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Biomedical subjects

Fang Tian

Publications and source records attributed to Fang Tian.

At least 19 recordsLinked to original sources
PubMed2026

Tripterygium Glycosides Alleviates Hemophagocytic Lymphohistiocytosis Accompanied With Aggressive NK Cell Leukemia and Epstein-Barr Virus Infection.

Hemophagocytic lymphohistiocytosis (HLH) is a group of hyperinflammatory disorders with a mortality rate exceeding 50%. We report a case of a female Asian patient who developed secondary HLH accompanied by aggressive natural killer cell leukemia and Epstein-Barr virus (EBV) infection, and was treated with tripterygium glycosides (TG), a Chinese patent medicine. Within 3 weeks of oral administration, the patient's recurrent high fever resolved, abdominal distension and splenomegaly improved, ascites diminished, serum soluble CD25 levels decreased, and hematopoietic and coagulation functions recovered. Triptolide, a major component of TG, exhibited cytotoxicity against the patient's ascitic cells and induced apoptosis in a dose-dependent manner ex vivo. Whole-genome and transcriptome sequencing of the patient's tumor cells revealed that TG regulated EBV-associated mutated genes such as PSMD7 and modulated inflammation-related pathways. Molecular docking further suggested direct targeting of PSMD7 by triptolide. Tripterygium glycosides quickly mitigated cytokine storm, alleviated symptoms of HLH, and showed no observed adverse effects with a good cost-benefit profile, thereby offering a potential bridge for follow-up hematopoietic stem cell transplantation.

Humans↗
PubMed2007

Low temperature CO oxidation over unsupported nanoporous gold.

Supported Au nanoclusters are well-known for their unusual properties in catalysis. We describe here that nanostructured porous Au made via dealloying represents a new class of unsupported catalysts with extraordinary activities in important reactions such as CO oxidation. Although nanoporous Au may contain some oxides on the surface, our results demonstrate that it is metallic Au that plays the main role in this catalytic reaction. Furthermore, this material has good low-temperature catalytic stability and is extremely CO tolerant.

Journal Article↗
PubMed2007

Influence of polymorphic form, morphology, and excipient interactions on the dissolution of carbamazepine compacts.

To gain a deeper understanding of the behavior of carbamazepine (CBZ) and CBZ dihydrate (DH) compacts during in vitro dissolution tests various factors were investigated: hydrate formation of CBZ, crystal morphology, surface area, and excipient influence. Dissolution tests were performed in three different dissolution media: distilled water, hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG) solutions. For the CBZ compacts, the dissolution rate of CBZ in water was fastest (0.338 mg L(-1) min(-1)). With increasing ability of the excipients to inhibit the hydration of CBZ (PEG < HPMC), surprisingly the dissolution rate of CBZ compacts decreased: PEG solution (0.314 mg L(-1) min(-1)) > HPMC solution (0.257 mg L(-1) min(-1)). This implies that DH formation resulted in an apparent increase in the dissolution rate rather than slowing it down. For the DH compacts, the dissolution rate in water (0.055 mg L(-1) min(-1)) was slower than that of PEG and HPMC solutions (0.174 and 0.178 mg L(-1) min(-1), respectively). The contact angle measurements showed a significantly higher value in water (61.0 degrees) than in PEG and HPMC solutions (44.8 degrees and 43.1 degrees, respectively). Although the dissolution of CBZ and DH compacts in various dissolution media are complex processes, the influence and relative importance of these factors were clearly detected providing better understanding of the dissolution behavior of the drug.

Carbamazepine↗
PubMed2006

Aqueous-organic phase-transfer of highly stable gold, silver, and platinum nanoparticles and new route for fabrication of gold nanofilms at the oil/water interface and on solid supports.

A simple but effective aqueous-organic phase-transfer method for gold, silver, and platinum nanoparticles was developed on the basis of the decrease of the PVP's solubility in water with the temperature increase. The present method is superior in the transfer efficiency of highly stable nanoparticles to the common phase-transfer methods. The gold, silver, and platinum nanoparticles transferred to the 1-butanol phase dispersed well, especially silver and platinum particles almost kept the previous particle size. Electrochemical synthesis of gold nanoparticles in an oil-water system was achieved by controlling the reaction temperature at 80 degrees C, which provides great conveniences for collecting metal particles at the oil/water interface and especially for fabricating dense metal nanoparticle films. A technique to fabricate gold nanofilms on solid supports was also established. The shapes and sizes of gold nanoparticles as the building blocks may be controllable through changing reaction conditions.

Journal Article↗
PubMed2006

Effective mass and flow patterns of fluids surrounding microcantilevers.

An analytical approach to determine the streamlines of fluid flow adjacent to the surfaces of vibrating cantilevers is presented. Fluid flow over the top and bottom surfaces of a microcantilever is established by solving two-dimensional Navier-Stokes equations for viscous flow. The x and y velocity components are used to establish streamlines for absolute fluid motion. These streamlines show a central stagnation core perpendicular and central to the cantilever surface extending along the full length of cantilevers, which most likely accounts for the added mass effect (induced mass) of fluid media around vibrating microcantilevers.

Air↗
PubMed2006

Pseudolarix acid B, a new tubulin-binding agent, inhibits angiogenesis by interacting with a novel binding site on tubulin.

Tubulin-binding agents have received considerable interest as potential tumor-selective angiogenesis-targeting drugs. Herein, we report that pseudolarix acid B (PAB), isolated from the traditional Chinese medicinal plant Pseudolarix kaempferi Gordon, is a tubulin-binding agent. We further demonstrate that PAB significantly and dose-dependently inhibits proliferation, migration, and tube formation by human microvessel enthothelial cells. It is noteworthy that PAB eliminated newly formed endothelial tubes and microvessels both in vitro and in vivo. In addition, PAB dramatically arrested the cell cycle at G2/M phase. PAB also induced endothelial cell retraction, intercellular gap formation, and promoted actin stress fiber formation in conjunction with disruption of the tubulin and actin cytoskeletons. All of these effects occurred at noncytotoxic concentrations of PAB. We found that these effects of PAB are attributable to depolymerization of tubulin by direct interaction with a distinct binding site on tubulin compared with those of colchicine and vinblastine. Taken together, these findings show that PAB is a candidate antiangiogenic agent for use in cancer therapy, and they provide proof of principle for targeting this novel binding site on tubulin as a new strategy for treating cancer.

Angiogenesis Inhibitors↗
PubMed2006

Bioinformatics-enabled identification of the HrpL regulon and type III secretion system effector proteins of Pseudomonas syringae pv. phaseolicola 1448A.

The ability of Pseudomonas syringae pv. phaseolicola to cause halo blight of bean is dependent on its ability to translocate effector proteins into host cells via the hypersensitive response and pathogenicity (Hrp) type III secretion system (T3SS). To identify genes encoding type III effectors and other potential virulence factors that are regulated by the HrpL alternative sigma factor, we used a hidden Markov model, weight matrix model, and type III targeting-associated patterns to search the genome of P. syringae pv. phaseolicola 1448A, which recently was sequenced to completion. We identified 44 high-probability putative Hrp promoters upstream of genes encoding the core T3SS machinery, 27 candidate effectors and related T3SS substrates, and 10 factors unrelated to the Hrp system. The expression of 13 of these candidate HrpL regulon genes was analyzed by real-time polymerase chain reaction, and all were found to be upregulated by HrpL. Six of the candidate type III effectors were assayed for T3SS-dependent translocation into plant cells using the Bordetella pertussis calmodulin-dependent adenylate cyclase (Cya) translocation reporter, and all were translocated. PSPPH1855 (ApbE-family protein) and PSPPH3759 (alcohol dehydrogenase) have no apparent T3SS-related function; however, they do have homologs in the model strain P. syringae pv. tomato DC3000 (PSPTO2105 and PSPTO0834, respectively) that are similarly upregulated by HrpL. Mutations were constructed in the DC3000 homologs and found to reduce bacterial growth in host Arabidopsis leaves. These results establish the utility of the bioinformatic or candidate gene approach to identifying effectors and other genes relevant to pathogenesis in P. syringae genomes.

Adenylyl Cyclases↗
PubMed2006

Nuclear factor-kB signaling pathway constitutively activated in esophageal squamous cell carcinoma cell lines and inhibition of growth of cells by small interfering RNA.

Although constitutive nuclear factor (NF)-kappaB activation has been reported in many human tumors, the role of the NF-kappaB pathway in esophageal squamous cell carcinoma (ESCC) has not been known. In this study, NF-kappaB pathway in two ESCC cell lines was investigated using immunocytochemistry, Western blot and reverse transcription-polymerase chain reaction. The activation of NF-kappaB DNA binding was determined by electrophoretic mobility-shift assay. RNA interference was used to specifically inhibit the expression of p65. Growth of cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results showed that p50, p65, IkappaBalpha p-IkappaBalpha and IkappaB kinase beta were expressed and mainly localized in the cytoplasm. Reverse transcription-polymerase chain reaction results showed the constitutive expressions of p50, p65 and IkappaBalpha mRNA in the two ESCC cell lines. Furthermore, the nuclear extracts revealed that p50 and p65 translocated to the nucleus had DNA-binding activity. Finally, small interfering RNA of p65 decreased the expression of p65, and the viability of cells transfected with p65 small interfering RNA was significantly suppressed at the same concentration of 5-fluorouracil (P < 0.05) compared to untransfected cells. The results of this study showed that there was the constitutively activated NF-kB signaling pathway in the ESCC cell lines. RNA interference targeting at p65 increased the sensitivity of the ESCC cell lines to 5-fluorouracil, suggesting that NF-kappaB might be a good target for cancer treatment.

Carcinoma, Squamous Cell↗
PubMed2006

[Study on up-regulation of the expression of angiotensin-converting enzyme-2 in human umbilical vein endothelial cells by telmisartan].

OBJECTIVE: To investigate the effect of telmisartan on the protein and gene expression of angiotensin-converting enzyme-2 (ACE2) in human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were treated with various concentrations of telmisartan (10(-7), 10(-6) and 10(-5) mol/L) for 24 hours. In a time-control experiment, HUVECs were treated with telmisartan at the final concentration of 10(-6) mol/L for 6, 12 and 24 hours, respectively. In another experiment, HUVECs were treated with PD123319 (10(-6) mol/L) only or combined with same final concentration of telmisartan for 12 hours, respectively. Changes in both protein and gene expression of ACE2 were determined with Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) technique, respectively. RESULTS: Telmisartan induced a concentration and time dependent increase in both protein and gene expression of ACE2 (P<0.05 or P<0.01). Compared with control group, treatment of HUVECs with telmisartan at the concentration of 10(-7), 10(-6) and 10(-5) mol/L stimulated 1.5-, 2.7- and 4.6-fold increase in the ACE2 protein expression, as well as 1.2-, 2.3- and 4.5-fold increase in its gene expression, respectively. After treatment of HUVECs with telmisartan for 6, 12, and 24 hours at the concentration of 10(-6) mol/L, the ACE2 protein expression increased 1.6-, 2.7- and 4.2-fold, and its gene expression increased 1.3-, 2.3- and 4.0-fold, respectively. Compared with control and telmisartan groups, PD123319 had no effect on both protein and gene expression of ACE2 (P>0.05). CONCLUSION: Telmisartan up-regulates the protein and gene expression of ACE2 in HUVECs in a concentration and time dependent manner. This effect may be mediated via its specific pathway.

Angiotensin-Converting Enzyme 2↗
PubMed2005

Smad3 is key to TGF-beta-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis.

Smads2 and 3 transduce signals of TGF-beta from the cell surface to the nucleus. We used mice with a targeted deletion of Smad3 to study the specific contributions of this signaling pathway to pathogenic effects of TGF-beta. Focusing on models involving epithelial-to-mesenchymal transition (EMT), including injury to the lens and retina of the eye and to the kidney, we have found that loss of Smad3 blocks EMT and attenuates development of fibrotic sequelae. Smad3 also plays a critical role in both the tumor suppressor and pro-metastatic effects of TGF-beta in carcinogenesis. These observations suggest that development of small molecule inhibitors of Smad3 might have clinical application in treatment of fibrotic diseases as well as late stage cancers.

Animals↗
PubMed2005

Determining molecular binding sites on human serum albumin by displacement of oleic acid.

An NMR method was developed for determining binding sites of small molecules on human serum albumin (HSA) by competitive displacement of (13)C-labeled oleic acid. This method is based on the observation that in the crystal structure of HSA complexed with oleic acid, two principal drug-binding sites, Sudlow's sites I (warfarin) and II (ibuprofen), are also occupied by fatty acids. In two-dimensional [(1)H,(13)C]heteronuclear single quantum coherence NMR spectra, seven distinct resonances were observed for the (13)C-methyl-labeled oleic acid as a result of its binding to HSA. Resonances corresponding to the major drug-binding sites were identified through competitive displacement of molecules that bind specifically to each site. Thus, binding of molecules to these sites can be followed by their displacement of oleic acids. Furthermore, the amount of bound ligand at each site can be determined from changes in resonance intensities. For molecules containing fluorine, binding results were further validated by direct observations of the bound ligands using (19)F NMR. Identifying the binding sites for drug molecules on HSA can aid in determining the structure-activity relationship of albumin binding and assist in the design of molecules with altered albumin binding.

Binding Sites↗
PubMed2005

The pH-dependent conformational transition of beta-lactoglobulin modulates the binding of protoporphyrin IX.

We have investigated the interaction between PPIX and beta-lactoglobulin (beta-lg) as a function of the pH of the solution. beta-lg is a small globular protein (MW approximately 18 kDa) with a very well characterized structure that reveals several possible binding sites for ligands. The interaction with beta-lg affects the photophysical properties of PPIX. The shift of PPIX emission maximum, excitation maximum and the increase of the fluorescence intensity is an indicator that binding between the porphyrin and beta-lg occurs. The binding constant appears to be modulated by the pH of the solution. Spectroscopic measurements do not reveal any significant energy transfer between the Trp residues of beta-lg and PPIX, however, fluorescence anisotropy decay measurements confirm the binding and the modulation introduced by the pH of the solution. Since beta-lg has been shown to be stable within the range of pH adopted in our experiments (5.0-9.0), the results suggest that PPIX binds a site affected by the pH of the solution. Because of the crystallographic evidence an obvious site is near the aperture of the interior beta-barrel however an alternative (or concurrent) binding site may still be present.

Animals↗
PubMed2005

Philinopside A, a novel marine-derived compound possessing dual anti-angiogenic and anti-tumor effects.

Philinopside A is a novel sulfated saponin isolated from the sea cucumber, Pentacta quadrangulari. The effects of philinopside A on angiogenesis and tumor growth were assessed in a series of models in vitro and in vivo. Our results demonstrated that philinopside A significantly inhibited the proliferation, migration and tube formation of human microvascular endothelial cells (HMECs) in a dose-dependent manner, with average IC(50) values of 1.4 +/- 0.17, 0.89 +/- 0.23 and 0.98 +/- 0.19 microM, respectively. Rat aortas culture assay provides a close imitation of in vivo angiogenesis process and 2-10 microM philinopside A suppressed the formation of new microvessels in cultured rat aortas. Philinopside A 2-10 nmol/egg obviously inhibited angiogenesis in chick embryo chorioallantoic membrane assay. In addition, philinopside A manifested strong anti-tumor activities both in vitro and in vivo. Through immunofluorescent analysis, we found the compound reduced mouse sarcoma 180 tumor volume by inducing apoptosis of tumor and tumor-associated endothelial cells. An examination of the effects of philinopside A on the angiogenesis-related receptor tyrosine kinases (RTKs) showed that philinopside A broadly inhibited all tested RTKs, including vascular endothelial growth factor (VEGF) receptor, fibroblast growth factor (FGF) receptor-1, platelet-derived growth factor (PDGF) receptor-beta and epithelial growth factor (EGF) receptor, with IC(50) values ranging from 2.6-4.9 microM. These results suggest that philinopside A is a promising anti-cancer agent that possesses dual cytotoxic and anti-angiogenic effects that were at least partly due to its inhibitory effects on RTKs.

Animals↗
PubMed2005

Dynamic microcantilever sensors for discerning biomolecular interactions.

Response of a conductive micromechanical cantilever placed in close proximity to a surface undergoing electrical excitation near the resonance frequency of the cantilever is influenced by the presence of microscopic dielectrics in the gap between the cantilever and the sample surface. The variations of the resonance response of unmodified cantilevers at gap distances below a few hundred nanometers are used to discern biomolecular differences of oligomeric nucleic acids in an array format without the use of extrinsic labels. The resonance response variation paves the way for the development of high throughput detection of biomolecular reactions, such as DNA hybridization reactions or antibody-antigen interactions without the use of external labels, in which the need is only to see the presence or absence of interaction. This dynamic method is simple, does not require immobilizing individual elements on a cantilever array, and is compatible with current generation DNA chips in which DNA spots are deposited in micro- and nanoarray format.

Biosensing Techniques↗
PubMed2005

The synthesis of substituted bipiperidine amide compounds as CCR3 antagonists.

Bipiperidine amide 1 has been identified as a CC chemokine receptor 3 (CCR3) antagonist. Optimization of its structure-activity relationship has resulted in the identification of cis (R,R)-4-[(3,4-dichlorophenyl)methyl]-3-hydroxymethyl-1'(6-quinolinylcarbonyl)-1,4'-bipiperidine 14n, which exhibits potent receptor affinity and inhibition of both calcium flux and eosinophil chemotaxis.

Amides↗
PubMed2005

Pseudomonas syringae type III chaperones ShcO1, ShcS1, and ShcS2 facilitate translocation of their cognate effectors and can substitute for each other in the secretion of HopO1-1.

The Pseudomonas syringae type III secretion system (TTSS) translocates effector proteins into plant cells. Several P. syringae effectors require accessory proteins called type III chaperones (TTCs) to be secreted via the TTSS. We characterized the hopO1-1, hopS1, and hopS2 operons in P. syringae pv. tomato DC3000; these operons encode three homologous TTCs, ShcO1, ShcS1, and ShcS2. ShcO1, ShcS1, and ShcS2 facilitated the type III secretion and/or translocation of their cognate effectors HopO1-1, HopS1, and HopS2, respectively. ShcO1 and HopO1-1 interacted with each other in yeast two-hybrid and coimmunoprecipitation assays. Interestingly, ShcS1 and ShcS2 were capable of substituting for ShcO1 in facilitating HopO1-1 secretion and translocation and each TTC was able to bind the other's cognate effectors in yeast two-hybrid assays. Moreover, ShcO1, ShcS1, and ShcS2 all bound to the middle-third region of HopO1-1. The HopS2 effector possessed atypical P. syringae TTSS N-terminal characteristics and was translocated in low amounts. A site-directed HopS2 mutation that introduced a common N-terminal characteristic from other P. syringae type III secreted substrates increased HopS2 translocation, supporting the idea that this characteristic functions as a secretion signal. Additionally, hopO1-2 and hopT1-2 were shown to encode effectors secreted via the DC3000 TTSS. Finally, a DC3000 hopO1-1 operon deletion mutant produced disease symptoms similar to those seen with wild-type DC3000 but was reduced in its ability to multiply in Arabidopsis thaliana. The existence of TTCs that can bind to dissimilar effectors and that can substitute for each other in effector secretion provides insights into the nature of how TTCs function.

Amino Acid Sequence↗