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Biomedical subjects

Jun Yan

Publications and source records attributed to Jun Yan.

At least 91 records · Page 5Linked to original sources
PubMed2004

Cloning of LjCYC1 gene and nuclear localization of LjCYC1 protein in Lotus japonicus.

The LjCYC1 (Lotus japonicus Cycloidea-like 1) gene, a homolog of CYC (Cycloidea) belonging to the TCP [TB1(teosinte branched 1), CYC, PCFs (PCF1 and PCF2)] gene family and encoding a predicted transcription factor and being proposed controlling different aspects of plant development, was isolated from the papilionaceous plant Lotus japonicus by screening the genomic DNA library, in order to test the functional conservation and divarication of CYC-like genes in legume. Sequence analyses indicate that LjCYC1 gene contains two exons and one intron and encodes a 370-AA peptide LjCYC1. The putative protein, LjCYC1, contains a TCP domain and an R domain, being a member of the CYC/TB1 subfamily of TCP family, and has 39.0% identity with and 42.6% similarity to CYC. LjCYC1-cDNA was cloned through RT-PCR. Different regions of the LjCYC1-cDNA were fused with the report gene GUS and then the fused constructs were transiently expressed in the onion epidermal cells through particle bombardment. Results of GUS and DAPI staining showed that the chimeric proteins with TCP domain were localized within the nucleus, confirming that LjCYC1 may act as a transcription factor. But the TCP domain itself could not confer the nuclear localization because the chimeric proteins with TCP domain alone were dispersed all over the transformed cells.

Amino Acid Sequence↗
PubMed2003

Trihydrophobin 1 is a new negative regulator of A-Raf kinase.

Our previous work indicated that instead of binding to B-Raf or C-Raf, trihydrophobin 1 (TH1) specifically binds to A-Raf kinase both in vitro and in vivo. In this work, we investigated its function further. Using confocal microscopy, we found that TH1 colocalizes with A-Raf, which confirms our former results. The region of TH1 responsible for the interaction with A-Raf is mapped to amino acids 1-372. Coimmunoprecipitation experiments demonstrate that TH1 is associated with A-Raf in both quiescent and serum-stimulated cells. Wild type A-Raf binds increasingly to TH1 when it is activated by serum and/or upstream oncogenic Ras/Src compared with that of "kinase-dead" A-Raf. The latter can still bind to TH1 under the same experimental condition. The binding pattern of A-Raf implies that this interaction is mediated in part by the A-Raf kinase activity. As indicated by Raf protein kinase assays, TH1 inhibits A-Raf kinase, whereas neither B-Raf nor C-Raf kinase activity is influenced. Furthermore, we observed that TH1 inhibited cell cycle progression in TH1 stably transfected 7721 cells compared with mock cells, and flow cell cytometry analysis suggested that the TH1 stably transfected 7721 cells were G(0)/G(1) phase-arrested. Taken together, our data provide a clue to understanding the cellular function of TH1 on Raf isoform-specific regulation.

Animals↗
PubMed2003

Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells.

The tumor-killing mechanisms available to monoclonal antibodies (mAbs; e.g., antagonism of growth factor receptors, antibody-dependent cell-mediated cytotoxicity) limit efficacy. Previous studies suggested that i.v. beta-glucan might function as an adjuvant for antitumor mAbs. beta- Glucan had been shown to function via the iC3b-receptor complement receptor 3 (CR3; CD11b/CD18) thereby enhancing leukocyte killing of tumor cells coated with iC3b via naturally occurring antitumor antibodies. Therapy with beta-glucans was limited by levels of natural antibodies and by tumor escape through elimination of antigen-positive cells. Accordingly, it was hypothesized that beta-glucan responses could be improved by combined administration with antitumor mAbs. Five tumor models were explored in BALB/c or C57Bl/6 mice using tumors that expressed either high levels of naturally occurring antigens (e.g., G(D2) ganglioside) or recombinant human MUC1. In comparison with antitumor mAb or beta-glucan alone, combined treatment with mAb plus beta-glucan produced significantly greater tumor regression in all models that included mammary, s.c., and hepatic tumors. Tumor-free survival only occurred in models that incorporated stable expression of the target antigen. beta-Glucan enhancement of the mAb tumoricidal response did not occur in mice deficient in either leukocyte CR3 (CD11b(-/-)) or serum C3, confirming the requirement for CR3 on leukocytes and iC3b on tumors. Granulocytes appeared to be primarily responsible for tumoricidal activity, because beta-glucan therapeutic responses did not occur in granulocyte-depleted mice. These data suggest that the therapeutic efficacy of mAbs known to activate complement (e.g., Herceptin, Rituxan, and Erbitux) could be significantly enhanced if they were combined with beta-glucan.

Adenocarcinoma↗
PubMed2003

A novel organoselenium compound induces cell cycle arrest and apoptosis in prostate cancer cell lines.

Thioredoxin reductase (TrxR) in conjunction with thioredoxin (Trx) is a ubiquitous intracellular oxidoreductase system with antioxidant and redox regulatory roles. The properties of TrxR in combination with the functions of Trx position this system at the core of cellular thiol redox control and antioxidant defense. In some human tumors, the thioredoxin system is found over-expressed. Because of its role in stimulating cancer cell growth and as an inhibitor of apoptosis, the Trx system offers a target for the development of drugs to treat and prevent cancer. In a previous research, we successfully synthesized a novel organoselenium compound BBSKE(1,2-[bis(1,2-Benzisoselenazolone-3(2H)-ketone)]ethane, BBSKE, PCT: CN02/00412) targeting the TrxR, and it has demonstrated the inhibitory effect on the growth of a variety of human cancer cells from various organs. In this study, we investigated the inhibitory effect of BBSKE on TrxR activity in PC-3 and DU145 human prostate cancer cell lines, and its antitumoral effect on these two cell lines. Treatment of BBSKE inhibited the TrxR activity in both of the cell lines in a dose-dependent manner and it also inhibited the proliferation of these two cell lines in a dose-dependent manner. Cell cycle analysis showed S phase arrest in both of the cell lines following 48 h exposure to BBSKE. During the S arrest, analysis of cell cycle regulatory proteins demonstrated that BBSKE increased the protein levels of cyclinA, cyclinE, and P21, but decreased the levels of cyclinB1, cyclinD1, and Cdk4. Furthermore, BBSKE decreased the protein level of Bcl-2 but increased the level of Bax, and induced apoptosis in PC-3 and DU145 human prostate cancer cell lines. These results suggest that this novel TrxR inhibitor inhibits the proliferation of prostate cancer cells via S phase arrest and apoptosis in association with the regulation of multiple molecules in the cell cycle.

Antineoplastic Agents↗
PubMed2003

IFN-gamma-producing gamma delta T cells help control murine West Nile virus infection.

West Nile (WN) virus causes fatal meningoencephalitis in laboratory mice, thereby partially mimicking human disease. Using this model, we have demonstrated that mice deficient in gammadelta T cells are more susceptible to WN virus infection. TCRdelta(-/-) mice have elevated viral loads and greater dissemination of the pathogen to the CNS. In wild-type mice, gammadelta T cells expanded significantly during WN virus infection, produced IFN-gamma in ex vivo assays, and enhanced perforin expression by splenic T cells. Adoptive transfer of gammadelta T cells to TCRdelta(-/-) mice reduced the susceptibility of these mice to WN virus, and this effect was primarily due to IFN-gamma-producing gammadelta T cells. These data demonstrate a distinct role for gammadelta T cells in the control of and prevention of mortality from murine WN virus infection.

Adoptive Transfer↗
PubMed2003

Lewis acid mediated reactions of zirconacyclopentenes with aldehydes affording homoallyl ketones via oppenauer-type oxidation.

Three different components involving alkynes, ethylene, and aldehydes were selectively integrated in a one-pot procedure to afford homoallyl ketones in good yields, via an effective combination of zirconocene-mediated C-C bond forming reactions and Lewis acid mediated organic transformation. Mechanistic studies revealed that a formal Oppenauer oxidation of seven-membered oxazirconacycles, generated in situ from the reactions of zirconacyclopentenes and aldehydes, was promoted by Lewis acid-aldehyde adducts. As a whole, the first aldehyde was incorporated into the product and the second aldehyde was reduced to an alcohol. Multiply deuterated homoallyl ketones could be readily prepared in high yields with more than 98% deuterium incorporation by using this method.

Journal Article↗
PubMed2003

Overexpression of beta-1,4-galactosyltransferase I in rat Schwann cells promotes the growth of co-cultured dorsal root ganglia.

The cell surface beta-1,4-galactosyltransferase I (beta-1,4-GalT-I) functions as one of the receptors of laminin during the neurite outgrowth on basal lamina by binding to N-linked oligosaccharides in the laminin E8 domain. In this study, we demonstrated that the purified rat Schwann cells transfected with the expression plasmid of beta-1,4-GalT-I cDNA transiently promoted outgrowth and elongation of the neurites from co-cultured rat dorsal root ganglia, while those transfected with the antisense expression plasmid of beta-1,4-GalT-I had the opposite effects. These results suggested that the expression of beta-1,4-GalT-I in Schwann cells of peripheral nerve might promote both growth of developmental neuron and regeneration of injured nerve.

Animals↗
PubMed2003

Aging effects on spatial tuning of hippocampal place cells in mice.

One reason the electrophysiological correlates of hippocampal neurons are of interest is the possibility that they reflect their representational properties, presumably spatial/relational ones. Stable spatial representations, based on activity of ensembles of hippocampal place cells, initially develop through a series of short-episodic spatial tunings. Hence these short-episodic spatial tunings are important for understanding the establishment of stable place fields. Studies of age-related changes in place cell activities traditionally focus on place fields. In the present study, we characterized the short-episodic spatial tunings (1-min bins) of hippocampal CA1 place cells of freely moving mice in a familiar cylinder arena, and compared these functions in young and old mice. Spatial tuning was expressed by spatial selectivity, which we found fluctuated across a 16-min recording session in both young and old mice. High spatial selectivity, which is mainly due to the low firing of a place cell out of the place field in young mice, was significantly higher in old mice. The high firing rate out of the place field was the main factor contributing to significantly lower spatial selectivity in old mice. In addition, young mice showed a broad peak in the spatial selectivity between 4 and 10 min. In contrast old mice showed no peak in the spatial selectivity during this time period. The stability of place fields after a 24-h interval was also lower in old mice than in young mice. The low spatial tuning and unstable place fields suggest that a hippocampal-based spatial representation was impaired in the old mice. Furthermore, we speculate that the age-related impairment in hippocampal inhibition system may be involved in the impaired spatial representation of hippocampal CA1 place cells in old mice.

Action Potentials↗
PubMed2003

[Arterial switch operation in older infants with severe pulmonary hypertension].

OBJECTIVE: To investigate the clinical efficacy of arterial swith operation on transposition of great artery (TGA) and Tausing-Bing anomaly. METHODS: Between June 2000 and December 2002, 30 consecutive patients, aged 3 days to 6 years (mean, 9.4 +/- 15 months) with the mean body weight was 6.1 kg +/- 2.7 kg, underwent arterial switch operation. Among the 30 patients 7 suffered from TGA with intact ventricular septum, 19 from TGA with ventricular septal defect (VSD), 3 from Taussing-Bing anomaly, and 1 from corrected TGA; 12 were complicated by atrial septal defect (ASD) and 18 complicated by patent ductus arteriosus (PDA); 23 had severe pulmonary hypertension; 2 had left ventricular outlet stenosis. Coronary type A distribution was recognized in 26 cases, type D in 4, and one of them having the origin of the left descending artery tunneled in the aortic wall. The operation was performed under general anesthesia and extracorporeal circulation with low temperature and low volume blood flow. Prostaglandin 1 was administered pre-operatively in 3 patients, one of which underwent balloon atrial septostomy and one underwent pulmonary banding and systemic to pulmonary shunt pre-operatively. The aorta and pulmonary artery were transected above the valvular commisures, the coronary ostia with all the adjacent sinus of Valsalva were excised and re-implanted to the proximal neo-aorta, and then aortic anastomosis was completed. The proximal neo-pulmonary trunk was reconstructed with a large autologous native pericardium as a posterior patch. The pulmonary anastomosis was completed after the aortic cross-clamp was released. The VSD was repaired through the atrium or proximal aorta with dacron patches. RESULTS: Two patients died with a hospital mortality rate of 6.7%. No death was directly related to any coronary artery problem. One 5 day-old neonate with TGA and an intact septum having refractory hypotension, hypoxemia, and acidosis pre-operatively underwent a smooth emergency operation. The patient had a refractory low cardiac output syndrome post-operatively and died 20 hours after the operation. Another patient with chylothorax died of allergy from iodophor 22 days postoperatively. The pulmonary pressure decreases significantly in 22 patients who had severe pulmonary hypertension preoperatively with the mean pressure 46.7 mm Hg preoperatively and 31.3 mm Hg postoperatively. 28 patients were discharged from hospital uneventfully. Follow-up of 1 to 31 months showed survival with no late complications and death. CONCLUSION: The arterial switch procedure has a satisfying effect on TGA for patients older than 1 month with severe pulmonary hypertension.

Cardiac Surgical Procedures↗
PubMed2003

The C-terminal kinase domain of the p34cdc2-related PITSLRE protein kinase (p110C) associates with p21-activated kinase 1 and inhibits its activity during anoikis.

The PITSLRE protein kinases are parts of the large family of p34cdc2-related kinases. During apoptosis induced by some stimuli, specific PITSLRE isoforms are cleaved by caspase to produce a protein that contains the C-terminal kinase domain of the PITSLRE proteins (p110C). The p110C induces apoptosis when it is ectopically expressed in Chinese hamster ovary cells. In our study, similar induction of this p110C was observed during anoikis in NIH3T3 cells. To investigate the molecular mechanism of apoptosis mediated by p110C, we used the yeast two-hybrid system to screen a human fetal liver cDNA library and identified p21-activated kinase 1 (PAK1) as an interacting partner of p110C. The association of p110C with PAK1 was further confirmed by in vitro binding assay, in vivo coimmunoprecipitation, and confocal microscope analysis. The interaction of p110C with PAK1 occurred within the residues 210-332 of PAK1. Neither association between p58PITSLRE or p110PITSLRE and PAK1 nor association between p110C and PAK2 or PAK3 was observed. Anoikis was increased and PAK1 activity was inhibited when NIH3T3 cells were transfected with p110C. Furthermore, the binding of p110C with PAK1 and inhibition of PAK1 activity were also observed during anoikis. Taken together, these data suggested that PAK1 might participate in the apoptotic pathway mediated by p110C.

3T3 Cells↗
PubMed2003

The beta-(1-->6)-branched beta-(1-->3) glucohexaose and its analogues containing an alpha-(1-->3)-linked bond have similar stimulatory effects on the mouse spleen as Lentinan.

The stimulatory effects of the synthetic beta-(1-->6)-branched beta-(1-->3) glucohexaose and its analogues containing an alpha-(1-->3)-linked bond on the mouse spleen were studied for elucidation of the mechanism of their antitumor activity, and their stimulatory effects were compared with Lentinan. The mouse spleen's weight was increased after the intraperitoneal (i.p.) injection of the oligosaccharides compared with the saline group. In addition, routinely hematoxylin and eosin (HE)-stained spleen sections showed that the injection also changed the spleen's histopathology. RNA samples were isolated from splenocytes of oligosaccharides, Lentinan or saline-injected mice. Reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot showed that the administration of the oligosaccharides or Lentinan enhanced mouse spleen mRNA production of TNF-alpha but not IL-2. The injection also enhanced Concanavalin A (Con A)-induced mouse splenocytes proliferation, but the in vitro administration of the oligosaccharides did not have the proliferation-enhancing effect. Taken together, these results suggest that the synthetic beta-(1-->6)-branched beta-(1-->3) glucohexaose and its analogues containing an alpha-(1-->3)-linked bond have similar stimulatory effects as Lentinan. Additionally, they may exert their antitumor effects through the induction of splenocytes mediated immune responses.

Animals↗
PubMed2003

Canadian Association of Neuroscience Review: development and plasticity of the auditory cortex.

The functions of the cerebral cortex are predominantly established during the critical period of development. One obvious developmental feature is its division into different functional areas that systematically represent different environmental information. This is the result of interactions between intrinsic (genetic) factors and extrinsic (environmental) factors. Following this critical period, the cerebral cortex attains its adult form but it will continue to adapt to environmental changes. Thus, the cerebral cortex is constantly adapting to the environment (plasticity) from its embryonic stages to the last minute of life. This review details important factors that contribute to the development and plasticity of the auditory cortex. The instructive role of thalamocortical innervation, the regulatory role of cholinergic projection of the basal forebrain and the potential role of the corticofugal modulation are presented.

Acetylcholine↗
PubMed2003

Memory CD4+ T cells do not induce graft-versus-host disease.

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Donor T cells that accompany stem cell grafts cause GVHD by attacking recipient tissues; therefore, all patients receive GVHD prophylaxis by depletion of T cells from the allograft or through immunosuppressant drugs. In addition to providing a graft-versus-leukemia effect, donor T cells are critical for reconstituting T cell-mediated immunity. Ideally, immunity to infectious agents would be transferred from donor to host without GVHD. Most donors have been exposed to common pathogens and have an increased precursor frequency of memory T cells against pathogenic antigens. We therefore asked whether memory CD62L-CD44+ CD4+ T cells would induce less GVHD than unfractionated or naive CD4+ T cells. Strikingly, we found that memory CD4 cells induced neither clinical nor histologic GVHD. This effect was not due to the increased number of CD4+CD25+ regulatory T cells found in the CD62L-CD44+ fraction because memory T cells depletion of these cells did not cause GVHD. Memory CD4 cells engrafted and responded to antigen both in vivo and in vitro. If these murine results are applicable to human alloSCT, selective administration of memory T cells could greatly improve post-transplant immune reconstitution.

Animals↗
PubMed2003

Tributyrin inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest.

AIM: To evaluate the effects of tributyrin, a pro-drug of natural butyrate and a neutral short-chain fatty acid triglyceride, on the growth inhibition of human gastric cancer SGC-7901 cell. METHODS: Human gastric cancer SGC-7901 cells were exposed to tributyrin at 0.5, 1, 2, 5, 10 and 50 mmol/L(-1) for 24-72 h. MTT assay was applied to detect the cell proliferation. [(3)H]-TdR uptake was measured to determine DNA synthesis. Apoptotic morphology was observed by electron microscopy and Hoechst-33258 staining. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to detect tributyrin-triggered apoptosis. The expressions of PARP, Bcl-2 and Bax were examined by Western blot assay. RESULTS: Tributyrin could initiate growth inhibition of SGC-7901 cell in a dose- and time-dependent manner. [(3)H]-TdR uptake by SGC-7901 cells was reduced to 33.6 % after 48 h treatment with 2 mmol/L(-1) tributyrin, compared with the control (P<0.05). Apoptotic morphology was detected by TUNEL assay. Flow cytometry revealed that tributyrin could induce apoptosis of SGC-7901 cells in dose-dependent manner. After 48 hours incubation with tributyrin at 2 mmol/L(-1), the level of Bcl-2 protein was lowered, and the level of Bax protein was increased in SGC-7901, accompanied by PARP cleavage. CONCLUSION: Tributyrin could inhibit the growth of gastric cancer cells effectively in vitro by inhibiting DNA synthesis and inducing apoptosis, which was associated with the down-regulated Bcl-2 expression and the up-regulated Bax expression. Therefore, tributyrin might be a promising chemopreventive and chemotherapeutic agent against human gastric carcinogenesis.

Antineoplastic Agents↗