Abstract:This work aimed to enhance the purposing profile of Etodolac (ETD) in Human Hepatocellular Carcinoma (HCC) HepG2 cells using sodium deoxycholate stabilized zein nanospheres (ETD-SDZN NSs). ETD-SDZN NSs were formulated using the nan-precipitation method and were characterized, in particular, in terms of mean particle size, zeta potential, encapsulation efficiency, colloidal stability and bioaccessibility. Estimations of cytotoxicity, cellular uptake, cell cycle progression, Annexin-V staining, mRNA expression of apoptotic genes and oxidative stress evaluations were conducted. The ETD-SDZN NSs selected formula obtained an average particle size of 113.6 7.4 nm, a zeta potential value of 32.7 2.3 mV, an encapsulation efficiency of 93.3 5.2%, enhanced bioaccessibility and significantly reduced IC50 against HepG2 cells, by approximately 13 times. There was also enhanced cellular uptake, accumulation in G2-M phase and elevated percentage cells in pre-G1 phase, significant elevated mRNA expression of P53, significant reduced expression of Cyclin-dependent kinase 1 (CDK1) and Cyclooxygenase-2 (COX-2) with enhanced oxidative stress by reducing glutathione reductase (GR) level, ameliorated reactive oxygen species (ROS) generation and lipid peroxidation outputs. ETD-SDZN NSs obtained a supreme cell death-inducing profile toward HepG2 cells compared to free ETD. The method of formulation was successful in acquiring the promising profile of ETD in HCC as a therapeutic molecule due to ameliorated cellular uptake, proapoptotic and oxidant potentials.Keywords: repurposing; apoptosis; etodolac; zein; HepG2; hepatocellular carcinoma; nanospheres
Previously, the presence of iron following acute MI was believed to be short-lived and cleared by macrophages within weeks after the MI5. The perceived role of iron in MI was focused on the ability of iron to promote free-radical formation via the Fenton Reaction with the ensuing death of cardiomyocytes, thereby contributing to MI expansion during the acute phase of MI6. It was further believed that physiological ramifications of MI size enhanced alterations in neurohormones and pro-inflammatory cytokine release following MI and that this was responsible for anatomic and functional remodeling during the chronic phase of MI resulting in CHF7,8,9,10. In this model, infarct size is believed to be the persistent driver of LV remodeling and poor prognosis: the role of iron is only transient.
nss pro v 0.46 free download
Hello, Switcher, Thank you for the plugin, it works wonderfully on my Windows system. I understand that you run Windows, do you know of anyone who is using it on Linux? I'm running into some trouble getting it working on Inkscape v0.46 under Ubuntu v8.04 LTS. I first tried installing in my user Inkscape extensions dir and received the following errors: --------------------------------------------------------Traceback (most recent call last):File "/home/UserName/.inkscape/extensions mydxf_outlines.py", line 24, in (module) import inkex, simplepath, simpletransform, cubicsuperpath, cspsubdiv, mydxf_templates, reImportError: No module named inkex--------------------------------------------------------*** NOTE that "(module)" was surrounded by "" chars but needed to be changed in order to post on the forum. I worked around the error by moving the plugin files from "/home/UserName/.inkscape/extensions" into the main Inkscpae extensions dir "/usr/share/inkscape/extensions" Now I do not get any errors but the DXF file that gets saved is 0 byte.Anyone using the plugin know of a fix for this?Thanks in advance for any help!
ericandmollie,Actually, once you learn a few basic things in Inkscape it's really easy to work with.Inkscape has a few quirks, but hey it's free. :)Thanks for stopping by. Switcher
RBRAGUE,1) I've only tried this plugin with Inkscape 0.462) Yes, the dxf exported with this plugin works fine with Vectric "Vcarve Pro".If you already have Vcarve Pro, you can use the .eps export inside Inkscape to create a .eps file, then import the .eps file to Vcarve Pro.
Ron,This plugin works inside both Inkscape 0.46 & 0.47I've tested both versions on the same PC & they are exporting R12 dxf files from the same plugin on this page (above).Let me know If you need more help.Thanks, Switcher
Hey Switcher,I've tried your method but it wasn't working for me (probably because I was doing something wrong). I downloaded v0.48 and it has a feature that I found works for me.Open image in InkscapeGo to PATH - Trace Bitmap - play with the settings till it looks goodSave As Desktop Cutting Plotter (R13)(.dxf)Doing this let me open .dxf in AutoCAD 2005 and my Torchmate CAD program.
OutputMarvins-MacBook-Pro: marvin$ /usr/bin/ruby -e "$(curl -fsSL )"Ignoring commonmarker-0.17.9 because its extensions are not built. Try: gem pristine commonmarker --version 0.17.9==> This script will install:/usr/local/bin/brew/usr/local/share/doc/homebrew/usr/local/share/man/man1/brew.1/usr/local/share/zsh/site-functions/_brew/usr/local/etc/bash_completion.d/brew/usr/local/HomebrewPress RETURN to continue or any other key to abort==> /usr/bin/sudo /bin/mkdir -p /Library/Caches/HomebrewPassword:==> /usr/bin/sudo /bin/chmod g+rwx /Library/Caches/Homebrew==> /usr/bin/sudo /usr/sbin/chown marvin /Library/Caches/Homebrew==> Downloading and installing Homebrew...HEAD is now at 545eb91c8 Merge pull request #4599 from reitermarkus/download-cache-directory==> Cleaning up /Library/Caches/Homebrew...==> Migrating /Library/Caches/Homebrew to /Users/marvin/Library/Caches/Homebrew...==> Deleting /Library/Caches/Homebrew...Already up-to-date.==> Installation successful!==> Homebrew has enabled anonymous aggregate user behaviour analytics.Read the analytics documentation (and how to opt-out) here: ==> Next steps:- Run `brew help` to get started- Further documentation: -MacBook-Pro: marvin$
OutputMarvins-MacBook-Pro: marvin$ brew install git==> Downloading -2.18.0.high_sierra.bottle.tar.gzAlready downloaded: /Users/marvin/Library/Caches/Homebrew/git-2.18.0.high_sierra.bottle.tar.gz==> Pouring git-2.18.0.high_sierra.bottle.tar.gz==> CaveatsBash completion has been installed to: /usr/local/etc/bash_completion.dzsh completions and functions have been installed to: /usr/local/share/zsh/site-functionsEmacs Lisp files have been installed to: /usr/local/share/emacs/site-lisp/git==> Summary? /usr/local/Cellar/git/2.18.0: 1,488 files, 295.6MBMarvins-MacBook-Pro: marvin$
Switched afl-plot to /bin/sh, since it seems bashism-free. Also triedto remove any obvious bashisms from other examples/ scripts,most notably including minimize_corpus.sh and triage_crashes.sh.Requested by Jonathan Gray.
Stimuli-responsive drug delivery systems offer the advantage of site-specific drug delivery and release in response to tumor chemical characteristics such as pH, intracellular enzymes, and redox gradient [31-33]. For instance, the concentration of glutathione (GSH) is higher in tumor cells (0.5-10 mM) compared to the normal cells (2-20 µM) [34]. This significant difference in terms of GSH concentration has prompt the design of GSH-responsive nanocarriers for tumor-targeted delivery of the drugs [35]. The presence of disulfide groups in the NSs promotes the release of drug molecules in response to the intracellular GSH concentrations. Daga and co-workers demonstrated the in vitro anti-cancer efficiency of doxorubicin (DOX)-loaded GSH-responsive NSs in different cancer cells [36]. Moreover, in vivo studies suggested a prolonged plasma circulation time of the DOX-GSH-NSs compared to free DOX [36]. GSH-responsive cyclodextrin NSs loaded with anticancer drug have been shown to kill preferentially cancer cells highly expressing GSH [37].
RV-loaded GSH-NSs were prepared by adding RV in a different weight ratio of 1:2, 1:4, and, 1:6 (w/w; drug: nanosponge) in a nanosuspension of GSH-NSs (10 mg/mL). Later, samples were sonicated for 20 minutes followed by continuous stirring for 24 hours in dark. Samples were subjected to mild centrifugation and supernatant was collected followed by dialysis in water for a few minutes to remove the unloaded drug. RV-loaded GSH-NSs were freeze-dried and stored in a desiccator for further characterization. Fluorescent NSs were prepared in a similar manner by taking NS suspension (10 mg/mL) in saline with 0.1 mg/mL coumarin-6 (C-6).
Cells plated on sterile coverslips and treated with the RV-GSH-NSs as indicated were labeled with the fluorescent dye Cell Tracker (Cell Tracker Blue-CMAC 7-amino-4-chloromethylcoumarin; incubation for 30 min in serum-free media at 37 C followed by additional 30 min in complete media at 37 C; cod. C2110, Life Technologies) as previously reported [40]. At the end of treatment, fluorescence stained coverslips were promptly observed under the fluorescence microscope.
GSH-responsive β-CD-NSs were prepared from pyromellitic dianhydride and 2-hydroxyethyl disulfide as the crosslinkers. A schematic of the structure of the GSH-NSs is shown in Supplementary Figure S1. After complete purification, we first performed an elemental analysis to determine the presence of sulfur in the blank GSH-NSs. The carbon and hydrogen contents were 54.42% and 5.33%, respectively as confirmed by CHNS analysis. Moreover, the sulfur content in the GSH-NSs was 0.75%. However, the sulfur content was lower than the theoretical value of 0.97%. The lower sulfur content could be attributed to the low reactivity of 2-hydroxyethyl disulfide as a crosslinking agent compared to β-CD. Furthermore, elemental analysis results are in agreement with the previously reported data [38]. The solubilization of RV in the presence of GSH-NSs was studied to confirm the enhancement in the aqueous solubility which showed more than four-fold higher solubilization (201 µg/mL) in water compared to free RV (46 µg/mL). The increase in the solubility could be attributed to the presence of multiple cavities of the CDs in the polymeric matrix of the GSH-NSs. The loading of RV with GSH-NSs was carried out by taking different weight ratios of 1:2, 1:4, and 1:6 (w/w; RV-GSH-NSs), respectively. The RV loading was 9.95% at 1:2 w/w which increased significantly to 16.12% at 1:4 w/w. However, RV loading decreased to 13.72% at 1:6 w/w, possibly due to the saturation of the RV into the GSH-NSs. As per the drug loading data, RV-GSH-NSs (1:4 w/w) were chosen to carry out further studies. In Supplementary Table 1, the particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency of GSH-NSs formulations are reported. The particle size of blank GSH-NSs was less than 200 nm, and zeta potential was high enough to ensure the physical stability of nano-formulation in order to avoid the agglomeration of the colloidal NS particles. The physical interaction of RV with GSH-NSs was evaluated by FTIR, DSC, and PXRD studies. The FTIR spectra of blank GSH-NSs, RV, and RV-GSH-NSs are shown in Supplementary Figure S2(A). The FTIR spectrum of RV showed characteristic peaks at 3210 cm-1 due to stretching of the O-H group, followed by C-H stretching of phenyl ring at 3017 cm-1, C=C stretching at 1608 cm-1, and O-H bending at 1325 cm-1. It was also observed that RV encapsulation within GSH-NSs led to the change and shift in the characteristic vibrations of the RV. This change in the FTIR spectrum of RV could be due to the interaction of the drug with GSH-NSs. 2ff7e9595c
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