Rapid Screening of Lipase Inhibitors in Scutellaria baicalensis by Using Porcine Pancreatic Lipase Immobilized on Magnetic Core-Shell Metal-Organic Frameworks.

As for ligand fishing, the current immobilization approaches have some potential drawbacks such as the small protein loading capacity and difficult recycle process. The core-shell metal-organic frameworks composite (Fe3O4-COOH@UiO-66-NH2), which exhibited both magnetic characteristics and large specific surface area, was herein fabricated and used as magnetic support for the covalent immobilization of porcine pancreatic lipase (PPL). The resultant composite Fe3O4-COOH@UiO-66-NH2@PPL manifested a high loading capacity (247.8 mg/g) and relative activity recovery (101.5%). In addition, PPL exhibited enhanced tolerance to temperature and pH after immobilization. Then, the composite Fe3O4-COOH@UiO-66-NH2@PPL was incubated with the extract of Scutellaria baicalensis to fish out the ligands. Eight lipase inhibitors were obtained and identified by UPLC-Q-TOF-MS/MS. The feasibility of the method was further confirmed through an in vitro inhibitory assay and molecular docking. The proposed ligand fishing technique based on Fe3O4-COOH@UiO-66-NH2@PPL provided a feasible, selective, and effective platform for discovering enzyme inhibitors from natural products.

[Identification of differentially expressed genes related to blastic crisis in chronic myeloid leukemia].

OBJECTIVE: To identify differentially expressed genes between chronic phase and blast crisis in chronic myeloid leukemia, explore the mechanism and screen potential biomarkers of disease progression. METHODS: The differences in the gene expression profiles of bone marrow mononuclear cells between chronic phase and blastic crisis were examined using DNA microarray. PANTHER database, Genomatix database and Bibliosphere software were used to analyze and predict the critical genes or transcription factors during disease progression. Some of the genes or transcription factors were selected for verification by semi-quantitative RT-PCR. RESULTS: In blastic crisis, 68 of the 1176 tested genes were obviously up-regulated. Sixteen of these differential genes were selectively expressed in leukocyte membranes. CD40, CCR3, LGALS3, RGS3, CEACAM3 and the related transcription factors RAC1, CTNNB1, TP53, and NF-κB, all as the nodes of the entire regulatory network, were presumed to play key roles in disease progression. The results of RT-PCR were consistent with the microarray data and showed high expression of CEACAM3, RGS3, CTNNB1 and RAC1 in blastic crisis. CONCLUSION: A group of genes have been identified to very likely play key roles or serve as biomarkers in the transition from the chronic phase to blastic crisis in chronic myeloid leukemia.

[Cytogenetic differences between adults and children with acute lymphoblastic leukemia: eight-probe fluorescence in situ hybridization and karyotype analyses].

OBJECTIVE: To investigate the cytogenetic differences between children and adults with acute lymphoblastic leukemia (ALL) using eight-probe fluorescence in situ hybridization and karyotype analysis. METHODS: Eight-probe (MYC, P16, E2A, TEL/AML1, BCR/ABL , MLL , IGH, and hyperdiploidy) fluorescence in situ hybridization and karyotype analysis were performed for 86 adults and 39 children with acute lymphoblastic leukemia. RESULTS: Eight-probe fluorescence in situ hybridization showed significant differences in the positivity rate of TEL/AML1, BCR/ABL, and hyperdiploidy between adult patients and children with ALL. By karyotype analysis, the positivity rate of t(9;22) and hyperdiploidy differed significantly between the children and adult patients (P<0.05). CONCLUSION: Adults and children with ALL have different expression profiles of the fusion genes. Eight-probe fluorescence in situ hybridization is time-saving, accurate and efficient in detecting common genetic abnormalities in ALL patients, and can be well complementary to karyotype analysis in clinical diagnosis of ALL.

[Application of multiprobe fluorescence in situ hybridization panel in the diagnosis of acute myeloid leukemia].

OBJECTIVE: To assess the value of multiprobe fluorescence in situ hybridization (FISH) panel in the diagnosis of acute myeloid leukemia (AML). METHODS: The multiprobe AML/MDS panel comprising 8 different FISH probes for AML1/ETO transfusion gene, PML-RARα transfusion gene, CBFß/MYH11 transfusion gene, MLL breakapart, P53 deletion, Del(5q), -7/Del(7q), and Del(20q) was tested in 40 cases of AML, and the results were compared with those by conventional cytogenetic G-banding (CCG) test. RESULTS: With multiprobe FISH panel, 22 of the 40 AML cases were found to carry 7 types of cytogenetic abnormalities, namely AML1/ETO transfusion gene, PML-RARα transfusion gene, MLL breakapart, P53 deletion, Del(5q), -7/Del(7q) and trisomy 8. The positive ratio of the multiprobe FISH was 57.5%. CCG only identified 8 cases with the corresponding cytogenetic abnormalities and 3 cases with other cytogenetic abnormalities, and the positive ratio was only 27.50%. CONCLUSION: Mutiprobe FISH panel is more rapid, accurate and effective than CCG in the diagnosis of AML.

Analysis of efficacy and cost-effectiveness of high-dose arabinoside versus daunorubicin chemotherapy in older adult patients with acute myeloid leukemia by cytogenetic risk profile: retrospective review from China.

High-dose arabinoside (HiDAC) and daunorubicin (DNR)-based chemotherapy are the primary consolidation treatment options for older adults (50-60 years old) with acute myeloid leukemia in China. We analyzed the event-free survival (EFS) and hospital treatment charges of older adult patients with different cytogenetic risk profiles. In patients with a better/intermediate risk profile, the average total treatment cost of HiDAC was similar to that of DNR (P = 0.11). A 5-year follow-up of patients with better/intermediate cytogenetic risk profiles revealed that the median EFS of patients who received HiDAC was significantly longer than for patients who received the DNR-based regimen (27 vs. 20 months, P = 0.03). Average cost per year of life saved was 18,746.84 USD for HiDAC, compared to 32,733.37 USD for DNR. In contrast, for patients with a poor cytogenetic risk profile, the average total treatment cost for HiDAC was higher than for DNR (P < 0.005). In addition, the median EFS in the HiDAC protocol group was significantly lower than in the DNR group (11 vs. 20 months, P = 0.003). Meanwhile, in this risk group, the average cost per year of life saved was 103,237.70 USD compared to 32,277.93 USD, respectively, in the HiDAC and DNR regimens. We conclude that HiDAC is a more efficacious and cost-effective consolidation treatment regimen in the better/intermediate risk group, while the DNR-based regimen is more cost-effective in the poor risk group.