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Biomedical subjects

H Liu

Publications and source records attributed to H Liu.

At least 37 records · Page 2Linked to original sources

Role of ERK1/2 in the anti-apoptotic and cardioprotective effects of nitric oxide after myocardial ischemia and reperfusion.

OBJECTIVE: Experimental results from cultured cells suggest that there is cross-talk between nitric oxide (NO) and extracellular signal-regulated kinase (ERK) in their anti-apoptotic effect. However, the cross-talk between these two molecules in either direction has not been confirmed in the whole organ or whole animal level. The aim of the present study was to determine whether ERK may play a role in the anti-apoptotic and cardioprotective effects of NO in myocardial ischemia/reperfusion (MI/R). METHODS: Isolated perfused mouse hearts were subjected to 20 min of global ischemia and 120 min of reperfusion and treated with vehicle or an NO donor (SNAP, 10 muM) during reperfusion. To determine the role of ERK1/2 in the anti-apoptotic and cardioprotective effects of NO, hearts were pre-treated (10 min before ischemia) with U0126, a selective MEK1/2 inhibitor (1 muM). RESULTS: Treatment with SNAP exerted significant cardioprotective effects as evidenced by reduced cardiac apoptosis (TUNEL and caspase 3 activity, p < 0.01), and improved cardiac functional recovery (p < 0.01). In addition, treatment with SNAP resulted in a 2.5-fold increase in ERK activation when compared with heart receiving vehicle. Pre-treatment with U0126 slightly increased post-ischemic myocardial apoptosis but had no significant effect on cardiac functional recovery in this isolated perfused heart model. However, treatment with U0126 completely blocked SNAP-induced ERK activation and markedly, although not completely, inhibited the cardioprotection exerted by SNAP. CONCLUSION: These results demonstrate that nitric oxide exerts its anti-apoptotic and cardioprotective effects, at least in part, by activation of ERK in ischemic/reperfused heart.

Animals↗

Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1.

In this study, we used small interfering RNA (siRNA) directed against vascular endothelial growth factor receptor 1 (vegfr1) mRNA to investigate the role of VEGFR1 in ocular neovascularization (NV). After evaluating many siRNAs, Sirna-027 was identified; it cleaved vegfr1 mRNA at the predicted site and reduced its levels in cultured endothelial cells and in mouse models of retinal and choroidal neovascularization (CNV). Compared to injection of an inverted control sequence, quantitative reverse transcriptase-PCR demonstrated statistically significant reductions of 57 and 40% in vegfr1 mRNA after intravitreous or periocular injection of Sirna-027, respectively. Staining showed uptake of 5-bromodeoxyuridine-labeled Sirna-027 in retinal cells that lasted between 3 and 5 days after intravitreous injection and was still present 5 days after periocular injection. In a CNV model, intravitreous or periocular injections of Sirna-027 resulted in significant reductions in the area of NV ranging from 45 to 66%. In mice with ischemic retinopathy, intravitreous injection of 1.0 mug of Sirna-027 reduced retinal NV by 32% compared to fellow eyes treated with 1.0 mug of inverted control siRNA. These data suggest that VEGFR1 plays an important role in the development of retinal and CNV and that targeting vegfr1 mRNA with siRNA has therapeutic potential.

Animals↗

Decapping the message: a beginning or an end.

Removal of the mRNA 5' cap is an important step in the regulation of mRNA stability. mRNAs are degraded by at least two distinct exonucleolytic decay pathways, one from the 5' end, and the second from the 3' end. Two major cellular decapping enzymes have been identified, and each primarily functions in one of the two decay pathways. The Dcp2 decapping enzyme utilizes capped mRNA as substrate and hydrolyses the cap to release m(7)GDP (N7-methyl GDP), while a scavenger decapping enzyme, DcpS, utilizes cap dinucleotides or capped oligonucleotides as substrate and releases m(7)GMP (N7-methyl GMP). In this review, we will highlight the function of different decapping enzymes and their role in mRNA turnover.

Animals↗

Preparation of novel cationic copolymer microspheres and evaluation of their function by in vitro and in vivo tests as pH-sensitive drug carrier systems.

Novel pH-sensitive copolymer microspheres containing methylacrylic acid and styrene cross-linking with divinylbenzene were synthesized by free radical polymerization. The microspheres that were formed were then characterized by Fourier-Transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), size analysis, and X-ray analysis. The copolymer microspheres showed pulsatile swelling behavior when the pH of the media changed. The pH-sensitive microspheres were loaded with diltiazem hydrochloride (DH). The release characteristics of the free drug and the drug-loaded microspheres were studied under both simulated gastric conditions and intestinal pH conditions. The in vivo evaluation of the pulsatile preparation was subsequently carried out using beagle dogs as experimental subjects. The results demonstrated that the drug release exhibited a pulsatile character both in vitro and in vivo.

Animals↗

Differentiation potential of human embryonic mesenchymal stem cells for skin-related tissue.

BACKGROUND: Mesenchymal stem cells (MSC) have the capacity to differentiate into cells of connective tissue lineages, including bone, fat, cartilage and muscle, but the differentiation of embryonic MSC into epidermal cells by mesenchymal-epithelial transition has not been confirmed. OBJECTIVES: To determine the biological characteristics of human embryonic MSC (hMSC) and their potential for differentiation into epithelial cells. METHODS: hMSC were derived from 4-7-week-old embryos; they were localized and isolated, then primary culture was done. The biological characteristics of hMSC were detected by immunohistochemical methods and flow cytometry. Their differentiation potential was determined by coculture with conditioning medium and in vivo injection. RESULTS: hMSC express the relative specific antigens of MSC, such as SH2, alpha-smooth actin, CD29, CD44, CD90 and S100. After stimulation and in vivo transplantation, hMSC possess the potential to differentiate into epidermal cells with the production of keratin 19 and E-cadherin. CONCLUSIONS: hMSC derived from the early human embryo have the ability to transform into epidermal cells in vivo and in vitro.

Animals↗

Expression of insulin-like growth factor-1 receptor, p-AKT and p-ERK1/2 protein in extramammary Paget's disease.

BACKGROUND: The insulin-like growth factor-1 (IGF-1) receptor (R)-induced phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/ERK signal transduction cascade, which have critical roles in prevention of apoptosis and regulation of cell cycle progression, plays an important role in tumorigenesis. The expression of IGF-1R, AKT and ERK1/2 has been described in some human malignancies, but not in extramammary Paget's disease (EMPD). OBJECTIVES: To study the expression of IGF-1R, p-AKT and p-ERK1/2 in EMPD and to evaluate the relationships among them. METHODS: Thirty-six tissue samples of 34 patients with primary EMPD were subjected to immunohistochemical staining for IGF-1R, p-AKT and p-ERK1/2. RESULTS: Of thirty-six EMPD tissue samples, 34, 34 and 28 were positive for IGF-IR, p-AKT and p-ERK1/2 expression, respectively; 27, 23 and 17 of the 36 specimens stained positive for IGF-IR, p-AKT and p-ERK1/2 in more than half of Paget's cells, respectively. There were significant correlations between the IGF-1R and p-AKT expression as well as between IGF-1R and p-ERK1/2 expression. Taken together, these results indicate that IGF-1R is overexpressed, and AKT and ERK1/2 are frequently phosphorylated in EMPD. CONCLUSIONS: Our study shows that the expression of IGF-1R and the induction of p-AKT and the p-ERK1/2 pathway may play an important role in the pathogenesis of EMPD. The IGF-IR system might be a potential therapeutic target in EMPD.

Aged↗

The costs and benefits in an unusual symbiosis: experimental evidence that bitterling fish (Rhodeus sericeus) are parasites of unionid mussels in Europe.

Interspecific symbiotic relationships involve a complex network of interactions, and understanding their outcome requires quantification of the costs and benefits to both partners. We experimentally investigated the costs and benefits in the relationship between European bitterling fish (Rhodeus sericeus) and freshwater mussels that are used by R. sericeus for oviposition. This relationship has hitherto been thought mutualistic, on the premise that R. sericeus use mussels as foster parents of their embryos while mussels use R. sericeus as hosts for their larvae. We demonstrate that R. sericeus is a parasite of European mussels, because it (i) avoids the cost of infection by mussel larvae and (ii) imposes a direct cost on mussels. Our experiments also indicate a potential coevolutionary arms race between bitterling fishes and their mussel hosts; the outcome of this relationship may differ between Asia, the centre of distribution of bitterling fishes, and Europe where they have recently invaded.

Animals↗

Association of asymptomatic oral candidal carriage, oral candidiasis and CD4 lymphocyte count in HIV-positive patients in China.

OBJECTIVES: To compare the prevalence of asymptomatic oral candidal carriage in healthy volunteers with human immunodeficiency virus (HIV)-positive patients in China, as well as to investigate the relationship between CD4+ lymphocyte count and oral candidal colonization or oral candidiasis. METHODS: Oral candidal carriage and oral candidiasis were investigated in 101 patients with HIV-infection seen at Youan Hospital, Beijing, China. Two hundred and seventeen healthy volunteers were involved as a control. Culture from saliva was used to test for the presence of oral Candida. CD4+ lymphocyte count was measured by flow cytometry. All data were analyzed statistically by SAS. RESULTS: Asymptomatic oral candidal carriage rate (28.6%) in HIV-positive group was similar to that in the healthy group (18.0%; P = 0.07). No significant difference in CD4+ lymphocyte count was found between oral Candida carriers and non-carriers among HIV-positive subjects (P = 0.89). However, the frequency of oral candidiasis increased with the decrease in CD4+ lymphocyte count (P < 0.0001), and pseudomembranous candidiasis was predominant in HIV-positive patients with CD4+ <200 cells microl(-1) (66.7%). CONCLUSIONS: In HIV-positive subjects, asymptomatic oral candidal colonization is not related to CD4+ lymphocyte count of blood, and the carriage rate is similar to that in the healthy population. Oral candidiasis is more likely to be observed in HIV-positive patients who have a low CD4+ lymphocyte count.

Adult↗

A flattening filter free photon treatment concept evaluation with Monte Carlo.

In principle, the concept of flat initial radiation-dose distribution across the beam is unnecessary for intensity modulated radiation therapy. Dynamic leaf positioning during irradiation could appropriately adjust the fluence distribution of an unflattened beam that is peaked in the center and deliver the desired uniform or nonuniform dose distribution. Removing the flattening filter could lead to reduced treatment time through higher dose rates and reduced scatter, because there would be substantially less material in the beam; and possibly other dosimetric and clinical advantages. This work aims to evaluate the properties of a flattening filter free clinical accelerator and to investigate its possible advantages in clinical intensity modulated radiation therapy applications by simulating a Varian 2100-based treatment delivery system with Monte Carlo techniques. Several depth-dose curves and lateral dose distribution profiles have been created for various field sizes, with and without the flattening filter. Data computed with this model were used to evaluate the overall quality of such a system in terms of changes in dose rate, photon and electron fluence, and reduction in out-of-field stray dose from the scattered components and were compared to the corresponding data for a standard treatment head with a flattening filter. The results of the simulations of the flattening filter free system show that a substantial increase in dose rate can be achieved, which would reduce the beam on time and decrease the out-of-field dose for patients due to reduced head-leakage dose. Also close to the treatment field edge, a significant improvement in out-of-field dose could be observed for small fields, which can be attributed to the change in the photon spectra, when the flattening filter is removed from the beamline.

Journal Article↗

Separation of THF and water by room temperature ionic liquids.

Liquid-liquid equilibrium data are presented for mixtures of 1-(2-hydroxyethyl)-3-methylimidazolium chloride or tetrafluoroborate + tetrahydrofuran(THF) + water at 293.15 K. The data presented provides a valuable insight into how the environmentally friendly ionic liquid solvent can have the separation power of THF-water azeotropic systems. The sloping of the tie lines towards the THF vertex is investigated for mixtures of 1-(2-hydroxyethyl)-3-methylimidazolium chloride (or tetrafluoroborate) + THF + water. Selectivity values, derived from the tie line data, indicate that these two ionic liquids are suitable solvents for the liquid-liquid extraction of water from THF.

Borates↗

Stimulative activity of Drynaria fortunei (Kunze) J. Sm. extracts and two of its flavonoids on the proliferation of osteoblastic like cells.

The osteoblastic activity of extracts of Drynaria fortunei (Kunze) J. Sm. rhizome was assayed in the UMR106 cell line cultured in vitro. An ethanol extract and its fractions were added to the cell culture at different concentrations. Osteoblastic proliferation stimulating activity was determined using the MTT method. The ethanol extract, and its ethyl acetate and n-butanol fractions exhibited stimulating activity. Two active constituents were isolated from n-butanol fraction by bioassay-directed isolation, and identified as naringin and neoeriocitrin. The latter is reported for the first time from this herbal medicine.

Cell Line↗

Perinatal seizures preferentially protect CA1 neurons from seizure-induced damage in prepubescent rats.

Neonatal seizures may increase neuronal vulnerability later in life. Therefore, status epilepticus was induced with kainate (KA) during the first and second postnatal (P) weeks to determine whether early seizures shift the window of neuronal vulnerability to a younger age. KA was injected (i.p.) once (1x KA) on P13, P20 or P30 or three times (3 x KA), once on P6 and P9, and then either on P13, P20 or P30. After 1x KA, onset to behavioral seizures increased with age. Electroencephalography (EEG) showed interictal events appeared with maturation. After 3 x KA, spike number, frequency, spike amplitude, and high-frequency synchronous events and duration were increased at P13 when compared to age-matched controls. In contrast, P20 and P30 rats had decreases in EEG parameters relative to P20 and P30 rats with 1x KA despite that these animals had the same history of perinatal seizures on P6 and P9. In P13 rats with 1x KA, silver impregnation, hematoxylin/eosin and TUNEL methods showed no significant hippocampal injury and damage was minimal with 3 x KA. In contrast, P20 and P30 rats with 1x KA had robust eosinophilic or TUNEL positive labeling and preferential accumulation of silver ions within inner layer CA1 neurons. After 3 x KA, the CA1 but not CA3 of P20 and P30 rats was preferentially protected following 3 or 6 days. Although paradoxical changes occur in the EEG with maturation, the results indicate that early perinatal seizures do not significantly shift the window of hippocampal vulnerability to an earlier age but induce a tolerance that leads to long-term neuroprotection that differentially affects endogenous properties of CA1 versus CA3 neurons.

Aging↗

Optical characterization of the nematic lyotropic chromonic liquid crystals: light absorption, birefringence, and scalar order parameter.

We report on the optical properties of the nematic (N) phase formed by lyotropic chromonic liquid crystals (LCLCs) in well aligned planar samples. LCLCs belong to a broad class of materials formed by one-dimensional molecular self-assembly and are similar to other systems such as "living polymers" and "wormlike micelles." We study three water soluble LCLC forming materials: disodium chromoglycate, a derivative of indanthrone called Blue 27, and a derivative of perylene called Violet 20. The individual molecules have a planklike shape and assemble into rodlike aggregates that form the phase once the concentration exceeds about 0.1 M. The uniform surface alignment of the N phase is achieved by buffed polyimide layers. According to the light absorption anisotropy data, the molecular planes are on average perpendicular to the aggregate axes and thus to the nematic director. We determined the birefringence of these materials in the N and biphasic N-isotropic (I) regions and found it to be negative and significantly lower in the absolute value as compared to the birefringence of typical thermotropic low-molecular-weight nematic materials. In the absorbing materials Blue 27 and Violet 20, the wavelength dependence of birefringence is nonmonotonic because of the effect of anomalous dispersion near the absorption bands. We describe positive and negative tactoids formed as the nuclei of the new phase in the biphasic N-I region (which is wide in all three materials studied). Finally, we determined the scalar order parameter of the phase of Blue 27 and found it to be relatively high, in the range 0.72-0.79, which puts the finding into the domain of general validity of the Onsager model. However, the observed temperature dependence of the scalar order parameter points to the importance of factors not accounted for in the athermal Onsager model, such as interaggregate interactions and the temperature dependence of the aggregate length.

Journal Article↗

Site-directed mutagenesis of gentisate 1,2-dioxygenases from Klebsiella pneumoniae M5a1 and Ralstonia sp. strain U2.

Gentisate 1,2-dioxygenase (GDO, EC 1.13.11.4) is the first enzyme in gentisate pathway that catalyses the ring fission of gentisate to form maleylpyruvate. Phylogenetic tree of amino acid sequences from 11 GDOs demonstrates that the GDOs from different genus share identities between 12.1% and 64.8%. According to the alignment result, four highly conserved histidine residues in GDO from Klebsiella pneumoniae M5a1 and Ralstonia sp. strain U2 were chosen to be substituted with aspartate residues. Enzyme analysis indicated that substitution of any of these four histidine residues had resulted in the complete loss of its catalytic activity.

Amino Acid Sequence↗