20 research outputs found
Apigenin inhibits TNFα/IL-1α-induced CCL2 release through IKBK-epsilon signaling in MDA-MB-231 human breast cancer cells - Fig 7
<p><b>A. IKBKe transcription in MDA-MB-231 cells ± TNFα ± Apigenin.</b> The data represent normalized expression and are expressed as the Mean ± S.E.M., n = 3. The significance of differences between the Ctrl and TNFα groups and TNFα vs. TNFα + Apigenin were determined by a Students t-test *p<0.05. <b>Figure 7B.</b> Protein expression of <b>IKBKe</b>/GAPDH with TNFα ± Apigenin at 24 hours.</p
NF-kB PCR microarray tabulated data on MDA-MB-231 cells ± TNFα ± Apigenin.
<p>The data displays differential transcription as Log2 (Fc) for controls vs. TNFα (Left Panel) and TNFα vs. TNFα + Apigenin (Right Panel) in MDA-MB-231 cells treated for 24 hours. The data show no significant changes at P < .05 for either analysis, with non-significant differences for only IL-1α.</p
NF-kB PCR microarray assessment on MDA-MB-231 cells ± TNFα ± Apigenin.
<p>The data displays differential transcription for controls vs. TNFα (A) and TNFα vs. TNFα + Apigenin (B) in MDA-MB-231 cells treated for 24 hours. The data show no significant changes at P < .05 for either analysis, with non-significant differences for only IL-1α.</p
Characterization of Clinically Relevant Fungi via SERS Fingerprinting Assisted by Novel Chemometric Models
Nonculture-based
tests are gaining popularity and upsurge in the
diagnosis of <b>invasive fungal infections (IFI)</b> fostered
by their main asset, the reduced analysis time, which enables a more
rapid diagnosis. In this project, three different clinical isolates
of relevant filamentous fungal species were discriminated by using
a rapid (less than 5 min) and sensitive <b>surface-enhanced Raman
scattering (SERS)</b>-based detection method, assisted by chemometrics.
The holistic evaluation of the SERS spectra was performed by employing
appropriate chemometric toolsîžclassical and <b>fuzzy principal
component analysis (FPCA)</b> in combination with <b>linear
discriminant analysis (LDA)</b> applied to the first relevant principal
components. The efficiency of the proposed robust algorithm is illustrated
on the data set including three fungal isolates (<i>Aspergillus
fumigatus</i> sensu stricto, cryptic <i>A. fumigatus</i> complex species, and <i>Rhizomucor pusillus</i>) that
were isolated from patient materials. The accurate and reliable discrimination
between species of common fungal pathogen strains suggest that the
developed method has the potential as an alternative, spectroscopic-based
routine analysis tool in IFI diagnosis
Progress of Hepatitis C elimination in Viennese people living with HIV after two decades of increasing cure rates
Interferon(IFN)-based hepatitis C virus (HCV) therapy has been replaced by direct-acting antivirals (DAAs). We assessed temporal trends in patient characteristics, transmission risks, treatment initiation, and cure rates in eras of IFN, restricted DAA-access, and unrestricted DAA-access in Viennese HCV/HIV-coinfected patients (HIV/HCV). Consecutive HIV/HCV-coinfected patients starting HCV treatment at the Vienna General Hospital between 2002 and 2020 were retrospectively enrolled. Of all Nâ=â508 HIV/HCV, 78% (398/508) were male and the mean age was 41.8â±â9.5âyears. âPeople-who-inject-drugsâ (PWID) accounted for 61% (311/508), while 31% (156/508) were âmen who have sex with menâ (MSM). In the IFN-era, restricted DAA-era and unrestricted DAA-era, Nâ=â152, Nâ=â129, and Nâ=â227 HCV treatments were started and 49% (74/152), 95% (122/129), and 88% (200/227) achieved sustained virologic response, respectively. Treatment during the IFN-era was a strong predictor for virologic non-response (aOR 12.69; 6.93â23.24) and loss-to-follow-up (aOR 6.12; 2.99â12.54), while virologic non-response was less common in âMSMâ (aOR 0.28; 0.13â0.62). Ninety three percent (50/54) of the observed HCV reinfections occurred in the unrestricted DAA-era. A substantial increase in âMSMâ transmission was observed since 2010 with 66% (107/161) in the DAA-era versus 15% (49/330) prior to the DAA-era. HCV cure rates in Viennese HIV patients increased from 49% in the IFN-era to 88â95% in the DAA-era. MSM-related risk behaviour and reinfections became the key challenges towards HCV elimination in HIV-coinfected patients.</p
Transjugular intrahepatic portosystemic shunts (TIPS) for the prevention of variceal re-bleeding â A two decades experience
<div><p>Background and aims</p><p>Transjugular intrahepatic portosystemic shunts (TIPS) are used in patients with cirrhosis for the prevention of variceal rebleeding.</p><p>Methods</p><p>We retrospectively evaluated re-bleeding rate, patency, mortality, and transplant-free survival (TFS) in cirrhotic patients receiving TIPS implantation for variceal bleeding between 1994â2014.</p><p>Results</p><p>286 patients received TIPS (n = 119 bare metal stents, n = 167 polytetrafluorethylene (PTFE)-covered stents) for prevention of variceal re-bleeding. Mean age was 55.1 years, median MELD was 11.8, and the main etiology of cirrhosis was alcoholic liver disease (70%). Median follow-up was 821 days. 67 patients (23%) experienced at least one re-bleeding event. Patients with PTFE-TIPS were at significantly lower risk for variceal re-bleeding than patients with bare metal stents (14% vs. 37%, OR:0.259; p<0.001) and had less need for stent revision (21% vs. 37%; p = 0.024). Patients with PTFE stent grafts showed lower mortality than patients with bare stents after 1 year (19% vs. 31%, p = 0.020) and 2 years (29% vs. 40%; p = 0.041) after TIPS implantation. Occurrence of hepatic encephalopathy after TIPS was similar between groups (20% vs. 24%, p = 0.449).</p><p>Conclusions</p><p>PTFE-TIPS were more effective at preventing variceal re-bleeding than bare metal stents due to better patency. Since this tended to translate in improved survival, only covered stents should be implemented for bleeding prophylaxis when TIPS is indicated.</p></div
<i>N</i><sup>Δ</sup>âAcryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, StructureâActivity Relationships, and Pharmacokinetic Profiling
Transglutaminase
2 (TGase 2)-catalyzed transamidation represents
an important post-translational mechanism for protein modification
with implications in physiological and pathophysiological conditions,
including fibrotic and neoplastic processes. Consequently, this enzyme
is considered a promising target for the diagnosis of and therapy
for these diseases. In this study, we report on the synthesis and
kinetic characterization of <i>N</i><sup>Δ</sup>-acryloyllysine
piperazides as irreversible inhibitors of TGase 2. Systematic structural
modifications on 54 new compounds were performed with a major focus
on fluorine-bearing substituents due to the potential of such compounds
to serve as radiotracer candidates for positron emission tomography.
The determined inhibitory activities ranged from 100 to 10âŻ000
M<sup>â1</sup> s<sup>â1</sup>, which resulted in comprehensive
structureâactivity relationships. Structureâactivity
correlations using various substituent parameters accompanied by covalent
docking studies provide an advanced understanding of the molecular
recognition for this inhibitor class within the active site of TGase
2. Selectivity profiling of selected compounds for other transglutaminases
demonstrated an excellent selectivity toward transglutaminase 2. Furthermore,
an initial pharmacokinetic profiling of selected inhibitors was performed,
including the assessment of potential membrane permeability and liver
microsomal stability
<i>N</i><sup>Δ</sup>âAcryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, StructureâActivity Relationships, and Pharmacokinetic Profiling
Transglutaminase
2 (TGase 2)-catalyzed transamidation represents
an important post-translational mechanism for protein modification
with implications in physiological and pathophysiological conditions,
including fibrotic and neoplastic processes. Consequently, this enzyme
is considered a promising target for the diagnosis of and therapy
for these diseases. In this study, we report on the synthesis and
kinetic characterization of <i>N</i><sup>Δ</sup>-acryloyllysine
piperazides as irreversible inhibitors of TGase 2. Systematic structural
modifications on 54 new compounds were performed with a major focus
on fluorine-bearing substituents due to the potential of such compounds
to serve as radiotracer candidates for positron emission tomography.
The determined inhibitory activities ranged from 100 to 10âŻ000
M<sup>â1</sup> s<sup>â1</sup>, which resulted in comprehensive
structureâactivity relationships. Structureâactivity
correlations using various substituent parameters accompanied by covalent
docking studies provide an advanced understanding of the molecular
recognition for this inhibitor class within the active site of TGase
2. Selectivity profiling of selected compounds for other transglutaminases
demonstrated an excellent selectivity toward transglutaminase 2. Furthermore,
an initial pharmacokinetic profiling of selected inhibitors was performed,
including the assessment of potential membrane permeability and liver
microsomal stability
<i>N</i><sup>Δ</sup>âAcryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, StructureâActivity Relationships, and Pharmacokinetic Profiling
Transglutaminase
2 (TGase 2)-catalyzed transamidation represents
an important post-translational mechanism for protein modification
with implications in physiological and pathophysiological conditions,
including fibrotic and neoplastic processes. Consequently, this enzyme
is considered a promising target for the diagnosis of and therapy
for these diseases. In this study, we report on the synthesis and
kinetic characterization of <i>N</i><sup>Δ</sup>-acryloyllysine
piperazides as irreversible inhibitors of TGase 2. Systematic structural
modifications on 54 new compounds were performed with a major focus
on fluorine-bearing substituents due to the potential of such compounds
to serve as radiotracer candidates for positron emission tomography.
The determined inhibitory activities ranged from 100 to 10âŻ000
M<sup>â1</sup> s<sup>â1</sup>, which resulted in comprehensive
structureâactivity relationships. Structureâactivity
correlations using various substituent parameters accompanied by covalent
docking studies provide an advanced understanding of the molecular
recognition for this inhibitor class within the active site of TGase
2. Selectivity profiling of selected compounds for other transglutaminases
demonstrated an excellent selectivity toward transglutaminase 2. Furthermore,
an initial pharmacokinetic profiling of selected inhibitors was performed,
including the assessment of potential membrane permeability and liver
microsomal stability
Re-bleeding rates and re-interventions after TIPS implantation.
<p>(A). Rebleeding rates after TIPS implantation. (B). Bleeding recurrence after TIPS implantation, by type of implanted stent.</p