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Biomedical subjects

Xin Wang

Publications and source records attributed to Xin Wang.

At least 73 records · Page 4Linked to original sources
PubMed2006

Assembly of a heterometallic polynuclear Sn(IV)-Cu(I) cluster based on Sn(edt)2 (edt = ethane-1,2-dithiolate) as a metalloligand.

Reaction of [Cu(PPh3)2(MeCN)2]ClO4 (1) and Sn(edt)2 (edt = ethane-1,2-dithiolate) in dichloromethane afforded a novel compound [Sn3Cu4(S2C2H4)6(mu3-O)(PPh3)4](ClO4)2 x 3 CH2Cl2 (2), which is the first example of the heptanuclear Sn(IV)-Cu(I) oxosulfur complex with a bottle-shaped cluster core. Complex 2 gives a blue-green luminescent emission in the solid state. Crystallographic data for 2: C87H90Cl8Cu4O9P4S12Sn3, trigonal, space group R3, M = 2682.02, a = 18.156(2) A, b = 18.156(2) A, c = 54.495(10) A, gamma = 120 degrees, V = 15558(4) A3, Z = 6 (T = 130.15 K).

Journal Article↗
PubMed2006

BCNU-loaded PEG-PLLA ultrafine fibers and their in vitro antitumor activity against Glioma C6 cells.

The purpose of the present study was to develop implantable BCNU-loaded poly(ethylene glycol)-poly(L-lactic acid) (PEG-PLLA) diblock copolymer fibers for the controlled release of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). BCNU was well incorporated and dispersed uniformly in biodegradable PEG-PLLA fibers by using electrospinning method. Environmental Scanning Electron Microscope (ESEM) images indicated that the BCNU-loaded PEG-PLLA fibers looked uniform and their surfaces were reasonably smooth. Their average diameters were below 1500 nm. The release rate of BCNU from the fiber mats increased with the increase of BCNU loading amount. In vitro cytotoxicity assay showed that the PEG-PLLA fibers themselves did not affect the growth of rat Glioma C6 cells. Antitumor activity of the BCNU-loaded fibers against the cells was kept over the whole experiment process, while that of pristine BCNU disappeared within 48 h. These results strongly suggest that the BCNU/PEG-PLLA fibers have an effect of controlled release of BCNU and are suitable for postoperative chemotherapy of cancers.

Animals↗
PubMed2006

Quantum-sized carbon dots for bright and colorful photoluminescence.

We report that nanoscale carbon particles (carbon dots) upon simple surface passivation are strongly photoluminescent in both solution and the solid state. The luminescence emission of the carbon dots is stable against photobleaching, and there is no blinking effect. These strongly emissive carbon dots may find applications similar to or beyond those of their widely pursued silicon counterparts.

Carbon↗
PubMed2006

[Expression of HIC-5/ARA55 in colonrectal cancer and its mechanisms of action].

OBJECTIVE: To investigate the relationship between HIC-5 and colonrectal cancer. METHODS: Samples were obtained from 42 patients with colonrectal cancer, and the mRNA and protein expressions of HIC-5/ARA55 were determined by RT-PCR and Western-blot respectively. FCM was used to investigate the apoptosis of Lovo in the HIC-5/ARA55 transfection cells. The expression of apoptosis related proteins Bax and Bcl-2 was determined by Western-blot, and the MTT assay was used to test cell growth speed affected by HIC-5/ARA55. RESULTS: The expression of HIC-5 significantly decreased on colonrectal cancer tissues as compared with adjacent normal tissues on mRNA level and protein level(P<0.05). The apoptosis rate increase significantly in the HIC-5/ARA55 transfected cells. HIC-5/ARA55 could restrain tumor cell grow speed. CONCLUSION: HIC-5/ARA55 is the protein that can reduce tumor cell growth rate, and induce apoptosis in colonrectal cancer cells.

Apoptosis↗
PubMed2006

Cortical influences on rapid brainstem plasticity.

Cortical contributions to brainstem plasticity in the somatosensory system are poorly understood. Tactile receptive fields (RFs) of brainstem dorsal column nuclei (DCN) neurons rapidly enlarge when peripheral inputs are disrupted by local anesthetic blocks with lidocaine (LID). Cortical inputs appear to influence this plasticity because enlargements have been shown to be greater when cortical inputs are disrupted. Like disruptions of peripheral inputs, disruptions of DCN inhibition by DCN administration of the GABAA receptor antagonist bicuculline methiodide (BMI) also cause rapid enlargements of DCN RFs when cortical inputs are intact. These findings leave questions about interactions between cortical inputs, DCN inhibition, and DCN RF plasticity. To study potential interactions, the present experiments evaluated RF sizes of DCN tactilely responsive neurons in anesthetized rats following DCN microinjection of BMI when cortical inputs were acutely disrupted or intact. These tests were also supplemented by subsequent LID tests to directly compare post-BMI and post-LID effects on the same RF. BMI caused DCN RF enlargements when cortical inputs were disrupted or intact; however, enlargements after cortical input disruption were greater than when cortical inputs were intact. Following RF enlargement and retraction after BMI, LID often caused a second enlargement of the same RF, across skin that partially matched skin involved in the enlargement after BMI. This occurred when cortical inputs were disrupted or intact. We hypothesize that cortical inputs are not required for BMI and LID to initiate partially matching enlargements in individual DCN tactile RFs, however, cortical inputs constrain magnitudes of these enlargements.

Action Potentials↗
PubMed2006

A practical synthesis of 2-((1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino)-5- fluoronicotinic acid.

A practical synthesis of a key pharmaceutical intermediate, 2-[(1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino]-5-fluoronicotinic acid (1), is described. To introduce the aminomethyl moiety of 2 via a palladium-catalyzed cyanation/reduction sequence, a regioselective chlorination of 7-azaindole via the N-oxide was developed. A highly selective monodechlorination of 2,6-dichloro-5-fluoronicotinic acid was discovered to afford the nicotinic acid 3. The two building blocks 2 and 3 were then coupled to complete the preparation of 1.

Molecular Structure↗
PubMed2006

Prenatal nicotine exposure alters the nicotinic receptor subtypes that modulate excitation of parasympathetic cardiac neurons in the nucleus ambiguus from primarily alpha3beta2 and/or alpha6betaX to alpha3beta4.

Nicotinic receptors play an essential role in central cardiorespiratory function, however, the types of nicotinic receptors responsible for activating cardiac vagal neurons in the nucleus ambiguus that control heart rate are unknown. This study tests whether alpha-conotoxin MII and alpha-conotoxin AuIB sensitive nicotinic receptors are involved in augmentation of glutamatergic neurotransmission and changes in holding current in cardiac vagal neurons, and whether exposure to nicotine in the prenatal period alters these responses. The nicotinic agonist cytisine significantly increased the holding current and amplitude of glutamatergic mEPSCs. In unexposed animals alpha-conotoxin MII (100nM) significantly reduced the increase in mEPSC amplitude and change in holding current evoked by cytisine. However, in animals prenatally exposed to nicotine, alpha-conotoxin MII blunted but did not block the increase in mEPSC amplitude but blocked the increase in holding current evoked by cytisine. In unexposed animals, alpha-conotoxin AuIB (10microM) blocked the cytisine evoked increase in mEPSC amplitude and inhibited but did not abolish the increase in holding current. In contrast, in animals exposed to nicotine, alpha-conotoxin AuIB blunted the increase in mEPSC amplitude, and completely abolished the cytisine evoked increase in holding current. These data demonstrate that the prenatal nicotine exposure alters the nicotinic receptors involved in excitation of cardiac vagal neurons.

Alkaloids↗
PubMed2006

Structure activity relationships of monocyte chemoattractant proteins in complex with a blocking antibody.

Monocyte chemoattractant proteins (MCPs) are cytokines that direct immune cells bearing appropriate receptors to sites of inflammation or injury and are therefore attractive therapeutic targets for inhibitory molecules. 11K2 is a blocking mouse monoclonal antibody active against several human and murine MCPs. A 2.5 A structure of the Fab fragment of this antibody in complex with human MCP-1 has been solved. The Fab blocks CCR2 receptor binding to MCP-1 through an adjacent but distinct binding site. The orientation of the Fab indicates that a single MCP-1 dimer will bind two 11K2 antibodies. Several key residues on the antibody and on human MCPs were predicted to be involved in antibody selectivity. Mutational analysis of these residues confirms their involvement in the antibody-chemokine interaction. In addition to mutations that decreased or disrupted binding, one antibody mutation resulted in a 70-fold increase in affinity for human MCP-2. A key residue missing in human MCP-3, a chemokine not recognized by the antibody, was identified and engineering the preferred residue into the chemokine conferred binding to the antibody.

Amino Acid Sequence↗
PubMed2006

Investigation of the phase diagrams of chiral praziquantel.

In the present work, thermal properties of praziquantel, including melting point phase diagram and solubility, were determined for the purpose of exploration on an integrated enantioseparation process of chromatography and crystallization. The solubility of racemic praziquantel in methanol and 2-propanol was measured in the temperature range between 0 and 40 degrees C. In agreement with previous conclusions, the resulting phase diagram reveals the racemic compound behavior of praziquantel arising from the existence of eutectics. A ternary phase diagram of praziquantel enantiomers and the methanol system was also determined. Based on the information provided by the ternary solubility phase diagram, an optimized integrated enantioseparation process was suggested. Pure praziquantel crystals were recovered, and the crystal structure was solved by X-ray crystallography.

2-Propanol↗
PubMed2006

Self-assembled supramolecular hydrogels formed by biodegradable PEO-PHB-PEO triblock copolymers and alpha-cyclodextrin for controlled drug delivery.

A materials design of a new supramolecular hydrogel self-assembled between alpha-cyclodextrin and a biodegradable poly(ethylene oxide)-poly[(r)-3-hydroxybutyrate]-poly(ethylene oxide) (PEO-PHB-PEO) triblock copolymer was demonstrated. The cooperation effect of complexation of PEO segments with alpha-cyclodextrin and the hydrophobic interaction between PHB blocks resulted in the formation of the supramolecular hydrogel with a strong macromolecular network. The in vitro release kinetics studies of fluorescein isothiocyanate labeled dextran (dextran-FITC) model drug from the hydrogel showed that the hydrogel was suitable for relatively long-term sustained controlled release of macromolecular drugs, which many simple triblock copolymer hydrogel systems could not achieve. The hydrogel was found to be thixotropic and reversible, and can be applied as a promising injectable drug delivery system.

Biocompatible Materials↗
PubMed2006

Repair of DNA interstrand cross-links: interactions between homology-dependent and homology-independent pathways.

DNA interstrand cross-links (ICLs) are complex DNA lesions generated by bifunctional alkylating agents, a class of compounds extensively used in cancer chemotherapy. Formation of an ICL covalently links the opposing strands of the double helix and results in severe disruptions of normal DNA functions, such as replication, transcription, and recombination. Because of the structural complexity, ICLs are most likely recognized by a variety of repair recognition proteins and processed through multiple mechanisms. To study the involvement of different repair pathways in ICL processing, we examined a variety of mammalian mutants with distinct DNA repair deficiencies. We found that the presence of ICLs induces frequent recombination between direct repeat sequences, suggesting that the single-strand annealing pathway may be an important mechanism for the removal of ICLs situated within direct repeats. Unlike recombination-independent ICL repair, ICL-induced single-strand annealing does not require the nucleotide excision repair (NER) mechanism. In cells defective in the mismatch repair protein Msh2, the level of recombination-independent ICL repair was significantly increased, suggesting that processing by the mismatch repair mechanism may lead to recombinational repair of ICLs. Our results suggest that removal of ICLs may involve two error-prone mechanisms depending on the sequence context of the cross-linked site.

Animals↗
PubMed2006

Design, synthesis, and evaluation of Leu*Ala hydroxyethylene-based non-peptide beta-secretase (BACE) inhibitors.

With the aim of developing small molecular non-peptide beta-secretase (BACE) inhibitors, Leu*Ala hydroxyethylene (HE) was investigated as a scaffold to design and synthesize a series of compounds. Taking advantage of efficient combinatorial synthesis approaches and molecular modeling, extensive structure-activity relationship (SAR) studies were carried out on the N- and C-terminal residues of the Leu*Ala HE scaffold. Isobutyl amine was found to be an optimal C-cap, and suitable hydroxylalkylamines at the 3-position and nitro or methyl(methylsulfonyl)amine at the 5-position of isophthalamide as the N-terminus could form additional hydrogen bonds with BACE active sites and help improve potency. Many new potent non-peptide BACE inhibitors were identified in this study. Among them, compounds 37 and 44 exhibited excellent enzyme-inhibiting potency, comparable to that of OM99-2, and obvious inhibitory effects in cell-based assay with low molecular weights (<600).

Amyloid Precursor Protein Secretases↗
PubMed2006

[Influences of decellularization processes on immunogenicity of chemically acellular nerve allografts].

OBJECTIVE: To investigate the relationship between immunogenicity and decellularization processes of chemically acellular nerve allografts. METHODS: Adult Sprague Dawley rats were used as nerve donors and adult male Wistar rats used as nerve recipient hosts. 25 mm nerve segments were excised from SD rats' sciatic nerves. The nerve segments were decellularized via an improved chemical decelluarization treatment as follows: (1) nerve segments were rinsed with cold sterile Ringer's solution; (2) stabilized by pinning the ends to a thin plastic support, and submerged in 4% Triton-100 solution 12 h; (3) soaked into 3% sodium deoxycholate for 12 h; (4) washed in distilled water for 6 h. The procedures were repeated once again. The acellular nerve allografts from SD rats were sterilized by gamma irradiation and implanted into Wistar rats subcutanously. The control group was implantation of fresh nerve allografts from SD rats. The immunogenicity of acellular nerve allograft was tested by immunohistochemical examination of the intensity of CD3(+), CD4(+) and CD8(+) cells that infiltrated the allografts. Ulnar nerve segments were obtained from forearms of dogs and decellularized according to above procedures. According as the decellularization times, The ulnar nerve segments were divided into three subgroups: in group I, group II and group III, the nerve segments were decellularized repeatedly two, three and four cycles respectively. Each ulnar nerve segment was subdivided into five portions from proximal to distal end. The degrees of decellularization, demyelination and basal lamina integrity of extracellular matrix scaffold were observed with microscope and assessed by a score system. The immunohistochemical staining of GAG was observed. RESULTS: The intensity of CD3(+), CD4(+) and CD8(+) T cells that infiltrated the allografts was greatly lower in acellular nerves than in fresh nerves. The mild cell-mediated host-graft immunorejection in acellular nerves was observed. On the decellularization procedures, the cells were completely extracted from nerves in all groups, but the myelin sheath were partially existed, and the GAG was present in the basal membrane of myelin sheath. In the score of demyelination, there were no statistical differences between groups (P > 0.05). The statistical difference of basal lamina integrity scores between group I and group II, group I and group III were significant (P < 0.05). As increasing the times of process, the degrees of disintegrity of basal lamina was significantly enhanced. CONCLUSIONS: Although decellularization processes significantly reduce the cell-mediated immunorejection of acellular nerve allografts, it can induce mild immunoreaction all the same, the antigen that responsible for immunogenicity may be the residual component of GAG in myelin sheath.

Animals↗
PubMed2006

Geometric and electronic structures of metal-substitutional fullerene C59Sm and metal-exohedral fullerenes C60Sm.

The geometric and electronic structures of metal-substituted fullerene C59Sm and exohedral fullerenes C60Sm are studied using the density-functional theory. The geometric optimization shows that the replacement of a C atom with a Sm in C60 yields a stable substitutionally doped fullerene C59Sm, and among the five possible optimized geometries for C60Sm, the most favorable exohedral sites are above the center of a hexagon and a pentagon ring. The calculations for electronic structures show that the magnetic moment of Sm is preserved for all the stable structures as tiny hybridization takes place between the orbitals of the Sm atom and those of their neighboring carbons. Because of the small energy gaps and the half occupation of the highest occupied molecular orbitals, all the stable C60Sm isomers are inferred to be conductors.

Journal Article↗
PubMed2006

The regulation of Bax by c-Jun N-terminal protein kinase (JNK) is a prerequisite to the mitochondrial-induced apoptotic pathway.

The signaling mechanism by which JNK affects mitochondria is critical to initiate apoptosis. Here we show that the absence of JNK provides a partial resistance to the toxic effect of the heavy metal cadmium. Both wild type and jnk-/- fibroblasts undergoing death exhibit cytosolic cytochrome c but, unlike wild type cells, the JNK-deficient fibroblasts do not display increased caspase activity and DNA fragmentation. The absence of apoptotic death correlates with a specific defect in activation of Bax. We conclude that JNK-dependent regulation of Bax is essential to mediate the apoptotic release of cytochrome c regardless of Bid and Bim activation.

Animals↗
PubMed2006

Changes of learning, memory and levels of CaMKII, CaM mRNA, CREB mRNA in the hippocampus of chronic multiple-stressed rats.

BACKGROUND: The effect of chronic stress on cognitive functions has been one of the hot topic in neuroscience. But there has been much controversy over its mechanism. Such single stressor applied in the past could not simulate complicated living circumstances that people confronted with. The aim of this study was to investigate the effects of chronic multiple-stress on learning and memory as well as on the levels of calcium/calmodulin-dependent protein kinase II (CaMKII), calmodulin (CaM) mRNA, and cAMP-response element binding protein (CREB) mRNA in the hippocampus of rats. METHODS: The rats were divided randomly into stressed and control groups. The stressed group was given chronic multiple-stress for 6 weeks to set up a chronic multiple-stressed model. The rats' performance of spatial learning and memory was tested using Morris Water Maze (MWM) and Y-maze. Meanwhile, the expressions of CaMKII, CaM mRNA and CREB mRNA of rats' hippocampus were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. In addition, the width of synaptic cleft and the thickness of post-synaptic densities (PSD) were observed in the hippocampal CA3 region of rats by electron microscopy. RESULTS: After exposure to chronic multiple-stress for 6 weeks, the ability of learning and memory of the stressed group was higher than that of the control group (P < 0.05, P < 0.01). The width of synaptic cleft was smaller and the thickness of PSD was larger in the hippocampal CA3 region of the stressed group than in that of the control group (P < 0.01). The CaMK II immunostaining of the stressed group was stronger than that of the control group in the stratum radiatum and oriens of the hippocampal CA1 and CA3, especially in the stratum oriens. Quantitative analysis indicated that the expression of CaMK II, CaM mRNA, and CREB mRNA in the hippocampus of the stressed group was higher than that of the control group (P < 0.05, P < 0.01). CONCLUSIONS: The capacity of learning and memory can be enhanced after chronic multiple-stress. The increased levels of CaMK II, CaM mRNA, and CREB mRNA may contribute to the enhancing effect of chronic multiple-stress on learning and memory.

Animals↗
PubMed2006

Growth mechanism of ZnO nanocrystals with Zn-rich from dots to rods.

ZnO nanocrystals from dot to rod were synthesized by simply changing Zn2+ concentration in ZnO seed solutions. The growth of ZnO nanocrystals was sensitive to the amount of Zn2+ in the solution. The growth process of ZnO from dot to rod was observed by optical spectra, transmission electron microscopy and X-ray diffraction spectra. From these results, the growth mechanism of ZnO from dots to rods was discussed.

Journal Article↗