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Biomedical subjects

Jian Zhang

Publications and source records attributed to Jian Zhang.

At least 55 records · Page 3Linked to original sources
PubMed2006

The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter.

The N-myc downstream-regulated gene 1 (ndrg1) is highly expressed in N-myc knock-out mice through an unknown regulatory mechanism. As one member of the human NDRG gene family, NDRG2 encodes a protein highly homologous to Ndrg1. However, it is uncertain whether the expression of human NDRG2 is regulated by Myc because mouse ndrg2 and -3 are not affected by Myc. In this study, we provide the novel evidence that the expression of human NDRG2 is down-regulated by Myc via transcriptional repression. A high level of NDRG2 was observed as Myc expression was reduced in differentiated cells, whereas a low level of NDRG2 was shown following increased Myc expression upon serum stimulation. The ectopic expression of c-Myc dramatically reduces the cellular Ndrg2 protein and mRNA level. We further identified the core promoter region of NDRG2 that is required for Myc repression on NDRG2 transcription, and we verified the interaction of Myc with the core promoter region both in vitro and in vivo. Moreover, the c-Myc-mediated repression of NDRG2 requires association with Miz-1, and possibly the recruitment of other epigenetic factors, such as histone deacetylases, to the promoter. The regulatory function of Myc on NDRG2 gene expression implicated the role of the Ndrg2 in regulating cell differentiation.

Animals↗
PubMed2006

Farnesyltransferase pharmacophore model derived from diverse classes of inhibitors.

A three-dimensional pharmacophore model was developed based on 25 currently available inhibitors, which were carefully selected with great diversity in both molecular structure and bioactivity as required by HypoGen program in the Catalyst software, for discovering new farnesyltransferase (FTase) inhibitors. The best hypothesis (Hypo1), consisting of four features, namely, two hydrogen-bond acceptors, one hydrophobic point, and one ring aromatic feature, has a correlation coefficient of 0.949, a root-mean-square deviation of 1.321, and a cost difference of 163.15, suggesting that a highly predictive pharmacophore model was successfully obtained. The application of the model shows great success in predicting the activities of 227 known FTase inhibitors in our test set with a correlation coefficient of 0.776 with a cross-validation of 98% confidence level. Accordingly, our model should be reliable in identifying structurally diverse compounds with desired biological activity.

Antineoplastic Agents↗
PubMed2006

Surface plasmon interferometric microscopy for three-dimensional imaging of dynamic processes.

A method, which we named surface plasmon interferometric microscopy, for real-time displaying of the dynamic evolution of the refractive index (RI) of a sample in three-dimensions is demonstrated experimentally. The Fourier fringe analysis technique is employed to get the phase variations of the samples by demodulating the interference patterns captured by a CCD camera, and the 3D RI distribution can be obtained through numerical interpolation from the relation between the phase and the RI of the samples. Our method may provide an interesting way to monitor fast dynamics of physical, biological, and chemical processes in real time.

Fourier Analysis↗
PubMed2006

Expression of discoidin domain receptor 2 (DDR2) extracellular domain in pichia pastoris and functional analysis in synovial fibroblasts and NIT3T3 cells.

Discoidin domain receptor 2 (DDR2) is a kind of protein tyrosine kinases associated with cell proliferation and tumor metastasis, and collagen, identified as a ligand for DDR2, up-regulates matrix metallloproteinase 1 (MMP-1) and MMP-2 expression in cellular matrix. To investigate the roles of DDR2 in destruction of cartilage in rheumatoid arthritis (RA) and tumor metastasis, we tried to express extracellular domain of DDR2 fused with a His tag to increase protein solubility and facilitate purification (without signal peptide and transmembrane domain, designated DR) in Pichia pastoris, purify the expressed protein, and characterize its function, for purpose of future application as a specific DDR2 antagonist. Two clones of relative high expression of His-DR were obtained. After purification by a Ni-NTA (nitric-tri-acetic acid) chromatographic column, soluble fused His-DR over 90% purity were obtained. Competitive binding inhibition assay demonstrated that expressed His-DR could block the binding of DDR2 and natural DDR2 receptors on NIT3T3 and synovial cell surfaces. Results of RT-PCR, Western blotting, and gelatinase zymography showed that His-DR was capable of inhibiting MMP-1 and MMP-2 secretion from NIT3T3 cells and RA synoviocytes stimulated by collagen II. For MMP-1, the inhibitory effect was displayed at the levels of mRNA and protein, whereas for MMP-2 it was demonstrated at the level of protein physiological activity. All these findings suggested that the fused expressed His-DR inhibited the activity of natural DDR2, and relevant MMP-1 and MMP-2 expression in synoviocytes and NIH3T3 cells provoked by collagen II.

Amino Acid Sequence↗
PubMed2006

Monocyte chemotactic protein-1 (MCP-1) acts as a paracrine and autocrine factor for prostate cancer growth and invasion.

BACKGROUND: Monocyte chemotactic protein-1 (MCP-1) plays a key role in the recruitment and activation of monocytes during inflammation. Increased MCP-1 serum levels in patients with various cancers were correlated with advanced stage. Here, we evaluated the role of MCP-1 on prostate cancer (CaP) cell proliferation and invasion. METHODS: Expression of MCP-1 in tissue specimens was analyzed by immunohistochemical staining. MCP-1 production was determined by ELISA in conditioned media collected from primary prostate epithelia (PrEC), LNCaP, C4-2B, PC3 cells, and hFOB. Cell proliferation and invasion were assayed by MTS assay and invasion chambers. RESULTS: All CaP cells, as well as hFOB, produced high amount of MCP-1 compared to PrEC cells. MCP-1 expression levels were associated with advanced pathologic stage. MCP-1 induced proliferation and invasion of CaP cells and this was abolished partially either by CCR2 antagonist or PI3 Kinase inhibitor. CONCLUSION: MCP-1 acts as a paracrine and autocrine factor for CaP growth and invasion.

Cell Line↗
PubMed2006

Biomechanical study of anterior cervical corpectomy and step-cut grafting with bioabsorbable screws fixation in cadaveric cervical spine model.

STUDY DESIGN: An in vitro biomechanical study. OBJECTIVE: To determine the initial stability of a novel construct in a 1-level cadaveric cervical spine model by comparing it with a conventional method. SUMMARY OF BACKGROUND DATA: Lots of endeavors have been made to enhance fusion rates and reduce complications in the anterior cervical spine procedure. METHODS: There were 12 fresh human cadaveric cervical spines (C3-C7) randomly divided into 2 groups: group 1, 1-level corpectomy of C5 and step-cut grafting with bioabsorbable screw fixation (SCAS); and group 2, 1-level corpectomy of C5 and strut grafting with anterior plate fixation (SP). For each specimen, the intact underwent a flexibility test first, followed by the instrumented construct. Rotational angles of the C4-C6 segment were measured to study the immediate stability of anterior cervical corpectomy and SCAS, compared with the intact and anterior cervical corpectomy and SP. RESULTS: Both anterior cervical corpectomy with SCAS and with SP significantly (P < 0.01) decreased the motions of C4-C6 in all 6 degrees of freedom after instrumentation. Compared with anterior cervical corpectomy and SP, anterior cervical corpectomy and SCAS had higher stability (P < 0.05) in extension, and comparable stability (P > 0.05) in flexion and axial rotation, but lower stability (P <or= 0.05) in lateral bending. CONCLUSION: Anterior cervical corpectomy and SCAS, a novel method of anterior cervical spine decompression and reconstruction, was introduced. The in vitro biomechanical study showed that anterior cervical corpectomy and SCAS had sufficient immediate stability except for the lateral bending, compared with anterior cervical corpectomy and SP, in a 1-level cadaveric cervical spine model. However, an animal experimental in vivo evaluation of anterior cervical corpectomy and SCAS still has to be performed.

Absorbable Implants↗
PubMed2006

Foxp3 controls autoreactive T cell activation through transcriptional regulation of early growth response genes and E3 ubiquitin ligase genes, independently of thymic selection.

To elucidate the mechanisms of autoreactive T cell activation and expansion, we used endogenous viral superantigens (VSAg)-reactive T cells as a model of self-antigens in two strains of Foxp3-mutant mice. These two strains, together with wild-type mice, provided us with an advantage to simultaneously study the positively and negatively selected as well as rescued autoreactive T cells. We show here that while both VSAg-reactive and non-VSAg-reactive T cells are equally activated in Foxp3-mutant mice, only the VSAg-reactive T cells are preferentially expanded independently of their selected states in the thymus. The T cell activation appears to be controlled by Foxp3 through transcriptional regulation of early growth response (Egr) genes Egr-2 and Egr-3, and E3 ubiquitin (Ub) ligase genes Cblb, Itch and GRAIL, subsequently affecting degradation of two key signaling proteins, PLCgamma1 and PKC-theta. Physiologically, the positively, but not negatively selected VSAg-reactive T cells are spontaneously activated without significant expansion. The results suggest that autoreactive T cell activation is controlled by Foxp3 through transcriptional regulation of early growth response genes and E3 ubiquitin ligase genes, independently of thymic selection.

Animals↗
PubMed2006

Conformational transition pathway in the allosteric process of human glucokinase.

Glucokinase (GK) is an important enzyme for regulating blood glucose levels and a potentially attractive target for diabetes of the young type 2 and persistent hyperinsulinemic hypoglycemia of infancy. To characterize the conformational transition of GK from the closed state to the superopen state, a series of conventional molecular dynamics (MD) and target MD (TMD) simulations were performed on both the wild-type enzyme and its mutants. Two 10-ns conventional MD simulations showed that, although the allosteric site of GK is approximately 20 A away from the active site, the activator is able to enhance the activity of the enzyme through conformational restriction. Fourteen TMD simulations on GK and five of its mutants revealed a reliably conformational transition pathway. The overall conformational transition includes three stages, and three likely stable intermediate states were identified by free energy scanning for the snapshots throughout the pathway. The conformational transition feature revealed by our TMD simulations rationalized several important mutagenesis and kinetic data. Remarkably, the TMD simulations predicted that Y61S, I159A, A201R, V203E, and V452S mutations, which have not been investigated so far, may facilitate the opening process of GK. These predictions also have been verified by mutagenesis and kinetic analyses in this study. These observations are beneficial to understanding the mechanism of GK regulation and designing the compounds for treating metabolic diseases.

Allosteric Regulation↗
PubMed2006

Prevalence and clinical characteristics of sleep apnea in Chinese patients with heart failure.

One hundred twenty-six eligible consecutive Chinese heart failure (HF) patients classified by New York Heart Association (NYHA) Classes II-IV underwent historic data collection and a sleep study. Seventy-one percent of HF patients were diagnosed with sleep apnea (SA), of which 65% were central sleep apnea (CSA) and 35% were obstructive sleep apnea (OSA). Higher body mass index (BMI), metabolic syndrome, habitual snoring, and nocturia were independent risk factors for OSA; NYHA classes III and IV were independent risk factors for CSA in the HF patients. There was a high prevalence of SA in Chinese patients with HF. HF patients with obesity, metabolic syndrome, snoring, nocturia and NYHA classes III and IV were more susceptible to OSA and CSA.

China↗
PubMed2006

mRNA secondary structure at start AUG codon is a key limiting factor for human protein expression in Escherichia coli.

Codon usage and thermodynamic optimization of the 5'-end of mRNA have been applied to improve the efficiency of human protein production in Escherichia coli. However, high level expression of human protein in E. coli is still a challenge that virtually depends upon each individual target genes. Using human interleukin 10 (huIL-10) and interferon alpha (huIFN-alpha) coding sequences, we systematically analyzed the influence of several major factors on expression of human protein in E. coli. The results from huIL-10 and reinforced by huIFN-alpha showed that exposing AUG initiator codon from base-paired structure within mRNA itself significantly improved the translation of target protein, which resulted in a 10-fold higher protein expression than the wild-type genes. It was also noted that translation process was not affected by the retained short-range stem-loop structure at Shine-Dalgarno (SD) sequences. On the other hand, codon-optimized constructs of huIL-10 showed unimproved levels of protein expression, on the contrary, led to a remarkable RNA degradation. Our study demonstrates that exposure of AUG initiator codon from long-range intra-strand secondary structure at 5'-end of mRNA may be used as a general strategy for human protein production in E. coli.

Base Sequence↗
PubMed2006

Two cobalt(II) 5-aminoisophthalate complexes and their stable supramolecular microporous frameworks.

Two stable supramolecular microporous cobalt(II) polymers, namely [Co(HAIP)2]n.3nH2O (1) and [Co(AIP)(H2O)]n (2), AIP = 5-aminoisophthalate, were hydrothermally synthesized and characterized by single-crystal X-ray diffraction, IR spectra, thermogravimetric analyses, and variable-temperature magnetic susceptibility measurements. The two complexes are constructed from the same Co2(CO2)2 SBU, which is extended into a 1D chain in 1 and a 2D layer in 2. As a result, 1 and 2 are 2D and 3D coordination polymers, respectively. The 3D supramolecular network of complex 1 is held up by strong hydrogen bonds formed between carboxylate groups and shows very high stability when the free H2O molecules are removed, indicating an extraordinarily stable H-bonding system. Upon water ligands being liberated, complex 2 becomes a stable microporous solid with coordination-unsaturated Co centers. The behavior of the susceptibility curve of 1 suggests the occurrence of an interesting intrachain antiferromagnetic coupling between the Co(II) ions and the presence of a significant orbital contribution, whereas the features of 2 indicate an antiferromagnetic coupling with T(N) = 3.5 K and a long-range antiferromagnetic order with a field-induced magnetic transition.

Cobalt↗
PubMed2006

Peptide deformylase is a potential target for anti-Helicobacter pylori drugs: reverse docking, enzymatic assay, and X-ray crystallography validation.

Colonization of human stomach by the bacterium Helicobacter pylori is a major causative factor for gastrointestinal illnesses and gastric cancer. However, the discovery of anti-H. pylori agents is a difficult task due to lack of mature protein targets. Therefore, identifying new molecular targets for developing new drugs against H. pylori is obviously necessary. In this study, the in-house potential drug target database (PDTD, http://www.dddc.ac.cn/tarfisdock/) was searched by the reverse docking approach using an active natural product (compound 1) discovered by anti-H. pylori screening as a probe. Homology search revealed that, among the 15 candidates discovered by reverse docking, only diaminopimelate decarboxylase (DC) and peptide deformylase (PDF) have homologous proteins in the genome of H. pylori. Enzymatic assay demonstrated compound 1 and its derivative compound 2 are the potent inhibitors against H. pylori PDF (HpPDF) with IC50 values of 10.8 and 1.25 microM, respectively. X-ray crystal structures of HpPDF and the complexes of HpPDF with 1 and 2 were determined for the first time, indicating that these two inhibitors bind well with HpPDF binding pocket. All these results indicate that HpPDF is a potential target for screening new anti-H. pylori agents. In addition, compounds 1 and 2 were predicted to bind to HpPDF with relatively high selectivity, suggesting they can be used as leads for developing new anti-H. pylori agents. The results demonstrated that our strategy, reverse docking in conjunction with bioassay and structural biology, is effective and can be used as a complementary approach of functional genomics and chemical biology in target identification.

Amidohydrolases↗
PubMed2006

Comorbidity between and risk factors for severe hearing and memory impairment in older Americans.

OBJECTIVE: Comorbidities complicate our understanding of impairments and their risk factors. The objective of the current study was to assess the comorbidity between hearing impairment (HI) and memory impairment (MI) in older Americans and to assess to what extent they share common risk factors. METHOD: Data were examined from 5252 participants aged 65 years or older from the Third National Health and Nutrition Examination Survey (1988-1994). RESULTS: The prevalence of HI and MI was 21.4 (SE 0.8)% and 8.3 (0.6)%, respectively, but the prevalence of concurrent impairment was only 2.1 (0.2)%. African Americans had higher odds of MI than whites (OR=3.75, 95% CI: 2.81, 5.00), but not of HI (OR=0.62, 95% CI: 0.42, 0.91). Leisure physical activity was associated with lower odds of MI, good lung function was associated with lower odds of HI, and moderate alcohol use was associated with lower odds of both HI and MI. Compared with individuals free of HI, the OR of MI was 1.07 (95% CI: 0.78, 1.47) for individuals with HI. CONCLUSION: Although prevalence was relatively high, comorbidity was surprisingly low, and the two impairments were not significantly associated. In addition to age, other factors appear to play critical but different roles in the development of these impairments.

Aged↗
PubMed2006

Percutaneous coronary intervention for chronic total occlusion in 1263 patients: a single-center report.

BACKGROUND: Coronary chronic total occlusion (CTO) remains one of the most challenging lesion subsets in interventional cardiology, even with the development of medical device and operator expertise. This study was conducted to examine the relationship between lesion characteristics and procedural success and the incidence of in-hospital major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) for CTO. METHODS: Clinical and coronary angiographic data of 1263 patients with CTO who underwent PCI between June 1995 and December 2005 in Shenyang General Hospital of PLA were retrospectively analyzed. RESULTS: There were 1625 CTO lesions located in 1596 vessels with a mean occlusion time of 48.9 months. A total of 1647 coronary stents were implanted to the target lesions. The overall patient and lesion success rates were 90.8% (1147/1263) and 88.9% (1445/1625), respectively. The success rate of PCI was declined with long duration of occlusion, abrupt missing stump, bridging collaterals > or = 15 mm in occluded length, moderate to severe calcification or tortuosity and ostial or distal location of CTO lesions (P < 0.05). Procedural failure occurred in 116 patients, caused by impossibility of guide-wire (81.0%) or balloon (19.0%) to pass through the occlusion. There was no death during procedure, but 2 patients suffered from acute stent thrombosis and other 9 patients had acute or late pericardial perforation. Those complications were all successfully treated. After procedure, 3 patients died, 4 experienced urgent target vessel revascularization because of subacute stent thrombosis and 1 underwent coronary bypass graft surgery due to coronary fistula during in-hospital period. The overall in-hospital MACE rate was 0.6% (8/1263). Drug-eluting stents were used in 198 patients without in-hospital MACE. CONCLUSIONS: In an experienced heart center, it is possible to obtain a relatively high success rate of PCI and favorable clinical outcomes for patients with coronary CTO lesions.

Adult↗
PubMed2006

The existence of CD11c+ sentinel and F4/80+ interstitial dendritic cells in dental pulp and their dynamics and functional properties.

Dental caries and pulpitis are the most common bacterial infections in humans. However, the immune responses against bacterial stimulation in dental pulp that is bounded by special hard tissues are poorly understood. We examined the initial immune responses in mouse dental pulp after cusp trimming and acid treatment. Using fluorescence immunohistochemistry, two distinct cell populations were identified in the intact pulp; CD11c+F4/80- and CD11c-F4/80+ cells. CD11c+F4/80- cells were localized in the pulp-dentin (P-D) border of the central pulp beneath the dental fissure, whereas CD11c-F4/80+ cells with dendritic morphology were distributed in the perivascular region of the inner pulp and the sub-odontoblastic layer. CD11c+F4/80- cells, but not CD11c-F4/80+ cells, constitutively expressed toll-like receptors 2 and 4 and CD205, and migrated to the P-D border of the treated side within 2 h after the treatment. In parallel, some of the F4/80+ cells migrated to the inner pulp of the treated side, increased in size and enhanced CD86 expression. At 24 h, the CD86+ cells with high fluorescence intensity had disappeared entirely from the pulp. Concurrently, CD86high cells expressing intermediate levels of CD11c and high levels of MHC class II and F4/80, assessed by using flow cytometry, increased significantly in the regional lymph nodes, suggesting migration of these cells from the dental pulp. Our results are the first to demonstrate the existence of at least two types of dendritic cells (DCs) in dental pulp. The CD11c+ sentinel and F4/80+ interstitial DCs might have distinct territories and unique roles in responding to external stimuli via the dentinal tubules.

Animals↗
PubMed2006

Apolipoprotein B is associated with metabolic syndrome in Chinese families with familial combined hyperlipidemia, familial hypertriglyceridemia and familial hypercholesterolemia.

There is a paucity of data concerning the metabolic syndrome (MetS) in families with familial combined hyperlipidemia (FCHL), familial hypertriglyceridemia (FHTG), familial hypercholesterolemia (FH) and normolipidemic families in China. This study investigated the prevalence of MetS in these families and explored potential factors relevant to MetS. We recruited 70 families with 560 individuals > or = 20 years of age, including 43 FCHL families with 379 individuals, 3 FHTG families with 30 individuals, 16 FH families with 102 individuals and 8 normolipidemic families with 49 individuals. The definition of MetS is determined using modified criteria of National Cholesterol Education Program substituting body mass index for waist circumference. MetS is identified in 60.7% of FCHL patients and 71.4% of FHTG patients. The prevalence of MetS in family members is 36.7% for FCHL, 33.3% for FHTG, 17.6% for FH and 16.3% for normolipidemic families, with an odds ratio (OR) of 2.97 (95% CI 1.29-7.07, P=0.007) in FCHL families compared with normolipidemic families. Apolipoprotein B (apoB) is associated with MetS by multiple logistic analysis with an OR of 1.05 (1.03-1.07, P<0.001) in FCHL families, OR of 1.26 (1.03-1.55, P=0.026) in FHTG and OR of 1.07 (1.01-1.12, P=0.014) in FH families, independent of variables including age, gender, apolipoprotein A1, and low density lipoprotein cholesterol. Apolipoprotein A1 provided an OR of 0.95 (0.94-0.97, P<0.001) in FCHL families and OR of 0.94 (0.90-0.97, P=0.011) in FH families, but neither in FHTG nor in normolipidemic families (both P>0.05). Thus, apoB may be regarded as a relevant factor in the assessment of MetS in FCHL, FHTG and FH families. However, this finding needs to be verified by prospective studies in diverse ethnicities and warrants additional studies to elucidate possible mechanisms linking apoB to MetS.

Adult↗
PubMed2006

[Transforaminal lumbar interbody fusion in treatment of upper lumbar disc herniation: analysis of 18 cases].

OBJECTIVE: To study the effectiveness and advantages of transforaminal lumbar interbody fusion (TLIF) in the treatment of upper lumbar disc herniation. METHODS: Eighteen cases with upper lumbar disc herniation, 12 males and 6 females, aged 21 - 67, underwent TLIF. Follow-up was conducted for 19.8 months (12 - 54 months). The surgical process, outcomes, and complications were reviewed retrospectively. In TLIF operation, pedicle screw fixation was performed first, unilateral or bilateral facet joints were then excised. Disc removal and titanium mesh or fusion cage insertion were completed via transforaminal approach. RESULTS: Unilateral TLIF was performed in 14 cases and bilateral TLIF was accomplished in 4 cases. The mean operation time was 82.4 minutes and the intraoperative blood loss was 323 ml. No injury of spinal cord or nerve roots happened during the operation. The follow-up showed that the operation results were excellent in 11 cases, good in 4 cases, and fair in 3 cases. No worsening or relapse of preoperative symptoms was observed. Disc spaces and lumbar lordosis were restored satisfactorily. No internal fixation failure was found. CONCLUSION: Able to excise disc completely, restore physiological lumbar curve effectively and prevent postoperative instability, TLIF is one of effective surgical treatments for upper lumbar disc herniation for selected patients.

Adult↗