Biomedical subjects

Zhong Chen

Publications and source records attributed to Zhong Chen.

At least 37 records · Page 2Linked to original sources

PubMed2006

Minocycline protects PC12 cells against NMDA-induced injury via inhibiting 5-lipoxygenase activation.

Recently, we have reported that minocycline, a semi-synthetic tetracycline with neuroprotective effects, inhibits the in vitro ischemic-like injury and 5-lipoxygenase (5-LOX) activation in PC12 cells. In the present study, we further determined whether minocycline protects PC12 cells from excitotoxicity via inhibiting 5-LOX activation. We used N-methyl-d-aspartate (NMDA, 200 microM) to induce early (exposure for 6 h) and delayed (exposure for 6 h followed by 24 h recovery) injuries. We found that NMDA receptor antagonist ketamine, 5-LOX inhibitor caffeic acid and minocycline concentration dependently attenuated NMDA-induced early and delayed cell injuries (viability reduction and cell death). However, only ketamine (1 microM) inhibited NMDA-evoked elevation of intracellular calcium. In addition, immunohistochemical analysis showed that NMDA induced 5-LOX translocation to the nuclear membrane after 1- to 6-h exposure which was confirmed by Western blotting, indicating that 5-LOX was activated. Ketamine, caffeic acid and minocycline (each at 1 microM) inhibited 5-LOX translocation after early injury. After delayed injury, PC12 cells were shrunk, and 5-LOX was translocated to the nuclei and nuclear membrane; ketamine, caffeic acid and minocycline inhibited both cell shrinking and 5-LOX translocation. As a control, 12-LOX inhibitor baicalein showed a weak effect on cell viability and death, but no effect on 5-LOX translocation. Therefore, we conclude that the protective effect of minocycline on NMDA-induced injury is partly mediated by inhibiting 5-LOX activation.

Analysis of Variance↗

PubMed2006

Multinuclear NMR spectroscopic and theoretical study on the interactions between diperoxovanadate complex and picoline-like ligands.

To understand the substituting effects of organic ligands on the reaction equilibrium, the interactions between diperoxovanadate complex [OV(O(2))(2)(H(2)O)](-) and a series of picoline-like ligands in solution were explored using 1D multinuclear ((1)H, (13)C, and (51)V) magnetic resonance, 2D diffusion ordered spectroscopy (DOSY), and variable temperature NMR in 0.15 mol/l NaCl ionic medium for mimicking the physiological conditions. The order of reactive capability of the picoline-like ligands with [OV(O(2))(2)(H(2)O)](-) is found to be picolinamide>N-methylpicolinamide>methyl picolinate>ethyl picolinate approximately propyl picoliniate>isopropyl picolinate. The substituting group influences the reactivity by either steric effect or electron-donating effect. Competitive coordination interactions result in a series of new seven-coordinated peroxovanadate species [OV(O(2))(2)L](-) (L=picoline-like ligands). Their coordination ways were confirmed by density functional calculations.

Carbon↗

PubMed2006

Oxidized low density lipoprotein impairs endothelial progenitor cells by regulation of endothelial nitric oxide synthase.

Oxidized low density lipoprotein (OxLDL) is one of the most important risk factors of cardiovascular disease. Here, we study the impact of OxLDL on endothelial progenitor cells (EPCs) and determine whether OxLDL affects EPCs by an inhibitory effect on endothelial nitric oxide synthase (eNOS). It was found that OxLDL decreased EPC survival and impaired its adhesive, migratory, and tube-formation capacities in a dose-dependent manner. However, all of the detrimental effects of OxLDL were attenuated by pretreatment of EPCs with lectin-like oxidized low density lipoprotein receptor (LOX-1) monoclonal antibody or l-arginine. Western blot analysis revealed that OxLDL dose-dependently decreased Akt phosphorylation and eNOS protein expression and increased LOX-1 protein expression. Furthermore, OxLDL caused a decrease in eNOS mRNA expression and an increase in LOX-1 mRNA expression. These data indicate that OxLDL inhibits EPC survival and impairs its function, and this action is attributable to an inhibitory effect on eNOS.

Apoptosis↗

PubMed2006

Carnosine, a precursor of histidine, ameliorates pentylenetetrazole-induced kindled seizures in rat.

Carnosine (beta-alanyl-l-histidine) has been characterized as a putative neurotransmitter. However, so far, understanding of the role of carnosine in the brain is very limited. The objective of this study was to examine the effects of carnosine on the development of pentylenetetrazol (PTZ) kindling seizures and protection against the PTZ kindled seizures in rats. Chemical kindling was elicited by repeated intraperitoneal injection of PTZ (35 mg/kg) once every 48 h until the occurrence of Stage 4-5 seizures, and the seizure activity of kindling was recorded for 30 min. In an acute PTZ challenge study, 60 mg/kg PTZ was used to induce kindled seizure. Injection of carnosine (200, 500 mg/kg, i.p.) significantly decreased seizure stage, and prolonged the latencies for myoclonic jerks, in a dose- and time-dependent manner. In the seizure development process, 500 mg/kg carnosine also significantly delayed the onset of PTZ kindled seizures. In addition, carnosine significantly reversed decreased histamine levels induced by PTZ kindled seizure in the hippocampus. These results indicate that carnosine can protect against PTZ-induced seizures in both the development of kindling and the challenge process in rats. The results suggest that carnosine might be an endogenous anticonvulsant factor in the brain and can be used as a new antiepileptic drug in future.

Animals↗

PubMed2006

Functional evaluation of a new bioartificial liver system in vitro and in vitro.

AIM: To evaluate the functions of a new bioartificial liver (BAL) system in vitro and in vitro. METHODS: The BAL system was configured by inoculating porcine hepatocyte spheroids into the cell circuit of a hollow fiber bioreactor. In the experiments of BAL in vitro, the levels of alanine aminotransferase (ALT), total bilirubin (TB), and albumin (ALB) in the circulating hepatocyte suspension and RPMI-1640 medium were determined during 6 h of circulation in the BAL device. In the experiments of BAL in vitro, acute liver failure (ALF) model in canine was induced by an end-side portocaval shunt combined with common bile duct ligation and transaction. Blood ALT, TB and ammonia levels of ALF in canines were determined before and after BAL treatment. RESULTS: During 6 h of circulation in vitro, there was no significant change of ALT, whereas the TB and ALB levels gradually increased with time both in the hepatocyte suspension and in RPMI-1640 medium. In the BAL treatment group, blood ALT, TB and ammonia levels of ALF in canines decreased significantly. CONCLUSION: The new BAL system has the ability to perform liver functions and can be used to treat ALF.

Alanine Transaminase↗

PubMed2006

Effect of endogenous histamine in the ventral hippocampus on fear memory deficits induced by scopolamine as evaluated by step-through avoidance response in rats.

In the present study, the effects of endogenous histamine in the ventral hippocampus on fear memory deficits induced by scopolamine were investigated as evaluated by step-through avoidance response in adult male rats. Bilateral ventral hippocampal injection of scopolamine (i.h., 2, 5 microg/site) significantly produced depressant effects on the active avoidance response in a dose-dependent manner. Histamine H(3)-antagonist clobenpropit (5, 10 microg/site) significantly ameliorated the fear memory deficits induced by scopolamine in a dose-dependent manner. Its procognitive effect was completely antagonized by immepip (10 microg/site), a selective histamine H(3)-agonist. Both histamine H(1)-antagonist pyrilamine and H(2)-antagonist cimetidine, also inhibited the procognitive effects of clobenpropit. Additionally, the procognitive effects of clobenpropit on the fear memory deficits induced by scopolamine were significantly potentiated by intraperitoneal (i.p.) injection of histidine, a precursor of histamine, but markedly reversed by i.h. injection of alpha-fluoromethylhistidine (FMH, 10 microg/site), a selective and potent histidine decarboxylase inhibitor. It is concluded that the increased endogenous histamine release in the ventral hippocampus ameliorates the scopolamine-induced fear memory deficits, and its action is mainly mediated by histamine presynaptic H(3)-receptors and postsynaptic H(1)- and H(2)-receptors.

Animals↗

PubMed2006

Variation in cisplatinum sensitivity is not associated with Fanconi Anemia/BRCA pathway inactivation in head and neck squamous cell carcinoma cell lines.

Fanconi Anemia has recently been associated with a high risk of head and neck squamous cell carcinoma (HNSCC). Inactivation of the Fanconi Anemia (FANC-BRCA) pathway via promoter methylation of the FANCF gene has been proposed to be responsible for variation in cisplatinum (CDDP) sensitivity seen in ovarian and HNSCCs. Promoter methylation of the FANCF gene has been observed in 15% of HNSCC specimens, but the relationship to FANC pathway activation and CDDP sensitivity has not been reported. In the present study, 10 HNSCC cell lines were examined for expression of nine genes involved in the FANC-BRCA pathway by RT-PCR: FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, BRCA1 and BRCA2. FANC pathway function was evaluated by western blotting for FANCD2 mono-ubiquitination. All of the cell lines were also analyzed for variation in CDDP cytotoxicity. While significant differences were found in CDDP cytotoxicity, Fanconi pathway defects are an infrequent cause, as no evidence of transcriptional down-regulation of FANCF or other FANC mRNAs, or functional FANC-BRCA pathway defects were observed. These findings suggest that the variation in CDDP sensitivity of many HNSCCs is most frequently due to factors other than FANC-BRCA pathway inactivation.

Adult↗

PubMed2006

Inhibitors of human mitotic kinesin Eg5: characterization of the 4-phenyl-tetrahydroisoquinoline lead series.

In a high-throughput screening effort, a series of tetrahydroisoquinolines was identified as modest inhibitors of human Eg5. A medicinal chemistry optimization effort led to the identification of R-4-(3-hydroxyphenyl)-N,N-7,8-tetramethyl-3,4-dihydroisoquinoline-2(1H)-carboxamide (32a) as a potent inhibitor of human Eg5 (ATPase IC50 104 nM) with good anti-proliferative activity in A2780 cells (IC50 234 nM).

Adenosine Triphosphatases↗

PubMed2006

Energetics and stability of transmembrane helix packing: a replica-exchange simulation with a knowledge-based membrane potential.

The energetics and stability of the packing of transmembrane helices were investigated by Monte Carlo simulations with the replica-exchange method. The helices were modeled with a united atom representation, and the CHARMM19 force field was employed. Based on known experimental structures of membrane proteins, an implicit knowledge-based potential was developed to describe the helix-membrane interactions at the residue level, whose validity was tested through prediction of the orientations when single helices were inserted into a membrane. Two systems were studied in this article, namely the glycophorin A dimer, and helices A and B of Bacteriorhodopsin. For the glycophorin A dimer, the most stable structure (0.5 A away from the experimental structure) is mainly stabilized by the favorable helix-helix interactions, and has the most population regardless of the helix-membrane interaction. However, for helices A and B of Bacteriorhodopsin, it was found that the packing determined by helix-helix interactions is nonspecific, and a native-like structure (0.2 A from the experimental one) can be identified from several structural analogs as the most stable one only after applying the membrane potential. Our results suggest that the contribution from the helix-membrane interaction could be critical in the correct packing of transmembrane helices in the membrane.

Computer Simulation↗

PubMed2006

Focal cerebral ischemia alters the spatio-temporal properties, but not the amount of activity in mice.

Cerebral ischemia induces sensorimotor and cognitive dysfunctions in rodents; however, little is known about the changes in the spatio-temporal organization of locomotor activity after ischemia. In this study, we continuously assessed the spatio-temporal properties of locomotor activity in an enclosure (40 cm x 40 cm x 65 cm, arbitrarily divided into 16 zones) with feeding and drinking supplies, and observed the spatio-temporal changes in mice with focal cerebral ischemia. Locomotor tracks were recorded from 3rd to 24th h (total 22 h) after middle cerebral artery occlusion (MCAO) or sham operation. The absolute and relative distance traveled or time spent in different regions was analyzed. We found that there was no significant difference in total traveled distances over 22 h between the two groups. Control mice moved and stayed primarily in feeding and drinking zones, frequently in peripheral but rarely in central zones. However, ischemic mice lost such a property, almost evenly moved and stayed in 16 zones. Mice in both groups were more active (traveled more distances) shortly after they entered the enclosure, while ischemic mice returned to stable levels slower. The traveled distance had a remarkable circadian variation with more locomotion in the night in control mice, but not in ischemic mice. Most of the spatial parameters (ratios) of locomotor activity were closely correlated with the ischemic infarction, neuron densities (in cortex, hippocampal CA1 region and striatum), and typical behavioral assessments (neurological scores and inclined board test). Thus, these findings indicate that focal cerebral ischemia does not alter the amount of locomotor activity in mice, but impairs the spatio-temporal properties-prolonging the initial hyperactivity and losing regionally special distribution of the activity.

Analysis of Variance↗

PubMed2006

Evidence for histamine as a neurotransmitter in the cardiac sympathetic nervous system.

The colocalization of histamine (HA) and norepinephrine (NE) immunoreactivities was identified within the superior cervical ganglia neurons of the guinea pig. HA and NE immunoreactivity levels were significantly attenuated after chemical sympathectomy with 6-hydroxydopamine (6-OHDA). Coexistence of NE and HA was also visualized in the cardiac sympathetic axon and varicosities labeled with anterograde tracer biotinylated dextran amine. Depolarization of cardiac sympathetic nerve endings (synaptosomes) with 50 mM potassium stimulated endogenous HA release, which was significantly attenuated by 6-OHDA or a vesicular monoamine transporter 2 (VMAT2) inhibitor reserpine pretreatments. Compound 48/80, a mast cell releaser, did not affect cardiac synaptosome HA exocytosis. Furthermore, K+ -evoked HA release was abolished by the N-type Ca2+ -channel blocker omega-conotoxin but was not affected by the L-type Ca2+ -channel blocker lacidipine. Cardiac synaptosome HA exocytosis was augmented by the enhanced synthesis of HA or the inhibition of HA metabolism. HA H3-receptor activation by (R)-alpha-methylhistamine inhibited high K+ -evoked histamine release. The HA H3 receptor antagonist thioperamide enhanced K+ -evoked HA release and blocked the (R)-alpha-methylhistamine effect. The K+ -evoked endogenous NE release was attenuated by preloading the cardiac synaptosomes with L-histidine or quinacrine. These inhibitory effects were reversed by thioperamide or antagonized by alpha-fluoromethylhistidine. Our findings indicate that high K+ -evoked corelease of NE and HA may be inhibited by endogenous HA via activation of presynaptic HA H3-receptors. The H3-receptor may function as an autoreceptor, rather than a heteroreceptor, in the regulation of sympathetic neurotransmission and HA may be a novel sympathetic neurotransmitter.

Animals↗

PubMed2006

Synergetic effects of quetiapine and venlafaxine in preventing the chronic restraint stress-induced decrease in cell proliferation and BDNF expression in rat hippocampus.

Clinical studies show better response rates of patients with depression and schizophrenia to combinations of atypical antipsychotics and antidepressants, compared to responses to either type of drugs alone. Animal studies demonstrate that some antipsychotics and antidepressants increase neurogenesis and BDNF expression in the hippocampus, which is reduced in volume in patients with depression or schizophrenia. We hypothesized that the better therapeutic effects of combined treatment seen in schizophrenia and depression patients are related to the additive or synergistic effects of combined treatment on hippocampal neurogenesis and BDNF expression. To test this hypothesis, we investigated the effects of chronic administration of quetiapine, venlafaxine, and their combination, on hippocampal cell proliferation and BDNF expression in rats, when subjected to chronic restraint stress (CRS) during the last 2 weeks of a 3-week drug administration period. We found (1) CRS decreased hippocampal cell proliferation and BDNF expression; (2) chronic administration of quetiapine or venlafaxine dose-dependently prevented these decreases in hippocampal cell proliferation and BDNF expression caused by CRS (6 h/day for 14 days); (3) the combination of lower doses of quetiapine (5 mg/kg) and venlafaxine (2.5 mg/kg) increased hippocampal cell proliferation and prevented BDNF decrease in stressed rats, whereas each of the drugs exerted mild or no effects; (4) individual higher doses of quetiapine (10 mg/kg) or venlafaxine (5 mg/kg) exerted effects comparable to those produced by their combination. These results support our hypothesis and can lead to future studies to develop new therapeutic approaches for treatment-resistant depression and the negative symptoms of schizophrenia.

Animals↗

PubMed2006

iDQC MRI weighted by longitudinal relaxation in the rotating frame.

A long-duration, low-power, off-resonance spin-locking pulse was incorporated into the COSY revamped by asymmetric z gradient-echo detection (CRAZED) pulse sequence in order to evaluate the effects of intermolecular double-quantum longitudinal relaxation in the tilted rotating frame (T1rho,DQ(eff)). This modified CRAZED sequence was followed by a standard fast spin-echo imaging sequence to form images with T1rho,DQ(eff)-weighted contrast. Imaging experiments were performed on an agarose-gel phantom and mouse-tail tissue at 600 MHz. Experimental results demonstrated the feasibility of imaging applications based on T1rho,DQ(eff) as a novel contrast mechanism, and showed that iDQC off-resonance longitudinal relaxation in the rotating frame T1rho,DQ(eff) is sensitive to the tilt angle theta and the effective spin-locking field omegae. Imaging based on T1rho,DQ(eff)) has reduced RF power deposition compared to on-resonance spin-locking, which is advantageous for human applications.

Animals↗

PubMed2006

The role of sICAM-1 detection in the diagnosis of acute rejection following liver transplantation.

In order to evaluate the applied value of soluble intracellular adhesion molecule-1 (sICAM-1) in acute rejection (AR) following liver transplantation, the expression of sICAM-1 protein was sequentially detected by using ELISA in serum and bile of 43 patients receiving liver transplantation. In AR group, the expression levels of sICAM-1 protein were increased 3 days before and immediately on the establishment of AR diagnosis, and there was significant difference in the expression of bile between AR group and control group (P<0.01). After reversion of AR with hormone intensive therapy, there was significant difference in the sICAM-1 protein expression of serum and bile between AR group and control group. It was concluded that the sequential detection of sICAM-1 protein level in serum and bile was a reliable and noninvasive method for the early diagnosis of AR after liver transplantation and was valuable to observe the curative effects of anti-AR therapy.

Adult↗

PubMed2006

Expression patterns of 5-lipoxygenase in human brain with traumatic injury and astrocytoma.

5-Lipoxygenase (5-LOX) is a key enzyme in the metabolism of arachidonic acid to leukotrienes. The levels of leukotrienes increase after brain injury and when tumors are present. It has been reported that 5-LOX is widely expressed in the brain and that 5-LOX inhibition provides neuroprotection. However, there is still no information available for the expression patterns of 5-LOX in human brain following trauma or with astrocytomas. We investigated its expression patterns by immunohistochemistry. We found that 5-LOX is normally expressed in neurons and glial cells. In neurons, it was expressed in two patterns: in the cytosol and nucleus or only in the cytosol. In traumatic brain injury, 5-LOX expression increased in glial cells and neutrophils. Double-labeling immunohistochemistry showed that part of the 5-LOX-positive glial cells were GFAP positive. No 5-LOX expression was found in brain microvessel endothelia, except in the regenerated endothelia of a patient 8 days following brain trauma. Furthermore, 5-LOX expression increased and showed a granular pattern in high-grade (grade III/IV) astrocytoma. These results indicate that 5-LOX has multiple expression patterns, and can be induced by brain injury, which implies that 5-LOX might have pathophysiological roles in the human brain.

Adult↗

PubMed2006

Histone deacetylase inhibitor trichostatin A inhibits the growth of bladder cancer cells through induction of p21WAF1 and G1 cell cycle arrest.

PURPOSE: To investigate whether Trichostatin A (TSA) possesses antitumor activity against human bladder cancer cells, and if any, its mechanism. MATERIALS AND METHODS: A human bladder cancer cell line, BIU-87, was treated with different concentrations of TSA. After treatment, cell growth was measured by MTT assay. Cell apoptosis and cell cycle changes were examined by means of flow cytometry (FCM). Apoptosis was confirmed by apoptotic ladder formation assay. mRNA expression of p21WAF1 and p53 was assessed by differential reverse transcription-polymerase chain reaction. RESULTS: Trichostatin A significantly inhibited the proliferation of bladder cancer cell at nanomolar concentrations in a time- and dose-dependent fashion. TSA treatment caused cell cycle arrest at the G1 phase and increased apoptotic cell death as shown by FCM and DNA fragmentation analysis, accompanied by increased p21WAF1 mRNA expression. In addition, TSA treatment did not alter p53 mRNA expression. CONCLUSION: Our results indicate that TSA is able to inhibit bladder cancer cell growth in vitro, possibly through p21WAF1 mediated cell cycle arrest and apoptotic cell death. This study suggests that TSA may be a potential therapeutic agent for the treatment of bladder cancer.

Cell Line, Tumor↗

PubMed2006

Histamine protects against NMDA-induced necrosis in cultured cortical neurons through H receptor/cyclic AMP/protein kinase A and H receptor/GABA release pathways.

Using histamine and the H3 receptor antagonist thioperamide, the roles of histamine receptors in NMDA-induced necrosis were investigated in rat cultured cortical neurons. Within 3 h of intense NMDA insult, most neurons died by necrosis. Histamine reversed the neurotoxicity in a concentration-dependent manner and showed peak protection at a concentration of 10(-7) m. This protection was antagonized by the H2 receptor antagonists cimetidine and zolantidine but not by the H1 receptor antagonists pyrilamine and diphenhydramine. In addition, the selective H2 receptor agonist amthamine mimicked the protection by histamine. This action was prevented by cimetidine but not by pyrilamine. 8-Bromo-cAMP also mimicked the effect of histamine. In contrast, both the adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purine-6-amine and the cAMP-dependent protein kinase inhibitor N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinolinesulfonamide reversed the protection by histamine. Thioperamide also attenuated NMDA-induced excitotoxicity, which was reversed by the H3 receptor agonist (R)-alpha-methylhistamine but not by pyrilamine and cimetidine. In addition, the protection by thioperamide was inhibited by the GABA(A) receptor antagonists picrotoxin and bicuculline. Further study demonstrated that the protection by thioperamide was due to increased GABA release in NMDA-stimulated samples. These results indicate that not only the H2 receptor/cAMP/cAMP-dependent protein kinase pathway but also the H3 receptor/GABA release pathway can attenuate NMDA-induced neurotoxicity.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2006

Cysteinyl leukotriene receptor 1 is involved in N-methyl-D-aspartate-mediated neuronal injury in mice.

AIM: To determine whether cysteinyl leukotriene receptor 1 (CysLT1 receptor) is involved in N-methyl-D-aspartate (NMDA)-induced excitotoxic injury in the mouse brain. METHODS: Brain injury was induced by NMDA microinjection (50-150 nmol in 0.5 microL) into the cerebral cortex. The changes in CysLT1 receptor expression 24 h after NMDA injection and the effects of a CysLT1 receptor antagonist, pranlukast (0.01 and 0.1 mg/kg), an NMDA receptor antagonist, ketamine (30 mg/kg), and an antioxidant, edaravone (9 mg/kg) were observed. RESULTS: In the NMDA-injured brain, the CysLT1 receptor mRNA, and protein expression were upregulated, and the receptor was mainly localized in the neurons and not in the astrocytes. Pranlukast, ketamine and edaravone decreased NMDA-induced injury; pranlukast (0.1 mg/kg) and ketamine inhibited the upregulated expression of the CysLT1 receptor. CONCLUSION: CysLT1 receptor expression in neurons is upregulated after NMDA injection, and NMDA-induced responses are inhibited by CysLT1 receptor antagonists, indicating that the increased CysLT1 receptor is involved in NMDA excitotoxicity.

Animals↗