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Biomedical subjects

Xu Wang

Publications and source records attributed to Xu Wang.

At least 73 records · Page 4Linked to original sources

Factors contributing to neuronal degeneration in retinas of experimental glaucomatous rats.

After our studies on ganglion cell degeneration in the glaucomatous retina, the current work further confirmed the reduction of amacrine cells in the retina after the onset of glaucoma. Present study also tried to understand the possible mechanisms underlying neuronal degeneration in the glaucomatous retina. Changes of expressions in immediate early genes (IEGs), glutamate receptors (GluRs), calcium-binding proteins (CaBPs), 8-hydroxy-deoxyguanosine (8-OH-dG) and nitric oxide synthase (NOS), as well as apoptotic-related factors including caspase 3, bax, and bcl-2 were examined. IEGs such as c-fos and c-jun were induced in the retina of the glaucomatous rat as early as 2 hr after the onset of glaucoma and lasted up to 2 weeks. Expressions of GluRs and CaBPs (i.e., parvalbumin and calbindin D-28k) were observed to be increased in the retinal ganglion cell layer (GCL) and inner nuclear layer (INL) at 3 days and 1 week after the onset of glaucoma. The increase occurred well before and during the phase where significant neuronal death was observed in the GCL and INL of the glaucomatous retinae. Induction of 8-OH-dG was present in both the GCL and INL of the glaucomatous retina at 3 days after the onset of glaucoma before significant neuronal death was observed. Furthermore, confocal microscopy study showed the complete colocalization of immunohistochemical expression of caspase 3 with glial fibrillary acidic protein (GFAP), but not with neuronal nuclei (NeuN). It indicates that astrocytes and Müller cells are involved in the pathological processes of neuronal death. The relationship between the linked factors and neuronal degeneration is also discussed.

8-Hydroxy-2'-Deoxyguanosine↗

Study on the supramolecular interaction of thiabendazole and beta-cyclodextrin by spectrophotometry and its analytical application.

The beta-cyclodextrin-thiabendazole (beta-CD-TBZ) inclusion complex was synthesized and its structure characterized by (1)H NMR and IR. The mechanism of the supramolecular interaction of TBZ and beta-CD has been studied and discussed by spectrophotometry. The results showed that the phenyl ring of TBZ was included in the beta-CD cavity to form a 1:1 host-guest complex with an apparent formation constant of 1.60 x 10(3) mol(-1).L. On the basis of the enhancement of the absorbance of TBZ produced through complex formation, a spectrophotometric method for the determination of TBZ in bulk aqueous solution in the presence of beta-CD was developed. The linear relationship between the absorbance and TBZ concentration was obtained in the range of 8.86 x 10(-7)-1.45 x 10(-5) mol/L. The detection limit was 2.71 x 10(-7)mol/L, and the relative standard deviation was 0.86%. The interference of 48 coexisting substances was slight. The proposed method has been successfully applied to the determination of TBZ in fruits with recoveries of 96-103%.

Buffers↗

CD8+ T cell depletion amplifies hepatitis C virus replication in peripheral blood mononuclear cells.

We investigated the ability of CD8+ T cells to inhibit hepatitis C virus (HCV) replication in peripheral blood mononuclear cells (PBMCs). PBMCs isolated from 11 of 20 HCV-infected subjects had no detectable HCV RNA. Removal of CD8+ T cells from these PBMCs resulted in detection of HCV RNA, and depletion of CD8+ T cells from PBMCs that had detectable HCV RNA amplified HCV replication. Reconstitution of CD8- PBMCs with autologous CD8+ T cells led to inhibition of HCV replication. Interferon-gamma produced by CD8+ T cells was partially responsible for CD8+ T cell-mediated noncytotoxic anti-HCV activity in PBMCs. This noncytotoxic anti-HCV activity was confirmed in HCV replicon cells. Supernatants from CD8+ T cell cultures inhibited HCV RNA expression in the replicon cells. These findings may have important implications for the immunopathogenesis of HCV in both immune and hepatic cells and are relevant to the development of host innate immunity-based anti-HCV interventions.

Antiviral Agents↗

Anti-cancer effect of iNOS inhibitor and its correlation with angiogenesis in gastric cancer.

AIM: To observe the anti-cancer effect of iNOS selective inhibitor (aminoguanidine, AG) and investigate the relationship between iNOS inhibitor and angiogenesis, infiltration or metastasis in MFC gastric cancer xenografts. METHODS: Fifty athymic mice xenograft models were established by inoculating gastric cancer cell MFC subcutaneously. Twenty-four hours later, 0.9% sodium chloride solution, mitomycin, low dosage AG, high dosage AG, mitomycin and AG were administered by intraperitoneal injection respectively. Thus these mice were divided into five groups of 10 each randomly: control group, MMC group, AG(L) group, AG(H) group, MMC+AG(H) group. Two weeks later the mice were killed, and the tumor weight, inhibitory rate were evaluated. Greiss assay was used to detect the nitric oxide levels in plasma. HE and immunohistochemistry staining were used to examine microvessel density (MVD) and the expression of iNOS, VEGF, and PCNA. Apoptosis was detected by using TUNEL assay. RESULTS: The inhibitory rates in MMC+AG(H) group and AG(H) group were 52.9% and 47.1% respectively, which is significant statistically compared with that of control group (0). In treatment groups, the cell proliferation index (PI) was lower and apoptosis index was higher than those of control group. Microvessel density, iNOS, and VEGF in MMC+ AG(H) group were 8.8+/-2.6, 2.4+/-1.1, and 2.1+/-1.4 respectively, which is significant statistically compared with those of control group (68.3+/-10.6, 11.3+/-1.3, and 10.3+/-1.6). The NO level in plasma of MMC+ AGH and AG(H) group were 12.7+/-2.1 and 12.9+/-2.0 mumol/L. Compared with that of control group (46.6+/-2.3 mumol/L), the difference is statistically significant. CONCLUSION: AG has anticancer effect on gastric cancer, and it has positive synergistic effect with chemotherapeutic drugs. It may play important inhibitory roles in angiogenesis of gastric cancer. The anticancer effect of iNOS inhibitors may include inducing cell apoptosis, suppressing cell proliferation and reducing angiogenesis.

Animals↗

Morphine inhibits CD8+ T cell-mediated, noncytolytic, anti-HIV activity in latently infected immune cells.

Opiates have profound effects on the function of human immune cells and are a possible cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) disease. We investigated the impact of morphine on CD8+ T cell-mediated, noncytotoxic, anti-HIV activity in latently infected human immune cells. Morphine inhibited the noncytotoxic, anti-HIV activity of CD8+ T cells in HIV latently infected cells (U1 and J1.1). Naltrexone abrogated the morphine-mediated, inhibitory effect on the noncytotoxic, anti-HIV activity of CD8+ T cells. Interferon-gamma (IFN-gamma), a potent antiviral cytokine produced by CD8+ T cells, was partially responsible for CD8+ T cell-mediated, noncytotoxic, anti-HIV activity. The anti-HIV activity of IFN-gamma was also compromised by morphine treatment. Further, morphine attenuated CD8+ T cell-mediated suppression of the HIV long-terminal repeat promoter activation. Morphine also inhibited CD8+ T cell-induced expression of the signal transducer and activator of transcription-1, an important transcriptional factor in the IFN signaling pathway. These data provide additional evidence to support the notion that opioids play a role in impairing the anti-HIV function of the immune system.

Anti-HIV Agents↗

Highly sensitive and selective room-temperature phosphorescence determination of thiabendazole by the supramolecular interaction of thiabendazole/beta-cyclodextrin/triton X-100.

A strong and stable room temperature phosphorescence (RTP) signal (lambda(ex)/lambda(em) = 298/481 nm) resulting from a 1:1:1 beta-cyclodextrin (beta-CD)/thiabendazole (TBZ)/triton X-100 (TX-100) supramolecular ternary inclusion complex was induced by KI as a heavy atom perturber. Based on the heavy-atom induced RTP, a new phosphorescence method for TBZ determination was established. The analytical curve of TBZ gave a linear range of 20-820 ng mL(-1) with a detection limit and relative standard deviation of 2.1 ng mL(-1) and 1.9%, respectively. The interference of 46 coexisting substances was studied. Compared with the method using a chemical oxygen scavenger, this method is simpler as deoxygenation of the solution is not required. The detection limit and the heavy-atom concentration of the proposed method were decreased about 8 and 4 times, respectively. The lifetime of the phosphorescence was prolonged 9 times and the pH range was greatly broadened. The proposed method has been successfully applied to the determination of TBZ in tap water, lake water and pineapples.

Anti-Infective Agents↗

Site-dependent inhibition of neuronal c-jun in the brainstem elicited by imidazoline I1 receptor activation: role in rilmenidine-evoked hypotension.

Clonidine (a mixed alpha2-adrenoceptor and imidazoline I1 receptor agonist)-evoked hypotension was associated with dissimilar reductions in c-jun gene expression in the rostral ventrolateral medulla (RVLM) and the nucleus tractus solitarius (NTS) in normotensive rats. In the present study, we investigated the relative contribution of the alpha2-adrenoceptor vs. the imidazoline I1 receptor to the reduction in c-jun gene expression in these two brainstem areas. In conscious spontaneously hypertensive rats (SHRs), equihypotensive doses of three centrally acting hypotensive drugs with different selectivity for the two receptors were administered intracisternally (4 microl) to limit their actions to the brain. As a control, a similar hypotensive response was elicited by i.v. hydralazine. Clonidine (0.5 microg), or alpha-methylnorepinephrine (alpha-MNE, 4 microg), a highly selective alpha2-adrenoceptor agonist, similarly reduced c-jun mRNA expression in the NTS and rostral ventrolateral medulla. In contrast, a similar hypotensive response (-37+/-3.5 mm Hg) caused by the selective imidazoline I1 receptor agonist rilmenidine (25 microg) was associated with reduction in c-jun mRNA expression in the rostral ventrolateral medulla, but not in the NTS. Further, intra-rostral ventrolateral medulla rilmenidine (40 nmol) reduced c-Jun protein expression in rostral ventrolateral medulla and blood pressure and both responses were antagonized by selective imidazoline I1 receptor (efaroxan, 4 nmol), but not alpha2-adrenoceptor (SK&F 86466, 10 nmol) blockade. These results suggest: (1) the c-jun containing neurons in the brainstem are involved in the centrally mediated hypotension elicited by centrally acting antihypertensive agents, and (2) the alpha2-adrenoceptor modulates c-jun gene expression in the NTS and rostral ventrolateral medulla implicated in centrally mediated hypotension, and (3) the imidazoline I1 receptor mediated inhibition of c-jun gene expression in the rostral ventrolateral medulla, but not in the NTS, contributes to the centrally mediated hypotension by the second generation drugs.

Adrenergic alpha-2 Receptor Agonists↗

Effect of chronic ethanol administration on hepatic eNOS activity and its association with caveolin-1 and calmodulin in female rats.

Although chronic and excessive alcohol consumption is associated with liver disease, the mechanism of alcoholic liver injury is still not clear. Whether reduced hepatic production of nitric oxide, which is evident in models of liver injury, is associated with alcohol-induced liver injury has not been investigated. We measured nitric oxide synthase (NOS) activity in the liver of pair-fed rats receiving liquid diet with or without alcohol [3% (vol/vol)] for 12 wk. Compared with control rats, hepatic NOS activity was significantly reduced in alcohol-treated rats along with the evidence of liver injury. Interestingly, there was no difference in the hepatic expression of endothelial NOS (eNOS) between ethanol-fed and pair-fed rats. We then tested the hypothesis that an imbalance between the binding of eNOS with inhibitory and stimulatory proteins may underlie the reduced activity of eNOS because eNOS catalytic activity is regulated partly through dynamic interactions with the inhibitory protein caveolin-1 and the stimulatory protein calmodulin. We found that hepatic caveolin-1 was markedly increased in alcohol-treated rats compared with control rats, whereas calmodulin remained unaltered. The binding of caveolin-1 and calmodulin with eNOS was increased and decreased, respectively, in alcohol-treated rats. Our results suggest that chronic alcohol intake attenuates hepatic eNOS activity by increasing the expression of the inhibitory protein caveolin-1 and enhancing its binding with eNOS.

Animals↗

Uncontrolled calcium sparks act as a dystrophic signal for mammalian skeletal muscle.

Most excitable cells maintain tight control of intracellular Ca(2+) through coordinated interaction between plasma membrane and endoplasmic or sarcoplasmic reticulum. Quiescent sarcoplasmic reticulum Ca(2+) release machinery is essential for the survival and normal function of skeletal muscle. Here we show that subtle membrane deformations induce Ca(2+) sparks in intact mammalian skeletal muscle. Spontaneous Ca(2+) sparks can be reversibly induced by osmotic shock, and participate in a normal physiological response to exercise. In dystrophic muscle with fragile membrane integrity, stress-induced Ca(2+) sparks are essentially irreversible. Moreover, moderate exercise in mdx muscle alters the Ca(2+) spark response. Thus, membrane-deformation-induced Ca(2+) sparks have an important role in physiological and pathophysiological regulation of Ca(2+) signalling, and uncontrolled Ca(2+) spark activity in connection with chronic activation of store-operated Ca(2+) entry may function as a dystrophic signal in mammalian skeletal muscle.

Animals↗

Cis/trans heterogeneity of Gln30-Pro31 peptide bond determines whether a 79-residue fragment of staphylococcal nuclease self-associates.

The self-association reaction of a 79-residue fragment of staphylococcal nuclease (SNase79) was studied by far-UV CD, size-exclusion chromatography, and heteronuclear multidimensional NMR spectroscopy. A large population of SNase79 is in self-associated state while a small population of SNase79 is essentially in a monomeric state. The sequence region Thr13-Val39 is responsible for association interface of SNase79. The trans-conformation of X-prolyl bond Gln30-Pro31 may make residues Tyr27-Gln30, serve as a folding nucleation site, and lead the segment Thr13-Val39 of SNase79 to adopt a native-like beta-sheet conformation, which results in the self-association of SNase79. The non-native conformation of the segment Thr13-Val39 of SNase79 associated with the cis-conformation of X-prolyl bond Gln30-Pro31 may preclude SNase79 from the soluble aggregates.

Amino Acid Substitution↗

Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a Chinese family.

Hypokalemic periodic paralysis (HypoPP) is an autosomal dominant disorder which is characterized by periodic attacks of muscle weakness associated with a decrease in the serum potassium level. The skeletal muscle calcium channel alpha-subunit gene CACNA1S is a major disease-causing gene for HypoPP, however, only three specific HypoPP-causing mutations, Arg528His, Arg1,239His and Arg1,239Gly, have been identified in CACNA1S to date. In this study, we studied a four-generation Chinese family with HypoPP with 43 living members and 19 affected individuals. Linkage analysis showed that the causative mutation in the family is linked to the CACNA1S gene with a LOD score of 6.7. DNA sequence analysis revealed a heterozygous C to G transition at nucleotide 1,582, resulting in a novel 1,582C-->G (Arg528Gly) mutation. The Arg528Gly mutation co-segregated with all affected individuals in the family, and was not present in 200 matched normal controls. The penetrance of the Arg528Gly mutation was complete in male mutation carriers, however, a reduced penetrance of 83% (10/12) was observed in female carriers. No differences were detected for age-at-onset and severity of the disease (frequency of symptomatic attacks per year) between male and female patients. Oral intake of KCl is effective in blocking the symptomatic attacks. This study identifies a novel Arg528Gly mutation in the CACNA1S gene that causes HypoPP in a Chinese family, expands the spectrum of mutations causing HypoPP, and demonstrates a gender difference in the penetrance of the disease.

Adolescent↗

High-performance optical code generation and recognition by use of a 511-chip, 640-Gchip/s phase-shifted superstructured fiber Bragg grating.

The generation and recognition of a record-length 511-chip optical code is experimentally demonstrated by use of a superstructured fiber Bragg grating (SSFBG) with a chip rate of 640 Gchips/s. Very high reflectivity (92%) is achieved with high-quality correlation properties. The temperature deviation tolerance is approximately +/- 0.3 degrees C, which is within the package's temperature stability range (+/- 0.1 degrees C). Experimental results show good agreement with the theory. They indicate the SSFBG's potential for processing a long optical code with an ultrahigh chip rate, which could significantly improve the system's performance.

Journal Article↗

[Sagittal mobility study on the first tarsometatarsal joint in hallux valgus patients and its clinical values].

OBJECTIVE: To study sagittal mobility about the FTJ (first tarsometatarsal joint) and its relationship with the pathophysiology and treatment of hallux valgus patients. METHODS: According to Lee's method, FTJ sagittal mobility of 300 normal feet and 200 hallux valgus was measured, and its correlative factors were statistically analysed. RESULTS: FTJ sagittal mobility of 300 normal feet was 8.4 degrees +/- 2.3 degrees , and that of 200 hallux valgus was 11.7 degrees +/- 3.2 degrees , the difference was significant. The normal range of FTJ sagittal mobility was less than 13 degrees . The sagittal overmotion of FTJ had relation to the anatomical configuration of FTJ (P < 0.05), intercuneiform splitting (P < 0.01), transferred pain under the second metatarsal head (P < 0.01), and FTJ osteoarthritis (P < 0.01) had no relation to HVA (hallux valgus angle), IMA (intermetatarsal angle), second metatarsus medial diaphyseal cortex hypertrophy (P > 0.05). CONCLUSION: Lee's method is convenient and accurate. Both HVA and IMA can not represent the sagittal mobility measurement of FTJ, which should be routinely evaluated, especially for hallux valgus patients with type I FTJ. Lapidus procedure should be considered for patients with larger FTJ in combination with transferred pain under the second metatarsal head, intercuneiform splitting, FTJ osteoarthritis.

Adolescent↗

Structural based insights into the role of troponin in cardiac muscle pathophysiology.

Troponin is a molecular switch, directly regulating the Ca2+-dependent activation of myofilament in striated muscle contraction. Cardiac troponin is subject to covalent and noncovalent modifications; phosphorylation modulates myofilament physiology, mutations are linked to familial hypertrophic cardiomyopathy, intracellular acidification causes myocardial infarction, and cardiotonic drugs modify myofilament response to Ca2+. The structure of troponin provides insights into the mechanism of this molecular switch and an understanding of the effects of protein modification under pathophysiological conditions. Although the structure of troponin C has been solved in various Ca2+-bound states for some time, structural information on troponin I and troponin T has only emerged recently. This review summarizes recent advances on the structure of complexes of troponin subunits with the aim of assessing how these proteins interact with each other to execute its role as a molecular switch and how covalent and noncovalent modifications affect the structure of troponin and the switch mechanism. We focus on pinpointing the specific amino acid residues involved in phosphorylation and mutation and the pH sensitive regions in the structure of troponin. We also present recent structural work that have identified the docking sites of several cardiotonic drugs on cardiac troponin C and discuss their relevance in the direction of troponin based drug design in the therapy of heart disease.

Animals↗

NSPc1, a mainly nuclear localized protein of novel PcG family members, has a transcription repression activity related to its PKC phosphorylation site at S183.

Nervous system polycomb 1 (NSPc1) shares high homology with vertebrate PcG proteins Mel-18 and Bmi-1. The mRNA of NSPc1 is highly expressed in the developmental nervous system [Mech. Dev. 102 (2001) 219-222]. However, the functional characterization of NSPc1 protein is not clear. In the present study, using Western blotting technique, we aimed to describe the distributions of NSPc1 protein in rat tissues and cell lines. The subcellular localization of NSPc1 was examined in HeLa and SH-SY5Ycell lines, and its transcriptional repression activity was examined in COS-7 cell line. We found that the NSPc1 protein was localized mainly in the nucleus. NSPc1 remarkably repressed the transcription. Most interestingly, both the C-terminal of NSPc1 and two phosphorylation sites in the C-terminal, especially the PKC phosphorylation site at S183, were important in mediating transcription repression. Taken together, results from our study suggest that NSPc1, as a typical PcG family member, has powerful transcriptional repression ability, which may be related to the PKC signaling pathway.

Animals↗

A serological survey on neutralizing antibody titer of SARS convalescent sera.

A seroepidemiologic study was conducted in North China in 2003 to determine the neutralizing antibody titer of severe acute respiratory syndrome (SARS) convalescent sera. A total of 99 SARS convalescent serum samples were collected from patients from the Inner Mongolia Autonomous Region, Hebei Province, and Beijing 35-180 days after the onset of symptoms. The anti-SARS antibodies were detected by enzyme-linked immunosorbent assay (ELISA), neutralization assay, and Western blot. Eighty-seven serum samples were confirmed to be positive for SARS antibodies. The neutralizing antibody titer of the 87 positive sera was analyzed quantitatively by neutralization assay. The geometric mean titer (GMT) of the 87 convalescent sera was 1:61. The Kolmogorov-Smirnov test showed that the neutralizing antibody titers conform to normal distribution, which suggests that the average anti-SARS antibody level in this study was representative of the convalescent antibody level of the SARS population. This result could be useful for the development and quality control of SARS vaccines.

Antibodies, Viral↗

P53 gene mutation and expression of MDM2, P53, P16 protein and their relationship in human glioma.

To investigate the effect of P53 protein accumulation and p53 gene mutation in the pathogenesis of glioma and to study the role of MDM2, P53 and P16 protein in glioma formation and progression and their relationship with each other, LSAB immunohistochemical staining method and non-isotopic PCR-SSCP techniques were used to detect the expression of MDM2, P53 and P16 protein and p53 gene mutation in 48 cases of gliomas. The results showed that the positive expression rate of MDM2, P53 and the negative rate of P16 was 22.9%, 41.7% and 60.4%, respectively. The latter two in high grade (grade III, IV) gliomas had a significantly higher rate than in the low grade (grade II) gliomas. Moreover, the co-expression of MDM2 and P53 protein was confirmed in only 1 of 48 cases. No significant difference was found in the rate of the expression of MDM2 between high grade and low grade gliomas (P > 0.1). PCR-SSCP results showed that mutation of 5-8 exons of p53 gene was detected in 17 out of 48 cases (35.42%). Mutation was detected in 16 of 20 cases of positive p53 expression, and another one was detected in 28 cases of negative expression cases. The correlation between p53 mutation and p53 immunopositivity was observed in 89.6% of the cases. P53 gene mutation and the level of MDM2, P53 and P16 protein were not related to age, gender of the patients, tumor location and size. It is concluded that the mutation of p53 and deletion of p16 might play important roles in the tumorigenesis of gliomas and it was significantly associated with the grade of tumor differentiation. P53 protein accumulation can indirectly reflect p53 mutation. MDM2 amplification and overexpression might be an early event in the growth of human gliomas.

Adolescent↗

Newly detected specific hydrogenation of the conjugated double bond of unsaturated alkaloid lactones by Aspergillus sp.

A new isolate of Aspergillus sp. hydrogenated the gamma,delta-double bond of securinine (143 mg l(-1)) to give 14,15-dihydrosecurinine at over 98% (w/w) yield after 8 h. It also hydrogenated the C11(13) double bond of 3-hydroxy-1(10),3,11(13)-guaiatriene-12,6-olide-2-one (HGT) (200 mg l(-1)) to give 3-hydroxy-1(10),3-guaiadiene-12,6-olide-2-one with over 98% (w/w) conversion after 24 h.

Alkaloids↗