Biomedical subjects

Hui Sun

Publications and source records attributed to Hui Sun.

At least 37 records · Page 2Linked to original sources

PubMed2006

Effects of histone deacetylase inhibitors on transcriptional regulation of the hsp70 gene in Drosophila.

Histone acetyltransferases/deacetylases contribute to the activation or inactivation of transcription by modifying the structure of chromatin. Here we examined the effects of histone deacetylase inhibitors (HDIs), trichostatin A, and sodium butyrate on hsp70 gene transcriptional regulation in Drosophila. The chromatin immunoprecipitation assays revealed that HDI treatments induced the hyperacetylation of histone H3 at the promoter and the transcribing regions of hsp70 gene, increased the accessibility of heat-shock factor to target heat-shock element, and promoted the RNA polymerase II-mediated transcription. Moreover, the quantitative real-time PCR confirmed that the HDI-induced hyperacetylation of histone H3 enhanced both the basal and the inducible expression of hsp70 mRNA level. In addition, the acetylation level of histone H3 at the promoter exhibited a fluctuated change upon the time of heat shock. These experimental data implicated a causal link between histone acetylation and enhanced transcription initiation of hsp70 gene in Drosophila.

Acetylation↗

PubMed2006

Slow and selective death of spinal motor neurons in vivo by intrathecal infusion of kainic acid: implications for AMPA receptor-mediated excitotoxicity in ALS.

Excitotoxicity mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors has been proposed to play a major role in the selective death of motor neurons in sporadic amyotrophic lateral sclerosis (ALS), and motor neurons are more vulnerable to AMPA receptor-mediated excitotoxicity than are other neuronal subclasses. On the basis of the above evidence, we aimed to develop a rat model of ALS by the long-term activation of AMPA receptors through continuous infusion of kainic acid (KA), an AMPA receptor agonist, into the spinal subarachnoid space. These rats displayed a progressive motor-selective behavioral deficit with delayed loss of spinal motor neurons, mimicking the clinicopathological characteristics of ALS. These changes were significantly ameliorated by co-infusion with 6-nitro-7-sulfamobenso(f)quinoxaline-2,3-dione (NBQX), but not with d(-)-2-amino-5-phosphonovaleric acid (APV), and were exacerbated by co-infusion with cyclothiazide, indicative of an AMPA receptor-mediated mechanism. Among the four AMPA receptor subunits, expression of GluR3 mRNA was selectively up-regulated in motor neurons but not in dorsal horn neurons of the KA-infused rats. The up-regulation of GluR3 mRNA in this model may cause a molecular change that induces the selective vulnerability of motor neurons to KA by increasing the proportion of GluR2-lacking (i.e. calcium-permeable) AMPA receptors. This rat model may be useful in investigating ALS etiology.

Amyotrophic Lateral Sclerosis↗

PubMed2006

Effects of ethanol on adenosine 5'-triphosphate-gated purinergic and 5-hydroxytryptamine receptors.

This report of the proceedings of a symposium presented at the 2005 annual meeting of the Research Society on Alcoholism highlights the actions of ethanol on purinergic (P2XRs) and 5-hydroxytryptamine3 (5-HT3Rs) receptors. Both P2XRs and 5-HT3Rs, are modulated by pharmacologically relevant concentrations of ethanol, with inhibition or stimulation of P2XR subtypes and stimulation of 5-HT3Rs, respectively. With regard to ethanol-modulatory actions, these 2 distinctly different receptor classes have been studied to a much lesser extent than other LGICs. The organizers and chairs were Daryl L. Davies and Tina K. Machu. John J. Woodward discusses the molecular pharmacology and physiology of P2XRs and 5-HT3Rs and sets the stage for a detailed investigation into the ethanol sensitivity of these channels by the invited speakers. Daryl L. Davies discusses the results from recent electrophysiological studies conducted in his and Dr. Woodward's laboratories, highlighting the actions of ethanol on P2XR subtypes. Jiang-Hong Ye discusses results from recent studies using loose-patch and whole-cell recordings on purinergic receptors expressed on neurons from the ventral tegmental area (VTA) in rats. Tina K. Machu discusses electrophysiological studies conducted in her and Dr. David Lovinger's laboratories on nonpore lining residues of the second transmembrane domain (TM2) of the 5-HT3A receptor. Li Zhang presents data demonstrating that F-actin cytoskeletons play a critical role in 5-HT3 receptor clustering in hippocampal neurons. Collectively, the presentations provided strong evidence that P2X and 5-HT3 receptors are important targets for ethanol action.

Animals↗

PubMed2006

Analysis of EGF receptor interactions with the alpha subunit of the stimulatory GTP binding protein of adenylyl cyclase, Gs.

Besides stimulating the mitogen-activated protein kinase, phospholipase Cgamma, and phosphatidylinositol 3-kinase cascades, in certain tissues and cells such as the heart, partotid gland, and luteal cells, activation of the epidermal growth factor (EGF) receptor also stimulates second-messenger systems that involve the heterotrimeric G proteins. For instance, in the heart EGF increases contractility and heart rate by elevating cellular cyclic adenosine monophosphate (cAMP) levels. This is the result of EGF-elicited activation of adenylyl cyclase via the stimulatory guanosine 5'-triphosphate (GTP)-binding protein Gs. In this context, the single transmembrane EGF receptor acts like a heptahelical G protein-coupled receptor. Here we have described the methods used to study interactions between the EGF receptor and heterotrimeric G proteins. Moreover, we have also described how the stoichiometry of EGF receptor association with the alpha subunit of Gs can be monitored in vitro. Several other single transmembrane receptors and proteins can also activate heterotrimeric G proteins, and, therefore, the methodologies described in this chapter can be adapted to other systems.

Adenylyl Cyclases↗

PubMed2006

The ternary IGF complex influences postnatal bone acquisition and the skeletal response to intermittent parathyroid hormone.

The role of circulating IGF-I in skeletal acquisition and the anabolic response to PTH is not well understood. We generated IGF-I-deficient mice by gene deletions of IGF ternary complex components including: (1) liver-specific deletion of the IGF-I gene (LID), (2) global deletion of the acid-labile (ALS) gene (ALSKO), and (3) both liver IGF-I and ALS inactivated genes (LA). Twelve-week-old male control (CTL), LID, ALSKO, and LA mice were treated with vehicle (VEH) or human PTH(1-34) for 4 weeks. VEH-treated IGF-I-deficient mice (i.e. LID, ALSKO and LA mice) exhibited reduced cortical cross-sectional area (P = 0.001) compared with CTL mice; in contrast, femoral trabecular bone volume fractions (BV/TV) of the IGF-I-deficient mice were consistently greater than CTL (P < 0.01). ALSKO mice exhibited markedly reduced osteoblast number and surface (P < 0.05), as well as mineral apposition rate compared with other IGF-I-deficient and CTL mice. Adherent bone marrow stromal cells, cultured in beta-glycerol phosphate and ascorbic acid, showed no strain differences in secreted IGF-I. In response to PTH, there were both compartment- and strain-specific effects. Cortical bone area was increased by PTH in CTL and ALSKO mice, but not in LID or LA mice. In the trabecular compartment, PTH increased femoral and vertebral BV/TV in LID, but not in ALSKO or LA mice. In conclusion, we demonstrated that the presentation of IGF-I as a circulating complex is essential for skeletal remodeling and the anabolic response to PTH. We postulate that the ternary complex itself, rather than IGF-I alone, influences bone acquisition in a compartment-specific manner (i.e. cortical vs trabecular bone).

Animals↗

PubMed2006

Streptococcus suis sequence type 7 outbreak, Sichuan, China.

An outbreak of Streptococcus suis serotype 2 emerged in the summer of 2005 in Sichuan Province, and sporadic infections occurred in 4 additional provinces of China. In total, 99 S. suis strains were isolated and analyzed in this study: 88 isolates from human patients and 11 from diseased pigs. We defined 98 of 99 isolates as pulse type I by using pulsed-field gel electrophoresis analysis of SmaI-digested chromosomal DNA. Furthermore, multilocus sequence typing classified 97 of 98 members of the pulse type I in the same sequence type (ST), ST-7. Isolates of ST-7 were more toxic to peripheral blood mononuclear cells than ST-1 strains. S. suis ST-7, the causative agent, was a single-locus variant of ST-1 with increased virulence. These findings strongly suggest that ST-7 is an emerging, highly virulent S. suis clone that caused the largest S. suis outbreak ever described.

Animals↗

PubMed2006

[Expression of SDF-1alpha and its receptor CXCR4 in acute leukemias and their relationship with extramedullary infiltration].

The study was aimed to explore the expression of stromal cell derived factor-1alpha (SDF-1alpha) and its receptor CXCR4, and their relationship with the extramedullary infiltration in acute lymphoblastic, grannulocytic and monocytic leukemia. 66 cases of acute leukemia included 31 cases of acute lymphoblatic leukemia (ALL), 20 cases of acute grannulocytic leukemia (M(2)) and 15 cases of acute monocytic leukemia (M(4)+M(5)). There were 41 cases with extramedullary infiltration and 25 cases without-extramedullary infiltration. Enzyme-linked immunoabsorbent assay (ELISA) and flow cytometry were used to determine expression of SDF-1alpha and CXCR4 respectively on leukemia cells in peripheral blood and bone marrow of different groups. The results showed that average plasma level of SDF-1alpha in the ALL, M(4)+M(5), M(2) patients and the normal control were 1317.87 +/- 220.76, 1339.79 +/- 187.06, 1063.70 +/- 190.74, 1908.34 +/- 135.55 (pg/ml) respectively. The average levels in the ALL, M(4)+M(5) and M(2) patients groups were lower than those in normal control group. Both levels in ALL and M(4)+M(5) patient groups were higher than that in M(2) patient group. The average levels of SDF-1alpha in patient group with extramedullary infiltration and patient groups without-extramedullary infiltration were 1252.49 +/- 263.12, 1234.91 +/- 185.50 (pg/ml) respectively. The former seemed as if higher than the latter, but without statistical significance. The MFI of CXCR4 expression in ALL, M(4)+M(5), M(2) patient group were 78.47 +/- 33.96, 67.21 +/- 24.29, 41.66 +/- 17.18, respectively. CXCR4 expression in ALL and M(4)+M(5) patient groups were higher than that in M(2) patient group (P > 0.05). There was no significant difference between the ALL and M(4)+M(5) patient group (P > 0.05). The MFI of CXCR4 expression in patients with extramedullary infiltration and patients without extramedullary infiltration were 81.72 +/- 27.63, 36.94 +/- 11.86 respectively. The former was higher than the latter (P < 0.05). It is concluded that the higher expression of CXCR4 on acute lymphoblatic and monocytic leukemia cells may be one of the molecular mechanisms of extramedullary infiltration in both kinds of leukemia. The average plasma levels of SDF-1alpha decreased in leukemia patients and this decrease not related to the extramedullar infiltration, which may be due to the SDF-1alpha local expression in the organ infiltrated.

Acute Disease↗

PubMed2006

[Effect of valsartan on Tribble 3 gene expression in rats with experimental diabetic cardiomyopathy].

OBJECTIVE: Tribbles, a protein family controlling mitogen-activated protein kinase cascades, might contribute to the remodeling process in dilated cardiomyopathy. We investigated the gene expression of Tribble 3 (TRB(3)), cardiac function and collagen changes in rats with diabetic cardiomyopathy (DCM) and the modulating effects of valsartan on them. METHODS: Male Wistar rats were fed with high cholesterol diet throughout the study period, streptozocin (30 mg/kg, i.p) was given at the 28th day, valsartan (30 mg.kg(-1).d(-1), n = 13) or placebo (n = 11) was administered at the 35th day to rats with fasting blood glucose > or = 11.1 mmol/L per gavage for another 12 weeks. Control rats (n = 8) were fed with regular chow. Fasting blood glucose was monitored throughout the study, left ventricular function was determined by echocardiography, myocardial collagen content quantified after Masson-staining and myocardial mRNA expression of TRB(3) detected by quantification real-time RT-PCR at the end of study. RESULTS: Cardiac function was significantly improved (EF: 74% +/- 10% vs. 66% +/- 7%, P < 0.05), myocardial collagen content decreased (13.23 +/- 3.14 vs. 16.92 +/- 3.18, P < 0.05) in rats with DCM treated with valsartan. Moreover, TRB(3) mRNA was significantly increased in rats with DCM compared to control rats (0.0198 +/- 0.0082 vs. 0.1108 +/- 0.0933, P < 0.05) and the increase could be significantly attenuated by valsartan (0.0367 +/- 0.0234, P < 0.05 vs. DCM). A significant positive correlation was observed between myocardial TRB(3) mRNA and myocardial collagen content (r = 0.67, P < 0.05) and between TRB(3) mRNA and fasting blood glucose (r = 0.69, P < 0.05) in rats with DCM. CONCLUSION: Our results show for the first time that myocardial TRB(3) mRNA is upregulated in rats with DCM and which could be down-regulated by valsartan.

Animals↗

PubMed2006

[The role of glucose/TSP-1/TGFbeta1 signal pathways in diabetic cardiomyopathy].

OBJECTIVE: Hyperglycemia could upregulate transforming growth factor-beta (TGFbeta(1)) via thrombospondin (TSP-1) and induce fibrotic renal disease in the rat in vivo and myocardial fibrosis was related to cardiac dysfunction in diabetic patients. We explored the role of glucose/TSP-1/TGFbeta(1) signal pathways in the development of diabetic cardiomyopathy (DCM). METHODS: Male Wistar rats were fed with high cholesterol diet for 17 weeks, streptozocin (30 mg/kg, i.p) was given at the 28th day, rats with fasting blood glucose > or = 11.1 mmol/L by the end of the 5th week were assigned to DCM group (n = 11). Control rats (n = 8) were fed with regular chow. Fasting blood glucose (FBG) was monitored throughout the study. After hemodynamic measurements by the end of the study, myocardial collagen content was quantified in Masson-stained samples and the mRNA expressions of TSP-1 and TGFbeta(1) were detected by quantification real-time RT-PCR. The protein levels of TSP-1, active and latent TGFbeta(1) were detected by Western blot. RESULTS: Compared with control group, cardiac function was decreased as shown by significantly reduced left ventricular systolic pressure, dp/dt(max) and dp/dt(min), while the myocardial collagen content was significantly increased in the DCM group (11.01 +/- 3.05 vs. 16.92 +/- 3.18, P < 0.01). The myocardial mRNA expressions of TSP-1, TGFbeta(1) and protein expressions of TSP-1, active and latent TGFbeta(1) in the DCM group were also significantly higher than those of the control group. Moreover, myocardial collagen was positively correlated to FBG (r = 0.746, P < 0.01); mRNA expressions of TSP-1 and TGFbeta(1), protein expressions of TSP-1 and active TGFbeta(1) were positively correlated to FBG and myocardial collagen (P < 0.05). However, there were no correlations between the protein expression of latent TGFbeta(1) and FBG and myocardial collagen. CONCLUSION: The pathway of glucose/TSP-1/TGFbeta(1) might play an important role in myocardial interstitial fibrosis of DCM. It may be the basis of novel therapeutic approaches for ameliorating DCM.

Animals↗

PubMed2006

[Expressions of survivin, Bcl-2 and VEGF in patients with myelodysplastic syndrome and their relationship].

To determine the possible roles of survivin in the pathogenesis of myelodysplastic syndrome (MDS) and to explore the relationship between apoptosis and angiogenesis in MDS, the expressions of survivin, Bcl-2 and VEGF were detected in the BM cells of de novo patients with MDS, patients with AML and individuals of control by immunochemical staining and their relationship was analyzed. The results showed that the expression rate and integral of all the three proteins in the low-risk group of MDS, high-risk group of MDS and de novo acute myeloid leukemia patients gradually increased, in addition to expression of Bcl-2 in low-risk group of MDS and control group. The significant differences were observed in every two groups and there were positive relations between the every two proteins. It is concluded that survivin, Bcl-2 and VEGF are all involved in the pathogenesis of MDS, and related with the progression of this disease, the deregulated apoptosis and angiogenesis may be involved in the pathogenesis of MDS through interaction among three proteins mentioned above.

Adult↗

PubMed2006

[Expression and role of beta-catenin in acute leukemia bone marrow cells].

The aim of this study was to explore the expression of beta-catenin in acute leukemia bone marrow cells and its role in the development of acute leukemia. The expression of beta-catenin of bone marrow cells was detected by immunocytochemistry and flow cytometry in 20 cases of newly diagnosed acute leukemia. Meanwhile the expression of the proliferating index Ki-67 was detected by immunocytochemistry. The results showed that the expression of beta-catenin and Ki-67 in acute leukemia bone marrow cells was significantly higher than those in control group (P < 0.05). The migration of beta-catenin from cytoplasm to nuclear was observed in acute leukemia bone marrow cells. There was a positive correlation between the expressions of beta-catenin and Ki-67 in all the cases and the Pearson correlation coefficient was 0.845. In conclusion, the expression of beta-catenin was significantly high in acute leukemia bone marrow cells and showed a positive correlation with the cell proliferation. It suggests that beta-catenin may be involved in the development of acute leukemia through promoting the excessive proliferation of cells.

Acute Disease↗

PubMed2006

[Influence of chemotherapy on expression of TRAIL in primary acute leukemic cells].

In order to explore the expression of TRAIL in primary acute leukemic cells and the effect of chemotherapeutic drug on TRAIL expression in acute leukemic cells, the expression of TRAIL was assessed by flow cytometry on day 0, day 1, day 3 and day 5 in 16 patients with acute leukemia received chemotherapy. Meanwhile, the bone marrow mononuclear cells of acute leukemia patients were cultured in vitro with VP-16 and INFalpha-2a. Expression of TRAIL was analyszed by flow cytometry at 24, 48 and 72 hours after treatment. The results showed that the expression of TRAIL in the peripheral blood mononuclear cells was upregulated significantly from day 1 after chemotherapy (P < 0.05). In in vitro culture test, VP-16 upregulated the expression of TRAIL on acute leukemia bone marrow mononuclear cells (P < 0.05). Compared with VP-16 alone, the combination of VP-16 with IFNalpha-2a showed no synergic effects on the expression of TRAIL. It is concluded that the expression of TRAIL increases after chemotherapy in vivo and after treatment with VP-16 and IFN in vitro, which suggests that the apoptosis induced by TRAIL may play an important role in chemotherapy of leukemia.

Acute Disease↗

PubMed2006

[Effects of interferon on the expressions of TRAIL and other apoptosis- inducing genes in peripheral blood mononuclear cells from polycythemia rubra vera].

OBJECTIVE: To investigate the effects of interferon (IFN) on the natural killer (NK) cytotoxicity and the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and other apoptosis-inducing genes in peripheral blood mononuclear cells (PBMNC) from polycythemia rubra vera (PV). METHODS: PBMNC were collected from 12 PV patients. The NK cytotoxicity was assessed by lactate dehydrogenase release assay and lytic units (LU) were calculated based on specific lysis. The TRAIL mRNA and other apoptosis-inducing genes were determined by RNase protection assay. RESULTS: The NK cytotoxicity of untreated PBMNC from PV was (152.0 +/- 146.6) LU. And of IFNalpha1b- and IFNalpha2b-treated PBMNC were up to (250.9 +/- 197.4) LU and (355.9 +/- 249.9) LU, respectively (P < 0.05 and P < 0.01, respectively). The expression of TRAIL mRNA was upregulated in IFNalpha1b and IFNalpha2b stimulated-PBMNC. Up-regulation of mRNA levels of FLICE, DR3, DR4 and TNFRp55 genes was observed in PBMNC after stimulated with IFNalpha, which also induced the mRNA expressions of FasL, Fas, TRADD and RIP. To explore the role of TRAIL in IFNalpha-augmented NK cytotoxicity, neutralizing assay was used and the results showed that IFNalpha-augmented NK activity could be blocked partially by peptides DR4-Fc and DR5-Fc. CONCLUSION: IFNalpha induced/upregulated the expression of TRAIL and other apoptosis-inducing genes in PBMNC from PV patients, which partially contribute to the IFNalpha-augmented NK cytotoxicity augmentation. This may be one of the mechanisms of IFNalpha therapy for PV.

Adult↗

PubMed2006

[Inhibition of hTERT antisense oligodeoxynucleotide on proliferation and telomerase activity in HL-60 cells].

This study was purposed to investigate the inhibition of hTERT antisense oligodeoxynucleotide (ASODN) on the proliferation and telomerase activity in HL-60 cells and to explore the relativity between the telomerase activity and the expression of hTERT gene in HL-60 cells. After treated by hTERT ASODN the expression of hTERT was detected by RT-PCR, the morphological changes of HL-60 cells was observed with inverted microscopy, the cell proliferation was measured by MTT method, and the telomerase activity was determined with TRAP-ELISA and TRAP-PAGE. The results showed that after sealing hTERT gene with ASODN for 72 hours, the expression of hTERT gene was significantly inhibited, the cell growth was repressed and the ability of proliferation decreased, and the effect was specific in sequence and dependent in dose and time. OD(450-690) values were 2.648 +/- 0.42, 1.504 +/- 0.47, 1.223 +/- 0.39, 0.944 +/- 0.16 respectively, as the cells were treated with 0, 10, 20, 30 micromol/L ASODN for 72 hours. The difference was significant as compared 10, 20, 30 micromol/L groups with 0 micromol/L ASODN group respectively (P < 0.05), but the difference was no significant when compared 20 micromol/L SODN group (2.376 +/- 0.65) with untreated group (2.648 +/- 0.42) (P > 0.05). TRAP-PAGE detection revealed that comparing ASODN groups with SODN groups the telomerase image bands were decreased and least was found in groups of 30 +/- mol/L. It is concluded that the hTERT ASODN may inhibit the proliferation and down-regulate the telomerase activity in HL-60 cells by sealing the expression of hTERT gene.

Cell Proliferation↗

PubMed2006

[Analysis and quality assessment standard of heavy metals and arsenic in Rhizoma et Radix Notopterygii from different localities].

OBJECTIVE: Five heavy metals (Hg, Cu, Cd, Pb, Cr) and arsenic (As) contents in 57 samples of from 19 localities in Sichuan, Qinghai and Gansu of Rhizoma et Radix Notopterygii sourcing from two plants Notoperygium incusum and N. forbesii has been analyzed to evaluate the content standard of heavy metal and arsenic for drafting the herbal medicine quality. METHOD: ICP-AES method was applied to determine As, Cu, Cd, Pb, Cr and CAAS method was applied to determine Hg. RESULT: Hg can not be determined through CAAS, and little Pb was determined except in limited N. forbesii samples from certain sites, while the contents of Cu in most samples are higher than 20 mg x kg(-1). As in N. forbesii samples, and Cd in N. incisum samples are higher or approximate the limitation of related standard of medicinal plants and production. Cr varies from different localities, ranging from 0.48 to 8.36 mg x kg(-1) for N. incisum and 1.44-8.03 mg x kg(-1) for N. forbesii. CONCLUSION: Referring to the related standards of medicine and vegetable, the heavy metals and arsenic contents of Rhizoma et Radix Notopterygii samples from traditional producing areas are confirmed the propositional standard, i. e., Pb < or = 5.0 mg x kg(-1), Cd < or = 0.3 mg x kg(-1), Hg < or = 0.2 mg x kg(-1), Cu < or = 28.0 mg x kg(-1), As < or = 2.0 mg x kg(-1), and Cr < or = 1.0 mg x kg(-1). Of these five heavy metals, Cu is much over the limitation standard, which suggested that GAP base of Rhizoma et Radix Notopterygii must be selected in lower Cu environmental condition in main producing area.

Apiaceae↗

PubMed2006

[Effect of hTERT ASODN on the oncogenicity and the inductive apoptosis of HL-60 cells].

OBJECTIVE: To investigate the effect of hTERT antisense oligodeoxynucleotide (ASODN) on the oncogenicity and the inductive apoptosis of HL-60 cells. METHODS: Apoptosis 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. RESULTS: After 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). CONCLUSION: The 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↗

PubMed2005

Delta9-tetrahydrocannabinol and endogenous cannabinoid anandamide directly potentiate the function of glycine receptors.

Anandamide (AEA) and delta9-tetrahydrocannabinol (THC) are endogenous and exogenous ligands, respectively, for cannabinoid receptors. Whereas most of the pharmacological actions of cannabinoids are mediated by CB1 receptors, there is also evidence that these compounds can produce effects that are not mediated by the activation of identified cannabinoid receptors. Here, we report that THC and AEA, in a CB1 receptor-independent manner, cause a significant potentiation of the amplitudes of glycine-activated currents (I(Gly)) in acutely isolated neurons from rat ventral tegmental area (VTA) and in Xenopus laevis oocytes expressing human homomeric (alpha1) and heteromeric (alpha1beta1) subunits of glycine receptors (GlyRs). The potentiation of I(Gly) by THC and AEA is concentration-dependent, with respective EC50 values of 86 +/- 9 and 319 +/- 31 nM for alpha1 homomeric receptors, 73 +/- 8 and 318 +/- 24 nM for alpha1beta1 heteromeric receptors, and 115 +/- 13 and 230 +/- 29 nM for native GlyRs in VTA neurons. The effects of THC and AEA are selective for I(Gly), because GABA-activated current in VTA neurons or in X. laevis oocytes expressing alpha2beta3gamma2 GABA(A) receptor subunits were unaffected by these compounds. The maximal potentiation by THC and AEA was observed at the lowest concentration of glycine; with increasing concentrations of glycine, the potentiation significantly decreased. The site for THC and AEA seems to be distinct from that of the alcohol and volatile anesthetics. The results indicate that THC and AEA, in pharmacologically relevant concentrations, directly potentiate the function of GlyRs through an allosteric mechanism.

Animals↗

PubMed2005

Underediting of GluR2 mRNA, a neuronal death inducing molecular change in sporadic ALS, does not occur in motor neurons in ALS1 or SBMA.

Deficient RNA editing of the AMPA receptor subunit GluR2 at the Q/R site is a primary cause of neuronal death and recently has been reported to be a tightly linked etiological cause of motor neuron death in sporadic amyotrophic lateral sclerosis (ALS). We quantified the RNA editing efficiency of the GluR2 Q/R site in single motor neurons of rats transgenic for mutant human Cu/Zn-superoxide dismutase (SOD1) as well as patients with spinal and bulbar muscular atrophy (SBMA), and found that GluR2 mRNA was completely edited in all the motor neurons examined. It seems likely that the death cascade is different among the dying motor neurons in sporadic ALS, familial ALS with mutant SOD1 and SBMA.

Aged↗