Biomedical subjects

Z Wu

Publications and source records attributed to Z Wu.

At least 19 recordsLinked to original sources

PubMed2006

Evaluation of expression of midkine in oral squamous cell carcinoma and its correlation with tumour angiogenesis.

Midkine, a new member of the heparin-binding growth factor family, was found recently to have a high expression level in many carcinoma specimens, including oesophagus, gall, bladder, pancreas, colorectum, breast and lung carcinomas, but few relevant studies have been performed. The aim of this study was to investigate the expression of midkine in oral squamous cell carcinoma (OSCC) and its correlation with tumour angiogenesis. Surgical specimens from 62 cases of OSCC and 10 cases of normal oral mucosa were examined by immunohistochemistry. The relationship between expression of midkine and the clinicopathological data and tumour angiogenesis was analysed. Midkine proteins were overexpressed in OSCC. The level of midkine expression was found to be significantly correlated with tumour size (P = 0.01), clinical stage (P = 0.002) and prognosis (P = 0.038). High midkine expression was associated with higher tumour angiogenesis as reflected by increased vascular endothelial growth factor expression (P = 0.005) and higher microvessel density (P = 0.004). These results indicate that midkine may be of great value in assessing the development and prognosis of OSCC, and could be taken as a new target for OSCC therapy.

Adult↗

PubMed2006

Molecular cloning and characterization of an Rcd1-like protein in excretory-secretory products of Trichinella pseudospiralis.

A cDNA library was constructed from muscle larvae of Trichinella pseudospiralis. A cDNA clone, designated as Tp8 contained a cDNA transcript of 1326 bp length with a single open reading frame, which encoded 303 amino acid residues (34,187 Da, estimated molecular mass). The predicted amino acid sequence of the clone had an identity of approximately 60% to the Rcd1 (Required cell differentiation 1) -like proteins among a wide range of organisms. Real-time quantitative polymerase chain reaction results showed that the transcription level of Tp8 gene reached the highest value in adult worms, and that the transcription level in muscle larvae before stichosome formation was higher than in muscle larvae after stichosome formation. The recombinant Tp8 protein migrated at 37 kDa and reacted to antibody against T. pseudospiralis excretory-secretory (E-S) products and sera from mice infected with T. pseudospiralis. An antibody against the Tp8 recombinant protein could stain proteins migrating at approximately 34 kDa (which is the expected size from the sequence) on Western blotting of E-S products from muscle larvae. An immunocytochemical study showed that the Tp8 protein was present within the stichocyte of muscle larvae and adults worms.

Amino Acid Sequence↗

PubMed2006

The intra-arterial injection of microglia protects hippocampal CA1 neurons against global ischemia-induced functional deficits in rats.

In the present study, we have attempted to elucidate the effects of the intra-arterial injection of microglia on the global ischemia-induced functional and morphological deficits of hippocampal CA1 neurons. When PKH26-labeled immortalized microglial cells, GMIR1, were injected into the subclavian artery, these exogenous microglia were found to accumulate in the hippocampus at 24 h after ischemia. In hippocampal slices prepared from medium-injected rats subjected to ischemia 48 h earlier, synaptic dysfunctions including a significant reduction of synaptic responses and a marked reduction of long-term potentiation (LTP) of the CA3-CA1 Schaffer collateral synapses were observed. At this stage, however, neither significant neuronal degeneration nor gliosis was observed in the hippocampus. At 96 h after ischemia, there was a total loss of the synaptic activity and a marked neuronal death in the CA1 subfield. In contrast, the basal synaptic transmission and LTP of the CA3-CA1 synapses were well preserved after ischemia in the slices prepared from the microglia-injected animals. We also found the microglial-conditioned medium (MCM) to significantly increase the frequency of the spontaneous postsynaptic currents of CA1 neurons without affecting the amplitude, thus indicating that MCM increased the provability of the neurotransmitter release. The protective effect of the intra-arterial injected microglia against the ischemia-induced neuronal degeneration in the hippocampus was substantiated by immunohistochemical and immunoblot analyses. Furthermore, the arterial-injected microglia prevented the ischemia-induced decline of the brain-derived neurotrophic factor (BDNF) levels in CA1 neurons. These observations strongly suggest that the arterial-injection of microglia protected CA1 neurons against the ischemia-induced neuronal degeneration. The restoration of the ischemia-induced synaptic deficits and the resultant reduction of the BDNF levels in CA1 neurons, possibly by the release of diffusible factor(s), might thus contribute to the protective effect of the arterial-injection of microglia against ischemia-induced neuronal degeneration.

Animals↗

PubMed2006

Conditional expression of PTEN alters the androgen responsiveness of prostate cancer cells.

BACKGROUND: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is lost as a function of prostate tumor androgen dependence. While the transcriptional activity of the androgen receptor (AR) is inhibited by PTEN in androgen sensitive prostate cancer (CaP), the role of PTEN in androgen disease is unclear. METHODS: We developed a system where PTEN can be conditionally re-expressed at physiologic levels into a PTEN null metastatic human CaP cell line, C4-2, and androgen responsiveness examined. RESULTS: PTEN induction reduces cell growth and blocks the growth effect of synthetic androgen R1881. The anti-androgen Casodex enhances the growth-inhibitory action of PTEN and this effect is independent of Akt phosphorylation. Combined PTEN induction and Casodex, result in a further decrease in prostate specific antigen promoter activity compared to PTEN but not Casodex alone. CONCLUSIONS: PTEN induction confers androgen independent CaP cells enhanced responsiveness to the anti-proliferative effects of anti-androgens and this action may involve non-AR mediated effects.

Androgen Antagonists↗

PubMed2006

Involvement of the c-Ski oncoprotein in cell cycle arrest and transformation during nurse cell formation after Trichinella spiralis infection.

The role of c-Ski, an oncoprotein encoded by the oncogene, c-ski, in Trichinella spiralis-infected muscle tissues during nurse cell formation, was investigated by following the expression kinetics and distribution of c-Ski (both protein and mRNA) in the infected muscle cell, as well as the expression kinetics of the transforming growth factor beta (TGF-beta) signaling pathway factor genes (TGF-beta, Smad2 and Smad4) which cooperate with c-Ski. Immunohistochemical analysis using an anti-c-Ski antibody indicated that in the early stages of infection (13 and 18 days post-infection (p.i.)) the increased expression of the c-Ski protein was limited to the eosinophilic cytoplasm and not the enlarged nuclei or basophilic cytoplasm. At a later stage of infection (23 and 28 days p.i.) the c-Ski protein was limited to the enlarged nuclei in the basophilic cytoplasm, rather than the eosinophilic cytoplasm. At 48 days p.i., the c-Ski protein was barely detectable. Real-time PCR analysis showed that expression of the c-ski gene increased from 13 days p.i., reached a peak at 23-28 days p.i. and then decreased to a low level by 48 days p.i. Expression kinetics for the TGF-beta signaling pathway factor genes (TGF-beta, Smad2 and Smad4) were similar to that of c-ski. These findings provide evidence that the c-Ski protein is involved in nurse cell formation through the TGF-beta signaling pathway process in the host cell nucleus.

Animals↗

PubMed2006

Suppression of tumor growth using a recombinant adenoviral vector carrying the dominant-negative mutant gene Survivin-D53A in a nude mice model.

Survivin (SVV), an inhibitor of apoptosis protein, is found to be upregulated in many cancers. We previously demonstrated that a dominant-negative mutant SVV-D53A was able to induce apoptosis in a p53-independent manner. Here, we report the construction and characterization of a recombinant replication-deficient adenoviral vector encoding a human SVV-D53A gene for its effectiveness against tumor growth both in vitro and in vivo. Transfection of liver tumor cells QGY-7703 with Ad-SVV-D53A results in significant apoptosis as measured by an increase in sub-G1 DNA content, procaspase-9 activation and further downstream PARP-1 cleavage. Furthermore, animal studies using QGY-7703 liver carcinoma xenografts in nude mice revealed that treatment of QGY-7703 cells with dominant-negative SVV-D53A, but not with wild-type SVV-adenovirus, prevents tumor outgrowth, inhibits growth of established tumors and results in a notably improved survival advantages in xenograft studies. Both the transferase-mediated dUTP nick-end labeling assay and immunostaining experiment demonstrated that tumor growth inhibition is associated with apoptosis induced by SVV-D53A expression. Taken together, these data suggest that recombinant adenovirus Ad-SVV-D53A carrying a Survivin dominant-negative gene SVV-D53A promotes apoptosis-mediated tumor suppression and could potentially be a promising candidate for cancer therapies.

Adenoviridae↗

PubMed2006

Role of Smad3 in the regulation of rat telomerase reverse transcriptase by TGFbeta.

Telomerase is induced in certain pathological conditions such as cancer and tissue injury and repair. This induction in fibroblasts from injured lung is repressed by transforming growth factor beta (TGFbeta) via yet unknown mechanisms. In this study, the role of Smad3 in the inhibition of telomerase reverse transcriptase (TERT) gene transcription by TGFbeta was investigated. The rat TERT (rTERT) gene promoter was cloned by PCR amplification and fused with a luciferase reporter gene. This construct was used to analyse regulation of promoter activity in fibroblasts isolated from bleomycin-injured lung with induced telomerase activity. The results showed that TGFbeta inhibited rTERT transcription while stimulating Smad3 expression. Interestingly, TGFbeta also inhibited the expression of c-myc. Cotransfection with a Smad3 expressing plasmid further repressed rTERT transcription and c-myc expression, while cotransfection with the corresponding antisense Smad3 construct had the opposite effect. Mutation of an E-box in the rTERT promoter suppressed its activity, which could be further reduced by TGFbeta treatment. In contrast, mutation at a Smad binding element enhanced promoter activity whose inhibition was impaired by TGFbeta treatment. Thus TGFbeta inhibition of rTERT gene expression was directly mediated by Smad3 via the Smad binding element, while c-myc appears to primarily regulate its constitutive or induced expression.

Animals↗

PubMed2006

Living environment and schooling of children with HIV-infected parents in southwest China.

A cross-sectional household survey was conducted in Longchuan County, China, to study the lives of children with HIV-infected parents. Registered HIV-infected drug users and their households were approached and information about the living environment of children < or =15 years of age was collected. Of the 266 households interviewed, there were 213 children < or =15 years old. Forty percent of the children had lost at least one parent. Most of the children resided in a household with low economic status and a high dependency ratio. One-half of the children experienced discordant family relations, family anxiety and shame. Compared to orphans, non-orphans and their families were less likely to receive social support from the community. Orphans and older children were less likely to attend school and more likely to be truant if enrolled in school. Findings in the current study suggest that many children whose parents are infected with HIV or have died from HIV are living in stressful environments with minimal support from the community. Efforts should be taken to provide support and supervision to these children.

Absenteeism↗

PubMed2006

Estimating the number of people at risk for and living with HIV in China in 2005: methods and results.

BACKGROUND: No new estimates of HIV infection have been available for China since 2003. However, since then, data availability has increased dramatically. OBJECTIVES: To use internationally recommended methods to make new estimates of the number of people exposed to HIV in China, the number living with HIV, and the number of new HIV infections and deaths in 2005. METHODS: The UNAIDS Workbook method was adapted to meet the needs of China. Local data were used to estimate the size of each risk population and HIV prevalence by risk group for every prefecture. These estimates were combined into provincial and national estimates. The UNAIDS Estimates and Projections Package and Spectrum were used to derive estimates of incidence and mortality from prevalence data, taking into account treatment. RESULTS: It was estimated that 650,000 people are living with HIV/AIDS in China (range 540,000-760,000), of whom 70,000 were newly infected in 2005 (range 60,000-80,000). Between 20,000 and 30,000 people are estimated to have died of HIV in 2005. The new estimate compares with an estimate of 840,000 people living with HIV/AIDS in 2003 (range 650,000-1,020,000). The estimated number of infected former plasma donors fell from 199,000 to 55,000. Infections remain concentrated among drug injectors, those buying and selling sex, and men who have sex with men. CONCLUSION: The new estimates are based on a much wider range of surveillance data as well as mass screening of former plasma donors, and are made at the prefecture level. More limited data from high prevalence provincial surveillance sites led to past estimates that now seem too high. New infections outpace death, and the HIV epidemic in China is still growing.

China↗

PubMed2006

A novel method for gene expression mapping of metastatic competence in human bladder cancer.

Expression profiling by DNA microarray analysis has provided insights into molecular alterations that underpin cancer progression and metastasis. Although differential expression of microarray-defined probes can be related to numerical or structural chromosomal alterations, it is unclear if such changes are also clustered in distinct chromosomes or genomic regions and whether chromosomal alterations always reflect changes in gene expression. Here we apply the dChip algorithm and a novel technique to test the hypothesis that expression changes occurring as a function of tumor progression and metastasis are nonrandomly distributed. Expression profiling of a human xenograft model of lung metastasis phenotype indicates that chromosomes 2, 11, and 20 contain higher percentages of differentially expressed genes (P < .05). Furthermore, we show that a number of differentially expressed probes mapped to chromosome 17q, defining the existence of an expression "hot spot" corresponding to an area of gain determined by comparative genomic hybridization (CGH). Interestingly, other areas of gains detected by CGH were not associated with expression hot spots. In summary, we show that gene expression changes during bladder cancer lung metastasis occur nonrandomly in specific chromosomes and intrachromosomal locations.

Algorithms↗

PubMed2005

Trichinella pseudospiralis infection is characterized by more continuous and diffuse myopathy than T. spiralis infection.

A time course study was performed to reveal the sequence of histopathology after Trichinella spiralis or T. pseudospiralis infection in mice. A cyst was formed in the former case by about 18 days post infection and prominent myopathy was restricted within the cyst. In the latter case, however, no typical cyst was formed, and myopathy spread diffusely over the infected muscle tissues occupying half the area of muscle sections. An electron microscope observation revealed that the disintegration of muscle cells was delayed in T. pseudospiralis infection than in T. spiralis infection. Quantitative reverse transcription polymerase chain reaction (RT-PCR) showed that apoptosis-related genes were expressed for a longer term in muscles infected with T. pseudospiralis than in those with T. spiralis, although the same spectrum of genes are mobilized. Examined apoptosis-related genes included tumor suppressor genes p53, p53; mouse double minute 2, MDM2; cyclin-dependent kinase inhibitor p21 (WAF1), p21(waf) ; Bcl-2 associated protein X, BAX; apoptotic protease activating factor 1, Apaf-1; Caspase 9 and serine/ threonine protein kinase, PKB. Micro-dissection of the infected muscle tissue and subsequent RT-PCR confirmed that the expressions of these genes are restricted to tissue with myopathy. Thus, the expression of the apoptosis-related genes correlated with continuous and diffuse myopathy caused by T. pseudospiralis infection.

3-Phosphoinositide-Dependent Protein Kinases↗

PubMed2005

Molecular cloning and functional expression of enolase from Trichinella spiralis.

The cDNA library was constructed from muscle larvae of Trichinella spiralis, and immunoscreened with sera from mice infected with T. spiralis. A cDNA clone, designated as TsENO, encoded 2-phospho-D-glycerate hydro-lyase (enolase) that catalyzed a reversible conversion of 2-phospho-D-glyceric acid (2PGA) to phosphoenolpyruvate (PEP) in the glycolytic pathway. The recombinant TsENO protein was produced in an Escherichia coli expression system. The recombinant full-length TsENO protein had no activity in the conversion of 2PGA to PEP, but gained enolase activity after cutting off the signal peptide from the full-length protein. There was no meaningful difference in the expression level of TsENO gene at three distinct stages of T. spiralis. Also, antibody against the recombinant TsENO protein reacted with crude extract of muscle larvae, but not with the excretory and secretory products.

Amino Acid Sequence↗

PubMed2005

Dietary rescue of fumble--a Drosophila model for pantothenate-kinase-associated neurodegeneration.

Hallervorden-Spatz syndrome (HSS) is a devastating neurological disease, characterized by iron accumulation in the globus pallidus in the basal ganglia. Most HSS cases are caused by mutations in one of the four human pantothenate kinases (PANK2). This PANK2-caused subgroup of HSS is sometimes referred as PKAN (pantothenate-kinase-associated neurodegeneration). No effective treatment for PKAN or HSS is currently available. fumble, a Drosophila mutant that carries a mutation in Drosophila Pank, has many features similar to those of PKAN patients. In this study, we used fumble as a model to evaluate various compounds or nutritional products for their possible therapeutic efficacy. While no product was found to dramatically improve the symptoms, GKE (containing Ginkgo biloba extract and flavone) and vitamin E showed statistically significant beneficial effects. Our studies indicate that pantothenate is of limited value in alleviating fumble phenotypes and also suggest that some compounds might have deleterious effects.

Acetylcysteine↗

PubMed2005

A spectrum of functional genes mobilized after Trichinella spiralis infection in skeletal muscle.

Trichinella spiralis infection causes the transformation of infected muscle cells, which leads to nurse cell formation. To search for the candidate genes responsible for nurse cell formation, cDNA microarray analysis of muscle tissues was performed before and after Trichinella infection. The Atlas mouse 1.2 cDNA expression microarray revealed the expression profiles of 1176 known genes. Out of these, 311 gene expressions were detected in normal and/or infected muscles. After the infection, 184 out of the 311 genes increased in expression by more than 3-fold. These included genes responsible for cell differentiation, proliferation, cell cycle and apoptosis. Thus this study suggested candidate genes for further investigation to dissect the molecular mechanisms of nurse cell formation.

Animals↗

PubMed2005

Tumor necrosis factor receptor-mediated apoptosis in Trichinella spiralis-infected muscle cells.

In order to reveal the mechanisms underlying nurse cell formation during Trichinella spiralis infection, the expression of the factors of tumor necrosis factor-alpha (TNF-alpha)/TNF receptor 1 (TNFR-1) signalling pathway mediating apoptosis was investigated. The analysed factors included TNF-alpha, TNFR-1, TNF receptor-associated death-domain (TRADD), caspase 3, caspase 8, TNF receptor associated factor-2 (TRAF2) and receptor interactive protein (RIP), all of which are involved in the TNF-alpha/TNFR-1 signalling pathway-mediated apoptosis. The quantitative RT-PCR indicated that the infected muscle tissues up-regulate the expression of pro-apoptosis genes (TNF-alpha, TNFR-1 and TRADD, caspase 3 and caspase 8), and anti-apoptosis genes (TRAF2 and RIP) at the beginning of cyst formation. The expression returned to the normal level after cyst formation. The quantitative RT-PCR analysis of mRNA from tissue samples isolated by laser capture micro-dissection confirmed that the up-regulation of these genes was restricted in infected muscle cells, was not in the inflammation cells around infected muscle cells nor in normal muscle cells. The in situ localization study of proapoptosis (TRADD, caspase 3) and anti-apoptosis gene products (TRAF2) indicated that these were expressed in the basophilic cytoplasm (infected muscle cell origin) of the nurse cells. Thus the present study suggests that the TNF-alpha/ TNFR-1 signalling pathway is involved in nurse cell formation.

Animals↗

PubMed2005

What is the role of p53 during the cyst formation of Trichinella spiralis ? A comparable study between knockout mice and wild type mice.

During the cyst formation of Trichinella spiralis, the infected muscle cell undergoes basophilic change and apoptosis, which results in nurse cell formation. This study revealed expression kinetics of some apoptosis genes such as p53 and its closely related genes (tumor suppressor genes p53, p53; mouse double minute 2, MDM2; cyclin-dependent kinase inhibitor p21, p21waf). RT-PCR (reverse transcription polymerase chain reaction) results showed that these genes were temporarily expressed in the infected muscles during the cyst formation period, but not in normal muscles (or very low if any), which suggested the involvement of these apoptosis genes in the nurse cell formation. Cysts and neighbouring muscle cells were separately collected and RT-PCR was performed, which suggested that p53 was expressed in the cysts. An immunocytochemical study showed that p53 was expressed in the nucleoplasm of basophilic cell in the cyst and Trichinella larvae, which suggested involvement of these apoptosis genes in the nurse cell formation. The same p53 expression kinetic study was performed on p53 knockout mice. The knockout mice did not express p53 genes, but expressed the other apoptosis genes in the same kinetics with only minor exceptions, suggesting that the expressions of these genes during the cyst formation were more or less p53-independent. There were no differences in the number and morphology of the cysts between the knockout mice and wild type mice. Thus apoptosis seen during the Trichinella cyst formation can be operated in the presence or absence of p53.

Animals↗

PubMed2005

Single-locus complementary sex determination absent in Heterospilus prosopidis (Hymenoptera: Braconidae).

In the haplodiploid Hymenoptera, haploid males arise from unfertilized eggs, receiving a single set of maternal chromosomes while diploid females arise from fertilized eggs and receive both maternal and paternal chromosomes. Under single-locus complementary sex determination (sl-CSD), sex is determined by multiple alleles at a single locus. Sex locus heterozygotes develop as females, while hemizygous and homozygous eggs develop as haploid and diploid males, respectively. Diploid males, which are inviable or sterile in almost all cases studied, are therefore produced in high frequency under inbreeding or in populations with low sex allele diversity. CSD is considered to be the ancestral form of sex determination within the Hymenoptera because members of the most basal taxa have CSD while some of the more derived groups have other mechanisms of sex determination that produce the haplo-diploid pattern without penalizing inbreeding. In this study, we investigated sex determination in Heterospilus prosopidis Viereck, a parasitoid from a relatively primitive subfamily of the Braconidae, a hymenopteran family having species with and without CSD. By comparing sex ratio and mortality patterns produced by inbred and outbred females, we were able to rule out sl-CSD as a sex determination mechanism in this species. The absence of sl-CSD in H. prosopidis was unexpected given its basal phylogenetic position in the Braconidae. This and other recent studies suggest that sex determination systems in the Hymenoptera may be evolutionary labile.

Animals↗

PubMed2005

Utilization of phosphorus in lactating cows fed varying amounts of phosphorus and sources of fiber.

This study was undertaken to determine the effect of dietary P content and fiber source on P utilization. Four dietary treatments were formed in a 2 x 2 factorial arrangement. The P content was 0.32 or 0.44%, and the fiber source was varied by substituting 10% soyhulls for 6% alfalfa hay on a dry matter (DM) basis. Diets also contained approximately 50% corn silage and alfalfa silage for all treatments. The diets were fed to 32 early to midlactation Holsteins for 10 wk. Fecal P excretion was estimated using indigestible acid detergent fiber marker determined with 12-d in situ incubation and grab sampling. Milk yield was high, averaging 43 kg/d across treatments, and 42.1 and 44.0 kg/d for the 0.32 and 0.44% P diets, respectively. Milk fat content was also high, averaging 3.68 and 4.12% for the 0.32 and 0.44% P diets, respectively. Milk protein yield averaged 1.240 and 1.323 kg/d. Differences in milk production were associated with 1.5 kg/d less DM intake for the lower P diets on average. Based on lactation performance, 0.32% P appeared inadequate for this level of production, whereas the calculated (National Research Council) requirement was 0.37%. Fecal P concentration increased linearly with P intake, and based on this relationship, reducing dietary P from 0.44 to 0.37% would reduce fecal P excretion by 12%. Partial substitution of soyhulls for alfalfa hay did not affect feed intake or milk production, but reduced fecal P excretion, partially because of increased P apparent digestibility. The reduction in fecal P excretion resulting from reduced P intake or substitution of soyhulls for alfalfa hay was apparently through reductions in the regulated portion of fecal P. Cows producing 43 kg/d of milk appeared to need > 0.32% P, whereas the requirement assessed from National Research Council data was 0.37%. Using highly digestible nonforage fiber sources in place of forage fiber sources in the diet may allow less P to be fed while still meeting the requirement.

Animal Nutritional Physiological Phenomena↗