Biomedical subjects

Ying Wang

Publications and source records attributed to Ying Wang.

At least 217 records · Page 12Linked to original sources

PubMed2005

Effects of processing on the structure of zein/oleic Acid films investigated by x-ray diffraction.

Zein films plasticized with oleic acid were formed by solution casting, by the stretching of moldable resins, and by blown film extrusion. The effects of the forming process on film structure were investigated by X-ray diffraction. Wide-angle X-ray scattering (WAXS) patterns showed d-spacings at 4.5 and 10 A, which were attributed to the zein alpha-helix backbone and inter-helix packing, respectively. The 4.5 A d-spacing remained stable under processing while the 10 A d-spacing varied with processing treatment. Small-angle X-ray scattering (SAXS) detected a long-range periodicity for the formed films but not for unprocessed zein, which suggests that the forming process-promoted film structure development is possibly aided by oleic acid. The SAXS d-spacing varied among the samples (130-238 A) according to zein origin and film-forming method. X-ray scattering data suggest that the zein molecular structure resists processing but the zein supramolecular arrangements in the formed films are dependent on processing methods. Structural model for a zein molecular aggregate (based on Matsushima et al.10). Rectangular prisms of individual zein molecules are hexagonally aligned parallel to each other.

Emulsifying Agents↗

PubMed2005

Changes of plasma inflammatory markers after withdrawal of statin therapy in patients with hyperlipidemia.

BACKGROUND: Atherosclerosis has been considered to be an inflammatory process. In addition to its lipid-lowering properties, statin has been shown to decrease the concentrations of inflammatory markers resulting in reduction of cardiovascular events. Emerging data suggest that withdrawal of statin might be associated with increased cardiac events. The mechanism for this phenomenon, however, is still unclear. We investigated whether acute termination of statin treatment could result in rebound of inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6), in patients with hyperlipidemia. METHODS: Seventeen patients (11 men and 6 women, mean age 51+/-7 years) with hyperlipidemia were given 40 mg/day of pravastatin for 6 weeks. The concentrations of plasma CRP and IL-6 were evaluated before receiving the statin therapy, immediately after 6 weeks of pravastatin therapy, and at days 1, 3 and 7 after withdrawal of pravastatin therapy. The lipid profile was also evaluated at baseline, 6 weeks of therapy, and at day 7 after terminating pravastatin. RESULTS: Pravastatin therapy induced significant reductions in total cholesterol (TC, 6.88+/-0.36 vs. 5.27+/-0.23 mmol/l, p<0.01), low-density lipoprotein (LDL) cholesterol (4.28+/-0.25 vs. 3.06+/-0.14 mmol/l, p<0.01), CRP (0.28+/-0.16 vs. 0.20+/-0.08 mg/l, p<0.01), and IL-6 (8.4+/-0.6 vs. 6.7+/-0.4 pg/dl, p<0.01). Although the TC and LDL-cholesterol did not change during the 7-day period after withdrawal of pravastatin therapy, the concentrations of CRP and IL-6 increased at day 3 (CRP: 0.20+/-0.08 vs. 0.27+/-0.12 mg/l, and IL-6: 6.7+/-0.4 vs. 7.7+/-0.6 pg/dl, p<0.05 respectively) and at day 7 (CRP: 0.20+/-0.08 vs. 0.30+/-0.14 mg/l, and IL-6: 6.7+/-0.4 vs. 8.7+/-0.8 pg/dl, p<0.01 respectively) after withdrawal of pravastatin therapy. No correlation between increase of CRP as well as IL-6 and small changes of LDL-cholesterol concentrations was found after withdrawal of pravastatin therapy at day 7 (r=-0.021 and r=-0.044 respectively, p>0.05 respectively). CONCLUSIONS: 6 weeks after pravastatin therapy could significant modify the lipid profile and decrease the inflammatory markers including CRP and IL-6 in patients with hyperlididemia. Moreover, statin therapy discontinuation could induce a rebound phenomenon of inflammatory response representing an increase in some inflammatory markers, which is independent of changes of lipid parameters.

Adult↗

PubMed2005

GoldIII porphyrin 1a induced apoptosis by mitochondrial death pathways related to reactive oxygen species.

Apoptosis is a tightly controlled multistep mechanism of cell death, and mitochondria are considered to play a central role in this process. Mitochondria initiate two distinct apoptosis pathways, one caspase-dependent and the other caspase-independent. In addition, mitochondrial production of reactive oxygen species (ROS) seems to play a role in cell death. Most chemotherapeutic agents induce apoptosis through at least one of these pathways. The post-initiation mechanisms of gold(III) porphyrin 1a were investigated in this study. HONE1 cells exposed to gold(III) porphyrin 1a underwent apoptosis after 24 hours. Functional proteomic studies revealed the alteration of several cytoplasmic protein expressions in HONE1 cells after treatment with the drug. These proteins include enzymes participating in energy production and proteins involved in cellular redox balance. There was a quick attenuation of mitochondrial membrane potential (DeltaPsi(m)) with the alterations of Bcl-2 family proteins, the release of cytochrome c, and apoptosis-inducing factor (AIF) following gold(III) porphyrin 1a treatment. Cytochrome c in turn activated caspase-9 and caspase-3. Cotreatment with caspase inhibitor (zVAD-fmk) showed that the activated caspases worked in conjunction with AIF-initiated apoptosis pathways. Further study showed that ROS played a part in gold(III) porphyrin 1a-induced apoptosis by regulating DeltaPsi(m). In summary, gold(III) porphyrin 1a induced apoptosis through both caspase-dependent and caspase-independent mitochondrial pathways, and intracellular oxidation affected gold(III) porphyrin 1a-induced apoptosis. These results support a role for gold(III) porphyrin 1a as a promising anticancer drug lead and as a possible novel therapeutic agent directed toward the mitochondria.

Apoptosis↗

PubMed2005

Two single-nucleotide polymorphisms with linkage disequilibrium in the human programmed cell death 5 gene 5' regulatory region affect promoter activity and the susceptibility of chronic myelogenous leukemia in Chinese population.

PURPOSE: Chronic myelogenous leukemia (CML) is a disease characterized cytogenetically by the presence of the Philadelphia chromosome. Recent studies suggested that altered PDCD5 expression may have significant implications in CML progression. The aim of this study was to identify single-nucleotide polymorphisms (SNP) within the programmed cell death 5 (PDCD5) promoter region and show their functional relevance to PDCD5 expression as well as their genetic susceptibility to CML. EXPERIMENTAL DESIGN: One hundred twenty-nine CML subjects and 211 healthy controls were recruited for identification of SNPs and subsequent genetic analysis. Luciferase reporter assays were carried out to show the functional significance of the SNPs located in the promoter region to PDCD5 expression. Real-time quantitative PCR and Western blot analysis were done to determine the expression differences of PDCD5 in CML patients with different genotypes. RESULTS: Two SNPs were identified within the PDCD5 promoter. They are -27A>G and -11G>A (transcription start site as position 1), respectively. The complete linkage disequilibrium was found between these two polymorphisms. The frequencies of -27G+/-11A+ genotype and -27G/-11A allele were significantly higher in CML patients than in healthy controls (genotype: 26.36% versus 11.85%, chi2=11.75, P<0.01; allele: 13.57% versus 6.40%, chi2=9.48, P<0.01). Luciferase reporter assays revealed that the promoter with -27G/-11A had significantly lower transcriptional activity and could not be up-regulated after apoptotic stimulations compared with the promoter with -27A/-11G. PDCD5 expression analysis in mononuclear cells derived from CML patients and cell lines with different -27/-11 genotypes showed consistent results with the reporter assays. CONCLUSIONS: These data suggest that -27G/-11A is associated with reduced PDCD5 promoter activity and increased susceptibility to CML.

5' Flanking Region↗

PubMed2005

Differential expression of CXCR4 is associated with the metastatic potential of human non-small cell lung cancer cells.

PURPOSE: To evaluate the relation between CXCR4 expression and the presence of metastatic disease in human non-small cell lung cancer (NSCLC) patients and investigate whether modulation of CXCR4 expression could serve as a potential pathway in preventing metastasis of NSCLC. EXPERIMENTAL DESIGN: CXCR4 expression in 36 patients with NSCLC and 10 normal lung tissues was detected by real-time PCR and immunohistochemistry. CXCR4 expression in two human NSCLC clones (95C and 95D) with different metastatic potential was determined by real-time PCR and flow cytometry. 95C and 95D cells were transfected with the plasmid DNA containing CXCR4 coding gene or CXCR4 antisense nucleotide fragment, respectively, and the effects on in vitro cell migration, invasion, and adhesion and in vivo metastasis were measured. RESULTS: Up-regulated expression of CXCR4 was detected in 34 tumors, which were further divided into 17 high expression cancers and 17 low expression cancers by their staining intensities. High CXCR4 tumors (13 of 17) were more prone to clinical metastasis in comparison with low expression tumors. CXCR4 was differentially expressed in 95C and 95D cells with low or high metastatic potential, and the surface expression of CXCR4 were 50% up-regulated or down-regulated following the stable transfection. The metastatic potential of NSCLC in vitro, such as migration, invasion, and adhesion, were significantly enhanced or impaired. In addition, neutralizing the interactions of stromal cell-derived factor-1/CXCR4 in vitro with CXCR4-specific antibodies inhibited the CXCR4-dependent migration, invasion, and adhesion. Furthermore, s.c. inoculation of lung cancer cells with low expression of CXCR4 in nude mice showed 0- to 2-fold decrease in lung metastatic foci than that with high expression of CXCR4. CONCLUSIONS: Differential expression of CXCR4 is associated with the metastatic potential of human NSCLC, raising the possibility that blockade of CXCR4/stromal cell-derived factor-1 interaction may lead the way to design novel therapeutic tools for the treatment of metastatic NSCLC patients.

Animals↗

PubMed2005

Monodisperse protein-based glycopolymers via a combined biosynthetic and chemical approach.

Helical protein polymers with sequences comprising primarily alanine and glutamine have been designed to contain glutamic acid residues at distances that are targeted to match the receptor spacing of certain toxins and lectins. These proteins are readily expressed and purified from E. coli and are highly helical under a variety of solution conditions. The helical artificial proteins are also competent for chemical modification with saccharides for inhibition of select bacterial toxins and lectins. In the investigations reported here, multivalent artificial glycoproteins bearing galactose moieties as pendant groups have been prepared via the coupling reaction of amine-functionalized galactose with the glutamic acid functional groups of the protein polymer. Glycosylation of proteins was confirmed via mass spectrometry, NMR spectroscopy, SDS-PAGE, and photometric methods. CD spectroscopy shows that the resulting glycosylated proteins maintain a highly helical structure, and competitive ELISA assays suggest the efficient binding of these glycoproteins to cholera toxin. These results demonstrate that the integration of biological and chemical approaches in the synthesis of well-defined polymeric structures offers significant opportunities in the purposeful design of glycopolymers for applications in biology.

Amino Acid Sequence↗

PubMed2005

FLT3-ITD-, but not BCR/ABL-transformed cells require concurrent Akt/mTor blockage to undergo apoptosis after histone deacetylase inhibitor treatment.

Leukemias are differentially sensitive to histone deacytelase inhibitor (HDI)-induced apoptosis, but molecular reasons for this remain unclear. We here show that BCR/ABL-, but not FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD)-transformed 32D cells or primary acute myeloid leukemia (AML) blasts undergo apoptosis after treatment with the HDI valproic acid (VPA) plus all-trans retinoic acid (VPA/ATRA). A particular VPA/ATRA responsiveness of Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (ALL) was confirmed in a therapy-refractory patient in vivo. HDI-stimulated apoptosis in Ph+ cells was caspase dependent, but independent from Akt pathway inhibition. Conversely, separate blockage of the Akt/mTor-signaling pathway was a prerequisite for overcoming apoptosis resistance to VPA/ATRA in FLT3-ITD cells, and primary AML blasts (n = 9). In conclusion, constitutive Akt activation causes apoptosis resistance to VPA/ATRA in AML, but not in Ph+ leukemia. This warrants the application of HDI-based therapies in poor-risk Ph+ ALL, and the use of Akt/mTor inhibitors to overcome HDI resistance in AML.

Antineoplastic Agents↗

PubMed2005

Event-related potentials in adolescents with combined ADHD and CD disorder: a single stimulus paradigm.

Some studies of the event-related potentials demonstrated a reduction of the voluntary component P3 (P300 or P3b) in youngsters with the attention deficit/hyperactivity disorder (ADHD) or in conduct disorders (CD), and a reduction of the automatic processing component, mismatch negativity, in patients with both ADHD and CD (ADHD+CD). Recently, a passive auditory P3 potential has been elicited by a single stimulus. We therefore tried this potential study in 20 healthy subjects and 20 teenagers with ADHD+CD to search for further evidence of the altered automatic cerebral processing in the latter. Subjects also answered a self-report Dimensional Assessment of Personality Pathology (DAPP). The patient group scored significantly higher on most DAPP traits that reflect problems of emotion control, showed significantly prolonged P2, N2, and P3, and reduced P3. In all subjects Stimulus Seeking was positively correlated with P3 latencies at Fz, Cz, and Pz, and with P3 amplitude at Cz. This study suggests that youngsters with ADHD+CD had pronounced emotion dysregulation, and prominent deficit in passive attention, as reflected by the automatic processing of auditory stimuli.

Adolescent↗

PubMed2005

Synthesis of a series of 4-pyridyl-1,2,4-triazole-containing cadmium(II) luminescent complexes.

Using two 4-substitued triazole ligands, 4-(pyrid-2-yl)-1,2,4-triazole (L(1)) and 4-(pyrid-3-yl)-1,2,4-triazole (L(2)), a series of novel triazole-cadmium(II) complexes varying from zero- to three-dimensional have been prepared and their crystal structures determined via single-crystal X-ray diffraction. [Cd(2)(micro(2)-L(1))(3)(L(1))(2)(NO(3))(mu(2)-NO(3))(H(2)O)(2)](NO(3))(2).1.75H(2)O (1) is a binuclear complex containing bidendate, monodedate and free nitrate anions. When the bridging anions SCN(-) and dca (dca = N(CN)(2)(-)) were added to the reaction system of 1, one-dimensional (1D) [Cd(L(1))(2)(NCS)(2)](n) (2) and two-dimensional (2D) [Cd(L(1))(2)(dca)(2)](n) (3) were isolated, respectively. When L(2) instead of L(1) was used, [Cd(L(2))(2)(NCS)(2)(H(2)O)(2)] (4) and 1D [Cd(L(2))(2)(dca)(2)](n) (5) were obtained. When the ratio of Cd to L(2) was changed from 1:2 to 1:1 in the reaction system of 5, three-dimensional (3D) {[Cd(3)(micro(2)-L(2))(3)(dca)(6)].0.75H(2)O}(n) (6) with 1D microporous channels along the a direction was isolated. Further investigations on other Cd(ii) salts and the L(2) ligand in a Cd to L(2) ratio of 1:1, an unexpected complex [Cd(mu(2)-L(2))(mu(3)-SO(4))(H(2)O)](n) (7) with a 3D open framework was obtained. All of the complexes exhibit strong blue fluorescence emission bands in the solid state at ambient temperature, of which the excitation and emission maxima are red-shifted to longer wavelength as compared to those in water. Powder X-ray diffraction and thermal studies were used to investigate the bulk nature of the 3D coordination polymers 6 and 7.

Journal Article↗

PubMed2005

Polymorphisms in the promoter regions of the matrix metalloproteinases-1, -3, -7, and -9 and the risk of epithelial ovarian cancer in China.

PURPOSE: To investigate the association of single nucleotide polymorphisms (SNP) in the promoter region of the matrix metalloproteinases-1 -1607bp1G/2G, matrix metalloproteinases-3 -1171bp5A/6A, matrix metalloproteinases-7 A-181G and matrix metalloproteinases-9 C-1562T with susceptibility to ovarian cancer in a population of North China. EXPERIMENTAL DESIGN: We analyzed four different functional promoter polymorphisms in the respective genes by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in a sample of patients with epithelium ovarian cancer and control women, all from North China. RESULTS: No significant difference was detected between the patient and control groups in genotype and allelotype distribution of MMP-1, MMP-3, MMP-9 of the polymorphisms studied. However, the genotype and allelotype of the MMP-7 distribution in ovarian cancer patients were significantly different from that in healthy controls. The frequency of the -181G allele of MMP-7 in patients was significantly higher than that in healthy controls women (8.2% vs. 2.8%, P = 0.002). Compared to the A/A genotype, the genotypes with the -181G allele (A/G + G/G) significantly increased susceptibility to ovarian cancer, with adjusted odds ratio [OR] = 3.53 95% confidence interval [CI] [1.58 to 7.89]. CONCLUSIONS: The study suggested that a possible association between the MMP-7 A/G polymorphism with susceptibility to epithelium ovarian cancer, but there is no support for an association of the selected MMP-1 1G/2G, MMP-3 5A/6A, and MMP-9 C/T polymorphisms with the risk for ovarian cancer.

Adult↗

PubMed2005

Molecular cloning and identification of mouse Cklfsf2a and Cklfsf2b, two homologues of human CKLFSF2.

Human chemokine-like factor superfamily (CKLFSF) is a novel gene family comprising CKLF and CKLFSF1-8. Among them, CKLFSF2 is highly expressed in testis and may play important roles in male reproduction. Besides, it is very active during evolution and has two counterparts in mouse. For further study, we cloned the two mouse genes by EST assembly and RT-PCR methods and designated them as mouse Cklfsf2a and Cklfsf2b. Their predicted open-reading frames (ORFs) that encode 169 and 210 amino acids, respectively, were obtained; and their predicted full-length molecular sizes that are approximately 1.2 kb for mCklfsf2a and 0.9 kb for mCklfsf2b were confirmed by Northern blot analysis. Mouse Cklfsf2a and Cklfsf2b show similarities with human CKLFSF2 in the expression patterns that are abundant in testis, hematopoietic and immune tissues; as well as in the chromosome localizations that neighbor CKLFSF1 and 3. Their putative protein products have 47.6 and 45.5% identities with hCKLFSF2, respectively; both of them contain four potential transmembrane regions and MARVEL domains, which are also similar with hCKLFSF2. Functionally, they all can affect the transcriptional activity of androgen receptor in PC-3 and HeLa cells, but mCklfsf2a is a repressor while mCklfsf2b and hCKLFSF2 are enhancers. Taken together, we conclude that mouse Cklfsf2a and Cklfsf2b are two homologues of human CKLFSF2. Studies on them would provide much help in further investigation of the latter.

Amino Acid Sequence↗

PubMed2005

All-trans retinoic acid biases immune response induced by DNA vaccine in a Th2 direction.

Vitamin A deficiency diminishes Th2-mediated Ab responses. Providing Vitamin A or its active metabolites reverses this defect. All-trans retinoic acid (ATRA), an acid derivation of Vitamin A, regulates the balance of immune response induced by TR421-hCGbeta DNA vaccine. Compared to DNA vaccine alone or treatment with vehicle, significantly higher level of antibody against the protein encoded by DNA vaccine was observed in mice 6 weeks after the first immunization. The IgG2a/IgG1 ratio was lower in mice treated with ATRA. We also found that treatment with ATRA also diminishes specific cellular immune response induced by gene immunization by measuring the marker of cellular immune response. We conclude that ATRA biases the immune response to Th2 direction induced by DNA vaccine and acts as a candidate adjuvant and immunomodulatory molecule.

Animals↗

PubMed2005

Regulation of EGF receptor signaling by the MARVEL domain-containing protein CKLFSF8.

It is known that chemokine-like factor superfamily 8 (CKLFSF8), a member of the CKLF superfamily, has four putative transmembrane regions and a MARVEL domain. Its structure is similar to TM4SF11 (plasmolipin) and widely distributed in normal tissue. However, its function is not yet known. We show here that CKLFSF8 is associated with the epidermal growth factor receptor (EGFR) and that ectopic expression of CKLFSF8 in several cell lines suppresses EGF-induced cell proliferation, whereas knockdown of CKLFSF8 by siRNA promotes cell proliferation. In cells overexpressing CKLFSF8, the initial activation of EGFR was not affected, but subsequent desensitization of EGF-induced signaling occurred rapidly. This attenuation was correlated with an increased rate of receptor endocytosis. In contrast, knockdown of CKLFSF8 by siCKLFSF8 delayed EGFR endocytosis. These results identify CKLFSF8 as a novel regulator of EGF-induced signaling and indicate that the association of EGFR with four transmembrane proteins is critical for EGFR desensitization.

Cell Line↗

PubMed2005

Two rings of negative charges in the cytosolic vestibule of type-1 ryanodine receptor modulate ion fluxes.

The tetrameric ryanodine receptor calcium release channels (RyRs) are cation-selective channels that have pore architecture similar to that of K+ channels. We recently identified, in close proximity to the selectivity filter motif GGGIG, a conserved lumenal DE motif that has a critical role in RyR ion permeation and selectivity. Here, we substituted three aspartate residues (D4938, D4945, D4953) with asparagine and four glutamate residues (E4942, E4948, E4952, E4955) with glutamine hypothesized to line the cytosolic vestibule of the skeletal muscle RyR (RyR1). Mutant single channel properties were determined using the planar lipid bilayer method. Two mutants (D4938N, D4945N) showed a reduced K+ ion conductance, with D4938N also exhibiting a reduced selectivity for Ca2+ compared to K+. The cytosolic location of D4938 and D4945 was confirmed using the polycation neomycin. Both D4938N and D4945N exhibited an attenuated block by neomycin to a greater extent from the cytosolic than lumenal side. By comparison, charge neutralization of lumenal loop residues (D4899Q, E4900N) eliminated the block from the lumenal but not the cytosolic side. The results suggest that, in addition to negatively charged residues on the lumenal side, rings of four negative charges formed by D4938 and D4945 in the cytosolic vestibule determine RyR ion fluxes.

Amino Acid Motifs↗

PubMed2005

Phelligridimer A, a highly oxygenated and unsaturated 26-membered macrocyclic metabolite with antioxidant activity from the fungus Phellinus igniarius.

[structure: see text] A highly oxygenated and unsaturated 26-membered macrocyclic metabolite, phelligridimer A (1), has been isolated from the Chinese medicinal fungus Phellinus igniarius. Its structure was elucidated by spectroscopic methods. A possible biogenesis of 1 mediated by the fungal metabolite hispidin was postulated. Phelligridimer A showed antioxidant activity (IC50 of 10.2 microM) but was inactive to several human cancer cell lines (IC50 > 50 microM) and enzymes PTP1B (IC50 > 25 microM) and thrombin (IC50 > 10 microM).

Animals↗

PubMed2005

Two major branches of anti-cadmium defense in the mouse: MTF-1/metallothioneins and glutathione.

Metal-responsive transcription factor 1 (MTF-1) regulates expression of its target genes in response to various stress conditions, notably heavy metal load, via binding to metal response elements (MREs) in the respective enhancer/promoter regions. Furthermore, it serves a vital function in embryonic liver development. However, targeted deletion of Mtf1 in the liver after birth is no longer lethal. For this study, Mtf1 conditional knockout mice and control littermates were both mock- or cadmium-treated and liver-specific transcription was analyzed. Besides the well-characterized metallothionein genes, several new MTF-1 target genes with MRE motifs in the promoter region emerged. MTF-1 is required for the basal expression of selenoprotein W, muscle 1 gene (Sepw1) that encodes a glutathione-binding and putative antioxidant protein, supporting a role of MTF-1 in the oxidative stress response. Furthermore, MTF-1 mediates the cadmium-induced expression of N-myc downstream regulated gene 1 (Ndrg1), which is induced by several stress conditions and is overexpressed in many cancers. MTF-1 is also involved in the cadmium response of cysteine- and glycine-rich protein 1 gene (Csrp1), which is implicated in cytoskeletal organization. In contrast, MTF-1 represses the basal expression of Slc39a10, a putative zinc transporter. In a pathway independent of MTF-1, cadmium also induced the transcription of genes involved in the synthesis and regeneration of glutathione, a cadmium-binding antioxidant. These data provide strong evidence for two major branches of cellular anti-cadmium defense, one via MTF-1 and its target genes, notably metallothioneins, the other via glutathione, with an apparent overlap in selenoprotein W.

Animals↗

PubMed2005

A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17.

Interleukin 17 (IL-17) has been linked to autoimmune diseases, although its regulation and function have remained unclear. Here we have evaluated in vitro and in vivo the requirements for the differentiation of naive CD4 T cells into effector T helper cells that produce IL-17. This process required the costimulatory molecules CD28 and ICOS but was independent of the cytokines and transcription factors required for T helper type 1 or type 2 differentiation. Furthermore, both IL-4 and interferon-gamma negatively regulated T helper cell production of IL-17 in the effector phase. In vivo, antibody to IL-17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused chemokine production and leukocyte infiltration. Thus, IL-17 expression characterizes a unique T helper lineage that regulates tissue inflammation.

Animals↗

PubMed2005

Synthesis and structure-activity relationships of 1,2,4-triazoles as a novel class of potent tubulin polymerization inhibitors.

A novel triazole-containing chemical series was shown to inhibit tubulin polymerization and cause cell cycle arrest in A431 cancer cells with EC(50) values in the single digit nanomolar range. Binding experiments demonstrated that representative active compounds of this class compete with colchicine for its binding site on tubulin. The syntheses and structure-activity relationship studies for the triazole derivatives are described herein.

Antineoplastic Agents↗