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Li, Ying

Publications and source records attributed to Li, Ying.

159 records · Page 9

Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer

Arachidonic acid (AA)-derived eicosanoids and its downstream pathways have been demonstrated to play crucial roles in growth control of breast cancer. Here, we demonstrate that isoliquiritigenin, a flavonoid phytoestrogen from licorice, induces growth inhibition and apoptosis through downregulating multiple key enzymes in AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. Isoliquiritigenin diminished cell viability, 5-bromo-2′-deoxyuridine (BrdU) incorporation, and clonogenic ability in both MCF-7 and MDA-MB-231cells, and induced apoptosis as evidenced by an analysis of cytoplasmic histone-associated DNA fragmentation, flow cytometry and hoechst staining. Furthermore, isoliquiritigenin inhibited mRNA expression of multiple forms of AA-metabolizing enzymes, including phospholipase A2 (PLA2), cyclooxygenases (COX)-2 and cytochrome P450 (CYP) 4A, and decreased secretion of their products, including prostaglandin E{sub 2} (PGE{sub 2}) and 20-hydroxyeicosatetraenoic acid (20-HETE), without affecting COX-1, 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP), and leukotriene B{sub 4} (LTB{sub 4}). In addition, it downregulated the levels of phospho-PI3K, phospho-PDK (Ser{sup 241}), phospho-Akt (Thr{sup 308}), phospho-Bad (Ser{sup 136}), and Bcl-x{sub L} expression, thereby activating caspase cascades and eventually cleaving poly(ADP-ribose) polymerase (PARP). Conversely, the addition of exogenous eicosanoids, including PGE{sub 2}, LTB{sub 4} and a 20-HETE analog (WIT003), and caspase inhibitors, or overexpression of constitutively active Akt reversed isoliquiritigenin-induced apoptosis. Notably, isoliquiritigenin induced growth inhibition and apoptosis of MDA-MB-231 human breast cancer xenografts in nude mice, together with decreased intratumoral levels of eicosanoids and phospho-Akt (Thr{sup 308}). Collectively, these data suggest that isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. - Highlights: • Isoliquiritigenin induces growth inhibition and apoptosis in human breast cancer. • The proapoptotic action of isoliquiritigenin has been studied in vitro and in vivo. • Arachidonic acid metabolic network mediates isoliquiritigenin-induced apoptosis. • PI3K/Akt deactivation is asssociated with isoliquiritigenin-induced apoptosis. • Isoliquiritigenin may be a multi-target drug in the treatment of breast cancer.

60 APPLIED LIFE SCIENCES↗

Measurement of neutron dose equivalent outside and inside of the treatment vault of GRID therapy

Purpose: To evaluate the neutron and photon dose equivalent rates at the treatment vault entrance (H{sub n,D} and H{sub G}), and to study the secondary radiation to the patient in GRID therapy. The radiation activation on the grid was studied.Methods: A Varian Clinac 23EX accelerator was working at 18 MV mode with a grid manufactured by .decimal, Inc. The H{sub n,D} and H{sub G} were measured using an Andersson–Braun neutron REM meter, and a Geiger Müller counter. The radiation activation on the grid was measured after the irradiation with an ion chamber γ-ray survey meter. The secondary radiation dose equivalent to patient was evaluated by etched track detectors and OSL detectors on a RANDO{sup ®} phantom.Results: Within the measurement uncertainty, there is no significant difference between the H{sub n,D} and H{sub G} with and without a grid. However, the neutron dose equivalent to the patient with the grid is, on average, 35.3% lower than that without the grid when using the same field size and the same amount of monitor unit. The photon dose equivalent to the patient with the grid is, on average, 44.9% lower. The measured average half-life of the radiation activation in the grid is 12.0 (±0.9) min. The activation can be categorized into a fast decay component and a slow decay component with half-lives of 3.4 (±1.6) min and 15.3 (±4.0) min, respectively. There was no detectable radioactive contamination found on the surface of the grid through a wipe test.Conclusions: This work indicates that there is no significant change of the H{sub n,D} and H{sub G} in GRID therapy, compared with a conventional external beam therapy. However, the neutron and scattered photon dose equivalent to the patient decrease dramatically with the grid and can be clinical irrelevant. Meanwhile, the users of a grid should be aware of the possible high dose to the radiation worker from the radiation activation on the surface of the grid. A delay in handling the grid after the beam delivery is suggested.

61 RADIATION PROTECTION AND DOSIMETRY↗

Radicicol, a heat shock protein 90 inhibitor, inhibits differentiation and adipogenesis in 3T3-L1 preadipocytes

Highlights: •Radicicol suppressed intracellular fat accumulation in 3T3-L1 adipocytes. •Radicicol inhibited the expression of FAS and FABP4. •Radicicol blocked cell cycle at the G1-S phase during cell differentiation. •Radicicol inhibited the PDK1/Akt pathway in adipocyte differentiation. -- Abstract: Heat shock protein 90 (Hsp90) is involved in various cellular processes, such as cell proliferation, differentiation and apoptosis. As adipocyte differentiation plays a critical role in obesity development, the present study investigated the effect of an Hsp90 inhibitor radicicol on the differentiation of 3T3-L1 preadipocytes and potential mechanisms. The cells were treated with different concentrations of radicicol during the first 8 days of cell differentiation. Adipogenesis, the expression of adipogenic transcriptional factors, differentiation makers and cell cycle were determined. It was found that radicicol dose-dependently decreased intracellular fat accumulation through down-regulating the expression of peroxisome proliferator-activated receptor γ (PPAR{sub γ}) and CCAAT element binding protein α (C/EBP{sub α}), fatty acid synthase (FAS) and fatty acid-binding protein 4 (FABP4). Flow cytometry analysis revealed that radicicol blocked cell cycle at G1-S phase. Radicicol redcued the phosphorylation of Akt while showing no effect on β-catenin expression. Radicicol decreased the phosphorylation of phosphoinositide-dependent kinase 1 (PDK1). The results suggest that radicicol inhibited 3T3-L1 preadipocyte differentiation through affecting the PDK1/Akt pathway and subsequent inhibition of mitotic clonal expansion and the expression/activity of adipogenic transcriptional factors and their downstream adipogenic proteins.

60 APPLIED LIFE SCIENCES↗

Analysis of five rice 4-coumarate:coenzyme A ligase enzyme activity and stress response for potential roles in lignin and flavonoid biosynthesis in rice

Highlights: ► 4CLs play important roles in both lignin and flavonoids biosynthesis. ► PA and FA are the two main substrates of 4CL (Os4CL1/3/4/5) for lignin biosynthesis. ► Os4CL2 is suggested for flavonoid formation in defense against UV radiation. -- Abstract: 4-Coumarate:coenzyme A ligase (4CL) catalyzes the conversion of hydroxycinnamates into corresponding CoA esters for biosynthesis of flavonoids and lignin. In this study, five members of the 4CL gene family from rice were cloned and analyzed. Recombinant 4CL data revealed that 4-coumaric acid and ferulic acid were the two main substrates of 4CL (Os4CL1/3/4/5) for monolignol biosynthesis in rice. Os4CL2 was specifically expressed in the anther and was strongly activated by UV irradiation, suggesting its potential involvement in flavonoid formation. Moreover, bioinformatics analysis showed that the existence of valine residue at the substrate-binding pocket may mainly affect rice 4CL activities toward sinapic acid.

60 APPLIED LIFE SCIENCES↗

Inverse-Micelle-Encapsulated Water-Enabled Bond Breaking of Dialkyl Diselenide/Disulfide: A Critical Step for Synthesizing High- Quality Gold Nanoparticles

Inverse-micelle-encapsulated water formed in the two-phase Brust-Schiffrin method (BSM) synthesis of Au nanoparticles (NPs) is identified as essential for dialkyl diselenide/disulfide to react with the Au(III) complex in which the Se-Se/S-S bond is broken, leading to formation of higher-quality Au NPs.

Environmental Molecular Sciences Laboratory↗

Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer

Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressing cells enhanced proliferation, migration and tube formation of human umbilical vein endothelial cells, and promoted angiogenesis in the zebrafish embryo and chorioallantoic membrane of the chick embryo. In addition, there were lower levels of myristic acid and lauric acid, and higher contents of 20-hydroxyeicosatetraenoic acid (20-HETE) in CYP4Z1-expressing T47D cells compared with vector control. CYP4Z1 overexpression significantly increased tumor weight and microvessel density by 2.6-fold and 1.9-fold in human tumor xenograft models, respectively. Moreover, CYP4Z1 transfection increased the phosphorylation of ERK1/2 and PI3K/Akt, while PI3K or ERK inhibitors and siRNA silencing reversed CYP4Z1-mediated changes in VEGF-A and TIMP-2 expression. Conversely, HET0016, an inhibitor of the CYP4 family, potently inhibited the tumor-induced angiogenesis with associated changes in the intracellular levels of myristic acid, lauric acid and 20-HETE. Collectively, these data suggest that increased CYP4Z1 expression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation. -- Highlights: ► CYP4Z1 overexpression promotes human breast cancer growth and angiogenesis. ► The pro-angiogenic effects of CYP4Z1 have been studied in vitro and in vivo. ► CYP4Z1 regulates expression and production of VEGF-A and TIMP-2. ► CYP4Z1-induced angiogenesis is associated with PI3K and ERK1/2 activation. ► CYP4Z1 may be an attractive target for anti-cancer therapy.

60 APPLIED LIFE SCIENCES↗

In-Situ TEM Study Of Lithiation Behavior Of Silicon Nanoparticles Attached To And Embedded In A Carbon Matrix

Rational design of silicon and carbon nanocomposite with a special topological feature has been demonstrated to be a feasible way for mitigating the capacity fading associated with the large volume change of silicon anode in lithium ion batteries. Although the lithiation behavior of silicon and carbon as individual component has been well understood, lithium ion transport behavior across a network of silicon and carbon are still lacking. In this paper, we probe the lithiation behavior of silicon nanoparticles attached to and embedded in a carbon nanofiber using in-situ TEM and continuum mechanical calculation. We found that aggregated silicon nanoparticles show contact flattering upon initial lithiation, which is characteristically analogous to the classic sintering of powder particles by neck-growth mechanism. As compared with the surface-attached silicon particle, particles embedded in the carbon matrix show delayed lithiation. Depending on the strength of the carbon matrix, lithiation of the embedded silicon nanoparticle can lead to the fracture of the carbon fiber. These observations provide insights on lithium ion transport in the network structured composite of silicon and carbon, and ultimately provide fundamental guidance for mitigating the failure of battery due to the large volume change of silicon anode.

Environmental Molecular Sciences Laboratory↗

Mechanistic insights on one-phase vs. two-phase Brust–Schiffrin method synthesis of Au nanoparticles with dioctyl-diselenides

Metal precursors in the one-phase (1p) and two-phase (2p) Brust-Schiffrin method (BSM) synthesis of Au nanoparticles (NPs) using dioctyl-diselenides were identified. A single dominant type of metal precursor was found in the 1p synthesis as compared to multiple ones in the 2p synthesis, which was proposed as the key reason why the former is better than the latter.

36 MATERIALS SCIENCE↗

Visible light responsive iodine-doped TiO 2 for photocatalytic reduction of CO 2 to fuels

Iodine-doped titanium oxide (I-TiO 2 ) nanoparticles that are photocatalitically responsive to visible light illumination have been synthesized by hydrothermal method. The structure and properties of I-TiO 2 nanocrystals prepared with different iodine doping levels and/or calcination temperatures were characterized by X-ray diffraction, transmission electron microscopy and diffraction, X-ray photoelectron spectroscopy, and UV-vis diffuse reflectance spectra. The three nominal iodine dopant levels (5, 10, 15 wt.%) and the two lower calcination temperatures (375, 450°C) produced mixture of anatase and brookite nanocrystals, with small fraction of rutile found at 550°C. The anatase phase of TiO 2 increased in volume fraction with increased calcination temperature and iodine levels. The photocatalytic activities of the I-TiO 2 powders were investigated by photocatalytic reduction of CO 2 with H 2 O under visible light (λ > 400 nm) and also under UV-vis illumination. CO was found to be the major photoreduction product using both undoped and doped TiO 2 . A high CO 2 reduction activity was observed for I-TiO 2 catalysts (highest CO yield equivalent to 2.4 micro mol g -1 h -1 ) under visible light, and they also had much higher CO 2 photoreduction efficiency than undoped TiO 2 under UV-vis irradiation. I-TiO 2 calcined at 375°C has superior activity to those calcined at higher temperatures. Optimal doping levels of iodine were identified under visible and UV-vis irradiations, respectively. This is the first study that investigates nonmetal doped TiO 2 without other co-catalysts for CO 2 photoreduction to fuels under visible light.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Lossless Video Sequence Compression Using Adaptive Prediction

We present an adaptive lossless video compression algorithm based on predictive coding. The proposed algorithm exploits temporal, spatial, and spectral redundancies in a backward adaptive fashion with extremely low side information. The computational complexity is further reduced by using a caching strategy. We also study the relationship between the operational domain for the coder (wavelet or spatial) and the amount of temporal and spatial redundancy in the sequence being encoded. Experimental results show that the proposed scheme provides significant improvements in compression efficiencies.

Li, Ying↗