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Biomedical subjects

Y Liu

Publications and source records attributed to Y Liu.

At least 19 recordsLinked to original sources

Tumor promoting properties of the ETS protein MEF in ovarian cancer.

We have previously shown that MEF (myeloid ELF1-like factor, also known as ELF4) functions as a transcriptional activator of the interleukin (IL)-8, perforin, granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-3 genes in hematopoietic cells. MEF is also expressed in non-hematopoietic tissues including certain ovarian cancer cells. To define the function of MEF in these cells, we examined primary human ovarian epithelial tumors and found that MEF is expressed in a significant proportion of ovarian carcinomas, and in the CAOV3 and SKOV3 ovarian cancer cell lines, but not in normal ovarian surface epithelium. Manipulating MEF levels in these cell lines altered their behavior; reducing MEF levels, using short hairpin RNA expressing vectors, significantly inhibited the proliferation of SKOV3 and CAOV3 cells in culture, and impaired the anchorage-independent growth of CAOV3 cells. Overexpression of MEF in SKOV3 cells (via retroviral transduction) significantly increased their growth rate, enhanced colony formation in soft agar and promoted tumor formation in nude mice. The oncogenic activity of MEF was further shown by the ability of MEF to transform NIH3T3 cells, and induce their tumor formation in nude mice. MEF is an important regulator of the tumorigenic properties of ovarian cancer cells and could be used a therapeutic target in ovarian cancer.

Animals↗

Contribution of VCAF-positive cells to neovascularization and calcification in atherosclerotic plaque development.

Calcification of the vessel wall is a regulated process with many similarities to osteogenesis. Progenitor cells may play a role in this process. Previously, we identified a novel gene, Vascular Calcification Associated Factor (VCAF), which was shown to be important in pericyte osteogenic differentiation. The aim of this study was to determine the localization and expression pattern of VCAF in human cells and tissues. Immunohistochemical analysis of seven atherosclerotic arteries confirmed VCAF protein expression within calcified lesions. In addition, individual VCAF-positive cells were detected within the intima and adventitia in areas where sporadic 3G5-positive pericytes were localized. Furthermore, VCAF-positive cells were identified in newly formed microvessels in association with CD34-positive/CD146-positive/c-kit-positive cells as well as in intact CD31-positive endothelium in internal mammary arteries. Western blot analysis confirmed the presence of VCAF (18 kD) in protein lysates extracted from human smooth muscle cells, endothelial cells, macrophages, and osteoblasts. In fracture callus samples from three patients, VCAF was detected in osteoblasts and microvessels. This study demonstrates the presence of VCAF in neovessels and raises the possibility that VCAF could be a new marker for vascular progenitor cells involved in a number of differentiation pathways. These data may have implications for the prevention or treatment of vascular disease.

Atherosclerosis↗

Advantages and challenges of using census and multiplier methods to estimate the number of female sex workers in a Chinese city.

Using census and multiplier methods to estimate the size of the population of female sex workers (FSWs) in a small city in western China, this study compared the advantages and challenges of the two methods. It was estimated that there were about 1,500 FSWs within the urban area using the census method, which was significantly lower than that estimated by the multiplier method (2,500). Each method has advantages and limitations, and could be applied to different situations. The census method is less time and resource consuming in smaller regions and has a tendency to underestimate, and therefore, the result can be viewed as a low limit. It is useful in a local setting, for example, when estimations are needed for planning HIV/AIDS prevention programmes in a single city. Using existing information or resources, multiplier method could be used to produce estimates for a large geographic area or at a national level.

Censuses↗

Screening and mutagenesis of a novel Bacillus pumilus strain producing alkaline protease for dehairing.

AIMS: To characterize and optimize a novel Bacillus pumilus strain isolated from biological waste which produces protease with excellent dehairing effect. This newly isolated strain could be utilized in the industrial leather dehairing process. METHODS AND RESULTS: Bacterial strains secreting proteases were screened from biological wastes. Positive clones were further characterized by analysing their efficacy in dehairing and effects on collagen integrity. Among 171 colonies tested, a strain BA06, identified as B. pumilus, was picked owing to its efficient dehairing capabilities with minimal impact on collagen. By combined mutagenesis using UV, N-methyl-N'-nitro-N-nitrosdguanidine and Co(60)-gamma-rays, this strain was further improved with regard to its alkaline protease production. The alkaline protease activity of the mutant strain SCU11was greatly improved up to 6000 U ml(-1), in comparison with its parent strain BA06 of 1200 U ml(-1). CONCLUSIONS: By using screening and mutagenesis methods, we have successfully created a B. pumilus strain that can produce high levels of alkaline proteases that are able to efficiently remove hair from skin with minimal damage on the collagen. SIGNIFICANCE AND IMPACT OF THE STUDY: This strain could be used in commercial alkaline protease production for leather dehairing.

Animals↗

Delivery mode and efficacy of BMP-2 in association with implants.

Bone healing may be improved in implant patients by the administration of osteogenic agents, such as bone morphogenetic protein 2 (BMP-2). But the efficacy of BMP-2 depends upon its mode of application. We hypothesized that BMP-2 is capable of a higher osteogenic efficacy when delivered physiologically, viz., when incorporated into a calcium-phosphate carrier that mimics mineralized bone matrix, than when administered via simple pharmacological modes, such as by adsorption onto a carrier surface. Using an ectopic rat model, we compared the osteoinductive efficacies of calcium-phosphate implant-coatings bearing either incorporated, adsorbed, or incorporated and adsorbed BMP-2. When adsorbed directly onto the naked implant surface, BMP-2 was not osteogenic. When adsorbed onto a calcium-phosphate coating, it was osteoinductive, but not highly efficacious. When BMP-2 was incorporated into calcium-phosphate coatings, it was a potent bone-inducer, whose efficacy was compromised, not potentiated, by the additional deposition of an adsorbed pool.

Adsorption↗

Distribution and expression of recombinant plasmid encoding chicken interleukin-2.

A plasmid DNA that encodes chicken interleukin-2 (pCI-ChIL-2-EGFP) was investigated for its distribution and expression after intramuscular (i.m.) injection in chickens. After the i.m. injection, serum distribution was detectable from 2 h post inoculation (p.i.), peaked at 8 h p.i., and disappeared at 7 days p.i. The plasmid DNA was also observed in several organs including heart, liver, lung, spleen, bursa and inoculated muscle at different time points, but at 19 days p.i. the plasmid DNA was not found in any organ except inoculated muscle. Fluorescence of enhanced green fluorescent protein (EGFP) was found in cytoplasm and nucleus of cultured Vero cells, chicken embryo fibroblasts and peripheral blood lymphocytes, which were transfected in vitro with the plasmid DNA or in vivo with Lipofectamine. The expression profile of the fusion gene (ChIL-2-EGFP) in vivo was measured by RT-PCR, ELISA and fluorescence microscopy. The EGFP expression was detected from 8 h p.i. to 14 days p.i. and peaked at 5 days p.i., when the number of EGFP-expression myocytes was about 5% in the injected site. These results demonstrate that intramuscular administration of plasmid DNA leads to widespread distribution and long-term expression in vivo.

Animals↗

Hyperdense intracranial epidermoid cysts: a study of 15 cases.

BACKGROUND: Although intracranial epidermoid cysts generally appear as hypodense lesions on CT scans, occasionally, they may appear hyperdense, making diagnosis difficult. The aim was to study clinical features and possible pathogenesis of hyperdense intracranial epidermoid cysts (HIECs). METHODS: Fifteen patients with HIECs were surgically treated in our department during a 21-year period (1985 up to 2005). We reviewed each patient's clinical records, radiological findings, operative reports, and pathological examinations, along with a review of the literature. FINDINGS: The incidence of HIECs in our series was approximately 3.02%, with female predominance. The average age was 32 years and the average duration of complaints was nine months. The most common location was the parasellar area (6 cases), followed by cerebellum (4 cases), clival region (3 cases), cerebello-pontine angle (1 case) and lateral ventricle (1 case). Gross-total excision of the tumor was achieved in ten patients (66.7%). Four (26.7%) patients underwent subtotal resection; and one (6.6%) patient underwent partial resection. Aseptic meningitis that occurred postoperatively in two cases was controlled by lumbar drainage. CONCLUSIONS: Recurrent leakage of the irritating cyst contents and subsequent chemical inflammatory response may be responsible for the high-density on CT scans and the cystic nature. A correct histological diagnosis is important because, in contrast to typical ECs and other lesions, HIECs are more prone to spread intra-operatively and result in severe aseptic meningitis.

Adolescent↗

Parabrachial nucleus influences the control of normal urinary bladder function and the response to bladder irritation in rats.

The contribution of the parabrachial nucleus to the mediation of bladder contraction was examined in the rat. Constant infusion (0.1 ml/min) of saline or 0.2% acetic acid evoked normal or abnormal bladder contractions, respectively. Single unit activity was recorded in the parabrachial nucleus with tungsten microelectrodes. Seven units with activity that was correlated with bladder contraction during saline infusion were located in the lateral subnuclei and three units were located in the medial subnuclei of the parabrachial nucleus. Twelve units with activity that was correlated with abnormal bladder contractions were found widely distributed in the parabrachial nucleus. An inverse correlation of activity to normal or abnormal bladder contractions was identified in 11 units in the parabrachial nucleus. Pressure injection of 5 mM CoCl(2) into the parabrachial nucleus was used to block synaptic transmission unilaterally. Normal bladder contractions evoked by saline infusion were disrupted by 5 of 10 injections, 4 of them in the medial subnuclei of the parabrachial nucleus and one in the lateral subnuclei. Abnormal bladder contractions were converted to a normal pattern in nine experiments where CoCl(2) injections lay in the lateral subnuclei of the parabrachial nucleus. In five experiments, CoCl(2) disrupted abnormal bladder contractions; four effective sites were located in the lateral subnucleus and one lay in the medial subnucleus of the parabrachial nucleus. These data demonstrated that single units responding to both normal and abnormal contractions were located throughout the parabrachial nuclei whereas the lateral subnuclei play a predominant role in mediation of abnormal bladder contractions and the medial subnuclei play a predominant role in the mediation of normal bladder contractions.

Action Potentials↗

Earlier flowering induced by over-expression of CO gene does not accompany increase of artemisinin biosynthesis in Artemisia annua.

The early flowering gene CONSTANS (CO) from Arabidopsis thaliana was transferred into Artemisia annua using the Agrobacterium tumefaciens-mediated transformation system. The plant expression vector pBI CO was constructed by inserting the CO gene into the binary vector pBI121 under the control of CaMV 35S promoter. Analyses of PCR, PCR Southern blot, and Southern blot revealed that the transgenic plants contained the foreign CO gene. The results of RT-PCT and RT-PCR Southern blot suggested that the foreign CO gene had expressed at the transcriptional level. Although the flowering time of the CO transgenic plant was about 2 weeks earlier than that of the non-transgenic plant under short-day conditions, no significant difference in artemisinin content was found between the flowering transgenic plant and the non-flowering non-transgenic plant. These results show that the usually observed increase of artemisinin content before plant flowering under natural conditions is not a direct consequence of flowering itself, perhaps there is even no direct linkage between flowering and artemisinin biosynthesis.

Agrobacterium tumefaciens↗

Psoriasis: genetic associations and immune system changes.

Psoriasis is a common inflammatory skin disease characterized by infiltration of inflammatory cells into the epidermis and altered keratinocyte differentiation. Psoriasis is currently thought of as a T-cell mediated 'Type-1' autoimmune disease. Gene expression changes in psoriasis lesions have been well documented, and strongly support an important role for tumor necrosis factor and interferon gamma signal pathways in its pathogenesis. The strongest genetic determinant of psoriasis identified to date lies within the class I region of the multiple histocompatibility locus antigen cluster, although its low penetrance implicates a requirement for other genetic risk factors. Multiple genome-wide linkage and an increasing number of association studies have been carried out, leading to multiple linkage peaks, and the identification of potential low risk variants. A number of these variants lie within genes encoding components of the immune system. However, the functional relationships between predisposing genetic variation is unclear, and presumably involves genetic susceptibility factors affecting both immune cell activation and keratinocyte differentiation. The interaction of environmental trigger factors with genetic effects is also not understood, but provide further evidence for the complex basis of this disease.

Animals↗

The quantification of ADAMTS expression in an animal model of cerebral ischemia using real-time PCR.

BACKGROUND: ADAMTS1 and ADAMTS8 are proteases involved in extracellular matrix proteolysis and antiangiogenesis, but little is known about their expression and function in cerebral ischemia. We investigated the changes in ADAMTS1 and ADAMTS8 in a rat model of permanent middle cerebral artery occlusion (pMCAO). The expressions of glyseraldehyde-3-phosphate dehydrogenase (GAPDH), beta-actin, cyclophilin, and RPL13A were examined in order to validate the appropriate housekeeping genes for a long duration after inducing cerebral ischemia. METHODS: Male Sprague-Dawley rats were subjected to pMCAO, and ischemic penumbra was collected at 2, 24 h, 3, 7, and 21 days after inducing ischemia, ADAMTS1, ADAMTS8, and the four housekeeping genes were quantified using real-time polymerase chain reaction (PCR). RESULTS: The expression of beta-actin increased up to 21 days, and that of GAPDH decreased at 24 h after pMCAO, with no statistically significant changes in RPL13A and cyclophilin being detected. ADAMTS1 mRNA increased at 2 h after pMCAO, peaked at 24 h, and remained at a high level until 21 days. The expression of ADAMTS8 mRNA decreased at 2 and 24 h after pMCAO, followed by a slight increase at 3 days, and then decreased again at 7 days. CONCLUSION: The results suggest that RPL13A and cyclophilin are two appropriate housekeeping genes for the rat pMCAO model up to 21 days. ADAMTS1 mRNA levels increased, but ADAMTS8 decreased after pMCAO. Our data provide new insight into the mechanism of brain ischemia and self-repair after injury.

ADAM Proteins↗

Relationship between LAPTM4B gene polymorphism and susceptibility of gastric cancer.

BACKGROUND: A novel gene called LAPTM4B (lysosome-associated protein transmembrane 4beta) was mapped to 8q22, and contains seven exons. The 2.25-kb messenger RNA of the gene encodes a putative lysosome-associated protein with four transmembrane regions. There are two alleles of the gene, named as LAPTM4B*1 and LAPTM4B*2. Allele *1 differs from allele *2 in that it contains only one copy of a 19-bp sequence in the 5' untranslated region (UTR), whereas this sequence is duplicated and tandemly arranged in allele *2. Studies showed that the allelic variation of LAPTM4B was associated with the genetic susceptibility of hepatocellular carcinoma but not with that of esophageal squamous cell carcinoma. This study was designed to investigate the possible association between the allelic variation of LAPTM4B and the genetic susceptibility of gastric cancer. MATERIALS AND METHODS: The genotype of LAPTM4B was analyzed in 350 unrelated healthy adult individuals and 214 patients with gastric cancer by utilizing polymerase chain reaction based on specific primers. The genotypic distribution of LAPTM4B was analyzed by chi(2) test. RESULTS: The allelic frequencies of the *2 were 33.88% and 24.14% in the gastric cancer group and the healthy control group, respectively, which was significantly different between the two groups (P < 0.001). There was a significant difference in the overall genotypic distribution between the patients and the controls (P = 0.023). The risk of suffering from gastric cancer was increased 1.819 times in the individuals of the *1/2 genotype [95% confidence interval (CI) 1.273-2.601] and 2.387 times in the individuals of the *2/2 genotype of LAPTM4B (95% CI 1.195-4.767) compared with the *1/1 genotype. No association between the genotypic distribution of LAPTM4B and the clinical information on patients of gastric cancer such as age, pathological type, differentiation classification of TNM, and infection of hepatitis B virus was shown. CONCLUSION: This study indicated that allele *2 of LAPTM4B might be the risk factor of gastric cancer, which could be associated with genetic susceptibility of gastric cancer.

Adenocarcinoma↗

Evidence for superfluidity of ultracold fermions in an optical lattice.

The study of superfluid fermion pairs in a periodic potential has important ramifications for understanding superconductivity in crystalline materials. By using cold atomic gases, various models of condensed matter can be studied in a highly controllable environment. Weakly repulsive fermions in an optical lattice could undergo d-wave pairing at low temperatures, a possible mechanism for high temperature superconductivity in the copper oxides. The lattice potential could also strongly increase the critical temperature for s-wave superfluidity. Recent experimental advances in bulk atomic gases include the observation of fermion-pair condensates and high-temperature superfluidity. Experiments with fermions and bosonic bound pairs in optical lattices have been reported but have not yet addressed superfluid behaviour. Here we report the observation of distinct interference peaks when a condensate of fermionic atom pairs is released from an optical lattice, implying long-range order (a property of a superfluid). Conceptually, this means that s-wave pairing and coherence of fermion pairs have now been established in a lattice potential, in which the transport of atoms occurs by quantum mechanical tunnelling and not by simple propagation. These observations were made for interactions on both sides of a Feshbach resonance. For larger lattice depths, the coherence was lost in a reversible manner, possibly as a result of a transition from superfluid to insulator. Such strongly interacting fermions in an optical lattice can be used to study a new class of hamiltonians with interband and atom-molecule couplings.

Journal Article↗

Re-activation of a dormant tumor suppressor gene maspin by designed transcription factors.

The controlled and specific re-activation of endogenous tumor suppressors in cancer cells represents an important therapeutic strategy to block tumor growth and subsequent progression. Other than ectopic delivery of tumor suppressor-encoded cDNA, there are no therapeutic tools able to specifically re-activate tumor suppressor genes that are silenced in tumor cells. Herein, we describe a novel approach to specifically regulate dormant tumor suppressors in aggressive cancer cells. We have targeted the Mammary Serine Protease Inhibitor (maspin) (SERPINB5) tumor suppressor, which is silenced by transcriptional and aberrant promoter methylation in aggressive epithelial tumors. Maspin is a multifaceted protein, regulating tumor cell homeostasis through inhibition of cell growth, motility and invasion. We have constructed artificial transcription factors (ATFs) made of six zinc-finger (ZF) domains targeted against 18-base pair (bp) unique sequences in the maspin promoter. The ZFs were linked to the activator domain VP64 and delivered in breast tumor cells. We found that the designed ATFs specifically interact with their cognate targets in vitro with high affinity and selectivity. One ATF was able to re-activate maspin in cell lines that comprise a maspin promoter silenced by epigenetic mechanisms. Consistently, we found that this ATF was a powerful inducer of apoptosis and was able to knock down tumor cell invasion in vitro. Moreover, this ATF was able to suppress MDA-MB-231 growth in a xenograft breast cancer model in nude mice. Our work suggests that ATFs could be used in cancer therapeutics as novel molecular switches to re-activate dormant tumor suppressors.

Amino Acid Sequence↗

Poly-epsilon-caprolactone/hydroxyapatite for tissue engineering scaffold fabrication via selective laser sintering.

Rapid prototyping (RP) techniques are becoming more popular for fabricating tissue engineering (TE) scaffolds owing to their advantages over conventional methods, such as the ability to fabricate scaffolds with predetermined interconnected networks without the use of organic solvents. A versatile RP technique, selective laser sintering (SLS), offers good user control of scaffold microstructure by adjusting the process parameters. This research focuses on a the use of biocomposite material, consisting of poly-epsilon-caprolactone (PCL) and hydroxyapatite (HA), to fabricate TE scaffolds using SLS. Biocomposite blends with different percentage weights of HA were physically blended and sintered to assess their suitability for fabrication via SLS. Optimal sintering conditions for the powders were achieved by varying parameters such as laser power and scan speed. Studies of the sintered specimen morphology were performed by scanning electron microscopy. Thermogravimetric analysis confirmed the homogeneity of the biocomposite blend. Simulated body fluid (SBF) samples show the formation of hydroxy carbonate apatite, as a result of soaking HA in a SBF environment. Cell culture experiment showed that Saos-2 cells were able to live and replicate on the fabricated scaffolds. The results show the favorable potential of PCL/HA biocomposite as TE scaffolds that are fabricated via SLS.

Cell Line↗

Long-term fate of neural precursor cells following transplantation into developing and adult CNS.

Successful strategies for transplantation of neural precursor cells for replacement of lost or dysfunctional CNS cells require long-term survival of grafted cells and integration with the host system, potentially for the life of the recipient. It is also important to demonstrate that transplants do not result in adverse outcomes. Few studies have examined the long-term properties of transplanted neural precursor cells in the CNS, particularly in non-neurogenic regions of the adult. The aim of the present study was to extensively characterize the fate of defined populations of neural precursor cells following transplantation into the developing and adult CNS (brain and spinal cord) for up to 15 months, including integration of graft-derived neurons with the host. Specifically, we employed neuronal-restricted precursors and glial-restricted precursors, which represent neural precursor cells with lineage restrictions for neuronal and glial fate, respectively. Transplanted cells were prepared from embryonic day-13.5 fetal spinal cord of transgenic donor rats that express the marker gene human placental alkaline phosphatase to achieve stable and reliable graft tracking. We found that in both developing and adult CNS grafted cells showed long-term survival, morphological maturation, extensive distribution and differentiation into all mature CNS cell types (neurons, astrocytes and oligodendrocytes). Graft-derived neurons also formed synapses, as identified by electron microscopy, suggesting that transplanted neural precursor cells integrated with adult CNS. Furthermore, grafts did not result in any apparent deleterious outcomes. We did not detect tumor formation, cells did not localize to unwanted locations and no pronounced immune response was present at the graft sites. The long-term stability of neuronal-restricted precursors and glial-restricted precursors and the lack of adverse effects suggest that transplantation of lineage-restricted neural precursor cells can serve as an effective and safe replacement therapy for CNS injury and degeneration.

Age Factors↗

Variation in proton affinity of the guanidino group between free and blocked arginine.

In this paper, the analog of arginine residues in peptides was synthesized and characterized by ESI-MS/MS (electrospray ionization with tandem mass spectrometry), (31)P NMR, (1)H NMR, IR and high-resolution mass spectrometry. When the Todd reaction activity of the guanidino group in free arginine and the arginine peptide analog were compared, it was found that the proton affinity of the guanidino group was decreased when both the N- and the C-terminal were blocked. As a result, the guanidino group of arginine residues in peptides could be phosphorylated under the Todd reaction condition, but not the free arginine. This result was further proved by the theoretical calculation of their proton affinity.

Arginine↗

Diversity of 16S rRNA gene, ITS region and aclB gene of the Aquificales.

The Aquificales are prevalent members of the microbial communities inhabiting many marine and terrestrial hydrothermal systems. Numerous new strains were obtained from deep-sea and terrestrial hydrothermal systems. In order to resolve the phylogenetic relationships within this group, three different phylogenetic datasets were used, namely the 16S rRNA gene, the intergenic transcribed spacer region between the 16S rRNA and 23S rRNA genes (ITS) and the gene coding for the ATP citrate lyase (aclB), a key enzyme in the reductive TCA cycle. The data were analyzed using neighbor-joining, parsimony and maximum likelihood. The resulting phylogenies appeared to be consistent between the three markers. The three genes confirmed the presence of isolates that merit further characterization and descriptions as new species and perhaps even new genera. The detailed phylogenetic interrelationships of these isolates are described here.

ATP Citrate (pro-S)-Lyase↗