Benzimidazoles and isosteric compounds as potent and selective factor Xa inhibitors.
Benzimidazoles and their isosteric compounds as factor Xa inhibitors are discussed.
Animals↗
Biomedical subjects
Wei He
Publications and source records attributed to Wei He.
Membrane distal cytokine binding domain of LIFR interacts with soluble CNTFR in vitro.
Ciliary neurotrophic factor (CNTF) is a member of the gp130 family of cytokines. The functional receptor complex of CNTF is composed of the CNTF receptor alpha (CNTFR), gp130 and the leukemia inhibitory factor receptor (LIFR). Three regions on CNTF have been identified as binding sites for its receptors. The ligand-receptor interactions are mediated through the cytokine binding domains (CBDs) and/or the immunoglobulin-like domains of the receptors. However, in the case of CNTF, the precise nature of the protein-protein contacts in the signaling complex has not yet been resolved. In this study, we provide the first demonstration that the membrane distal CBD (CBD1) of LIFR associates in vitro with soluble CNTFR in the absence of CNTF. Moreover, purified CBD1 partially blocks CNTF signaling, but not that of interleukin-6 or LIF, in human embryonal carcinoma cell line Ntera/D1 cells. These data raise the possibility that LIFR has the capability to form a ligand-free complex with CNTFR.
Animals↗
K14-GLp65 transactivator induces transgene expression in embryonic epidermis.
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Animals↗
Evolution of the regulators of G-protein signaling multigene family in mouse and human.
The regulators of G-protein signaling (RGS) proteins are important regulatory and structural components of G-protein coupled receptor complexes. RGS proteins are GTPase activating proteins (GAPs) of Gi-and Gq-class Galpha proteins, and thereby accelerate signaling kinetics and termination. Here, we mapped the chromosomal positions of all 21 Rgs genes in mouse, and determined human RGS gene structures using genomic sequence from partially assembled bacterial artificial chromosomes (BACs) and Celera fragments. In mice and humans, 18 of 21 RGS genes are either tandemly duplicated or tightly linked to genes encoding other components of G-protein signaling pathways, including Galpha, Ggamma, receptors (GPCR), and receptor kinases (GPRK). A phylogenetic tree revealed seven RGS gene subfamilies in the yeast and metazoan genomes that have been sequenced. We propose that similar systematic analyses of all multigene families from human and other mammalian genomes will help complete the assembly and annotation of the human genome sequence.
Animals↗
RGS function in visual signal transduction.
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Animals↗
Complete 1H, 15N and 13C assignments of the carboxyl terminal domain of the ciliary neurotrophic factor receptor (CNTFR).
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Amino Acid Sequence↗
alpha4beta1 integrin regulates lamellipodia protrusion via a focal complex/focal adhesion-independent mechanism.
alpha4beta1 integrin plays an important role in cell migration. We show that when ectopically expressed in Chinese hamster ovary cells, alpha4beta1 is sufficient and required for promoting protrusion of broad lamellipodia in response to scratch-wounding, whereas alpha5beta1 does not have this effect. By time-lapse microscopy of cells expressing an alpha4/green fluorescent protein fusion protein, we show that alpha4beta1 forms transient puncta at the leading edge of cells that begin to protrude lamellipodia in response to scratch-wounding. The cells expressing a mutant alpha4/green fluorescent protein that binds paxillin at a reduced level had a faster response to scratch-wounding, forming alpha4-positive puncta and protruding lamellipodia much earlier. While enhancing lamellipodia protrusion, this mutation reduces random motility of the cells in Transwell assays, indicating that lamellipodia protrusion and random motility are distinct types of motile activities that are differentially regulated by interactions between alpha4beta1 and paxillin. Finally, we show that, at the leading edge, alpha4-positive puncta and paxillin-positive focal complexes/adhesions do not colocalize, but alpha4beta1 and paxillin colocalize partially in ruffles. These findings provide evidence for a specific role of alpha4beta1 in lamellipodia protrusion that is distinct from the motility-promoting functions of alpha5beta1 and other integrins that mediate cell adhesion and signaling events through focal complexes and focal adhesions.
Animals↗
Partial rescue of taste responses of alpha-gustducin null mice by transgenic expression of alpha-transducin.
The transduction of responses to bitter and sweet compounds utilizes guanine nucleotide binding proteins (G proteins) and their coupled receptors. Alpha-gustducin, a transducin-like G protein alpha-subunit, and rod alpha-transducin are expressed in taste receptor cells. Alpha-gustducin knockout mice have profoundly diminished behavioral and electrophysiological responses to many bitter and sweet compounds, although these mice retain residual responses to these compounds. Alpha-gustducin and rod alpha-transducin are biochemically indistinguishable in their in vitro interactions with retinal phosphodiesterase, rhodopsin and G protein betagamma-subunits. To determine if alpha-transducin can function in taste receptor cells and to compare the function of alpha-gustducin versus alpha-transducin in taste transduction in vivo, we generated transgenic mice that express alpha-transducin under the control of the alpha-gustducin promoter in the alpha-gustducin null background. Immunohistochemistry showed that the alpha-transducin transgene was expressed in about two-thirds of the alpha-gustducin lineage of taste receptor cells. Two-bottle preference tests showed that transgenic expression of rod alpha-transducin partly rescued responses to denatonium benzoate, sucrose and the artificial sweetener SC45647, but not to quinine sulfate. Gustatory nerve recordings showed a partial rescue by the transgene of the response to sucrose, SC45647 and quinine, but not to denatonium. These results demonstrate that alpha-transducin can function in taste receptor cells and transduce some taste cell responses. Our results also suggest that alpha-transducin and alpha-gustducin may differ, at least in part, in their function in these cells, although this conclusion must be qualified because of the limited fidelity of the transgene expression.
Analgesics, Non-Narcotic↗
Variations of elemental distribution in brain regions of neonatal rats at different iodine intakes.
Iodine deficiency (ID) can result in irreversible damage to the brain during the fetal and neonatal stages. As the active center of many enzymes, trace elements play essential roles in brain function. In this work, the relative contents and distributions of elements (Cl, Br, Fe, Cu, and Zn) in two important brain regions, the cerebral cortex and hippocampus, of the iodine-deficient model rats were determined by the synchrotron radiation X-ray fluorescence (SRXRF) method. Meanwhile, the ID rats were supplemented with adequate and excessive iodine, respectively. The results indicated that the distributions of trace elements could be influenced by the different iodine intakes in the stage of brain development. In contrast to the control group, the contents of Cl, Br, and Zn in two brain regions showed a significant increase in the ID group; however, both Fe and Cu decreased in the cerebral cortex and increased in the hippocampus in the ID group. In addition, only slight changes of elemental contents in brain were found between the adequate and excessive iodine-supplemented rats.
Animals↗
[Detection of the HBV DNA with Sybr green 1 realtime polymerase chain reaction].
BACKGROUND: To search a novel sensitive, specific and lower cost method applicable for quantitative analysis of the hepatitis B virus DNA extensively. METHODS: Quantitative analysis of the DNA from 100 sera by real-time PCR with Sybr green 1. The results of Sybr's assay were compared with the results obtained with Taqman's fluorescent quantitative assay. RESULTS: Taqman real-time PCR could help evaluate the level of virus reliably. The results of Sybr's assay were in agreement with the Taqman's assay, but detection rate was lower. CONCLUSIONS: Sybr green 1 real-time PCR appeared to be convenient and cheap, but detection rate was lower.
Benzothiazoles↗
The protective immunity produced in infected C57BL/6 mice of a DNA vaccine encoding Schistosoma japonicum Chinese strain triose-phosphate isomerase.
The development of a SjCTPI DNA vaccine for Schistosoma japonicum and the detection of the immune responses to and the protective efficacy of immunization were performed and challenged in C57BL/6 mice. According to the gene sequence of SjCTPI and murine IL-12, three pairs of primers were designed. The full length cDNA encoding SjCTPI and P35, P40 amplified from pUC19-SjCTPI and murine IL-12 by PCR were subcloned into an eukaryotic expression vector (pcDNA3.1). Forty-five female C57BL/6 mice were divided into three groups; each mouse of the control group was injected with 100 pg of pcDNA3.1 by i.m. route; the TPI group was injected with 100 microg of pcDNA3. 1-SjCTPI; the TPI+IL- 12 group was injected with 100 microg of pcDNA3.1-SjCTPI and 100 pg of mixture of pcDNA3.1-P35 and pcDNA3.1-P40. Each mouse was immunized at weeks 1 and 5 and challenged with 45 cercariae of Schistosoma japonicum Chinese strain at week 9. The mice were killed and perfused 45 days after challenge; the numbers of recovered worms and hepatic eggs were counted. The expression of SjCTPI in muscle tissue was determined by an immunohistochemical method. Culture of spleen cells showed the production of IL-2, IL-4, IL-10 and IFN-gamma with the stimulation of specific antigen before and after challenge. Sera were collected from each group before immunization, before challenge and two weeks post challenge; ELISA and Western-blot tests were performed for detection of anti-rTPI antibodies. The antigen of SjCTPI was expressed in the membrane and plasma of the muscle cells of C57BL/6 mice. The obvious rising of IL-2 in TPI group and TPI+IL-12 group before and after challenge was seen. The anti-rTPI antibody detection with Western-blot showed that ten serum samples from the control group were negative; nine of ten serum samples from the TPI group were weakly positive, eight of ten from the TPI+IL-12 group were weakly positive. The worm and egg reduction rates of TPI group and TPI+IL- 12 group were 27.9% and 13.7%, 31.9% and 18.6% respectively in comparison with the pcDNA group. pcDNA3.1-TPI DNA vaccine could confer partial protection against a subsequent challenge of Schistosoma japonicum in C57BL/6 mice and might therefore be a potential DNA vaccine.
Animals↗
[Current status of study on selective cyclooxygenase-2 inhibitors and evaluation of its application].
Selective cyclooxygenase-2 inhibitors have anti-inflammatory efficacy and can reduce the side effects and toxicity induced by inhibition of cyclooxygenase-1, thus can be widely used in clinical practice. However, the adverse effects of these drugs should be given their due attention. Currently, looking for better selective cyclooxygenase-2 inhibitors has become a hot topic in developing the non-steroidal anti-inflammatory drugs.
Anti-Inflammatory Agents, Non-Steroidal↗
Developmental toxicity of cocaine exposure in mid-pregnancy mice.
AIM: To investigate the toxic effects of mid-pregnancy cocaine exposure on embryo-fetus. METHODS: A transplacental murine model of cocaine exposure on embryo-fetus mice was established, in which pregnant dams of comparable weight were assigned into three groups: cocaine with food ad lib (COC), saline and pair-fed with COC (SPF), and saline with food ad lib (SAL). From embryonic d 8 (E8) to E17, physiological variables of dams and offspring were recorded and concentrations of dopamine and serotonin in fetal striatum were examined. RESULTS: Compared with SAL dams, COC and SPF dams showed lower weight gain. But only COC fetuses demonstrated low brain weight and low striatum weight on E17, as well as small biparietal diameter (BPD) on postnatal d1 (P1). Surprisingly, low brain/body weight ratio was seen in COC offspring, which might reflect disproportionate growth delay in these fetuses. Neurotransmitter and histological analysis revealed high level of dopamine and serotonin in COC fetal striatum, as well as morphological alterations of liver. CONCLUSION: Mid-pregnancy cocaine exposure induces fetal growth delay in utero, especially disproportionate brain developmental retardation. Maternal undernutrition does not play a key role in fetal developmental retardation when exposed to cocaine in utero.
Animals↗
[Clinical analysis of laparoscopic pelvic and paraaortic lymphadenectomy treated patients with gynecological malignancies].
OBJECTIVE: To investigate the possibility and value of laparoscopic radial hysterectomy with lymphadenectomy in patients with gynecology malignancies. METHODS: From July 2000 through June 2002, we performed laparoscopic radial hysterectomy with lymphadenectomy on 56 patients with biopsy-proven endometrial or cervical carcinoma (21 endometrial cancer and 35 cervical cancers). Pelvic, para-aortic, and combinations of both pelvic and para-aortic lymphadenectomies were performed depending on the primary site of the disease and indication for lymph node dissection. RESULTS: Laparoscopic procedure required an average of 3.1 h, with an average blood loss of 198 ml. The average number of nodes was 16. Patients undergoing laparoscopic assisted vaginal radical hysterectomy and lymphadenectomy alone were admitted for 9.6 days on average. There were 5 patients with intraoperative complications. Two patients were bladder injury and other two patients with venous injury. One patient was colon injury and converted to an abdominal procedure. There were no ureteral or intestinal injuries. Postoperative complications occurred in 3% of patients and only one was considered ureteral constriction 1 month after operation. There has been one patient with trocar site recurrences 4 weeks after operation. Three patients have retention of urine. CONCLUSIONS: Laparoscopic assisted vaginal radical hysterectomy and lymphadenectomy was feasible and safe for treatment of cervical or endometrial cancer. Also it was a less invasive, and recovery time was reduced. This was reliable and accurate method for evaluating lymph node metastasis of cervical or endometrial carcinoma.
Adult↗
[Determination of aconitine alkaloids in a pesticide--0.25% aconitine alkaloids mixed with emulsion by high performance liquid chromatography].
The raw root of Aconitum, an important Chinese traditional medicine, contains some very toxic alkaloids such as aconitine, mesaconitine and hypaconitine etc. They are usually processed to lower the alkaloid content before used as a drug. The extract of crude drug (aconite) can be made into a plant pesticide by means of mixing with some emulsion. In order to evaluate the quality of the pesticide, we developed a rapid, specific and precise method using high performance liquid chromatography (HPLC) for the separation and quantitation of the alkaloids in the aconite extract and the mixed products (the aconite extract is mixed with emulsion). Before the determination by HPLC, the sample must be acidified with 2% (mass percentage) HCl at first. Extract the acid liquid with CHCl3. Alkalize the extract with ammonia, and add a little of 0.1 mol/L NaHCO3 and 0.1 mol/L Na2CO3 till pH 9. Extract it with CHCl3. Evaporate the extract and add a certain amount of methanol. Add the internal standard into the sample. Inject the combined sample solution onto a column of chemically bonded octadecylsilane phase and develop the chromatogram with MeOH-H2O-CHCl3-triethylamine (68:32:2:0.1, volume ratio). Aconitine, mesaconitine, hypaconitine and medroxyprogesteroni acetas (internal standard) were on base line separated. Quantify the alkaloids by peak area ratio (aconitine alkaloids vs internal standard). This method has high recovery (> 92%) and good reproducibility (RSD < 3.2%).
Aconitine↗
[Serum levels of macrophage colony stimulating factor in the patients with Alzheimer's disease].
OBJECTIVE: To investigate the availability of serum level of macrophage clony stimulating factor (M-CSF) as a marker for early diagnosis of Alzheimer's disease (AD). METHODS: The serum levels of M-CSF in 70 patients with AD, 52 healthy controls, 22 patients with VAD (vascular dementia) were measured and the serum levels of IL-1 beta, IL-6, TNF-alpha in 32 patients with AD and 20 controls were measured as well. RESULTS: Serum levels of M-CSF were significantly elevated in patients with AD when compared with healthy controls (P < 0.01) and VAD controls (P < 0.05) respectively. At the early stage of mild dementia and middle dementia, serum levels of M-CSF were significantly elevated, but at the later stage of severe dementia, they returned to normal level. Serum levels of IL-1 beta were significantly elevated in AD patients compared with controls (P < 0.05), and serum levels of TNF-alpha and IL-6 were within the normal range in patients with AD. CONCLUSIONS: The results suggest that serum M-CSF level may provide a convenient and sensitive means for the early diagnosis of Alzheimer's disease.
Aged↗
[Toll-like receptor and innate immunity in phylogenesis].
In protection against microbes, an organism recognizes the pathogen associated molecular pattern (PAMP) on microbes by pattern recognition receptor (PRR). Toll-like receptor is called innate immunity. A family of cell membrane receptor was found in recent years that can mediate innate immune responses through the activation of a series of immune-related genes. In phylogenesis, it is highly conservative. However, its functions are getting more diversified with the complication of the immune functions of organisms.
Animals↗
[Killing cell by granzyme].
Granzyme is an effector molecule of activated cytotoxic T cells and natural killer cells. It mainly mediates cell apoptosis. Its function could be explained by its molecular characteristics to some extent. Its cytotoxic effect is related to some other factors contributing to apoptosis induction. It deserves studying if perforin mediates entrance of granzyme into cells. As potential substrates of granzyme caspases and their substrates have been paid much attention to.
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