Oxidative stress contributes to myocardial ischemia-reperfusion injury, which causes cardiomyocyte death and precipitate life-threatening heart failure. Propofol has been proposed to protect cells or ...tissues against oxidative stress. However, the mechanisms underlying its beneficial effects are not fully elucidated. In the present study, we employed an in vitro oxidative injury model, in which rat cardiac H9c2 cells were treated with H2O2, and investigated roles of propofol against oxidative stress. Propofol treatment reduced H2O2-induced apoptotic cell death. While H2O2 induced expression of the antioxidant enzyme HO-1, propofol further increased HO-1 mRNA and protein levels. Propofol also promoted nuclear localization of Nrf2 in the presence of H2O2. Knockdown of Nrf2 using siRNA suppressed propofol-inducible Nrf2 and expression of Nrf2-downstream antioxidant enzyme. Knockdown of Nrf2 suppressed the propofol-induced cytoprotection. In addition, Nrf2 overexpression induced nuclear localization of Nrf2 and HO-1 expression. These results suggest that propofol exerts antioxidative effects by inducing nuclear localization of Nrf2 and expression of its downstream enzyme in cardiac cells. Finally, we examined the effect of propofol on cardiomyocytes using myocardial ischemia-reperfusion injury models. The expression level of Nrf2 protein was increased at 15 min after reperfusion in the ischemia-reperfusion and propofol group compared with ischemia-reperfusion group in penumbra region. These results suggest that propofol protects cells or tissues from oxidative stress via Nrf2/HO-1 cascade.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Context: .Scatter around the relationship between central black hole masses in active galactic nuclei (AGNs) obtained by reverberation-mapping methods and host-galaxy bulge velocity dispersion ...indicates that the masses are uncertain typically by a factor of about three. Aims: .In this paper, we try to identify the sources and systematics of this uncertainty. Methods: .We characterize the broad Hbeta emission-line profiles by the ratio of their full-width at half maximum (FWHM) to their line dispersion, i.e., the second moment of the line profile. We use this parameter to separate the reverberation-mapped AGNs into two populations, the first with narrower Hbeta lines that tend to have relatively extended wings, and the second with broader lines that are relatively flat-topped. The first population is characterized by higher Eddington ratios than the second. Within each population, we calibrate the black-hole mass scale by comparison of the reverberation-based mass with that predicted by the bulge velocity dispersion. We also use the distribution of ratios of the reverberation-based mass to the velocity-dispersion mass prediction in a comparison with a "generalized thick disk" model in order to see if inclination can plausibly account for the observed distribution. Results: .We find that the line dispersion is a less biased parameter in general than FWHM for black hole mass estimation, although we show that it is possible to empirically correct for the bias introduced by using FWHM to characterize the emission-line width. We also argue that inclination effects are apparent only in some small subset of the reverberation-based mass measurements; it is primarily the objects with the narrowest emission lines that seem to be most strongly affected. Conclusions: .Our principal conclusion is that the Hbeta profile is sensitive primarily to Eddington ratio, but that inclination effects play a role in some cases.
Considering the impaired function of regenerative cells in myocardial infarction (MI) patients with comorbidities and associated risk factors, cell therapy to enhance the regenerative ...microenvironment was designed using regeneration-associated cells (RACs), including endothelial progenitor cells (EPCs) and anti-inflammatory cells.
RACs were prepared by quality and quantity control culture of blood mononuclear cells (QQMNCs). Peripheral blood mononuclear cells (PBMNCs) were isolated from Lewis rats and conditioned for 5 days using a medium containing stem cell factors, thrombopoietin, Flt-3 ligand, vascular endothelial growth factor, and interleukin-6 to generate QQMNCs.
A 5.3-fold increase in the definitive colony-forming EPCs and vasculogenic EPCs was observed, in comparison to naïve PBMNCs. QQMNCs were enriched with EPCs (28.9-fold, P<0.0019) and M2 macrophages (160.3-fold, P<0.0002). Genes involved in angiogenesis (angpt1, angpt2, and vegfb), stem/progenitors (c-kit and sca-1), and anti-inflammation (arg-1, erg-2, tgfb, and foxp3) were upregulated in QQMNCs. For in vivo experiments, cells were administered into syngeneic rat models of MI. QQMNC-transplanted group (QQ-Tx) preserved cardiac function and fraction shortening 28 days post-MI in comparison with PBMNCs-transplanted (PB-Tx) (P<0.0001) and Control (P<0.0008) groups. QQ-Tx showed enhanced angiogenesis and reduced interstitial left ventricular fibrosis, along with a decrease in neutrophils and an increase in M2 macrophages in the acute phase of MI. Cell tracing studies revealed that intravenously administered QQMNCs preferentially homed to ischemic tissues via blood circulation. QQ-Tx showed markedly upregulated early cardiac transcriptional cofactors (Nkx2-5, 29.8-fold, and Gata-4, 5.2-fold) as well as c-kit (4.5-fold) while these markers were downregulated in PB-Tx. In QQ-Tx animals, de novo blood vessels formed a "Biological Bypass", observed macroscopically and microscopically, while PB-Tx and Control-Tx groups showed severe fibrotic adhesion to the surrounding tissues, but no epicardial blood vessels.
QQMNCs conferred potent angiogenic and anti-inflammatory properties to the regenerative microenvironment, enhancing myocardiogenesis and functional recovery of rat MI hearts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We use the BH masses deduced from the empirical relation of Kaspi et al. (2000) between the size of the Broad Line Region (BLR) of Active Galactic Nuclei (AGN) and the optical luminosity, to compute ...their accretion rates in four samples of AGN, assuming that the optical luminosity is provided by the accretion disc. We show that Narrow Line Seyfert Galaxies 1 (NLS1s) accrete at super-Eddington rates, while their luminosity stays of the order of the Eddington limit. We take into account the possibility of a non-viscous energy release inversely proportional to the square of the distance in the gravitationally unstable region of the disc emitting a fraction of the optical luminosity. It leads to a smaller accretion rate and to a redder continuum than a standard disc, which agrees better with the observations. The observed bolometric luminosities appear to saturate at a few times the Eddington luminosity for super-Eddington accretion rates, as predicted by slim disc models. They favor a Kerr BH rather than a Schwarzschild one. Even when the accretion rate is super-Eddington, it stays always of the order of a few M sub( )/yr, irrespective of the BH mass, indicating that the growing of the BH is mass-supply-limited and therefore regulated by an exterior mechanism, and not Eddington-limited. The mass of the BH increases by one order of magnitude in a few 10 super(7) years, a time smaller than that necessary for changing the bulge mass. This is in agreement with recent claims that the BHs of NLS1s do not follow the same black hole - bulge relation as other galaxies. Since they represent about 10% of AGN up to a redshift of 0.5, these "super-active" phases should play an important role in shaping the mass function of local BHs. We finally discuss the possibility that the masses could be systematically underestimated due to an inclination effect, and we conclude that this could indeed be the case, and that the accretion rates could thus be strongly overestimated in a small fraction of objects, possibly explaining the existence of apparently extremely high accretors.
Recently, it was reported that plasma microRNAs (miRNAs) are low-invasive useful biomarkers for cancer. We attempted to isolate gastric cancer (GC)-associated miRNAs comparing pre- and post-operative ...paired plasma, thereby excluding the possible effects of individual variability.
This study was divided into four steps: (1) microarray analysis comparing pre- and post-operative plasma; (2) validation of candidate miRNAs by quantitative RT-PCR; (3) validation study of selected miRNAs using paired plasma; and (4) comparison of the levels of selected miRNAs in plasma between healthy controls and patients.
From the results of microarray analysis, nine candidate miRNAs the levels of which were markedly decreased in post-operative plasma were selected for further studies. After confirmation of their post-operative marked reduction, two candidate miRNAs, miR-451 and miR-486, were selected as plasma biomarkers, considering the abundance in plasma, and marked decrease in post-operative samples. In validation, the two miRNAs were found to decrease in post-operative plasma in 90 and 93% of patients (both P<0.01). In comparison with healthy controls, the levels of both miRNAs were found to be significantly higher in patients, and the area under the curve values were high at 0.96 and 0.92.
Plasma miR-451 and miR-486 could be useful blood-based biomarkers for screening GC.
We present a novel approach to the solid-state synthesis of garnet-type cubic Li
7
La
3
Zr
2
O
12
(c-LLZO) nanostructured particles with 1.0 mass% Al at 750 °C within 3 h. In contrast to conventional ...solid-state processes, a highly reactive precursor was prepared in two steps: (i) by homogenizing the stoichiometric mixture without Li, and (ii) subsequent addition of Li in the form of an ethanolic solution of lithium acetate. The actual composition determined by ICP analysis was Li
6.61
La
3
Zr
2
Al
0.13
O
11.98
. Sintering these nanoparticles at 1100 °C for 3 h in air after cold isostatic pressing brought a dense ceramic pellet with a relative density of 90.5%. The corresponding ionic conductivity with Au electrodes was 1.6 × 10
−4
S cm
−1
at room temperature. To study its electrochemical behavior as an electrolyte, a model cell of Li//(1 M LiPF
6
+ c-LLZO)//LiCoO
2
configuration was constructed. Cyclic voltammetry of the cell delivered one set of redox couple with narrow voltage separation (15 mV) with a Li
+
diffusion coefficient at room temperature of about 2 × 10
−11
cm
2
s
−1
at the interface between LiCoO
2
and 1 M LiPF
6
+ c-LLZO. The cell received an average discharge capacity of 64.4, 60.3, 56.1, 51.9 and 46.9 μA h cm
−2
μm
−1
at discharge rates 0.5C, 1C, 2C, 4C and 6C, respectively. The cell exhibited complete oxidation and reduction reactions with an average initial discharge capacity of about 64 μA h cm
−2
μm
−1
, which is 92.7% of LiCoO
2
theoretical value. These observations indicate the applicability of the present c-LLZO as an electrolyte for a solid-state Li-ion battery.
Garnet Li
7
La
3
Zr
2
O
12
nanoparticles with 1 mass% Al were prepared
via
a solid-state route at 750 °C within 3 h. A model cell sandwiched by Li and LiCoO
2
exhibited initial discharge capacity of 64 μA h cm
−2
μm
−1
, being 93% of LiCoO
2
theoretical value.
Simultaneous poisoning by carbon monoxide (CO) and hydrogen cyanide is the major cause of mortality in fire gas accidents. Here, we report on the invention of an injectable antidote against CO and ...cyanide (CN
) mixed poisoning. The solution contains four compounds: iron(III)porphyrin (Fe
TPPS, F), two methyl-β-cyclodextrin (CD) dimers linked by pyridine (Py3CD, P) and imidazole (Im3CD, I), and a reducing agent (Na
S
O
, S). When these compounds are dissolved in saline, the solution contains two synthetic heme models including a complex of F with P (hemoCD-P) and another one of F with I (hemoCD-I), both in their iron(II) state. hemoCD-P is stable in its iron(II) state and captures CO more strongly than native hemoproteins, while hemoCD-I is readily autoxidized to its iron(III) state to scavenge CN
once injected into blood circulation. The mixed solution (hemoCD-Twins) exhibited remarkable protective effects against acute CO and CN
mixed poisoning in mice (~85% survival vs. 0% controls). In a model using rats, exposure to CO and CN
resulted in a significant decrease in heart rate and blood pressure, which were restored by hemoCD-Twins in association with decreased CO and CN
levels in blood. Pharmacokinetic data revealed a fast urinary excretion of hemoCD-Twins with an elimination half-life of 47 min. Finally, to simulate a fire accident and translate our findings to a real-life scenario, we confirmed that combustion gas from acrylic cloth caused severe toxicity to mice and that injection of hemoCD-Twins significantly improved the survival rate, leading to a rapid recovery from the physical incapacitation.
Chlorine resistant reverse osmosis (RO) membranes were fabricated using a multi-walled carbon nanotube-polyamide (MWCNT-PA) nanocomposite. The separation performance of these membranes after chlorine ...exposure (4800 ppm·h) remained unchanged (99.9%) but was drastically reduced to 82% in the absence of MWCNT. It was observed that the surface roughness of the membranes changed significantly by adding MWCNT. Moreover, membranes containing MWCNT fractions above 12.5 wt.% clearly improved degradation resistance against chlorine exposure, with an increase in water flux while maintaining salt rejection performance. Molecular dynamics and quantum chemical calculations were performed in order to understand the high chemical stability of the MWCNT-PA nanocomposite membranes, and revealed that high activation energies are required for the chlorination of PA. The results presented here confirm the unique potential of carbon nanomaterials embedded in polymeric composite membranes for efficient RO water desalination technologies.
Despite the fact that phase-change materials are widely used for data storage, no consensus exists on the unique mechanism of their ultrafast phase change and its accompanied large and rapid optical ...change. By using the pump-probe observation method combining a femtosecond optical laser and an x-ray free-electron laser, we substantiate experimentally that, in both GeTe and Ge_{2}Sb_{2}Te_{5} crystals, rattling motion of mainly Ge atoms takes place with keeping the off-center position just after femtosecond-optical-laser irradiation, which eventually leads to a higher symmetry or disordered state. This very initial rattling motion in the undistorted lattice can be related to instantaneous optical change due to the loss of resonant bonding that characterizes GeTe-based phase change materials. Based on the amorphous structure derived by first-principles molecular dynamics simulation, we infer a plausible ultrafast amorphization mechanism via nonmelting.
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