Amino Acid Metabolism, Inborn Errors ; diagnosis ; metabolism ; therapy ; Diagnosis, Differential ; Diet ; Glutarates ; metabolism ; urine ; Humans ; Infant ; Male ; Riboflavin ; therapeutic use ; Treatment Outcome

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

BACKGROUNDNurr1 is a member of the nuclear receptor superfamily of transcription factors. The objective of the present study was to identify novel splicing variants of the gene in neuronal and non-neuronal tissues and determine their functions.

METHODSReverse transcription-polymerase chain reaction (RT-PCR) analysis was used to screen for Nurr1 splice variants in the adult human central nervous system (CNS) and in other tissues such as lymphocytes, and liver, muscle, and kidney cells. Functional assays of the variants were performed by measuring Nurr1 response element (NuRE) transcriptional activity in vitro.

RESULTSIn this study, the authors identified a novel splicing variant of Nurr1 within exon 5, found in multiple adult human tissues, including lymphocytes, and liver, muscle, and kidney cells, but not in the brain or spinal cord. Sequencing analysis showed the variant has a 75 bp deletion between nucleotides 1402 and 1476. A functional assay of the Nurr1-c splicing variant, performed by measuring NuRE transcriptional activity in vitro, detected a 39% lower level of luciferase (LUC) activity (P < 0.05).

CONCLUSIONA novel splicing variant of Nurr1 exists in human non-neuronal tissues and functional assays suggest that the variant may act as an alternate transcription regulator.

Adult ; Alternative Splicing ; DNA-Binding Proteins ; analysis ; genetics ; Humans ; Nuclear Receptor Subfamily 4, Group A, Member 2 ; Transcription Factors ; analysis ; genetics

Warfarin is prone to cause thromboembolism or bleeding due to its narrow therapeutic window.Studies have shown that both genetic and environmental factors affect individual difference of warfarin dose.This review will summarize the recent progress of models building and valida-ting at home and abroad to provide a reference for individualized treat-ment of warfarin.

Objective To explore the protocol that induced marrow mesenchymal stem cells (MSCs) differentiating into islet-secreting cells in vitro and to provide new clues for the sources of islet transplantation.Methods Using a defined culture medium and technique for transdifferentiation, MSCs from adult SD rats were guided into specific insulin-secreting cells. The expressions of nestin and islet-specific hormones and proteins, such as insulin, glucagon, somatostatin and pancreatic duodenal homeobox 1 (Pdx-1) were analyzed by indirect immunofluorescence cytochemistry staining before and after induction. The expressions of pancreatic islet cell differentiation-related transcripts, such as nestin, insulin 1, glucose transporter 2 (GLUT 2), Isl-1, Pdx-1, Pax-4 and Pax-6 were detected by reverse transcription-PCR (RT-PCR). In addition, the quantity of insulin secretion was examined using radioimmunoassay. Results Five hours after induction, (44.6±7.3)% of differentiated MSCs expressed nestin and it increased to (61.8±8.4)% 24 hs after induction, but the expression of nestin almost disappeared at day 14. In the meantime, islet-like cellular clusters appeared after day 14 and became more apparent by day 28. Differentiated cells were found to be immunoreactive to insulin, glucagon, somatostatin and Pdx-1, and expressed insulin 1, GLUT 2, GK, Isl-1, PDX-1, Pax-4, Pax-6 mRNA. In addition, the results of cumulative quantities of insulin of 24 hs and the stimulation index showed that differentiated cells were able to produce insulin at higher levels, and displayed glucose-dependent insulin release in vitro. Conclusions Adult rat MSCs can be differentiated into insulin-secreting cells in vitro. This approach might lead to widespread cell replacement therapy for Type 1 diabetes.

OBJECTIVETo investigate the relationship between apolipoprotein A5(apoA5) - 1131T > C polymorphism and the susceptibility of coronary artery disease (CAD) in Chinese.

METHODSThe restriction fragment length polymorphism of apoA5 gene - 1131T > C was studied using PCR in a case-control study which enrolled 235 patients with CAD diagnosed by angiography and 262 healthy controls from Jiangsu province.

RESULTSThe frequencies of T, C allele were 59.57%ì40.43% and 65.65%, 34.35% in CAD group and control group respectively. There was statistically significant difference in allele frequencies between CAD group and control group (P < 0.05). The susceptibility to CAD for the CC genotype was much higher than that for wild type TT (OR = 1.872, 95% CI = 1.039 - 3.376, P = 0.037), even after the use of Logistic regression models (OR = 2.285, 95% CI = 1.222 - 4.274, P = 0.012). In control group, there was significant difference in TG levels among different genotypes, the C allele carriers had higher serum TG concentration (P = 0.007).

CONCLUSIONapoA5 - 1131T > C polymorphism is associated with an increased risk of CAD and is also in strong association with serum TG levels.

Aged ; Apolipoprotein A-V ; Apolipoproteins A ; genetics ; Asian Continental Ancestry Group ; genetics ; China ; Coronary Artery Disease ; blood ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Humans ; Lipids ; blood ; Logistic Models ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Triglycerides ; blood

OBJECTIVETo investigate the effect of hTERT antisense oligodeoxynucleotide (ASODN) on the oncogenicity and the inductive apoptosis of HL-60 cells.

METHODSApoptosis of HL-60 cells was detected by flow cytometry (FCM) and agarose gel electrophoresis. Both treated and untreated HL-60 cells were collected and transplanted into 5 BALB/c nude mice respectively, the formation of transplanted neoplasm and its morphologic change were observed. After the transplanted neoplasms were uniform with the ameliorated method in another 10 BALB/c nude mice, they were divided into 2 groups and injected ASODN and PBS into the neoplasm respectively. Seven days later, the tumor were measured, its morphology were observed, and the apoptotic cells were detected with a TUNEL kit.

RESULTSAfter 72 h treatment there were DNA ladders and early apoptosis peak in hTERT ASODN treated HL-60 cells but was none in SODN treated and blank control cells. In tumor formation experiment, neoplasms were formed in ASODN treated group at 16-17 d and untreated group at 12-13 d. Neoplasm was formed in 2 of 5 ASODN treated mice and 4 of 5 untreated mice respectively. In untreated mice tumor tissues were rich in blood vasa and stromal tissue compared with that in ASODN treated mice. In tumor therapy experiment, before treatment, there was no difference in the average neoplasm physical volume between ASODN treated group [(100.9 +/- 24.6) mm3] and PBS treated group [(98.4 +/- 23.1) mm3] (P > 0.05). After treatment, the neoplasm volume in ASODN treated group [(422.7 +/- 326.4) mm3] was smaller than that in PBS treated group [(786.4 +/- 357.6) mm3] (P < 0.05). Histologically, there were many apoptosis cells in ASODN treated group, but was seldom seen in PBS treated group. The TUNEL positive cells in ASODN treated group were much more than that in PBS treated group (P < 0.05).

CONCLUSIONThe hTERT ASODN induces apoptosis of HL-60 cells in vitro, reduces the tumor formation in BALB/c nude mice and inhibits the growth of the transplanted neoplasm.

Animals ; Apoptosis ; drug effects ; HL-60 Cells ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Oligodeoxyribonucleotides, Antisense ; pharmacology ; Telomerase ; genetics ; Transfection ; Xenograft Model Antitumor Assays

Comparative Genomic Hybridization ; methods ; Female ; Humans ; Infant ; Wolf-Hirschhorn Syndrome ; diagnosis

Child ; Child, Preschool ; Female ; Humans ; Kidney Neoplasms ; pathology ; Logistic Models ; Male ; Prognosis ; Retrospective Studies ; Wilms Tumor ; pathology

OBJECTIVETo explore the role of monitoring sex chromosome chimeric status by fluorescence in situ hybridization (FISH) in the identification of leukemic extramedullary relapse and post-transplant lymphoproliferative disease (PTLD) in acute lymphocytic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSSix ALL patients who received sex-mismatched allo-HSCT and manifested extravisceral lymphadenectasis or local lump were investigated. The sex chromosome chimeric status in tumor tissues and bone marrows (BM) were monitored by FISH, and EBV-RNA in the tumor tissues were detected by in situ hybridization (ISH).

RESULTSThe sex chromosomes in BM of all 6 patients were 100% donor-derived. Among the sex chromosome chimeric status of tumor tissues, three patients were mainly recipient-derived, and the percentage of sex chromosomes derived from recipients were 100%, 100% and 98.0%, respectively, and then they were diagnosed leukemic extramedullary relapse. The other 3 patients were donor-derived, the percentage was 98.5%, 96.0% and 91.5%, respectively, and were diagnosed PTLD. EBV-RNA and latent membrane protein (LMP-1) were positive in 2 patients with PTLD and negative in the other 4 patients. One patient with extramedullary relapse obtained partial remission, one with PTLD gained complete remission, and the others died eventually after therapy.

CONCLUSIONMonitoring the sex chromosome chimeric status by FISH is an effective method to distinguish leukemic extramedullary relapse from PTLD in ALL received sex-mismatched donor HSCT.

Adolescent ; Adult ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Lymphoproliferative Disorders ; pathology ; surgery ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; pathology ; physiopathology ; surgery ; Recurrence ; Sex Chromosomes ; genetics ; physiology ; Transplantation Conditioning ; Young Adult