Anesthetic Activity of Acetylated MS-222 in Tilapia (Oreochromis Niloticus)

A group of 8 tilapia (Oreochromis niloticus) were anesthetized once per week for six consecutive weeks, using tricaine methanesulfonate (MS-222) in the water. Time for the fish to reach anesthesia decreased significantly over the first four weeks, and then plateaued at about 27% below the first anesthetic exposure. These results suggest induction of the liver enzymes that convert MS-222 into metabolites, one or more of which have higher anesthetic activity than the parent compound. Major metabolites of MS-222 have been identified as part of regulatory studies evaluating residue persistence in food fishes. One of these metabolites, N-acetyl-3-aminobenzoic acid ethyl ester, which is acetylated MS-222, was selected for testing of anesthetic activity in tilapia. This report shows results of the testing, and speculates as to the potential utility of the acetylated metabolite of MS-222 as an alternate anesthetic agent in fish

Nanobubbles at hydrophilic particle–water interfaces

The puzzling persistence of nanobubbles breaks Laplace’s law for bubbles, which is of great interest for promising applications in surface processing, H2 and CO2 storage, water treatment, and drug delivery. So far, nanobubbles are mostly reported on the hydrophobic planar substrates with atom flatness. It remains a challenge to quantify nanobubbles on rough and irregular surfaces due to the lack of characterization technique that can detect both the nanobubble morphology and chemical composition inside individual nanobubble-like objects. Here, by using synchrotron-based scanning transmission soft X-ray microscopy (STXM) with nanometer resolution, we discern nanoscopic gas bubbles > 25 nm with direct in-situ proof of O2 inside the nanobubbles at a hydrophilic particle-water interface under ambient conditions. We find a stable cloud of O2 nanobubbles at the diatomite particle-water interface hours after oxygen aeration and temperature variation. The in situ technique may be useful for many surface nanobubble related studies such as material preparation and property manipulation, phase equilibrium, nucleation kinetics and their relationships with chemical composition within the confined nanoscale space. The oxygen nanobubble clouds may be important in modifying particle-water interfaces and offering breakthrough technologies for oxygen delivery in sediment and/or deep water environment

Fucosyltransferase 1 and 2 play pivotal roles in breast cancer cells.

FUT1 and FUT2 encode alpha 1, 2-fucosyltransferases which catalyze the addition of alpha 1, 2-linked fucose to glycans. Glycan products of FUT1 and FUT2, such as Globo H and Lewis Y, are highly expressed on malignant tissues, including breast cancer. Herein, we investigated the roles of FUT1 and FUT2 in breast cancer. Silencing of FUT1 or FUT2 by shRNAs inhibited cell proliferation in vitro and tumorigenicity in mice. This was associated with diminished properties of cancer stem cell (CSC), including mammosphere formation and CSC marker both in vitro and in xenografts. Silencing of FUT2, but not FUT1, significantly changed the cuboidal morphology to dense clusters of small and round cells with reduced adhesion to polystyrene and extracellular matrix, including laminin, fibronectin and collagen. Silencing of FUT1 or FUT2 suppressed cell migration in wound healing assay, whereas FUT1 and FUT2 overexpression increased cell migration and invasion in vitro and metastasis of breast cancer in vivo. A decrease in mesenchymal like markers such as fibronectin, vimentin, and twist, along with increased epithelial like marker, E-cadherin, was observed upon FUT1/2 knockdown, while the opposite was noted by overexpression of FUT1 or FUT2. As expected, FUT1 or FUT2 knockdown reduced Globo H, whereas FUT1 or FUT2 overexpression showed contrary effects. Exogenous addition of Globo H-ceramide reversed the suppression of cell migration by FUT1 knockdown but not the inhibition of cell adhesion by FUT2 silencing, suggesting that at least part of the effects of FUT1/2 knockdown were mediated by Globo H. Our results imply that FUT1 and FUT2 play important roles in regulating growth, adhesion, migration and CSC properties of breast cancer, and may serve as therapeutic targets for breast cancer

Biological Characterization of 3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145) as a Selective Sphingosine Kinase-2 Inhibitor and Anticancer Agent

In our effort to develop selective sphingosine kinase-2 (SphK2) inhibitors as pharmacological tools, a thiazolidine-2,4-dione analogue, 3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione(K145), was synthesized and biologically characterized. Biochemical assay results indicate that K145 is a selective SphK2 inhibitor. Molecular modeling studies also support this notion. In vitro studies using human leukemia U937 cells demonstrated that K145 accumulates in U937 cells, suppresses the S1P level, and inhibits SphK2. K145 also exhibited inhibitory effects on the growth of U937 cells as well as apoptotic effects in U937 cells, and that these effects may be through the inhibition of down-stream ERK and Akt signaling pathways. K145 also significantly inhibited the growth of U937 tumors in nude mice by both intraperitoneal and oral administration, thus demonstrating its in vivo efficacy as a potential lead anticancer agent. The antitumor activity of K145 was also confirmed in a syngeneic mouse model by implanting murine breast cancer JC cells in BALB/c mice. Collectively, these results strongly encourage further optimization of K145 as a novel lead compound for development of more potent and selective SphK2 inhibitors

Δ\Delta-scaling and heat capacity in relativistic ion collisions

The $\Delta$-scaling method has been applied to the total multiplicity distribution of the relativistic ion collisions of p+p, C+C and Pb+Pb which were simulated by a Monte Carlo package, LUCIAE 3.0. It is found that the $\Delta$-scaling parameter decreases with the increasing of the system size. Moreover, the heat capacities of different mesons and baryons have been extracted from the event-by-event temperature fluctuation in the region of low transverse mass and they show the dropping trend with the increasing of impact parameter.Comment: version 2: major change: 4 pages, 3 figures; Proceeding of International Conference on "Strangeness in Quark Matter" (SQM2004), Cape Town, South Africa, Spet. 2004 (Submitted to J. Phys. G.

Effective Lagrangian for sˉbg\bar{s}bg and sˉbγ\bar{s}b\gamma Vertices in the mSUGRA model

Complete expressions of the $\bar{s}bg$ and $\bar{s}b\gamma$ vertices are derived in the framework of supersymmetry with minimal flavor violation. With the minimal supergravity (mSUGRA) model, a numerical analysis of the supersymmetric contributions to the Wilson Coefficients at the weak scale is presented.Comment: 12 pages + 7 ps figures, Late

|Delta B|=1 Weak Effective Lagrangian in the Minimal Flavor Violation Supersymmetry

To evaluate the weak decays of b-hadrons, the $\Delta B=1$ weak effective Lagrangian is the foundation. Any new physics beyond the standard model (SM) would contribute to the effective Lagrangian through the loop integration at the weak scale and evolution from the weak scale down to the hadronic scale. In this work we present a systematic analysis on the effective Lagrangian which mediates hadronic $|\Delta B|=1$ processes in the framework of the minimal flavor violation supersymmetry as well as a numerical evaluation of the Wilson coefficients in the effective theory.Comment: Latex,16 pages plus 5 figures, PRD versio

Targeting the BRD4/FOXO3a/CDK6 Axis Sensitizes AKT Inhibition in Luminal Breast Cancer

BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or CDK6 significantly overcomes the resistance of luminal breast cancer cells to AKT inhibitors in vitro and in vivo. Our study reports the involvement of BRD4/FOXO3a/CDK6 axis in AKTi resistance and provides potential therapeutic strategies for treating resistant breast cancer

Title page Regulation of Inflammatory Pain by Inhibition of Fatty Acid Amide Hydrolase (FAAH)

Abstract Although cannabinoids are efficacious in laboratory animal models of inflammatory pain, their established cannabimimetic actions diminish enthusiasm for their therapeutic development. Conversely, fatty acid amide hydrolase (FAAH), the chief catabolic enzyme regulating the endogenous cannabinoid N-arachidonoylethanolamine (anandamide), has emerged as an attractive target to treat pain and other conditions. Here, we tested WIN55,212-2, a cannabinoid receptor agonist, as well as genetic deletion or pharmacological inhibition of FAAH in the lipopolysaccharide (LPS) mouse model of inflammatory pain. WIN55,212 significantly reduced edema and hotplate hyperalgesia caused by LPS infusion into the hind paws, though the mice also displayed analgesia and other CNS effects. FAAH (-/-) mice exhibited reduced paw edema and hyperalgesia in this model, without apparent cannabimimetic effects. Transgenic mice expressing FAAH exclusively on neurons continued to display the anti-edematous, but not the anti-hyperalgesic, phenotype. The CB 2 receptor antagonist, SR144528, blocked this non-neuronal, anti-inflammatory phenotype, and the CB 1 receptor antagonist, rimonabant, blocked the anti-hyperalgesic phenotype. The FAAH inhibitor, URB597 attenuated the development of LPS-induced paw edema and reversed LPS-induced hyperalgesia through respective CB 2 and CB 1 receptor mechanisms of action. However, the TRPV1 receptor antagonist, capsazepine, did not affect either the anti-hyperalgesic or antiedematous effects of URB597. Finally, URB597 attenuated levels of the pro-inflammatory cytokines IL-1β and TNF-α in LPS-treated paws. These findings demonstrate that simultaneous elevations in non-neuronal and neuronal endocannabinoid signaling are possible through inhibition of a single enzymatic target, thereby offering a potentially powerful strategy to treat chronic inflammatory pain syndromes that operate at multiple levels of anatomical integration