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Biomedical subjects

Qian Li

Publications and source records attributed to Qian Li.

At least 55 records · Page 3Linked to original sources

[Value of carboxyhemoglobin in the diagnosis of neonatal jaundice].

OBJECTIVE: To study the value of carboxyhemoglobin (COHb) in the diagnosis of neonatal jaundice. METHODS: This study consisted of 189 patients with neonatal jaundice due to hemolytic disease (n=75), infectious disease (n=52), intracranial hemorrhage (n=32) and breast-milk feeding (n=30). One hundred and forty-two neonates without pathological jaundice that were gestational age, postnatal age- and birth weight-matched were used as the Control group. The level of arterial capillary blood COHb was detected by a 270 CO-oximeter connected to an 800 series system. Total serum bilirubin (STB) content was measured using an Abbott Spectrum CCX chemistry analyzer. The levels of COHb and STB were measured at baseline, and again in patients with jaundice due to hemolytic disease after intravenous gammaglobulin treatment for 2 days. RESULTS: The levels of COHb [(3.64 +/- 0.83)%] and STB (330.84 +/- 77.15 micromol/L) in patients with jaundice due to hemolytic disease were significantly higher than those measured in the Control group [COHb (2.38 +/- 0.35) %; STB 130.18 +/- 32.86 micromol/L] (P < 0.01). The levels in patients with jaundice due to intracranial hemorrhage were also significantly higher than those in the Control group [COHb (2.48 +/- 0.53) % vs (2.24 +/- 0.32) %; STB 184.15 +/- 29.35 micromol/L vs 112.11 +/- 17.45 micromol/L; P < 0.05]. The patients with jaundice due to infectious disease or breast-milk feeding only demonstrated higher levels of serum STB (P < 0.01) while COHb levels were not different compared with the Control group. The patients with jaundice due to hemolytic disease or intracranial hemorrhage presented with hemolytic unconjugated hyperbilirubinemia and had significantly higher COHb levels and lower STB levels than those patients with nonhemolytic unconjugated hyperbilirubinemia (caused by breast jaundice) (P < 0.01). The levels of COHb [(2.68 +/- 0.51) %] and STB (230.18 +/- 42.96 micromol/L) in patients with jaundice due to hemolytic disease decreased markedly after intravenous gammaglobulin treatment (P < 0.01). CONCLUSIONS: The COHb level can be used as a supplementary indicator of increased bilirubin production. The elevation of COHb can be useful in the diagnosis of neonatal jaundice since COHb is elevated in hemolytic disease and intracranial hemorrhage.

ABO Blood-Group System↗

[Effect of baicalin on HSP70 expression of hippocampal neurons in focal brain ischemia-reperfusion injury rats].

AIM: To investigate the effect of baicalin on the hippocampal neuronal apoptosis and the expression of HSP70 in rats with focal brain ischemia-reperfusion injury. METHODS: One hundred and twenty male Wistar rats were randomly divided into six groups:sham operated group, ischemia-reperfusion group, nimodipine group and three baicalin groups,to which baicalin was administered at doses of 50, 100 and 200 mg x kg(-1), separately. The models of focal brain ischemia-reperfusion injury induced by middle cerebral artery occlusion (MCAO) were used in this study. HE stain was used to observe the pathological changes. Flow cytometry (FCM) was used for determination of neuronal apoptosis. HSP70 protein expression of the neurons was detected with immunohistochemistry. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of the mRNA level of HSP70. RESULTS: Baicalin can significantly relieve the pathological changes and inhibit apoptosis in hippocampus CA1 area, and at the same time increase the expression of HSP70 and HSP70 mRNA. CONCLUSION: Baicalin can relieve brain damage induced by focal brain ischemia-reperfusion in rats, which may be related to inhibiting the process of the neuronal apoptosis. The mechanism of antiapoptosis effect of baicalin may be related to the promotion of transcription of HSP70 mRNA and increasing the expression of the protein.

Animals↗

[Studies on chemical constituents of Euphorbia sororia].

OBJECTIVE: To study the chemical constituents of the aerial parts of Euphorbia sororia. METHOD: Isolation and purification were carried out by silica gel and Sephadex LH -20 column chromatographies. Compounds were identified by physicochemical properties and spectral analysis. RESULT: Ten compounds were isolated from the plant . Their structures were identified as kaempferol (1), scopoletin (2) , kaempferol 3-O-glucopyranoside (3) , quercetin (4) , vanillic acid (5) , E-p-hydroxycinnamic acid (6) , protocatechuic acid (7), 6, 7-dihydroxycoumarin (8), beta-sitosterol (9), and daucosterol (10) , respectively. CONCLUSION: All the above compounds were isolated from the plant for the first time.

Euphorbia↗

Genomic instability in radiation-induced mouse lymphoma from p53 heterozygous mice.

Although radiation can directly induce DNA damage and is a known human and animal carcinogen, the number of genetic changes in radiation-induced tumors, and the pathways responsible for generating them, are unknown. We have used high-density BAC arrays covering >95% of the mouse genome for analysis of genomic patterns of aberrations in spontaneous and radiation-induced mouse lymphomas. The majority of radiation-induced tumors exhibit one of three 'signatures' based on gene copy number changes. Some exhibit extensive scrambling of the genome, with very high numbers of recurrent gains and losses. Two other signatures are characterized by excess gains but relatively few losses, or vice versa. Changes in spontaneous tumors often involve whole chromosomes, whereas radiation-induced tumors exhibit a high frequency of localized deletion/amplification events. The number of copy number abnormalities does not correlate with the latency or pathology of the tumors. We propose that specific early events following radiation exposure induce changes in 'caretaker' genes that control specific downstream pathways involved in DNA damage repair. The nature of these early events may determine the overall genomic signature observed in the resulting tumor.

Animals↗

Desorption/ionization on porous silicon mass spectrometry studies on pentose-borate complexes.

Desorption/ionization on porous silicon mass spectrometry (DIOS-MS) was used to investigate the binding affinities between aldopentose isomers and boron. Boron has been recognized for its importance in pentose synthesis and stabilization in prebiotic conditions. Boron may also account for the fact that ribose, among other aldopentoses, is the favored building block in RNA synthesis. This research started with the detection of aldopentoses in the positive mode through cationization and the aldopentose-borate complexes in the negative mode. Then two competition schemes, one using a pentose structure analogue and the other using 13C-labeled ribose, were designed to compare the relative binding affinities of four aldopentoses (xylose, lyxose, arabinose, and ribose) to boron. Both approaches determined the binding preference to be ribose > lyxose > arabinose > xylose. This work illustrates the potential of DIOS-MS in the analyses of nonvolatile, small molecules in delicate chemical equilibria. Without externally introduced matrices, background signals are not a limiting factor. Furthermore, the possible dramatic change of pH associated with the matrix introduction, which may disturb the equilibria of interest, is avoided.

Boron↗

Changes of gastrointestinal myoelectric activity and bile acid pool size after cholecystectomy in guinea pigs.

AIM: To investigate the bile acid pool size after cholecystectomy whether or not correlated to the gastrointestinal migrating myoelectric complex (MMC) in guinea pigs. METHODS: Gallbladder motilities were assessed before cholecystectomy. Furthermore, we continuously monitored interdigestive gastrointestinal motilities using bipolar electrodes in conscious guinea pigs before and after surgery at 4 wk in standard diet group and high cholesterol diet (cholesterol gallstone) group. Total bile acid pool sizes were measured by isotope dilution method at meantime. RESULTS: After cholecystectomy, there were parallel falls in duration of phase I, II, III and MMC cycle duration but increase in amplitude in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones. However, There were not significantly differences. On the other hand, the bile acid pool was definitely small in the GS guinea pigs compared to normal guinea pigs and became slightly smaller after cholecystectomy. Similarly, bile acid in gallbladder bile, fecal bile acid was slightly increased in GS guinea pigs after cholecystectomy, to the same degree as normal. These differences, however, were not significant. CONCLUSION: It is concluded that in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones: (1) Cholecystectomy produce a similar but less marked trend in bile acid pool; and (2) MMC are linked to enterohepatic circulation of bile acids, rather than surgery, which is consistent with changes of the bile acid pool size. As a result, gastrointestinal dyskinesia is not involved in occurrence of postcholecystectomy syndrome.

Animals↗

Binding affinity difference induced by the stereochemistry of the sulfoxide bridge of the cyclic peptide inhibitors of Grb2-SH2 domain: NMR studies for the structural origin.

The SAR study on a phage library-derived non-phosphorylated cyclic peptide ligand of Grb2-SH2 domain indicates that the configuration of the cyclization linkage is crucial for assuming the active binding conformation. When the thioether linkage was oxidized to the two chiral sulfoxides, the R-configured sulfoxide-cyclized peptide displayed 10-30 times more potency than the corresponding S-configured one in binding affinity to the Grb2-SH2 domain. In this paper, the solution structures of such a pair of sulfoxide-bridged cyclic peptide diastereoisomers, i.e., cyclo[CH(2)CO-Gla(1)-L-Y-E-N-V-G-NPG-Y-(R/S)C(O)(10)]-amide, were determined by NMR and molecular dynamics simulation. Results indicate that the consensus sequence of Y(3)-E(4)-N(5)-V(6) in both diastereoisomers adopt a beta-turn conformation; however, the R-configured peptide forms an extended structure with a circular backbone conformation, while the S-configured isomer forms a compact structure with key residues buried inside the molecule. The average root-mean-square deviations were found to be 0.756 and 0.804 A, respectively. It is apparent that the chiral S-->O group played a key role in the solution structures of the sulfoxide-bridged cyclic peptides. The R-sulfoxide group forms an intramolecular hydrogen bond with the C-terminal amide, conferring a more rigid conformation with all residues protruding outside except for Leu2, in which the Gla1 and Tyr3 share an overlapping function as previous SAR studies proposed. Additionally, the extended structure endows a more hydrophilic binding surface of the R-configured peptide to facilitate its capture by its targeted protein. In comparison, the S-configured sulfoxide was embedded inside the ligand peptide leading to a compact structure, in which the essential residues of Gla1, Tyr3, and Asn5 form multiple intramolecular hydrogen bonds resulting in an unfavorable conformational change and a substantial loss of the interaction with the protein. The solution structures disclosed by our NMR and molecular dynamics simulation studies provide a molecular basis for understanding how the chirality of the cyclization linkage remarkably discriminates in terms of the binding affinity, thus advancing the rational design of potent non-phosphorylated inhibitors of Grb2-SH2 domain as antitumor agents.

Adaptor Proteins, Signal Transducing↗

Inhibitory activity of a ceramide library on interleukin-4 production from activated T cells.

Allergic diseases are hypersensitivity disorders associated with the production of specific immunoglobulin E (IgE) to environmental allergens. Interleukin (IL)-4, produced primarily by CD4(+) T cells, is an important stimulus for the switch of the antibody isotype to IgE in both mice and humans. In this study we investigated the inhibitory activity of IL-4 production in activated T cells by screening ceramide derivatives prepared by solid phase combinatorial chemistry. Many ceramide derivatives significantly inhibited IL-4 production in T cells. In particular, ceramide derivatives with a lauroyl group showed strong inhibitory activities on IL-4 production in both phorbol 12-myristate 13-acetate (PMA)-activated EL4 T cells and antigen-primed cells, suggesting that they can be used as compounds for the development of anti-allergic agents.

Animals↗

Study on hepatoprotective effect of peptide S-8300 from shark liver.

AIM: To explore the effects of peptide S-8300 from shark liver (S-8300) on liver function as well as in regulating immune functions in experimental injury models. METHODS: Mice were administered with different doses of S-8300 for four consecutive days, followed by mice injected with tetrachloromethane (CCl(4)) on d 3. The activity of ALT, AST, LDH, SOD and contents of MDA and GSH in the mice liver were tested. And mice were treated with Cy (100 mg/kg) at the beginning of the experiment to induce immunosuppression model. The S-8300 groups were treated with S-8300 seven days after the beginning of Cy administration. The effects of S-8300 on the formulation of serum hemolysin and the content of IL-2 in serum in the immunosuppression mice were observed. RESULTS: S-8300 obviously decreased the level of ALT (52.2+/-11.0 U/dL vs 135.9+/-6.5 U/dL, P<0.01), AST (67.5+/-6.9 U/dL vs 238.8+/-8.7 U/dL, P<0.01), LDH (155.1+/-46.8 U/dL vs 240.4+/-6.0 U/dL, P<0.01) and MDA (0.64+/-0.027 nmol/mg vs 1.06+/-0.040 nmol/mg, P<0.01) and increased SOD (24.51+/-1.01 U/mg vs 19.05+/-0.73 U/mg, P<0.01) and GSH (24.17+/-0.91 microg/mg vs 14.93+/-0.45 microg/mg, P<0.01) in mice liver damaged by CCl(4). S-8300 also markedly improved the formulation of serum hemolysin (0.094+/-0.005 A(540) vs 0.063+/-0.006 A(540), P<0.01) and increased the level of IL-2 (9.74+/-1.16 pg/mL vs 5.81+/-0.87 pg/mL, P<0.01) in serum of the immunosuppression mice. CONCLUSION: The results suggested S-8300 has significant hepatoprotective, immunomodulatory and inhibiting of lipid peroxidation activity.

Animals↗

A phosphatidyl-inositol-3-kinase-dependent anti-inflammatory pathway activated by Salmonella in epithelial cells.

Salmonella activates the phosphatidyl-inositol-3-kinase (PI3K)/Akt pathway in epithelial cells, but its role in inflammation has not been previously elucidated. We show here that inhibition of PI3K in T84 intestinal epithelial cells results in augmentation of Salmonella-induced interleukin-8 (IL-8) production at the level of both protein and mRNA. The mechanism of this effect appears to involve altered activation of the extracellular growth factor-regulated kinase (ERK), a molecule that is implicated in the regulation of IL-8 expression. These results identify activation of the PI3K/Akt pathway as an anti-inflammatory signal that may contribute to the establishment of Salmonella in the intestine.

Cell Line↗

Effects of oxymatrine on experimental hepatic fibrosis and its mechanism in vivo.

AIM: Hepatic fibrogenesis has close relation with hepatic stellate cells (HSC) and tissue inhibitors of metalloproteinase (TIMP). Oxymatrine (OM) is a kind of Chinese herb that is found to have some effects on liver fibrosis. We aimed to determine the effects of OM on hepatic fibrosis and explore the possible mechanism. METHODS: Thirty-two rats were randomly divided into four groups; 16 were used to develop hepatic fibrosis by carbon tetrachloride (CCl4) and treated with or without OM, and 16 were used as controls. The expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and alpha-smooth muscle actin (alpha-SMA) in the livers of rats was detected by immunohistochemical assay. Liver pathology was determined by H and E staining and reticulum staining. RESULTS: In CCl4-injured rats, the normal structure of lobules was destroyed, and pseudolobules were formed. Hyperplasia of fibers was observed surrounding the lobules. While the degree of fibrogenesis in liver tissues was significantly decreased in those rats with OM-treatment compared with those without OM treatment. The pseudolobules were surrounded by strong, multi-layer reticular fibers, which netted into pseudolobules in CCl4-injured rats, however, there was a significant decrease in reticular fibers in OM-treated rats. The expression of TIMP-1 in hepatic cells was weak in control groups, but strong in CCl4-injured groups, however, the expression of TIMP-1 was significantly inhibited by OM (F = 52.93, P<0.05). There was no significant change in the expression of alpha-SMA between CCl4-injured rats with or without OM treatment (F = 8.99, P>0.05). CONCLUSION: OM effectively inhibits CCl4-induced fibrogenesis in rat liver tissues, probably by reducing the expression level of TIMP-1.

Alkaloids↗

Perisinusoidal B cells in the bone marrow participate in T-independent responses to blood-borne microbes.

Mature recirculating B cells are generally assumed to exist in follicular niches in secondary lymphoid organs, and these cells mediate T-dependent humoral immune responses. We show here that a large proportion of mature B lymphocytes occupy an anatomically and functionally distinct perisinusoidal niche in the bone marrow. Perisinusoidal B cells circulate freely, as revealed by parabiosis studies. However, unlike their counterparts in the follicular niche, these cells are capable of being activated in situ by blood-borne microbes in a T-independent manner to generate specific IgM antibodies. The bone marrow represents a unique type of secondary lymphoid organ in which mature B cells are strategically positioned in the path of circulating microbes.

Animals↗

Analysis of protein covalent modification by xenobiotics using a covert oxidatively activated tag: raloxifene proof-of-principle study.

Numerous xenobiotics, including therapeutics agents, are substrates for bioactivation to electrophilic reactive intermediates that may covalently modify biomolecules. Selective estrogen receptor modulators (SERMs) are in clinical use for long-term therapy of postmenopausal syndromes and chemoprevention and provide a potential alternative for hormone replacement therapy (HRT). Raloxifene, in common with many SERMs and other xenobiotics, is a polyaromatic phenol that has been shown to be metabolically bioactivated to electrophilic and redox active quinoids. Nucleic acid and glutathione adduct formation have been reported, but little is known about protein covalent modification. A novel COATag (covert oxidatively activated tag) was synthesized in which raloxifene was linked to biotin. The COATag was reactive toward a model protein, human glutathione-S-transferase P1-1, in the presence but not the absence of monooxygenase. The covalent modification of proteins in rat liver microsomal incubations was NADPH-dependent implicating cytochrome P450 oxidase. The COATag facilitated isolation and identification of covalently modified microsomal proteins: cytosolic glucose regulated protein (GRP78/BiP), three protein disulfide isomerases, and microsomal glutathione S-transferase 1. Oxidative metabolism of raloxifene produces reactive intermediates of sufficient lifetimes to covalently modify proteins in tissue microsomes, behavior anticipated for other polyaromatic phenol xenobiotics that can be tested by the COATag methodology. The combined use of a COATag with a simple biotin-linked electrophile (such as an iodoacetamide tag) is a new technique that allows quantification of protein covalent modification via alkylation vs oxidation in response to xenobiotic reactive intermediates. The identification of modified proteins is important for defining pathways that might lead alternatively to either cytotoxicity or cytoprotection.

Animals↗

Prevalence of calcidiol deficiency in CKD: a cross-sectional study across latitudes in the United States.

BACKGROUND: Recent Kidney Disease Outcomes Quality Initiative guidelines have raised concerns of 25-hydroxyvitamin D, or calcidiol, insufficiency and deficiency in patients with chronic kidney disease (CKD) not yet on dialysis therapy; however, no cross-sectional study across latitudes has been performed to support this assertion. METHODS: Baseline screening data from a prospective study were used to determine calcidiol levels in subjects with moderate to severe CKD not yet on dialysis therapy from 12 geographically diverse regions of the United States. Calcidiol deficiency is defined as levels less than 10 ng/mL (< 25 nmol/L), and insufficiency, as levels of 10 to 30 ng/mL (25 to 75 nmol/L). RESULTS: Two hundred one subjects with a mean age 65 +/- 13 years and calculated glomerular filtration rate (GFR) of 27 +/- 11 mL/min (0.45 mL/s) were evaluated. Overall mean calcidiol level was 19.4 +/- 13.6 ng/mL (48 +/- 34 nmol/L), with a range of 0 to 65 ng/mL (0 to 162 nmol/L). Only 29% and 17% of subjects with moderate and severe CKD had sufficient levels, respectively. Mean calcidiol levels were less than sufficient levels in all geographic locations tested. Multivariate analysis found log calcidiol level correlated with calcium level (P = 0.016), log calcitriol level (P = 0.024), sex (P = 0.041), geographic location (P = 0.045), and inverse intact parathyroid hormone level (P = 0.013), but not calculated GFR or phosphorous level. Calcidiol levels changed modestly in 18 patients who had calcidiol levels measured in winter and late summer after confirmed exposure to sunlight, with mean calcidiol levels of 17.9 +/- 11.7 to 21.2 +/- 10.0 ng/mL (45 +/- 29 to 53 +/- 25 nmol/L; P = 0.015). CONCLUSION: This cross-sectional cohort study found a high prevalence of calcidiol deficiency and insufficiency in patients with moderate and severe CKD not on dialysis therapy regardless of geographic location.

Adult↗

Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice. II. The design of a CAPs exposure system for biometric telemetry monitoring.

We modified, assembled, tested, and validated the versatile aerosol concentration enrichment system (VACES) developed by Sioutas et al. (1999) for use in a subchronic experiment that involved exposure of mice in vivo and of respiratory epithelial cells in vitro to concentrated ambient particles (CAPs). Since the labor-intensive nose-only exposure regimen is not an option in a long-term experiment, a whole-body exposure mouse chamber was designed specifically for use with the VACES. The exposure system concsists of a stainless-steel (SS) tub with 32 cubicles (1 mouse per cubicle) separated by perforated SS sheets. The tops of these cubicles are covered with perforated plastic sheets to allow telemetry monitoring during the exposure. In each exposure chamber, perforated aluminum tubes are used to distribute CAPs evenly (within 2% difference) throughout the exposure chamber. The exhaust consists of perforated aluminum tubes covered with a urine shield. The modification to the original design of the VACES facilitated the operation of the system in a subchronic study. Mass flow controllers maintain a constant flow rate into the exposure chambers. For a sham control exposure, the identical system is used, except that a HEPA filter at the inlet to the VACES removes 98% of ambient particles. The entire system allow for simultaneous exposure of 64 mice to CAPs, with an equal number of sham-expose mice as controls. Telemetry receives have been modified so that 16 mice per group with electrocardiograph (EKG) transmitters can be monitored during exposure. Furthermore, a BioSampler is used to collect CAPs (one sample per day) for the in vitro exposures. In this article, the assessments of flow and particle distribution of the exposure chamber as well as the performance of the system during the subchronic exposure experiment are described.

Aerosols↗

Protein kinase C blockade inhibits differentiation of myeloid blasts into dendritic cells by calcium ionophore A23187.

Direct differentiation of myeloid leukemia blasts into antigen-presenting dendritic cells (DCs) for use as cellular vaccines is unique in that identification of tumor-specific antigens may not be necessary because the antigens should already be endogenously expressed. We hypothesized that signaling through protein kinase C (PKC) is required for differentiation of HL-60 promyeloblasts into DCs upon stimulation with calcium ionophore A23187. To demonstrate the inhibitory effect of PKC blockade, we pretreated HL-60 myeloid blasts with the protein kinase inhibitor bisindolylmaleimide I (Bis-1) for 24 hours and then treated the cells with calcium ionophore A23187 for an additional 24 hours. Controls consisted of HL-60 blasts treated with A23187, Bis-1 alone, or media. We noted that blasts cultured in media, Bis-1, or Bis-1 then A23187 did not develop the morphologic and phenotypic DC characteristics, up-regulate Rel B, or activate allogeneic T-cells. Our findings suggested that PKC blockade inhibits morphologic, phenotypic, and functional differentiation of HL-60 promyeloblasts into antigen-presenting DCs. Our findings supported the role of PKC as an obligatory pathway for calcium ionophore A23187-induced differentiation of HL-60 myeloblasts into antigen-presenting DCs.

Antigen-Presenting Cells↗