OBJECTIVETo study the effect on apoptotic of CD4+ T, CD19+ B in spleen of BXSB mice with systemic lupus erythematosus treated with Langchuangjing Granule and to probe into the mechanism of treatment.

METHODSThe apoptosis was examined by the flow cytometric analysis and immunofluorescence double-staining method.

RESULTSApoptosis of male BXSB mice speeds up. Langchuangjing Granule can restrain the excessive apoptosis of CD4+ T and CD19+ B cells in spleen.

CONCLUSIONLangchuangjing Granule treated systemic lupus erythematosus by restraining the excessive apoptotic of T, B lymphocytes, probably restraining the release of excessive amount of apoptotic DNA fragments, so decreasing abnormal proliferation of B cells and the produce of autoantibodies.

Animals ; Antigens, CD19 ; analysis ; Apoptosis ; drug effects ; B-Lymphocytes ; pathology ; CD4-Positive T-Lymphocytes ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Lupus Erythematosus, Systemic ; immunology ; pathology ; Male ; Mice ; Mice, Inbred Strains ; Random Allocation ; Spleen ; pathology

OBJECTIVETo explore the molecular mechanism via which the chemotherapeutic drug hydroxyurea (HU) enhances K562 cell apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

METHODSChronic myelogenous leukemia-derived K562 and SVT-35 cells were treated with recombinant soluble TRAIL (rsTRAIL) alone or combined with HU for a time course, and the cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-4-sulfophenyl-2H-tetrazolium-phenazine methosulphate assay. Western blot was performed to analyze the activation of apoptosis-related protein kinases and the expression of apoptosis inhibitor molecules.

RESULTSThe survival rates of SVT-35 and K562 cells treated with 1 μg/ml rsTRAIL for 24 hours were 32% and 93%, respectively. HU significantly increased the sensitivity of K562 cells to rsTRAIL cytotoxicity. Combination of rsTRAIL and HU resulted in the phosphorylation of rat sarcoma (RAS), mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase and in the significant reduction of apoptosis-inhibited molecule Fas associated death domain protein-like interleukin-1 beta-convening enzyme inhibitory protein and cellular inhibitor of apoptosis protein-1 in K562 cells.

CONCLUSIONSHU enhanced K562 cell sensitivity to rsTRAIL is mediated by Ras-MEK-ERK signaling pathway. Expression of antiapoptotic proteins cellular Fas associated death domain protein-like interleukin-1 beta-convening enzyme inhibitory protein and cellular inhibitor of apoptosis protein-1 is also down-regulated during this process. These results may through light on the therapeutic study of human chronic myelogenous leukemia.

Apoptosis ; drug effects ; physiology ; CASP8 and FADD-Like Apoptosis Regulating Protein ; metabolism ; Humans ; Hydroxyurea ; pharmacology ; Inhibitor of Apoptosis Proteins ; metabolism ; K562 Cells ; MAP Kinase Signaling System ; TNF-Related Apoptosis-Inducing Ligand ; pharmacology

OBJECTIVETo characterize the variation in V3 loop of HIV-1 B'strains circulating in Chinese blood donors.

METHODSThe c2-c3 regions of the HIV envelop gene were amplified by nest-PCR from 32 HIV-1-infected blood donors in He Nan province in China. The BIOEDIT and MEGA software are used to analyze the sequences of V3 loop.

RESULTSThere are five types of central motifs of the 32 samples, in which GPGR and GPGQ are most common. More variations associated with T tropic/SI phenotype can be seen in AIDS group.

CONCLUSIONThe V3 tip motifs of HIV-1B' strains circulating in Chinese blood donors are various, the different characterization of V3 loop between AIDS and asymptomatic patients indicates different biological phenotype and pathogenesis which warrant additional investigation.

Adult ; Aged ; Amino Acid Motifs ; Amino Acid Sequence ; Blood Donors ; China ; Female ; Genetic Variation ; genetics ; HIV Envelope Protein gp120 ; analysis ; chemistry ; genetics ; HIV Infections ; blood ; virology ; HIV-1 ; chemistry ; classification ; genetics ; isolation & purification ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Oligopeptides ; chemistry ; Phenotype

OBJECTIVETo investigate the compatibility of a modified prescription of Simiao Pill in the treatment of acute gouty arthritis and to verify the clinical efficacy and safety of the drug through a clinical trial.

METHODSA randomized and controlled clinical trial was designed based on clinical epidemiological principles. A total of 107 patients with acute gouty arthritis were enrolled and randomly assigned to four groups. The first group (Group I) included 27 patients taking gout prescription I; the second group (Group II) included 27 patients taking gout prescription II; the third group (Group III) included 28 patients taking gout prescription III; and the fourth group (control group) included 25 patients taking indomethacin and Benzobromarone as a control group. The duration of the treatment in all 4 groups was two weeks. After the treatment, the index of blood uric acid, blood leukocyte count, score of clinical symptoms, etc. were observed and measured.

RESULTSThe total clinical effective rate of the three different modified prescriptions of the Simiao Pill was above 96%, significantly superior to that of the control group (68%, P<0.05). In terms of the improvement of main symptoms, the scores of four symptoms in all TCM treatment and control groups decreased after treatment, with statistically significant differences (P<0.05). Moreover, the scores markedly fell more so in the three Chinese herb groups than in the control group, and especially in Group III (P<0.05). There was a statistically significant difference in blood uric acid values before and after the treatment in the same group but no significant inter-group difference was seen.

CONCLUSIONThe modified prescriptions, based on the clinical research, clinical experience and traditional Chinese medicine theory, did show a better effect than Western medicine in this clinical study. Moreover, the prescriptions were precise, with the herbs inexpensive and readily available. The patients had good compliance with less adverse reactions noted. The modified prescription has a favorable prospect for future development and is worthy of further blind trials with larger samples.

Acute Disease ; Adult ; Aged ; Arthritis, Gouty ; drug therapy ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Uric Acid ; blood

OBJECTIVETo investigate the relationship between the biological features and the treatment efficacy and prognosis in acute myeloid leukemia subtype M2 (AML-M2) patients with chromosome 8 and 21 translocation.

METHODSBy using Cox regression model and Kaplan-Meier analyses, prognostic factors in 54 cases of de novo adult AML with t(8;21) in our institute from 1990 to 2003 were retrospectively analyzed.

RESULTThe complete remission (CR) rates were 81.9% for all M2 patients, 82.4% for patients with normal karyotype, 88.5% for patients with t(8;21) [P > 0.05 for normal karyotype vs t(8;21)], 100.0% for 28 patients with t(8;21) alone and 75.0% for 24 patients with additional chromosome abnormalities (P < 0.01). The actuarial 3 year overall survival(OS) was 26% for M2 patients with normal karyotype, 25% for patients with t(8;21) [P > 0.05 for normal karyotype vs t(8;21)], in whole t(8;21) group, 46.4% for patients with t(8;21) alone and 0% for patients with additional chromosome abnormalities (P < 0.01). Multivariate analysis of prognostic factors showed that chromosome abnormalities besides t(8;21) was the only factor affecting CR, disease-free survival (DFS) and OS. DFS of allogeneic hematopoietic stem cell transplantation (HSCT) and intermediate-dose cytarabine/high dose cytarabine (IDAC) groups were better than the group received routine dose cytarabine as postremission therapy (P < 0.01).

CONCLUSIONAML with t(8;21) is not a single defined AML subset, and patients with additional chromosome abnormalities have a worse prognosis. HSCT and IDAC could improve the outcome. HSCT is the best choice for patients with high risks, especially with additional chromosome abnormalities.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chromosomes, Human, Pair 21 ; genetics ; Chromosomes, Human, Pair 8 ; genetics ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; surgery ; therapy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Translocation, Genetic

Animals ; Antibodies, Bacterial ; blood ; Bacterial Proteins ; genetics ; immunology ; Brucella Vaccine ; immunology ; Brucella abortus ; immunology ; Female ; Immunization ; Interferon-gamma ; biosynthesis ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Periplasmic Binding Proteins ; genetics ; immunology ; Ribosomal Proteins ; genetics ; immunology ; Vaccines, DNA ; immunology

OBJECTIVETo clone human CCL3L1 cDNA and to express and purify the glutathione-S-transferase (GST) fusion protein and human CCL3L1 protein.

METHODSTotal RNA was isolated from breast cancer cell line MCF7. CCL3L1 cDNA including open reading frame was obtained by RT-PCR. PCR product was digested with EcoR I and cloned into the pGEX-4T-1 vector. The plasmids from positive clone was prepared and sequenced to confirm the CCL3L1 in correct fusion form. pGEX-4T-CCL3L1 was transfected to BL21 E. coli via isopropyl-beta-D-thiogalactoside (IPTG) induction to produce GST-CCL3L1 fusion protein, which was further detected by SDS-PAGE and Western blotting.

RESULTSAs shown and confirmed by restriction endonuclease digestion analysis, CCL3L1 was correctly inserted into pGEX-4T-1 vector. The expressed fusion protein had a relative molecular weight of approximately 34 kD.

CONCLUSIONGST-CCL3L1 fusion protein can be successfully expressed using appropriate vector.

Cell Line, Tumor ; Chemokines, CC ; biosynthesis ; genetics ; Cloning, Molecular ; DNA, Complementary ; genetics ; Escherichia coli ; drug effects ; genetics ; metabolism ; Female ; Genetic Vectors ; Glutathione Transferase ; biosynthesis ; genetics ; Humans ; Isopropyl Thiogalactoside ; pharmacology ; Recombinant Fusion Proteins ; biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction

AIM To analyze the effects of α-mangostin on the proliferation and apoptosis of osteoarthritis (OA) chondrocytes.METHODS Human OA chondrocytes were isolated and then treated with 5,10 or 20 μmol/L α-mangostin.24,48 or 72 h after the treatment,the cell proliferation was measured by MTT assay,and the cell apoptosis was detected by flow cytometry.The expression check on MMP-1,MMP-3,MMP-13,PPARγ,PPARδ,PGC-lα and TNF-α was accomplished by Western blot.The contents of collagen-Ⅱ,PG,IL-1β and IL-6 were tested by ELISA.RESULTS α-Mangostin significantly induced cell proliferation and suppressed cell apoptosis,and it significantly increased the production of collagen-Ⅱ and PG,decreased the expressions of MMP-1,MMP-3 and MMP-13,induced the expressions of PPARγ,PPARδ and PGC-1α,and decreased the expression of TNF-α.Furthermore,α-mangostin significantly inhibited the production of IL-1β and IL-6.CONCLUSION α-Mangostin attenuates the destruction and degradation of cartilago articularis by inducing OA chondrocytes proliferation,inhibiting cell apoptosis and inflammation,and increasing expressions of PPARγand PPARδ.

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC₅₀ = 0.33 μmol·L^-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L^-1, 21.2% inhibition at 1 μmol·L^-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

Stroke is one of the most serious complications of transcatheter aortic valve replacement(TAVR),tremendously increasing mortality and the loss of neurocognitive function.Since TAVR is expected to further spread into lower-risk patient groups,there will be greater emphasis to obviate such serious complications.One possible technique for preventing stroke is using cerebral embolic protection devices(CEPDs).CEPDs are designed for capturing or deflecting emboli that are enter route to the brain and hence to protect the brain from embolism.Since this is a rapidly growing field with recent advances,and the impact of CEPD on preventing neurological events is still limited,there is an urgent need for understanding the role of CEPD in preventing clinically significant strokes.Although their clinical utilization is increasing,the risk factors for stroke related to TAVR and evidence for using CEPDs are not yet clear.In this review,we present an overview of the available literature on TAVR related stroke and CEPD,and outline recent advances within this field.