Biomedical subjects

F Liu

Publications and source records attributed to F Liu.

At least 37 records · Page 2Linked to original sources

PubMed2006

Differentiation of hematopoietic stem cells into hepatocytes in liver fibrosis in rats.

It has been reported that hematopoietic stem cells (HSC) can differentiate into hepatocytes in the normal liver and in some pathologic environments. The aim of this study was to investigate whether HSC can differentiate into hepatocytes in cases of established liver fibrosis. Rat liver fibrosis was induced by subcutaneous injection of tetrachloride (CCl4). Thy+ CD3- CD45RA- HSC in bone marrow cells, which had been enriched by fluorescence-activated cell sorting (FACS), were labeled with PKH26-GL, and autologously transplanted into CCl4-treated rats. The expressions of albumin (Alb), cytokeratin 8 (CK8), and alpha-smooth muscle actin (SMA) were determined by immunofluorescence methods. The PKH26-GL labeled Thy+ CD3- CD45RA- HSC expressed the hepatocyte-specific markers Alb and CK8, but did not express alpha-SMA in liver fibrosis. Thy+ CD3- CD45RA- HSC differentiated into hepatocytes, but not into hepatic stellate cells. In conclusion, autologous stem cell transplantation may be helpful to treat hepatic fibrosis.

Animals↗

PubMed2006

Overexpression of von Hippel-Lindau tumor suppressor protein and antisense HIF-1alpha eradicates gliomas.

The von Hippel-Lindau tumor suppressor protein (pVHL) suppresses tumor formation by binding the alpha subunits of hypoxia-inducible-factors responsible for stimulating tumor angiogenesis and glycolysis, and targeting them for ubiquitination and proteasomal destruction. Loss of pVHL leads to tumorigenesis and development of sporadic renal cell carcinomas and central nervous system hemangioblastomas. In the present study, we investigated whether engineered overexpression of pVHL in C6 glioma cells, which already express endogenous pVHL, would suppress the tumorigenicity of this particular tumor cell type. C6 cells overexpressing VHL displayed a reduced growth rate (70% inhibition) compared to the parental cell line when subcutaneously implanted in athymic (nu/nu) mice. Growth inhibition was associated with a 50% reduction in the number of tumor vessels and a 60% increase in tumor cell apoptosis, due in part to downregulation of HIF-1, VEGF, and the antiapoptotic factor Bcl-2, respectively. Gene transfer of VHL suppressed the growth of established C6 gliomas, and synergized with antisense HIF-1 to completely eradicate tumors. The data suggest that VHL gene therapy and/or agents that increase VHL expression could have utility in the treatment of gliomas, particularly when combined with agents that inhibit the expression or function of HIF-1.

Animals↗

PubMed2006

Upregulation of osteopontin gene expression in diabetic rat proximal tubular cells revealed by microarray profiling.

Progression of diabetic nephropathy appears directly related to renal tubulointerstitial injury, but the involved genes are incompletely delineated. To identify such genes, DNA microarray analysis was performed with RNA from renal proximal tubules (RPTs) of streptozotocin-induced diabetic Wistar rats, spontaneously diabetic BioBreeding rats, and rat immortalized renal proximal tubular cells (IRPTCs) exposed to high glucose (25 mM) medium for 2 weeks. Osteopontin (OPN) mRNA expression was quantified by real time-quantitative polymerase chain reaction (RT-qPCR) or conventional reverse transcriptase-polymerase chain reaction (RT-PCR). OPN mRNA expression was upregulated (5-70-fold increase) in diabetic rat RPTs and in IRPTCs chronically exposed to high glucose compared to control RPTs and IRPTCs. High glucose, angiotensin II, phorbol 12-myristate 13-acetate and transforming growth factor-beta 1 (TGF-beta1) stimulated OPN mRNA expression in IRPTCs in a dose- and time-dependent manner. This effect was inhibited by tiron, taurine, diphenylene iodinium, losartan, perindopril, calphostin C, or LY 379196 but not PD123319. IRPTCs overexpressing dominant-negative protein kinase C-beta 1 (PKC-beta1) cDNA or antisense TGF-beta1 cDNA prevented the high glucose effect on OPN mRNA expression. We concluded that high glucose-mediated increases in OPN gene expression in diabetic rat RPTs and IRPTCs are mediated, at least in part, via reactive oxygen species generation, intrarenal rennin-angiotensin system activation, TGF-beta1 expression, and PKC-beta1 signaling.

Angiotensin II↗

PubMed2006

RAS blockade decreases blood pressure and proteinuria in transgenic mice overexpressing rat angiotensinogen gene in the kidney.

Angiotensinogen (ANG) is the sole substrate of the renin-angiotensin system (RAS). Clinical studies have shown that RAS activation may lead to hypertension, a major cardiovascular and renal risk factor. To delineate the underlying mechanisms of hypertension-induced nephropathy, we generated transgenic mice that overexpress rat ANG (rANG) in the kidney to establish whether intrarenal RAS activation alone can evoke hypertension and kidney damage and whether RAS blockade can reverse these effects. Transgenic mice overexpressing renal rANG were generated by employing the kidney-specific, androgen-regulated protein promoter linked to rANG cDNA. This promoter targets rANG cDNA to renal proximal tubules and responds to androgen stimulation. Transgenic mice displayed kidney-specific expression of rANG, significantly increased blood pressure (BP) and albuminuria in comparison to non-transgenic littermates. Administration of losartan (an angiotensin II (type 1)-receptor antagonist) or perindopril (an angiotensin-converting enzyme inhibitor) reversed these abnormalities in transgenic animals. Renal injury was evident on examination of the kidneys in transgenic mice, and attenuated by losartan and perindopril treatment. We conclude that the overproduction of ANG alone in the kidney induces an increase in systemic BP, proteinuria, and renal injury. RAS blockers prevent these abnormalities. These data support the role of the intrarenal RAS in the development of hypertension and renal injury.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2006

Dorsal hippocampal administration of triiodothyronine enhances long-term memory for trace cued and delay contextual fear conditioning in rats.

Thyroid hormones play critical roles in brain maturation and cognitive functions. The present study investigated the role of thyroid hormone in emotional learning and memory using trace and delay contextual and cued fear conditioning tasks, respectively. Rats were administered triiodothyronine (T3) into the dorsal hippocampal area 10 min before training or immediately after training, and were scored for freezing behaviour in the same context and in a novel context with and without an auditory cue that had been paired previously with an aversive stimulus, a foot shock. Rats administered T3 before and after training both exhibited significantly increased long-term fear memory in the trace cued and the delay contextual fear conditioning procedures compared to their control groups. The T3-administered rats were not significantly different from their respective controls on the acquisition and short-term fear memory in the trace and delay fear conditioning tasks. No significant difference on long-term trace contextual and delay cued fear memory, respectively, was found. These results indicate that the observed T3-induced enhancement of long-term contextual and cued fear memory was specific to the hippocampus-dependent conditioning tasks. These findings are the first to demonstrate that infusion of T3 into the dorsal hippocampus can improve performance on an emotional memory task.

Animals↗

PubMed2006

Ignoring distant genealogic loops leads to false-positives in homozygosity mapping.

Distant consanguineous loops are often unknown or ignored during homozygosity mapping analysis. This may potentially lead to an increased rate of false-positive linkage results. We show that failure to take into account the distant loops may seriously underestimate the degree of consanguinity, especially for people from genetically isolated populations; in 6 Alzheimer's disease (AD) patients the distant loops accounted for 57.7 % of inbreeding on average. Theoretical evaluation showed that ignoring distant loops, which account for 18-75% of inbreeding, inflates the frequency of false positive conclusions substantially in 2-point linkage analysis, up to several hundred times. In multipoint linkage analysis of the 6 AD patients a chromosome-wide "empirical" significance of 5% corresponded to a true false positive rate of 11.1%. We show that converting multiple loops to a hypothetical loop capturing all inbreeding may be a convenient solution to avoid false positive results. When extended genealogic data are not available a hypothetical loop may still be constructed based on genomic data.

Alzheimer Disease↗

PubMed2006

ADAMTS-13 plasma level determination uncovers antigen absence in acquired thrombotic thrombocytopenic purpura and ethnic differences.

BACKGROUND: The recently discovered plasma enzyme ADAMTS-13 cleaves the A2-domain of von Willebrand factor (VWF). A defective cleaving protease results in unusually large VWF multimers, which cause thrombotic thrombocytopenic purpura (TTP). AIM: Analysis of the ADAMTS-13 antigen levels in TTP patients compared with normal donors. METHODS: An antigen ELISA test was built, based on high affinity anti-ADAMTS-13 monoclonal antibodies, which were generated using genetic immunization. RESULTS: Specificity of the ADAMTS-13 antigen test was confirmed, as (i) plasma from a patient with acquired TTP but presenting without inhibitor did not contain antigen and (ii) the binding of recombinant ADAMTS-13 was inhibited by increasing amounts of normal plasma. The assay is sensitive as it can detect antigen levels as low as 1.6% of normal. The concentration in normal pooled human plasma was determined (1.03 +/- 0.15 microg mL(-1)) and arbitrarily set to 1 U mL(-1). The antigen levels in congenital TTP samples (34 +/- 21 mU mL(-1), n = 2), as well as in samples from patients with acquired TTP (231 +/- 287 mU mL(-1), n = 11), were clearly reduced when compared with normal Caucasian donors (951 +/- 206 mU mL(-1), n = 16). Remarkably, normal Chinese donors have a significantly lower antigen titer (601 +/- 129 mU mL(-1), n = 15), when compared with normal Caucasians. CONCLUSIONS: Our results show that acquired TTP patients suffer mainly from ADAMTS-13 antigen depletion, thereby indicating the importance of ADAMTS-13 antigen determination in diagnosis and patient follow-up.

ADAM Proteins↗

PubMed2006

A polysaccharopeptide complex and a condensed tannin with antioxidant activity from dried rose (Rosa rugosa) flowers.

In this study, the fraction (P) from an aqueous extract of dried rose (Rosa rugosa) flowers was obtained by ethanol precipitation. P was chromatographed on DEAE-cellulose. The components retained on DEAE-cellulose were eluted with a linear gradient of 0-2 M NaCl solution. Two fractions, eluted at concentrations of 0.5 M NaCl and 1 M NaCl, respectively, were obtained. These two components were designated as P1 and P2, respectively. P1 was further purified using gel filtration on Sephadex G-200. P(1) yielded two peaks, and the two components were designated as P(1-a) and P(1-b), respectively. P(1-a) was a polysaccharide-peptide complex, and P(1-b) exhibited chemical properties of a condensed tannin as revealed by FTIR and NMR assay of carbohydrate and protein contents and HPLC-ESI-MS. The molecular masses of P(1-a) and P(1-b) were 150 kDa and 8 kDa, respectively. Both P(1-a) and P(1-b) possessed antioxidant activity, with the activity of P(1-b) higher than that of P(1-a). This study demonstrated that different components from rose flowers exhibited antioxidant activity.

Animals↗

PubMed2006

Compounds from rose (Rosa rugosa) flowers with human immunodeficiency virus type 1 reverse transcriptase inhibitory activity.

The aqueous extracts and ethanol precipitates of aqueous extracts of 18 medicinal herbs traditionally used in China were screened for their ability to inhibit human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) in-vitro. Among the samples screened at a concentration of 500 microg mL-1, dried rose (Rosa rugosa) flowers showed the strongest inhibition. The ethanol precipitate of the aqueous extract of R. rugosa was processed and two components (P1 and P2) were obtained after ion exchange chromatography on DEAE-cellulose. Then, P1-a (Mr 150 kDa) and P1-b (Mr 8 kDa) were isolated from P1 by gel filtration on Sephadex G-200. They inhibited the activity of HIV-1 RT with an IC50 of 158 nM and 148.16 microg mL-1 (18.5 microM), respectively. Further structural analyses revealed that P1-a was a polysaccharide-peptide complex, and P1-b was a polymer consisting of acteoside and acteoside derivatives identified by Fourier transform infrared spectroscopy, nuclear magnetic resonance, assays of carbohydrate and protein contents and high-performance liquid chromatography electrospray ionization mass spectrometry.

Chromatography, Gel↗

PubMed2006

Hyperphosphorylation of tau and protein phosphatases in Alzheimer disease.

Aggregation of abnormal hyperphosphorylated tau to neurofibrillary tangles in affected neurons is one of the hallmarks for Alzheimer disease (AD). Studies during the last decade have strongly suggested that hyperphosphorylation of tau is site-specifically responsible for the loss of biological activity, the gain of toxic activity, and the aggregation into paired helical filaments. Hence, the abnormal hyperphosphorylation of tau appears to be critical to the pathogenesis of AD. The state of tau phosphorylation is controlled by a balance between tau phosphatase(s) activity and tau kinase(s) activity. Many studies have shown that hyperphosphorylation of tau in AD brain might be due to decreased tau phosphatase(s) activity. This article reviews the recent research advances in regulation of tau phosphorylation by phosphoseryl/phosphothreonyl protein phosphatases, and also summarizes the role of each tau phosphatase on abnormal hyperphosphorylation of tau in AD brain.

Alzheimer Disease↗

PubMed2006

Electrodynamic heart model construction and ECG simulation.

OBJECTIVES: In this paper, we present a unified electrodynamic heart model that permits simulations of the body surface potentials generated by the heart in motion. The inclusion of motion in the heart model significantly improves the accuracy of the simulated body surface potentials and therefore also the 12-lead ECG. METHODS: The key step is to construct an electromechanical heart model. The cardiac excitation propagation is simulated by an electrical heart model, and the resulting cardiac active forces are used to calculate the ventricular wall motion based on a mechanical model. The source-field point relative position changes during heart systole and diastole. These can be obtained, and then used to calculate body surface ECG based on the electrical heart-torso model. RESULTS: An electromechanical biventricular heart model is constructed and a standard 12-lead ECG is simulated. Compared with a simulated ECG based on the static electrical heart model, the simulated ECG based on the dynamic heart model is more accordant with a clinically recorded ECG, especially for the ST segment and T wave of a V1-V6 lead ECG. For slight-degree myocardial ischemia ECG simulation, the ST segment and T wave changes can be observed from the simulated ECG based on a dynamic heart model, while the ST segment and T wave of simulated ECG based on a static heart model is almost unchanged when compared with a normal ECG. CONCLUSIONS: This study confirms the importance of the mechanical factor in the ECG simulation. The dynamic heart model could provide more accurate ECG simulation, especially for myocardial ischemia or infarction simulation, since the main ECG changes occur at the ST segment and T wave, which correspond with cardiac systole and diastole phases.

Electrocardiography↗

PubMed2005

Observation of a resonance in Chi(1835) in J/psi --> gammapi+ pi- eta-.

The decay channel J/psi --> gamma(pi)(+)pi(-)eta is analyzed using a sample of 5.8 x 10(7) J/psi events collected with the BESII detector. A resonance, the Chi(1835), is observed in the pi(+)pi(-)eta invariant-mass spectrum with a statistical significance of 7.7 sigma. A fit with a Breit-Wigner function yields a mass M = 1833.7 +/- 6.1(stat) +/- 2.7(syst) MeV/c(2), a width Tau = 67.7 +/- 20.3(stat) +/- 7.7(syst) MeV/c(2), and a product branching fraction B(J/psi --> gammaChi) . B(Chi --> pi(+)pi(-)eta) = [2.2 +/- 0.4(stat) +/- 0.4(syst)] x 10(-4). The mass and width of the Chi(1835) are not compatible with any known meson resonance. Its properties are consistent with expectations for the state that produces the strong pp mass threshold enhancement observed in the J/psi --> gammapp process at BESII.

Journal Article↗

PubMed2005

Precision measurements of the timelike electromagnetic form factors of pion, kaon, and proton.

Using 20.7 pb(-1) of e(+)e(-) annihilation data taken at sq.rt(r) = 3.671 GeV with the CLEO-c detector, precision measurements of the electromagnetic form factors of the charged pion, charged kaon, and proton have been made for timelike momentum transfer of |Q(2)| = 13.48 GeV(2) by the reaction e(+)e(-) --> h(+)h(-). The measurements are the first ever with identified pions and kaons of |Q(2)| > 4 GeV(2), with the results F(13.48 GeV(2)) = 0.075 +/- 0.008(stat) +/- 0.005(syst) and F(K)(13.48 GeV(2)) = 0.063 +/- 0.004(stat) +/- 0.001(syst). The result for the proton, assuming G(p)(E) = G(p)(M), is G(p)(M)(13.48 GeV(2)) = 0.014 +/- 0.002(stat) +/- 0.001(syst), which is in agreement with earlier results.

Journal Article↗

PubMed2005

Secondary degeneration reduced by inosine after spinal cord injury in rats.

STUDY DESIGN: Assessment of the potential protective effects of inosine on an animal model of spinal cord injury. OBJECTIVES: Our previous studies have demonstrated that inosine can directly protect neurons in vitro from zinc-induced injury and axotomized retinal ganglion cells of rats in vivo. This investigation was carried out to examine the possible protective effects of inosine on spinal cord secondary degeneration. SETTING: Institute of Neurosciences, The Fourth Military Medical University, Xi'an, China. METHODS: Compressive spinal cord injury (95-g load for 1 min) model was established in rats, and inosine was administrated beginning at different time points (2, 12, or 24 h) after spinal cord injury. RESULTS: Using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and hematoxylin and eosin staining, our study demonstrated that administration of inosine as late as 12 h after injury significantly reduced the total volume of spinal cord degenerative areas and the number of apoptotic cells 3 days following the trauma. CONCLUSION: Inosine can significantly reduce the spread of secondary degeneration and the cell death following spinal cord injury in adult rats. These findings may find a clinical application in the treatment of acute spinal cord injury.

Animals↗

PubMed2005

Search for rare and forbidden decays D+ --> h+/- e+/- e+.

Using 0.8 x 10(6) D+ D- pairs collected with the CLEO-c detector at the psi(3770) resonance, we have searched for flavor-changing neutral current and lepton-number-violating decays of D+ mesons to final states with dielectrons. We find no indication of either, obtaining 90% confidence level upper limits of B(D+ --> pi+ e+ e-) < 7.4 x 10(-6), B(D+ --> pi- e+ d+) < 3.6 x 10(-6), B(D+ --> K+ e+ e-) < 6.2 x 10(-6), and B(D+ --> K- e+ e+) < 4.5 x 10(-6).

Journal Article↗

PubMed2005

A technique to detect and to quantify fasciocutaneous blood vessels in small laboratory animals ex vivo.

PURPOSE: A microangiographical technique is described, which allows visualization of small and capillary blood vessels and quantification of fasciocutaneous blood vessels by means of digital computer analysis in very small laboratory animals. MATERIALS AND METHODS: The left carotid artery of 20 nu/nu mice was cannulated (26 gauge) and a mixture of gelatin, bariumsulfate, and green ink was injected according to standardized protocol. Fasciocutaneous blood vessels were visualized by digital mammography and analyzed for vessel length and vessel surface area as standardized units [SU] by computer program. RESULTS: With the described microangiography method, fasciocutaneous blood vessels down to capillary size level can be clearly visualized. Regions of interest (ROIs) can be defined and the containing vascular network quantified. Comparable results may be obtained by calculating the microvascular area index (MAI) and the microvascular length index (MLI), related to the ROIs size. Identical ROIs showed a high reproducibility for measured [SU] < 0.01 +/- 0.0012%. CONCLUSION: Combining microsurgical techniques, pharmacological knowledge, and modern digital image technology, we were able to visualize small and capillary blood vessels even in small laboratory animals. By using our own computer analytical program, quantification of vessels was reliable, highly reproducible, and fast.

Angiography↗

PubMed2005

Absolute branching fraction measurements of exclusive D+ semileptonic decays.

Using data collected at the psi(3770) resonance with the CLEO-c detector at the Cornell e+e- storage ring, we present improved measurements of the absolute branching fractions of D+decays to K0e+ve, pi0e+ve, K*0e+ve, and p0e+ve, and the first observation and absolute branching fraction measurement of D+ --> omega e+ve. We also report the most precise tests to date of isospin invariance in semileptonic D0 and D+ decays.

Journal Article↗

PubMed2005

Absolute branching fraction measurements of exclusive D0 semileptonic decays.

With the first data sample collected by the CLEO-c detector at the psi(3770) resonance we have studied four exclusive semileptonic decays of the D0 meson. Our results include the first observation and absolute branching fraction measurement for D0 --> p-e+ve and improved measurements of the absolute branching fractions for D0 decays to K-e+ve, pi-e+ve, and K*-e+ve.

Journal Article↗