Biomedical subjects

Zhong Chen

Publications and source records attributed to Zhong Chen.

At least 55 records · Page 3Linked to original sources

PubMed2006

Structure prediction of helical transmembrane proteins at two length scales.

As the first step toward a multi-scale, hierarchical computational approach for membrane protein structure prediction, the packing of transmembrane helices was modeled at the residue and atom levels, respectively. For predictions at the residue level, the helix-helix and helix-membrane interactions were described by a set of knowledge-based energy functions. For predictions at the atom level, CHARMM19 force field was used. To facilitate the system to overcome energy barriers, the Wang-Landau method was employed, where a random walk is performed in the energy space with a uniform probability. Native-like structures were predicted at both levels for two model systems, each of which consists of two transmembrane helices. Interestingly, consistent results were obtained from simulations at the residue and atom levels for the same system, strongly suggesting the feasibility of a hierarchical approach for membrane protein structure predictions.

Amino Acid Sequence↗

PubMed2006

Epigenetic modification of SOCS-1 differentially regulates STAT3 activation in response to interleukin-6 receptor and epidermal growth factor receptor signaling through JAK and/or MEK in head and neck squamous cell carcinomas.

Signal transducer and activator of transcription 3 (STAT3) has been reported to be activated by interleukin-6 receptor (IL-6R) or epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC), which may have important implications for responsiveness to therapeutics targeted at EGFR, IL-6R, or intermediary kinases. Suppressor of cytokine signaling-1 (SOCS-1) has been implicated recently in the negative regulation of IL-6R/Janus-activated kinase (JAK)-mediated activation of STAT3, suggesting that SOCS-1 could affect alternative activation of STAT3 by EGFR, IL-6R, and associated kinases. We investigated whether epigenetic modification of SOCS-1 affects STAT3 activation in response to IL-6R-, EGFR-, JAK-, or mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-mediated signal activation. STAT3 was predominantly activated by IL-6R via Jak1/Jak2 in HNSCC lines UMSCC-9 and UMSCC-38 in association with transcriptional silencing of SOCS-1 by hypermethylation. In UMSCC-11A cells with unmethylated SOCS-1, STAT3 activation was regulated by both EGFR and IL-6R via a JAK-independent pathway involving MEK. Pharmacologic inhibitors of JAK and MEK and expression of SOCS-1 following demethylation or transient transfection inhibited STAT3 activation and cell proliferation and induced cell apoptosis in corresponding cell lines. Hypermethylation of SOCS-1 was found in about one-third of human HNSCC tissues, making it a potentially relevant marker for STAT-targeted therapy in HNSCC patients. We conclude that SOCS-1 methylation status can differentially affect STAT3 activation by IL-6R and EGFR through JAK or MEK in different HNSCC and response to pharmacologic antagonists. Identifying the potential factors and the regulatory pathways in STAT3 activation has important implications for the development and selection of molecularly targeted therapy in HNSCC.

Carcinoma, Squamous Cell↗

PubMed2006

[Effect of chronic transauricular kindled seizures on passive-avoidance test memory retention in rats].

OBJECTIVE: To investigate effect of chronic transauricular kindled seizures on passive-avoidance test memory retention in rats. METHODS: Chronic transauricular kindled seizures was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. A passive avoidance test was used to measure memory retention ability. Morphological changes in neurons of hippocampal CA1 region was examined after HE staining. Histamine, gamma-aminobutyric acid (GABA) and glutamate levels in the hippocampus were measured by high performance liquid chromatography (HPLC). RESULT: Chronic transauricular kindled seizures impaired passive-avoidance test memory retention in rats. The damaged CA1 neurons were observed and histamine content in the hippocampus markedly decreased 24 h after the end of kindling in the chronic transauricular kindled rats. CONCLUSION: Chronic transauricular kindled seizure impaired passive-avoidance test memory retention, and it might be due to the damaged CA1 neurons and a decrease of histamine in the hippocampus induced by epilepsy.

Animals↗

PubMed2006

[Role of brain mast cell in multiple sclerosis and Wernicke's encephalopathy].

OBJECTIVE: Mast cell which is considered to participate in immune response has long been studied. However its true role in center nervous system is still unknown. Recently,mast cell has been found to play an important function during the process of multiple sclerosis and Wernicke's encephalopathy in the brain. Multiple sclerosis is an inflammatory demyelinating disease, and Wernicke's encephalopathy is caused by deficiency of thiamine. Mast cell deteriorates the neuronal damage and the course of diseases by their mediators. Such studies may supply new idea on the therapy of these diseases.

Animals↗

PubMed2006

[Effects of PTEN gene transfection on proliferation and invasion of human bladder cancer cell line BIU87].

BACKGROUND & OBJECTIVE: PTEN (phosphatase and tensin homologue deleted from chromosome 10) is the first antioncogene with phosphatase activity till now, and was found absent or mutational in many primary malignant tumors and cell lines. Its inactivation is correlated to tumor development and prognosis. This study was to investigate the effects of PTEN transfection on proliferation and invasion of human bladder cancer cell line BIU87. METHODS: A eukaryotic expression plasmid containing PTEN, pBp-PTEN, was introduced into E. coli DH5alpha and amplified. The plasmid was prepared and purified, and then identified by restrictive enzyme digestion. pBp-PTEN was transfected into BIU87 cells, and positive cell clones (pBp-PTEN-BIU87) were selected and amplified. Empty plasmid-transfected BIU87 cells (pBp-BIU87) and normal BIU87 cells were set as control. The expression of PTEN was detected by reverse transcription-polymerase chain reaction (RT-PCR). Proliferation and invasion ability of BIU87 cells were measured before and after transfection by MTT assay and cell invasion assay. RESULTS: Plasmid pBp-PTEN containing PTEN was successfully constructed and transfected into BIU87 cells. After transfection, the inhibitory rates of cell growth at the first, second, third, and fourth days were 4.27%, 18.92%, 19.54%, and 17.69%, respectively. The penetrating cells were significantly less in pBp-PTEN-BIU87 group than in pBp-BIU87 and BIU87 groups (39.3+/-7.7 vs. 48.1+/-13.2 and 48.9+/-11.0, P<0.05). CONCLUSION: Transfection with PTEN might suppress proliferation and invasive ability of bladder cancer BIU87 cells.

Cell Line, Tumor↗

PubMed2006

[H2 receptor mediates the protective effect of histamine against the cellular edema and viability reduction induced by oxygen-glucose deprivation in rat hippocampal slices].

AIM: To determine the effect of histamine on ischemia-induced cellular edema and viability reduction in rat hippocampal slices, and the involved subtypes of histamine receptor in this effect. METHODS: In vitro ischemic injury of hippocampal slices was induced by oxygen-glucose deprivation (OGD). The slice injury was determined by real-timely measuring the changes of light transmittance (LT) for the cellular edema in CA1 region of the hippocampal slice, and by detecting the product of 2, 3, 5-triphenyltetrazolium chloride (TTC), formazan, for the slice viability. The effect of histamine at various concentrations on the slice injury was observed, and the blockage by antagonists of histamine receptors was also investigated. RESULTS: Histamine (0.01-10 micromol x L(-1)) inhibited the peak value of LT during OGD in hippocampal slices and improved the reduced viability after OGD. Diphenhydramine (0.1-10 micromol x L(-1)), an H1 receptor antagonist, did not affect the effect of histamine, while cimetidine (0.1-10 micromol x L(-1)), an H2 receptor antagonist, partly abolished the protective effect of histamine. CONCLUSION: Histamine protects hippocampal slices against ischemia-induced cellular edema and viability reduction; this effect might be mediated via, at least partly, H2 receptor.

Animals↗

PubMed2006

[Participation of endogenous brain histamine on learning and memory].

It is well known that histamines play an important role as a neurotransmitter in the central nervous system and participate in several physiological functions, such as the regulation of body temperature, food intake, circadian rhythm and analgesia. Since the first report by de Almeida and Izquierdo that histamines facilitate memory performance in mice, it has been revealed that the histaminergic nervous system in the brain plays a crucial role in learning and memory functions. First, we demonstrate the effects of histamines and histaminergic drugs on learning and memory using active avoidance and 8-arm radial maze tests. Many reports suggest that acetylcholine and N-methyl-D-aspartate (NMDA) receptors play an important role in learning and memory. In this report, we also describe the interaction between histamine-induced memory facilitation and acetylcholine or NMDA receptors.

Animals↗

PubMed2006

[Expression of recombinant human hemangiopoietin and preparation of its polyclonal antibody].

AIM: To express the recombinant fusion protein of hemangiopoietin (HAPO) and prepare the rabbit-anti-human HAPO polyclonal antibody. METHODS: The sequence encoding HAPO was amplified by PCR and cloned into plasmid pET32c to construct recombinant prokaryotic expression system. The recombinant expression vectors were identified by enzyme digestion analysis and transformed into E. coli. The HAPO protein was purified by affinity chromatography. Rabbits were immunized with the HAPO protein, and the immune sera of rabbits were collected. Antibodies (IgG) obtained from the immune sera were purified. RESULTS: The purified HAPO protein was successfully obtained. The purified polyclonal antibody of rabbit-anti-human HAPO was also obtained from the immune sera of rabbits, and could response to human HAPO. CONCLUSION: A prokaryotic expression system of human HAPO has been prepared and the polyclonal antibody against HAPO has been prepared, which can be used to determine HAPO protein.

Animals↗

PubMed2006

Effects of fire on major forest ecosystem processes: an overview.

Fire and fire ecology are among the best-studied topics in contemporary ecosystem ecology. The large body of existing literature on fire and fire ecology indicates an urgent need to synthesize the information on the pattern of fire effects on ecosystem composition, structure, and functions for application in fire and ecosystem management. Understanding fire effects and underlying principles are critical to reduce the risk of uncharacteristic wildfires and for proper use of fire as an effective management tool toward management goals. This overview is a synthesis of current knowledge on major effects of fire on fire-prone ecosystems, particularly those in the boreal and temperate regions of the North America. Four closely related ecosystem processes in vegetation dynamics, nutrient cycling, soil and belowground process and water relations were discussed with emphases on fire as the driving force. Clearly, fire can shape ecosystem composition, structure and functions by selecting fire adapted species and removing other susceptible species, releasing nutrients from the biomass and improving nutrient cycling, affecting soil properties through changing soil microbial activities and water relations, and creating heterogeneous mosaics, which in turn, can further influence fire behavior and ecological processes. Fire as a destructive force can rapidly consume large amount of biomass and cause negative impacts such as post-fire soil erosion and water runoff, and air pollution; however, as a constructive force fire is also responsible for maintaining the health and perpetuity of certain fire-dependent ecosystems. Considering the unique ecological roles of fire in mediating and regulating ecosystems, fire should be incorporated as an integral component of ecosystems and management. However, the effects of fire on an ecosystem depend on the fire regime, vegetation type, climate, physical environments, and the scale of time and space of assessment. More ecosystem-specific studies are needed in future, especially those focusing on temporal and spatial variations of fire effects through long-term experimental monitoring and modeling.

Air Pollution↗

PubMed2006

[Influence of intravenous infusion of D-fructose on post-operative blood glucose level in burn patients].

OBJECTIVE: To investigate the influence of intravenous infusion of 50 g/L fructose on post-operative blood glucose level in burn patients, and to evaluate its therapeutic value and safety. METHODS: A prospective, randomized, double blinded clinical trial was conducted. Forty-one burn patients with burn area ranging between 10% -30% of total body surface (TBSA) and third degree burns ranging between 1% -10% TBSA were enrolled in the study and randomized into experiment group (E, n = 21, with intravenous infusion of 500 ml of 50 g/L fructose daily for 3 days after escharectomy) and control group ( C, n = 20, with intravenous infusion of glucose 1 day after escharectomy for 3 days). Intravenous infusion of other carbohydrate liquids or oral intake of sugar was withhold within 4 hours of fructose or glucose infusion. Physical signs and side effects were observed during the administration. The plasma glucose contents before operation and on 1, 2 and 3 post-operation day( POD) were measured. The serum content of lactic acid, uric acid, hepatic and renal function were determined before operation and on 4 POD. RESULTS: Physical signs before and after drug administration, and plasma glucose content before operation, as well as before and after fructose administration in 3 POD exhibited no obvious difference between the two groups ( P > 0. 05 ). The plasma glucose content was increased 3 days after operation in the control group, and it reached the peak on 3 POD [ (8. 4+/-3. 5) mmol/L] , which was markedly higher than that before glucose administration [ (6. 4+/-2.4) mmol/L, P <0. 01) ]. The plasma contents of lactic acid and uric acid showed no obvious difference ( P >0.05) between the two groups, and also no difference before and after operation ( P > 0. 05). No changes were observed in hepatic and renal functions. CONCLUSION: Intravenous infusion of 50 g/L D-fructose is safe because it exerts little influence on blood glucose level.

Adolescent↗

PubMed2005

Quetiapine and venlafaxine synergically regulate heme oxygenase-2 protein expression in the hippocampus of stressed rats.

HO-2 is a constitutive isoform of heme oxygenase (HO), a microsomal enzyme that catalyzes the cleavage of the heme ring to form ferrous iron, carbon monoxide, and biliverdin. In contrast to HO-1, which is inducible, HO-2 is not responsive to stimuli tested to date except for prolonged exposure to the adrenal glucocorticoids (GCs). Previous studies have shown that high GC concentrations or stress damage or kill hippocampal neurons. In the present study, it was found that chronic restraint stress decreased HO-2 protein levels in hippocampal neurons, as demonstrated by immunohistochemistry and Western blot analysis. Moreover, our results showed that the combination of 2.5mg/kg of venlafaxine and 5mg/kg of quetiapine effectively prevented the HO-2 protein decrease in hippocampal neurons of stressed rats, whereas either of the drugs alone did not show any effect. At higher dose levels, both quetiapine (10mg/kg) and venlafaxine (5mg/kg) produced significant effects comparable to that of their combination. Quetiapine is an atypical antipsychotic and venlafaxine an antidepressant. In previous studies, these two drugs have been shown to prevent or protect against the stress-induced decrease in hippocampal neurogenesis and BDNF expression. These data suggest that both quetiapine and venlafaxine share the hippocampus as their common target by enhancing hippocampal resilience, which may be impaired in patients with schizophrenia or depression.

Animals↗

PubMed2005

Two estrogen replacement therapies differentially regulate expression of estrogen receptors alpha and beta in the hippocampus and cortex of ovariectomized rat.

As estrogens have been implicated in altered cognitive function associated with menopause, the purpose of the present study was to determine the regulatory effects of different estrogen preparations on the expression of estrogen receptor subtypes in the hippocampus and cortex of ovariectomized rats. The expression of estrogen receptor mRNA and protein was determined with RT-PCR and immunohistochemistry, respectively. Two estrogen reagents, Premarin and Progynova, were used in the present study. Premarin, a conjugated equine estrogen, down-regulated ER alpha expression in the hippocampus and cortex of ovariectomized rats and had no effect on levels of ER beta expression in the same two regions. However, Progynova (valerate estradiol) was shown to up-regulate ER beta expression in the hippocampus and cortex and had no effect on the levels of ER alpha expression. Our present data suggest that different estrogen reagents used in estrogen replacement therapy could have different regulatory effects on the expression of estrogen receptor subtypes, which might, at least in part, explain why clinically, different estrogen preparations have distinct estrogenic effects on target organs.

Animals↗

PubMed2005

Pyrrolopyridazine MEK inhibitors.

The synthesis and SAR of a series of pyrrolopyridazine MEK inhibitors are reported. Optimal activity was achieved by incorporation of a 4-phenoxyaniline substituent at C4 and an acylated amine at C6.

Acylation↗

PubMed2005

[Protective effects of ulinastatin against multiple organic damage after severe burn injury: experimental and clinic studies].

OBJECTIVE: To study the protective effects of ulinastatin (UTI), a human trypsin inhibitor, on the damage to the functions of multiple organs at the early stage of severe burn. METHODS: (1) Twelve male mini-pigs, inflicted with III degrees burn with 35% total body surface area (TBSA), were randomly divided into two equal groups: Group A (control group, treated with fluid resuscitation immediately after injury and normal saline by intravenous drip tid) and Group B (UTI-treated group, in addition to fluid resuscitation UTI 5000 U/kg was given one hour after injury, 3 times/day). Blood samples were taken for the determination of serum TNF-alpha, IL-6, malonyldiadehyde (MDA), superoxide dismutase (SOD), alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase (CK), MB isoenzyme of CK (CK-MB), blood urea nitrogen (BUN), creatinine (Cr), diamine oxidase (DAO), and D-lactate before and 6, 24, 48, and 72 hours after injury. (2) Forty hospitalized patients with 50%-70% TBSA partial and full thickness burn, 28 males and 12 females, aged 18-60, were randomly divided into routine treatment group (n = 16, receiving routine fluid resuscitation and wound management and normal saline IV drop bid for 7 days) and UTI treatment group (n = 24, in addition to the routine treatment UTI 400,000 U was given IV drop bid for 7 days). Sixteen healthy volunteers served as controls to undergo blood examination. The average body temperature (T), respiratory rate (R), systole blood pressure (BP) were detected 48 hours after burn. Blood samples were taken to determine the plasma lipopolysaccharide (LPS), and serum TNF-alpha, norepinephrine (NE), myeloperoxidase (MPO), ALT, AST, CK, CK-MB, lactic dehydrogenase (LDH), BUN, and Cr 1, 3, and 7 days after burn. RESULTS: (1) The serum TNF-alpha, IL-6, and MDA levels significantly increased, and the serum SOD level significantly decreased 6 hours after burn in the mini-pings in both groups (all P < 0.05), and the changes in Group A were more significant than in Group B (all P < 0.05). The serum AST, CK, CK-MB, BUN, Cr, DAO, and D-lactate levels increased in the mini-pigs of both groups after severe burn in comparison with those before burn (all P < 0.05), especially in Group A in comparison with Group B (all P < 0.05). However, the serum levels of ALT and LDH of Group B did not increase significantly in comparison with those before burn. (2) The serum LPS, TNF-alpha, NE, ALT, AST, CK, CKMB, LDH, BUN, Cr, and MPO significantly increased after burn and began to decrease since the 7th day after burn, and the decrease levels in the UTI group were more significant than in the routine treatment group (all P < 0.05). In the routine treatment group 2 cases of sepsis were found and one case died of multiple organ failure; no complication was found in the UTI treatment group. CONCLUSION: UTI can significantly lessen the production of inflammatory mediators and oxygen free radical and protect the functions of multiple organs after severe burn.

Adolescent↗

PubMed2005

The human Penumbra gene is mapped to a region on chromosome 7 frequently deleted in myeloid malignancies.

We previously cloned the murine Penumbra gene based on its differential expression in proerythroblasts/erythroblasts. Subsequently, we identified human Penumbra cDNA from a human bone marrow cDNA library and the human Penumbra gene from a BAC library. Penumbra is a new member of the tetraspanin protein family and exhibits growth-suppressive activity in vitro. In this study, we designed a human Penumbra probe contig and used fluorescent in situ hybridization (FISH) to analyze seven cases of myeloid malignancies with 7q deletions. Five patients with cytogenetic deletions involving 7q31.2 approximately q32 also showed deletions of Penumbra by FISH; these were not present in two patients with cytogenetic deletions not involving 7q31.2 approximately q32. Our findings provide the first FISH evidence supporting the mapping of human Penumbra to 7q31.2 approximately q32 and demonstrate the potential of the Penumbra probe in the detection of 7q31 approximately q32-related deletions in myeloid malignancies.

Adult↗

PubMed2005

NMR and theoretical study on the coordination and solution structures of the interaction between diperoxovanadate complexes and histidine-like ligands.

To simulate the types of coordination and solution structures of the active site of haloperoxidases, the interaction systems between diperoxovanadate complexes [OV(O2)2L]n- (n = 1 or 3, L = oxalate or H2O) and a series of histidine-like ligands in solution have been studied by using 1D multinuclear (1H, 13C, and 51V) NMR, 2D diffusion ordered spectroscopy, and variable-temperature NMR in 0.15 mol/L NaCl ionic medium, representing the physiological conditions of human blood. Some direct NMR data are given for the first time. The reactivity among the histidine-like ligands is imidazole > 2-methylimidazole > carnosine approximately 4-methylimidazole > histidine. Competitive coordination interactions result in a series of new peroxovanadate species [OV(O2)2L']- (L' = histidine-like ligands). When the ligands are 4-methylimidazole, histidine, and carnosine, a pair of isomers have been observed, which are attributed to different types of coordination between vanadium atom and ligands. The results of density functional theory calculations provided a reasonable explanation on the relative reactivity of the histidine-like ligands and the molar ratios of isomers. Theoretical results signify the importance of the solvation effect for the reactivity and stability of the interaction systems.

Histidine↗

PubMed2005

Efficient target strategies for contagion in scale-free networks.

Organizations or individuals often have an incentive to target a certain number of agents to launch a contagion process effectively and efficiently, for example, sampling consumers in the diffusion of new products. We present an effective strategy for contagion in scale-free networks. The proposed strategy, hub strategy, calls for targeting mostly the highly connected nodes. The biased level implemented in this strategy characterizes its ability to identify hub nodes. We demonstrate that hub strategy can improve the contagion effects evidently. We find that biased level increases first with heterogeneity level of contagion network but decreases with that after a certain value, and decreases with initial adopter rate all the time. Moreover, degree correlations in contagion networks may reduce biased level.

Journal Article↗

PubMed2005

Effect of oxygen-glucose deprivation on degranulation and histamine release of mast cells.

The purpose of this study was to investigate the effect of oxygen-glucose deprivation (OGD) on degranulation and histamine release of mast cells. Cultured mast cells were exposed to OGD for 1, 2, 4, 8, or 16 h. At 2 h of OGD exposure, the degranulation percentage of mast cells had increased and subsequently showed a progressive further increase, associated with a similar change in lactate dehydrogenase release. Histamine release increased significantly from 1 h of OGD exposure. These results indicate that OGD induces mast cells to degranulate, possibly via a cytotoxic response. This in vitro ischemic model of mast cells might clarify their roles in the pathological processes induced by cerebral ischemia.

Animals↗