Biomedical subjects
Publications and source records attributed to Jian Hou.
The macroscopic molecular self-assembly of an amphiphilic hyperbranched copolymer in acetone generated multiwalled tubes millimeters in diameter and centimeters in length. The thickness of the tube walls approaches 400 nanometers, and the walls have an inhomogeneous lamella structure that alternates between ordered hydrophilic domains and amorphous, partly irregular hydrophilic domains.
Multiple myeloma (MM) remains largely incurable despite conventional and high-dose therapies. Therefore, novel biologically based treatment approaches are urgently required. Here we demonstrate that expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in MM cells and its agonists 15-d-PGJ2 and troglitazone completely abolished IL-6-inducible MM cell proliferation and induced apoptosis through affecting expression of multiple cell cycle or apoptosis genes, whereas PPARgamma antagonist GW9662 and PPARalpha agonist WY14643 did not display this inhibitory effect. These PPARgamma agonists significantly inhibited DNA binding and transactivation of STAT3 bound to the promoter of target genes in chromatin, but did not affect the expression of IL-6 receptor and phosphorylation of JAK/STAT3, MAPK, and PI3K/Akt. Interestingly, although inactivation of STAT3 by PPARgamma agonists is in a PPARgamma-dependent manner, the molecular mechanism by which two structurally distinct PPARgamma agonists suppress IL-6-activated STAT3 shows the divergent interactions between PPARgamma and STAT3 including direct or SMRT-mediated association.
BACKGROUND: There were only 3 multiple myeloma (MM) cell lines established in China. In this study, we succeeded in establishing a novel MM cell line and analyzed its biological characteristics. METHODS: Mononuclear cells isolated from the peripheral blood (PB) and bone marrow (BM) of a patient with advanced MM (lambda light chain type) were cultured in medium. Cell morphology was analyzed by Wright-Giemsa-staining and cytochemical staining, immunophenotyping by flow cytometry and cytogenetic analysis by chromosome RHG-banding technique. Quantitative fluorescent polymerase chain reaction (PCR) was used to detect Epstein - Barr virus (EBV) DNA. RESULTS: The established cell line could survive and proliferate in the presence of feeder cells or conditioned medium. The cells secreted lambda light chain and were negative for EBV. The Wright-Giemsa-staining showed typical plasmablast or plasma cell morphology. The cytochemical staining of the cells showed the following reactivity patterns: positive for acid phosphatase, negative for myeloperoxidase. The immunoprofile of the cells was concordant with that of MM cells: positive for CD10, CD28, CD38, CD138, CD56, CD49d, CD44, CD54 and CD58, negative for CD19, CD40, CD95, CD95L, CD34, CD2 and CD5. The cytogenetic analysis showed complex chromosome abnormality of i (1q+), 8q+, 13q+, i (17q), i (18q) and +M. There was no difference in morphology, immunophenotype and cytogenetics between cells from PB and BM. CONCLUSIONS: An MM cell line secreting lambda light chain named CZ-1 was established. The cells from both PB and BM have the same biological characteristics.
STI571 is a new antileukemia agent targeting BCR-ABL tyrosine kinase and successfully used in treatment of leukemia patients. Despite strong efficacy of the tyrosine kinase inhibitor STI571, resistance has been observed in a significant proportion of leukemia patients. This review focuses on the diverse mechanisms of ST1571 resistance and its preventive measures.
OBJECTIVE: To explore the molecular mechanism involved in patient with congenital FV deficiency. METHODS: Activity of FV was determined by biochemical method. The PCR products of FV gene was analyzed by DNA sequencing directly or cloned into T-vector prior to DNA analysis. The mutation of FV gene in proband and his family numbers was analysed by restriction enzyme analysis. Its occurrence was investigated in the control group. DNA was extracted from the peripheral blood mono1nuclear cells of the proband, male, 18 years old, and his parents. The PCR products were analyzed by direct sequencing or cloned into T-vector prior to DNA analysis. One hundred patients with different kind of hemotopathy were used as controls. RESULTS: A single point mutation, AG-->GG was found at position 3' splice site of intron 8 of the proband. This mutation was confirmed by family screening. CONCLUSION: A single point mutation, AG-->GG at position 3' splice site of intron 8 mutation of FV gene is related to the pathogenesis of congenital FV deficiency.
OBJECTIVE: To explore the molecular mechanisms involved in the patient with congenital FV deficiency. METHODS: Activity of FV was determined by biochemical method. The PCR products of FV gene was analysed by directly sequencing or sequencing after cloned into T-vector. The mutative FV gene was analysed by restriction enzyme analysis in the proband and her family members. RESULTS: A homozygous missense mutation G5729T resulting in Gly1880Val was revealed in the proband and confirmed in the family screening. Structure-function studies of the factor V mutants (Gly1880Val) demonstrated the importance of Gly1880 for structural stability of the Factor V. CONCLUSION: G5729T mutation of FV gene is related to the pathogenesis of congenital FV deficiency.
OBJECTIVE: To study the effects of arsenic trioxide (As(2)O(3)) on cell cycle and expression of cyclin dependent kinase inhibitors (CDKIs) in multiple myeloma (MM) cells, and explore its pharmacological mechanism. METHODS: The DNA content of MM cells line HS-Sultan was analyzed by flow cytometry after exposure to As(2)O(3), the effects on expression of CDKI P15, P16 AND P21 were studied by reverse transcriptase PCR. RESULTS: DNA flow cytometric analysis showed that As(2)O(3) induced most of HS-Sultan cells, arrest at G(0)/G(1) phase and a small fraction at G(2)/M phase and apoptosis occurred mainly in S phase. There was no expression of P15 and P16 mRNA in untreated HS-Sultan cells and 1.0 micromol/L As(2)O(3) could make them expressed after exposed 24 or 48 hours respectively. Expression of P12 mRNA was obviously elevated by As(2)O(3) comparing with that of control. CONCLUSION: One of the pharmacological mechanisms of As(2)O(3) is to activate the expression of CDKI P15, P16 and P21, and consequently affect cell proliferation cycle.
A CD30+ anaplastic large cell lymphoma (ALCL) cell line was established from the mononuclear cells isolated from pleural effusion of a patient with non-Hodgkin's lymphoma. The cell line's biological characteristics were analyzed. The results showed that the established cell line could survive and proliferate in RPIM 1640 medium; the Wright-Giemsa-stained cells were exactly similar to malignant cells of CD30+ ALCL in morphology, with many diffuse virus granules in cytoplasm; the cytochemical staining of the cells showed the following reactivity pattern: positive for acid phosphatase (ACP) and periodic acid-Schiff (PAS), negative for peroxidase (POX), myeloperoxidase (MPO) and platelet peroxidase (PPO). The immunoprofile of the cells was positive for CD45, HLA-DR, CD30 and negative for EMA, CD34, CD38, CD2, CD3, CD4, CD7, CD8, CD10, CD15, CD19 and CD20. The cytogenetic analysis showed complicate d qualitative and quantitative abnormality of chromosomes, without typical t(2;5). It is concluded that the established cell line is CD30+ anaplastic large cell lymphoma cell line.
In order to explore the role of real-time PCR in detecting minimal residual disease in multiple myeloma and Waldenstrom's macroglobulinemia after autologous peripheral blood stem cell transplantation (APBSCT), real-time PCR was used to quantitate the IgH rearrangement in 8 patients with multiple myeloma (MM) and 1 case of Waldenstrom's macroglobulinemia before and after APBSCT. The results showed that the copies of IgH rearrangement pre- or post-APBSCT were 3108 +/- 1043 and 549 +/- 660 (P < 0.05) respectively. The number of IgH copies was positively correlated with the amount of plasmocytes in patient 's bone marrow and the M-protein in peripheral blood (r = 0.86, P < 0.05). Similar result was obtained in a case of relapsed Waldenstrom's macroglobulinemia. In conclusion, the quantitative analysis of IgH rearrangement by real-time PCR is a novel way to evaluate the therapeutic efficaciousness and predict the prognoses in MM patients.
OBJECTIVE: To explore the inhibitory effect and its mechanism of salviae miltiorrhizae and beta-aescinom natrium on the postburn acute lung injury in rats. METHODS: Forty-five rats were randomly divided into sham control (C, n = 9), sodium chloride group (S, n = 9), salviae miltiorrhizae group (M, n = 9), beta-aescinom natrium group (A, n = 9), and combination group (MA, n = 9). The rats in M, A and MA groups were subjected to 30% TBSA III degree scald on the back, and all the rats were sacrificed at 24 PBH. The blood and pulmonary tissue samples were harvested from the rats at 24 PBH for the determination of leukocyte adhesiveness/aggregation (LAA) in peripheral blood, myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD) contents, and the ratio of wet to dry weights (W/D) of lung tissue. RESULTS: Compared with those in S group, the LAA in blood and the pulmonary tissue contents of MPO, MDA and W/D rate in M and A groups, and especially in MA group, were decreased significantly, but the SOD content in pulmonary tissue increased obviously in M and A groups, especially in MA group. Furthermore, blood LAA was positively correlated with pulmonary tissue MDA content. CONCLUSION: Postburn intra-pulmonary agglutination and aggregation of PMNs and pulmonary injury by oxygen free radicals (OFRs) and their products could be inhibited by either Salviae Miltiorrhizae or beta-aescinom natrium. In addition, these agents could also increase the tissue content of antioxidant capacity and decrease pulmonary microvascular permeability and lung water content. The results indicated that all the agents used might be effective in prevention and treatment of postburn pulmonary injury, especially when used together.
OBJECTIVE: To detect the IgH-MMSET fusion gene resulted from t (4;14) translocation in multiple myeloma and illuminate its significance. METHODS: IgH-MMSET fusion gene was detected in bone marrow specimens of 25 multiple myeloma (MM) patients and MM cell line NCI-H929 using reverse-transcription PCR (RT-PCR) assay followed by nested PCR to increase the sensitivity. The purified PCR products were cloned into pGEM-T vector and then sequenced using M13 forward primers. The fragment sequences were compared with that in GenBank to find matched sequences. RESULTS: Only a 438 base pair long fragment was obtained after RT-PCR assay and was confirmed by sequencing to be a fusion gene product of IgH gene and MMSET gene in MM cell line NCI-H929. The breakpoints were located within the C micro region of IgH gene on chromosome 14 and intron 3 of MMSET gene on chromosome 4. IgH-MMSET hybrid transcripts were detected in 3 of 25 MM patients through nested PCR assay. The amplified fragments of the 3 patients were 237 base pairs (bp), 239 bp and 239 bp in length, respectively. The breakpoints on chromosome 4 were identical to that of NCI-H929 cell. CONCLUSIONS: The formation of IgH-MMSET fusion gene is resulted from t (4;14) translocation in MM. The incidence rate is 12.0%. The presence of IgH-MMSET fusion gene may predict poor prognosis.
BACKGROUND & OBJECTIVE: Multiple myeloma (MM), a plasma cell tumor, is difficult to cure by now. Previous study showed that As2O3 could inhibit the proliferation and induce the apoptosis of myeloma cell in vitro. The aim of this study was to explore the possible mechanism of arsenic trioxide (As2O3) on multiple myeloma cells. METHODS: The cytotoxic effects of As2O3 on five myeloma cell lines U266, SKO-007, LP-1, HS-Sultan, and KM3 were examined using MTT bioassay, and the concentration of 50% growth inhibition (IC(50)) was calculated. The synergistic or antagonistic effects of menadione (VK(3)), N-acetyl-cysteine (NAC), and reduced glutathione (GSH) combined with As2O3 were also examined. The cellular GSH levels in five MM cell lines and its changes in U266 cells after treated with As2O3, VK(3), NAC, and exogenous GSH were determined by colorimetric assay, and the relationship between IC(50) and cellular GSH levels was analyzed. RESULTS: As2O3 inhibited the proliferation of all five myeloma cells, but with different sensitivity. GSH contents in five MM cells were correlated with its IC(50) significantly (r=0.87,P< 0.05). Oxidant VK(3) had significant synergistic effect with As2O3, and antioxidants NAC and GSH partly blocked the growth inhibition of As2O3. Both As2O3 and VK(3) decreased the GSH contents, NAC and GSH increased them contrarily. CONCLUSION: One of the mechanisms of effect of As2O3 on myeloma cells may be through decreasing the cellular GSH levels and inducing myeloma cell apoptosis.
Myostatin, a member of the TGF-beta family, negatively regulates skeletal muscle development. Mutation of myostatin activity leads to increases muscle growth and carcass lean yield. The bovine myostatin mutation cDNA was amplified by polymerase chain reaction, and then sub-cloned into the expression vector pET-30a( + ) to form the expression plasmid pET30a (+)-action/ Myostatin. The recombinant plasmid was transformed into E. coli BL21. The overexpression product of pET30a (+)-action/ Myostatin was been showed in vitro. Sheep skeletal muscle cell were cultured with the purified myostatin mutation C-terminal peptide. The results of this study suggest that had a powerful activity to stimulate the hyperplasia and proliferation of sheep muscle cells and shows high biochemical activity.
Spark discharge method was used to take simulative investigations on the conversion reaction from CS2 to COS by lightning. The results showed that 1.33 x 10(3) Pa CS2 could act with O2 or H2O in the atmosphere (25 degrees C, 10(5) Pa) under electric discharge conditions (V = 3000 V), and COS was produced as well as other species such as CO, CO2, SO2 and so on. Factors such as CS2 concentration, water vapor and discharge time played important roles in the formation of COS. Based on these results and several theories, possible mechanisms of correlative processes during thunderstorms were proposed here, which could contribute to give evidence for the conversion from CS2 to COS by lightning during thunderstorms.
OBJECTIVE: To establish a multiple myeloma (MM) cell line and analyze its biological characteristics. METHODS: Mononuclear cells isolated from the peripheral blood (PB) and bone marrow (BM) of an advanced MM patient (lambda light chain type) were incubated by liquid cell culture, cell morphology was analyzed by Wright-Giemsa-staining and cytochemical staining, immunophenotyping by flow cytometry, cytogenetic analysis by chromosome RHG-banding method. Quantitative fluorescent polymerase chain reaction was used to detect EBV DNA. RESULTS: The established cell line could survive and proliferate in the presence of feeder cells or conditioned medium. The cells secreted lambda light chain and were negative for EBV. The Wright-Giemsa-staining showed typical plasmablast or plasma cell morphology. The cytochemical staining of the cells showed the following reactivity pattern: positive for acid phosphatase, negative for myeloperoxidase. The immunoprofile of the cells was concordant with that of MM cells: positive for CD(10), CD(28), CD(38), CD(138), CD(56), CD(49d), CD(44), CD(54) and CD(58), negative for CD(19), CD(40), CD(95), CD(95)L, CD(34), CD(2) and CD(5). The cytogenetic analysis showed complex chromosome abnormality of i (1q +), 8q +, 13q +, i (17q), i (18q) and + M. There was no difference in morphology, immunophenotype and cytogenetics between cells from PB and BM. CONCLUSION: A MM cell line secreting lambda light chain named CZ-1, was established. The cells from both PB and BM have the same biological characteristics.