, relapse or refractory). No significant difference was observed between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). AL at diagnosis had a higher pig7 level than those with relapsed or refractory disease (1.43 vs 0.16, median, P < 0.05). The complete remission (CR) rate after chemotherapy was found to be significantly correlated with pig7 expression levels (P < 0.05). Differentiated NB4 cells showed an increased level of pig7 expression (from 1.61 +/- 0.72 to 44.75 +/- 3.93, P < 0.01). Only one form of pig7 transcripts i.e., Small integral membrane protein of late endosome (SIMPLE), was detected in AL patients. Hypermethylation of pig7 promoter was identified in K562 and HL-60 cells, in contrast to non-methylation predominant in U937 cells.</p><p><b>CONCLUSION</b>Aberrant down-regulation of pig7 provides novel insights into leukemogenesis and therapy response prediction in AL.</p>


Subject(s)
Acute Disease , Cell Differentiation , Cell Line, Tumor , DNA Methylation , Gene Expression Regulation, Leukemic , Humans , Leukemia , Genetics , Nuclear Proteins , Genetics , Promoter Regions, Genetic , RNA, Messenger , Genetics , Transcription Factors , Genetics , Tretinoin , Pharmacology
9.
Chinese Journal of Hematology ; (12): 677-680, 2007.
Article in Chinese | WPRIM | ID: wpr-262963

ABSTRACT

<p><b>OBJECTIVE</b>To explore the signal transduction pathway in the differentiation and apoptosis of leukemia cells induced by heat shock protein 90 (HSP90) inhibitor 17-Allyl amide-17-demethoxygeldanamycin (17AAG).</p><p><b>METHODS</b>Kasumi-1 cells were treated with increasing concentrations or exposure time of 17AAG. The total kit protein (CD117), phosphorylated kit protein and its downstream signaling molecules were measured by Western blot analysis. Mutated kit protein from control and 17AAG-treated Kasumi-1 cells was immunoprecipitated and immunoblotted for associated chaperones.</p><p><b>RESULTS</b>Total kit protein and kit activity were decreased in 17AAG treated cells, but c-kit mRNA level was not. Total AKT protein and phospho-AKT, as well as phospho-STAT3 were rapidly down-regulated in Kasumi-1 cell after treatment with 17AAG. There was no change in total STAT3 protein. Immunoprecipitation showed that 1 microM 17AAG treatment for 1 hour caused kit associated HSP90 decrease and HSP70 increase.</p><p><b>CONCLUSION</b>17AAG-induced apoptosis of Kasumi-1 cells is associated with a decline in Asn822Lys mutated kit protein level and phosphorylated kit, and with a downregulation in its downstream activated signaling molecules involved in proliferation. AKT is a client protein of HSP90. The changes of kit associated HSP90 and HSP70 satisfy the circulation mode of molecular chaperone complex.</p>


Subject(s)
Apoptosis , Benzoquinones , Pharmacology , Cell Differentiation , HSP90 Heat-Shock Proteins , Heat-Shock Proteins , Metabolism , Humans , Lactams, Macrocyclic , Pharmacology , Leukemia , Metabolism , Pathology , Proto-Oncogene Proteins c-akt , Metabolism , Proto-Oncogene Proteins c-kit , Metabolism , STAT3 Transcription Factor , Metabolism , Signal Transduction , Tumor Cells, Cultured
10.
Chinese Journal of Hematology ; (12): 299-302, 2005.
Article in Chinese | WPRIM | ID: wpr-255886

ABSTRACT

<p><b>OBJECTIVE</b>To explore the relationship between CCAAT/enhancer binding protein alpha (C/EBPalpha) gene mutations and the development of acute myeloid leukemia (AML).</p><p><b>METHODS</b>The whole coding region of C/EBPalpha gene were screened in 48 cases of AML and 11 normal subjects by PCR-single strand conformation polymorphism (PCR-SSCP) and sequencing.</p><p><b>RESULTS</b>C/EBPalpha mutations were detected in 5 of 48 AML patients. Four duplications and 1 deletion were confirmed by DNA sequencing. All of those are newly identified mutations.</p><p><b>CONCLUSIONS</b>Different mutation types of C/EBPalpha gene exist in a small number of patients with AML and might be related to the pathogenesis of some leukemias.</p>


Subject(s)
Adolescent , Adult , Aged , CCAAT-Enhancer-Binding Protein-alpha , Genetics , Child , Female , Humans , Leukemia, Myeloid, Acute , Genetics , Male , Middle Aged , Mutation
11.
Acta Pharmaceutica Sinica ; (12): 818-820, 2002.
Article in Chinese | WPRIM | ID: wpr-312042

ABSTRACT

<p><b>AIM</b>To study the inhibition of oxygen consumption by annonaceous acetogenins (ACG) and their structure-activity relationship (SAR).</p><p><b>METHODS</b>The inhibition of oxygen consumption in chicken liver cell respiration by different structural ACG was studied by using oxygen electrode technique.</p><p><b>RESULTS</b>Six ACG showed potent inhibitory effects like rotenone which was a classical inhibitor of mitochondrial complex I, and was more potent than complex IV inhibitor KCN. The IC50 values of six ACG for inhibiting oxygen consumption suggested that bistetrahydrofuran (THF) ACG was 7-11 times more active than non-THF ACG, and A1-type ACG was more potent than A2-type ACG.</p><p><b>CONCLUSION</b>The terminal gamma-lactone was crucial for the inhibition of oxygen consumption. The distance between THF and gamma-lactone, the hydroxyl groups in the alkyl chain, were the important factors of SAR, but the 4-OH group possibly played some negative role in the exhibit of potent activity.</p>


Subject(s)
Acetogenins , Animals , Annona , Chemistry , Cell Separation , Chickens , Fatty Alcohols , Chemistry , Pharmacology , Furans , Chemistry , Pharmacology , Lactones , Chemistry , Pharmacology , Liver , Cell Biology , Mitochondria, Liver , Metabolism , Oxygen Consumption , Plants, Medicinal , Chemistry , Seeds , Chemistry , Structure-Activity Relationship
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