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Biomedical subjects

Xuejun Zhang

Publications and source records attributed to Xuejun Zhang.

At least 19 recordsLinked to original sources
PubMed2007

Nerve growth factor prevents the apoptosis-associated increase in acetylcholinesterase activity after hydrogen peroxide treatment by activating Akt.

Acetylcholinesterase (AChE) is thought to play an important role during apoptosis. Our results showed that H2O2 induced AChE activity, a functional marker in apoptosis, increases in neuronal-like PC12 cells. Glutathione, which is involved in cellular redox homeostasis, inhibited the increase of AChE activity, suggesting that reactive oxygen species (ROS) play a key role in this process. Further investigation showed that the elevation of AChE was observed after the degradation of Akt, release of cytochrome c from mitochondria into the cytosol, and activation of caspase family members. When nerve growth factor (NGF) was present, with the maintenance of Akt level, the elevation of AChE, the cytochrome c diffusion, as well as apoptosis were markedly attenuated in H2O2-treated PC12 cells. However, wortmannin, an inhibitor of the PI3K/Akt pathway, accelerated the apoptosis and increased the AChE activity. The overexpression of constitutively activated Akt, which is a downstream signalling element of the NGF receptor TrkA, delayed mitochondrial collapse and inhibited elevation of AChE activity. Thus, NGF prevented apoptosis and elevation of AChE activity by activating the Akt pathway and stabilizing the function of mitochondria.

Acetylcholinesterase↗
PubMed2006

Structure of a conserved hypothetical protein SA1388 from S. aureus reveals a capped hexameric toroid with two PII domain lids and a dinuclear metal center.

BACKGROUND: The protein encoded by the SA1388 gene from Staphylococcus aureus was chosen for structure determination to elucidate its domain organization and confirm our earlier remote homology based prediction that it housed a nitrogen regulatory PII protein-like domain. SA1388 was predicted to contain a central PII-like domain and two flanking regions, which together belong to the NIF3-like protein family. Proteins like SA1388 remain a poorly studied group and their structural characterization could guide future investigations aimed at understanding their function. RESULTS: The structure of SA1388 has been solved to 2.0A resolution by single wavelength anomalous dispersion phasing method using selenium anomalous signals. It reveals a canonical NIF3-like fold containing two domains with a PII-like domain inserted in the middle of the polypeptide. The N and C terminal halves of the NIF3-like domains are involved in dimerization, while the PII domain forms trimeric contacts with symmetry related monomers. Overall, the NIF3-like domains of SA1388 are organized as a hexameric toroid similar to its homologs, E. coli ybgI and the hypothetical protein SP1609 from Streptococcus pneumoniae. The openings on either side of the toroid are partially covered by trimeric "lids" formed by the PII domains. The junction of the two NIF3 domains has two zinc ions bound at what appears to be a histidine rich active site. A well-defined electron density corresponding to an endogenously bound ligand of unknown identity is observed in close proximity to the metal site. CONCLUSION: SA1388 is the third member of the NIF3-like family of proteins to be structurally characterized, the other two also being hypothetical proteins of unknown function. The structure of SA1388 confirms our earlier prediction that the inserted domain that separates the two NIF3 domains adopts a PII-like fold and reveals an overall capped toroidal arrangement for the protein hexamer. The six PII-like domains form two trimeric "lids" that cap the central cavity of the toroid on either side and provide only small openings to allow regulated entry of small molecules into the occluded chamber. The presence of the electron density of the bound ligand may provide important clues on the likely function of NIF3-like proteins.

Bacterial Proteins↗
PubMed2006

A histidine/tryptophan pi-stacking interaction stabilizes the heme-independent folding core of microsomal apocytochrome b5 relative to that of mitochondrial apocytochrome b5.

The outer mitochondrial membrane isoform of mammalian cytochrome b5 (OM b5) is considerably more stable than its microsomal counterpart (Mc b5), whereas the corresponding apoproteins (OM and Mc apo-b5) exhibit similar stability. OM and Mc apo-b5 are also similar in that their empty heme-binding pockets (core 1) are highly disordered but that the remainder of each apoprotein (core 2) displays substantial hololike structure. Core 1 residue 71 is leucine in all known mammalian OM b5's and serine in the corresponding Mc proteins. Replacing Leu-71 in rat OM (rOM) b5 with Ser has been shown to (1) decrease apoprotein thermodynamic stability by >2 kcal/mol and (2) extend conformational disorder beyond core 1 and into core 2, as evidenced in part by loss of a near-UV circular dichroism signal associated with the side chain of invariant residue Trp-22. Herein we report identification of a conserved Mc b5 core 2 packing motif that plays a key role in stabilizing apoprotein conformation in the vicinity of Trp-22, thereby compensating for the presence of Ser at position 71: a pi-stacking interaction between the side chains of Trp-22 and His-15 that is extended by hydrogen bonding between the side chains of His-15, Ser-20, and Glu-11. The corresponding conserved packing motif in OM b5's differs in having arginine at position 15 and glutamate at position 20. We also present evidence indicating that the conserved Mc b5 packing motif noted above contributes to the unusually extensive secondary structure exhibited by bovine Mc apo-b5 in the urea-denatured state.

Animals↗
PubMed2006

Lymphotoxin pathway-directed, autoimmune regulator-independent central tolerance to arthritogenic collagen.

Ectopic expression of peripherally restricted Ags by medullary thymic epithelial cells (mTECs) is associated with negative selection. Autoimmune regulator (AIRE) is considered to be the master regulator of these Ags. We show in this study that the ectopic expression of type II collagen (CII) in mTECs and the corresponding central tolerance to CII are AIRE independent but lymphotoxin dependent. The failure to properly express CII in mTECs of Lta(-/-) and Ltbr(-/-) mice leads to overt autoimmunity to CII and exquisite susceptibility to arthritis. These findings define the existence of additional pathways of ectopic peripheral Ag expression, parallel to and independent of AIRE, which may cover an extended spectrum of peripheral Ags in the thymus.

Animals↗
PubMed2006

Copper(II)-catalyzed amidations of alkynyl bromides as a general synthesis of ynamides and Z-enamides. An intramolecular amidation for the synthesis of macrocyclic ynamides.

A general and efficient method for the coupling of a wide range of amides with alkynyl bromides is described here. This novel amidation reaction involves a catalytic protocol using copper(II) sulfate-pentahydrate and 1,10-phenanthroline to direct the sp-C-N bond formation, leading to a structurally diverse array of ynamides including macrocyclic ynamides via an intramolecular amidation. Given the surging interest in ynamide chemistry, this atom economical synthesis of ynamides should invoke further attention from the synthetic organic community.

Amides↗
PubMed2006

Double-deformable-mirror adaptive optics system for phase compensation.

Two kinds of algorithm for an adaptive optics (AO) system that uses two deformable mirrors (DMs), one with large stroke and the other with high spatial frequency, to correct different aberrations are described. The algorithms are based on modal method and direction-gradient method, respectively. Numerical simulations for the algorithms have been made. The simulation results indicate that the two DMs in the AO system can correct different aberrations with different characteristics, and the closed-loop performance of a double-DM AO system will be almost the same as that of an AO system that uses a single DM with an ideal stroke.

Journal Article↗
PubMed2006

Effect of the mobile phase on the retention behavior of optical isomers of the mandelic acid derivative methyl 2-phenyl-2-(tetrahydropyranyloxy) acetate by chiral HPLC.

Conditions for separation of enantiomers of a mandelic acid derivative, methyl 2-phenyl-2-(tetrahydropyranyloxy) acetate (the analyte) were studied. Because of the presence of two chiral carbons, the analyte consists of four stereoisomers stable at ambient temperature. Chiral HPLC of the analyte resulted in four peaks, using an (S,S)-Whelk-O1 column with the mobile phase consisting of hexane and the t-butyl methyl ether (TBME). It was found that TBME dramatically changed the retention of the isomers, though it produced the best enantioseparation on (S,S)-Whelk-O1. The amount of TBME in the mobile phase influenced the degree of retention shift; 5% (v/v) TBME gave a bigger shift than 8% (v/v) and 10% (v/v). 2-Propanol did not produce the same results. The chiral separation was also tried on cellulose tris (3, 5-dimethyl phenylcarbamate) (CDMPC), but only three peaks were seen, indicating some but not full enantiomer resolution.

Acetates↗
PubMed2006

Diverse phenotype of Brooke-Spiegler syndrome associated with a nonsense mutation in the CYLD tumor suppressor gene.

Brooke-Spiegler syndrome (BSS) is an autosomal dominant disease characterized by cylindromas, trichoepitheliomas and occasionally spiradenomas. The disease gene was mapped to 16q12-13, and mutations in the CYLD gene were identified in families with BSS. In the present report, we describe a large consanguineous Chinese family with BSS showing an intra-family phenotypic variability. Clinically, some affected individuals only revealed discrete small skin-coloured tumors whereas the proband showed an expansion of multiple large tumors on the back of nose and numerous dome-shaped papules on her scalp. Histologically, both trichoepitheliomas and cylindromas were found in the affected individuals. By sequence analysis, we identified a recurrent mutation 2272C>T (R758X) of the CYLD gene in the affected individuals of this family, which was previously identified in other ethnic families with familial cylindromatosis. Our result provided additional information for phenotype-genotype correlation in BSS.

Adult↗
PubMed2005

V alpha 24-invariant NKT cells from patients with allergic asthma express CCR9 at high frequency and induce Th2 bias of CD3+ T cells upon CD226 engagement.

We have demonstrated that Valpha24(+)Vbeta11(+) invariant (Valpha24(+)i) NKT cells from patients with allergic asthma express CCR9 at high frequency. CCR9 ligand CCL25 induces chemotaxis of asthmatic Valpha24(+)i NKT cells but not the normal cells. A large number of CCR9-positive Valpha24(+)i NKT cells are found in asthmatic bronchi mucosa, where high levels of Th2 cytokines are detected. Asthmatic Valpha24(+)i NKT cells, themselves Th1 biased, induce CD3(+) T cells into an expression of Th2 cytokines (IL-4 and IL-13) in cell-cell contact manner in vitro. CD226 are overexpressed on asthmatic Valpha24(+)i NKT cells. CCL25/CCR9 ligation causes directly phosphorylation of CD226, indicating that CCL25/CCR9 signals can cross-talk with CD226 signals to activate Valpha24(+)i NKT cells. Prestimulation with immobilized CD226 mAb does not change ability of asthmatic Valpha24(+)i NKT cells to induce Th2-cytokine production, whereas soluble CD226 mAb or short hairpin RNA of CD226 inhibits Valpha24(+)i NKT cells to induce Th2-cytokine production by CD3(+) T cells, indicating that CD226 engagement is necessary for Valpha24(+)i NKT cells to induce Th2 bias of CD3(+) T cells. Our results are providing with direct evidence that aberration of CCR9 expression on asthmatic Valpha24(+)i NKT cells. CCL25 is first time shown promoting the recruitment of CCR9-expressing Valpha24(+)i NKT cells into the lung to promote other T cells to produce Th2 cytokines to establish and develop allergic asthma. Our findings provide evidence that abnormal asthmatic Valpha24(+)i NKT cells induce systemically and locally a Th2 bias in T cells that is at least partially critical for the pathogenesis of allergic asthma.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2005

Induction of CD4+CD25+ regulatory T cells by copolymer-I through activation of transcription factor Foxp3.

Copolymer-I (COP-I) has unique immune regulatory properties and is a treatment option for multiple sclerosis (MS). This study revealed that COP-I induced the conversion of peripheral CD4+CD25- to CD4+CD25+ regulatory T cells through the activation of transcription factor Foxp3. COP-I treatment led to a significant increase in Foxp3 expression in CD4+ T cells in MS patients whose Foxp3 expression was reduced at baseline. CD4+CD25+ T cell lines generated by COP-I expressed high levels of Foxp3 that correlated with an increased regulatory potential. Furthermore, we demonstrated that the induction of Foxp3 in CD4+ T cells by COP-I was mediated through its ability to produce IFN-gamma and, to a lesser degree, TGF-beta1, as shown by antibody blocking and direct cytokine induction of Foxp3 expression in T cells. It was evident that in vitro treatment and administration with COP-I significantly raised the level of Foxp3 expression in CD4+ T cells and promoted conversion of CD4+CD25+ regulatory T cells in wild-type B6 mice but not in IFN-gamma knockout mice. This study provides evidence for the role and mechanism of action of COP-I in the induction of CD4+CD25+ regulatory T cells in general and its relevance to the treatment of MS.

Animals↗
PubMed2005

Brønsted acid-catalyzed highly stereoselective arene-ynamide cyclizations. A novel keteniminium Pictet-Spengler cyclization in total syntheses of (+/-)-desbromoarborescidines A and C.

[reaction: see text] A Brønsted acid-catalyzed highly stereoselective arene-ynamide cyclization is described. These reactions constitute a keteniminium variant of Pictet-Spengler cyclizations, leading to efficient synthesis of nitrogen heterocycles and related alkaloids. Total syntheses of desbromoarborescidines A and C are illustrated here as first applications of this methodology.

Catalysis↗
PubMed2005

Reduction of the incidence and severity of collagen-induced arthritis by constitutive Nur77 expression in the T cell lineage.

OBJECTIVE: To test the hypothesis that constitutive expression of Nur77 in the T cell lineage will suppress the development and pathogenesis of collagen-induced arthritis (CIA) and to understand the mechanisms by which Nur77 overexpression influences the arthritogenic response to type II collagen (CII). METHODS: Nur77-transgenic and wild-type C57BL/6 mice were immunized with CII and were monitored for the development and severity of arthritis. Pathologic changes were examined by histology and radiography. The effects of Nur77 overexpression on immune responses were evaluated by cytokine production in vitro and serum levels of CII-specific antibodies. Sensitivity of T cells to apoptosis induction was analyzed in vitro following stimulation with anti-CD3 monoclonal antibody or glucocorticoid. RESULTS: The incidence and severity of CIA was significantly decreased in Nur77-transgenic mice compared with wild-type controls. Attenuation of the disease was associated with increased apoptosis induction in transgenic T cells and decreased production of CII-specific IgG2a antibodies in transgenic mice. Overexpression of Nur77 in the T cell compartment did not affect Th1/Th2 cytokine production or balance. CONCLUSION: Nur77 overexpression in the T cell lineage attenuates the development and progression of CIA, probably by promoting activation-induced T cell apoptosis and by inhibiting CII-specific antibody production.

Animals↗
PubMed2005

CXCL13 neutralization reduces the severity of collagen-induced arthritis.

OBJECTIVE: To investigate the role of CXCL13 in the development and pathogenesis of collagen-induced arthritis (CIA), and to determine the mechanisms involved in the modulation of arthritogenic response by CXCL13 neutralization. METHODS: Mice were immunized with type II collagen (CII) and treated with anti-CXCL13 or control antibodies during boosting. Mice were monitored for the development and severity of arthritis. The effects of CXCL13 neutralization on immune response to CII were evaluated by cytokine production by CII-specific T cells and CII-specific antibody production. Follicular response in the spleen and in synovial tissue was determined by in situ immunohistology. RESULTS: Mice receiving neutralizing antibodies to CXCL13 developed significantly less severe arthritis compared with mice injected with phosphate buffered saline or control antibodies. Follicular response both in the spleen and in synovial tissue was inhibited by anti-CXCL13 treatment. Injection with anti-CXCL13 antibodies did not significantly affect antigen-specific recall lymphocyte proliferation or type 1 cytokine production in vitro. Antibody response specific to CII was not inhibited by anti-CXCL13 treatment. However, anti-CXCL13 treatment induced significantly higher levels of interleukin-10 production after in vitro CII stimulation. CONCLUSION: Neutralization of CXCL13 inhibits the development of CIA and reduces follicular response in both lymphoid and nonlymphoid tissues. These findings may have important implications regarding the pathogenesis and treatment of autoimmune arthritis.

Animals↗
PubMed2005

Blockade of lymphotoxin pathway exacerbates autoimmune arthritis by enhancing the Th1 response.

OBJECTIVE: To study the role of the lymphotoxin (LT) signaling pathway in the development and pathogenesis of collagen-induced arthritis (CIA), and to understand the mechanisms by which blockade of the LT pathway influences the arthritogenic response to type II collagen (CII). METHODS: LTalpha-deficient and wild-type C57BL/6 mice were immunized with CII. Male DBA/1 mice were immunized with CII and treated with LTbeta receptor immunoglobulin fusion protein (LTbetaR-Ig) or control Ig. Mice were monitored for the development and severity of arthritis. The effects of LT blockade on immune responses were evaluated by cytokine production and antigen-specific proliferation in vitro, the delayed-type hypersensitivity (DTH) response, and serum levels of CII-specific antibodies. RESULTS: CIA that developed in LTalpha-deficient mice was more severe and prolonged than that which developed in wild-type mice. Blocking LT signaling with LTbetaR-Ig significantly exacerbated the disease. Exacerbation of CIA was associated with an enhanced Th1-type response, including increased type 1 cytokine production, an enhanced DTH response, and elevated production of CII-specific IgG2a antibodies. CONCLUSION: Blockade of the LT signaling pathway exacerbates the development and progression of CIA, probably by skewing the Th1/Th2 balance that determines the outcome of autoimmune responses.

Animals↗
PubMed2005

STD/AIDS knowledge, attitude, practice, and characteristics of market vendors in Hefei, China.

Little is known about the information on sexually transmitted disease (STD)/AIDS in the population working in congregating trading markets in China. A cross-sectional study was conducted among three big congregating trading markets in Hefei City. Seven hundred fifty-two market vendors completed a questionnaire, 333 of two markets provided specimen for STD/HIV testing. The majority of market vendors in China are sexually active youths and adults, and have little education. The market vendors had poor knowledge of STD/AIDS. The rates of correct answers to questions about STD/AIDS varied between 21.1%-81.9%. More than 50% of the market vendors had a negative attitude toward HIV-infected individuals. Among the subjects, 27.6% had had premarital or extramarital sex; 15.9% reported using condoms in the past 12 months. Among those who provided specimens, 3.9% were identified with STD, approximately 9 times higher than that in the general population of Hefei (0.4%). Our study suggests China should implement STD/HIV prevention interventions for market vendors to prevent STD/HIV infection.

Adult↗
PubMed2005

Neutral lipid isolated from endosperm of Job's tears inhibits the growth of pancreatic cancer cells via apoptosis, G2/M arrest, and regulation of gene expression.

BACKGROUND: The neutral lipid isolated from the endosperm of Job's tears (NLEJ) has been known to possess an anticancer activity with relatively low toxicity. The present study was designed to examine its antiproliferative effects in the PaTu-8988 and SW1990 human pancreatic cancer cells and to investigate its potential mechanism(s). METHODS: Pancreatic cancer cells were treated with NLEJ to evaluate cell viability, cell cycle progression, nuclear morphology, DNA fragmentation and annexin V binding analysis. Regulation of gene expression was determined by using cDNA microarrays and western immunoblotting. RESULTS: The NLEJ induced a dose- and time-dependent inhibition of proliferation in both PaTu-8988 and SW1990 cell lines. Further studies were carried out with only the PaTu-8988 cells. Flow cytometry analysis showed that NLEJ blocked cell cycle progression at the G(2)/M phase. There was also an increase in annexin V binding and DNA fragmentation, indicative of apoptosis. The cDNA microarray analysis with cell cycle- and apoptosis-targeted arrays showed that the expression signals of 24 genes were found to be significantly altered at 24 h of NLEJ treatment. These genes are involved in cell cycle control (e.g. p21, p27, CDK2, and cyclins), apoptosis regulation (e.g. bcl-2 and bax), and signal transduction (e.g. ATM, RAD50, and p53). Some of these results were confirmed by western blot analysis. CONCLUSIONS: These data show that NLEJ inhibits pancreatic cancer cell growth through induction of apoptosis and cell cycle arrest as well as regulation of gene expression in vitro. Therefore, NLEJ might be a chemotherapeutic agent against pancreatic cancer.

Apoptosis↗