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Wen Jiang

Publications and source records attributed to Wen Jiang.

At least 55 records · Page 3Linked to original sources
PubMed2003

Identification of a potent and selective noncovalent cathepsin S inhibitor.

Cathepsin S is considered crucial for normal presentation of major histocompatibility complex (MHC) class II-restricted antigens by antigen presenting cells to CD4+ T cells. It is a key enzyme for the degradation of the class II-associated invariant chain, a process that is required for effective antigen loading of class II molecules. Here, we report a selective, orally available, high-affinity cathepsin S inhibitor, 1-[3-[4-(6-Chloro-2,3-dihydro-3-methyl-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]propyl]-4,5,6,7-tetrahydro-5-(methylsulfonyl)-3-[4-(trifluoromethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine. (JNJ 10329670), that represents a novel class of immunosuppressive compounds. JNJ 10329670 is a highly potent (Ki of approximately 30 nM), nonpeptidic, noncovalent inhibitor of human cathepsin S, but it is much less active against the mouse, dog, monkey, and bovine enzymes. The compound is inactive against other proteases, including the closely related cathepsins L, F, and K. This selectivity makes JNJ 10329670 an excellent tool for exploring the role of cathepsin S in human systems. Treatment of human B cell lines and primary human dendritic cells with JNJ 10329670 resulted in the accumulation of the p10 fragment of the invariant chain (IC50 of approximately 1 microM). In contrast, inhibition of invariant chain proteolysis was much less effective in a human monocytic cell line, suggesting that other enzymes may degrade the invariant chain in this cell type. JNJ 10329670 was shown to block the proteolysis of the invariant chain in vivo by using immunocompromised mice injected with human peripheral blood mononuclear cells (PBMCs). Furthermore, this inhibitor blocks the presentation of tetanus toxoid and giant ragweed by human PBMCs. The properties of JNJ 10329670 make it a candidate for immunosuppressive therapy of allergies and autoimmune diseases.

Animals↗
PubMed2003

Stimulation of proteinase-activated receptor 2 excites jejunal afferent nerves in anaesthetised rats.

Proteinase-activated receptor 2 (PAR2) is a receptor for mast cell tryptase and trypsins and might participate in brain-gut communication. However, evidence that PAR2 activation can lead to afferent impulse generation is lacking. To address this issue, we examined the sensitivity of jejunal afferent nerves to a hexapeptide agonist of PAR2, SLIGRL-NH2, and the modulation of the resulting response to treatment with drugs and vagotomy. Multiunit recordings of jejunal afferent activity were made using extracellular recording techniques in anaesthetised male rats. SLIGRL-NH2 (0.001-1 mg kg-1, I.V.) increased jejunal afferent firing and intrajejunal pressure. The reverse peptide sequence (1 mg kg-1, I.V.), which does not stimulate PAR2, was inactive. Naproxen (10 mg kg-1, I.V.), but not a cocktail of omega-conotoxins GVIA and SVIB (each at 25 mug kg-1, I.V.), curtailed both the afferent response and the intrajejunal pressure rise elicited by the PAR2 agonist. Although neither treatment modulated the peak magnitude of the afferent firing, they each altered the intestinal motor response, unmasking an initial inhibitory component. Nifedipine (1 mg kg-1, I.V.) reduced the peak magnitude of the afferent nerve discharge and abolished the initial rise in intrajejunal pressure produced by SLIGRL-NH2. Vagotomy did not significantly influence the magnitude of the afferent response to the PAR2 agonist, which involves a contribution from capsaicin-sensitive fibres. In conclusion, intravenous administration of SLIGRL-NH2 evokes complex activation of predominantly spinally projecting extrinsic intestinal afferent nerves, an effect that involves both direct and indirect mechanisms.

Anesthesia↗
PubMed2003

The first potent and selective non-imidazole human histamine H4 receptor antagonists.

Following the discovery of the human histamine H4 receptor, a high throughput screen of our corporate compound collection identified compound 6 as a potential lead. Investigation of the SAR resulted in the discovery of novel compounds 10e and 10l, which are the first potent and selective histamine H4 receptor antagonists to be described.

Animals↗
PubMed2003

Architecture of the herpes simplex virus major capsid protein derived from structural bioinformatics.

The dispositions of 39 alpha helices of greater than 2.5 turns and four beta sheets in the major capsid protein (VP5, 149 kDa) of herpes simplex virus type 1 were identified by computational and visualization analysis from the 8.5A electron cryomicroscopy structure of the whole capsid. The assignment of helices in the VP5 upper domain was validated by comparison with the recently determined crystal structure of this region. Analysis of the spatial arrangement of helices in the middle domain of VP5 revealed that the organization of a tightly associated bundle of ten helices closely resembled that of a domain fold found in the annexin family of proteins. Structure-based sequence searches suggested that sequences in both the N and C-terminal portions of the VP5 sequence contribute to this domain. The long helices seen in the floor domain of VP5 form an interconnected network within and across capsomeres. The combined structural and sequence-based informatics has led to an architectural model of VP5. This model placed in the context of the capsid provides insights into the strategies used to achieve viral capsid stability.

Amino Acid Motifs↗
PubMed2003

Dentate granule cell neurogenesis after seizures induced by pentylenetrazol in rats.

Epileptic seizures originating from the limbic system have been shown to stimulate the proliferation rate of granule cell precursors in the adult brain, but it is not clear if other type(s) of seizures have the similar effects. This study examined the effects of pentylenetrazol (PTZ)-induced generalized clonic seizures on dentate granule cell neurogenesis in adult rats. Using systemic bromodeoxyuridine (BrdU) to label dividing cells, we studied the proliferation rate of neural precursor cells in the dentate gyrus at various time points after PTZ-induced seizures. The double-label immunofluorescence with confocal microscopy was used to determine the newborn cell phenotypes. Quantitative analysis of BrdU labeling revealed a significant increase in the proliferation rate of neural precursor cells in the dentate gyrus 3, 7, and 14 days after seizures. The number of BrdU-labeled cells in the dentate gyrus returned to baseline levels by 28 days after the initial seizures. Most of newborn cells migrated into the granule cell layer from the subgranular zone, displayed the neuronal phenotype, and developed morphological characteristics of differentiated dentate granule cells. These results indicated that neuron proliferation in the dentate gyrus was enhanced during a time window (3-14 days) after PTZ-induced seizures. Its underlying mechanism is discussed.

Animals↗
PubMed2003

Valproic acid enhances axonal regeneration and recovery of motor function after sciatic nerve axotomy in adult rats.

It has recently been demonstrated that valproic acid (VPA) robustly promotes neurite outgrowth, activates the extracellular signal regulated kinase pathway, and increases growth cone-associated protein 43 and bcl-2 levels in cultured human neuroblastoma SH-SY5Y cells. We hypothesized that VPA could also enhance peripheral nerve regeneration in adult animals. To test this hypothesis, we examined the effects of VPA (300 mg/kg daily for 16 weeks) on sciatic axonal regeneration following single or conditional axotomies in rats. The results showed that in VPA-treated rats there was a significant increase in the total numbers of regenerated myelinated nerve fibers and reinnervated muscle fibers in comparison with those rats not treated with VPA. As measured by sciatic function index and toe spread index, the motor function of the reinnervated hind limbs of rats receiving single axotomy without VPA treatment significantly improved at week 8 and reached plateau levels at about week 11, whereas the motor function of the reinnervated hind limbs of rats receiving single axotomy plus VPA and rats receiving conditional axotomy with or without VPA treatment significantly improved at week 4 and reached plateau levels at about week 8; there was no significant difference of the motor function among the three later groups. The results demonstrated that VPA is able to enhance sciatic nerve regeneration and recovery of motor function in adult rats, suggesting the potential clinical application of VPA for the treatment of peripheral nerve injury in humans.

Algorithms↗
PubMed2003

Control of electroosmotic flow and wall interactions in capillary electrophoresis capillaries by photografted zwitterionic polymer surface layers.

A novel capillary with covalently bonded zwitterionic surface modification was prepared by photograft polymerization of the zwitterionic monomer N,N-dimethyl-N-methacryloxyethyl-N-(3-sulfopropyl)ammonium betaine, onto the inner surface of a UV-transparent fused-silica capillary. Although the zwitterionic moieties in the resulting polymeric "tentacles" comprise both a positive quaternary ammonium group and a negative sulfonate group, the coating has a net zero charge. The electroosmotic flow (EOF) was therefore extensively suppressed on the grafted capillary compared to the native silica capillary and to the silica capillary that had been activated for graft polymerization by reaction with 3-(methacryloyl)oxypropyltrimethoxysilane. It was also found that the EOF can be varied by adding chaotropic anions or divalent cations such as perchlorate ion and magnesium ion to the running buffer, due to the interaction between these ions and zwitterionic functional group. This provides a new way of altering the EOF and the wall interaction without changing the pH or the overall ionic strength of the separation buffer. The influence of pH and ionic strength of separation buffer on the EOF were also investigated to optimize the separation conditions. Good separations of a mixture containing eight inorganic anions were achieved within 5 min under optimal conditions by capillary zone electrophoresis. The newly prepared capillary was also well suited for the separation of peptides or proteins.

Anions↗
PubMed2003

Sodium tanshinone IIA sulfonate mediates electron transfer reaction in rat heart mitochondria.

In this paper, an electron transfer reaction mediated by sodium tanshinone IIA sulfonate (STS) was studied in rat heart mitochondria. It was found that STS could stimulate mitochondrial NADH oxidation dose-dependently and partly restore NADH oxidation in the presence of respiratory inhibitor (rotenone or antimycin A or KCN). It was likely that STS could accept electrons from complex I similar to ferricyanide and could be converted to its semiquinone form that could then reduce oxygen molecule. The data also showed that cytochrome c (Cyt c) could be reduced by STS in the presence of KCN, or STS could transfer the electron to oxygen directly. Free radicals were involved in the process. The results suggest that STS may protect ischemia-reperfusion injury through an electron transfer reaction in mitochondria against forming reactive oxygen radicals.

Animals↗
PubMed2003

Coat protein fold and maturation transition of bacteriophage P22 seen at subnanometer resolutions.

Bacteriophage P22 is a prototypical biological machine used for studying protein complex assembly and capsid maturation. Using cryo-EM, we solved the structures of P22 before and after the capsid maturation at 8.5 A and 9.5 A resolutions, respectively. These structures allowed visualization of alpha-helices and beta-sheets from which the capsid protein fold is derived. The capsid fold is similar to that of the coat protein of HK97 bacteriophage. The cryo-EM shows that a large conformational change of the P22 capsid during maturation transition involves not only the domain movement of individual subunits, but also refolding of the capsid protein.

Bacteriophage P22↗
PubMed2003

Localization of orexin-1 receptors to vagal afferent neurons in the rat and humans.

BACKGROUND & AIMS: Orexin-A and -B are brain-gut peptides that stimulate food intake via orexin-R1 and -R2 receptors. Cholecystokinin (CCK) inhibits food intake via CCK(A) receptors expressed on vagal afferent neurons. The purpose of the study was to determine whether vagal afferent neurons express OX-R1 and OX-R2 and whether orexin-A inhibits responses to CCK. METHODS: OX-R1 and -R2 expression by rat and human nodose ganglia was examined by reverse-transcriptase polymerase chain reaction (RT-PCR). Receptor localization was determined by immunohistochemistry. Responses of rat jejunal afferent fibers were examined by electrophysiology. RESULTS: Both rat and human nodose ganglia expressed OX-R1 as detected by RT-PCR, and humans also expressed OX-R2. The identity of the products was confirmed by sequencing. Immunohistochemistry indicated expression of OX-R1 in both species in neurons that also expressed CCK(A) and leptin receptors. In human ganglia there was also expression in glial cells that was absent in rats. Orexin-A had no effect on the resting discharge of afferent nerve fibers but inhibited responses to CCK. CONCLUSIONS: OX-R1 and CCK(A) receptors are expressed by human and rat vagal afferent neurons. Orexin inhibits responses to CCK suggesting a role in modulation of gut to brain signaling.

Animals↗
PubMed2003

[Selection of operative approaches for rhinosinusal malignant tumor involving in the anterior skull base and exploration for reconstruction].

OBJECTIVE: To investigate operative approaches and techniques of reconstruction for rhinosinusal malignant tumors involving in the anterior skull base. METHOD: In a retrospective study, clinical data of 22 patients treated surgically in our department from 1988 to 2002 were analysed. Lateral rhinotomy was carried out in 8 patients and ampliative rhinotomy in 4 patients; in 10 patients craniofacial operation was performed. Multiple layer fascia flaps were used to repair lager defect in the anterior skull base. RESULT: All tumors were totally resected. In lateral rhinotomy, local locoeled meningitis happened in 1 case, and 4 patients in craniofacial operation. None complication with cerebrospinal fluid leaks, encephalomeningocele and intracranial air. All patients were followed up from 6 months to 11 years after surgery. 7 patients died from intracranial infection or metastasis of tumor. 3-year survival rates was 15/19(78.9%); 5-year survival rates was 13/19(68.4%). The tumor invaded the orbital fascia in 9 patients. Vs 4/9 (44.4%) and 2/9(22.2%) for these 3 and 5-year survival rates. CONCLUSION: Selection of operative approaches depends on the size of defects in the anterior skull base, extent of intracranial invasion and location of rhinosinusal malignant tumors; multiple layer fascia flaps can be used to reconstruct bigger defects of the skull base. It is safe, technically easy, effective procedure and worthy to be recommended.

Adolescent↗
PubMed2003

[Nonlinear analysis on the EEG information of rat epileptic model].

The aim of this study was to develop a new method of epileptic prediction using nonlinear dynamic theory. When rat was falling sickness, its EEG was researched by using approximate entropy and correlation dimension. The results showed the approximate entropy and correlation dimension during epileptic seizure are obviously lower than those before seizure and after seizure. The span of time before seizure is a special phase. Before the seizure symptom appeared, the complexity of EEG had begun declining. Thus, the outbreak of epilepsy could be predicted in short time using nonlinear dynamic methods.

Algorithms↗
PubMed2002

Tentacle-type zwitterionic stationary phase prepared by surface-initiated graft polymerization of 3-[N,N-dimethyl-N-(methacryloyloxyethyl)-ammonium] propanesulfonate through peroxide groups tethered on porous silica.

A novel stationary phase with tentacle-type zwitterionic interaction layer was synthesized by free radical graft polymerization of 3-[N,N-dimethyl-N-(methacryloyloxyethyl)ammonium]propanesulfonate (SPE) from the surface of Kromasil porous silica particles. The polymerization was initiated by thermal cleavage of tert-butylperoxy groups covalently attached to the particle surface, and the material therefore carries a tentacle-type polymeric interaction layer with 3-sulfopropylbetaine functional moieties. The composition of the surface graft was determined by elemental analysis, and the surface charge was measured using photon correlation spectroscopy. The measured zeta-potentials were close to 0 and nearly independent of pH, and the tentacle character of the interactive layers were evident from the lack of colloidal stability in the absence of salt (antipolyelectrolytic behavior) and a marked increase in column back-pressure when the concentration of perchloric acid or perchlorate salt was increased. The chromatographic properties were evaluated on columns packed with the functionalized material, and it was shown that this zwitterionic stationary phase could simultaneously and independently separate inorganic anions and cations using aqueous solutions of perchloric acid or perchlorate salts as eluents. The material was also capable of separating two acidic and three basic proteins in a single run, using gradient salt elution at constant pH.

Journal Article↗
PubMed2002

The skeletal muscle Ca2+ release channel has an oxidoreductase-like domain.

We used a combination of bioinformatics, electron cryomicroscopy, and biochemical techniques to identify an oxidoreductase-like domain in the skeletal muscle Ca2+ release channel protein (RyR1). The initial prediction was derived from sequence-based fold recognition for the N-terminal region (41-420) of RyR1. The putative domain was computationally localized to the clamp domain in the cytoplasmic region of a 22A structure of RyR1. This localization was subsequently confirmed by difference imaging with a sequence specific antibody. Consistent with the prediction of an oxidoreductase domain, RyR1 binds [3H]NAD+, supporting a model in which RyR1 has a oxidoreductase-like domain that could function as a type of redox sensor.

Amino Acid Sequence↗
PubMed2002

Deriving folds of macromolecular complexes through electron cryomicroscopy and bioinformatics approaches.

Intermediate-resolution (7-9A) structures of large macromolecular complexes can be obtained by electron cryomicroscopy. This structural information, combined with bioinformatics data for the individual protein components or domains, can lead to a fold model for the entire complex. Such approaches have been demonstrated with the 6.8 A structure of the rice dwarf virus to derive models for the major capsid shell proteins.

Amino Acid Sequence↗
PubMed2002

Endosperm-specific expression of green fluorescent protein driven by the hordein promoter is stably inherited in transgenic barley (Hordeum vulgare) plants.

The expression of green fluorescent protein (GFP) and its inheritance were studied in transgenic barley (Hordeum vulgare L.) plants transformed with a synthetic green fluorescent protein gene [sgfp(S65T)] driven by either a rice actin promoter or a barley endosperm-specific d-hordein promoter. The gene encoding phosphinothricin acetyltransferase (bar), driven by the maize ubiquitin promoter and intron, was used as a selectable marker to identify transgenic tissues. Strong GFP expression driven by the rice actin promoter was observed in callus cells and in a variety of tissues of T0 plants transformed with the sgfp(S65T)-containing construct. GFP expression, driven by the rice actin promoter, was observed in 14 out of 17 independent regenerable transgenic callus lines; however, expression was gradually lost in T0 and later generation progeny of diploid lines. Stable GFP expression was observed in T2 progeny from only 6 out of the 14 (43%) independent GFP-expressing callus lines. Four of the 8 lines not expressing GFP in T2 progeny, lost GFP expression during T0 plant regeneration from calli; one lost GFP expression in the transition from the T0 to T1 generations and three lines were sterile. Similarly, expression of bar driven by the maize ubiquitin promoter was lost in T1 progeny; only 21 out of 26 (81%) independent lines were Basta-resistant. In contrast to actin-driven expression, GFP expression driven by the d-hordein promoter exhibited endosperm-specificity. All seven lines transformed with d-hordein-driven GFP (100%) expressed GFP in the T1 and T2 generations, regardless of ploidy levels, and expression segregated in a Mendelian fashion. We conclude that the sgfp(S65T) gene was successfully transformed into barley and that GFP expression driven by the d-hordein promoter was more stable in its inheritance pattern in T1 and T2 progeny than that driven by the rice actin promoter or the bar gene driven by the maize ubiquitin promoter.

Journal Article↗