Biomedical subjects
Publications and source records attributed to N Zhu.
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We reported recently that the inflammatory cytokine tumour necrosis factor alpha (TNF-alpha) can upregulate integrin expression, cell attachment and invasion of cells through fibronectin in a human melanoma cell line (HBL). Furthermore, the actions of TNF-alpha were suppressed by the addition of an anti-inflammatory peptide alpha-melanocyte-stimulating hormone (alpha-MSH). In the current study, we extend this work investigating to what extent TNF-alpha might stimulate melanoma invasion by promoting cell migration and whether alpha-MSH is also inhibitory. Two human melanoma cell lines were examined in vitro (HBL and C8161) using a scratch migration assay. Analysis using either time-lapse video microscopy or imaging software analysis of migrating 'fronts' of cells revealed that C8161 cells migrated more rapidly than HBL cells. However, when cells were stimulated with TNF-alpha both cell types responded with a significant increase in migration distance over a 16-26 h incubation time. alpha-Melanocyte-stimulating hormone had an inhibitory effect on TNF-alpha-stimulated migration for HBL cells, completely blocking migration at 10(-9) M. In contrast, C8161 cells did not respond to alpha-MSH (as these cells have a loss-of-function melanocortin-1 receptor). However, stable transfection of C8161 cells with the wild-type melanocortin-1 receptor produced cells whose migration was significantly inhibited by alpha-MSH. In addition, the use of a neutralising antibody to the beta(1)-integrin subunit significantly reduced migration in both cell types. This data therefore supports an inflammatory environment promoting melanoma cell migration, and in addition shows that alpha-MSH can inhibit inflammatory stimulated migration. The data also support a fundamental role of the beta(1)-integrin receptor in melanoma cell migration.
Aerobic granular sludge is a promising biotechnology for wastewater treatment system. In this report, aerobic granular sludge was successfully cultivated in a sequential batch shaking reactor in which horizontal circular flow could be formed by shaking. In this way, granulation and aeration could be simultaneously achieved. In comparison with sequential batch airlift reactor, more homogeneous circular flow was formed in the sequential batch shaking reactor. The aerobic granules obtained in the reactor were smooth, 1.2 mm in average diameter, and had a settling velocity of 50-52 m h(-1). In addition, an increase in the hydrophobicity of the cell surface of granules indicated that granulation could be related to the change in cell hydrophobicity. Finally, microbial observation showed that rod-shape and coccoid bacteria were the dominant species in mature granules. Results of this study have important implications on the mechanism of the granulation process and further practical application.
We present the synthesis and photophysical and electroluminescent properties for a series of platinum(II) alpha-diimine bis(arylacetylide) complexes. The molecular structures of five derivatives have been elucidated by X-ray crystallography. Intermolecular pi-pi interactions (between aromatic diimine and phenylacetylide moieties) are apparent in the crystal lattices of two of these. All bis(phenylacetylide) derivatives exhibit intense triplet metal-to-ligand charge transfer (MLCT) photoluminescence in the solid state and in fluid solutions at room temperature. The impact of different solvents, substituents on the diimine ligands, and complex concentrations upon their emissive behavior have been examined and demonstrates that their emission energies can be systematically modified. Application of the 3MLCT excited state of the [Pt(alpha-diimine) (C(triple bond)CPh)2] materials in single- and double-layer organic light-emitting devices are described. The bis(butadiynyl) complex [Pt(4,4'-dtbpy)(C(triple bond)C-C(triple bond)CPh)2] (dtbpy = 4,4'-di-tert-butyl-2,2'-bipyridine) displays strong solid-state and solution phosphorescence at 77 and 298 K; the associated excited state is proposed to arise from both acetylenic 3pi pi*(C(triple bond)C-C(triple bond)CPh) and 3MLCT [Pt --> pi*(diimine)] transitions.
Kv4.3 channels are important molecular components of transient K(+) currents (Ito currents) in brain and heart. They are involved in setting the frequency of neuronal firing and heart pacing. Altered Kv4.3 channel expression has been demonstrated under pathological conditions like heart failure indicating their critical role in heart function. Thyroid hormone studies suggest that their expression in the heart may be hormonally regulated. To explore the possibility that sex hormones control Kv4.3 expression, we investigated whether its expression changes in the pregnant uterus. This organ represents a unique model to study Ito currents, because it possesses this type of K(+) current and undergoes dramatic changes in function and excitability during pregnancy. We cloned Kv4.3 channel from myometrium and found that its protein and transcript expression is greatly diminished during pregnancy. Experiments in ovariectomized rats demonstrate that estrogen is one mechanism responsible for the dramatic reduction in Kv4.3 expression and function prior to parturition. Furthermore, the reduction of plasma membrane Kv4.3 protein is accompanied by a perinuclear localization suggesting that cell trafficking is also controlled by sex hormones. Thus, estrogen remodels the expression of Kv4.3 in myometrium by directly diminishing its transcription and, indirectly, by altering Kv4.3 delivery to the plasma membrane.
Hepatitis C virus (HCV) core protein has been shown to interact with the death domain (DD) of tumor necrosis factor receptor-1 (TNFR1). In this study, we further examined the interaction of the core protein with the signaling molecules of TNFR1, including FADD, TRADD, and TRAF2, in a human embryonic kidney cell line, HEK-293, that overexpresses the HCV core protein. This core protein-expressing cell line exhibited enhanced sensitivity to TNF-induced apoptosis. By in vitro binding and in vivo coimmunoprecipitation assays, we showed that the HCV core protein interacted with the DD of FADD and enhanced apoptosis induced by FADD overexpression. This enhancement could be blocked by a dominant-negative mutant of FADD. In contrast, the core protein did not directly interact with the DD of TRADD, but could disrupt the binding of TRADD to TNFR1. TRAF2 recruitment to the TNFR1 signaling complex was also disrupted by the core protein. Correspondingly, TRAF2-dependent activation of the protein kinase JNK was suppressed in the core protein-expressing cells. However, NF kappa B activation by TNF was not significantly altered by the HCV core protein, suggesting the existence of TRAF2-independent pathways for NF kappa B activation. These results combined indicate that the HCV core protein sensitizes cells to TNF-induced apoptosis primarily by facilitating FADD recruitment to TNFR1. The inhibition of JNK activation by the HCV core protein may also contribute to the increased propensity of cells for apoptosis. These results, in comparison with other published studies, suggest that the effects of the HCV core protein and their underlying mechanisms vary significantly among cells of different origins.
[structure in text] From the leaves of Morinda citrifolia, a new unusual iridoid, named citrifolinoside (1), showing significant inhibition of UVB-induced Activator Protein-1 (AP-1) activity in cell cultures, has been isolated. Its structure was elucidated on the basis of detailed high-field 1D and 2D spectral analysis.
We identified a novel MaxiK alpha subunit splice variant (SV1) from rat myometrium that is also present in brain. SV1 has a 33-amino acid insert in the S1 transmembrane domain that does not alter S1 overall hydrophobicity, but makes the S0-S1 linker longer. SV1 was transfected in HEK293T cells and studied using immunocytochemistry and electrophysiology. In non-permeabilized cells, N-terminal c-Myc- or C-terminal green fluorescent protein-tagged SV1 displayed no surface labeling or currents. The lack of SV1 functional expression was due to endoplasmic reticulum (ER) retention as determined by colabeling experiments with a specific ER marker. To explore the functional role of SV1, we coexpressed SV1 with the alpha (human SLO) and beta1 (KCNMB1) subunits of the MaxiK channel. Coexpression of SV1 inhibited surface expression of alpha and beta1 subunits approximately 80% by trapping them in the ER. This inhibition seems to be specific for MaxiK channel subunits since SV1 was unable to prevent surface expression of the Kv4.3 channel or to interact with green fluorescent protein. These results indicate a dominant-negative role of SV1 in MaxiK channel expression. Moreover, they reveal down-regulation by splice variants as a new mechanism that may contribute to the diverse levels of MaxiK channel expression in non-excitable and excitable cells.
Bioactivity-directed fractionation and purification afforded cytotoxic components of Commiphora wightii. The exudates of C. wightii were extracted with EtOAc and the extract was subjected to repeated column chromatography. A fraction showing cytotoxic activity was characterized as a mixture of two ferulates with an unusual skeleton by spectral and chemical methods, including by NMR, GC-MS and chemical derivatization. This fraction also showed moderate scavenging effect against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals.
Quinoa (Chenopodium quinoa) is a hardy and nutritious Latin American pseudo-cereal. Studies on the seeds led to the isolation of five ecdysteroids using column chromatography. Their structures were determined as ecdysterone, makisterone A, 24-epi-makisterone A, 24(28)-dehydromakisterone A, and 20,26-dihydroxyecdysone by spectroscopic methods. This study demonstrates that quinoa seeds are a source of ecdysteroids, which were reported to be molting hormones in insects.
One new iridoid glycoside and five known flavonol glycosides have been isolated from the leaves of Morinda citrifolia. The new iridoid exists as an epimeric mixture in solution. Complete assignments of the proton and carbon chemical shifts for the individual epimers were accomplished on the basis of high-resolution 1D and 2D NMR data. Their antioxidative activities were measured. All of these compounds showed DPPH free radical scavenging activity at the concentration of 30 microM.
Seven triterpene saponins were isolated from n-butanol fractions of blue cohosh (Caulophyllum thalictroides) roots and rhizomes. Their structures were established by spectral ((1)H NMR, (13)C NMR, 2D-NMR, and APCI-MS) techniques and chemical reactions as hederagenin 3-O-alpha-L-arabinopyranoside (1); caulophyllogenin 3-O-alpha-L-arabinopyranoside (2); hederagenin 3-O-beta-D-glucopyranosyl-(1-->2)-alpha-L-arabinopyranoside (3); 3-O-alpha-L-arabinopyranosyl-hederagenin 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside (4); 3-O-alpha-L-arabinopyranosyl- caulophyllogenin 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside (5); 3-O-beta-D-glucopyranosyl-(1-->2)-alpha-L-arabinopyranosyl- echinocystic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside (6); 3-O-beta-D-glucopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-hederagenin 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside (7). All seven compounds were identified in this species for the first time.
The structures of two new cycloartane-type saponin constituents of the roots of Cimicifuga foetida were established by the interpretation of spectroscopic data as 2'-O-acetylactein (1) and 2'-O-acetyl-27-deoxyactein (2), respectively. Also isolated were the known compounds actein, 27-deoxyactein, cimicifugoside H-1, and 15alpha-hydroxycimicidol 3-O-beta-D-xyloside.
A new iridoid glucoside (1), named citrifolinoside A, was isolated from the leaves of Morinda citrifolia along with the known iridoids asperuloside and asperulosidic acid. The structure of 1 was established by interpretation and full assignments of NMR spectroscopic data.
An investigation on the gum exudates of Commiphora myrrha has led to the isolation of six sesquiterpenoids. On the basis of spectroscopic data interpretation, they were determined as two new furanosesquiterpenoids, rel-1S,2S-epoxy-4R-furanogermacr-10(15)-en-6-one (1) and rel-2R-methyl-5S-acetoxy-4R-furanogermacr-1(10)Z-en-6-one (2), and four known furanosesquiterpenoids, rel-3R-methoxy-4S-furanogermacra-1E,10(15)-dien-6-one (3), rel-2R-methoxy-4R-furanogermacr-1(10)E-en-6-one (4), furanogermacra-1(10)Z,4Z-dien-6-one, and curzerenone [6,7-dihydro-5beta-isopropenyl-3,6beta-dimethyl-6-vinylbenzofuran-4(5H)-one]. This is the first report of the relative stereochemistry for the known compounds 3 and 4. Compound 1 exhibited weak cytotoxic activity against a MCF-7 breast tumor cell line in a clonogenic assay, while the other five compounds were inactive in this assay.
Nonmethane organic carbon (NMOC) is a measure of total organic carbon except for that from CH4. We recently reported the development of online instrumentation for continuous NMOC monitoring. This instrument, referred to as C-NMOC, uses a microsorbent trap in combination with a gas-sampling valve as the sampling interface. A conventional oxidation/reduction NMOC detector is used for quantitation. In addition to being an online concentrator and an injector, the microtrap serves as a separator that isolates NMOC from H2O, CO, CO2, CH4, and other background gases. Therefore, the C-NMOC is able to handle high concentrations of background gases commonly found in stack emissions and has detection limits in the ppb levels. This paper reports the results of field validation and testing of a C-NMOC analyzer at a coatings facility in the eastern United States. The instrument was able to monitor the process transients in real time, based on which corrective actions could be taken. It demonstrated good accuracy, high precision, and long-term stability.
Enhancement of biodegradability of polychlorinated dibenzo-p-dioxins (PCDDs) was studied with new isolated bacterial strains from soil and oxic-sediments contaminated by PCDDs. The results indicated that mono- and di-chlorinated dibenzo-p-dioxins could be utilized as a sole carbon source and degraded by isolated bacterial strains, but tri-chlorinated dibenzo-p-dioxin (TrCDD) was hardly degraded. The biodegradability of TrCDD and tetra-chlorinated dibenzo-p-dioxin (TCDD) by the strain Pseudomonas sp. EE41, a new isolated one, could be enhanced through primary nutrient of co-metabolism of o-dichlorobenzene (o-DCB). In this case, TrCDD (1.2mg/l for 3 weeks) was degraded by 33.1% and the degradation rate enhanced more than 2 fold; also TCDD (0.1 mg/l for 3 weeks) biodegraded by 37.8%. Most highly chlorinated, Penta-, Hexa-, Hepta-, and Octa-chlorinated, dibenzo-p-dioxins (P-CDD, H6, H7-CDD and OCDD) tested in this study could not be degraded while accumulated in bacterial cells.
The possible beneficial effects of tea consumption have attracted a great deal of attention. Many of the biological effects have been attributed to tea catechins, but the metabolic fate of these compounds is not clear. In the present study, a major metabolite observed in human blood and urine samples after green tea administration was identified as a O-methylated derivative of (-)-epigallocatechin (EGC) by comparison with products from chemical and enzymatic O-methylation of EGC. The structure of this metabolite was elucidated as 4'-O-methyl-(-)-epigallocatechin (4'-O-MeEGC) by (1)H and (13)C NMR and heteronuclear multiple bond connectivity experiment. The human plasma level of 4'-O-MeEGC reached its peak value within the first 2 h following tea ingestion. Its maximum concentration was 4 to 6 times higher than that of EGC. The half-lives of EGC and 4'-O-MeEGC in the blood were 1.02 +/- 0.07 and 4.39 +/- 1.14 h, respectively. The amount of 4'-O-MeEGC excreted in urine was about 3 times higher than that of EGC, and 88% of 4'-O-MeEGC was excreted in urine within 8 h. The present structural information and concentration-time profile of this metabolite provide the basis for understanding the biotransformation of EGC and for future elucidation of its biological activities.