Biomedical subjects

Ke Liu

Publications and source records attributed to Ke Liu.

At least 19 recordsLinked to original sources

PubMed2026

ZBTB16-associated NK cell alterations reveal shared immunometabolic signatures linking primary Sjögren's syndrome and type 1 diabetes mellitus.

BACKGROUND: Primary Sjögren's syndrome (pSS) and type 1 diabetes mellitus (T1DM) share immune-inflammatory features, yet conserved pathogenic signatures linking these autoimmune disorders remain incompletely understood. The present research sought to uncover common molecular markers and dissect the underlying immune-metabolic cross-talk underlying pSS and T1DM. METHODS: Gene expression profiles of patients with pSS and T1DM were retrieved from the Gene Expression Omnibus database, normalized, and corrected for batch effects prior to downstream analyses. Overlapping potential biomarkers were screened by integrating differential expression analysis, weighted gene co-expression network analysis and least absolute shrinkage and selection operator regression. Functional enrichment based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases was implemented to interpret gene biological properties, and a protein-protein interaction network was further established afterwards. Diagnostic performance was evaluated using receiver operating characteristic analysis. Experimental validation was conducted in non-obese diabetic (NOD) mice using quantitative PCR, immunohistochemistry, and flow cytometry. The CIBERSORT algorithm was adopted to quantify immune cell infiltration levels. RESULTS: ZBTB16 was identified as a shared hub biomarker in both pSS and T1DM and exhibited favorable diagnostic performance. Experimental validation confirmed significantly reduced ZBTB16 expression in peripheral blood mononuclear cells, salivary gland tissues, and pancreatic tissues of NOD mice. Gene Set Enrichment Analysis indicated that ZBTB16-associated signatures were enriched in mitochondrial-related processes, neuroactive ligand-receptor interactions, and ribosome-related pathways. Immune infiltration analysis revealed that resting natural killer (NK) cells were positively correlated with ZBTB16 expression in both diseases. Flow cytometric analysis further confirmed a reduced proportion of resting NK cells in peripheral blood of NOD mice, consistent with the CIBERSORT-based prediction. CONCLUSION: This study identifies ZBTB16 as a shared biomarker linking pSS and T1DM. Reduced resting NK-cell abundance was consistently observed in both computational and experimental analyses, and bioinformatic correlation analysis suggested a positive association with ZBTB16 expression. These findings provide evidence for shared molecular and immunological signatures underlying the two autoimmune disorders and support further investigation of the biological role and diagnostic value of ZBTB16 in pSS and T1DM.

Sjogren's Syndrome↗

PubMed2006

Association of complement factor H polymorphisms with exudative age-related macular degeneration.

PURPOSE: Variants in the complement factor H (CFH) gene have been reported to be associated with age-related macular degeneration (AMD). We conducted a case-control association study to investigate the association of 6 single nucleotide polymorphisms (SNPs) in CFH with exudative AMD in the Chinese population. METHODS: We recruited 163 cases and 244 controls, all ethnic Chinese, with complete ophthalmic examination including fundus investigation. Cigarette smoking was recorded. Six SNPs (dbSNP ID: rs3753394, rs800292, rs1061147, rs1061170, rs380390, and rs1329428) in the CFH gene were genotyped by Taqman assays. RESULTS: Y402H (1277 T>C) has low frequencies in our study population, 5.8% in patients and 3.9% in controls. It was not associated with exudative AMD adjusted for age, gender and smoking. Significant associations were detected for AMD with rs3753394 (p=0.003, p(corr)=0.018), rs800292 (p=0.00053, p(corr)=0.0032), and rs1329428 (p=0.00092, p(corr)=0.0028), p(corr) values obtained after adjustment for multicomparison. A haplotype containing these four SNPs (TGTC) was found to confer a significantly increased likelihood of exudative AMD with an odds ratio of 1.68 (95% CI: 1.26-2.23) p=0.0003 (p(corr)=0.0026 after correction by permutation test). Logistic regression analysis detected no interactions between the SNPs and age, gender or smoking. CONCLUSIONS: We have found differences in the association between the CFH gene and exudative AMD in Chinese from Caucasians and Japanese. We detected SNP rs3753394 in the CFH promoter carrying a significantly increased risk for exudative AMD.

Aged↗

PubMed2006

Yeast P4-ATPases Drs2p and Dnf1p are essential cargos of the NPFXD/Sla1p endocytic pathway.

Drs2p family P-type ATPases (P4-ATPases) are required in multiple vesicle-mediated protein transport steps and are proposed to be phospholipid translocases (flippases). The P4-ATPases Drs2p and Dnf1p cycle between the exocytic and endocytic pathways, and here we define endocytosis signals required by these proteins to maintain a steady-state localization to internal organelles. Internalization of Dnf1p from the plasma membrane uses an NPFXD endocytosis signal and its recognition by Sla1p, part of an endocytic coat/adaptor complex with clathrin, Pan1p, Sla2p/End4p, and End3p. Drs2p has multiple endocytosis signals, including two NPFXDs near the C terminus and PEST-like sequences near the N terminus that may mediate ubiquitin (Ub)-dependent endocytosis. Drs2p localizes to the trans-Golgi network in wild-type cells and accumulates on the plasma membrane when both the Ub- and NPFXD-dependent endocytic mechanisms are inactivated. Surprisingly, the pan1-20 temperature-sensitive mutant is constitutively defective for Ub-dependent endocytosis but is not defective for NPFXD-dependent endocytosis at the permissive growth temperature. To sustain viability of pan1-20, Drs2p must be endocytosed through the NPFXD/Sla1p pathway. Thus, Drs2p is an essential endocytic cargo in cells compromised for Ub-dependent endocytosis. These results demonstrate an essential role for endocytosis in retrieving proteins back to the Golgi, and they define critical cargos of the NPFXD/Sla1p system.

ATP-Binding Cassette Transporters↗

PubMed2006

Neuroprotective effects of safflor yellow B on brain ischemic injury.

The present study was conducted to investigate whether safflor yellow B (SYB) had a protective effect on cerebral ischemic injury and to determine the possible mechanisms in vivo and in vitro. In vivo, Male Wistar-Kyoto (WKY) rats were used to make the model of middle cerebral artery occlusion (MCAO). The behavioral test was used to measure neurological deficit scores for evaluation of the ischemic damage of brain. The infarction area of brain was assessed in brain slices stained with 2% solution of 2,3,5-triphenyl tetrazolium chloride (TTC). Spectrophotometric assay was used to determine the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), contents of malondialdehyde (MDA) and adenosine triphosphate (ATP) of the brain. Furthermore, the respiratory control ratio (RCR = state 3/state 4) was assessed in the brain mitochondria. In vitro, the effect of SYB was tested in cultured fetal cortical cells exposed to glutamate to identify its neuroprotection against neurons damage. The results in vivo showed that SYB at doses of 3.0 and 6.0 mg kg(-1) markedly decreased the neurological deficit scores and the infarction area in MCAO rats. At the same time, SYB significantly improved mitochondrial energy metabolism, decreased MDA content, and increased SOD and GPx activities in ischemic brain. The results in vitro showed that SYB remarkably inhibited neuron damage induced by glutamate in cultured fetal cortical cells. These suggest that SYB might act as a potential neuroprotective agent against the cerebral ischemia-induced injury in rat brain through reducing lipid peroxides, scavenging free radicals, and improving the energy metabolism.

Adenosine Triphosphate↗

PubMed2006

Roles for the Drs2p-Cdc50p complex in protein transport and phosphatidylserine asymmetry of the yeast plasma membrane.

Drs2p, a P-type adenosine triphosphatase required for a phosphatidylserine (PS) flippase activity in the yeast trans Golgi network (TGN), was first implicated in protein trafficking by a screen for mutations synthetically lethal with arf1 (swa). Here, we show that SWA4 is allelic to CDC50, encoding a membrane protein previously shown to chaperone Drs2p from the endoplasmic reticulum to the Golgi complex. We find that cdc50Delta exhibits the same clathrin-deficient phenotypes as drs2Delta, including delayed transport of carboxypeptidase Y to the vacuole, mislocalization of resident TGN enzymes and the accumulation of aberrant membrane structures. These trafficking defects precede appearance of cell polarity defects in cdc50Delta, suggesting that the latter are a secondary consequence of disrupting Golgi function. Involvement of Drs2p-Cdc50p in PS translocation suggests a role in restricting PS to the cytosolic leaflet of the Golgi and plasma membrane. Annexin V binding and papuamide B hypersensitivity indicate that drs2Delta or cdc50Delta causes a loss of plasma membrane PS asymmetry. However, clathrin and other endocytosis null mutants also exhibit a comparable loss of PS asymmetry, and studies with drs2-ts and clathrin (chc1-ts) conditional mutants suggest that loss of plasma membrane asymmetry is a secondary consequence of disrupting protein trafficking.

Amino Acid Sequence↗

PubMed2006

Computer simulation model on ultrasonic myocardial backscatter.

Myocardial ultrasonic tissue characterization with integrated backscatter (IB) has been studied in recent years. To evaluate the dynamic characters of the myocardium, dynamic tracing of each unit volume of myocardium is a key point. Thus, a 2D CVIB imaging algorithm based on an auto-tracing method was developed in our previous work. Where, an auto-tracking method was used in CVIB-weighted images so that the POI in each frame throughout the cardiac cycle is automatically traced to reflect the real myocardial tissue movement. It is necessary to validate the auto-tracing method. However, at present there are no appropriate models to support the process. In order to validate the auto-tracing method, two myocardium models have been established to simulate the short and long axis view of echocardiography. The motions of partially ischemic myocardium have been simulated. The models have been used to validate the 2D CVIB imaging methods in the detection of myocardial ischemia. The simulation results show that the auto-tracing algorithm is effective. The model developed in this work provides a tool for studying and developing technologies in myocardial behavior.

Algorithms↗

PubMed2006

Pharmacokinetics and in vitro and in vivo correlation of huperzine A loaded poly(lactic-co-glycolic acid) microspheres in dogs.

The purpose of this study was to investigate the pharmacokinetics and in vitro/in vivo correlation (IVIVC) of huperzine A loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in dogs. Several huperzine A loaded PLGA microspheres were prepared by an O/W method and three of them (single dose) were injected intramuscularly (i.m.) or subcutaneously (s.c.) to five beagle dogs, respectively. With the increase of the molecular weight of PLGA and the particle size of microspheres, the in vitro and in vivo release periods of huperzine A were prolonged. After s.c. injection, the release of huperzine A from microspheres was faster than that after i.m. injection. The IVIVC models of huperzine A loaded PLGA microspheres were established successfully and after i.m. administration the linear relationship between the in vitro and the in vivo releases was better than that after s.c. administration. It was also found when the particle size of the microspheres was smaller; the values of correlation coefficient were higher.

Alkaloids↗

PubMed2006

Role of a 5'-enhancer in the transcriptional regulation of the human endothelial cell protein C receptor gene.

The endothelial cell protein C receptor (EPCR) is expressed by endothelial cells of large blood vessels and by hematopoietic stem cells. DNaseI hypersensitive (DH) site mapping across 38 kb of the human EPCR gene (hEPCR) locus identified 3 potential regulatory elements. By itself, the DH region spanning the proximal promoter (PP) was unable to direct cell-specific transcription in transgenic mice. A second DH element, located upstream of PP and termed -5.5HS was hypersensitive only in endothelial cells (ECs) and immature hematopoietic cell lines. Transgenes expressing LacZ under the control of -5.5HS coupled to either PP or the SV40 promoter were able to direct beta-galactosidase activity to the endothelium of large vessels during embryogenesis and adulthood. The -5.5HS exhibited enhancer activity that was conferred by the interplay of transcription factors interacting with conserved Ets and composite GATA/Tal1 motifs. The third DH element, located in intron 2, was primarily hypersensitive in EPCR-negative cells, and capable of initiating antisense transcription, suggesting a role in hEPCR silencing. This study identifies critical elements required for the tissue specificity of hEPCR and suggests a mechanism for endothelial and hematopoietic stem cell-specific transcriptional regulation that reflects the common origin of these cell types.

5' Flanking Region↗

PubMed2006

Optical parameters and upconversion fluorescence in Tm3+/Yb3+-doped alkali-barium-bismuth-tellurite glasses.

Tm(3+)/Yb(3+)-doped alkali-barium-bismuth-tellurite (LKBBT) glasses have been fabricated and characterized. Density, refractive index, optical absorption, absorption and emission cross-sections of Yb(3+), Judd-Ofelt parameters and spontaneous transition probabilities of Tm(3+) have been measured and calculated, respectively. Intense blue three-photon upconversion fluorescence and near-infrared two-photon upconversion fluorescence were investigated under the excitation of a 980 nm diode laser at room temperature. Wide infrared transmission window, high refractive index and strong blue three-photon upconversion emission of Tm(3+) indicate that Tm(3+)/Yb(3+) co-doped LKBBT glasses are promising upconversion optical and laser materials.

Fluorescence↗

PubMed2006

Estimation of p-coumaric acid as metabolite of E-6-O-p-coumaroyl scandoside methyl ester in rat plasma by HPLC and its application to a pharmacokinetic study.

A rapid and simple high-performance liquid chromatographic (HPLC) method has been developed for the determination of p-coumaric acid in rat plasma and applied to a pharmacokinetic study in rats after administration of a prodrug, E-6-O-p-coumaroyl scandoside methyl ester, isolated from Hedyotis diffusa (Willd.). Sample preparation involved protein precipitation with acetonitrile. The supernatant was then injected onto a Diamonsil C(18) column (250 mm x 4.6mm i.d., 5 microm). The mobile phase consisted of acetonitrile-water (21:79, v/v) with 1% glacial acetic acid. The UV detector was set at 310 nm. The lower limit of quantification of p-coumaric acid in rat plasma was 0.02 microg/mL. The calibration curves were linear over the concentration range 0.02-5 microg/mL with correlations greater than 0.999. The assay procedure was applied to the study of the metabolite pharmacokinetics of E-6-O-p-coumaroyl scandoside methyl ester in rat.

Animals↗

PubMed2006

FasL expression in colorectal carcinoma and its significance in immune escape of cancer.

To study the significance of FasL expression in immune escape of colorectal carcinoma, FasL protein expression and the number of tumor infiltrating lymphocytes (TILs) in 80 specimens of colorectal carcinoma were detected by immunohistochemitry. The mRNA of FasL was measured by in situ hybridization in the consecutive tissue slices of 80 colorectal carcinomas respectively. Using terminal deoxynucleotidyl transferase-mediaed dUTP nick end labeling (TUNEL), apoptotic cells were detected in 80 specimens of colorectal carcinoma. The expression of FasL was detected in all 80 specimens, but it was not even in the same or among different tissues. In the consecutive tissue slices, the location of expression of FasL protein corresponded with that of FasL mRNA. In those with FasL extensive expression, the number of TILs was less than that of FasL weak expression (P < 0.05), and the apoptotic index (AI) of TILs was higher and that of tumor cells was lower than that of FasL with weak expression respectively (P < 0.01). The Al of TILs was correlated with that of tumor cells (r = -0.631, P < 0.01). It was suggested that colorectal carcinoma cells can induce the apoptosis of TILs through the expression of FasL, which can counterattack the immune system. This may be one of the mechanisms of immune evasion in colorectal carcinoma.

Adult↗

PubMed2006

neo-Clerodane diterpenoids from Scutellaria barbata with cytotoxic activities.

Three neo-clerodane diterpenoids, named barbatins A-C (1-3), and the neo-clerodane diterpenoid nicotinyl ester, named scutebarbatine B (4), were isolated from the whole plant of Scutellaria barbata D. Don. Their structures were elucidated by spectroscopic analyses (UV, IR, HRFAB-MS, 1D NMR and 2D NMR). In vitro, compounds 1-4 showed significant cytotoxic activities against three human cancer lines, namely, HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells, with IC50 values in the range 3.5-8.1 microM.

Cell Line, Tumor↗

PubMed2006

Pharmacokinetics and excretion of hydroxysafflor yellow A, a potent neuroprotective agent from safflower, in rats and dogs.

Studies were conducted to characterize the pharmacokinetics and excretion of hydroxysafflor yellow A (HSYA) in rats and dogs after administration by intravenous injection or infusion. Plasma, urine, feces and bile concentrations of HSYA were measured using five validated mild HPLC methods. Linear pharmacokinetics of HSYA after the intravenous administrations were found at doses ranging from 3 to 24 mg/kg in rats and from 6 to 24 mg/kg in dogs. At a dose of 3 mg/kg, HSYA in urine, feces and bile was determined. For 48 h after dosing, the amount of urinary excretion accounted for 52.6 +/- 17.9 % (range: 31.1 - 78.7%, n = 6) of the dose, and the amount of fecal amount accounted for 8.4 +/- 5.3% (range 1.7 - 16.4%, n = 6) of the dose. Biliary excretion amount accounted for 1.4 +/- 1.0% (range 0.4-2.9%; n = 6) of the dose for 24 h after dosing. Percent plasma protein binding of HSYA ranged from 48.0 to 54.6% at 72 h. In summary, five mild HPLC methods for the determinations of HSYA in rat plasma, urine, feces, bile and dog plasma have been developed and successfully applied to preclinical pharmacokinetics and excretion of HSYA in rats and dogs. The results of excretion studies indicated that HSYA was rapidly excreted as unchanged drug in the urine. In view of previous pharmacological work, the concentration-dependent neuroprotective effect of HSYA in rats was defined.

Animals↗

PubMed2006

Pharmacokinetics of huperzine A in dogs following single intravenous and oral administrations.

The pharmacokinetics of huperzine A in dogs after single intravenous and oral administrations was investigated. Concentrations of huperzine A were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were calculated by non-compartmental methods. After single intravenous administration, the Cmax, T1/2, AUC0-t, AUC0-infinity, CL, Vd and Vss were 5.55 +/- 1.61 microg/L, 5.02 +/- 0.31 h, 16.04 +/- 5.24, 16.49 +/- 5.29 microgh/L, 0.66 +/- 0.19 L/h/kg, 4.76 +/- 1.46, and 3.93 +/- 1.54 L/kg, respectively. After single oral administration, the Cmax, Tmax, T1/2, AUC0-t, AUC0-infinity and oral bioavailability were 2.60 +/- 0.60 microg/L, 1.25 +/- 0.50 h, 5.71 +/- 2.25 h, 12.90 +/- 3.19, 13.78 +/- 3.24 microgh/L, and 94.4 +/- 36.5%, respectively. In conclusion, huperzine A had a rapid and nearly complete oral absorption and was extensively distributed into tissues after drug administration in dogs.

Administration, Oral↗

PubMed2006

Ginsenoside Rh(2) enhances antitumour activity and decreases genotoxic effect of cyclophosphamide.

Ginsenoside Rh(2), a panaxadiol saponins, possesses various antitumour properties. Cyclophosphamide, an alkylating agent, has been shown to possess various genotoxic and carcinogenic effects, however, it is still used extensively as an antitumour agent and immunosuppressant in the clinic. Previous reports reveal that cyclophosphamide is involved in some secondary neoplasms. In this study, the antitumour activity and genotoxic effect of oral intake of ginsenoside Rh(2) combined with intraperitoneal injection of cyclophosphamide was investigated. Meanwhile, C57BL/6 mice bearing B16 melanoma and Lewis lung carcinoma cells were respectively used to estimate the antitumour activity in vivo. The clastogenic activity in bone marrow polychromatic erythrocytes was assayed by frequency of micronucleus. The DNA damage in peripheral white blood cells was assayed by single cell gel electrophoresis as well. The results indicated that oral administration of Rh(2) (5, 10 and 20 mg/kg body weight) alone has no obvious antitumour activity and genotoxic effect in mice, while Rh(2) synergistically enhanced the antitumour activity of cyclophosphamide (40 mg/kg body weight) in a dose-dependent manner. Rh(2) decreased the micronucleus formation in polychromatic erythrocytes and DNA strand breaks in white blood cells in a dose-dependent way. Our results suggest that ginsenoside Rh(2) is able to enhance the antitumour activity and decrease the genotoxic effect of cyclophosphamide.

Animals↗

PubMed2006

Ginsenoside 20(S)-protopanaxadiol inhibits the proliferation and invasion of human fibrosarcoma HT1080 cells.

Ginsenoside 20(S)-protopanaxadiol, one of metabolites of ginseng saponins, has been well characterized to possess the pleiotropic anticancer capabilities in several cancer cell lines. The object of this study was to investigate the effects of ginsenoside 20(S)-protopanaxadiol on the invasion in vitro and the expression of matrix metalloproteinase-2 in human fibrosarcoma HT1080 cells in absence of cytotoxicity. Our results showed that ginsenoside 20(S)-protopanaxadiol exerted a concentration-dependent inhibitory effect on the proliferation of HT1080 cells (IC50 was 76.78+/-2.24 microM, 48 hr). Treatment with 20(S)-protopanaxadiol significantly declined the invasive capacity of HT1080 cells compared to the control cells (P<0.01) in the in vitro invasion assay. Further analysis with gelatin zymography and western blotting revealed that both the activity and the expression of matrix metalloproteinase-2 decreased dramatically in a concentration-dependent manner (P<0.01). Taken together, these results indicated that ginsenoside 20(S)-protopanaxadiol is able to inhibit the invasiveness of HT1080 cells significantly in vitro and this action may be primarily due to down-regulating the expression of matrix metalloproteinase-2. Ginsenoside 20(S)-protopanaxadiol, a metabolite of ginseng, may be applied as a potential therapeutic agent in the prevention and treatment of cancer.

Antineoplastic Agents, Phytogenic↗

PubMed2006

Four new neo-clerodane diterpenoid alkaloids from Scutellaria barbata with cytotoxic activities.

Four new neo-clerodane diterpenoid alkaloids, named scutebarbatines C-F (1-4), were isolated from the whole plants of Scutellaria barbata D. DON. Their structures were elucidated by spectral analyses (UV, IR, FAB-MS, 1D-NMR and 2D-NMR). In vitro, compounds 1-4 showed significant cytotoxic activities against three human cancer cell lines, namely, HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells, and gave IC(50) values in the range 3.9-7.8 muM.

Cell Proliferation↗

PubMed2006

[Effects of Naomaitong Recipe on expressions of nuclear factor-kappaB and nitric-oxide synthases in brain tissue after focal cerebral ischemia reperfusion in aged rats].

OBJECTIVE: To study the effects of Naomaitong Recipe, a compound Chinese herbal medicine, on the expressions of nuclear factor-kappaB (NF-kappaB) and nitric-oxide synthases (NOSs) in brain tissue after focal cerebral ischemia reperfusion in aged rats and the dosage-effect relationship. METHODS: We adopted the middle cerebral artery occlusion (MCAO) in aged rats as the focal cerebral ischemia model, with 3-hour ischemia and 12-day reperfusion, and observed the changes of the nerve dysfunction score, the water content of cerebral constitution and the expressions of NF-kappaB, heat-shock protein 70 (HSP70) and NOSs in cerebral cortex. RESULTS: The nerve dysfunction score, the water content of cerebral constitution, the expressions of NF-kappaB, HSP70, neuronal nitric-oxide synthase (nNOS), endothelial nitric-oxide synthase (eNOS) and inducible nitric-oxide synthase (iNOS) in the untreated group were higher than those of the sham-operated group. The nerve dysfunction score, the water content of cerebral constitution, the expressions of NF-kappaB, iNOS and nNOS were lower, while the expressions of HSP70 and eNOS were higher in the high-, medium- and low-dose Naomaitong-treated groups and nimodipine-treated group than those of the untreated-group. The nerve dysfunction score and the expression of nNOS were lower, while the expression of eNOS was higher in the medium-dose Naomaitong-treated group than those of the nimodipine-treated group. The expressions of HSP70 and eNOS were higher, while the other indices were lower in the medium-dose Naomaitong-treated group than those of the low-dose Naomaitong-treated group. CONCLUSION: Naomaitong Recipe can protect the brain cells from damage after focal cerebral ischemia reperfusion injury by adjusting the expressions of NF-kappaB, HSP70 and NOSs, and the medium-dose Naomaitong Recipe is more effective.

Aging↗