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Biomedical subjects

Yu Wang

Publications and source records attributed to Yu Wang.

At least 73 records · Page 4Linked to original sources

A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development.

The chemokine stromal cell-derived factor (SDF-1; also known as chemokine ligand 12 [CXCL12]) regulates many essential biological processes, including cardiac and neuronal development, stem cell motility, neovascularization, angiogenesis, apoptosis, and tumorigenesis. It is generally believed that SDF-1 mediates these many disparate processes via a single cell surface receptor known as chemokine receptor 4 (CXCR4). This paper characterizes an alternate receptor, CXCR7, which binds with high affinity to SDF-1 and to a second chemokine, interferon-inducible T cell alpha chemoattractant (I-TAC; also known as CXCL11). Membrane-associated CXCR7 is expressed on many tumor cell lines, on activated endothelial cells, and on fetal liver cells, but on few other cell types. Unlike many other chemokine receptors, ligand activation of CXCR7 does not cause Ca2+ mobilization or cell migration. However, expression of CXCR7 provides cells with a growth and survival advantage and increased adhesion properties. Consistent with a role for CXCR7 in cell survival and adhesion, a specific, high affinity small molecule antagonist to CXCR7 impedes in vivo tumor growth in animal models, validating this new receptor as a target for development of novel cancer therapeutics.

Animals↗

Differentiation of rat bone marrow stem cells in liver after partial hepatectomy.

AIM: To investigate the differentiation of rat bone marrow stem cells in liver after partial hepatectomy. METHODS: Bone marrow cells were collected from the tibia of rat with partial hepatectomy, the medial and left hepatic lobes were excised. The bone marrow stem cells (Thy(+)CD3(-)CD45RA(-) cells) were enriched from the bone marrow cells by depleting red cells and fluorescence-activated cell sorting. The sorted bone marrow stem cells were labeled by PKH26-GL in vitro and autotransplanted by portal vein injection. After 2 wk, the transplanted bone marrow stem cells in liver were examined by the immunohistochemistry of albumin (hepatocyte-specific marker). RESULTS: The bone marrow stem cells (Thy(+)CD3(-)CD45RA(-) cells) accounted for 2.8% of bone marrow cells without red cells. The labeling rate of 10 microM PKH26-GL on sorted bone marrow stem cells was about 95%. There were sporadic PKH26-GL-labeled cells among hepatocytes in liver tissue section, and some of the cells expressed albumin. CONCLUSION: Rat bone marrow stem cells can differentiate into hepatocytes in regenerative environment and may participate in liver regeneration after partial hepatectomy.

Animals↗

Vibrational spectra of metals treated with allyltrimethoxysilane sol-gel and self-assembled monolayer of allytrichlorosilane.

A sol-gel has been prepared by using allyltrimethoxysilane (ATMS) as precursor, ethanol as homogenizer as well as solvent, and hydrochloric acid as catalyst. The sol-gel was employed for the coating treatment of aluminum. Self-assembled monolayer (SAM) with allyltrichlorosilane (ATCS) is another method used for the metal surface treatment in the present work. The treated metal surfaces were characterized with reflection adsorption infrared spectra (RAIR). Detailed interpretation and vibrational assignment have been given to the collected IR spectra of the sol-gel, xerogel and surface films of ATMS and the SAM of ATCS on aluminum as well as pure silanes. A series of investigation of the UV exposure and temperature effects has been carried out. Results from the investigation indicate that the UV radiation exposure or the high temperature thermal treatment will induce a chemical process on the organosilica coated surfaces.

Adsorption↗

[Effects of GLP-1 treatment on protection of B cells in Otsuka Long-Evans Tokushima fatty rats].

OBJECTIVE: To investigate the effect of GLP-1 on the blood glucose in type 2 diabetic rats, and its protective effects on the islet B cells. METHODS: Thirty rats were divided into three groups: spontaneous type 2 diabetes animal model OLETF rats, GLP-1 [from the twelfth week 56 micro/(kg.d), sc] therapy group and LETO rats as control. In the 14th and 20th weeks, standard OGTT including fast and 2 h-plasma glucose were measured respectively. In the 14th weeks, 3 rats from each group were killed randomly, and the rest of the rats were killed until the 20th week. Immunostaining with the marker of PCNA, TUNEL, and insulin assessed metabolic changes in the islet. Ultrastructure of the B cell was observed with the electronic microscope. RESULTS: In the 14th and 20th week, AUC for insulin were higher in treated animals (10.86+/-1.56 vs. 9.07+/-1.28, P<0.01) and (13.00+/-1.50 vs. 10.35+/-0.86, P<0.01), which was paralleled by a decrease in AUC for glucose, (29.93+/-3.15 vs. 34.99+/-4.30, P<0.01) and (38.37+/-3.18 vs. 42.38+/-2.37, P<0.01). Ex vivo immunostaining with the marker of cell proliferation, PCNA, showed that the metabolic changes observed in rats treated with GLP-1 were associated with an increase in cell proliferation of the B cell (48.9+/-39.6 vs. 39.6+/-9.3, P<0.05). TUNEL staining, a marker of cellular apoptosis, indicated a reduction of apoptotic cells within the islet in GLP-1-treated rats (24.8+/-4.2 vs. 30.8+/-5.8, P<0.01). Immunostaining for the insulin showed a significant increase in insulin content in GLP-1-treated animals. GLP-1-treatment ameliorated the ultrastructure of the B cell. CONCLUSION: Our findings have provided evidence that the beneficial effects of GLP-1 in OLETF rats are mediated by an increase in islet cell proliferation and a decrease of cellular apoptosis.

Animals↗

Significant sequence similarities in promoters and precursors of Arabidopsis thaliana non-conserved microRNAs.

Some plant microRNAs have been shown to be de novo generated by inverted duplication from their target genes. Subsequent duplication events potentially generate multigene microRNA families. Within this article we provide supportive evidence for the inverted duplication model of plant microRNA evolution. First, we report that the precursors of four Arabidopsis thaliana microRNA families, miR157, miR158, miR405 and miR447 share nearly identical nucleotide sequences throughout the whole miRNA precursor between the family members. The extent and degree of sequence conservation is suggestive of recent evolutionary duplication events. Furthermore we found that sequence similarities are not restricted to the transcribed part but extend into the promoter regions. Thus the duplication event most probably included the promoter regions as well. Conserved elements in upstream regions of miR163 and its targets were also detected. This implies that the inverted duplication of target genes, at least in certain cases, had included the promoters of the target genes. Sequence conservation within promoters of miRNA families as well as between miRNA and its potential progenitor gene can be exploited for understanding the regulation of microRNA genes.

Arabidopsis↗

Rapamycin-mediated enrichment of T cells with regulatory activity in stimulated CD4+ T cell cultures is not due to the selective expansion of naturally occurring regulatory T cells but to the induction of regulatory functions in conventional CD4+ T cells.

Rapamycin is an immunosuppressive drug currently used in different clinical settings. Although the capacity of rapamycin to inhibit the mammalian target of rapamycin serine/threonine protein kinase and therefore T cell cycle progression is well known, its effects are complex and not completely understood. It has been reported recently that TCR-mediated stimulation of murine CD4+ T cells in the presence of rapamycin results in increased proportions of CD4+ T cells with suppressive functions, suggesting that the drug may also exert its immunosuppressive activity by promoting the selective expansion of naturally occurring CD4+ regulatory T cells (Treg). In this study, we show that stimulation of human circulating CD4+ T cells in the presence of rapamycin results indeed in highly increased suppressor activity. By assessing the effect of rapamycin on the growth of nonregulatory and Treg populations of defined differentiation stages purified ex vivo from circulating CD4+ T cells, we could demonstrate that this phenomenon is not due to a selective expansion of naturally occurring Tregs, but to the capacity of rapamycin to induce, upon TCR-mediated stimulation, suppressor functions in conventional CD4+ T cells. This condition, however, is temporary and reversible as it is dependent upon the continuous presence of rapamycin.

Antibodies, Monoclonal↗

[A cross-sectional study of hyperuricemia in state-employees in Beijing: prevalence and risk factors].

OBJECTIVE: To investigate prevalence of hyperuricemia and its risk factors in Beijing. METHODS: A cross-sectional study was carried out in four groups of state-employees in Beijing, China. Demographic, dietary and clinical data were collected by questionnaires, physical examination, and biochemical assay. Data were analyzed by multivariate logistic regression models. RESULTS: 1217 men and 780 women participated in the study. HDL and LDL were excluded as they were not missing completely at random in missing variable analysis. The serum uric acid level was (331 +/- 74) micromol/L (mean +/- SD) for men and (254 +/- 61) micromol/L (mean +/- SD) for women. It was stable for both sexes before the age of 50, increased in women but tended to decrease in man thereafter. 13.8% of men and 6.0% of women had hyperuricemia, which was defined as serum uric acid >or= 416.4 micromol/L in men and >or= 356.9 micromol/L in women, or taking medication for it. The prevalence of hyperuricemia increased steadily as women aged and surpassed that of men after the age of 70, while it appeared to decrease after 60 in men. Multivariate logistic regression models found that male gender (OR 2.46, 95% CI 1.63 - 3.69), non-Han Chinese ethnicity (OR 2.47, 95% CI 1.02 - 5.98 for Chinese Muslim), renal dysfunction (OR 12.88, 95% CI 4.07 - 40.79 for GFR < 30 ml/min), and diuretics (OR 2.25, 95% CI 1.42 - 3.57) were associated with increased risk of hyperuricemia, whereas retirement (OR 0.21, 95% CI 0.12 - 0.38) was associated with substantially reduced risk of hyperuricemia, after adjusted for overweight/obesity, hypertension and hypertriglyceridemia. Age, menopause, low-dose aspirin were not found to be associated with hyperuricemia independently. Although retirement was associated with less consumption of meat, fat, alcohol (beer, hard liquor, and wine), and more physical exercises, neither of these factors were found to be associated with hyperuricemia independently. CONCLUSIONS: Male gender, non-Han Chinese ethnicity (Muslim), renal dysfunction, diuretics, overweight/obesity, hypertension and hypertriglyceridemia are associated with increased risk of hyperuricemia. Retirement is associated with reduced risk of hyperuricemia.

Adult↗

Chiral layered zincophosphate [d-Co(en)3]Zn3(H0.5PO4)2(HPO4)2 assembled about d-Co(en)(3)3+ complex cations.

A new chiral layered zincophosphate [d-Co(en)3]Zn3(H(0.5)PO4)2(HPO4)2, designated ZnPO-CJ16, has been hydrothermally synthesized by using the optically pure chiral metal complex d-Co(en)3I3 as the template. It contains 4.6-net sheets which array in a helical fashion with an ABCDEF stacking sequence along the [001] direction. The chiral d-Co(en)3(3+) complex cations reside in the interlayer regions. Interestingly, there exist symmetrical O...H...O H-bonds between inorganic sheets, which results in a pseudo-three-dimensional open-framework structure stabilized by strong H-bonds. The crystal data are as follows: ZnPO-CJ16, [d-Co(en)3]Zn3(H(0.5)PO4)2(HPO4)2; M = 818.26; hexagonal; P6(5)22 (No. 179); a = 8.5832(12) A; c = 52.610(11) A; U = 3356.6(9) A(3); T = 293(2) K; Z = 6; R1 = 0.0415 (I > 2sigma(I)); wR2 = 0.1383 (all data); Flack parameter, 0.04(4).

Journal Article↗

Citrobacter rodentium-induced NF-kappaB activation in hyperproliferating colonic epithelia: role of p65 (Ser536) phosphorylation.

1. The transcription factors of the NF-kappaB/Rel family form dimeric complexes that control expression of various genes involved in inflammation and proliferation. 2. During transmissible murine colonic hyperplasia (TMCH) induced by Citrobacter rodentium, nuclear translocation of NF-kappaB in isolated colonic crypts increased 3 day's post-infection and continued over 12 days paralleling peak hyperplasia. Antibody supershifts for both p65/p50 hetero- and p50/p50 homodimers occurred. Expression levels of both p50 and p65 subunits increased in cytosolic/nuclear extracts and correlated with NF-kappaB activation kinetics. IkappaB alpha levels decreased during this time. 3. Phosphorylation of IKK alpha (at Ser(176/180)) and -beta (at Ser(177/181)) increased significantly during TMCH suggesting activation in vivo. 4. p65-Ser536 (p65(536)) exhibited increased phosphorylation on immunoblotting and immunohistochemistry (IHC) both at day 6 and 12 TMCH. p65(536) translocated to nucleus and interacted with transcriptional coactivator CREB binding protein (CBP). 5. Proteasomal inhibitor bortezomib (Velcade) caused accumulation of Ser(32/36)-phosphorylated IkappaB alpha and significant inhibition of NF-kappaB activity in vivo. Velcade also blocked nuclear translocation of activated p65: both immunoblotting and IHC failed to detect p65(536) nuclear immunoreactivity. Velcade, however, did not abrogate TMCH. 6. p65 interacted strongly with ribosomal S6 kinase 1 (RSK-1) during coimmunoprecipitation but not with IKK alpha or -beta. 7. Thus, NF-kappaB activation during TMCH involves both IkappaB alpha degradation and p65-Ser536 phosphorylation. p65/RSK-1 interaction and concomitant increase in p65(536) complexed with CBP may be important in modulating NF-kappaB activity in vivo. Activated NF-kappaB, besides modulating proliferation, may aid in providing protective immunity against C. rodentium infection in vivo.

Animals↗

Growth mechanism of textured MgO thin films via SSCVD.

Magnesium oxide thin films have been deposited with use of single source chemical vapor deposition (SSCVD). The resultant films were examined by using transmission electron microscopy, X-ray texture analysis, and pole figure analysis. Due to the nature of the chemical reactions occurring at the surface during SSCVD growth, which result in a high growth rate/low flux environment, films of (111) orientation have been achieved without an amorphous underlayer, an unusual result for films of this orientation. Moreover the films have a strong degree of biaxial texturing in the x-y plane as found with X-ray texture analysis. These findings have important implications for buffer layers in perovskite thin film devices. The mechanism producing these structures has been revealed by using TEM and is discussed here.

Journal Article↗

Neurotransmitter inactivation is important for the origin of nerve system in animal early evolution: a suggestion from genomic comparison.

Metazoans possess complicated multicellular structure among the multicellularities of eukaryotes. One evolutionary pressure that permits such complexity relates to the directed and precise informational transmission performed by numerous synapses in neuron system. Neurotransmitter inactivations play essential roles in the termination of synaptic transmission and are thus crucial for precise synaptic transmission. Here, we performed a genomic comparison among 11 eukaryotic organisms including five bilaterian species and six pan-unicellular eukaryotes to search for genes related to metazoan multicellular function. The result showed that the majority of genes related to neurotransmitter inactivation in the synaptic cleft endured high and stable selective pressure and were specifically present in bilaterians, whereas genes related to transmitter release and postsynaptic transmitter receptors did not show these properties. From these data we conclude that neurotransmitter inaction may play a critical role in the origin of the nerve system encountered in the early evolution of metazoan. In addition, we suggest that neurotransmitter inactivation probably participates in the formation or refinement of the synapse, following the concept of "ontogeny recapitulates phylogeny." Further experimental evidence is needed to support the suggestion and to explain the importance of neurotransmitter inactivation to metazoan multicellular function.

Animals↗

Genistein inhibits radiation-induced activation of NF-kappaB in prostate cancer cells promoting apoptosis and G2/M cell cycle arrest.

BACKGROUND: New cancer therapeutic strategies must be investigated that enhance prostate cancer treatment while minimizing associated toxicities. We have previously shown that genistein, the major isoflavone found in soy, enhanced prostate cancer radiotherapy in vitro and in vivo. In this study, we investigated the cellular and molecular interaction between genistein and radiation using PC-3 human prostate cancer cells. METHODS: Tumor cell survival and progression was determined by clonogenic analysis, flow cytometry, EMSA analysis of NF-kappaB, and western blot analysis of cyclin B1, p21WAF1/Cip1, and cleaved PARP protein. RESULTS: Genistein combined with radiation caused greater inhibition in PC-3 colony formation compared to genistein or radiation alone. Treatment sequence of genistein followed by radiation and continuous exposure to genistein showed optimal effect. Cell cycle analysis demonstrated a significant dose- and time-dependent G2/M arrest induced by genistein and radiation that correlated with increased p21WAF1/Cip1 and decreased cyclin B1 expression. NF-kappaB activity was significantly decreased by genistein, yet increased by radiation. Radiation-induced activation of NF-kappaB activity was strongly inhibited by genistein pre-treatment. A significant and striking increase in cleaved PARP protein was measured following combined genistein and radiation treatment, indicating increased apoptosis. CONCLUSION: A mechanism of increased cell death by genistein and radiation is proposed to occur via inhibition of NF-kappaB, leading to altered expression of regulatory cell cycle proteins such as cyclin B and/or p21WAF1/Cip1, thus promoting G2/M arrest and increased radiosensitivity. These findings support the important and novel strategy of combining genistein with radiation for the treatment of prostate cancer.

Anticarcinogenic Agents↗

Post-translational modifications of the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high molecular weight oligomeric complex.

Adiponectin is a multifunctional adipokine that circulates as several oligomeric complexes in the blood stream. However, the molecular basis that regulates the production of the adiponectin oligomers remains largely elusive. We have shown previously that several conserved lysine residues (positions 68, 71, 80, and 104) within the collagenous domain of adiponectin are modified by hydroxylation and glycosylation (Wang, Y., Xu, A., Knight, C., Xu, L. Y., and Cooper, G. J. (2002) J. Biol. Chem. 277, 19521-19529). Here, we investigated the potential roles of these post-translational modifications in oligomeric complex formation of adiponectin. Gel filtration chromatography revealed that adiponectin produced from mammalian cells formed trimeric, hexameric, and high molecular weight (HMW) oligomeric complexes. These three oligomeric forms were differentially glycosylated, with the HMW oligomer having the highest carbohydrate content. Disruption of hydroxylation and glycosylation by substitution of the four conserved lysines with arginines selectively abrogated the intracellular assembly of the HMW oligomers in vitro as well as in vivo. In type 2 diabetic patients, both the ratios of HMW to total adiponectin and the degree of adiponectin glycosylation were significantly decreased compared with healthy controls. Functional studies of adiponectin-null mice revealed that abrogation of lysine hydroxylation/glycosylation markedly decreased the ability of adiponectin to stimulate phosphorylation of AMP-activated protein kinase in liver tissue. Chronic treatment of db/db diabetic mice with wild-type adiponectin alleviated hyperglycemia, hypertriglyceridemia, hepatic steatosis, and insulin resistance, whereas full-length adiponectin without proper post-translational modifications and HMW oligomers showed substantially decreased activities. Taken together, these data suggest that hydroxylation and glycosylation of the lysine residues within the collagenous domain of adiponectin are critically involved in regulating the formation of its HMW oligomeric complex and consequently contribute to the insulin-sensitizing activity of adiponectin in hepatocytes.

Adipocytes↗

Fast simultaneous determination of urinary 1-hydroxypyrene and 3-hydroxybenzo[a]pyrene by liquid chromatography-tandem mass spectrometry.

A fast analysis method using liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry was developed for the simultaneous determination of the 1-hydroxypyrene (1-OHP) and 3-hydroxybenzo[a]pyrene (3-OHBaP) in urine. Mass transitions were monitored at m/z 219.3-200.0 for 1-OHP and m/z 269.2-252.2 for 3-OHBaP. Only 10 min was needed for the analysis. The recovery was 60% for 3-OHBaP and 91% for 1-OHP, respectively. And the method detection limits were 0.49 microg/L for 1-OHP and 1.03 microg/L for 3-OHBaP. The inter- and intra-day relative standard deviations were in the range of 2.8-8.9% for 1-OHP and 9.7-20.8% for 3-OHBaP, respectively. The developed method was successfully used to measure urinary PAH metabolites of student volunteers in a high school.

Adolescent↗

Streptococcal toxic shock syndrome caused by Streptococcus suis serotype 2.

BACKGROUND: Streptococcus suis serotype 2 (S. suis 2, SS2) is a major zoonotic pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most if not all cases of Streptococcal toxic shock syndrome (STSS) that have been well-documented to date were associated with the non-SS2 group A streptococcus (GAS). However, a recent large-scale outbreak of SS2 in Sichuan Province, China, appeared to be caused by more invasive deep-tissue infection with STSS, characterized by acute high fever, vascular collapse, hypotension, shock, and multiple organ failure. METHODS AND FINDINGS: We investigated this outbreak of SS2 infections in both human and pigs, which took place from July to August, 2005, through clinical observation and laboratory experiments. Clinical and pathological characterization of the human patients revealed the hallmarks of typical STSS, which to date had only been associated with GAS infection. Retrospectively, we found that this outbreak was very similar to an earlier outbreak in Jiangsu Province, China, in 1998. We isolated and analyzed 37 bacterial strains from human specimens and eight from pig specimens of the recent outbreak, as well as three human isolates and two pig isolates from the 1998 outbreak we had kept in our laboratory. The bacterial isolates were examined using light microscopy observation, pig infection experiments, multiplex-PCR assay, as well as restriction fragment length polymorphisms (RFLP) and multiple sequence alignment analyses. Multiple lines of evidence confirmed that highly virulent strains of SS2 were the causative agents of both outbreaks. CONCLUSIONS: We report, to our knowledge for the first time, two outbreaks of STSS caused by SS2, a non-GAS streptococcus. The 2005 outbreak was associated with 38 deaths out of 204 documented human cases; the 1998 outbreak with 14 deaths out of 25 reported human cases. Most of the fatal cases were characterized by STSS; some of them by meningitis or severe septicemia. The molecular mechanisms underlying these human STSS outbreaks in human beings remain unclear and an objective for further study.

Adult↗

The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration.

Dyslexia is one of the most prevalent childhood cognitive disorders, affecting approximately 5% of school-age children. We have recently identified a risk haplotype associated with dyslexia on chromosome 6p22.2 which spans the TTRAP gene and portions of THEM2 and KIAA0319. Here we show that in the presence of the risk haplotype, the expression of the KIAA0319 gene is reduced but the expression of the other two genes remains unaffected. Using in situ hybridization, we detect a very distinct expression pattern of the KIAA0319 gene in the developing cerebral neocortex of mouse and human fetuses. Moreover, interference with rat Kiaa0319 expression in utero leads to impaired neuronal migration in the developing cerebral neocortex. These data suggest a direct link between a specific genetic background and a biological mechanism leading to the development of dyslexia: the risk haplotype on chromosome 6p22.2 down-regulates the KIAA0319 gene which is required for neuronal migration during the formation of the cerebral neocortex.

Animals↗