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Biomedical subjects

X Y Liu

Publications and source records attributed to X Y Liu.

At least 19 recordsLinked to original sources

Potent antitumor efficacy of XAF1 delivered by conditionally replicative adenovirus vector via caspase-independent apoptosis.

XAF1 is a newly identified tumor-suppressor gene that can antagonize XIAP and sensitize cells to other cell death triggers. In this study, we utilized ZD55, a conditionally replicative adenovirus (CRAd) similar to ONYX-015 as the vector to transfer XAF1 into the tumor cells to evaluate its antitumor efficacy in vitro and in vivo. Potent and specific cytopathic effect (CPE) was observed upon infection with ZD55-XAF1 in tumor cell lines. Importantly, ZD55-XAF1 exhibited a superior suppression of tumor growth in an animal model of colorectal carcinoma in nude mice compared with Ad-XAF1 (E1-deleted replication-defective viral) and ONYX-015. Complete eradication of the established tumors was observed in four of eight mice. Our data also showed that infection with ZD55-XAF1 resulted in caspase-independent apoptosis. Although caspase-3, poly(ADP-ribose) polymerase were mildly activated in response to ZD55-XAF1 infection, pretreatment with pan-caspase inhibitor hardly influence its apoptosis-inducing activity. In summary, our study strongly suggested that ZD55-XAF1 could serve as an effective gene-virotherapy strategy and has highly potential against human cancers.

Adaptor Proteins, Signal Transducing↗

Evaluation of cytotoxic activities of some medicinal polypore fungi from China.

The petrol ether, ethyl acetate and methanol extracts of eight medicinal polypore fungi from China were evaluated for cytotoxic activities using MTT-dye assay. All the petrol ether and ethyl acetate extracts exhibited cytotoxicity against human cervix epitheloid carcinoma cell lines (Hela) and human hepatoma cell lines (SMMC-7721). Cytotoxicity activity was also observed in the methanol extracts of Phellinus conchatus and Pycnoporus sanquineus, but the methanol extracts from Cryptoporus volvatus, Fomitopsis pinicola, Fomes hornodermus, Lenzites betulina, Trametes gibbosa and Trametes orientalis showed weak activity when compared with quercetin.

Antibiotics, Antineoplastic↗

Mesoscopic resistance fluctuations in cobalt nanoparticles.

We present measurements of mesoscopic resistance fluctuations in cobalt nanoparticles and study how the fluctuations with bias voltage, bias fingerprints, respond to magnetization-reversal processes. Bias fingerprints rearrange when domains are nucleated or annihilated. The domain wall causes an electron wave function-phase shift of approximately equal to 5pi. The phase shift is not caused by the Aharonov-Bohm effect; we explain how it arises from the mistracking effect, where electron spins lag in orientation with respect to the moments inside the domain wall. Dephasing time in Co at 0.03 K is short, tau phi approximately 1 ps, which we attribute to the strong magnetocrystalline anisotropy.

Journal Article↗

Pathogenic effects of the coccidium Eimeria ninakohlyakimovae in goats.

Twenty-four coccidia-free goats were reared artificially in indoor cages and allocated to 6 groups of 4 animals each. At 20 days of age, goats in groups 1-3 received 10(4),10(5) and 10(6) sporulated oocysts of Eimeria ninakohlyakimovae per goat, respectively, each as a single dose. Goats in group 4 received daily doses increasing over a 3-week period, starting with 100/day for the first week, followed by 1000, and 10,000/day in weeks 2, 3, respectively. Goats in group 5 received 10(4) oocysts following a challenge dose of 10(6) oocysts on day 32. Goats in group 6 were kept as uninoculated controls. Infected animals showed diarrhoea and weight loss. Goats in group 4 showed longer periods of diarrhoea and patency than other infected goats. Goats in group 5 showed the same severe clinical signs as those in group 3 but produced very low oocyst output after a challenge dose. The diarrhoea was associated with a reduction in alkaline phosphatase activity and increases in packed cell volume and haemoglobin. No significant differences were found in serum aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, Na+, K+,Cl- between groups during 48 days after inoculation. There were no serum enzyme indications of damage to the liver. Histological examination performed 100 days after inoculation revealed that inoculated goats had mild subacute to chronic proliferative enteritis in the lower small intestine and the large intestine, and the mesenteric lymph nodes, gallbladders and livers also showed slight histological lesions. The results showed that E. ninakohlyakimovae was highly pathogenic.

Alanine Transaminase↗

Traditional Chinese medicine Bao Gan Ning increase phosphorylation of CREB in liver fibrosis in vivo and in vitro.

Previous studies have demonstrated that traditional Chinese medicine Bao Gan Ning, which contains six different drugs: Trionyx sinensis Wiegmann shell, Prunus persica (L.) Batsch seed, Salvia miltiorrhiza Bge. root, Mallotus opelta (Lour.) Muell-Arg root, Astragalus membranaceus (Fisch.) Bge. var. mongho-licus (Bge.) Hsiao root and Scutellaria baicalensis Georgi root, was able to protect liver against fibrosis in CCL4 models. In an effort to elucidate molecular mechanisms by which Bao Gan Ning exerts its anti-fibrosis activity, effects of Bao Gan Ning on liver fibrosis and cAMP response element binding protein (CREB), an important transcription factor involved in liver fibrosis, were evaluated in animal and cell models in this work. Results showed that Bao Gan Ning (2.16 or 4.32 g/kg/day) significantly decreased alanine aminotransferase (ALT) and hyaluronidase levels and reversed liver fibrosis in rat liver fibrosis models. The proliferation of HSC-T6, a hepatic stellate cell line, was also significantly inhibited by incubation with serums that were prepared from rats fed with Bao Gan Ning. Most interestingly, results from Western blot, immunohistochemistry and electrophoretic mobility shift assay (EMSA) showed that Bao Gan Ning up-regulated CREB phosphorylation both in rat liver fibrosis models and in HSC-T6 cells, but did not affect protein level of CREB and the DNA binding activity of CREB. These results suggested that up-regulation of CREB phosphorylation may be involved in anti-fibrosis activity of Chinese medicine Bao Gan Ning.

Animals↗

Corrosion resistance, surface mechanical properties, and cytocompatibility of plasma immersion ion implantation-treated nickel-titanium shape memory alloys.

Nickel-titanium shape memory alloys are promising materials in orthopedic applications because of their unique properties. However, for prolonged use in a human body, deterioration of the corrosion resistance of the materials becomes a critical issue because of the increasing possibility of deleterious ions released from the substrate to living tissues. We have investigated the use of nitrogen, acetylene, and oxygen plasma immersion ion implantation (PIII) to improve the corrosion resistance and mechanical properties of the materials. Our results reveal that the corrosion resistance and mechanical properties such as hardness and elastic modulus are significantly enhanced after surface treatment. The release of nickel is drastically reduced as compared with the untreated control. In addition, our in vitro tests show that the plasma-treated surfaces are well tolerated by osteoblasts. Among the three types of samples, the best biological effects are observed on the nitrogen PIII samples.

Alloys↗

SMGA gels for the skin permeation of haloperidol.

Small molecule gelling agent (SMGA) gels were developed using the gelator GP-1 in the solvents, namely, isostearyl alcohol (ISA) and propylene glycol (PG), to deliver haloperidol through the skin. The concentrations of the drug, haloperidol, the enhancer, farnesol and the gelator, GP-1 are 3 mg/ml, 5% (w/v) and 5% (w/v), respectively. The study employed a three-factor full factorial statistical design to investigate the influence of factor level changes on the permeability coefficient and permeation lag-time of haloperidol. Gels were prepared by raising temperature to 120 degrees C, followed by natural cooling under room temperature of 22+/-1 degrees C. The rheological properties of the gels were examined with a strain-controlled dynamic mechanical method. The in vitro permeation study was conducted with automated flow-through type cells. The gels successfully incorporated the drug and enhancer without losing their aesthetic properties. The in vitro human skin permeation study showed the permeation of the drug in ISA-based gels reached the pseudo steady state faster than PG-based gels and were less affected by gelator. PG-based gels delivered the drug at a faster rate with the incorporation of the enhancer. GP-1 did not influence the drug permeation rate but it increased permeation lag-time. The co-existence of gelator or enhancer increased the lag-time to a larger extent than when used separately. The novel SMGA gels are suitable for topical or transdermal delivery.

Administration, Cutaneous↗

Molecular dynamics simulation of paracetamol molecules ordering around glycogen.

By the use of classical atomistic molecular dynamics simulations, we demonstrate that paracetamol molecules exist in a highly ordered phase in the presence of a glycogen substrate at 317 K whereas the paracetamol fluid exists in an isotropic phase in the absence of the glycogen substrate at the same temperature. This result further validates the studies made on polysaccharide regarding its abilities to promote nucleation of paracetamol via liquid preordering. As little is known regarding liquid ordering induced by a polymeric substrate, we seek to explore the ordering mechanism from an energy perspective. This is accomplished using conformation mappings. Our analysis shows that the conformation space accessible to the paracetamol molecule at 317 K in the vicinity of glycogen is smaller than the one in the absence of glycogen. An investigation on the orientation of the dipole moments of the glycogen monomers and paracetamol molecules were carried out as well. From the investigations, we show that dipolar interactions play an important role in the ordering process. These studies bear significance to the understanding of the ordering process as well as the promotion and effective control of the nucleation rate.

Acetaminophen↗

Investigation of nickel suppression and cytocompatibility of surface-treated nickel-titanium shape memory alloys by using plasma immersion ion implantation.

Nickel-titanium (NiTi) shape memory alloys are increasingly being used in orthopedic applications. However, there is a concern that Ni is harmful to the human body. We have recently investigated the use of nitrogen, or oxygen plasma immersion ion implantation to mitigate this deleterious effect. Our results reveal that the near-surface Ni concentration in all the treated samples is significantly suppressed. In addition, our in vitro tests show that the plasma-treated surfaces are cytologically compatible allowing the attachment and proliferation of osteoblasts. Among the two types of samples, the best biological effects are found on the samples with nitrogen implantation.

Animals↗

Carbon plasma immersion ion implantation of nickel-titanium shape memory alloys.

Nickel-titanium (NiTi) shape memory alloys possess super-elasticity in addition to the well-known shape memory effect and are potentially suitable for orthopedic implants. However, a critical concern is the release of harmful Ni ions from the implants into the living tissues. We propose to enhance the corrosion resistance and other surface and biological properties of NiTi using carbon plasma immersion ion implantation and deposition (PIII&D). Our corrosion and simulated body fluid tests indicate that either an ion-mixed amorphous carbon coating fabricated by PIII&D or direct carbon PIII can drastically improve the corrosion resistance and block the out-diffusion of Ni from the materials. Our tribological tests show that the treated surfaces are mechanically more superior and cytotoxicity tests reveal that both sets of plasma-treated samples favor adhesion and proliferation of osteoblasts.

Animals↗

Bioactivity of titanium following sodium plasma immersion ion implantation and deposition.

Bio-activation of titanium surface by Na plasma immersion ion implantation and deposition (PIII and D) is illustrated by precipitation of calcium phosphate and cell culture. The bioactivity of the plasma-implanted titanium is compared to that of the untreated, Na beam-line implanted and NaOH-treated titanium samples. Our data show that the samples can be classified into two groups: non-bioactive (untreated titanium and beam-line Na implanted titanium) and bioactive (Na-PIII and D and NaOH-treated titanium). None of the four types of surfaces exhibited major cell toxicity as determined by lactate dehydrogenase (LDH) release. However, the LDH release was higher on the more bioactive PIII and NaOH-treated surfaces. From a morphological point of view, cell adherence on the NaOH-treated titanium is the best. On the other hand, the cell activity and protein production were higher on the non-bioactive surfaces. The high alkaline phosphatase activity per cell suggests that the active surfaces support an osteogenic differentiation of the bone marrow cells at the expense of lower proliferation. The use of Na-PIII and D provides an environmentally cleaner technology to improve the bioactivity of Ti compared to conventional wet chemical processes. The technique is also particularly useful for the uniform and conforming treatment of medical implants that typically possess an irregular shape and are difficult to treat by conventional ion beam techniques.

Animals↗

Chitosan/cellulose acetate microspheres preparation and ranitidine release in vitro.

New microspheres containing hydrophilic core and hydrophobic coating as a controlled-release system with no toxic reagents were proposed. Water in oil in water (W/O/W) emulsion and solvent evaporation methods were used to make chitosan/ cellulose acetate (CCA) microspheres sized 200 - 400 microm. Ranitidine hydrochloride, as a model drug, was investigated for its release properties in vitro. The loading efficiency and release rate of ranitidine were affected by chitosan concentration and molecular weight. Higher loadings were obtained at lower concentrations in the interval of 1% to 2%. With chitosan at a 2% concentration microspheres could be obtained with more spherical appearance, smaller size, and higher ranitidine loading efficiency microspheres than at other concentrations. Among the different molecular weight chitosan (47, 145, 308, 499, and 1130 KD) microspheres, the high molecular weight chitosan (1130 KD) microspheres had relatively high loading efficiency (10%). Molecular weight and concentration of chitosan as well as the size of microspheres affected the release of ranitidine. Microspheres smaller than 280 microm released the drug faster than did the bigger by about 10%. The optimal condition for the preparation of the microspheres was chitosan concentration 2%, molecular weight 1130 KD. The ranitidine release from the microspheres was 30% during 48 h in phosphate-buffer saline medium.

Administration, Oral↗

Icariin, a flavonoid from the herb Epimedium enhances the osteogenic differentiation of rat primary bone marrow stromal cells.

The herb Epimedium has long been used in Traditional Chinese Medicine to treat bone fracture and prevent osteoporosis. Researchers believe that the flavonoids contained in the herb are the effective component for this activity. However, no single flavonoid has been studied for its effect on bone-related cells. In the present study, icariin, one of the major flavonoids of the herb, supplemented the primary culture medium of rat bone marrow stromal cells (rMSCs) at 0.1 microM , 1 microM and 10 microM respectively. It was found that icariin stimulated the proliferation of rMSCs and increased the number of CFU-F stained positive for alkaline phosphatase in a dose-dependent manner. Icariin also dose-dependently increased the alkaline phosphatase activity, osteoalcin secretion and calcium deposition level of rMSCs during osteogenic induction. The addition of 10 microM icariin caused four times more mineralized bone nodules to be formed by rMSCs than in the control. The results demonstrated that icariin should be an effective component for bone-strengthening activity, and one of the mechanisms is to stimulate the proliferation and enhance the osteogenic differentiation of MSCs.

Alkaline Phosphatase↗

Surfactant free fabrication of polymeric nanoparticles by combined liquid-liquid phase separation and solvent/nonsolvent mixing technology.

It is generally agreed that, in most cases, surfactants are required to obtain stable polymeric nanoparticle dispersions. Here, we report a method which can be used to produce surfactant free yet stable polymeric nanoparticle dispersions. This method is based on explored mechanism of selective solvation of nanoparticles and EPD (electron pair donor)/EPA (electron pair acceptor) complexes formed among solvent and nonsolvent molecules. Using polyimide P84 (copolyimide 3,3(') 4,4(')-benzophenone tetracarboxylic dianhydride and 80% methylphenylene diamine+20% methylene dianiline) as the model polymer, this mechanism was realized through a combined liquid-liquid phase separation and solvent/nonsolvent mixing technology. Surfactant-free polyimide nanoparticles (<100 nm) were produced. Experimental details and principles of this technology were given based on the ternary diffusion, the liquid-liquid phase separation and the advanced nucleation and growth theory. Two types of methods [denoted as the forward titration method and the backward titration (BT) method] were examined. It was found that the BT method is extremely helpful to prepare polyimide nanoparticles (<100 nm). As another important aspect, explored stabilization mechanism of the resultant nanoparticle dispersions was supported by the comparative experiments, implying that selective solvation of nanoparticles and EPD/EPA complexes may play key roles in stabilization.

Benzophenones↗

Protein interactions in undersaturated and supersaturated solutions: a study using light and x-ray scattering.

Protein interactions in undersaturated and supersaturated solutions were investigated using static and dynamic light scattering and small angle x-ray scattering. A morphodrom of lysozyme crystals determined at 35 degrees C and pH = 4.6 was used as a guideline in selecting the protein and precipitant concentrations. The osmotic second virial coefficient, B(22), was determined by static and dynamic light scattering. At low ionic strengths for which no crystals were formed, B(22) was positive indicating repulsive interactions between the protein molecules. Negative B(22) at higher ionic strengths corresponds to attractive interactions where crystallization becomes possible. At two extreme salt concentrations, small angle x-ray scattering data were collected and fitted with a statistical mechanical model based on Derjaguin-Landau-Verwey-Overbeek potential using Random Phase Approximation. This model accounted well for the small angle x-ray scattering data at undersaturated condition with constant potential parameters. At very high salt concentration corresponding to supersaturated solution this model seems to fail, possibly due to the presence of non-Derjaguin-Landau-Verwey-Overbeek hydration repulsion between the molecules.

Animals↗

Adenovirus-mediated interleukin-2 gene therapy of nociception.

The effect of adenovirus-mediated interleukin-2 (IL-2) gene on rat basal nociceptive response and chronic neuropathic pain was explored. The paw withdrawal latency induced by radiant heat was used to evaluate the antinociceptive effect of adenovirus type 5 (Ad5) and Ad5-IL-2. The results showed that intrathecal delivery of Ad5-IL-2 exhibited obvious antinociceptive effects on basal nociceptive response and chronic neuropathic pain, which were maintained for 3 and 4 weeks, respectively. This suggested that the antinociceptive effect of Ad5-IL-2 on chronic neuropathic pain was greater than its effect on basal nociceptive response. Human IL-2 mRNA was detected by in situ hybridization in the spinal pia mater and parenchyma of the lumbar, sacral, thoracic and cervical regions, and gray matter had higher level of IL-2 expression than white matter. These data demonstrated that the IL-2 gene was transfected into spinal cord regions relevant to pain modulation. The expressed IL-2 protein profile in spinal cord detected by enzyme-linked immunosorbent assay coincided almost exactly with its antinociceptive effect. This supported the hypothesis that the therapeutic effect of IL-2 gene was related to IL-2 protein expression. The study indicates that intrathecal delivery of adenovirus-mediated IL-2 gene has a relatively long antinociceptive effect.

Adenoviridae↗

Effects of active immunization against GnRH on serum LH, inhibin A, sexual development and growth rate in Chinese female pigs.

Surgical castration of young female pigs is common practice in Chinese pig farming today. The purpose of the present study is to investigate anti-GnRH immunization as a practical alternative to surgical castration for female pigs. Thirty-six Chinese female crossbred pigs (Chinese Yanan x Yorkshire) were selected from 12 litters, three pigs from each litter, at the age of 10-13 weeks. One pig from each litter was immunized with 62.5 microg D-Lys6-GnRH-tandem-dimer peptide conjugated to ovalbumin in Specol adjuvant at Week 0 (0 week post-vaccination, wpv), and a booster vaccination was given 8 weeks later (8 wpv). Its intact and castrate littermates (surgically castrated at the time of weaning, i.e. at 6 weeks of age) were administered the vehicle and served as controls. Antibody titers, serum LH and inhibin A were determined at the day of first vaccination, every 4 weeks thereafter and at the day of slaughter (18 wpv). At slaughter, ovaries were inspected for the presence of follicles and corpora lutea, and ovarian and uterine weights were recorded. Ten of twelve immunized pigs responded well to the immunization (immunocastrated animals), while the remaining two pigs responded poorly (nonresponders). Antibody titres in immunocastrated animals steadily increased after immunization, became maximal at 12 wpv and remained high until slaughter. Serum LH levels were reduced (P < 0.05) in immunocastrated pigs as compared to intact controls and surgical castrates. Serum inhibin A levels decreased after vaccination, and equaled surgical castrate levels from 8 wpv until the end of the experiment. Ovarian and uterine weights (1.3 +/- 0.2 and 43.9 +/- 11.4 g, respectively; mean +/- S.E.M.) were significantly lower (P < 0.05) in immunocastrates than in intact controls (9.4 +/- 1.1 and 390.9 +/- 67.2 g, respectively). Antibody titers were significantly lower (P < 0.05) in nonresponders than in immunocastrated pigs from 12 wpv to slaughter. Ovarian and uterine weights were similar in nonresponders and in intact controls. Macroscopically, no follicular structures were found in ovaries of immunocastrated pigs, while large follicles or corpora lutea were observed in the ovaries of both nonresponders and intact controls. Although not significant, immunocastrates had a numerically higher average daily gain than surgical castrates and intact controls (0.74 +/- 0.04 versus 0.66 +/- 0.04 versus 0.66 +/- 0.03 kg per day, respectively; mean +/- S.E.M., P = 0.09). Results obtained in the present study demonstrate that anti-GnRH immunization can be an attractive alternative to surgical castration for Chinese crossbred female pigs. Our results also question the beneficial effect of surgical castration on growth as compared to intact controls.

Animals↗

Functional interactions between arginine-133 and aspartate-88 in the human reduced folate carrier: evidence for a charge-pair association.

The human reduced folate carrier (hRFC) is an integral membrane protein that mediates cellular uptake of reduced folates and antifolates. hRFC contains several highly conserved charged residues predicted to lie in the transmembrane domains (TMDs). To explore the possible roles of the conserved arginine-133, located in TMD 4, in hRFC structure and function, this residue was systematically mutagenized to histidine, leucine, lysine and glutamate. When transfected into transport-impaired K562 cells, the mutant hRFC constructs were expressed at high levels; however, only lysine-133 hRFC was able to transport methotrexate and (6S)-5-formyl tetrahydrofolate. Substitution of aspartate-453 (in hRFC TMD 12) by valine largely preserved transport activity for both substrates. Although mutagenesis of aspartate-88 (in TMD 2) to leucine completely abolished transport activity in transfected cells, substitution with a glutamate preserved low levels ( approximately 12%) of transport. To assess the possibility that arginine-133 and aspartate-88 may form a charge-pair to stabilize hRFC tertiary structure, both charges were neutralized (by substituting leucine and valine, respectively) in the same construct. In contrast to the singly mutated hRFCs, the double mutant exhibited high levels of transport with both methotrexate and 5-formyl tetrahydrofolate. These results strongly suggest that arginine-133 and aspartate-88 form a charge-pair and that TMD 4 lies next to TMD 2 in the hRFC tertiary structure.

Amino Acid Sequence↗