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Biomedical subjects

S Qu

Publications and source records attributed to S Qu.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of hepatocarcinoma by systemic delivery of Apoptin gene via the hepatic asialoglycoprotein receptor.

Specificity is a prerequisite for systemic gene therapy of hepatocarcinoma. In vitro, the tumor-specific viral death effector Apoptin selectively induces apoptosis in malignant hepatic cells. Intratumoral treatment of xenografted subcutaneous hepatomas with Apoptin results in tumor regression. Here, we report a systemic delivery vehicle containing the Apoptin gene linked to asialoglycoprotein (Asor), which targets asialoglycoprotein receptor (ASGPR) present only on the surface of hepatocytes. In vitro, the protein-DNA complex Asor-Apoptin induced apoptosis in HepG2 hepatocarcinoma cells but not in normal L-02 hepatocytes. Non-hepatocyte-derived tumorigenic human A549 cells lacking the membrane ASGPR were not affected by Asor-Apoptin. In vivo systemic delivery of Asor-Apoptin via the tail vein into mice bearing in situ hepatocarcinoma resulted in specific and efficient distribution of Apoptin in both hepatocarcinoma cells and normal hepatocytes. Five days after injection of Asor-Apoptin, the in situ hepatocarcinomas showed significant signs of regression, whereas the surrounding normal hepatocytes did not. Systemically delivered Asor-LacZ expressing non-apoptotic LacZ gene did not inhibit tumor growth. Our data reveal that systemic delivery of Asor-Apoptin specifically induces apoptosis in malignant hepatocytes and thus constitutes a powerful and safe therapeutics against hepatocarcinomas.

Animals↗
PubMed2005

Projections of diencephalic dopamine neurons into the spinal cord in mice.

The aim of this study is to investigate the pathway of diencephalic dopaminergic (DA) neuronal innervating into the spinal cord in mice, the pathway is postulated relevant to clinical restless legs syndrome (RLS). Tyrosine hydroxylase (TH) immunohistochemistry was used to identify the DA neuron. The fluorescent tracer Fluoro-Gold (FG) was stereotaxically injected into the T10-L5 spinal cord of CBL57 mice (n=20) seven days before the animals were sacrificed. The diencephalic sections were stained with TH antibody and the FG tracer present in the diencephalic DA neurons were examined under fluoresce microscope. The average number of total DA neurons per side in A11, A12, A13 and A14 was 66+/-8, 221+/-12, 350+/-17 and 254+/-21 respectively. After being injected into the spinal cord, FG reached the DA neurons within the A10 and A11 groups, but didn't target to any other DA neuron groups including the A8 and A9 groups in substantia nigra (SN). The diencephalic A11 DA neurons possessed long axons extending over several segments and possibly traversing the entire length of the spinal cord. It is the first time to report A10 and A11 DA neuron projections into the spinal cord in mice.

Animals↗
PubMed2005

Inhibition of angiogenesis is associated with reduced islet engraftment in diabetic recipient mice.

Rapid reestablishment of a functional microvasculature in transplanted islets is crucial for islet survival and function. To illustrate the importance of angiogenesis in islet engraftment, we took a loss-of-function approach to block angiogenesis in newly transplanted islets and determined the extent of islet engraftment in correlation with islet mass and glycemic control in diabetic recipient mice. Diabetic mice were transplanted with a marginal mass of 200 islets under the renal capsule, followed by once-daily oral administration of saline or 150 mg/kg of C-statin, a potent angiogenic inhibitor, for 14 days. Blood glucose profiles and the amplitude of glucose-stimulated insulin secretion in engrafted islets were determined. At 30 days posttransplant, islet grafts were retrieved for the determination of insulin content and vascular density by immunohistochemistry. When compared to sham-treated controls, diabetic recipient mice receiving a daily oral dose of C-statin exhibited significantly impaired blood glucose profiles and diminished glucose-stimulated insulin secretion in response to glucose challenge, correlating with significantly reduced intragraft insulin content and vascular density. Selective inhibition of angiogenesis was associated with reduced islet mass in diabetic mice. These data extend our view that rapid onset of angiogenesis is crucial for islet survival and engraftment and support the development of therapeutic strategies to stimulate angiogenesis in newly implanted islets for enhancing islet engraftment and improving the outcome of marginal islet transplantation.

Angiogenesis Inhibitors↗
PubMed2005

Functional polymorphisms in cell death pathway genes FAS and FASL contribute to risk of lung cancer.

BACKGROUND: The FAS and FASL system plays a key role in regulating apoptotic cell death and corruption of this signalling pathway has been shown to participate in immune escape and tumorigenesis. There is reduced expression of FAS but elevated expression of FASL in many types of human cancers including lung cancer. We recently reported an association between functional polymorphisms in FAS (-1377G-->A) and FASL (-844T-->C) and risk of oesophageal cancer. OBJECTIVE: To examine the contribution of these polymorphisms to risk of developing lung cancer. METHODS: Genotypes of 1000 lung cancer patients and 1270 controls were analysed by PCR based restriction fragment length polymorphism. Associations with risk of lung cancer were estimated by logistic regression. RESULTS: Compared with non-carriers, there was a 1.6 fold excess risk of developing lung cancer for carriers of the FAS -1377AA genotype (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.21 to 2.10; p = 0.001), and 1.8 fold excess risk (OR 1.79, 95% CI 1.26 to 2.52; p = 0.001) for carriers of FASL -844CC. Gene-gene interaction of FAS and FASL polymorphisms increased risk of lung cancer in a multiplicative manner (OR for the carriers of both FAS -1377AA and FASL -844CC genotypes 4.18, 95% CI 2.83 to 6.18). Gene-environment interaction of FAS or FASL polymorphism and smoking associated with increased risk of lung cancer was also found. CONCLUSION: These results are consistent with our initial findings in oesophageal cancer and further support the hypothesis that the FAS and FASL triggered apoptosis pathway plays an important role in human carcinogenesis.

Aged↗
PubMed2003

The recent expansion of Pluto's atmosphere.

Stellar occultations--the passing of a relatively nearby body in front of a background star--can be used to probe the atmosphere of the closer body with a spatial resolution of a few kilometres (ref. 1). Such observations can yield the scale height, temperature profile, and other information about the structure of the occulting atmosphere. Occultation data acquired for Pluto's atmosphere in 1988 revealed a nearly isothermal atmosphere above a radius of approximately 1,215 km. Below this level, the data could be interpreted as indicating either an extinction layer or the onset of a large thermal gradient, calling into question the fundamental structure of this atmosphere. Another question is to what extent Pluto's atmosphere might be collapsing as it recedes from the Sun (passing perihelion in 1989 in its 248-year orbital period), owing to the extreme sensitivity of the equilibrium surface pressure to the surface temperature. Here we report observations at a variety of visible and infrared wavelengths of an occultation of a star by Pluto in August 2002. These data reveal evidence for extinction in Pluto's atmosphere and show that it has indeed changed, having expanded rather than collapsed, since 1988.

Journal Article↗
PubMed2001

The binding ability analysis of the normal VLDL receptor and its mutant.

The ligand-binding domain of VLDL receptor contains eight imperfectly similar repeats. To discuss the contribution of each repeat to ligand binding, the RT-PCR technique was used to clone the VLDLR-cDNA from the heart muscle of Chinese people. Two recombinants were further constructed, which contained the full-length cDNA of VLDLR and the mutant lacking repeats 1-5. CHO cell line was transfected with two recombinants. The expression of VLDLR gene could be detected by RT-PCR from the CHO cells transfected with pCD-VR. The results of binding experiments showed that the ability of the CHO cells transfected with the full-length cDNA of VLDL-R binding DiI-labeled beta-VLDL was higher than that of the CHO cells transfected with the mutant. Our findings indicated that human VLDL-R gene could be expressed effectively on CHO cells, and the receptor was almost inactivated when repeats 1-5 were deleted.

Animals↗
PubMed2001

Cloning and identification of a novel variant of human vascular endothelial growth factor.

A novel variant of human vascular endothelial growth factor (h'VEGF165) cDNA was amplified by nested PCR method from the HL601 cells and was cloned into a eukaryotic expressing vector pcDNA3 to construct a recombinant plasmid pCD-h'VEGF165. The amplified h'VEGF165 cDNA fragment was identified by enzyme digestion and DNA sequencing methods. Also, wild-type hVEGF165 cDNA was obtained, identified and cloned into a eukaryotic expressing vector pcDNA3 by using the same methods. The results of DNA sequencing showed that h'VEGF165 cDNA cloned from HL601 was 600 bp in size with 8% of the base sequence in h'VEGF165 cDNA being changed as compared with the base sequence in the wild-type hVEGF165 cDNA. The results of sequencing of hVEGF165 which was cloned from HL60 by us were consistent with the reports completely.

Base Sequence↗
PubMed2001

Human vascular endothelial growth factor cDNA cloning and expression in osteoblasts.

Human vascular endothelial growth factor (VEGF) cDNA was amplified by nested polymerase chain reaction method from the HL60 cells. Then a pCD-hVEGF165 recombinant plasmid was constructed. Rabbit osteoblasts were transfected with pCD-hVEGF165 plasmid by lipofectin mediated gene transfer. The transient expressive results were detected by immunohistochemical method. It was observed that the expression of human VEGF gene was detected 72 h after transfecting distinctly.

Animals↗
PubMed2001

Radiation-mediated control of drug delivery.

Clinical trials of radiotherapy to control drug delivery were initiated in 1999 at Vanderbilt University. The initial studies exploited the findings that platelets are activated in tumor blood vessels after high-dose irradiation as used in radiosurgery and high-dose-rate brachytherapy. Platelets labeled with 111In showed binding in tumor blood vessels. However, the platelet labeling process caused platelets to also accumulate in the spleen. That clinical trial was closed, and subsequent clinical trials targeted protein activation in irradiated tumor blood vessels. Preclinical studies showed that peptide libraries that bind within irradiated tumor blood vessels contained the peptide sequence Arg-Gln-Asp (RGD). RGD binds to integrin receptors (e.g., receptors for fibrinogen, fibronectin, and vitronectin). We found that the fibrinogen receptor (GPIIb/IIIa, alpha2bbeta3) is activated within irradiated tumor blood vessels. RGD peptidemimetics currently in clinical trials include GPIIb/IIIa antagonists and the platelet-imaging agent biapcitide. Biapcitide is an RGD mimetic that is labeled with 99Tc to allow gamma camera imaging of the biodistribution of the GPIIb/IIIa receptor in neoplasms of patients treated with radiosurgery. This study has shown that the schedule of administration of the RGD mimetic is crucial. The peptide mimetic must be administered immediately before irradiation, whereas the natural ligands to the receptor compete for biapcitide binding if biapcitide is administered after irradiation. The authors currently are conducting a dose deescalation study to determine the threshold dosage required for RGD mimetic binding to radiation activated receptor. Radiation-guided clinical trials have been initiated by use of high-dose-rate brachytherapy. In a separate trial, the pharmacokinetics of radiation-inducible gene therapy are being investigated. In this trial, the radiation-activated promoter Egr-1 regulates expression of the tumor necrosis factor alpha gene, which is administered by use of the attenuated adenovirus vector. The Ad.Egr-TNF (ADGV) gene is administered by intratumoral injection of vector followed by irradiation in patients with soft-tissue sarcomas. This review highlights recent findings in these phase I pharmacokinetic studies of radiation-controlled drug delivery systems.

Animals↗
PubMed2001

[Intraspinal implantation of genetically modified myoblasts with brain-derived neurotrophic factor gene in treating spinal cord injury in rats: neurophysiological study].

OBJECTIVE: To observe the value of gene therapy to spinal cord injury in vivo by transferring gene of brain-derived neurotrophic factor (BDNF) to rat myoblast with retroviral vector electrophysiologically. METHODS: Transection of spinal cord at the level of T9 was produced in 30 adult SD rats that were divided randomly into three groups: BDNF gene modified myoblast implantation (group A), myoblast implantation (group B), and no cell implantation as controls (group C). Three months after operation, whether the axon had regenerated and how the neural function was restored were observed, using the techniques of cerebral somatosensory evoked potential (CSEP) and motor evoked potential (MEP). RESULTS: Three months after injury, 3 rats in group A showed CSEP signals and 5 rats MEP signals, but no electrophysiological response was found in group B or group C. The amplitudes of the recovery of CSEP or MEP signals decreased and their latencies increased as compared with those before injury. The neural function of the spinal cord was greater in group A than in B and C. CONCLUSION: Treatment with genetically modified myoblasts producing BDNF can accelerate recovery from traumatic spinal cord injury in adult rats.

Animals↗
PubMed2001

[Effects of angiotensin II on proliferation and expression of interleukin-6 of human kidney fibroblasts].

OBJECTIVE: To investigate the effects of Angiotensin(Ang) II on the proliferation and expression of Interleukin (IL)-6 in human kidney fibroblasts(KFB). METHODS: The human KFB were cultured and identified, the proliferation of KFB was measured by MTT, and the level of IL-6 was measured by radioimmunoassay(RIA). RESULTS: Angiotensin II could stimulate the proliferation of KFB and enhance the expression of IL-6 in protein level on KFB. CONCLUSION: Angiotensin II can stimulate KFB's proliferation and enhance the expression of IL-6 of KFB. These findings suggest that Ang II might play a part in the mechanisms for modulating tubulointerstitial changes and induceing renal fibrosis.

Angiotensin II↗
PubMed2001

[A therapeutical approach by administering reduced glutathione to patients with uremic anemia].

OBJECTIVE: To verify the therapeutical effect of exogenous reduced glutathione (GSH) on the patients with uremic anemia. METHODS: Forty two patients with uremic anemia were randomly divided into treatment group and control group. All patients received subcutaneously recombinant human erythropoietin (r-HuEPO) at the dose of 3000U twice a week for 12 weeks. Each of the patients in the treatment group was given intravenously reduced glutathione at the dose of 1200 mg twice a week for 12 weeks. The measurements of hemoglobin, red blood cells and hematocrit were performed. RESULTS: After administration of r-HuEPO, the levels of hemoglobin, red blood cells and hematocrit were significantly elevated in both treatment and control groups (P < 0.01). The levels of hemoglobin, red blood cells and hematocrit in treatment group were elevated much more obviously, compared with those in control group (P < 0.05). CONCLUSION: These findings seem to indicate that exogenous GSH could enhance the effect of r-HuEPO on uremic anemia, and therefore it might represent a useful drug in the treatment and management of uremic anemia.

Adult↗
PubMed2000

Characterization of peroxide ions in hydroxyapatite lattice.

The incorporation of peroxide ions was confirmed in the heat treatment of hydroxyapatite (HA) powder under air as well as under oxygen atmosphere, by using X-ray diffraction, Raman, and infrared spectroscopy. Peroxide ions associated with vacancies were sited in the channel of HA lattice along the c-axis through the substitution of a portion of OH radicals. The molecular ions constituted a symmetric vibrator with a stretching vibration active in Raman spectrometry. This vibration was recorded at 750 cm(-1) in the Raman spectra of O(2)(2-)-containing HA samples. The final product was a solid solution of hydroxyl- and peroxide-apatite. However, the existence of peroxide ions in the HA lattice caused the contraction of the unit-cell dimensions of HA materials. In addition, a new hydrogen bond was formed between peroxide ions and adjacent OH radicals by using molecular spectroscopy analysis. During annealing treatment in air, peroxide ions decomposed and the substituted OH radicals re-enter the HA lattice, resulting in the elimination of the structural aberrations caused by the incorporation of peroxide ions. Concentration of the peroxide ions included in HA samples was measured by chemical analysis.

Biocompatible Materials↗
PubMed2000

Cloning and expression of rat transforming growth factor beta 1 cDNA in osteoblasts.

Rat transforming growth factor beta 1 (rTGF beta 1) cDNA from rat lymphocytes was cloned by RT-PCR and inserted into pcDNA3 to construct an eukaryotic expression vector, which was named pcDNA3-TGF beta 1. The cloned gene was confirmed to code rat TGF beta 1 by restriction enzyme analysis. pcDNA3-TGF beta 1 plasmid was transfected into rat osteoblasts by using liposome-mediated gene transfer technique and the expression of TGF beta 1 was detected by using immunohistochemical staining assay. It was found that the rat TGF beta 1 expression product was obviously detectable in the transfected osteoblasts in 48 h. High expression of TGF beta 1 was obtained in the rat osteoblasts in which the constructed TGF beta 1 expression vector was transfected.

Animals↗
PubMed2000

Investigation of the distribution and changes of VLDLR subtype in fibrotic cardiac muscles.

Very low-density lipoprotein receptor (VLDLR) is the major receptor with which cells can uptake the triacylglycerol from blood. It is divided into two subtypes according to presence of O-linked sugar domain located in the VLDLR receptor immediately outside of the membrane. Type I VLDLR contains the O-link domain, while type II has no such domain. The type I VLDLR are mainly found on the surface of human myocardial cells. The result of our quantitative polymerase chain reaction on the normal and fibrotic cardiac muscles showed that both subtypes and expression level of VLDLR on the myocardial cell surface did not vary significantly between the normal and the fibrotic cardiac muscles despite the presence of malfunction due to fibrosis. This finding suggests that fibrosis doesn't exert significant influence on the subtype and the expression of VLDLR on the surface of myocardial cells. Such inconsistence with the changes found in other fibrotic tissues is awaiting further studies.

Fibrosis↗
PubMed2000

Microcalorimetric study of Escherichia coli growth inhibited by the selenomorpholine complexes.

The inhibitory or antibiotic action of four kinds of the selenomorpholine complex on a strain of Escherichia coli was studied by microcalorimetry. Differences in their capacities to inhibit the metabolism of this bacterium were observed. The extent and duration of the inhibitory effect on the metabolism as judged from the rate constant, k, and the half-inhibitory concentration, IC50, varied with the different drugs. The rate constant (k) of Escherichia coli (in the log phase) in the presence of the drugs decreased with increasing concentrations of the drugs (C). The relationship of k and C is nearly linear for (1) selenomorpholine and (2) selenomorpholine hydrochloride, but for (3) N,N'-methylene bisselenomorpholine and (4) N-dodecyl selenomorpholine, it is not linear. The experimental results reveal that the sequence of antibiotic activity of selenomorpholines is (3) and (4) > (1) > (2).

Calorimetry↗
PubMed2000

Microcalorimetric study of the toxic effect of sodium selenite on the mitochondria metabolism of Carassius auratus liver.

The fundamental thermogenesis curves of the metabolic process of liver mitochondria from Carassius auratus and the toxic effect of Na2SeO3 on it were studied by using an LKB-2277 bioactivity monitor, ampoule method, at 28 degrees C. From the thermogenesis curves, the thermokinetic equations were established under different conditions. The kinetics show that a low concentration of Na2SeO3 (1-4 mg/L) had promoting action on the metabolism process of Carassius aurantus liver mitochondria, but that a high concentration of Na2SeO3 (8-16 mg/L) inhibited the mitochondria metabolism.

Animals↗