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Biomedical subjects

X Li

Publications and source records attributed to X Li.

At least 91 records · Page 5Linked to original sources

[Preparation and characterization of the monoclonal antibodies against Japanese encephalitis virus.].

BACKGROUND: To prepare mouse monoclonal antibodies (McAbs) against Japanese encephalitis virus (JEV)and evaluate their biological characteristics. METHODS: McAbs against JEV were prepared by immunizing, fusing, cloning and screening. Their sensitivity, specificity, universality and neutralizing function were analyzed with ELISA, IFA, NT and Western blot. RESULTS: Titers of three McAbs against JEV were higher than 106. Three McAbs only reacted with JEV and not with other nine arboviruses. F12.37 could react with ten strains of JEV and sensitively detected ten replicating strains of viruses in BHK cell. The strains P3 and SH03-103 of JEV were neutralized by F12.37, its titers of protecting 50% cell were 3.2x105 and 105. Western blot showed that F12.37 reacted with envelop(E)protein of JEV. CONCLUSION: Three McAbs against JEV had high titer and good specificity. And F12.37 was very sensitive and universal in reacting with JEV, and neutralized JEV of Genotype I and Genotype .The binding site of F12.37 lays in E protein of JEV.

Animals↗

Redox control of K+ channel remodeling in rat ventricle.

Electrical remodeling of the diseased heart contributes to contractile dysfunction and arrhythmias, and is characterized by down-regulation of K(+) channels that control action potential morphology. We have recently shown that remodeling of K(+) channels underlying the transient outward current (I(to)) involves a shift in cell redox balance that is reflected by a depletion of the endogenous redox buffer, glutathione (GSH). This study used a pharmacological model to further examine the role of redox-mediated mechanisms in regulating cardiac K(+) currents. Inhibition of major redox pathways was elicited in normal rats by daily injections of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of thioredoxin and glutathione reductases, and buthionine sulfoximine (BSO), a blocker of GSH synthesis. Fluorescence microscopy studies showed that [GSH] in isolated ventricular myocytes was decreased ~50% from control after 3 days of BCNU/BSO treatment (P<0.05), consistent with a shift in cell redox state. In voltage-clamp experiments, maximum I(to) density was decreased 33% from control in left ventricular myocytes from BCNU/BSO-treated rats (P<0.05), while the inward rectifier and steady state outward currents were not significantly altered. Decreased I(to) density correlated with significant decreases in Kv4.2 mRNA and proteins levels of Kv4.2 and Kv1.4. Down-regulation of I(to) in myocytes from BCNU/BSO rats was reversed in vitro by exogenous GSH or N-acetylcysteine, a GSH precursor and antioxidant. I(to) density and [GSH] were also up-regulated by receptor tyrosine kinase activation with insulin or a tyrosine phosphatase inhibitor. The effect of these activators on I(to) was blocked by inhibitors of PI 3-kinase, MEK and p38 MAP kinases. These data suggest that expression of cardiac I(to) channels is regulated by endogenous oxidoreductase systems and that receptor tyrosine kinase signaling functionally impacts K(+) channel remodeling through its control of cell redox state.

Animals↗

Persistent sodium currents and repetitive firing in motoneurons of the sacrocaudal spinal cord of adult rats.

Months after sacral spinal transection in rats (chronic spinal rats), motoneurons below the injury exhibit large, low-threshold persistent inward currents (PICs), composed of persistent sodium currents (Na PICs) and persistent calcium currents (Ca PICs). Here, we studied whether motoneurons of normal adult rats also exhibited Na and Ca PICs when the spinal cord was acutely transected at the sacral level (acute spinal rats) and examined the role of the Na PIC in firing behavior. Intracellular recordings were obtained from motoneurons of acute and chronic spinal rats while the whole sacrocaudal spinal cord was maintained in vitro. Compared with chronic spinal rats, motoneurons of acute spinal rats were more difficult to activate because the input resistance was 22% lower and resting membrane potential was hyperpolarized 4.1 mV further below firing threshold (-50.9 +/- 6.2 mV). In acute spinal rats, during a slow voltage ramp, a PIC was activated subthreshold to the spike (at -57.2 +/- 5.0 mV) and reached a peak current of 1.11 +/- 1.21 nA. This PIC was less than one-half the size of that in chronic spinal rats (2.79 +/- 0.94 nA) and usually was not large enough to produce bistable behavior (plateau potentials and self-sustained firing not present), unlike in chronic spinal rats. The PIC was composed of two components: a TTX-sensitive Na PIC (0.44 +/- 0.36 nA) and a nimodipine-sensitive Ca PIC (0.78 +/- 0.82 nA). Both were smaller than in chronic spinal rats (but with similar Na/Ca ratio). The presence of the Na PIC was critical for normal repetitive firing, because no detectable Na PIC was found in the few motoneurons that could not fire repetitively during a slow ramp current injection and motoneurons that had large Na PICs more readily produced repetitive firing and had lower minimum firing rates compared with neurons with small Na PICs. Furthermore, when the Na PIC was selectively blocked with riluzole, steady repetitive firing was eliminated, even though transient firing could be evoked on a rapid current step and the spike itself was unaffected. In summary, only small Ca and Na PICs occur in acute spinal motoneurons, but the Na PIC is essential for steady repetitive firing. We discuss how availability of monoamines may explain the variability in Na PICs and firing in the normal and spinal animals.

Animals↗

Alginate microparticles prepared by spray-coagulation method: preparation, drug loading and release characterization.

A spray-coagulation method was developed for the preparation of large scale of porous alginate microparticles. The effect of three variables on porosity was evaluated: (1) alginate solution concentration (2) the concentration of CaCl2 in the coagulation medium and (3) the ratio of guluronic acid to manuronic acid of the alginate. Methylene blue (MB), a highly water-soluble compound and a practically water-insoluble compound, 4-phenylazoaniline (PAA) were used as the model drugs to study drug loading and release characteristics from alginate microparticles. The release of the model compounds from the microparticles was found to depend upon the release medium. Incomplete in vitro release of both model drugs in deionized (DI) water was observed. The release of MB in simulated gastrointestinal fluid (0.1N HCl) was fast and complete, while the release of PAA was slow in 0.1N HCl and fast in phosphate buffer solution (pH 6.8). Interactions between the model drugs and alginate microparticles were identified from scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) analysis. The results indicated that (1) porous alginate microparticles can be produced by the spray-coagulation method; (2) drugs can be loaded by the adsorption method; (3) and the obtained microparticles may be used for delaying the release of drugs of low water solubility in acidic conditions.

Adsorption↗

Failure to find association between TRAR4 and schizophrenia in the Chinese Han population.

The TRAR4 gene locates in SCZD5 (MIM 603175), which a number of studies have linked with schizophrenia. One recent study suggested that three TRAR4 variants (M1: rs4305745, P=0.0014; M2: rs6903874, P=0.0026; M3: rs6937506, P=0.0052) in the 3'-UTR were associated with schizophrenia. To replicate these findings, we conducted a family-based association study within a sample of 235 Chinese Han trios. However, we didn't find significant evidence of preferential transmission of the three variants across all the trios (all P values>0.2). Thus, we conclude that TRAR4 is not a major or independent determinant in the occurrence of schizophrenia in the Chinese Han population.

Adult↗

Acute and chronic effects of the incretin enhancer vildagliptin in insulin-resistant rats.

The enzyme dipeptidyl peptidase-IV (DPP-4) inactivates the incretin hormone glucagon-like peptide-1 (GLP-1). Because GLP-1 has therapeutic effects in patients with type 2 diabetes, but its potential is limited by a short half-life, DPP-4 inhibition is a promising approach to diabetes treatment. This study examined acute (single dose) and chronic (once-a-day dosing for 21 days) effects of the DPP-4 inhibitor vildagliptin (0.03-10 mg/kg) on plasma DPP-4 activity, intact GLP-1, glucose, and insulin after an oral glucose load in insulin-resistant Zucker fatty rats and acute effects in mildly insulin-resistant high-fat-fed normal rats. A single oral dose of vildagliptin in Zucker rats produced a rapid and dose-related inhibition of DPP-4: the minimum effective dose (MED) was 0.3 mg/kg. Glucose-induced increases of intact GLP-1 were greatly but similarly enhanced by vildagliptin at doses > or =0.3 mg/kg. Postload glucose excursions decreased, and the insulinogenic index (Deltainsulin/Deltaglucose at 10 min) increased, with an MED of 0.3 mg/kg and a maximally effective dose of 3 mg/kg. The effects of vildagliptin after chronic treatment were nearly identical to those of acute administration, and vildagliptin had no effect on body weight. In fat-fed normal rats, vildagliptin (3 mg/kg) also decreased postload glucose excursions and increased the insulinogenic index, but these effects were smaller than those in Zucker rats. Thus, vildagliptin is an orally effective incretin enhancer with antihyperglycemic activity in insulin-resistant rats and exhibits no tachyphylaxis. GLP-1-mediated augmentation of glucose-induced insulin release seems to make the major contribution to the antidiabetic properties of vildagliptin.

Adamantane↗

Activation of glycogen synthase kinase-3 induces Alzheimer-like tau hyperphosphorylation in rat hippocampus slices in culture.

Formation of neurofibrillary tangle from hyperphosphorylated tau is one of the hallmark lesions seen in Alzheimer's disease (AD) brain, and neuronal deregulation of glycogen synthase kinase-3 (GSK-3) activity plays key role in tau hyperphosphorylation. In the present study, the role of GSK-3 on tau phosphorylation in hippocampus slice culture was examined by incubating the slice with wortmannin (WT), an inhibitor of phosphatidylinositol 3-kinase (PI3K) and GF-109203X (GFX), an inhibitor of protein kinase C (PKC). It was found that treatment of the slices with GFX or WT separately induced tau hyperphosphorylation both at Ser396/Ser404 (PHF-1) and Ser199/Ser202 (Tau-1) sites. The phosphorylation rate of tau at PHF-1 and Tau-1 epitopes was further increased when GFX and WT were used in combination, and at this condition, AD-like tau accumulation was observed. GSK-3 activity was significantly increased with a concurrently decreased level of inactivated form of GSK-3. Lithium chloride (LiCl), a GSK-3 inhibitor, prevented tau from WT- and GFX-induced hyperphosphorylation. It suggests that GSK-3 is regulated through PI3K and PKC pathway, and activation of GSK-3 not only induces hyperphosphorylation of tau but also leads to accumulation of tau in cultured rat brain slice.

Alzheimer Disease↗

p53 gene (Gendicine) and embolisation overcame recurrent hepatocellular carcinoma.

Transcatheter arterial chemoembolisation (TACE) has become the standard treatment for unresectable hepatocellular carcinoma (HCC). However, this method is often unsuccessful. The p53 gene, which is present as a mutant form in many human tumours, is known to have broad spectrum antitumour effects when expressed normally. In this study, we report a 23 year old patient with recurrent HCC who was treated with the p53 gene (Gendicine) combining TACE, which resulted in a good clinical prognosis.

Adult↗

Targeted disruption of LH receptor gene revealed the importance of uterine LH signaling.

Numerous previous studies have demonstrated that LH and hCG can directly regulate several uterine functions. We investigated in the present study, whether uterine phenotype in LH receptor knockout animals resulted also from the absence of direct actions of LH in the uterus. The phenotype consisted of marked growth reduction of uterus, decreased thickness of endometrial and myometrial layers, number of endometrial glands, height of luminal epithelium and vascular space. Analysis of uterine gene expression by mouse genome U74Av2 Affymetrix genechips revealed a differential expression of 155 genes by more than 3-fold (range 3-53-fold) between null and wild-type animals. Of these, 89 genes decreased and 66 increased in uterus of null animals. Semi-quantitative RT-PCR confirmed the differential expression of several selected genes. The decreased genes can be clustered into 18 functional families and the increased into 15 functional families. Semi-quantitative RT-PCR, Western blotting and immunocytochemistry demonstrated a decreased expression of ERbeta, PR-A, PR-B and AR in uterus of null animals as compared with wild-type siblings. Twenty-one-day estradiol and progesterone replacement therapy did not normalize the decrease in the number of endometrial glands and several genes that either decreased or increased in expression. The partial success of therapy suggests that direct LH actions could be required to completely normalize the uterus. In summary, findings on the knockout model reaffirm that LH and hCG control uterine functions directly as well as indirectly through increasing ovarian synthesis of steroid hormones and both actions are required for normal uterine biology.

Animals↗

Second primary malignancies in patients with male breast cancer.

An international multicentre study of first and second primary neoplasms associated with male breast cancer was carried out by pooling data from 13 cancer registries. Among a total of 3409 men with primary breast cancer, 426 (12.5%) developed a second neoplasia; other than breast cancer, a 34% overall excess risk of second primary neoplasia, affecting the small intestine (standardised incidence ratio, 4.95, 95% confidence interval, 1.35-12.7), rectum (1.78, 1.20-2.54), pancreas (1.93, 1.14-3.05), skin (nonmelanoma, 1.65, 1.16-2.29), prostate (1.61, 1.34-1.93) and lymphohaematopoietic system (1.63, 1.12-2.29). A total of 225 male breast cancers was recorded after cancers other than breast cancer, but an increase was found only after lymphohaematopoietic neoplasms. BRCA2 (and to some extent BRCA1) mutations may explain the findings for pancreatic and prostate cancers. Increases at other sites may be related to unknown factors or to chance. This large study shows that the risks for second discordant tumours after male breast cancer pose only a moderate excess risk.

Adult↗

Age and gender differences in health service utilization.

BACKGROUND: This study of age and gender profiles of health care populations fills a gap in the research literature by providing a population study of both single health agency and inter-agency 'Shared Care' populations. METHODS: It combines anonymous data to link individual cases across Community Health (N = 82 751), Mental Health (N = 19 029) and Social Services (N = 19 461) populations in one county Health Authority (N = 646 239) over 3 years. It compares age and gender characteristics of single care populations and overlapping inter-agency 'Shared Care'populations. RESULTS: Approximately two-thirds of all care populations were female compared to half (513.1) in the general Health Authority population. These differences were accentuated for almost all inter-agency 'Shared Care' populations, where, whilst a younger care profile emerged for mental health and social services dual agency clients, for other shared populations a distinct care profile emerged of greater proportions of older, female and older female patients. Gender differences were also apparent for different care groups within a total Community Health care population. Whilst females made much more use of services overall, in Community Health, older males were more likely to receive rehabilitative support services. CONCLUSION: Age and gender profiles of health care agency and inter-agency populations clarify service use patterns and identify high proportions of women in health and social care populations, particularly in older care populations. This type of care population analysis could inform single agency and inter-agency shared care planning and commissioning.

Adolescent↗

Antitumor effect of beta-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death.

Beta-elemene is a novel anticancer drug, which was extracted from the ginger plant. However, the mechanism of action of beta-elemene in non-small-cell lung cancer (NSCLC) remains unknown. Here we show that beta-elemene had differential inhibitory effects on cell growth between NSCLC cell lines and lung fibroblast and bronchial epithelial cell lines. In addition, beta-elemene was found to arrest NSCLC cells at G2-M phase, the arrest being accompanied by decreases in the levels of cyclin B1 and phospho-Cdc2 (Thr-161) and increases in the levels of p27(kip1) and phospho-Cdc2 (Tyr-15). Moreover, beta-elemene reduced the expression of Cdc25C, which dephosphorylates/activates Cdc2, but enhanced the expression of the checkpoint kinase, Chk2, which phosphorylates/ inactivates Cdc25C. These findings suggest that the effect of beta-elemene on G2-M arrest in NSCLC cells is mediated partly by a Chk2-dependent mechanism. We also demonstrate that beta-elemene triggered apoptosis in NSCLC cells. Our results clearly show that beta-elemene induced caspase-3, -7 and -9 activities, decreased Bcl-2 expression, caused cytochrome c release and increased the levels of cleaved caspase-9 and poly(ADP-ribose) polymerase in NSCLC cells. These data indicate that the effect of beta-elemene on lung cancer cell death may be through a mitochondrial release of the cytochrome c-mediated apoptotic pathway.

Apoptosis↗

Antiproliferative effect of beta-elemene in chemoresistant ovarian carcinoma cells is mediated through arrest of the cell cycle at the G2-M phase.

Elemene is a natural antitumor plant drug. However, the effect of elemene on cell growth in ovarian cancer is unknown. In this study, we show that beta-elemene inhibited the proliferation of cisplatin-resistant human ovarian cancer cells and their parental cells, but had only a marginal effect in human ovary cells, indicating differential inhibitory effects on cell growth between ovarian cancer cells and normal ovary cells. We also demonstrated for the first time that beta-elemene markedly enhanced cisplatin-induced growth inhibition in resistant cells compared to sensitive cells. In addition, cell cycle analysis revealed a synergistic effect of beta-elemene and cisplatin on the induction of cell cycle G2-M arrest in our resistant ovarian carcinoma cells. Furthermore, we showed that treatment of these cells with both drugs downregulated cyclin B1 and Cdc2 expression, but elevated the levels of p53, p21waf1/cip1, p27kip1 and Gadd45. Finally, the combination of beta-elemene and cisplatin was found to increase the phosphorylation of Cdc2 and Cdc25C, which leads to a reduction in Cdc2-cyclin B1 activity. These novel findings suggest that beta-elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced growth suppression partly through modulating the cell cycle G2 checkpoint and inducing cell cycle G2-M arrest, which lead to blockade of cell cycle progression.

Antineoplastic Combined Chemotherapy Protocols↗

Alfalfa as a single dietary source for molt induction in laying hens.

Molting is a process by which a hen's reproductive tract is rejuvenated prior to the beginning of a laying cycle. This process is often artificially induced in commercial settings in order to extend the productive life of a flock of hens. The most common method for the induction of molt is feed withdrawal for a period of several days. It has been noted that feed withdrawal, while effective in inducing molt and allowing an adequate reproductive rest period for the hen, may cause deleterious effects on the animal. This has prompted the investigation of alternatives to feed deprivation for the induction of molt in commercial laying hens. This study involved feeding alfalfa to hens to assess its ability to induce molt. Results show that alfalfa meal and alfalfa pelleted diets were equally effective as feed withdrawal in causing ovary weight regression in birds. Molted hens induced by alfalfa diets exhibited postmolt levels of egg production over a twelve week period that were similar to that of hens molted by feed withdrawal. The postmolt eggs laid by hens molted by alfalfa were of comparable quality to eggs from feed deprived hens. Alfalfa, a fibrous feed with low metabolizable energy, may be provided to hens on an ad libitum basis for an effective molt induction that retains comparable egg quality and production.

Analysis of Variance↗

Are national quality standards for traditional Chinese herbal medicine sufficient? Current governmental regulations for traditional Chinese herbal medicine in certain Western countries and China as the Eastern origin country.

Traditional Chinese herbal Medicine (TCHM) has been gaining interest and acceptance world wide. TCHM provides on the one side promising perspective of scientific interest and on the other side possible health risks if TCHM drugs are not controlled with respect to quality standards or if practitioners for TCHM are not well trained. This paper outlines an introduction to the scientific aspects and potential risks of TCHM therapy followed by a brief, exploratory overview of the current status of TCHM regulations in certain Western countries like the USA, United Kingdom, Germany, Australia and in China as the Eastern origin country of TCHM. Legal foundations to establish quality and safety standards for TCHM crude drugs and ready-made formulas exist in some countries on a local basis but in practice are poorly enforced, where this products have no drug status. In addition practitioners treating patients with TCHM should be well versed in the pharmacology, side effects, and interactions of these substances with Western medicines and should be certified on a regular basis.

Consumer Product Safety↗

Tumor necrosis factor receptor 1 expression and early spontaneous abortion.

OBJECTIVES: To compare tumor necrosis factor receptor 1 (TNFR1) protein expression in women with unexplained early spontaneous abortion (UESA) and normal pregnancy. METHODS: In a prospective study, 62 women with UESA and 60 with normal pregnancy were studied. Decidual membrane TNFR1 was detected by flow cytometry and immunohistochemistry, and serum soluble TNFR1 were by ELISA. Statistical analyses of resulting data employed the student's t test, the Fisher's Exact, and the nonparametric Wilcoxon test RESULTS: The percentage of membrane tumor necrosis factor receptor 1 (mTNFR1) positive decidual cells was 16.42+/-7.1 for women with UESA and 12.47+/-5.3 for women with normal pregnancy (p<0.05). The number of mTNFR1 positive cells was more in decidual stromal and vessel endothelial cells in women with UESA, and serum soluble tumor necrosis factor receptor 1 (sTNFR1) concentration was significantly higher than in women with normal pregnancy (554.56+/-126.7 pg/ml vs. 175.3+/-52.4 pg/ml; p<0.001). CONCLUSION: The overexpression of TNFR1 may contribute to the development of ESA.

Abortion, Spontaneous↗