Biomedical subjects
Publications and source records attributed to Tao Yang.
Four new sesterterpenoids, terretonins A-D (1-4), and a new alkaloid, asterrelenin (5), together with five known compounds, were isolated from the ethyl acetate extract of a solid-state fermented culture of Aspergillus terreus. Their structures were elucidated on the basis of spectroscopic analysis. The structures of 1, 2, and 5 were confirmed by X-ray crystallographic analysis.
Elucidation of mechanisms by which receptor protein tyrosine phosphatases (PTPs) regulate neurite outgrowth will require characterization of ligand-receptor interactions and identification of ligand-induced signalling components mediating neurite outgrowth. The first identified ligand of the leucocyte common antigen-related (LAR) receptor PTP consists of a 99-residue ectodomain isoform, termed LARFN5C, which undergoes homophilic binding to LAR and promotes neurite outgrowth. We employed peptide mapping of LARFN5C to identify an active neurite-promoting domain of LAR. A peptide mimetic consisting of 37 residues (L59) and corresponding to the fifth LAR fibronectin type III (FNIII) domain prevented LARFN5C homophilic binding, demonstrated homophilic binding to itself and promoted neurite outgrowth of mouse E16-17 hippocampal neurons and of dorsal root ganglia explants. Response to L59 was partially lost when using neurons derived from LAR-deficient (-/-) mice or neurons treated with LAR siRNA, consistent with homophilic interaction of L59 with LAR. L59 neurite-promoting activity was decreased in the presence of inhibitors of Src, Trk, PLCgamma, PKC, PI3K and MAPK. L59 activated Src (a known substrate of LAR), FAK and TrkB and also activated downstream signalling intermediates including PKC, ERK, AKT and CREB. BDNF augmented the maximal neurite-promoting activity of L59, a finding consistent with the presence of shared and distinct signalling pathways activated by L59 with BDNF and L59 with TrkB. These studies are the first to identify an ectodomain of LAR (located within the fifth FNIII domain) capable of promoting neurite outgrowth and point to novel approaches for promotion of neurite outgrowth.
BACKGROUND: A recent in vitro model of oxidative stress-induced renal fibrosis demonstrated that activated or phosphorylated extracellular signal-regulated protein kinase (pERK) played a role in apoptosis of renal fibroblasts, but not tubular epithelium where it promoted cell growth and survival. The present study utilized an in vivo model of renal fibrosis after unilateral ureteral obstruction (UUO) to examine the relationship between pERK, apoptosis, proliferation, and differentiation in renal fibroblast and tubular epithelial cells, in comparison with the in vitro results. METHODS: UUO was induced in rats for 0 (controls, untreated), 6, and 24 hours, 2, 4, and 7 days (N= 4), and tissue analyzed for fibrotic characteristics using microscopy and special stains, Western immunoblots and reverse transcription-polymerase chain reaction (RT-PCR). Controls and UUO animals were also treated with vitamin E, N-acetylcysteine (NAC), or fluvastatin to assess any antioxidant effect on attenuation of fibrosis and pERK expression. RESULTS: Azan stain and alpha-smooth muscle actin (alpha-SMA), collagen III, and fibronectin expression confirmed development of UUO-induced fibrosis. Oxidative stress markers heme oxygenase-1 (HO-1) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) confirmed oxidative stress at all UUO time points. Tubular epithelial and interstitial mitosis and apoptosis were significantly increased over controls at 2 to 7 days after UUO (P < 0.01). The pERK/ERK ratio increased significantly at 1 to 7 days of UUO in comparison with controls (three- to fivefold, P < 0.05). There was a significant spatiotemporal correlation between pERK and tubular epithelial proliferation (P < 0.001). pERK occasionally colocalized with apoptotic cells (dual labeling) in the interstitium but not in the tubular epithelium. Fluvastatin was the only treatment that attenuated fibrosis (decreased alpha-SMA, fibronectin, tubular epithelial apoptosis) and it also significantly decreased expression of 8-OHdG at 2 and 7 days (P < 0.05). It was associated with decreased pERK at 7 days, compared with UUO alone (P < 0.05). CONCLUSION: Promotion of tubular epithelial proliferation and survival, and interstitial cell apoptosis, may minimize renal fibrosis after UUO. In the present study, both were linked spatially and temporally with increased pERK expression. Fluvastatin treatment attenuated UUO-induced fibrosis via an antioxidant and pERK-related mechanism.
OBJECT: Pyridoxal-5-phosphate (PLP), the biologically active form of pyridoxine, can rescue neurons from death in vitro and in vivo. In the present project, the authors have studied whether MC-1, an analog of PLP, alone or in combination with the thrombolytic agent tissue plasminogen activator (tPA), can protect the brains of rats injured by ischemia. METHODS: Ischemic brain injury was induced in rats by injecting a preformed blood clot in the middle cerebral artery (MCA). Neurological deficits and infarct volumes caused by the embolus were measured to evaluate the effects of MC-1 on the ischemic injury. Systemic blood pressure and local brain blood flow were also monitored. Administration of different doses of MC-1 1 hour after embolization significantly reduced the infarct volume and improved functional recovery. Injection of MC-1 (40 mg/kg) at 3 or 6 hours after embolization also reduced the volume of the infarct significantly and improved functional recovery. Combined treatment with MC-1 and tPA was also neuroprotective, although it was not superior to treatment involving either MC-1 or tPA alone. Treatment with MC-1 did not result in significant changes in either systemic blood pressure or local blood flow in the ischemic brain. CONCLUSIONS: These data support the hypothesis that in the focal embolic stroke model in rats MC-1 is a neuroprotective agent. The neuroprotection this compound provides still exists when MC-1 administration is delayed up to 6 hours after ischemic injury.
OBJECTIVE: To assess the relationship between plasma homocysteine with chronic complications in type 2 diabetes mellitus. METHOD: Plasma homocysteine levels, blood glucose, and HbA1c were measured in 60 diabetic patients (including 30 with and 30 without complications) and 31 normal subjects. The difference in the occurrence of chronic complications between patients with and without hyperhomocysteinemia was investigated. RESULTS: Plasma homocysteine level was significantly higher in type 2 diabetic patients with chronic complication than in normal control subjects (P<0.01), and patients with chronic complications had higher homocysteine levels than those without chronic complications (P<0.01). CONCLUSION: Hyperhomocysteinemia is related to chronic complication in 2 diabetes mellitus, possibly due to the injury to the vascular endothelium by homocysteine.
The study showed that the upper reaches of main petroleum-containing wastewater irrigation channels had the highest accumulation and distribution of total petroleum hydrocarbon (TPH) (5 213.37 mg x kg(-1) dry soil),and the CFU of soil bacteria and fungi was increased with increasing soil TPH concentration, the correlation coefficient being 0.928 (P < 0.001) and 0.772 (P < 0.05), respectively. The activities of soil dehydrogenase, catalase and polyphenoloxidase had a significantly positive correlation with soil TPH concentration, their correlation coefficient being 0.974 (P < 0.001), 0.957 (P < 0.001) and 0.886 (P < 0.001), respectively, while soil urease activity showed a significantly negative correlation (P = 0.002), which could be used as the most sensitive indicator of petroleum contamination. The substrate-induced respiration (SIR) of polluted soil was significantly correlated with soil TPH concentration (P < 0.001), dehydrogenase activity (P < 0.001), and heterotrophic bacterial CFU (P = 0.006).
Netherton syndrome (NS) is a human autosomal recessive skin disease caused by mutations in the SPINK5 gene, which encodes the putative proteinase inhibitor LEKTI. We have generated a transgenic mouse line with an insertional mutation that inactivated the mouse SPINK5 ortholog. Mutant mice exhibit fragile stratum corneum and perinatal death due to dehydration. Our analysis suggests that the phenotype is a consequence of desmosomal fragility associated with premature proteolysis of corneodesmosin, an extracellular desmosomal component. Our mouse mutant provides a model system for molecular studies of desmosomal stability and keratinocyte adhesion, and for designing therapeutic strategies to treat NS.
A new anhydrous aluminoborate Al4B6O15 (PKU-5) has been synthesized in a boric acid flux in a closed system at 350 degrees C. PKU-5, which crystallizes in the space group R3 with the lattice constants a=11.43398(9) and c=6.48307(5) A, consists of Al octahedra and triangularly coordinated boron. The Al octahedron adopts the (10,3)-a network, in which each octahedron shares three edges with the neighboring octahedra forming ten-membered-ring channels. The octahedral backbone in PKU-5 can be considered as a primary octahedral framework topology and, setting out from the structures of the aluminoborates (PKU-1 and PKU-5), we propose construction rules for the octahedral frameworks. There are two types of connections for edge-sharing octahedra in porous frameworks, trans and cis type, by which various microporous octahedral frameworks of different topologies can be constructed. The borate groups share oxygens with the Al octahedral frameworks forming two kinds of three-membered-ring units consisting of two octahedra and one triangle (2Al+B) and one octahedron and two triangles (Al+2B), respectively.
Quantum-mechanical entanglement of three or four particles has been achieved experimentally, and has been used to demonstrate the extreme contradiction between quantum mechanics and local realism. However, the realization of five-particle entanglement remains an experimental challenge. The ability to manipulate the entanglement of five or more particles is required for universal quantum error correction. Another key process in distributed quantum information processing, similar to encoding and decoding, is a teleportation protocol that we term 'open-destination' teleportation. An unknown quantum state of a single particle is teleported onto a superposition of N particles; at a later stage, this teleported state can be read out (for further applications) at any of the N particles, by a projection measurement on the remaining particles. Here we report a proof-of-principle demonstration of five-photon entanglement and open-destination teleportation (for N = 3). In the experiment, we use two entangled photon pairs to generate a four-photon entangled state, which is then combined with a single-photon state. Our experimental methods can be used for investigations of measurement-based quantum computation and multi-party quantum communication.
Normal membrane protein function requires trafficking from the endoplasmic reticulum. Here, we studied processing of the KCNQ1 channel mutated in LQT1, the commonest form of the long QT syndrome. Serial C terminus truncations identified a small region (amino acids (aa) 610-620) required for normal cell surface expression. Non-trafficked truncations assembled as tetramers but were nevertheless retained in the endoplasmic reticulum. Further mutagenesis did not identify specific residues mediating channel processing; cell surface expression was preserved with the mutation of known trafficking motifs in the channel and with alanine scanning across aa 610-620. Structural prediction algorithms place aa 610-620 at the C-terminal end of an alpha-helix (aa 586-618) that includes a leucine zipper and is part of a coiled coil. Mutants disrupting the leucine zipper but preserving the predicted coiled coil reached the cell surface, whereas those disrupting the coil did not. These data suggest that specific protein-protein interactions are required for normal channel processing. Further biochemical studies ruled out three candidate proteins, namely KCNE1, yotiao, and KCNQ1 itself, as effectors of this coiled coil-mediated trafficking. Four LQT1 mutations within this helix generated little or no current and were not expressed on the cell surface, whereas LQT1 mutations in adjacent residues, which produce a milder clinical phenotype, generate only slightly reduced current and are expressed on the cell surface. These data suggest that mutations within this domain cause human disease by interfering with normal channel processing. More generally, we have identified a domain whose structural integrity is required for normal surface expression of the KCNQ1 channel.
Zinc is prevalent in the mammalian central nervous system and its role in ischemic brain injury is still controversial. In the present study, the effect of zinc in ischemic brain injury was examined in an embolic model of stroke in rats. Furthermore, the effect of zinc in combination with bicuculline, a GABAa antagonist, was also examined in the ischemic injury. Treatment with zinc or zinc plus bicuculline increased infarct volume significantly and also worsened neurological deficits. Moreover, treatment with zinc plus bicuculline also enhanced ischemic brain edema. These results thus support the hypothesis that administration of zinc i.p. worsens the outcome of ischemic brain injury in the embolic model of stroke in rats.
Oxidative stress frequently leads to altered function of membrane proteins. Isoketals are highly reactive products of the isoprostane pathway of free radical-induced lipid peroxidation that rapidly form covalent protein adducts and exhibit a remarkable proclivity to form protein cross links in vitro. Examination of isoketal adducts from an animal model of oxidative injury revealed that initial adducts were formed by isoketals esterified in phospholipids, representing a novel oxidative injury-associated modification of proteins by phospholipids. Maturation of adducts involved cleavage from phospholipids and conversion of adducts to a more stable chemical form that can be detected for extended periods. Because initial adducts were formed by phospholipid-esterified isoketals, the functional consequence of isoketal adduction was examined using a model membrane protein (a cardiac K(+) channel). These studies revealed that isoketal adduction profoundly altered protein function, inhibiting potassium current in a dose-dependent manner. These findings indicate that phospholipid-esterified isoketals rapidly adduct membrane proteins and that such modification can alter protein function, suggesting a generalized cellular mechanism for alteration of membrane function as a consequence of oxidative stress.
The purpose of this study was to delineate the traffic patterns of EGF and EGF receptors (EGFR) in primary cultured acinar epithelial cells from rabbit lacrimal glands. Uptake of [(125)I]-EGF exhibited saturable and non-saturable, temperature-dependent components, suggesting both receptor-mediated and fluid phase endocytosis. Accumulation of [(125)I] was time-dependent over a 120-min period, but the content of intact [(125)I]-EGF decreased after reaching a maximum at 20 min. Analytical fractionation by sorbitol density gradient centrifugation and phase partitioning indicated that within 20 min at 37 degrees C [(125)I] reached an early endosome, basal-lateral recycling endosome, pre-lysosome, and lysosome. Small components of the label also appeared to reach the Golgi complex and trans-Golgi network. Intact [(125)I]-EGF initially accumulated in the recycling endosome; the content in the recycling endosome subsequently decreased, and by 120 min increased amounts of [(125)I]-labeled degradation products appeared in the pre-lysosomes and lysosomes. Confocal microscopy imaging of FITC-EGF and LysoTrackerRed revealed FITC enriched in a dispersed system of non-acidic compartments at 20 min and in acidic compartments at 120 min. Both confocal immunofluorescence microscopy and analytical fractionation indicated that the intracellular EGFR pool was much larger than the plasma membrane-expressed pool at all times. Cells loaded with [(125)I]-EGF released a mixture of intact EGF and [(125)I]-labeled degradation products. The observations indicate that in lacrimal acinar cells, EGFR and EGF-EGFR complexes continually traffic between the plasma membranes and a system of endomembrane compartments; EGF-stimulation generates time-dependent signals that initially decrease, then increase, EGF-EGFR traffic to degradative compartments.
DNA single-strand break repair (SSBR) is important for maintaining genome stability and homeostasis. The current SSBR model derived from an in vitro-reconstituted reaction suggests that the SSBR complex mediated by X-ray repair cross-complementing protein 1 (XRCC1) is assembled sequentially at the site of damage. In this study, we provide biochemical data to demonstrate that two preformed XRCC1 protein complexes exist in cycling HeLa cells. One complex contains known enzymes that are important for SSBR, including DNA ligase 3 (DNL3), polynucleotide kinase 3'-phosphatase, and polymerase beta; the other is a new complex that contains DNL3 and the ataxia with oculomotor apraxia type 1 (AOA) gene product aprataxin. We report the characterization of the new XRCC1 complex. XRCC1 is phosphorylated in vivo and in vitro by CK2, and CK2 phosphorylation of XRCC1 on S518, T519, and T523 largely determines aprataxin binding to XRCC1 though its FHA domain. An acute loss of aprataxin by small interfering RNA renders HeLa cells sensitive to methyl methanesulfonate treatment by a mechanism of shortened half-life of XRCC1. Thus, aprataxin plays a role to maintain the steady-state protein level of XRCC1. Collectively, these data provide insights into the SSBR molecular machinery in the cell and point to the involvement of aprataxin in SSBR, thus linking SSBR to the neurological disease AOA.
PURPOSE: Inactivation of the retinoblastoma gene in human retinoblasts or mouse lens fiber cells causes inappropriate cell cycle entry, presumably as a consequence of elevated activity of the E2F transcription factors. Although E2Fs are known to be critical regulators of the cell cycle, it is still unclear whether family members E2F3a, E2F4 or E2F5 are individually capable of inducing cell cycle entry in vivo. In this study, we designed experiments to test whether lens-specific expression of these E2F family members would induce postmitotic fiber cells to re-enter the cell cycle. METHODS: Transgenic mice were generated by microinjection of constructs that contained E2F cDNAs (E2F3a, E2F4 or E2F5) linked to the mouse lens-specific alphaA-crystallin promoter. The mice were characterized by histology, in situ hybridization, immunohistochemistry, BrdU incorporation, TUNEL assay and Western blots. RESULTS: E2F3a expression was sufficient to induce cell cycle entry in lens fiber cells. Cell cycle re-entry was accompanied by apoptotic cell death resulting in microphthalmia. E2F4 expression stimulated a modest level of cell cycle re-entry, but the transgenic lenses remained normal in size and did not show significant apoptosis. Transgenic mice expressing E2F5 did not show lens defects. In both the E2F3a and E2F4 transgenic lenses, cyclin A2 and cyclin B1 expression were upregulated. Phosphorylated histone H3, a marker for mitosis, was detected in the E2F3a fiber cells. Western blots showed that both p53 and p73alpha were upregulated in the E2F3a lenses. However, expression of p21, a well-known p53 target gene, was not activated, suggesting that p73alpha might be responsible for inducing apoptosis and blocking unregulated proliferation in lens cells overexpressing E2F3a. CONCLUSIONS: E2F3a and E2F4, but not E2F5, function to induce cell cycle entry, although E2F4 has more modest activity. E2F3a may induce cell death primarily through activation of p73alpha.
OBJECTIVE: To observe the changes of peristalsis of small intestine in guinea pigs after administration of traditional Chinese medicines activating blood to resolve stasis (Compound Danshen Decoction, CDSD) or/and medicines dredging intestines (Dachengqi Decoction, DCQD), and to explore the synergetic or intensive effect of CDSD on DCQD. METHODS: By means of BL-420 Biological Experimental System, peristalsis of small intestine was recorded and analyzed following administration of DCQD, CDSD or Huoxue Chengqi Decoction (HXCQD, compound of CDSD and DCQD) respectively in different experimental periods. RESULTS: The amplitude and frequency of intestinal peristaltic wave obviously increased following administration of the three decoctions, but HXCQD appeared to be most dominantly. CONCLUSION: The effect of DCQD can be further enhanced by combining use of CDSD, suggesting that the traditional Chinese medicines activating blood to resolve stasis have an intensive effect on medicines dredging intestines.
Ultraviolet Absorption Spectrum of Difference in Temperature (UVSDT) of C60 was studied in different solvents by UV-240 ultraviolet-visible spectrophotometer. Two samples were tested, one of which acted as reference sample and the other as ready test sample. During the period of the experiment, the temperature of the reference sample remained constant, while that of the ready test sample was changed to obtain difference in temperature. The two samples were scanned in succession by UV-240 ultraviolet-visible spectrophotometer using a certain range of wavelength. By changing the temperature of the ready test sample, we can get the ultraviolet absorption spectrum changing curve with temperature differential. In addition, the curve was studied by putting C60 in different solvents (alcohol, cyclohexane, n-hexane and 2-propanol). The curve indicates that the intensity of the absorption peak wavelength of C60 decreased with increasing the temperature of the sample, and a negative peak was observed in UVSDT. And the greater the difference in temperature, the higher the intensity of the negative peak. The result reflects that the structure of C60 depends strongly on its temperature, and the dependent relationship is closely related to the type of pi-pi electron transition. So it's valuable to test the absorption rate of C60 and obtain the changing curve in real time. It'll help us to separate, purify, analyze, and characterize C60. And it'll also help to do research on the mechanism of the chemical reactions, which take place in solvents, as well as to improve veracity.
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