OBJECTIVETo study the expression of Foxp3 and NFAT1 protein in peripheral blood (PB) in children with aplastic anemia (AA) and their roles in the pathogenesis of AA.

METHODSThe expression levels of Foxp3 and NFAT1 protein of mononuclear cells in PB were measured by Western blot in 68 children with AA before and after treatment and in 60 normal children (control group). The correlation between Foxp3 and NFAT1 protein expression and the correlation of the Foxp3 and NFAT1 protein expression with blood Hb, WBC and platelet levels were analyzed.

RESULTSThe expression levels of Foxp3 and NFAT1 protein in PB in the acute phase in the AA group were significantly lower than in the control group (P<0.05). After treatment (recovery phase) the expression levels of Foxp3 and NFAT1 protein increased obviously compared with those in the acute phase (P<0.05). The Foxp3 protein level was positively correlated with the NFAT1 protein level (r=0.812, P<0.05). Both the Foxp3 and NFAT1 protein levels were positively correlated with blood Hb, WBC and platelet levels in children with AA in the recovery phase (r=0.537, 0.579, 0.655 respectively; P<0.05).

CONCLUSIONSThe Foxp3 and NFAT1 protein levels in PB are reduced in children with AA, suggesting that they are involved in the pathogenesis of AA. The measurement of Foxp3 and NFAT1 protein levels may be useful in the severity evaluation of AA.

Adolescent ; Anemia, Aplastic ; blood ; etiology ; Child ; Child, Preschool ; Female ; Forkhead Transcription Factors ; blood ; Humans ; Male ; NFATC Transcription Factors ; blood

Blood Vessels ; physiology ; Humans ; Kruppel-Like Transcription Factors ; metabolism ; physiology

BACKGROUND: N-myc downstream-regulated gene 2 (NDRG2), a member of a newly described family of differentiation-related genes, has been characterized as a regulator of dendritic cells. However, the role of NDRG2 on the expression and activation of transcription factors in blood cells remains poorly understood. In this study, we investigated the effects of NDRG2 overexpression on GATA-1 expression in PMA-stimulated U937 cells. METHODS: We generated NDRG2-overexpressing U937 cell line (U937-NDRG2) and treated the cells with PMA to investigate the role of NDRG2 on GATA-1 expression. RESULTS: NDRG2 overexpression in U937 cells significantly induced GATA-1 expression in response to PMA stimulation. Interestingly, JAK2/STAT and BMP-4/Smad pathways associated with the induction of GATA-1 were activated in PMA-stimulated U937-NDRG2 cells. We found that the inhibition of JAK2 activation, but not of BMP-4/Smad signaling, can elicit a decrease of PMA-induced GATA-1 expression in U937-NDRG2 cells. CONCLUSION: The results reveal that NDRG2 promotes the expression of GATA-1 through activation of the JAK2/STAT pathway, but not through the regulation of the BMP-4/Smad pathway in U937 cells. Our findings further suggest that NDRG2 may play a role as a regulator of erythrocyte and megakaryocyte differentiation during hematopoiesis.
Blood Cells ; Dendritic Cells ; Erythrocytes ; Hematopoiesis ; Humans ; Megakaryocytes ; Transcription Factors ; U937 Cells

Giant platelet syndrome is a group of unique disorders characterized by the presence of abnormally large platelets, and usually accompanied by thrombocytopenia. Most cases of giant platelets are encountered in idiopathic thrombocytopenic purpura(ITP). In contrast, inherited giant platelet disorders, a group of heterogeneous diseases, are rare. Bernard-Soulier syndrome and its variants, and MYH9 related diseases have been defined at the molecular level. Abnormalities in transcription factors are implicated in a couple of macrothrombocytopenia syndromes. However, the molecular defects are unknown in gray platelet syndrome. It is important to make a proper diagnosis of congenital macrothrombocytopenia to avoid unnecessary medications and potentially dangerous treatment for presumed ITP.
Bernard-Soulier Syndrome* ; Blood Platelets ; Diagnosis ; Gray Platelet Syndrome ; Thrombocytopenia ; Transcription Factors

BACKGROUND: Angiogenin, a 14.1-kDa protein isolated from the medium conditioned by HT-29 human colon carcinoma cells, induces the angiogenesis. In contrast to the human angiogenin, thought to have one homologue, the mouse angiogenin is known to have several angiogenin homologues. During we were investigating the target genes, overexpressed by the chimeric PAX3/FKHR transcription factor, new gene closely similar to the mouse angiogenin rather than angiogenin itself was obtained. We report this Ang-vl gene to understand the process of angiogenesis by comparing the mouse angiogenin family genes. METHODS: The representational difference analysis was used to investigate the target genes over expressed by the PAX3/FKHR chimeric transcription factor. The target genes were subcloned into the pBluescriptSK + and sequenced using the 73 and 77 vector itself primers. Analyses of the completed consensus nucleic acid and peptide sequences were performed using the intelligenetics and GCG software packages as well as BLAST algorithms. RESULTS: The Ang-vl gene, including the glutamine that becomes the N-terminal amino acid by the post-translational peptidase reaction and stop codon, was obtained. CONCLUSIONS: We cloned the one member of the mouse angiogenin family genes. From the point of protein chemistry, the mechanism of angiogenin or, for that matter, of any other blood vessel inducing proteins is not yet known. However, the homologues of the angiogenin might interact each other to regulate the angiogenesls. In this regard, the Ang-vl gene provides an opportunity to understand the mechanism of angiogenesis.
Animals ; Blood Vessels ; Chemistry ; Clone Cells ; Codon, Terminator ; Colon ; Consensus ; Glutamine ; Humans ; Mice* ; Transcription Factors*

OBJECTIVETo study the frequency of rare blood group Lu(a-b-) phenotype in a population from Shanghai region, and to explore the molecular basis of Lu(a-b-) by detecting the Lu and Lu relative mediator gene EKLF/KLF1.

METHODSDonors from Shanghai region were screened for Lutheran blood group by monoclonal anti-Lub using serological methods. Individuals with Lu(b-) were determined Lua, P1 and i antigens. Fifteen exons of the LU gene and 3 exons of the EKLF/KLF1 gene for the identified Lu(a-b-) samples were amplified and sequenced.

RESULTSTen Lu(a-b-) donors were obtained from 44 331 donors from Shanghai region. No homozygous or heterozygous mutations were found in the LU gene, whilst 7 mutations in EKLF/KLF1 gene were identified in the 10 samples.

CONCLUSIONThe frequency of rare Lu(a-b-) blood group in Shanghai was approximately 0.02%, and all the individuals had an In(Lu) phenotype. The molecular basis of such samples may be related to mutations in the EKLF/KLF1 gene.

China ; ethnology ; Humans ; Kruppel-Like Transcription Factors ; genetics ; Lutheran Blood-Group System ; genetics ; Mutation ; Phenotype

Pleckstrin homology like domain family A member 1(PHLDA1) is also known as T-cell death-associated gene 51 (TDAG51).Studies have demonstrated that the abnormal expression of PHLDA1 is closely associated with the formation,development,and metastasis of tumors.We summarized the latest research advances in the structure and biological properties of PHLDA1,as well as the roles of PHLDA1 in multiple malignanttumors such as breast cancer,cancer,liver gastric cancer,liver cancer,melanoma,and osteosarcoma,aiming to comprehensively reveal the significance of PHLDA1 in the clinical diagnosis of tumors.
Humans ; Female ; Transcription Factors/genetics* ; Phosphoproteins ; Blood Proteins ; Breast Neoplasms/genetics*

OBJECTIVETo evaluate serum Nkx2-1 (NKX homeobox-1) levels in diagnosis of primary lung cancer.

METHODSThe serum NKX2-1 and CEA (carcinoma embryonic antigen) levels were measured in 61 patients with primary lung cancer admitted from May 2009 to December 2010 and 49 healthy individuals served as controls. The receiver operating characteristic curve (ROC) of NKX2-1 in diagnosis for primary lung cancer was analyzed. The value of serum NKX2-1 in diagnosing primary lung cancer was compared with that of CEA by X(2) test and Kappa test.

RESULTSThe serum Nkx2-1 levels in lung cancer were significantly higher than those in controls [(1.4206 ±0.1257)ng/ml compared with (0.7646 ±0.0734)ng/ml,P<0.01]. ROC analysis showed the area under the curve of serum NKX2-1 was 0.859. The Kappa value of NKX2-1 was higher than that of CEA (0.586 compared with 0.396,P<0.05). Combination of serum NKX2-1 with CEA improved the Kappa value to 0.704, and also had high sensitivity (83.6%) and specificity (87.0%) for diagnosis of primary lung cancer.

CONCLUSIONSerum NKX2-1 protein can be used as a marker for diagnosis of lung cancer, the combination of NKX2-1 with CEA may further improve the diagnostic value.

Biomarkers, Tumor ; blood ; Carcinoembryonic Antigen ; blood ; Case-Control Studies ; Humans ; Lung Neoplasms ; blood ; diagnosis ; Nuclear Proteins ; blood ; Sensitivity and Specificity ; Thyroid Nuclear Factor 1 ; Transcription Factors ; blood

BACKGROUNDRecent studies have shown that T helper type-2 (Th2) cells can induce the apoptosis of CD4+CD25+ Treg cells or resist the immunosuppressive effect of Treg cells. We hypothesize that an imbalance of Th2/Treg is present in patients with allergic asthma.

METHODSTwenty-two patients with mild asthma, 17 patients with moderate to severe asthma, and 20 healthy donors were enrolled. All patients were allergic to house dust mites. The proportion of peripheral blood CD4+CD25+ Treg cells and Th2 cells were determined by flow cytometry. The concentration of interleukin (IL)-10, transforming growth factor (TGF)-β and IL-4 in plasma was determined by enzyme linked immunosorbent assay. In these subjects, peripheral blood mononuclear cells from 17 mild asthmatic patients, 13 moderate to severe asthmatic patients and 14 healthy donors were acquired and expression of forkhead box P3 (Foxp3) and GATA-3 mRNA was detected by reverse-transcriptase polymerase chain reaction.

RESULTSCompared with healthy donors and patients with mild asthma, the percent of CD4+CD25+ Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. There were no significant differences in Foxp3 mRNA expression among three groups, but a downward trend seen among patients with asthma. However, the percent of Th2 cells, IL-4 levels and expression of GATA-3 mRNA was markedly higher in patients with mild and moderate to severe asthma than in the control group. The ratio of Th2/Treg and their cytokines was increased in allergic asthma, especially for moderate to severe asthma. The ratio of GATA-3/Foxp3 mRNA was also increased in allergic asthma. In patients with moderate to severe asthma, the percentage of peripheral blood Treg cells was negatively correlated to the percentage of Th2 cells and IL-4 levels.

CONCLUSIONSThe decline of CD4+CD25+ Treg cells in patients with moderate to severe asthma may play an important role in progress of the disease. Furthermore, the deficiency of CD4+CD25+ Treg cells was associated with the over-expression of Th2 response.

Asthma ; etiology ; immunology ; Cytokines ; blood ; Forkhead Transcription Factors ; genetics ; GATA3 Transcription Factor ; genetics ; Humans ; RNA, Messenger ; analysis ; T-Lymphocytes, Regulatory ; immunology ; Th2 Cells ; immunology

OBJECTIVETo investigate the variation of serum thyroid transcription factor-1 (TTF-1) in different patients and explore its significance in the diagnosis of lung carcinoma.

METHODSDot-enzyme linked immunosorbent assay (dot-ELISA) and Leica Q500 MC image analysis system were used to quantitatively detect TTF-1 protein in the serum samples from normal healthy adults and from patients with benign lung disease, lung cancer, thyroid carcinoma and non-thyroid carcinoma.

RESULTSThe sensitivity, specificity, standardized positive predicative value, standardized negative predicative value, standardized accuracy and standardized wrong diagnostic rate of the method were 90.91%, 82.22%, 83.64%, 90.04%, 86.57% and 13.43%, respectively. The cutoff value of serum TTF-1 in healthy normal adults was 36.39, with a ROC value of 0.95. Serum TTF-1 PU was significantly higher in patients with lung adenocarcinoma, squamous cell lung carcinoma and thyroid carcinoma than in healthy adults and patients with benign lung diseases and non-thyroid carcinoma (P=0.000). Serum TTF-1 PU was similar in lung adenocarcinoma, squamous cell lung carcinoma, small cell lung carcinoma, large cell lung carcinoma and thyroid carcinoma (P=0.744, 0.677, and 0.333, respectively). Serum TTF-1 PU was greater than the PU in the corresponding homogenate of lung adenocarcinoma, squamous cell lung carcinoma, small cell lung carcinoma, large cell lung carcinoma and thyroid carcinoma (P=0.000). Serum and homogenate TTF-1 PU was correlated to TNM stage of lung cancer patients (P=0.000) but not to gender, tumor types, differentiation or lymph node metastasis.

CONCLUSIONSLung adenocarcinoma, squamous cell lung carcinoma and thyroid carcinoma are suspected when serum TTF-1 PU is higher than 36.39. Serum TTF-1 is not helpful in differentiating the types of lung carcinomas and thyroid carcinoma. After exclusion of thyroid carcinoma, detection of serum TTF-1 can be helpful in the diagnosis of lung cancer. In different lung carcinomas and thyroid carcinomas, the serum TTF-1 is higher than the corresponding homogenate TTF-1 level. Serum TTF-1 increases with the progression of TNM stage of lung carcinoma.

Case-Control Studies ; Humans ; Lung Neoplasms ; blood ; classification ; diagnosis ; Nuclear Proteins ; blood ; Predictive Value of Tests ; Sensitivity and Specificity ; Thyroid Nuclear Factor 1 ; Transcription Factors ; blood